今日の臨床サポート

勃起不全

著者: 白井雅人 順天堂大学医学部附属浦安病院 泌尿器科

監修: 堀江重郎 順天堂大学大学院医学研究科 泌尿器外科学

著者校正済:2022/09/28
現在監修レビュー中
参考ガイドライン:
  1. 日本性機能学会:ED診療ガイドライン 第3版
  1. European Association Urology:Guidelines for sexual and reproductive health
患者向け説明資料

概要・推奨   

  1. EDの有病率は加齢に伴って上昇する。その原因としては、加齢に伴う陰茎の組織学的変化、内分泌環境の変化のほか、種々のリスクファクターの増加が考えられる。
  1. 喫煙は明らかにEDを引き起こす。できるだけ喫煙しない(受動喫煙も含め)ことを心がけるべきである。禁煙のEDリスク減少効果は明白ではないが、患者には禁煙を勧めるべきである(推奨度1)
  1. 高血圧患者ではEDを合併する頻度が高く、重症化しやすい。高血圧とEDの合併頻度が高い理由は、血管機能障害が両疾患の原因になっている可能性と、高血圧による血管障害がEDの原因となっている可能性がある。降圧薬のなかにはEDを増悪させる作用を持つものがあり、注意を要する。
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  1. EDと下部尿路症状・前立腺肥大症(LUTS/BPH)は合併することが多く、しかも重症度が比例する。BPHの薬物療法に関しては、α1遮断薬はEDを起こす可能性は少ない。5α還元酵素阻害薬はEDを起こす。BPHの手術療法に関しては、ホルミウムレーザー前立腺核出術(HoLEP)以外はEDを起こす可能性が高い(推奨度1)
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
白井雅人 : 特に申告事項無し[2022年]
監修:堀江重郎 : 特許使用料(アステラス製薬,大塚製薬,日本新薬,セティ,アストラゼネカ,杏林製薬,小野薬品,ファイザー),原稿料(キッセイ薬品工業,小野薬品工業,サノフィ,武田薬品工業,中外製薬,アステラス,旭化成ファーマ,ファイザー,日本新薬)[2022年]

改訂のポイント:
  1. EAU guidelinesに基づき、Low intensity-Shock Wave Therapy(Li-SWT)を治療の項に追加した。
  1. レビトラ錠が販売中止となったため、ジェネリック医薬品のバルデナフィル錠の名称とした。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 勃起障害(erectile dysfunction、ED)は、「満足な性行為を行うのに十分な勃起が得られないか、または(and/or)維持できない状態が持続または(or)再発すること」と定義されている。
  1. EDの診断は、患者が満足な性交を営むことができる勃起が得られないという訴えがあれば成り立つ。
  1. 発病率はさまざまなリスクファクターによって変化するが、中高年男性を中心に発生し、人口の高齢化に伴って有病者は増加傾向にある。
  1. わが国の有病率は中等度EDが約870万人、完全EDが約260万人、合わせて1,130万人と推定された。加齢に伴って増加し、50歳代前半で55%、60歳代前半では75%にものぼる。
  1. 診断は、患者の77%は、質問紙、問診、身体所見、臨床検査といった基本的な診断手段でEDの原因診断が可能である。
  1. 機能性(心因性、精神病性)か器質性(血管性、神経性)かを問診で明らかにする。
    早朝勃起やマスターベーションで勃起が得られるのに性交時に得られない場合は機能性と考える。心因性勃起障害は緊張やストレスによる交感神経亢進状態が原因となる。新婚EDと呼ばれる新婚カップルに多いものや挙児を得る重圧が引き起こすことが多い。
  1. 勃起機能質問紙としては、International Index of Erectile Function 5(IIEF5)やIIEF5に性交頻度を加味した Sexual Health Inventory for Males(SHIM)、Erection Hardness Score(EHS)などが日本語でも使用できる。
 
  1. EDの有病率は加齢に伴って上昇する。その原因としては、加齢に伴う陰茎の組織学的変化、内分泌環境の変化のほか、種々のリスクファクターの増加が考えられる。
  1. マサチューセッツ男性加齢研究(MMAS)でも日本人の調査でも、加齢とともにEDの有病率は上昇している[1][2]。また、289人の日本人と2,115人の米国人の地域住民を対象とした疫学調査でも、日本人のほうが性機能の低下が著しく、70歳代では71%が中等度ないし完全EDであると報告されている[3]。また、わが国の企業従事者とその家族に対する調査でも、加齢によりEDの有病率の上昇がみられた[4]。さらに、国内で慢性疾患のため通院中の患者4,609人を対象とした調査でも、2,084人の人間ドックのデータを解析した調査でも、同様の結果であった[5][6]
  1. 加齢によるEDの原因としては、陰茎海綿体白膜の弾性線維の減少などの組織学的変化の結果として静脈流出系の閉鎖機能の低下、血清男性ホルモン濃度の低下に加えて、後述する種々のリスクファクターが加齢とともに増加することによると考えられている[7][8][9]
 
  1. 海外の報告では高脂血症はEDのリスクとされているが、日本人では、高脂血症はEDのリスクファクターとは言い難い。コレステロール低下薬による薬剤性のEDに関しての関連は、むしろ勃起機能を改善するという報告とEDを起こすという報告があるが、いまだ結論は出ていない(推奨度1)<図表>
  1. 米国でのマネージドケアのデータベース(n=27万2,000)を用いた調査では、ED患者の42.4%が高脂血症を有していたとされる[10]。やはり米国で、調査開始時にはEDでなかった3,250人を6~48カ月フォローした結果、総コレステロールの高値とHDLの低値がED発症のリスクファクタ―であった[11]。一方、ボストンの地域住民1,899人(30~79歳)を調査した研究(Boston Area Community Survey: BACS)では、高脂血症を総コレステロール>240mg/dlで定義し、IIEF5で勃起機能を評価すると、高脂血症で無治療群が21.6、高脂血症なし群で20.6と差がなかった[12]
  1. わが国における疫学研究をみてみると、企業従業員とその家族を調査した研究(n=1,517人、高脂血症は自己申告)、慢性疾患のために通院中の患者を調査した研究(n=4,609人、高脂血症は自己申告)、人間ドックのデータを解析した研究(n=2,084人、総コレステロール>220mg/dl or LDL>140mg/dlを高脂血症と定義)、3つの研究すべてで高脂血症とEDの関連を認めていない[4][5][6]。また隣国の韓国での疫学調査(n=1,570人)でも、総コレステロール、HDL、LDLのいずれもED患者と健常者間で差を認めていない[13]。したがって、脂質異常症に関しては、欧米人と日本人を含むアジア人種ではリスクファクターとしての寄与度が異なるのかもしれない。
  1. さて、脂質異常症に対する薬物療法の勃起機能への影響に関しては結果がまちまちである。高脂血症治療薬が勃起機能を改善したとする研究は、
  1. 高脂血症のみがEDのリスクファクターである患者にスタチン(アトルバスタチン)を投与した観察研究
  1. シルデナフィルにアトルバスタチンかプラセボを上乗せするRCTで、IIEFのEFドメインを有意に実薬が改善した。
  1. 神経温存前立腺全摘術後の勃起機能回復をシルデナフィル単独群とアトルバスタチン併用群で比較した研究では、併用群で有意に早い回復を認めている(n=50)[14]
  1. 一方、高脂血症治療薬が勃起機能を改善したとする研究は、①高脂血症で外来を受診した患者を、薬物治療を受けていた群(n=339)と受けていなかった群(n=339)に分け、ED(NIHの定義による)の有無を調べたところ、薬物治療群では12.1%、対照群では5.6%(p=0.0029)と有意差をもって薬物治療群にEDを多く発症していた。心血管リスクの高い患者群(n=93)にスタチンを6カ月投与したところ、IIEF5が18.7から10.4に低下し、新たに22%の患者にEDが発生した[14]。前述のBACS研究でも、55歳以下で糖尿病か心血管疾患を有する患者では、高脂血症治療薬はEDのリスクを上昇させた(オッズ比10.39、95%CI:3.25~33.20)[12]
病歴・診察のポイント  
  1. 問診の目的は、機能性(心因性、精神病性)か器質性(血管性、神経性)かを明らかにすることである。

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文献 

H A Feldman, I Goldstein, D G Hatzichristou, R J Krane, J B McKinlay
Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study.
J Urol. 1994 Jan;151(1):54-61.
Abstract/Text We provide current, normative data on the prevalence of impotence, and its physiological and psychosocial correlates in a general population using results from the Massachusetts Male Aging Study. The Massachusetts Male Aging Study was a community based, random sample observational survey of noninstitutionalized men 40 to 70 years old conducted from 1987 to 1989 in cities and towns near Boston, Massachusetts. Blood samples, physiological measures, socio-demographic variables, psychological indexes, and information on health status, medications, smoking and lifestyle were collected by trained interviewers in the subject's home. A self-administered sexual activity questionnaire was used to characterize erectile potency. The combined prevalence of minimal, moderate and complete impotence was 52%. The prevalence of complete impotence tripled from 5 to 15% between subject ages 40 and 70 years. Subject age was the variable most strongly associated with impotence. After adjustment for age, a higher probability of impotence was directly correlated with heart disease, hypertension, diabetes, associated medications, and indexes of anger and depression, and inversely correlated with serum dehydroepiandrosterone, high density lipoprotein cholesterol and an index of dominant personality. Cigarette smoking was associated with a greater probability of complete impotence in men with heart disease and hypertension. We conclude that impotence is a major health concern in light of the high prevalence, is strongly associated with age, has multiple determinants, including some risk factors for vascular disease, and may be due partly to modifiable para-aging phenomena.

PMID 8254833
N Masumori, T Tsukamoto, Y Kumamoto, L A Panser, T Rhodes, C J Girman, M M Lieber, S J Jacobsen
Decline of sexual function with age in Japanese men compared with American men--results of two community-based studies.
Urology. 1999 Aug;54(2):335-44; discussion 344-5.
Abstract/Text OBJECTIVES: To investigate the self-reported sexual function of Japanese men aged 40 to 79 years in a community-based study and compare the results to a similarly conducted study in Olmsted County, Minnesota.
METHODS: Two hundred eighty-nine Japanese and 2115 American men from the community were queried about ability to have erections when stimulated, sexual drive, and satisfaction with sexual activity using a self-administered questionnaire.
RESULTS: Both Japanese and American men showed an age-related decline in erectile function, sexual libido, and sexual satisfaction. In particular, 71% of Japanese men aged 70 to 79 years reported having erections only a little of the time or less when sexually stimulated, and 80% perceived sexual drive once per month or less during the past month. Although more Japanese than American men reported erectile dysfunction and decreased libido, there were no striking differences in self-reported sexual satisfaction between the studies. However, cultural and perceptual differences could play a role in these results, despite attempts to ensure linguistic equivalency in the questionnaires.
CONCLUSIONS: Although erectile dysfunction and decreased libido were noted by a greater proportion of Japanese than American men, the self-reported degree of satisfaction was comparable between the studies. Perceptions of elderly male sexual function and its impact on health-related quality of life may differ among races, sites, and countries.

PMID 10443735
Abstract/Text BACKGROUND: The effects of age and concomitant chronic illness on male sexual function were investigated to obtain insight into the prevention of erectile dysfunction (ED).
METHODS: A questionnaire from the International Index of Erectile Function (IIEF) was given to 2311 non-institutionalized men aged 23-79 years along with a survey of health status. The study sample consisted of 1517 men who provided complete responses to the questionnaire. For statistical analysis, ANOVA was conducted to evaluate the effect of aging on the sexual functions and a logistic regression model was used to identify significant independent risk factors for ED.
RESULTS: There was a significant correlation between age and the scores for erectile function, orgasmic function, sexual desire and intercourse satisfaction. The prevalence of moderate and severe cases of ED were 1.8% and 0% for ages 23-29; 2.6% and 0% for ages 30-39; 7.6% and 1.0% for ages 40-49; 14.0% and 6.0% for ages 50-59; 25.9% and 15.9% for ages 60-69; and 27.9% and 36.4% for ages 70-79 years, respectively. Hypertension, diabetes mellitus, heart disease, chronic hepatitis, disc herniation and cerebral infarction under treatment with anticoagulants were significant independent risk factors for ED.
CONCLUSIONS: The results obtained indicated a significant association between aging and chronic diseases and erectile function. Further epidemiologic research and analysis of individual risk factors are required to allow more effective future strategies for the treatment and prevention of ED.

PMID 11240826
Shigetake Sasayama, Nobuhisa Ishii, Fuminobu Ishikura, Gombei Kamijima, Satoshi Ogawa, Katsuo Kanmatsuse, Yasusuke Kimoto, Ichiro Sakuma, Hiroshi Nonogi, Akira Matsumori, Yasuhiro Yamamoto
Men's Health Study: epidemiology of erectile dysfunction and cardiovascular disease.
Circ J. 2003 Aug;67(8):656-9.
Abstract/Text The present study collected data about 6,112 Japanese male patients from 447 outpatient clinics. Of those who underwent medical examination by a general practitioner on an outpatient basis, up to 81% had some degree of erectile dysfunction (ED), ranging from mild to severe. ED was noted to be predominant among patients affected by cardiovascular disease (CVD) or diabetes mellitus (DM), and the presence of CVD increased the risk of ED. In an aging society, patients undergoing treatment for ED as part of their routine medical care are highly likely to have concomitant CVD. As shown in the present survey, clinicians need to be aware of the high incidence of ED among such patients, because ED represents a symptom originating from damage to the vascular endothelium. A total of 41% of ED patients are either willing to receive pharmacotherapy for ED or will consider treatment. Active treatment of ED with sildenafil is suitable for patients with CVD.

PMID 12890904
Akito Terai, Kentaro Ichioka, Yoshiyuki Matsui, Koji Yoshimura
Association of lower urinary tract symptoms with erectile dysfunction in Japanese men.
Urology. 2004 Jul;64(1):132-6. doi: 10.1016/j.urology.2004.02.019.
Abstract/Text OBJECTIVES: To assess the age-stratified prevalence of erectile dysfunction (ED) and how lower urinary tract symptoms (LUTS) are associated with ED, and to estimate the correlates of ED among Japanese men.
METHODS: A self-administered questionnaire of the International Prostate Symptom Score and the abridged 5-item version of the International Index of Erectile Function were given to 3189 noninstitutionalized men during a multiphasic health screening. The data from 2084 men who provided complete responses to the questionnaire were analyzed.
RESULTS: The prevalence of moderate to severe ED increased from 13.4% among those younger than 40 years to 20.6%, 39.9%, and 63.1% among those aged 40 to 49, 50 to 59, and 60 years or older, respectively. Most were dissatisfied with their sex life regardless of age. The severity of ED was significantly associated with moderate to severe International Prostate Symptom Scores (age-adjusted odds ratio 1.52), specifically in the urgency (1.75) and nocturia (1.36) domains, and for those with diabetes mellitus (2.54) and coronary artery disease (8.04).
CONCLUSIONS: ED is highly prevalent among Japanese men with LUTS and is significantly associated with the severity of LUTS after controlling for age. This significant aspect of life for men of all ages should be taken into account when treating patients with LUTS.

PMID 15245950
E Akkus, S Carrier, K Baba, G L Hsu, H Padma-Nathan, L Nunes, T F Lue
Structural alterations in the tunica albuginea of the penis: impact of Peyronie's disease, ageing and impotence.
Br J Urol. 1997 Jan;79(1):47-53.
Abstract/Text OBJECTIVE: To investigate whether changes in the structure of the tunica albuginea influence the development of erectile dysfunction.
PATIENTS AND METHODS: Biopsy specimens taken from the tunica of 64 patients (both potent and impotent) with and without Peyronie's disease were evaluated. Tissue samples were stained and examined under light and electron microscopy, and the concentration of elastic fibres present in each was measured using computerized image analysis.
RESULTS: The concentration of elastic fibres was lower in impotent than in potent patients (P = 0.0365) and was also significantly less in patients with Peyronie's disease. Furthermore, the concentration of elastic fibres decreased with age. Electron and light microscopy revealed the presence of distinct alterations in the tunica albuginea in impotent patients and patients with Peyronie's disease that might interfere with function.
CONCLUSION: The decrease in elastic fibre concentration and changes in microscopic features may contribute to erectile dysfunction by impairing the veno-occlusive function of the tunica albuginea.

PMID 9043496
Allen D Seftel
Erectile dysfunction in the elderly: epidemiology, etiology and approaches to treatment.
J Urol. 2003 Jun;169(6):1999-2007. doi: 10.1097/01.ju.0000067820.86347.95.
Abstract/Text PURPOSE: Erectile dysfunction is experienced at least some of the time by most men who have reached 45 years of age, and it is projected to affect 322 million men worldwide by 2025. The prevalence of erectile dysfunction is high in men of all ages and increases greatly in the elderly.
MATERIALS AND METHODS: This paper reviews the epidemiology of erectile dysfunction with an emphasis on the experience of older men, normal age related changes in the structure and function of the penis that may contribute to increased risk with age, how the accumulation of risk factors with age may contribute to the high prevalence of the disease in older men, and established and emerging therapies. The normal aging process and age related risk factor accumulation contribute to the increased prevalence of erectile dysfunction in the elderly.
RESULTS: Remarkable progress has been made in the treatment of erectile dysfunction. At present inhibition of phosphodiesterase 5 with oral agents such as sildenafil would appear to be the initial treatment of choice. These drugs have been shown to be safe and effective, and sildenafil has demonstrated efficacy in patients with many of the comorbidities observed in older men with erectile dysfunction. New treatments, in particular transfection with genes for key mediators of erectile function that are known to be down-regulated in elderly men, also hold promise.
CONCLUSIONS: Further research into the neural, vascular and molecular mechanisms involved in penile erection will lead to the development of even safer, more effective and more convenient therapies for men with erectile dysfunction.

PMID 12771705
Allen D Seftel, Peter Sun, Ralph Swindle
The prevalence of hypertension, hyperlipidemia, diabetes mellitus and depression in men with erectile dysfunction.
J Urol. 2004 Jun;171(6 Pt 1):2341-5.
Abstract/Text PURPOSE: We quantified the prevalence of diagnosed hypertension, hyperlipidemia, diabetes mellitus and depression in male health plan members with erectile dysfunction (ED).
MATERIALS AND METHODS: We used a nationally representative managed care claims database that covered 51 health plans with 28 million lives for 1995 through 2002. Based on 272325 identified patients with ED population and age specific prevalence rates were calculated for the same period.
RESULTS: The crude population prevalence rates were 41.6% for hypertension, 42.4% for hyperlipidemia, 20.2% for diabetes mellitus, 11.1% for depression, 23.9% for hypertension and hyperlipidemia, 12.8% for hypertension and diabetes mellitus, and 11.5% for hyperlipidemia and depression. The crude age specific prevalence rates varied across age groups significantly for hypertension (4.5% to 68.4%), hyperlipidemia (3.9% to 52.3%), and diabetes mellitus (2.8% to 28.7%), and significantly less for depression (5.8% to 15.0%). Region adjusted population prevalence rates were 41.2% for hypertension, 41.8% for hyperlipidemia, 19.7% for diabetes mellitus and 11.9% for depression. Only 87163 patients with ED (32%) had no comorbid diagnosis of hypertension, hyperlipidemia, diabetes mellitus or depression.
CONCLUSION: Hypertension, hyperlipidemia, diabetes mellitus and depression were prevalent in patients with ED. This evidence supported the proposition that ED shares common risk factors with these 4 concurrent conditions. Therefore, as a pathophysiological event, ED could be viewed as a potential observable marker for these concurrent diseases. This finding suggests that clinicians could include ED in the assessment profile of these concurrent conditions for earlier detection and treatment.

PMID 15126817
M Wei, C A Macera, D R Davis, C A Hornung, H R Nankin, S N Blair
Total cholesterol and high density lipoprotein cholesterol as important predictors of erectile dysfunction.
Am J Epidemiol. 1994 Nov 15;140(10):930-7.
Abstract/Text Although erectile dysfunction is frequently seen in patients with manifestations of arteriosclerotic disease, the independent contribution of serum cholesterol in predicting erectile dysfunction is unclear. The aim of this study was to examine the relation between serum cholesterol and erectile dysfunction. Medical histories, physical examinations, and blood tests were obtained at Cooper Clinic, Dallas, Texas, from 3,250 men aged 26-83 years (mean, 51 years) without erectile dysfunction at their first visit, who had one more clinic visit, all between 1987 and 1991. These men were followed 6-48 months after the first clinic visit (mean, 22 months). Erectile dysfunction was reported in 71 men (2.2%) during follow-up. Every mmol/liter of increase in total cholesterol was associated with 1.32 times the risk of erectile dysfunction (95% confidence interval 1.04-1.68), while every mmol/liter of increase in high density lipoprotein cholesterol was associated with 0.38 times the risk (95% confidence interval 0.18-0.80). Men with a high density lipoprotein cholesterol measurement over 1.55 mmol/liter (60 mg/dl) had 0.30 times the risk (95% confidence interval 0.09-1.03) as did men with less than 0.78 mmol/liter (30 mg/dl). Men with total cholesterol over 6.21 mmol/liter (240 mg/dl) had 1.83 times the risk (95% confidence interval 1.00-3.37) as did men with less than 4.65 mmol/liter (180 mg/dl). Those differences remained essentially unchanged after adjustment for other potential confounders. The authors conclude that a high level of total cholesterol and a low level of high density lipoprotein cholesterol are important risk factors for erectile dysfunction.

PMID 7977280
Susan A Hall, Varant Kupelian, Raymond C Rosen, Thomas G Travison, Carol L Link, Martin M Miner, Peter Ganz, John B McKinlay
Is hyperlipidemia or its treatment associated with erectile dysfunction?: Results from the Boston Area Community Health (BACH) Survey.
J Sex Med. 2009 May;6(5):1402-13. doi: 10.1111/j.1743-6109.2008.01207.x. Epub 2009 Feb 9.
Abstract/Text INTRODUCTION: Studies and reports suggest that both hyperlipidemia and its pharmacologic treatment may lead to an increased risk of erectile dysfunction (ED).
AIMS: Our objectives were to examine the association between (i) treated hyperlipidemia and ED; and (ii) untreated hyperlipidemia and ED.
METHODS: Data from 1,899 men aged 30-79 were used from the Boston Area Community Health Survey of community-dwelling residents of Boston, MA, collected during 2002-2005 using an in-person interview, self-administered questionnaires, and a venous blood draw.
MAIN OUTCOME MEASURES: ED was measured using the short form International Index of Erectile Function. A case of treated hyperlipidemia was defined by use of anti-lipemics in the past month, while untreated hyperlipidemia was serum total cholesterol > or =240 milligrams per deciliter with no anti-lipemic use. We estimated associations using odds ratios (ORs) and 95% confidence intervals (CIs) from multivariate logistic regression.
RESULTS: Men with treated hyperlipidemia were older, had more comorbidities, and used more medications compared with men with untreated hyperlipidemia or no hyperlipidemia. In multivariate models stratified by age and the presence of diabetes and/or cardiovascular disease (CVD), we saw no association between hyperlipidemia drug treatment and ED, except among younger men (<55) who had diabetes and/or CVD, where a strong association with an imprecise CI was observed (OR = 10.39, 95% CI: 3.25, 33.20). There was no significant positive association between untreated hyperlipidemia and ED in any multivariate model.
CONCLUSION: Lipid-lowering medications may be associated with ED among some men. The well-established benefits of lipid-lowering therapy should always be weighed against potential adverse effects.

PMID 19210709
Tai Young Ahn, Jong Kwan Park, Sung Won Lee, Jun Hyuk Hong, Nam Cheol Park, Je Jong Kim, Kwangsung Park, Hyesook Park, Jae Seog Hyun
Prevalence and risk factors for erectile dysfunction in Korean men: results of an epidemiological study.
J Sex Med. 2007 Sep;4(5):1269-76. doi: 10.1111/j.1743-6109.2007.00554.x. Epub 2007 Jul 17.
Abstract/Text INTRODUCTION: The prevalence of erectile dysfunction (ED) and associated risk factors has been described in many countries, but there are still only a few studies from Asia.
AIM: We investigated the prevalences of ED and premature ejaculation (PE) in Korean men and the impact of general health, lifestyle, and psychosocial factors on these conditions.
METHODS: To assess ED and PE, 1,570 Korean men aged 40-79 years were interviewed with a self-administered questionnaire on sexual function and the International Index of Erectile Function (IIEF)-5. In addition, blood chemistry was analyzed for each subject.
MAIN OUTCOME MEASURES: The prevalences of ED and PE were obtained from self-reported ED, IIEF-5 scoring, EF (erectile function) domain scoring, and self-reported intravaginal ejaculatory latency time (IELT). The data were analyzed for the presence of risk factors and the relationship of general health, lifestyle, and psychosocial factors with ED.
RESULTS: The prevalences of ED among Korean men were 13.4% (self-reported ED) and 32.4% (IIEF-5 score CONCLUSIONS: The prevalences of ED and PE in Korean men were 13.4% (self-reported ED) and 11% (IELT
PMID 17635695
Martin Miner, Kevin L Billups
Erectile dysfunction and dyslipidemia: relevance and role of phosphodiesterase type-5 inhibitors and statins.
J Sex Med. 2008 May;5(5):1066-78. doi: 10.1111/j.1743-6109.2008.00783.x. Epub 2008 Mar 5.
Abstract/Text INTRODUCTION: There is a close link between hyperlipidemia/dyslipidemia and erectile dysfunction (ED), with endothelial dysfunction as a common mechanism. Both ED and hyperlipidemia/dyslipidemia are rising in prevalence with mounting evidence that these conditions are harbingers of cardiovascular disease.
AIM: This review was conducted to provide an update on the epidemiology and oral therapy of both dyslipidemia and ED, the connection between these two conditions, and clinical outcomes relating to the use of statins and phosphodiesterase type-5 (PDE5) inhibitors in men with ED who have associated dyslipidemia.
METHODS: A systematic search was performed of MEDLINE and EMBASE research databases to obtain articles pertaining to the epidemiology, mechanism, and clinical outcomes of statins and PDE5 inhibitors in men with ED and associated dyslipidemia.
MAIN OUTCOME MEASURES: The clinical and preclinical studies related to ED and dyslipidemia are analyzed and their findings are assessed and summarized. Results. Hyperlipidemia/Dyslipidemia constitute a vascular risk factor having a considerable impact on erectile function. Furthermore, the role of endothelial dysfunction in the pathophysiology of both ED and dyslipidemia is paramount suggesting the importance of comanaging these conditions. Therefore, hyperlipidemia/dyslipidemia when present in patients with ED should prompt management with diet/exercise as well as appropriate pharmacotherapy. With ED being often associated with comorbidities, the use of concomitant pharmacotherapies enhances opportunities for managing the overall global cardiometabolic risk. Newer studies assessing the effect of PDE5 inhibitors in men with dyslipidemia will shed more light on the clinical profile of these agents when used in this patient population.
CONCLUSIONS: While dyslipidemia and ED are important concerns for clinicians, there exists a gap that needs to be closed between the number of individuals who have either or both conditions and those who are receiving appropriate therapy based on evidence and patient-driven goals regarding clinical outcomes.

PMID 18331271
K T McVary, S Carrier, H Wessells, Subcommittee on Smoking and Erectile Dysfunction Socioeconomic Committee, Sexual Medicine Society of North America
Smoking and erectile dysfunction: evidence based analysis.
J Urol. 2001 Nov;166(5):1624-32.
Abstract/Text PURPOSE: We examined available evidence concerning the role of smoking in the development of erectile dysfunction. This task involved a complete review of the smoking literature as it pertained to erectile dysfunction and select endothelial diseases.
MATERIALS AND METHODS: We comprehensively reviewed the literature, including PubMed and recent abstract proceedings from national meetings relevant to smoking, erectile dysfunction and endothelial diseases. The quality of the evidence was assessed by methods used to develop clinical practice guidelines. Our review involved an objective evaluation of the basic science literature and clinical studies. When necessary, we examined studies of endothelial diseases other than erectile dysfunction because of obvious gaps in the literature.
RESULTS: There are strong parallels and shared risks among smoking, coronary artery disease, atherosclerosis and erectile dysfunction. Clinical and basic science studies provide strong indirect evidence that smoking may affect penile erection by the impairment of endothelium dependent smooth muscle relaxation. The association of erectile dysfunction with risk factors such as coronary artery disease and hypertension appears to be amplified by cigarette smoking. Smoking may increase the likelihood of moderate or complete erectile dysfunction 2-fold. The prevalence of erectile dysfunction in former smokers was no different from that in individuals who had never smoked, implying that smoking cessation may decrease the risk of erectile dysfunction. Case studies and retrospective series have shown an association of smoking with erectile dysfunction.
CONCLUSIONS: Available evidence on the association of smoking with erectile dysfunction is not complete insofar as association linking factors are concerned. However, the evidence of such an association is likely due to the consistency of the relationship of smoking and endothelial disease, and the strength of the association of erectile dysfunction with other endothelial diseases.

PMID 11586190
M P Rosen, A J Greenfield, T G Walker, P Grant, J Dubrow, M A Bettmann, L E Fried, I Goldstein
Cigarette smoking: an independent risk factor for atherosclerosis in the hypogastric-cavernous arterial bed of men with arteriogenic impotence.
J Urol. 1991 Apr;145(4):759-63.
Abstract/Text We investigated the relationship between cigarette smoking and atherosclerosis of the hypogastric-cavernous arterial bed by evaluating arteriograms of young impotent men referred for selective pudendal angiography. Those patients with hemodynamically significant atherosclerosis had smoked more pack-years than had patients without arterial disease. These differences were statistically significant (p less than 0.05) for the common penile artery (32.8 pack-years, 40 patients versus 22.3 pack-years 57 patients) and the dorsal artery (31.3 pack-years, 48 patients versus 22.0 pack-years, 49 patients). The effect of cigarette smoking as an independent risk factor for atherosclerotic disease in the hypogastric-cavernous arterial bed was evaluated as well. When controlled for age, trauma history, hypertension and diabetes, cigarette smoking was independently associated with atherosclerosis in the internal pudendal artery (p less than 0.05). The relative risk (and 95% confidence interval) of developing internal pudendal artery atherosclerosis for each 10 pack-years smoked was 1.31 (1.05 to 1.64). A third analysis investigated the potential interactive effects of cigarette smoking and pelvic or perineal trauma. A significantly higher incidence (p less than 0.05) of cavernous artery atherosclerosis was found among smokers with a history of chronic perineal trauma (33 patients) compared to nonsmokers with a similar history (25 patients). The findings of this study indicate that cigarette smoking is an independent risk factor in the development of atherosclerotic lesions in the internal pudendal and common penile arteries of young impotent men. Cigarette smoking appears to predispose these patients to early atherosclerotic lesions in the cavernous artery following chronic perineal trauma.

PMID 2005695
M Hirshkowitz, I Karacan, J W Howell, M O Arcasoy, R L Williams
Nocturnal penile tumescence in cigarette smokers with erectile dysfunction.
Urology. 1992 Feb;39(2):101-7.
Abstract/Text We examined the relationship between cigarette smoking and erectile physiology in 314 men with erectile dysfunction. All of the men studied were currently cigarette smokers. Evaluations included interviews, physical examinations, and polysomnographic assessment of sleep-related erections. Penile rigidity during nocturnal erection inversely correlated with the number of cigarettes smoked per day. Smoking was also associated with indices of impairment on autonomic function tests and some measures of penile blood pressure. The group of men who smoked the most (more than 40 cigarettes per day) had the fewest minutes of nocturnal tumescence and detumesced fastest. These data are discussed with respect to the results of studies performed in dogs that demonstrated smoking-related reduction in arterial flow and venous restriction. Our findings suggest that smoking may further compromise penile physiology in men experiencing difficulty in maintaining erections long enough for satisfactory intercourse.

PMID 1736499
C Millett, L M Wen, C Rissel, A Smith, J Richters, A Grulich, R de Visser
Smoking and erectile dysfunction: findings from a representative sample of Australian men.
Tob Control. 2006 Apr;15(2):136-9. doi: 10.1136/tc.2005.015545.
Abstract/Text OBJECTIVES: To examine whether there is an association between smoking and erectile dysfunction in a representative sample of Australian men.
DESIGN: Secondary analysis of cross-sectional survey data from the Australian Study of Health and Relationships.
PARTICIPANTS: 8367 Australian men aged 16-59 years.
MAIN OUTCOME MEASURES: Erectile dysfunction was identified in men who reported having had trouble keeping an erection when they wanted to, a problem which persisted for at least one month over the previous year. Variables examined in multivariate logistic regression analyses included age, education, presence of cardiovascular disease and diabetes, and current alcohol and tobacco consumption.
RESULTS: Almost one in 10 of the respondents (9.1%) reported erectile dysfunction that lasted for at least one month over the previous year. More than a quarter (27.2%) of respondents were current smokers, with 20.9% smoking < or = 20 cigarettes per day, and 6.3% smoking > 20 cigarettes per day. Compared with non-smokers, the adjusted odds ratios for erectile dysfunction were 1.24 (95% confidence interval (CI) 1.01 to 1.52, p = 0.04) for those smoking < or = 20 cigarettes per day and 1.39 (95% CI 1.05 to 1.83, p = 0.02) for those smoking > 20 cigarettes per day, after adjusting for other confounding factors. Older age, low level of education, and taking medications for cardiovascular disease were also independently and positively associated with erectile dysfunction. In contrast, moderate alcohol consumption (1-4 drinks per day) significantly reduced the likelihood of having erectile dysfunction.
CONCLUSIONS: Erectile dysfunction is a significant health concern affecting around one in 10 Australian men aged 16-59 years. Current smoking is significantly associated with erectile dysfunction in Australian males. This association was strengthened as the number of cigarettes smoked increased. Health promotion programmes could use the link between smoking and erectile dysfunction to help reduce smoking levels among men.

PMID 16565463
T H Lam, A S M Abdullah, L M Ho, A W C Yip, S Fan
Smoking and sexual dysfunction in Chinese males: findings from men's health survey.
Int J Impot Res. 2006 Jul-Aug;18(4):364-9. doi: 10.1038/sj.ijir.3901436. Epub 2005 Dec 15.
Abstract/Text To describe the prevalence of erectile dysfunction (ED) and its association with smoking among the Chinese in Hong Kong, we conducted a cross-sectional study among 819 men (aged 31-60 years) who were randomly selected among the Hong Kong residents and interviewed by trained interviewers. A structured questionnaire was used for data collection. We found that current smokers who smoked 20 cigarettes or more daily had more dissatisfaction, erection difficulty and ED than never smokers. The prevalence of dissatisfaction, difficulty in erection and ED increased significantly (P<0.05) with increasing age. Compared with never-smokers, current smokers of more than 20 cigarettes daily had a greater risk of ED (age-adjusted odds ratio=1.47, 95% confidence interval: 1.00-2.16). Our results support that there are association between ED and smoking among the Chinese and suggest linking ED with smoking in the antismoking campaign and promoting smoking cessation to reduce ED among smokers.

PMID 16355108
Jane Y Polsky, Kristan J Aronson, Jeremy P W Heaton, Michael A Adams
Smoking and other lifestyle factors in relation to erectile dysfunction.
BJU Int. 2005 Dec;96(9):1355-9. doi: 10.1111/j.1464-410X.2005.05820.x.
Abstract/Text OBJECTIVE: To assess the association between erectile dysfunction (ED) and various lifestyle and medical factors, including smoking and cardiovascular disease (CVD) medications, among men attending urology clinics in Kingston, Canada.
SUBJECTS AND METHODS: We conducted a case-control study of men aged 50-80 years in Kingston, Ontario who agreed to participate at visits to urology clinics during 1997-99. We compared 101 men with clinically diagnosed ED and 234 controls with various benign urological conditions. All men completed a questionnaire on lifestyle and medical factors.
RESULTS: Men with ED were twice as likely to be former smokers (odds ratio 2.2, 95% confidence interval, 1.2-3.9), and cumulative smoking in pack-years suggests a dose-response pattern with the risk of ED. Having diabetes was associated with double the risk of ED, and increased alcohol intake appeared to increase the risk.
CONCLUSION: There was a greater risk of ED among former smokers, and the suggestion of a dose-response relationship with cumulative smoking.

PMID 16287457
A Nicolosi, D B Glasser, E D Moreira, M Villa, Erectile Dysfunction Epidemiology Cross National Study Group
Prevalence of erectile dysfunction and associated factors among men without concomitant diseases: a population study.
Int J Impot Res. 2003 Aug;15(4):253-7. doi: 10.1038/sj.ijir.3901010.
Abstract/Text We interviewed a population sample of 2412 men aged 40-70 y in Brazil, Italy, Japan and Malaysia about medical history, lifestyle habits and sexual behavior. Men were classified as having moderate or complete erectile dysfunction (ED) if they reported to be sometimes or never able to achieve and maintain an erection satisfactory for sexual intercourse, respectively. There were 1335 men with no diagnosis of cardiovascular or prostate diseases, diabetes, ulcer or depression, nor taking hormones. The prevalence of ED was 16.1%. ED was associated with age (the risk increased 8% per y), moderate (odds ratio (OR)=2.2) or severe (OR=4.9) lower urinary tract symptoms and smoking (OR=2.3 for >30 cigarettes/day). It was inversely associated with physical activity (OR=0.5) and higher educational levels. Between the ages of 40 and 70 y, almost one in six 'healthy' men is affected by ED. Further research should look at preclinical disease stages and genetic factors.

PMID 12934052
Varant Kupelian, Carol L Link, John B McKinlay
Association between smoking, passive smoking, and erectile dysfunction: results from the Boston Area Community Health (BACH) Survey.
Eur Urol. 2007 Aug;52(2):416-22. doi: 10.1016/j.eururo.2007.03.015. Epub 2007 Mar 16.
Abstract/Text INTRODUCTION: Although previous studies report an association between erectile dysfunction (ED) and smoking, few have examined the impact of passive smoke exposure on ED. This analysis examines the association of active and passive smoking and ED and investigates a dose-response effect of smoking.
METHODS: The Boston Area Community Heath (BACH) survey is a study of urologic symptoms in a racially and ethnically diverse population. BACH used a multistage stratified random sample to recruit 2301 men, aged 30-79 yr, from the city of Boston. ED was assessed using the five-item International Index of Erectile Function. Smoking and passive smoking were assessed by self-report. Analyses adjusted for sociodemographic and lifestyle factors and important chronic illnesses.
RESULTS: An association between smoking and ED was observed with a significant trend in increased risk of ED with cumulative pack-years of smoking (adjusted odds ratio [OR]=1.68; 95% confidence interval [CI], 1.03, 2.30 for > or =20 pack-years). Compared to never smokers not exposed to passive smoking, men who never smoked but were exposed to passive smoking had a moderate, statistically nonsignificant, increase in risk of ED (adjusted OR=1.33; 95%CI: 0.69, 2.55) comparable to the OR observed for a cumulative exposure of 10-19 pack-years of active smoking (adjusted OR=1.25; 95%CI, 0.68, 2.30).
CONCLUSIONS: Results indicate a dose-response association between smoking and ED with a statistically significant effect observed with > or =20 pack-years of exposure. Passive smoking is associated with a small, statistically nonsignificant increase in risk of ED comparable to approximately 10-19 pack-years of active smoking.

PMID 17383811
D M Mannino, R M Klevens, W D Flanders
Cigarette smoking: an independent risk factor for impotence?
Am J Epidemiol. 1994 Dec 1;140(11):1003-8.
Abstract/Text The authors sought to determine whether current cigarette smoking was associated with impotence among middle-aged men. This is a secondary analysis of a cross-sectional survey of 4,462 US Army Vietnam-era veterans aged 31-49 years who took part in the Vietnam Experience Study in 1985-1986. The main outcome measurement was the odds ratio for reported impotence, which was calculated by comparing current smokers with nonsmokers while controlling for multiple confounders. The study sample consisted of 1,162 never smokers, 1,292 former smokers, and 2,008 current smokers. The prevalence of impotence was 2.2% among never smokers, 2.0% among former smokers, and 3.7% among current smokers (p = 0.005). The unadjusted odds ratio (OR) of the association between smoking and reported impotence was 1.8 (95% confidence interval (CI) 1.2-2.6). The association held even after adjustments were made for confounders, including vascular disease, psychiatric disease, hormonal factors, substance abuse, marital status, race, and age (OR = 1.5, 95% CI 1.0-2.2). Neither years smoked nor cigarettes smoked daily were significant predictors of impotence in current smokers. The authors concluded that, among the men in this study, a higher percentage of cigarette smokers reported impotence than did nonsmokers. This observation could not be totally explained by comorbidity factors related to smoking.

PMID 7985647
A T Guay, J B Perez, G J Heatley
Cessation of smoking rapidly decreases erectile dysfunction.
Endocr Pract. 1998 Jan-Feb;4(1):23-6. doi: 10.4158/EP.4.1.23.
Abstract/Text OBJECTIVE: To assess the relationship between cessation of smoking and rapid improvement in erectile capacity as well as the effect of nicotine patches on nocturnal penile tumescence and rigidity.
METHODS: Nocturnal penile erections were studied in 10 smokers with use of the RigiScan portable home monitor. Two nights were monitored: for the first night, the patients had not stopped smoking; for the second night, the patients had stopped smoking for 24 hours. In addition, four men were monitored after cessation of smoking and wearing nicotine patches for 1 month.
RESULTS: Multiple variables studied showed a statistically significant improvement in nocturnal penile tumescence and rigidity in the men who had stopped smoking for 24 hours. Continued improvement was noted in the four men who were monitored while not smoking and wearing nicotine patches for 1 month.
CONCLUSION: Stopping cigarette smoking is a factor that rapidly improves penile tumescence and rigidity. Because the improvement continues while the patient is receiving nicotine from transdermal patches, some factor or factors other than the nicotine are responsible for the erectile dysfunction.

PMID 15251760
C A Derby, B A Mohr, I Goldstein, H A Feldman, C B Johannes, J B McKinlay
Modifiable risk factors and erectile dysfunction: can lifestyle changes modify risk?
Urology. 2000 Aug 1;56(2):302-6.
Abstract/Text OBJECTIVES: To prospectively examine whether changes in smoking, heavy alcohol consumption, sedentary lifestyle, and obesity are associated with the risk of erectile dysfunction.
METHODS: Data were collected as part of a cohort study of a random sample of men 40 to 70 years old, selected from street listings in the Boston Metropolitan Area, Massachusetts. In-home interviews were completed by 1709 men at baseline in 1987 to 1989 and 1156 men at follow-up in 1995 to 1997 (average follow-up 8.8 years). Analyses included 593 men without erectile dysfunction at baseline, who were free of prostate cancer, and had not been treated for heart disease or diabetes. The incidence of moderate to complete erectile dysfunction was determined by discriminant analysis of responses to a self-administered sexual function questionnaire.
RESULTS: Obesity status was associated with erectile dysfunction (P = 0.006), with baseline obesity predicting a higher risk regardless of follow-up weight loss. Physical activity status was associated with erectile dysfunction (P = 0.01), with the highest risk among men who remained sedentary and the lowest among those who remained active or initiated physical activity. Changes in smoking and alcohol consumption were not associated with the incidence of erectile dysfunction (P >0.3).
CONCLUSIONS: Midlife changes may be too late to reverse the effects of smoking, obesity, and alcohol consumption on erectile dysfunction. In contrast, physical activity may reduce the risk of erectile dysfunction even if initiated in midlife. Early adoption of healthy lifestyles may be the best approach to reducing the burden of erectile dysfunction on the health and well-being of older men.

PMID 10925098
Raymond C Rosen, William A Fisher, Ian Eardley, Craig Niederberger, Andrea Nadel, Michael Sand, Men's Attitudes to Life Events and Sexuality (MALES) Study
The multinational Men's Attitudes to Life Events and Sexuality (MALES) study: I. Prevalence of erectile dysfunction and related health concerns in the general population.
Curr Med Res Opin. 2004 May;20(5):607-17. doi: 10.1185/030079904125003467.
Abstract/Text OBJECTIVE: The aims of the Men's Attitudes to Life Events and Sexuality (MALES) study were to identify prevalence of erectile dysfunction (ED) and related health issues in the general male population in Europe, North and South America, and to examine the attitudes and behavior of men in relation to these health issues.
RESEARCH DESIGN AND METHODS: Phase I of the MALES study involved 27839 men aged 20-75 years who were interviewed in eight countries (United States, United Kingdom, Germany,France, Italy, Spain, Mexico, and Brazil) using a standardized questionnaire. Phase II of the MALES study involved 2912 men who were recruited from the sub-sample of Phase I MALES participants who reported ED together with additional men with ED recruited from other sources.
MAIN OUTCOME MEASURE: Prevalence of ED and associated attitudes.
RESULTS: The overall prevalence of ED in the MALES sample was 16%. ED prevalence varied markedly by country, however, from a high of 22%of men in the US reporting ED to a low of 10% in Spain. The prevalence of self-reported ED increased with increasing age. Men with co-morbid medical conditions and risk factors, including cardiovascular disease, hypertension, dyslipidemia,and depression all reported higher prevalence of ED. Men with ED also reported increased prevalence rates of these co-morbid conditions. MALES Phase II data indicated that among men who reported ED, 58% had actively sought medical attention for their condition; however, only 16% of men with ED were currently being treated with oral PDE-5 therapy.
CONCLUSIONS: The MALES study confirms the high prevalence rates of ED and its association with co-morbid medical conditions, such as diabetes and depression, reported in other large-scale, epidemiological studies. Despite the advent of oral phosphodiesterase inhibitors, only 58% of ED sufferers consult a physician about their problem, and only 16% of men with self-reported ED maintain their use of oral therapy.

PMID 15171225
François A Giuliano, Albert Leriche, Eric O Jaudinot, Anne Solesse de Gendre
Prevalence of erectile dysfunction among 7689 patients with diabetes or hypertension, or both.
Urology. 2004 Dec;64(6):1196-201. doi: 10.1016/j.urology.2004.08.059.
Abstract/Text OBJECTIVES: To survey the presence of, and attitudes toward, erectile dysfunction (ED) among patients with hypertension and/or diabetes mellitus who sought general medical care for any reason.
METHODS: The abbreviated five-item version of the International Index of Erectile Function (IIEF-5) was used to determine the presence of ED. A patient questionnaire was used to assess attitudes about ED.
RESULTS: We surveyed 7689 patients (mean +/- SD age 58.9 +/- 9.2 years), including 6719 (87%) in a stable sexual relationship. In patients with hypertension alone (n = 3906) and diabetes alone (n = 2377), ED was reported by 2379 (61%) and 1603 (67%) and was present in 2634 (67%) and 1677 (71%), respectively, as defined by an IIEF-5 score of less than 21. The corresponding mean scores were 12.0 (+/-4.6) and 11.5 (+/-4.6) in patients with ED and 20.5 (+/-3.6) and 20.2 (+/-3.8) in those without ED. Prevalence was affected by disease characteristics and history, and the number and type of antihypertensive medications. ED was reported by 924 (78%) of 1186 patients with both diseases and was present in 917 (77%) according to the IIEF-5 score. Overall, ED was reported by 5063 patients (66%) with hypertension and/or diabetes, was present in 5391 (70%) according to the IIEF-5 score, and increased in prevalence with age. ED was fairly to very bothersome in 4027 (80%) but untreated in 3312 (65%), of whom 2278 (69%) wanted treatment. Most of those wanting treatment would have welcomed discussion with their physician (1861 [82%] of 2278), and most wanted their physician to broach the subject (1292 [69%] of 1861).
CONCLUSIONS: Our study results have shown that patients with diabetes and/or hypertension have a high prevalence of bothersome untreated ED and want their general practitioner to initiate a discussion and provide treatment.

PMID 15596196
Pedro Aranda, Luis M Ruilope, Carlos Calvo, Manuel Luque, Antonio Coca, Angel Gil de Miguel
Erectile dysfunction in essential arterial hypertension and effects of sildenafil: results of a Spanish national study.
Am J Hypertens. 2004 Feb;17(2):139-45.
Abstract/Text BACKGROUND: The aim of this study was to establish the prevalence of erectile dysfunction (ED) in hypertensive patients in specialized care hypertension units (SCHUs) and to assess the effectiveness and tolerability of sildenafil treatment.
METHODS: This was a multicenter, prospective, open, observational pharmacoepidemiology study conducted in 25 Spanish SCHUs. A total of 2130 men with essential hypertension under treatment were recruited. In a second phase, 291 subjects with a score < or = 21 in the Sexual Health Inventory for Men (SHIM) received sildenafil (50 mg/day) as required 30 to 60 minutes before sexual activity, and were evaluated by the International Index of Erectile Function (IIEF).
RESULTS: A total of 975 subjects (45.8%) had a score < or = 21 in the SHIM. In the second phase, sildenafil improved the score in the erectile function domain in 232 patients (83.2%). Severity of ED significantly improved (P <.001); severe (22.3% to 7.7%), moderate (23% to 5.6%), and mild impairment (36.3% to 44.8%). The IIEF was normalized in 39.1% of patients who completed post-treatment IIEF. In all, 33 subjects (11.8%) failed to complete the study: two (0.7%) because of lack of efficacy, two (0.7%) intercurrent disease, 10 (3.6%) failure to return to the visits, three (1.1%) fear of therapy, four (1.4%) adverse effects requiring treatment discontinuation, and 12 (4.3%) protocol violations. No statistically significant association was found between the prevalence of adverse effects and antihypertensive treatment with single drug or combination therapy.
CONCLUSIONS: A high incidence of ED was found in hypertensive patients from Spanish SCHUs. Sildenafil showed an excellent response and safety profile.

PMID 14751656
Peter Sun, Ralph Swindle
Are men with erectile dysfunction more likely to have hypertension than men without erectile dysfunction? A naturalistic national cohort study.
J Urol. 2005 Jul;174(1):244-8. doi: 10.1097/01.ju.0000162050.84946.86.
Abstract/Text PURPOSE: : We examined whether men with erectile dysfunction (ED) are more likely to have hypertension than men without ED in a managed care setting.
MATERIALS AND METHODS: : We used a naturalistic cohort design to compare hypertension prevalence rates in 285,436 men with ED to that in 1,584,230 men without ED from 1995 through 2001. We also used a logistic regression model to isolate the effect of ED on the likelihood of hypertension after controlling for subject age, census regions and 9 concurrent diseases. The ED and the nonED cohort came from a nationally representative, managed care claims database that covers 51 health plans and 28 million members in the United States. Finally, the prevalence rate difference between members with and without ED, and the OR of having hypertension were calculated.
RESULTS: : The hypertension prevalence rate was 41.2% in men with ED and 19.2% in men without ED. After controlling for subject age, census region and 9 concurrent diseases the OR was 1.383 (p <0.0001), which implies that the odds for men with ED to have hypertension were 38.3% higher than the odds for men without ED.
CONCLUSIONS: : Men with ED were more likely to have hypertension than men without ED. This evidence supports the hypothesis that ED shares common risk factors with hypertension. It also suggests that men with ED and clinicians could use ED as an alerting signal to detect and treat undiagnosed hypertension earlier.

PMID 15947647
Charalambos Vlachopoulos, Konstantinos Aznaouridis, Nikolaos Ioakeimidis, Konstantinos Rokkas, Dorothea Tsekoura, Carmen Vasiliadou, Elli Stefanadi, Athanasios Askitis, Christodoulos Stefanadis
Arterial function and intima-media thickness in hypertensive patients with erectile dysfunction.
J Hypertens. 2008 Sep;26(9):1829-36. doi: 10.1097/HJH.0b013e3283050886.
Abstract/Text OBJECTIVE: Erectile dysfunction is a predictor of cardiovascular risk with high prevalence in hypertensive men. We investigated whether erectile dysfunction is related to arterial structure and function in hypertensive patients.
METHODS: We evaluated arterial structural and functional characteristics and measured systemic endothelial/inflammatory markers in 52 hypertensive men with vasculogenic erectile dysfunction and in 34 hypertensive men with normal erectile function, matched for age, blood pressure, risk factors and treatment.
RESULTS: Hypertensive patients with erectile dysfunction had higher common carotid intima-media thickness (0.95 +/- 0.19 vs. 0.83 +/- 0.18 mm, P = 0.003) and carotid-femoral pulse-wave velocity (8.89 +/- 1.38 vs. 8.11 +/- 1.10 m/s, P = 0.007), lower flow-mediated dilation of the brachial artery (absolute values of 2.96 +/- 1.64 vs. 4.07 +/- 1.68%, P = 0.003) and a higher level of the systemic endothelial dysfunction marker asymmetric dimethylarginine (0.67 +/- 0.13 vs. 0.57 +/- 0.16 mumol/l, P = 0.003), and the inflammatory markers high-sensitivity C-reactive protein [2.03 (1.16-2.89) vs. 1.23 (0.67-1.90) mg/l, P = 0.029] and interleukin-6 (4.13 +/- 2.38 vs. 2.77 +/- 1.92 pg/ml, P = 0.011). Multivariable analysis adjusting for age, mean pressure, other risk factors and treatment showed independent associations between erectile dysfunction and parameters of arterial structure and function. In the erectile dysfunction group, there were no significant relationships between the severity of erectile dysfunction (as expressed by the Sexual Health Inventory for Men score) and the above arterial indices and level of circulating markers (all P = NS).
CONCLUSION: In hypertensive men, the presence but not the severity of vasculogenic erectile dysfunction is associated with subclinical atherosclerosis, impairment of arterial function and systemic endothelial and inflammatory activation.

PMID 18698219
M Burchardt, T Burchardt, L Baer, A J Kiss, R V Pawar, A Shabsigh, A de la Taille, O R Hayek, R Shabsigh
Hypertension is associated with severe erectile dysfunction.
J Urol. 2000 Oct;164(4):1188-91.
Abstract/Text PURPOSE: The prevalence and severity of erectile dysfunction in patients with hypertension need to be further evaluated. We evaluate medical and hypertension status, and erectile function in patients with hypertension.
MATERIALS AND METHODS: The International Index of Erectile Function, which is a detailed questionnaire, including well established components to evaluate patient medical history, hypertension status and erectile dysfunction, was mailed to 476 male patients of the outpatient Hypertension Center of Columbia Presbyterian Medical Center.
RESULTS: The questionnaire was completed by 104 (22.3%) patients, and mean age was 62.2 years (range 34 to 75). Of the patients 84.8% were sexually active and 68. 3% had various degrees of erectile dysfunction, which was mild in 7. 7%, moderate in 15.4% and severe in 45.2%. Compared to the general population of erectile dysfunction cases in the literature our study population with hypertension had a higher incidence of severe erectile dysfunction. Although correlations of antihypertensive medications with incidence of erectile dysfunction did not reach statistical significance, there was a clear trend with patients treated with diuretics and beta-blockers having the highest incidence and those treated with alpha-blockers having the lowest incidence of erectile dysfunction.
CONCLUSIONS: In addition to the observation that erectile dysfunction is more prevalent in patients with hypertension than in an age matched general population, our study shows that it is more severe in those with hypertension than in the general population.

PMID 10992363
C B Johannes, A B Araujo, H A Feldman, C A Derby, K P Kleinman, J B McKinlay
Incidence of erectile dysfunction in men 40 to 69 years old: longitudinal results from the Massachusetts male aging study.
J Urol. 2000 Feb;163(2):460-3.
Abstract/Text PURPOSE: We estimated the incidence of erectile dysfunction in men 40 to 69 years old at study entry during an average 8.8-year followup, and determined how risk varied with age, socioeconomic status and medical conditions.
MATERIALS AND METHODS: Data from a randomly sampled population based longitudinal study of Massachusetts men were analyzed. A total of 1,709 men completed the baseline interview during 1987 to 1989 and 1,156 survivors completed followup from 1995 to 1997. The analysis sample consisted of 847 men without erectile dysfunction at baseline and with complete followup information. Erectile dysfunction was assessed by discriminant analysis of 13 questions from a self-administered sexual function questionnaire and a single global self-rating question.
RESULTS: The crude incidence rate for erectile dysfunction was 25.9 cases per 1,000 man-years (95% confidence interval [CI] 22.5 to 29.9). The annual incidence rate increased with each decade of age and was 12.4 cases per 1,000 man-years (95% CI 9.0 to 16.9), 29.8 (24.0 to 37.0) and 46.4 (36.9 to 58.4) for men 40 to 49, 50 to 59 and 60 to 69 years old, respectively. The age adjusted risk of erectile dysfunction was higher for men with lower education, diabetes, heart disease and hypertension. Population projections for men 40 to 69 years old suggest that 17,781 new cases of erectile dysfunction in Massachusetts and 617,715 in the United States (white males only) are expected annually.
CONCLUSIONS: Although prevalence estimates and cross-sectional correlates of erectile dysfunction have recently been established, incidence estimates were lacking. Incidence is necessary to assess risk, and plan treatment and prevention strategies. The risk of erectile dysfunction was about 26 cases per 1,000 men annually, and increased with age, lower education, diabetes, heart disease and hypertension.

PMID 10647654
Hideyuki Sasaki, Hiroshi Yamasaki, Kenichi Ogawa, Kishio Nanjo, Ryuzo Kawamori, Yasuhiko Iwamoto, Shigehiro Katayama, Masafumi Shirai
Prevalence and risk factors for erectile dysfunction in Japanese diabetics.
Diabetes Res Clin Pract. 2005 Oct;70(1):81-9. doi: 10.1016/j.diabres.2005.02.018. Epub 2005 Apr 15.
Abstract/Text We evaluated the prevalence and risk factors for erectile dysfunction (ED) and interest in ED treatment among Japanese men being treated for type 2 diabetes mellitus. Patients (40-79 years; n=1118) completed the 5-item version of the International Index of Erectile Function (IIEF-5), and questions related to interest in ED pharmacotherapy, subjective symptoms of diabetes, and general quality of life. A separate survey completed by physicians examined the relationships between age, diabetic treatments (insulin or oral), symptoms of diabetes (poor glycemic control, microangiopathy), complications of diabetes (hypertension, ischemic heart disease, cerebrovascular disease), and ED. The prevalence of ED in patients with diabetes was 90%, a rate double that of non-diabetic individuals. Multivariate analyses revealed that age, insulin therapy, microangiopathy, hypertension, history of cerebrovascular or cardiovascular disease, leg dysesthesia, dysuria, insomnia, and anorexia all represented significant risk factors for ED. Half of all respondents were interested (29%) or would consider pharmacotherapy for ED (21%). These findings suggest that ED is a significant problem in Japanese men with diabetes, and that specific risk factors increase the prevalence of ED. Furthermore, the survey results expose national attitudes toward treatment of ED.

PMID 16126126
Lasantha S Malavige, Jonathan C Levy
Erectile dysfunction in diabetes mellitus.
J Sex Med. 2009 May;6(5):1232-47. doi: 10.1111/j.1743-6109.2008.01168.x. Epub 2009 Feb 10.
Abstract/Text INTRODUCTION: Type 2 diabetes is reaching pandemic levels and young-onset type 2 diabetes is becoming increasingly common. Erectile dysfunction (ED) is a common and distressing complication of diabetes. The pathophysiology and management of diabetic ED is significantly different to nondiabetic ED.
AIM: To provide an update on the epidemiology, risk factors, pathophysiology, and management of diabetic ED.
METHOD: Literature for this review was obtained from Medline and Embase searches and from relevant text books.
MAIN OUTCOME MEASURES: A comprehensive review on epidemiology, risk factors, pathophysiolgy, and management of diabetic ED.
RESULTS: Large differences in the reported prevalence of ED from 35% to 90% among diabetic men could be due to differences in methodology and population characteristics. Advancing age, duration of diabetes, poor glycaemic control, hypertension, hyperlipidemia, sedentary lifestyle, smoking, and presence of other diabetic complications have been shown to be associated with diabetic ED in cross-sectional studies. Diabetic ED is multifactorial in aetiology and is more severe and more resistant to treatment compared with nondiabetic ED. Optimized glycaemic control, management of associated comorbidities and lifestyle modifications are essential in all patients. Psychosexual and relationship counseling would be beneficial for men with such coexisting problems. Hypogonadism, commonly found in diabetes, may need identification and treatment. Maximal doses of phosphodiesterase type 5 (PDE5) inhibitors are often needed. Transurethral prostaglandins, intracavenorsal injections, vacuum devices, and penile implants are the available therapeutic options for nonresponders to PDE5 inhibitors and for whom PDE5 inhibitors are contraindicated. Premature ejaculation and reduced libido are conditions commonly associated with diabetic ED and should be identified and treated.
CONCLUSIONS: Aetiology of diabetic ED is multifactorial although the relative significance of these factors are not clear. A holistic approach is needed in the management of diabetic ED.

PMID 19210706
G Corona, E Mannucci, L Petrone, V Ricca, G Balercia, R Mansani, V Chiarini, R Giommi, G Forti, M Maggi
Association of hypogonadism and type II diabetes in men attending an outpatient erectile dysfunction clinic.
Int J Impot Res. 2006 Mar-Apr;18(2):190-7. doi: 10.1038/sj.ijir.3901391.
Abstract/Text Patients with diabetes mellitus (DM) were more often hypogonadal than normal fasting glucose subjects. The aim of this investigation is the assessment of characteristics and psychobiological correlates of DM associated with hypogonadism (DMAH). The Structured Interview SIEDY was used along with several biochemical, psychological and instrumental investigations in a series of more than 1200 patients with erectile dysfunction (ED); 16% of whom with type II DM. Hypogonadism was defined as circulating total testosterone (T) below 10.4 nmol/l. The prevalence of hypogonadism was 24.5% in DM versus 12.6% in the rest of the sample (P < 0.0001); differences in the prevalence of hypogonadism retained significance after adjustment for age and BMI. DMAH was associated with typical hypogonadism-related symptoms, such as reduction in sexual desire, leading to a decreased number of sexual attempts, and with higher depressive symptomatology. In DMAH, testis size and LH concentrations were significantly reduced, suggesting a central origin of the disease. At penile Duplex ultrasound examination, diabetic patients and in particular hypogonadal type II diabetic patients showed lower levels of basal and dynamic (after PGE1 injection) peak systolic velocity and acceleration, when compared to the rest of the sample, even after adjustment for age and BMI. Our results show that hypogonadism is frequently associated with type II DM, at least in the 6th decade. DMAH might exacerbate sexual dysfunction by reducing libido and mood and further compromising penile vascular reactivity.

PMID 16136189
Carla Costa, Raquel Soares, Angela Castela, Sara Adães, Véronique Hastert, Pedro Vendeira, Ronald Virag
Increased endothelial apoptotic cell density in human diabetic erectile tissue--comparison with clinical data.
J Sex Med. 2009 Mar;6(3):826-35. doi: 10.1111/j.1743-6109.2008.01110.x. Epub 2008 Nov 27.
Abstract/Text INTRODUCTION: Erectile dysfunction (ED) is a common complication of diabetes. Endothelial cell (EC) dysfunction is one of the main mechanisms of diabetic ED. However, loss of EC integrity has never been assessed in human diabetic corpus cavernosum.
AIM: To identify and quantify apoptotic cells in human diabetic and normal erectile tissue and to compare these results with each patient's clinical data and erection status.
METHODS: Eighteen cavernosal samples were collected, 13 from diabetics with ED and 5 from nondiabetic individuals. Cavernosal structure and cell proliferation status were evaluated by immunohistochemistry. Tissue integrity was assessed by terminal transferase dUTP nick end labeling assay, an index of apoptotic cell density (ACD) established and compared with each patient age, type of diabetes, arterial risk factors number, arterial/veno-occlusive disease, response to intracavernous vasoactive injections (ICI), and penile nitric oxide release test (PNORT).
MAIN OUTCOME MEASURES: Establish an index of ACD and correlate those results with patient clinical data.
RESULTS: Nondiabetic samples presented few scattered cells in apoptosis and an ACD of 7.15 +/- 0.44 (mean apoptotic cells/tissue area mm(2) +/- standard error). The diabetic group showed an increased ACD of 23.82 +/- 1.53, and apoptotic cells were located specifically at vascular sites. Rehabilitation of these endothelial lesions seemed impaired, as no evidence of EC proliferation was observed. Furthermore, higher ACD in diabetic individuals correlated to poor response to PNORT and to ICI.
CONCLUSIONS: We provided evidence for the first time that loss of cavernosal EC integrity is a crucial event involved in diabetic ED. Furthermore, we were able to establish a threshold between ACD values and cavernosal tissue functionality, as assessed by PNORT and vasoactive ICI.

PMID 19067790
Carmine Gazzaruso, Stefano Giordanetti, Emanuela De Amici, Gianandrea Bertone, Colomba Falcone, Diego Geroldi, Pietro Fratino, Sebastiano B Solerte, Adriana Garzaniti
Relationship between erectile dysfunction and silent myocardial ischemia in apparently uncomplicated type 2 diabetic patients.
Circulation. 2004 Jul 6;110(1):22-6. doi: 10.1161/01.CIR.0000133278.81226.C9. Epub 2004 Jun 21.
Abstract/Text BACKGROUND: Erectile dysfunction (ED) is associated with coronary artery disease (CAD). In diabetic patients, CAD is often silent. Among diabetic patients with silent CAD, the prevalence of ED has never been evaluated. We investigated whether ED is associated with asymptomatic CAD in type 2 diabetic patients.
METHODS AND RESULTS: We evaluated the prevalence of ED in 133 uncomplicated diabetic men with angiographically verified silent CAD and in 127 diabetic men without myocardial ischemia at exercise ECG, 48-hour ambulatory ECG, and stress echocardiography. The groups were comparable for age and diabetes duration. Patients were screened for ED using the validated International Index of Erectile Function (IIEF-5) questionnaire. The prevalence of ED was significantly higher in patients with than in those without silent CAD (33.8% versus 4.7%; P=0.000). Multiple logistic regression analysis showed that ED, apolipoprotein(a) polymorphism, smoking, microalbuminuria, HDL, and LDL were significantly associated with silent CAD; among these risk factors, ED appeared to be the most efficient predictor of silent CAD (OR, 14.8; 95% CI, 3.8 to 56.9).
CONCLUSIONS: Our study first shows a strong and independent association between ED and silent CAD in apparently uncomplicated type 2 diabetic patients. If our findings are confirmed, ED may become a potential marker to identify diabetic patients to screen for silent CAD. Moreover, the high prevalence of ED among diabetics with silent CAD suggests the need to perform an exercise ECG before starting a treatment for ED, especially in patients with additional cardiovascular risk factors.

PMID 15210604
Carmine Gazzaruso, Sebastiano B Solerte, Arturo Pujia, Adriana Coppola, Monia Vezzoli, Fabrizio Salvucci, Cinzia Valenti, Andrea Giustina, Adriana Garzaniti
Erectile dysfunction as a predictor of cardiovascular events and death in diabetic patients with angiographically proven asymptomatic coronary artery disease: a potential protective role for statins and 5-phosphodiesterase inhibitors.
J Am Coll Cardiol. 2008 May 27;51(21):2040-4. doi: 10.1016/j.jacc.2007.10.069.
Abstract/Text OBJECTIVES: We sought to investigate whether erectile dysfunction (ED) is a predictor of future cardiovascular events and death in diabetic patients with silent coronary artery disease (CAD) and whether there are predictors of cardiovascular events and death among CAD diabetic patients with ED.
BACKGROUND: Case-control studies showed that ED is associated with CAD in diabetic patients, but no prospective study is available.
METHODS: Type 2 diabetic men (n = 291) with silent CAD angiographically documented were recruited. Erectile dysfunction was assessed by the International Index Erectile Function-5 questionnaire.
RESULTS: During a follow-up period of 47.2 +/- 21.8 months (range 4 to 82 months), 49 patients experienced major adverse cardiac events (MACE). The difference in ED prevalence between patients with and those without MACE was significant (61.2% vs. 36.4%; p = 0.001). Cox regression analysis showed that ED predicted MACE (hazard ratio [HR] 2.1; 95% confidence interval [CI] 1.6 to 2.6; p < 0.001). Among patients with CAD and ED, the Kaplan-Meier method showed that the statin (Mantel log-rank test: 3.921; p = 0.048) and 5-phosphodiesterase (5-PDE) inhibitor use (Mantel log-rank test: 4.608; p = 0.032) were associated with a lower rate of MACE. Cox regression analysis showed that statin use (HR 0.66; 95% CI 0.46 to 0.97; p = 0.036) reduced MACE. Treatment with 5-PDE inhibitors did not enter the model, but its p value was very near to the significant level (HR 0.68; 95% CI 0.46 to 1.01; p = 0.056).
CONCLUSIONS: Our data first show that ED is a powerful predictor of cardiovascular morbidity and mortality in diabetic patients with silent CAD and that the treatment with statins and 5-PDE inhibitors might reduce the occurrence of MACE among CAD diabetic patients with ED.

PMID 18498958
Kwanjin Park, Ja Hyun Ku, Soo Woong Kim, Jae-Seung Paick
Risk factors in predicting a poor response to sildenafil citrate in elderly men with erectile dysfunction.
BJU Int. 2005 Feb;95(3):366-70. doi: 10.1111/j.1464-410X.2005.05301.x.
Abstract/Text OBJECTIVE: To assess the clinical efficacy of sildenafil and the potential predictors of poor response to sildenafil in elderly patients with erectile dysfunction (ED).
PATIENTS AND METHODS: The study included 162 patients (aged > or = 60 years) treated with sildenafil for at least 8 weeks; all patients were evaluated with a history, physical examination, measurement of total testosterone and a pharmacological erection test. Sexual function before and 8 weeks after treatment was assessed using the self-administered International Index of Erectile Function (IIEF). Treatment was considered successful when the patient attained a higher grade on the erectile function (EF) domain score, and an affirmative response to the overall assessment question. Factors influencing treatment outcome were evaluated by univariate and multivariate statistical analysis.
RESULTS: The overall efficacy with sildenafil was 47% (76/162). On univariate analysis, uncontrolled diabetes, current smoking, hypogonadism (<3 microg/L testosterone) and low pretreatment EF domain score (<17) were selected as predictors of a poor response. On multivariate logistic regression, a low pretreatment EF domain score was the strongest independent prognostic factor for a poor response (odds ratio 2.25, 95% confidence interval, 1.45-7.33), and this was followed by hypogonadism (1.89, 1.12-3.16) and current smoking (1.34, 1.04-3.52).
CONCLUSION: In a real clinical setting, sildenafil was effective for about half of the elderly men. The baseline EF domain score, hypogonadism and current smoking were significantly associated with failure of sildenafil. These results suggest that modifying reversible risk factors, e.g. stopping smoking and replacing testosterone, would be beneficial in augmenting the efficacy of sildenafil in elderly men.

PMID 15679795
V Fonseca, A Seftel, J Denne, P Fredlund
Impact of diabetes mellitus on the severity of erectile dysfunction and response to treatment: analysis of data from tadalafil clinical trials.
Diabetologia. 2004 Nov;47(11):1914-23. doi: 10.1007/s00125-004-1549-6. Epub 2004 Nov 25.
Abstract/Text AIMS/HYPOTHESIS: A retrospective analysis of pooled data from twelve placebo-controlled trials was conducted to characterise the efficacy and safety of tadalafil for the treatment of erectile dysfunction in men with diabetes compared with that in men without diabetes.
METHODS: Patients were randomly allocated to tadalafil 10 mg, 20 mg, or placebo, taken as needed for 12 weeks. The study population comprised 637 men with diabetes (mean age 57 years) and 1681 men without diabetes (mean age 56 years).
RESULTS: At baseline, patients with diabetes had more severe erectile dysfunction than patients without diabetes, with mean International Index of Erectile Function (IIEF) erectile function domain scores of 12.6 and 15.0 respectively (p<0.001). Compared with placebo, tadalafil 10 mg and 20 mg improved all primary efficacy outcomes in both patient groups (p<0.001). Men with diabetes receiving tadalafil 20 mg experienced a mean improvement of 7.4 in their IIEF erectile function domain score against baseline versus 0.9 for placebo (p<0.001). This group reported on average that 53% of their attempts at intercourse were successful, compared with 22% for placebo (p<0.001 for the change from baseline). Baseline IIEF erectile function domain scores correlated inversely with baseline HbA(1)c levels. The responses to tadalafil were similar regardless of levels of baseline glycaemic control, diabetic therapy received, or previous use of sildenafil.
CONCLUSIONS/INTERPRETATION: Despite more severe baseline erectile dysfunction in men with diabetes, tadalafil was efficacious and well tolerated in this population. As reported for other phosphodiesterase 5 inhibitors, the response to tadalafil was slightly lower in men with diabetes than in men without diabetes.

PMID 15599697
K K Ng, H C P Lim, F C Ng, M K Li, D Consigliere, S J Chia, Perianan Moorthy, Malathy Munisamy
The use of sildenafil in patients with erectile dysfunction in relation to diabetes mellitus--a study of 1,511 patients.
Singapore Med J. 2002 Aug;43(8):387-90.
Abstract/Text Erectile dysfunction (ED) seriously impairs the quality of life. Patients with diabetes mellitus (DM) are prone to ED due to various factors, including vasculopathy, neuropathy and sex hormone abnormalities. This is a retrospective study involving 1,511 patients taking sildenafil. Patients with DM have significantly more comorbidities like hypertension and ischaemic heart disease. They are also more likely to be on medications which may affect erectile function, including various antihypertensive drugs. 77.9% of patients with DM reported success with sildenafil, as compared to 86.5% of patients without DM. A significant number of patients with DM require a higher dose of sildenafil as compared to those without DM.

PMID 12507022
M A Vickers, R Satyanarayana
Phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction in patients with diabetes mellitus.
Int J Impot Res. 2002 Dec;14(6):466-71. doi: 10.1038/sj.ijir.3900910.
Abstract/Text Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, has become a first-line therapy for diabetic patients with erectile dysfunction (ED). The efficacy in this subgroup, based on the Global Efficacy Question, is 56% vs 84% in a selected group of non-diabetic men with ED. Two novel PDE5 inhibitors, tadalafil (Lilly ICOS) and vardenafil (Bayer), have recently completed efficacy and safety clinical trials in 'general' and diabetic study populations and are now candidates for US FDA approval. A summary analysis of the phase three clinical trials of sildenafil, tadalafil and vardenafil in both study populations is presented to provide a foundation on which the evaluation of the role of the individual PDE5 inhibitors for the treatment of patients with ED and DM can be built.

PMID 12494279
David F Penson, David M Latini, Deborah P Lubeck, Katrine L Wallace, James M Henning, Tom F Lue, Comprehensive Evaluation of Erectile Dysfunction (ExCEED) database
Do impotent men with diabetes have more severe erectile dysfunction and worse quality of life than the general population of impotent patients? Results from the Exploratory Comprehensive Evaluation of Erectile Dysfunction (ExCEED) database.
Diabetes Care. 2003 Apr;26(4):1093-9.
Abstract/Text OBJECTIVE: Little is known regarding how diabetic men with erectile dysfunction (ED) differ from the general population of impotent men. The primary objective of this study was to compare disease-specific health-related quality of life (HRQOL) and severity of ED in impotent men with and without diabetes.
RESEARCH DESIGN AND METHODS: Validated functional and HRQOL questionnaires (including the International Index of Erectile Function, the Sexual Self-Efficacy Scale, and the Psychological Impact of Erectile Dysfunction scales) were administered to patients in an ED disease registry. Men with ED and a history of diabetes (n = 20) were compared with men with ED and no history of diabetes (n = 90) at baseline and at the 12-month follow-up.
RESULTS: Diabetic impotent men reported worse erectile function and intercourse satisfaction at baseline, and ED had a greater impact on their emotional life. Diabetic men with ED had significantly different trends over time in the Erectile Function (P < 0.001), Intercourse Satisfaction (P < 0.013), Sexual Desire (P < 0.016), Overall Satisfaction (P < 0.023), and the Sexual Experience-Psychological Impact domains (P < 0.002). In addition, there was a trend toward a difference over time in the Emotional Life-Psychological Impact domain (P < 0.067).
CONCLUSIONS: Impotent men with diabetes present with worse ED than nondiabetic men with ED, resulting in worse disease-specific HRQOL in the diabetic men. Although diabetic patients initially respond well to ED treatment, responses do not appear to be durable over time. Therefore, clinicians must provide longer-term follow-up when treating ED in diabetic patients.

PMID 12663579
J Y W Cheng, E M L Ng, J S N Ko, R Y L Chen
Physical activity and erectile dysfunction: meta-analysis of population-based studies.
Int J Impot Res. 2007 May-Jun;19(3):245-52. doi: 10.1038/sj.ijir.3901521. Epub 2006 Aug 24.
Abstract/Text We searched for population-based cross-sectional studies, cohort studies and randomized controlled trials (RCTs) on erectile dysfunction (ED) through Medline, PubMed, PsychInfo and scanned though reference lists. Studies that did not include adjusted odds ratios (OR) of physical activity were excluded. Seven cross-sectional studies were suitable for meta-analysis, and the results from one cross-section study, two cohort studies and one RCT were summarized. Pooling the ORs using random effects models, we derived summary estimate for adjusted OR of physical activity in those with ED compared with those without ED, which was 0.53 (0.31, 0.91). Moderate and high physical activities were associated with a lower risk of ED, with ORs at 0.63 (0.43, 0.93) and 0.42 (0.22, 0.82), respectively. Funnel plot by visual inspection, and Begg's test and Egger's test did not detect significant publication bias. Sensitivity analyses revealed that the summary estimate from the random effects model was robust to changes in study sample size and level of statistical adjustment, but not so robust to changes in ED definition, although the summary estimate for each ED definition did not differ significantly. Although causality cannot be demonstrated from cross-sectional studies, the apparent 'protective' effect of physical activity on ED should be further investigated using large-scale cohort studies or RCTs.

PMID 16929337
Frank Sommer, Irwin Goldstein, Joanna Beate Korda
Bicycle riding and erectile dysfunction: a review.
J Sex Med. 2010 Jul;7(7):2346-58. doi: 10.1111/j.1743-6109.2009.01664.x. Epub 2010 Jan 19.
Abstract/Text INTRODUCTION: For many years, reports in the literature have implicated bicycle riding as causing increased risk of erectile dysfunction (ED). Perineal compression during cycling has been associated with the development of sexual complications.
AIM: To review current literature on the rationale for ED from bicycle riding and outcome of bicycle riding on erectile function and to present available research on preventative measures specifically regarding bicycle riding.
METHODS: A systematic comprehensive literature review.
RESULTS: There is a significant relationship between cycling-induced perineal compression leading to vascular, endothelial, and neurogenic dysfunction in men and the development of ED. Research on female bicyclists is very limited but indicates the same impairment as in male bicyclists. Preventative measures including use of a properly fitted bicycle, a riding style with a suitable seat position and an appropriate bicycle seat can help prevent impairment of erectile function.
CONCLUSIONS: There is a need for further research on safe bicycle and bicycle seat design and investigations that address the underlying mechanisms leading to cycling-related sexual dysfunction in both male and female bicyclists.

PMID 20102446
Katherine Esposito, Francesco Giugliano, Carmen Di Palo, Giovanni Giugliano, Raffaele Marfella, Francesco D'Andrea, Massimo D'Armiento, Dario Giugliano
Effect of lifestyle changes on erectile dysfunction in obese men: a randomized controlled trial.
JAMA. 2004 Jun 23;291(24):2978-84. doi: 10.1001/jama.291.24.2978.
Abstract/Text CONTEXT: Healthy lifestyle factors are associated with maintenance of erectile function in men.
OBJECTIVE: To determine the effect of weight loss and increased physical activity on erectile and endothelial functions in obese men.
DESIGN, SETTING, AND PATIENTS: Randomized, single-blind trial of 110 obese men (body mass index > or =30) aged 35 to 55 years, without diabetes, hypertension, or hyperlipidemia, who had erectile dysfunction that was determined by having a score of 21 or less on the International Index of Erectile Function (IIEF). The study was conducted from October 2000 to October 2003 at a university hospital in Italy.
INTERVENTIONS: The 55 men randomly assigned to the intervention group received detailed advice about how to achieve a loss of 10% or more in their total body weight by reducing caloric intake and increasing their level of physical activity. Men in the control group (n = 55) were given general information about healthy food choices and exercise.
MAIN OUTCOMES MEASURES: Erectile function score, levels of cholesterol and triglycerides, circulating levels of interleukin 6, interleukin 8, and C-reactive protein, and endothelial function as assessed by vascular responses to l-arginine.
RESULTS: After 2 years, body mass index decreased more in the intervention group (from a mean [SD] of 36.9 [2.5] to 31.2 [2.1]) than in the control group (from 36.4 [2.3] to 35.7 [2.5]) (P<.001), as did serum concentrations of interleukin 6 (P =.03), and C-reactive protein (P =.02). The mean (SD) level of physical activity increased more in the intervention group (from 48 [10] to 195 [36] min/wk; P<.001) than in the control group (from 51 [9] to 84 [28] min/wk; P<.001). The mean (SD) IIEF score improved in the intervention group (from 13.9 [4.0] to 17 [5]; P<.001), but remained stable in the control group (from 13.5 [4.0] to 13.6 [4.1]; P =.89). Seventeen men in the intervention group and 3 in the control group (P =.001) reported an IIEF score of 22 or higher. In multivariate analyses, changes in body mass index (P =.02), physical activity (P =.02), and C-reactive protein (P =.03) were independently associated with changes in IIEF score.
CONCLUSION: Lifestyle changes are associated with improvement in sexual function in about one third of obese men with erectile dysfunction at baseline.

PMID 15213209
J Khoo, C Piantadosi, S Worthley, G A Wittert
Effects of a low-energy diet on sexual function and lower urinary tract symptoms in obese men.
Int J Obes (Lond). 2010 Sep;34(9):1396-403. doi: 10.1038/ijo.2010.76. Epub 2010 Apr 20.
Abstract/Text OBJECTIVE: Abdominal obesity and type 2 diabetes mellitus are associated with erectile and urinary dysfunction in men. The extent to which sexual function and lower urinary tract symptoms (LUTSs) are improved by weight loss remains unclear.
SUBJECTS: We compared the effects of 8 weeks of a low-calorie diet using meal replacements (Kicstart) on insulin sensitivity, plasma testosterone levels, erectile function (measured by the five-item version of the International Index of Erectile Function, IIEF-5), sexual desire (measured by the Sexual Desire Inventory, SDI) and LUTS (measured by the International Prostate Symptom Score, IPSS), in abdominally obese (body mass index >or=30 kg m(-2), waist circumference (WC) >or=102 cm) men (mean age 49.7 years) with uncomplicated diet or oral hypoglycemic-treated type 2 diabetes mellitus (n = 19) or without type 2 diabetes mellitus (n=25), with a control group of nondiabetic men (n = 26) with similar body mass index and WC.
RESULTS: Weight loss of ∼ 10% was significantly associated with increased insulin sensitivity, plasma testosterone levels, IIEF-5 and SDI scores, as well as reduced WC and IPSS scores, in diabetic as well as nondiabetic men. The degree of weight loss was significantly associated with improvements in plasma testosterone levels (r = -0.34), erectile function (r = -0.26) and LUTS (r=0.65). Reduction in LUTS was significantly associated with increased plasma testosterone (r = -0.35), erectile function (r = -0.42) and sexual desire (r = -0.40).
CONCLUSIONS: Diet-induced weight loss significantly and rapidly improves sexual function, and reduces LUTS, in obese middle-aged men with or without diabetes.

PMID 20404829
Giuseppe Maio, Salim Saraeb, Antonio Marchiori
Physical activity and PDE5 inhibitors in the treatment of erectile dysfunction: results of a randomized controlled study.
J Sex Med. 2010 Jun;7(6):2201-8. doi: 10.1111/j.1743-6109.2010.01783.x. Epub 2010 Mar 30.
Abstract/Text INTRODUCTION: Physical activity (PhA) has proven to be a protective factor for normal erectile function in numerous epidemiological studies.
AIM: The aim of this study was to establish if PhA could have a therapeutic role in the treatment of erectile dysfunction (ED).
METHODS: This was a randomized, open-label study. A total of 60 patients complaining of ED were studied. Patients were assessed at baseline and after 3 months of study treatment. At baseline, patients were randomized to receive phosphodiesterase type 5 inhibitor (PDE5i) alone (group A) or PDE5i plus regular (≥3 hours/week), aerobic, non-agonistic PhA (group B).
MAIN OUTCOME MEASURES: All subjects completed the International Index of Erectile Function (IIEF-15) questionnaire and performed total testosterone (TT).
RESULTS: Mean PhA was 3.4 hours/week in group B vs. 0.43 in group A; mean energy expenditure in group B was 1,868 kcal/ week or 22.8 metabolic equivalent (MET)/week. IIEF restoration of ED occurred in 77.8% (intervention group) vs. 39.3% (control) (P < 0.004). The IIEF-15 score resulted in statistical improvement in intervention group in all the domains but one (orgasm): erectile function 24.7 vs. 26.8 (P = 0.003); confidence (Q15) 3.53 vs. 4.07 (P = 0.006); sexual desire 6.46 vs. 7.18 (P = 0.028); intercourse satisfaction 9.85 vs. 11.25 (P = 0.001); total satisfaction 7.17 vs. 8.07 (P = 0.009); total score 56.2 vs. 61.07 (P = 0.007). TT was statistically similar in the two groups; separate analysis in each group showed statistical increase in group B 4.24 vs. 4.55 (P = 0.012). At multivariate logistic regression analysis, PhA was the only independent variable for normal erection (P = 0.010) (95% confidence interval [CI] 0.036-0.643), higher sexual satisfaction (P = 0.022) (95% CI 0.084-0.821) and normal total IIEF-15 score (P = 0.023) (95% CI 0.85-0.837).
CONCLUSION: In this randomized controlled pilot study, PDE5i plus PhA was more effective than PDE5i alone in the treatment of ED.

PMID 20367777
A B Araujo, R Durante, H A Feldman, I Goldstein, J B McKinlay
The relationship between depressive symptoms and male erectile dysfunction: cross-sectional results from the Massachusetts Male Aging Study.
Psychosom Med. 1998 Jul-Aug;60(4):458-65.
Abstract/Text OBJECTIVE: Studies have shown that there is an association between depression and male erectile dysfunction (MED). However. these earlier studies suffer considerable methodological flaws including: a) lack of a multidisciplinary approach; b) poor sampling techniques; and finally, c) poor and variable measures of MED and depression. Our objectives are: a) to determine whether MED is associated with depressive symptoms and b) to determine whether this association is independent of aging and para-aging factors.
METHOD: Data were obtained from the Massachusetts Male Aging Study (MMAS). The MMAS was a cross-sectional, population-based multidisciplinary survey of health in normally aging men (aged 40-70 years) conducted from 1986 to 1989. In the analytic model, depressive symptoms, as measured by a score of 16 or greater on the Center for Epidemiological Studies-Depression (CES-D) scale, was used as a predictor of MED, which was assessed with a self-administered questionnaire.
RESULTS: MED was associated with depressive symptoms after controlling for potential confounders (odds ratio (OR) 1.82, 95% confidence interval (Ct) 1.21-2.73).
CONCLUSIONS: We conclude that the relationship between depressive symptoms and MED in middle-aged men is robust and independent of important aging and para-aging confounders, such as demographic, anthropometric and lifestyle factors, health status, medication use, and hormones.

PMID 9710291
R Shabsigh, L T Klein, S Seidman, S A Kaplan, B J Lehrhoff, J S Ritter
Increased incidence of depressive symptoms in men with erectile dysfunction.
Urology. 1998 Nov;52(5):848-52.
Abstract/Text OBJECTIVES: To investigate the hypothesis that men with erectile dysfunction (ED) have a higher incidence of depressive symptoms compared with age-matched control subjects. We also hypothesized that depressive symptoms impact on the level of libido and on the success of treatment of ED.
METHODS: One hundred twenty men with ED or benign prostatic hyperplasia (BPH) were divided into three groups. Group 1 had ED only, group 2 had BPH only, and group 3 had both ED and BPH. Patients were screened for depressive symptoms using the Primary Care Evaluation of Mental Disorders and the Beck Depression Inventory. They were also surveyed for comorbidity, marital status, severity of ED, level of libido, prior ED treatment choice (if any), success of treatment, and others.
RESULTS: One hundred patients completed the questionnaires. Depressive symptoms were reported by 26 (54%) of 48 men with ED alone, 10 (56%) of 18 men with ED and BPH, and 7 (21 %) of 34 men with BPH alone. Patients with ED were 2.6 times more likely to report depressive symptoms than men with BPH alone (P < 0.005). Patients with depressive symptoms reported lower libido than other patients (P < 0.0001). Severity of comorbidities did not differ among the three groups. A total of 33 patients with ED had prior treatment for ED using penile injections or vacuum devices. All 15 (100%) patients with ED only continued treatment and were satisfied with its outcome, whereas only 7 (38.9%) of 18 patients with ED and depressive symptoms continued treatment (P < 0.00021).
CONCLUSIONS: ED is associated with high incidence of depressive symptoms, regardless of age, marital status, or comorbidities. Patients with ED have a decreased libido compared with control subjects. In addition, patients with depressive symptoms have a lower libido than patients without depressive symptoms. Patients with ED and depressive symptoms are more likely to discontinue treatment for ED than other patients with ED. These data emphasize the importance of a multidisciplinary approach to the treatment of erectile dysfunction.

PMID 9801112
R Shabsigh, L Zakaria, A G Anastasiadis, A S Seidman
Sexual dysfunction and depression: etiology, prevalence, and treatment.
Curr Urol Rep. 2001 Dec;2(6):463-7.
Abstract/Text Sexual dysfunction and depression are very common conditions that are age-related and chronic. In men, epidemiologic studies have confirmed a strong correlation between erectile dysfunction and symptoms of depression. Both conditions have a significant negative impact on the quality of life of patients and their partners. Several studies showed that restoration of normal sexual function improves the quality of life of patients and their partners, regardless of treatment method. The literature review and recent observations emphasize the multifactorial nature of sexual dysfunction and, more specifically, erectile dysfunction and underline the importance of the comorbidity and bidirectional relationship between erectile dysfunction and depression. Research is progressing on the possible link between andropause, sexual dysfunction, and depression, thus opening potential new opportunities to address issues of aging-related morbidities.

PMID 12084232
Julia Strand, Thomas N Wise, Peter J Fagan, Chester W Schmidt
Erectile dysfunction and depression: category or dimension?
J Sex Marital Ther. 2002 Mar-Apr;28(2):175-81. doi: 10.1080/00926230252851906.
Abstract/Text Depression, as a risk factor for erectile dysfunction (ED), has received minimal systematic attention. One-hundred twenty men with ED evaluated in a sexual behaviors clinic were studied. The categorical Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) diagnosis of a depressive disorder was found in only 14 subjects (14.7%). Dimensional quantification of depression was measured with the Brief Symptom Inventory (BSI). The BSI data revealed clinically significant elevations of depression and other dysphoric affects. The presence of a comorbid medical diagnosis did not affect the rates of categorical diagnosis of depression or the dimensional levels. The five factors of personality in the NEO-PI were within normal range. The data demonstrates that men with ED are affectively distressed but infrequently meet criteria for categorical DSM-IV depression.

PMID 11894799
L R Derogatis, J K Meyer, K M King
Psychopathology in individuals with sexual dysfunction.
Am J Psychiatry. 1981 Jun;138(6):757-63.
Abstract/Text The literature contains contradictory reports on the psychiatric status of individuals with sexual dysfunction. As a step toward resolving the controversy the authors administered the SCL-90-R to a large series of patients who sought treatment for sexual disorders (N = 325). Psychiatric evaluations were also done for each patient. Results showed disproportionate levels of psychological distress, reflected in SCL-90-R symptom profiles; approximately one-third of the 199 men and one-half of the 126 women in the series were also assigned psychiatric diagnoses. Findings provided evidence suggesting that the various sexual dysfunctions have characteristic symptom profiles; however, interpretation should be cautious because the cause-and-effect relationship between psychological distress and sexual dysfunctions remains complex and uncharted.

PMID 7246804
Hiroki Sugimori, Katsumi Yoshida, Toshiaki Tanaka, Katsuyuki Baba, Takayasu Nishida, Ryuto Nakazawa, Teruaki Iwamoto
Relationships between erectile dysfunction, depression, and anxiety in Japanese subjects.
J Sex Med. 2005 May;2(3):390-6. doi: 10.1111/j.1743-6109.2005.20354.x.
Abstract/Text AIMS: This study aimed to elucidate the relationships between erectile dysfunction (ED) and depression or anxiety.
METHODS: Subjects were 1,419 Japanese men aged 40-64 years. ED was assessed by the International Index of Erectile Function 5 (IIEF-5) score (Japanese version), and depression and anxiety symptoms were assessed by the Hospital Anxiety and Depression Scale (HADS). In this study ED cases were defined as those whose IIEF-5 value was less than 12, and a score of 8 or higher was used to classify a subject as suffering from depression or anxiety, respectively. The prevalence odds ratio (OR) of ED was calculated with confidence interval (CI) estimated by the Woolf's method by five age groups (40-44, 45-49, 50-54, 55-59, 60-64 years). To control for age, body mass index, smoking, and alcohol drinking factors, we conducted the multivariate logistic regression analysis for calculating adjusted ORs and 99% CIs.
RESULTS: ED was significantly associated with depression in age groups 45-49 (OR 3.42, 99% CI 1.51-7.76) and 50-54 years (OR 2.43, 99% CI 1.11-5.35). After using multivariate analysis, adjusted OR also showed statistical significance. (OR 2.02, 99% CI 1.32-3.08). ED was significantly associated with anxiety in the 50-55-year-old age group (OR 2.48, 99% CI 1.12-5.47). After using multivariate analysis, adjusted OR also showed statistical significance (OR 1.77, 99% CI 1.15-2.72). The concomitant depression and anxiety group (A+D+) had significantly higher prevalence of ED than the control group (A-D-) in both the 45-49 and 50-54 age groups. (P < 0.01)
CONCLUSION: ED associated significantly with depression and anxiety status only in late 40s to early 50s (45-55 years) in male Japanese. Furthermore, comorbidities of depression and anxiety strengthen this association. Our results might be useful in furthering understanding of ED etiology and determining a target population for prevention in ED subjects.

PMID 16422871
Giovanni Corona, Valdo Ricca, Elisa Bandini, Edoardo Mannucci, Luisa Petrone, Alessandra D Fisher, Francesco Lotti, Giancarlo Balercia, Carlo Faravelli, Gianni Forti, Mario Maggi
Association between psychiatric symptoms and erectile dysfunction.
J Sex Med. 2008 Feb;5(2):458-68. doi: 10.1111/j.1743-6109.2007.00663.x. Epub 2007 Nov 14.
Abstract/Text INTRODUCTION: Erectile dysfunction (ED) is often associated with a wide array of psychiatric symptoms, although few studies systematically address their specific association with ED determinants.
AIM: The aim of this study is to explore the relationship between ED (as assessed by SIEDY Structured Interview, a 13-item tool which identifies and quantifies the contribution of organic, relational, and intrapsychic domains of ED) and different psychopathological symptoms (as assessed by the Middlesex Hospital Questionnaire, a self-reported test for the screening of mental disorders in a nonpsychiatric setting).
METHODS: A consecutive series of 1,388 (mean age 51 +/- 13 years) male patients with ED was studied.
MAIN OUTCOME MEASURES: Several hormonal and biochemical parameters were investigated, along with SIEDY Interview and the Middlesex Hospital Questionnaire.
RESULTS: Psychiatric symptoms resulted differentially associated with SIEDY domains. Depressive and phobic-anxiety symptoms were associated with the relational domain, somatization with the organic one, while free-floating anxiety, obsessive-compulsive, and phobic symptoms were significantly related with higher intrapsychic SIEDY scores. In addition, relevant depressive symptomatology was associated with hypogonadism, the presence of low frequency of intercourse, hypoactive sexual desire (HSD), and conflictual relationships within the couple and the family. Patients with high free-floating anxiety symptoms were younger, and complained of an unsatisfactory work and a conflictual relationship within family. Conversely, subjects with higher phobic anxious symptoms displayed a more robust relational functioning. Similar results were observed in subjects with obsessive-compulsive symptoms, who also reported a lower prevalence of HSD. Finally, subjects with somatization symptoms showed the worst erectile function.
CONCLUSIONS: The main value of this study is that it alters various clinicians' belief that many psychiatric symptoms can be found among ED patients. Systematic testing of patients with ED, through psychiatric questionnaires, is recommended to detect even slight or moderate psychopathological distresses, which specifically associate and exacerbate sexual disturbances.

PMID 18004996
Stuart N Seidman
Exploring the relationship between depression and erectile dysfunction in aging men.
J Clin Psychiatry. 2002;63 Suppl 5:5-12; discussion 23-5.
Abstract/Text Normal sexual function is a biopsychosocial process; sexual dysfunction almost always has organic and psychological components and requires multidisciplinary, goal-directed evaluation and treatment. Factors such as aging, declining testosterone levels, medical illness, certain medications. and comorbid depressive illness can contribute to sexual dysfunction. Erectile dysfunction is one of the more common male sexual dysfunctions encountered in the clinical setting. Comorbidity between erectile dysfunction and depressive illness is high, but the causal relationship is unclear. The psychosocial distress that often accompanies erectile dysfunction might stimulate the development of depressive illness, or, as some data suggest, depression might cause erectile dysfunction. This article reviews the literature on the relationship between depression and erectile dysfunction, as well as the design of a new study that may provide some answers, and concludes that erectile dysfunction is a common, treatable condition that may cause or be the result of depression. Recent data suggest that sildenafil is an effective treatment for erectile dysfunction in men with comorbid depression. Erectile dysfunction should be considered a multifactorial condition that may require a multidisciplinary approach to treatment, especially when depression is present.

PMID 11964139
Mireille Bonierbale, Christophe Lançon, Jean Tignol
The ELIXIR study: evaluation of sexual dysfunction in 4557 depressed patients in France.
Curr Med Res Opin. 2003;19(2):114-24. doi: 10.1185/030079902125001461.
Abstract/Text OBJECTIVES: This survey was conducted in order to determine the extent and nature of disorders of sexual function in depressed patients treated in the community in France.
METHODS: Patients with DSM-IV major depressive episodes were included. The inclusion criteria stipulated that only patients with no antecedents of sexual dysfunction could be included. Information on sexual function was collected with a questionnaire which included physician observations as well as the Arizona Sexual Experience Scale.
RESULTS: Overall, 4557 patients were included in the study. The prevalence of disorders of sexual function observed was 35% for spontaneously reported problems and 69% for problems identified by physician questioning. Impaired sexual function in depressed patients is also revealed by a high score on the Arizona Sexual Experience Scale (mean overall score of 21.4). Frequency of sexual dysfunction was somewhat higher in patients treated with antidepressants than in untreated patients (71% and 65% respectively). Treatment with tianeptine was associated with a lower incidence of sexual dysfunction than was treatment with tricyclic antidepressants or with selective serotonin reuptake inhibitors. Although in 39% of cases, physicians managed the sexual problems encountered by changing the antidepressant treatment, the most frequently adopted approach (42% of cases) was to await spontaneous remission. Drug holidays or adjunctive therapy were very rarely proposed.
CONCLUSIONS: The prevalence of sexual dysfunction in patients with major depression is high. Antidepressant drugs appear to aggravate such problems, with certain classes of drug better tolerated than others. Sexual dysfunction in depressed patients is often not optimally treated.

PMID 12740155
S N Seidman, S P Roose, M A Menza, R Shabsigh, R C Rosen
Treatment of erectile dysfunction in men with depressive symptoms: results of a placebo-controlled trial with sildenafil citrate.
Am J Psychiatry. 2001 Oct;158(10):1623-30.
Abstract/Text OBJECTIVE: Depressed men commonly have erectile dysfunction, and men with erectile dysfunction are frequently depressed. Since the etiologic and modulatory relationships between depression and erectile dysfunction have been poorly characterized, a 12-week, randomized, double-blind, placebo-controlled trial was conducted at 20 urologic clinics to evaluate the effects of sildenafil treatment in men with erectile dysfunction and mild-to-moderate comorbid depressive illness.
METHOD: Men (N=152, mean age=56 years) with erectile dysfunction for > or =6 months (mean=5.7 years), a DSM-IV diagnosis of depressive disorder not otherwise specified, and a Hamilton Depression Rating Scale score > or =12 (mean at baseline=16.9) were randomly assigned to flexible-dose treatment with sildenafil citrate or matching placebo. Interviewer-rated and self-report instruments were used to assess changes in sexual function, depressive symptoms, and quality of life. Conservative criteria were used to classify erectile dysfunction treatment response and nonresponse.
RESULTS: Sildenafil was strongly associated with erectile dysfunction treatment response. Fifty-eight men met the conservative criteria for response (48 given sildenafil, 10 given placebo), and 78 men did not respond (18 given sildenafil, 60 given placebo). Mean decreases of 10.6 and 2.3 in Hamilton depression scale scores were seen in treatment responders and nonresponders, respectively; 76% of treatment responders showed a > or =50% decline in Hamilton depression scale score versus 14% of nonresponders. Quality of life was similarly improved in treatment responders.
CONCLUSIONS: Sildenafil is efficacious for erectile dysfunction in men with mild-to-moderate depressive illness. Improvement of erectile dysfunction is associated with marked improvement in depressive symptoms and quality of life.

PMID 11578994
Raymond Rosen, Jens Altwein, Peter Boyle, Roger S Kirby, B Lukacs, Eric Meuleman, Michael P O'Leary, Paolo Puppo, Chris Robertson, Francois Giuliano
Lower urinary tract symptoms and male sexual dysfunction: the multinational survey of the aging male (MSAM-7).
Eur Urol. 2003 Dec;44(6):637-49.
Abstract/Text OBJECTIVES: Lower urinary tract symptoms (LUTS), which are often caused by benign prostatic hypertrophy (BPH), and sexual dysfunction are common in older men, with an overall prevalence of >50% in men aged > or =50 years. Men with LUTS have been reported to experience sexual dysfunction, including ejaculatory loss, painful ejaculation, and erectile dysfunction. This study was conducted to investigate the relationship between LUTS and sexual problems in aging men.
METHODS: A large-scale, multinational survey was conducted in the US and six European countries to systematically investigate the relationship between LUTS and sexual dysfunction in older men. Detailed questionnaires were mailed to a national representative sample of men aged 50 to 80 years in each country. Selection was made on the basis of age, occupation, geographic region, and population density. LUTS and sexual function were assessed by validated symptom scales, including the International Prostate Symptom Score, the Danish Prostatic Symptom Score, and the International Index of Erectile Function. Subjects also completed a health and demographics questionnaire.
RESULTS: A total of 34,800 surveys were mailed out, 14,254 were completed and returned, and 12,815 were deemed evaluable and included in the analysis. Results were consistent from one country to another. Although 90% of the men had LUTS, only 19% had sought medical help for urinary problems and only 11% were medically treated. Sexual activity was reported by 83% of the sample, with 71% reporting at least one episode of sexual activity during the previous 4 weeks. Sexual disorders and their bothersomeness were strongly related to both age and severity of LUTS. The relationship between sexual problems and LUTS is independent of comorbidities such as diabetes, hypertension, cardiac disease, and hypercholesterolemia.
CONCLUSIONS: Sexual activity is common in a majority of men over age 50 and is an important component of overall quality of life. The presence and severity of LUTS are independent risk factors for sexual dysfunction in older men. These results highlight the clinical importance of evaluating LUTS in patients with sexual dysfunction, and the need to consider sexual issues in the management of patients with benign prostatic hypertrophy.

PMID 14644114
Abstract/Text Lower urinary tract symptoms (LUTS) and sexual dysfunction are highly prevalent in aging men. Both conditions also are significant contributors to overall quality of life. New data have emerged to indicate potential links in epidemiological, physiologic, pathophysiologic, and treatment aspects of these two entities. There are numerous publications based on sophisticated community and clinical-based data, suggesting a strong and consistent association between LUTS and erectile dysfunction (ED). The association is supported by the consistent linear relationship of more severe LUTS with more severe ED. The link between ED and LUTS has biologic plausibility given the four leading theories of how these diseases inter-relate.

PMID 15260924
R D Mann, P Biswas, S Freemantle, G Pearce, L Wilton
The pharmacovigilance of tamsulosin: event data on 12484 patients.
BJU Int. 2000 Mar;85(4):446-50.
Abstract/Text OBJECTIVE: To determine drug effectiveness and adverse effects in a noninterventional observational cohort study of over 10 000 patients treated with tamsulosin in general medical practice.
METHODS: Using prescription-event monitoring, data were collected of all prescriptions for tamsulosin issued nationally during June 1996 to January 1998. For each patient entered into the cohort a computerized longitudinal record of exposure was constructed. The outcome data, patient information and an opinion about the effectiveness of the drug were provided by the prescriber, using a standard questionnaire sent 6 months after the initial prescription for tamsulosin. The incidence of each of almost 2000 events listed in the Drug Safety Research Unit computerized dictionary was calculated and scrutinized by medical assessors for possible adverse reactions, and any difference determined between the incidence of each event in the first month and subsequent months of exposure. All deaths were followed up to detect possibly drug-related causes.
RESULTS: Event data were obtained on 12484 patients, from the 52.9% of questionnaires returned and that contained valid event data. Tamsulosin was reported to have been effective in 7428 (78.3%) of the 9487 patients in whom the general practitioners expressed an opinion about effectiveness. Suspected adverse drug reactions were reported in only 171 (1.4%) of the cohort. Dizziness, headache, malaise and hypotension were common to the reported adverse reactions, reasons for stopping the drug and events of greatest incidence density. None of the 282 deaths that occurred in this elderly cohort were attributed to the drug.
CONCLUSION: This study suggests that tamsulosin has a highly acceptable benefit-to-risk ratio. No untoward features not already mentioned in the prescribing guidance were identified.

PMID 10691824
Kazuki Kawabe, Masaki Yoshida, Yukio Homma, Silodosin Clinical Study Group
Silodosin, a new alpha1A-adrenoceptor-selective antagonist for treating benign prostatic hyperplasia: results of a phase III randomized, placebo-controlled, double-blind study in Japanese men.
BJU Int. 2006 Nov;98(5):1019-24. doi: 10.1111/j.1464-410X.2006.06448.x. Epub 2006 Aug 31.
Abstract/Text OBJECTIVE: To verify the efficacy and safety of the new alpha1A-adrenoceptor-selective antagonist silodosin compared with tamsulosin and placebo in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).
PATIENTS AND METHODS: This randomized, double-blind, placebo-controlled study was conducted at 88 centres in Japan. Men aged > or = 50 years with an International Prostate Symptom Score (IPSS) of > or = 8, a quality-of-life (QoL) score of > or = 3, a maximum urinary flow rate (Qmax) of < 15 mL/s, a prostate volume of > or = 20 mL and a postvoid residual urine volume of < 100 mL were eligible for enrolment. Patients were randomized to receive silodosin 4 mg twice daily, tamsulosin 0.2 mg once daily, or placebo, for 12 weeks. The primary endpoint was the change in IPSS from baseline. Safety was assessed by adverse events, physical examination, vital signs and laboratory tests.
RESULTS: In all, 457 patients were randomized (silodosin 176, tamsulosin 192 and placebo 89). The change in the total IPSS from baseline in the silodosin, tamsulosin and placebo groups was -8.3, -6.8 and -5.3, respectively. There was a significant decrease in the IPSS vs placebo in the silodosin group from 1 week. In the early-stage comparison, silodosin showed a significant decrease in IPSS vs tamsulosin at 2 weeks. The change in QoL from baseline was -1.7, -1.4 and -1.1 in the silodosin, tamsulosin and placebo groups, respectively; silodosin showed a significant improvement in the QoL score vs placebo. In the subgroup of patients with severe symptoms (IPSS > or = 20) silodosin also gave a significantly better improvement than placebo (-12.4 vs -8.7). The incidence rates of adverse events and drug-related adverse events were, respectively, 88.6%, 82.3% and 71.6% and 69.7%, 47.4% and 36.4%, respectively. The most common adverse event in the silodosin group was abnormal ejaculation, which occurred more often in the silodosin than in the tamsulosin group (22.3% vs 1.6%). However, only five men (2.9%) discontinued treatment for abnormal ejaculation.
CONCLUSION: Silodosin was generally effective in the absence of obtrusive side-effects. This study suggests that silodosin is clinically useful for treating LUTS associated with BPH.

PMID 16945121
Abstract/Text OBJECTIVE: The objective of this paper is to examine safety and tolerability data from a number of recently completed clinical trials with the novel, dual 5alpha-reductase inhibitor, dutasteride.
METHODS: Intent-to-treat analyses were conducted on data for dutasteride 0.5 mg/day for drug-related adverse events, clinical laboratory test results, and prostate-specific antigen (PSA) levels derived from four large, randomised, double-blind clinical trials (n=5655). Further data were derived from a randomised, double-blind combination study of dutasteride 0.5 mg/day and tamsulosin 0.4 mg/day (n=327), and several safety studies conducted in healthy volunteers.
RESULTS: Data from two-year blinded clinical studies demonstrate that dutasteride is well tolerated, with a profile comparable with that of placebo. The exception is a modestly elevated incidence of impotence, decreased libido, ejaculation disorders, and gynaecomastia. Clinical laboratory test abnormalities were reported by <1% of patients treated with dutasteride, and abnormal values occurred with similar frequency versus placebo-treated patients. In a healthy volunteer study, when dutasteride was administered daily for 1 year, it did not significantly affect bone metabolism markers, bone mineral density or lipid profiles. Dutasteride reduced total serum PSA concentrations by approximately 50% following 6, 12, and 24 months of treatment but had no effect on free-to-total PSA levels. The safety profile of dutasteride did not differ from that of finasteride in a large, parallel-group, comparator trial. Additionally, when dutasteride was used in combination with an alpha(1)-blocker, the drug-related adverse event profiles were as would be expected for the individual agents.
CONCLUSIONS: Considered together, these data demonstrate dutasteride to be well-tolerated.

PMID 12814679
Taiji Tsukamoto, Yukihiro Endo, Michiro Narita
Efficacy and safety of dutasteride in Japanese men with benign prostatic hyperplasia.
Int J Urol. 2009 Sep;16(9):745-50. doi: 10.1111/j.1442-2042.2009.02357.x. Epub 2009 Aug 5.
Abstract/Text OBJECTIVES: To assess the efficacy and safety of dutasteride in Japanese men with benign prostatic hyperplasia (BPH).
METHODS: This was a randomized, double-blind, placebo-controlled, parallel-group study. A total of 378 subjects with clinical BPH having an International Prostate Symptom Score (IPSS) of 8 points or greater, a prostate volume of 30 mL or greater, and a maximal urinary flow rate (Qmax) of 15 mL/s or less were randomized to receive placebo or dutasteride once daily for 52 weeks. Subjects were stratified according to tamsulosin use at baseline. The numbers of subjects with and without tamsulosin use were 242 and 136, respectively. IPSS, Qmax, prostate volume and drug safety were evaluated.
RESULTS: Continued improvement in IPSS was noted in the dutasteride group, and dutasteride significantly decreased IPSS compared with placebo. At week 52, dutasteride significantly improved Qmax and prostate volume compared with placebo. Drug-related sexual function events in the dutasteride group were infrequent and generally were not treatment limiting.
CONCLUSIONS: Dutasteride improves urinary symptoms and flow rate and reduces prostate volume. In Japanese men with BPH, it is effective and generally well tolerated during the one-year treatment period.

PMID 19674165
Kevin T McVary, William Monnig, Joseph L Camps, Jay M Young, Li-Jung Tseng, Gene van den Ende
Sildenafil citrate improves erectile function and urinary symptoms in men with erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia: a randomized, double-blind trial.
J Urol. 2007 Mar;177(3):1071-7. doi: 10.1016/j.juro.2006.10.055.
Abstract/Text PURPOSE: We evaluated sildenafil for erectile dysfunction and lower urinary tract symptoms in men with the 2 conditions.
MATERIALS AND METHODS: This was a 12-week, double-blind, placebo controlled study of sildenafil in men 45 years or older who scored 25 or less on the erectile function domain of the International Index of Erectile Function and 12 or greater on the International Prostate Symptom Score. Men with confirmed or suspected prostate malignancy, or prostate specific antigen 10 ng/ml or more were excluded. End points were changes in International Index of Erectile Function domain scores, International Prostate Symptom Score (irritative, obstructive and quality of life), the Benign Prostatic Hyperplasia Impact Index, the Self-Esteem And Relationship questionnaire and Erectile Dysfunction Inventory of Treatment Satisfaction Index Score.
RESULTS: The 189 men receiving sildenafil had significant improvements in erectile function domain score vs the 180 on placebo (9.17 vs 1.86, p<0.0001) and on all other International Index of Erectile Function domains. In men on sildenafil vs placebo significant improvements were observed in International Prostate Symptom Score (-6.32 vs -1.93, p<0.0001), Benign Prostatic Hyperplasia Impact Index (-2.0 vs -0.9, p<0.0001), mean International Prostate Symptom Score quality of life score (-0.97 vs -0.29, p<0.0001) and total Self-Esteem And Relationship questionnaire scores (24.6 vs 4.3, p<0.0001). There was no difference in urinary flow between the groups (p=0.08). Significantly more sildenafil vs placebo treated patients were satisfied with treatment (71.2 vs 41.7, p<0.0001). Sildenafil was well tolerated.
CONCLUSIONS: Improved erectile dysfunction and lower urinary tract symptoms with sildenafil in men with the 2 conditions were associated with improved quality of life and treatment satisfaction. Daily dosing with sildenafil may improve lower urinary tract symptoms. However, the lack of effect on urinary flow rates may mean that a new basic pathophysiology paradigm is needed to explain the etiology of lower urinary tract symptoms.

PMID 17296414
Kevin T McVary, Claus G Roehrborn, Jed C Kaminetsky, Stephen M Auerbach, Barton Wachs, Jay M Young, Anne Esler, Gregory D Sides, Bela S Denes
Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia.
J Urol. 2007 Apr;177(4):1401-7. doi: 10.1016/j.juro.2006.11.037.
Abstract/Text PURPOSE: We assessed the efficacy and safety of tadalafil dosed once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia.
MATERIALS AND METHODS: Following a 4-week, single-blind, placebo run-in 281 men were randomly assigned (1:1) to 5 mg tadalafil for 6 weeks, followed by dose escalation to 20 mg for 6 weeks or 12 weeks of placebo.
RESULTS: Tadalafil significantly improved the mean change from baseline in International Prostate Symptom Score at 6 weeks (5 mg tadalafil -2.8 vs placebo -1.2) and at 12 weeks (5/20 mg tadalafil -3.8 vs placebo -1.7). Larger changes were observed with inclusion of the placebo run-in at 12 weeks (5/20 mg tadalafil -7.1 vs placebo -4.5). Significant improvements were also seen in the International Prostate Symptom Score irritative and obstructive domains, the International Prostate Symptom Score quality of life index, a question about urinary symptom improvement and the Benign Prostatic Hyperplasia Impact Index (significant at 12 weeks) vs placebo. International Prostate Symptom Score and International Index of Erectile Function erectile function domain scores significantly improved in the 56% of men with lower urinary tract symptoms/benign prostatic hyperplasia who were sexually active and had erectile dysfunction. Changes in uroflowmetry parameters were similar in the placebo and tadalafil groups. Commonly reported (2% or greater) treatment emergent adverse events were "erection increased," dyspepsia, back pain, headache, nasopharyngitis and upper respiratory tract infection (each 5.1% or less). No change in post-void residual volume was seen with tadalafil treatment.
CONCLUSIONS: Tadalafil once daily was well tolerated and demonstrated clinically meaningful and statistically significant symptomatic improvement for lower urinary tract symptoms/benign prostatic hyperplasia. Tadalafil also improved erectile function in men with lower urinary tract symptoms and erectile dysfunction.

PMID 17382741
Christian G Stief, Hartmut Porst, Dieter Neuser, Manfred Beneke, Ernst Ulbrich
A randomised, placebo-controlled study to assess the efficacy of twice-daily vardenafil in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia.
Eur Urol. 2008 Jun;53(6):1236-44. doi: 10.1016/j.eururo.2008.01.075. Epub 2008 Feb 4.
Abstract/Text INTRODUCTION: Benign prostatic hyperplasia (BPH) is associated with bothersome lower urinary tract symptoms (LUTS) and reduced patient quality of life (QoL). Phosphodiesterase (type) 5 (PDE5) inhibitors such as vardenafil are commonly used for the treatment of erectile dysfunction (ED), but have also been shown to improve the symptoms of BPH. This randomised, double-blind, placebo-controlled study investigated the effects of vardenafil on LUTS and QoL in men with BPH/LUTS, with or without concomitant ED.
METHODS: Men aged 45-64 yr with BPH/LUTS and an International Prostate Symptom Score (IPSS) > or =12 were randomised to receive either 10mg vardenafil or placebo twice daily. LUTS were assessed with the use of two primary efficacy parameters, IPSS score and maximum urinary flow rate (Qmax), as well as postvoid residual (PVR) urine volume; ED was measured with the use of the erectile function (EF) domain score of the International Index of Erectile Function (IIEF-EF); and QoL was assessed with the Urolifetrade mark QoL-9 questionnaire.
RESULTS: After 8 wk of treatment, there was a significant improvement in the IPSS total score in the vardenafil group compared with placebo (-5.9 and -3.6, respectively; p=0.0013). Nominally significant improvements in irritative and obstructive IPSS subscores (p=0.0017 and p=0.0081, respectively), EF (p=0.0001), and Urolife QoL-9 (p<0.0001) were also associated with vardenafil treatment. Qmax and PVR urine volume did not change significantly with treatment, although baseline values were already considered close to normal. Vardenafil was generally well tolerated, with most adverse events considered mild or moderate in severity.
CONCLUSIONS: Vardenafil treatment significantly improved LUTS, EF, and QoL in men with BPH/LUTS. Vardenafil may be considered a promising treatment option for men with symptoms secondary to BPH.

PMID 18281145
J H Wasson, D J Reda, R C Bruskewitz, J Elinson, A M Keller, W G Henderson
A comparison of transurethral surgery with watchful waiting for moderate symptoms of benign prostatic hyperplasia. The Veterans Affairs Cooperative Study Group on Transurethral Resection of the Prostate.
N Engl J Med. 1995 Jan 12;332(2):75-9. doi: 10.1056/NEJM199501123320202.
Abstract/Text BACKGROUND: Transurethral resection of the prostate is the most common surgical treatment for benign prostatic hyperplasia. We conducted a multicenter randomized trial to compare this surgery with watchful waiting in men with moderate symptoms of benign prostatic hyperplasia.
METHODS: Of 800 men over the age of 54 years who were screened between July 1986 and July 1989, 556 (mean [+/- SD] age, 66 +/- 5 years) were studied (280 in the surgery group and 276 in the watchful-waiting group). Patients' symptoms and the degree to which they were bothered by urinary difficulties were measured with standardized questionnaires and medical evaluations. The primary outcome measure was treatment failure, which was defined as the occurrence of any of the following: death, repeated or intractable urinary retention, a residual urinary volume over 350 ml, the development of bladder calculus, new and persistent incontinence, a high symptom score, or a doubling of the serum creatinine concentration. Patients were followed for three years.
RESULTS: Of the men randomly assigned to the surgery group, 249 underwent surgery within two weeks after the assignment. Surgery was not associated with impotence or urinary incontinence. The average follow-up period was 2.8 years. In an intention-to-treat analysis, there were 23 treatment failures in the surgery group, as compared with 47 in the watchful-waiting group (relative risk, 0.48; 95 percent confidence interval, 0.30 to 0.77). Of the men assigned to the watchful-waiting group, 65 (24 percent) underwent surgery within three years after the assignment. Surgery was associated with improvement in symptoms and in scores for urinary difficulties and interference with activities of daily living (P < 0.001 for all comparisons). The outcomes of surgery were best for the men who were most bothered by urinary symptoms at base line.
CONCLUSIONS: For men with moderate symptoms of benign prostatic hyperplasia, surgery is more effective than watchful waiting in reducing the rate of treatment failure and improving genitourinary symptoms. Watchful waiting is usually a safe alternative for men who are less bothered by urinary difficulty or who wish to delay surgery.

PMID 7527493
Y Arai, Y Aoki, K Okubo, H Maeda, N Terada, Y Matsuta, S Maekawa, K Ogura
Impact of interventional therapy for benign prostatic hyperplasia on quality of life and sexual function: a prospective study.
J Urol. 2000 Oct;164(4):1206-11.
Abstract/Text PURPOSE: Treatment for benign prostatic hyperplasia (BPH), including minimally invasive therapy, can impair the quality of life. We prospectively determined the impact of 4 different interventional therapies on quality of life and sexual function.
MATERIALS AND METHODS: A total of 173 patients were prospectively evaluated between February 1995 and August 1997. Treatment modalities consisted of standard transurethral resection of the prostate in 55 cases, transurethral microwave thermotherapy in 34, interstitial laser coagulation of the prostate in 42 and transurethral needle ablation in 42. Disease specific quality of life was assessed using the International Prostate Symptom Score quality of life assessment index and BPH impact index. In addition, a self-reporting questionnaire was completed before and 3 months after treatment to determine the impact on sexual function.
RESULTS: All 4 treatment groups showed significant improvement in the symptom score, International Prostate Symptom Score quality of life assessment score and BPH impact index score. Satisfaction with treatment was highest in patients treated with transurethral resection or laser coagulation. A mild to moderate decrease in erectile function was noted in 26.5%, 18.2%, 18.4% and 20.0% of the transurethral resection, microwave thermotherapy, laser coagulation and needle ablation groups, respectively, but there was no significant difference of mean pretreatment and posttreatment erectile function or libido scores in any group. Ejaculation loss or severe decrease in ejaculate volume was reported by 48.6%, 28.1%, 21.6% and 24.3% of the patients, respectively. Interestingly, 20 of the 44 patients (45. 5%) with loss of ejaculation or severe decrease in ejaculate reported deterioration of the sex life, while only 2 (3.6%) of the 56 without any change in ejaculate volume reported such deterioration. The association of ejaculatory dysfunction with an adverse impact on sexual activity was highly significant (p <0.0001).
CONCLUSIONS: Significant improvement in quality of life could be achieved with the present assessed interventional therapies. There was no significant change in sexual desire or erectile function with these therapies. Posttreatment sexual dysfunction appears to be mainly related to impaired ejaculatory function. Urologists should provide proper counseling regarding the possibility of this complication even in patients receiving minimally invasive treatment.

PMID 10992367
H H J Leliefeld, H J Stoevelaar, J McDonnell
Sexual function before and after various treatments for symptomatic benign prostatic hyperplasia.
BJU Int. 2002 Feb;89(3):208-13.
Abstract/Text OBJECTIVE: To determine the effect of various treatments for benign prostatic hyperplasia (BPH) on sexual function.
PATIENTS AND METHODS: In a longitudinal multicentre study carried out in the Netherlands, 670 consecutive patients with BPH (aged > or = 50 years) were examined at baseline and 9 months after inclusion. All patients completed a questionnaire about symptomatology, bothersomeness and sexual function before and after treatment. Other diagnostic information was retrieved from the medical records.
RESULTS: At baseline, 49-59% of the population (mean age 66 years) reported normal potency and 69% a normal libido. Outcomes at 9 months were stratified by type of treatment, i.e. surgery in 207, alpha-blockers in 43, finasteride in 47 and watchful waiting in 234 men. Patients with multiple or other treatments (131) or recent surgery (eight) were excluded from the analyses. For the four sexual items included, 84% of the patients reported no changes. All treatments showed both improvement and deterioration in 3-14% and 0-16% of the patients, respectively.
CONCLUSION: For sexual function, most patients remained stable after treatment for BPH, while positive and negative changes occurred in equal proportions for all treatments. These results question the previously reported high incidence of sexual adverse events, particularly after surgical intervention.

PMID 11856100
Sara T Brookes, Jenny L Donovan, Tim J Peters, Paul Abrams, David E Neal
Sexual dysfunction in men after treatment for lower urinary tract symptoms: evidence from randomised controlled trial.
BMJ. 2002 May 4;324(7345):1059-61.
Abstract/Text OBJECTIVE: To examine the impact on sexual function of treatments for lower urinary tract symptoms in men.
DESIGN: Multicentre pragmatic randomised controlled trial of standard surgery (transurethral resection of the prostate), non-contact laser therapy, and conservative management (no active intervention).
SETTING: Three clinical centres in the United Kingdom.
PARTICIPANTS: 340 men aged between 48 and 90 years with lower urinary tract symptoms related to benign prostatic enlargement.
MAIN OUTCOME MEASURES: ICSsex questionnaire items concerned with erectile stiffness, ejaculatory volume, pain or discomfort on ejaculation, whether sex life was spoilt by urinary symptoms.
RESULTS: Erectile and ejaculatory dysfunction were common (70%) and problematic at baseline and showed the expected trends with ageing. After treatment, reduced ejaculation was reported in all groups but was not significantly worse after standard surgery than after laser therapy. Erectile function was significantly improved after standard surgery; no significant difference was found between standard surgery and laser therapy (odds ratio 0.70, 95% confidence interval 0.36 to 1.38). Standard surgery was significantly better at relieving pain or discomfort on ejaculation than either conservative management (0.06, 0.007 to 0.49) or laser therapy (0.09, 0.01 to 0.73).
CONCLUSIONS: Compared with laser therapy standard surgery for lower urinary tract symptoms has a beneficial effect on aspects of sexual function-particularly in improving erectile function and reducing reported pain or discomfort on ejaculation. Older men who need treatment and want to retain or improve sexual function may thus want to consider standard surgery rather than non-contact laser therapy.

PMID 11991908
M Jaidane, N B Arfa, W Hmida, A Hidoussi, A Slama, N B Sorba, F Mosbah
Effect of transurethral resection of the prostate on erectile function: a prospective comparative study.
Int J Impot Res. 2010 Mar-Apr;22(2):146-51. doi: 10.1038/ijir.2009.56. Epub 2009 Nov 26.
Abstract/Text The effect of transurethral resection of the prostate (TURP) on erectile function is still controversial, and available evidence is conflicting. One of the possible mechanisms of post-TURP erectile dysfunction (ED) is direct thermal injury to the erectile nerves. The aim of this study was to investigate the effect of TURP on erectile function. Fifty patients undergoing TURP for obstructive benign prostatic hyperplasia (HBP) were prospectively included in the study, and 50 age-matched patients undergoing transurethral resection of the superficial bladder tumor were also prospectively included as a control group. All patients completed the international index of erectile function (IIEF-15), the international prostatic symptom score (IPSS) and the Hospital Anxiety and Depression Scale at inclusion in the study and then at the 3- and 6-month follow-up evaluation. Capsular perforations during TURP were prospectively reported by the operating surgeon. There was a significant improvement of erectile function in the TURP group despite the onset of ejaculation disorders in 70% of the patients. Improvement of erectile function was also found in the subgroup of patients with capsular perforation during TURP. Comparison with the control group showed that at preoperative evaluation, patients in the TURP group had more severe urinary symptoms and worse erectile function than did those of the control group. At the postoperative period, the IPSS score became comparable in the two groups, with major improvement of erectile function in the TURP group. We concluded that TURP improved erectile function in HBP patients with severe urinary symptoms. This improvement of erectile function was observed even in case of capsular perforation.

PMID 19940854
Fanwei Meng, Baohua Gao, Qiang Fu, Jun Chen, Yuqiang Liu, Benkang Shi, Zhishun Xu
Change of sexual function in patients before and after Ho:YAG laser enucleation of the prostate.
J Androl. 2007 Mar-Apr;28(2):259-61. doi: 10.2164/jandrol.106.000372. Epub 2006 Oct 4.
Abstract/Text The aim of this study is to evaluate the effect of Ho:YAG laser enucleation of the prostate (HOLEP) to the sexual function of patients with benign prostatic hyperplasia (BPH). In the course of the study, 108 patients with BPH were recruited and accepted treatment with HOLEP. The effectiveness of treatment was evaluated by flow rate and the International Prostate Symptom Score (IPSS) before HOLEP and 6 months afterwards. Meanwhile, the sexual functions were evaluated with the Danish Prostate Symptom Score Sexual Function Questionnaire (DanPSS Sex). Before and 6 months after HOLEP treatment, the mean residual urine volume was reduced from 106.0 +/- 51.7 mL to 5.6 +/- 1.7 mL (P<.01), maximum flow rate was improved from 7.2 +/- 3.9 mL/s to 21.7 +/- 1.3 mL/s (P<.01), nocturia frequency was reduced from 5.5 to 1.5 (P<.01), and the mean IPSS score was decreased from 19.4 +/- 5.6 to 7.4 +/- 2.6 (P<.01). The proportion of patients satisfied with their libido was 55% before HOLEP and 57% 6 months afterwards, while 23.5% of the patients had no libido before and after HOLEP; 37% of the patients were satisfied with their erection before HOLEP and 40% after 6 months; 30% of the patients had completely satisfactory sex life before HOLEP, and 32% did 6 months later. The corresponding percentages of fully impotent patients increased from 33% before the procedure to 35% 6 months postoperation. Early morning erections were reported by 45% of the patients before the procedure and by 62% 6 months later (P<.01). In 70% of the patients with normal sex life, ejaculation was retrograde 6 months after HOLEP (P<.01). HOLEP does not affect the sexual function of patients with BPH but does did improve the ability of early morning erection, while causing retrograde ejaculation.

PMID 17021335
T F Lue
Neurogenic erectile dysfunction.
Clin Auton Res. 2001 Oct;11(5):285-94.
Abstract/Text Penile erection is a neurovascular event modulated by psyche and hormones. Erectile dysfunction (ED) has been classified as psychogenic, arteriogenic, neurogenic, endocrinologic, and cavernosal, based on the organs that are involved in penile erection. Among these types, neurogenic ED may be the most common, probably because a deficiency of neurotransmitters is the final common pathway in many diseases and conditions. This review discusses the physiology, pathophysiology, diagnosis, and treatment of erectile function and dysfunction, as well as strategies for future research.

PMID 11758794
Peter M Rees, Clare J Fowler, Cornelis P Maas
Sexual function in men and women with neurological disorders.
Lancet. 2007 Feb 10;369(9560):512-25. doi: 10.1016/S0140-6736(07)60238-4.
Abstract/Text The advent of non-invasive functional brain imaging has clarified which regions of the brain are recruited during sexual arousal. Injuries to those regions, and to the spinal cord and peripheral nerves that link genitalia to limbic and cognitive centres, can profoundly influence sexual wellbeing. In epilepsy, expressions of hypersexuality and hyposexuality interact with the location of epileptogenic foci in the temporolimbic circuitry, and are tempered by the sexual effects of drug treatments. We outline the sexual consequences of epilepsy, stroke, multiple sclerosis, Parkinson's disease, and other common neurological disorders. Management of sexual dysfunction from both disease and treatment is discussed. Nerve-sparing techniques could mitigate the substantial sexual dysfunction in both men and women through surgical disruption of the autonomic nerves during radical pelvic surgery.

PMID 17292771
Ryuji Sakakibara, Tomoyuki Uchiyama, Tomonori Yamanishi, Masahiko Kishi
Genitourinary dysfunction in Parkinson's disease.
Mov Disord. 2010 Jan 15;25(1):2-12. doi: 10.1002/mds.22519.
Abstract/Text Bladder dysfunction (urinary urgency/frequency) and sexual dysfunction (erectile dysfunction) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, genitourinary autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the genitourinary dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life.

PMID 20077468
F Biering-Sørensen, J Sønksen
Penile erection in men with spinal cord or cauda equina lesions.
Semin Neurol. 1992 Jun;12(2):98-105. doi: 10.1055/s-2008-1041162.
Abstract/Text
PMID 1502437
M Zorzon, R Zivadinov, A Bosco, L M Bragadin, R Moretti, L Bonfigli, P Morassi, L G Iona, G Cazzato
Sexual dysfunction in multiple sclerosis: a case-control study. I. Frequency and comparison of groups.
Mult Scler. 1999 Dec;5(6):418-27.
Abstract/Text Sexual dysfunction is a very important but often overlooked symptom of multiple sclerosis. To investigate the type and frequency of symptoms of sexual dysfunction in patients suffering from multiple sclerosis, we performed a case-control study comparing 108 unselected patients with definite multiple sclerosis, 97 patients with chronic disease and 110 healthy individuals with regard to sexual function, sphincteric function, physical disorders impeding sexual activity and the impact of sexual dysfunction on social life. Information has been collected from a face-to-face structured interview performed by a doctor of the same gender as the patient. The disability, the cognitive performances, the psychiatric conditions and the psychological profile of patients and controls have been assessed. Sexual dysfunction was present in 73.1% of cases, in 39.2% of chronic disease controls and in 12.7% of healthy controls (P<0.0001). Male cases reported symptoms of sexual dysfunction more frequently than female cases (P<0.002). Symptoms of sexual dysfunction more commonly reported in patients with multiple sclerosis were anorgasmia or hyporgasmia (37.1%), decreased vaginal lubrication (35.7%) and reduced libido (31.4%) in women, and impotence or erectile dysfunction (63.2%), ejaculatory dysfunction and/or orgasmic dysfunction (50%) and reduced libido (39.5%) in men. Seventy-five per cent of cases, 51.5% of chronic disease controls and 28.2% of healthy controls (P<0.0001) experienced symptoms of sphincteric dysfunction. In conclusion, a substantial part of our sample of patients with multiple sclerosis reported symptoms of sexual and sphincteric dysfunction. Both sexual and sphincteric dysfunction were significantly more common in patients with multiple sclerosis than in either control group. Our findings suggest that a peculiar damage of the structures involved in sexual function is responsible for the dysfunction in patients with multiple sclerosis, but the highly significant lower frequency of symptoms of depression and anxiety in healthy controls may also imply a possible causative role of psychological factors.

PMID 10618699
Mohammadreza Nikoobakht, Mahmood Motamedi, Amirhossein Orandi, Alipasha Meysamie, Ala Emamzadeh
Sexual dysfunction in epileptic men.
Urol J. 2007 Spring;4(2):111-7.
Abstract/Text INTRODUCTION: The aim of this study was to evaluate the frequency of sexual dysfunction among epileptic patients.
MATERIALS AND METHODS: Eighty married men between 22 and 50 years with a confirmed diagnosis of epilepsy were enrolled in this study. Patients with other neurological diseases, hypertension, cardiovascular diseases, diabetes mellitus, underlying urogenital diseases, and impaired general health status were excluded. Furthermore, those with mental health problems were identified by the standardized General Health Questionnaire-28 and were excluded. Demographic and clinical characteristics of the disease were evaluated, and sexual function was assessed by the self-administered questionnaire of the International Index of Erectile Function-15 (IIEF-15).
RESULTS: Of 80 patients, 34 (42.5%) had erectile dysfunction. There were no differences between the patients in the 3 age groups in the IIEF scores. Type of seizure had a significant correlation with erectile function score (P = .008). None of the IIEF domains scores were different between the patients with controlled epilepsy and those with uncontrolled epilepsy during the previous 6 months. However, frequency of epileptic seizures (before treatment) correlated with the scores for erectile function (r = 0.31; P = .005), orgasmic function (r = 0.23; P = .04), and sexual desire (r = 0.24; P = .03).
CONCLUSION: It seems that the main aspects of sexual activity such as erectile function, orgasmic function, and sexual desire are frequently impaired in epileptic patients. Our findings were also indicative of a higher risk of sexual dysfunction in patients with partial seizures.

PMID 17701932
Gila Bronner, Vladimir Royter, Amos D Korczyn, Nir Giladi
Sexual dysfunction in Parkinson's disease.
J Sex Marital Ther. 2004 Mar-Apr;30(2):95-105. doi: 10.1080/00926230490258893.
Abstract/Text Sexual dysfunction is common in Parkinson's disease (PD). We investigated the premorbid and present sexual functioning of 75 people with PD (32 women and 43 men). Women reported difficulties with arousal (87.5%), with reaching orgasm (75.0%), with low sexual desire (46.9%), and wih sexual dissatisfaction (37.5%). Men reported erectile dysfunction (68.4%), sexual dissatisfaction (65.1%), premature ejaculation (40.6%), and difficulties reaching orgasm (39.5%). Premorbid sexual dysfunction may contribute to cessation of sexual activity during the course of the disease (among 23.3% men and 21.9% women). Associated illnesses, use of medications, and advanced stage of PD contributed to sexual dysfunction.

PMID 14742099
A G Papatsoris, C Deliveliotis, C Singer, S Papapetropoulos
Erectile dysfunction in Parkinson's disease.
Urology. 2006 Mar;67(3):447-51. doi: 10.1016/j.urology.2005.10.017. Epub 2006 Feb 28.
Abstract/Text
PMID 16504269
R O Beck, C D Betts, C J Fowler
Genitourinary dysfunction in multiple system atrophy: clinical features and treatment in 62 cases.
J Urol. 1994 May;151(5):1336-41.
Abstract/Text Multiple system atrophy is a disorder characterized by progressive neuronal atrophy at certain sites of the central nervous system, several of which are important in the control of urogenital function. The neuro-urological features of 62 patients with this condition are described. All patients had abnormal urethral or anal sphincter electromyography when individual motor unit analysis was performed, a finding diagnostic of the condition in the appropriate clinical setting. Impotence occurred in 96% of the men and was the first symptom alone in 37%. Urinary symptoms resulted from a combination of detrusor hyperreflexia and urethral sphincter weakness followed by failure of detrusor contraction. In men these symptoms simulated those of outflow obstruction so that 43% underwent prostatic or bladder neck surgery before the correct diagnosis was made. Stress incontinence occurred in 57% of the women and of these half had undergone surgery. The results of surgery in both sexes were poor. Treatment with intermittent catheterization, anticholinergic medication and desmopressin spray markedly improved continence in 82%. The importance of recognizing this disorder and introducing effective, nonoperative treatments is stressed.

PMID 8158782
K Kirchhof, A N Apostolidis, C J Mathias, C J Fowler
Erectile and urinary dysfunction may be the presenting features in patients with multiple system atrophy: a retrospective study.
Int J Impot Res. 2003 Aug;15(4):293-8. doi: 10.1038/sj.ijir.3901014.
Abstract/Text Multiple system atrophy (MSA) is a progressive neurodegenerative disease characterized by parkinsonism and cerebellar, autonomic, urinary, and/or pyramidal dysfunction. Urinary and erectile dysfunction (ED) symptoms are prominent early features in men with MSA. Autonomic failure, considered until recently to be the cause of ED in these men, is commonly expressed through symptoms of orthostatic hypotension (OH). The aim of this retrospective study is to examine the chronological relationship between the development of urogenital symptoms and those of OH in patients diagnosed with MSA and discuss its significance in the aetiology of ED in these patients. A total of 71 male patients, referred to a Uro-Neurology department with a diagnosis of 'probable MSA', were reviewed in terms of 'autonomic' symptoms only--OH and lower urinary tract symptoms, accompanied by ED--present at the time of their referral. Laboratory investigations including anal sphincter EMG and/or autonomic function tests (AFTs) were performed in 75 and 90% of the patients, respectively. At presentation, urinary complaints were recorded in 96% of patients and ED in all patients that this was inquired about. The onset of ED had preceded the onset of bladder symptoms in 58% and the onset of OH symptoms in 91% of these men. Bladder symptoms also preceded symptoms of OH in 76% of patients. Sphincter EMG was abnormal in 91% and AFTs in 77% of the patients tested. Almost all patients with abnormal EMG had troublesome urinary symptoms. AFTs showed similar sensitivity relating to symptoms. At presentation, urogenital symptoms are common in patients with probable MSA and are often not accompanied by symptoms of OH. The earlier occurrence of ED in men with MSA suggests a lack of a causal relationship to hypotension. The notion that MSA possibly affects the dopaminergic mechanism of erectile function is discussed.

PMID 12934060
M Smaldone, T Sukkarieh, A Reda, A Khan
Epilepsy and erectile dysfunction: a review.
Seizure. 2004 Oct;13(7):453-9. doi: 10.1016/j.seizure.2003.12.006.
Abstract/Text The association between epilepsy and erectile dysfunction (ED) has often been described but not clearly defined. This is a review of the literature regarding the current theories on the causes of ED in epilepsy, as well as the evaluation and treatment options available.

PMID 15324820
R G Brown, B MacCarthy, A M Gotham, G J Der, C D Marsden
Depression and disability in Parkinson's disease: a follow-up of 132 cases.
Psychol Med. 1988 Feb;18(1):49-55.
Abstract/Text Patients with Parkinson's disease, 132 in number, were followed up after approximately one year, and measures of depression and disability re-administered. Depression was common on both occasions, and was characterized by dysphoria, pessimism and somatic symptoms, but not guilt or self-blame. Depression and disability were associated on both occasions. The relationship between changes in disability and depression across time was complex. In trying to understand changes in depression, the absolute change in disability may be less important than the relative change and rate of change. The results were discussed in relation to findings from other disease groups, and the implications for the clinical management of depression in Parkinson's disease.

PMID 3363044
F Giuliano, C Hultling, W S El Masry, M D Smith, I H Osterloh, M Orr, M Maytom
Randomized trial of sildenafil for the treatment of erectile dysfunction in spinal cord injury. Sildenafil Study Group.
Ann Neurol. 1999 Jul;46(1):15-21.
Abstract/Text Erectile dysfunction is a common complication of spinal cord injury. This double-blind, placebo-controlled, two-way crossover study assessed the efficacy and safety of oral sildenafil in men with erectile dysfunction caused by traumatic spinal cord injury. A total of 178 men (mean age, 38 years) received placebo or sildenafil 1 hour before sexual activity for 6 weeks; after a 2-week washout period, the men received the alternate treatment for 6 weeks. The 50-mg starting dose could be adjusted to 100 or 25 mg based on efficacy and tolerability. Efficacy was assessed by using global efficacy questions, the International Index of Erectile Function (IIEF), and a patient log of erectile activity. Of 143 men with residual erectile function at baseline, 111 (78%) reported improved erections and preferred sildenafil to placebo. For all men (including those who reported no residual erectile function at baseline), 127 of 168 (76%) reported improved erections and preferred sildenafil to placebo. For all men, 132 of 166 (80%) reported that sildenafil improved sexual intercourse compared with 17 of 166 men (10%) reporting improvement with placebo. IIEF questions assessing the ability to achieve and maintain erections and satisfaction with sexual intercourse demonstrated significant improvement with sildenafil. Sildenafil was well tolerated, with a low rate of discontinuation because of treatment-related adverse events (2% vs 1% for placebo). Oral sildenafil is an effective and well-tolerated treatment for erectile dysfunction caused by spinal cord injury.

PMID 10401776
C Hultling, F Giuliano, F Quirk, B Peña, A Mishra, M D Smith
Quality of life in patients with spinal cord injury receiving Viagra (sildenafil citrate) for the treatment of erectile dysfunction.
Spinal Cord. 2000 Jun;38(6):363-70.
Abstract/Text STUDY DESIGN: A multicenter, randomized, double-blind, placebo-controlled, flexible-dose, two-way crossover study conducted June 1996 through January 1997.
OBJECTIVES: To evaluate the effect of sildenafil citrate (VIAGRA(R)) on the quality of life (QoL) of men with erectile dysfunction (ED) caused by spinal cord injury (SCI).
SETTING: Study centers in Australia, Belgium, France, Germany, Norway, Sweden and the United Kingdom.
METHODS: Questions 13 and 14 of the 15-item International Index of Erectile Function (IIEF) addressed QoL issues directly related to ED in 178 men with SCI. A 5-item questionnaire addressing concerns that men had about their erection problems was also used to evaluate the impact of ED on QoL. Several commonly used psychometric instruments, including the Medical Outcomes Survey (MOS) Short Form-12, Psychological General Well-Being Index, and MOS Family Survey, assessed general QoL issues.
RESULTS: Significant improvements were seen for overall satisfaction with sex life (IIEF Q13), sexual relationship with partner (IIEF Q14), and concerns about erectile problems (P<0.0001). Improvements were reported in scores for the generic QoL parameters of mental health, well-being, depression, and anxiety (P<0.05 sildenafil versus placebo).
CONCLUSION: Treatment with sildenafil can significantly improve key QoL parameters in men with ED caused by SCI.
SPONSORSHIP: This study was funded by Pfizer Inc. Spinal Cord (2000) 38, 363 - 370.

PMID 10889565
F Giuliano, E Rubio-Aurioles, M Kennelly, F Montorsi, E D Kim, A E Finkbeiner, P J Pommerville, M W Colopy, H J Wilkins, B H Wachs, Vardenafil Study Group
Efficacy and safety of vardenafil in men with erectile dysfunction caused by spinal cord injury.
Neurology. 2006 Jan 24;66(2):210-6. doi: 10.1212/01.wnl.0000194260.43583.32.
Abstract/Text OBJECTIVE: To assess the efficacy and tolerability of vardenafil in men with erectile dysfunction (ED) due to traumatic spinal cord injury (SCI).
METHODS: In this multicenter, double-blind, placebo-controlled, parallel-group 12-week study, 418 men aged 18 years and older with ED for more than 6 months consequent to SCI were randomized to vardenafil (n = 207) or placebo (n = 211) (10 mg for 4 weeks, then maintained or titrated to 5 or 20 mg at weeks 4 and 8). Efficacy assessments included the erectile function (EF) domain score of the International Index of Erectile Function questionnaire and diary questions regarding penetration, maintenance of erection to completion of intercourse, and ejaculation.
RESULTS: Baseline patient characteristics were similar in the vardenafil (mean age 40 years) and placebo (mean age 39 years) groups. Mean baseline EF domain scores were 11.6 in the vardenafil group and 12.1 (moderate ED) in the placebo group. EF domain score in the vardenafil group improved to 22.0 (mild ED) at last observation carried forward vs 13.5 in the placebo group (p < 0.001). Over 12 weeks of treatment, mean per-patient penetration (76% vs 41%), maintenance (59% vs 22%), and ejaculation (19% vs 10%) success rates were significantly greater vs placebo (all p < 0.001). The most frequently reported drug-related adverse events were headache (vardenafil 15%, placebo 4%), flushing (vardenafil 6%, placebo 0%), nasal congestion (vardenafil 5%, placebo 0%), and dyspepsia (vardenafil 4%, placebo 0%).
CONCLUSION: Vardenafil significantly improved erectile and ejaculatory function and was generally well tolerated in men with erectile dysfunction due to spinal cord injury.

PMID 16434656
Yasusuke Kimoto, Sadaaki Sakamoto, Keita Fujikawa, Takashi Tachibana, Noriyuki Yamamoto, Toshikazu Otani
Up-titration of vardena fi l dose from 10 mg to 20 mg improved erectile function in men with spinal cord injury.
Int J Urol. 2006 Nov;13(11):1428-33. doi: 10.1111/j.1442-2042.2006.01584.x.
Abstract/Text AIM: Vardenafil is a highly selective phosphodiesterase type-5 inhibitor for the treatment of erectile dysfunction (ED). Efficacy of vardenafil has been demonstrated in various ED populations, but that in Japanese patients with spinal cord injury (SCI) has not been assessed.
METHODS: This was an open-label, multicenter, flexible dose, 12-week study in patients with ED due to SCI. Following a 4-week observation period, patients received vardenafil 10 mg for 4 weeks, and based on efficacy, tolerability and patient preference, doses for the remaining 8 weeks were decided by investigators. The primary efficacy parameter was erectile function domain score of the International Index of Erectile Function.
RESULTS: Ten patients took 10 mg all through the study, while 22 patients took 20 mg after completing 4 weeks' treatment with 10 mg. The erectile function domain score increased from 12.2 at baseline to 25.0 at Last Observation Carried Forward (LOCF) in the former group and from 10.3 to 22.5 in the latter group, respectively. Importantly, there was a 5.0 point increase in erectile function domain score after up-titration in the latter group. Drug-related adverse events were observed in 22% of patients including hot flushes (9%) and headache (6%), but these were transient and mild in intensity. Serious adverse events and adverse events leading to discontinuation of the study drug were not reported.
CONCLUSIONS: Vardenafil 10 and 20 mg was well tolerated and improved erectile function in patients with SCI. Of interest, erectile function was further improved by 20 mg in patients who were not sufficiently treated with 10 mg.

PMID 17083398
François Giuliano, Antonio Sanchez-Ramos, Dieter Löchner-Ernst, Giulio Del Popolo, Natalio Cruz, Albert Leriche, Giuseppe Lombardi, Susanne Reichert, Palle Dahl, Albert Elion-Mboussa, Joaquin Casariego
Efficacy and safety of tadalafil in men with erectile dysfunction following spinal cord injury.
Arch Neurol. 2007 Nov;64(11):1584-92. doi: 10.1001/archneur.64.11.nct70001. Epub 2007 Sep 10.
Abstract/Text OBJECTIVE: To determine the efficacy and safety of tadalafil when taken on demand by men with erectile dysfunction (ED) secondary to traumatic spinal cord injury (SCI).
DESIGN AND SETTING: Multicenter, randomized, double-blind, placebo-controlled, flexible dose-titration, parallel-group study in clinical practices in Europe. Patients Enrolled patients had ED secondary to SCI (all spinal levels) and sustained 6 months or longer before visit 1.
INTERVENTIONS: After a 4-week run-in period, patients were randomly assigned to tadalafil, 10 mg, (n = 142) or placebo (n = 44) for a 12-week, on-demand treatment period with assessments at 4-week intervals. The dose of tadalafil was maintained or titrated (10 or 20 mg) at 4 and 8 weeks.
MAIN OUTCOME MEASURES: Efficacy was measured using the International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP), and Global Assessment Question (GAQ). Treatment-emergent adverse events and vital signs were collected at each visit.
RESULTS: Mean age was 38 years. Mean baseline IIEF erectile function domain score was 13.4, and following 12 weeks of treatment, 22.6 for tadalafil and 13.6 for placebo (P < .001). After treatment, the tadalafil group compared with the placebo group was significantly greater (P < .001) in mean per-patient percentage of successful penetration attempts (SEP question 2; 75.4% vs 41.1%) and intercourse attempts (SEP question 3; 47.6% vs 16.8%); percentage of improved erections (GAQ question 1; 84.6% vs 19.5%); and ejaculatory frequency (IIEF question 9; P = .03). The 2 most common treatment-emergent adverse events in the tadalafil group compared with placebo were headache (8.5% vs 4.5%) and urinary tract infection (7.7% vs 6.8%).
CONCLUSIONS: Tadalafil (10 mg and 20 mg) improved erectile function and was well tolerated by men with ED secondary to traumatic SCI.

PMID 17846260
M R Safarinejad, A Taghva, B Shekarchi, Sh Safarinejad
Safety and efficacy of sildenafil citrate in the treatment of Parkinson-emergent erectile dysfunction: a double-blind, placebo-controlled, randomized study.
Int J Impot Res. 2010 Sep-Oct;22(5):325-35. doi: 10.1038/ijir.2010.23. Epub 2010 Sep 23.
Abstract/Text Parkinson's disease (PD) is one of the most commonly occurring neurodegenerative disorders, with lifetime incidence between 1 and 2% among people older than 65 years. ED is one of the more disabling and poorly addressed aspects of PD. The purpose of this study was to assess the efficacy and safety of sildenafil citrate in Parkinson-emergent ED. Sexual function of participants was assessed using responses to the 15-question International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP) diary questions 2 and 3, Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire and a Global Efficacy Question 'Has the treatment you have been taking over the study period improved your erections?' This randomized, double-blind, placebo-controlled study, comprised a screening period of at least 1 month, a placebo-lead in period of 1 week and treatment period. Two hundred thirty-six patients entered the trial. These patients had mild-to-moderate PD (stages I-III Hoehn-Yahr) and were experiencing Parkinson-emergent neurogenic ED. They were randomized to receive 100 mg sildenafil on demand 1 h before sexual activity (group 1, n=118), or similar regimen of placebo (group 2, n=118). Patients were instructed to use at least 24 doses/attempts at home. At the end of the trial, differences between sildenafil and placebo groups were significant for the IIEF erectile function (EF) score (22.6 ± 4.6 vs 14.8 ± 4.2, P=0.01), for percent Global Efficacy Question 'Yes' responses (68.1 ± 4.6 vs 12.2 ± 3.2, P=0.001), for SEP2 'Yes' responses (68.1 ± 4.2 vs 32.5 ± 2.2, P=0.003), for SEP3 'Yes' responses (75.9 ± 5.4 vs 33.5 ± 4.4, P=0.004) and for mean EDITS score (69.8 ± 4.2 vs 13.0 ± 2.7, P=0.004). A normal EF domain score (>or=26) at end point was achieved by 56.9 and 8.7% of the patients in the sildenafil and placebo groups, respectively (P=0.001). Sildenafil can be considered as an effective treatment in patients with Parkinson-emergent ED.

PMID 20861846
C J Fowler, J R Miller, M K Sharief, I F Hussain, V J Stecher, M Sweeney
A double blind, randomised study of sildenafil citrate for erectile dysfunction in men with multiple sclerosis.
J Neurol Neurosurg Psychiatry. 2005 May;76(5):700-5. doi: 10.1136/jnnp.2004.038695.
Abstract/Text OBJECTIVE: Identifying and effectively treating erectile dysfunction (ED) can result in an improvement of the quality of life (QoL) in men with multiple sclerosis (MS).
METHODS: This randomised, double blind (DB), placebo controlled, flexible dose study with an open label extension (OLE) assessed efficacy, QoL, and safety of sildenafil citrate in men with MS and ED. Overall, 217 men received sildenafil (25-100 mg; n = 104) or placebo (n = 113) for 12 weeks. Efficacy was assessed by the International Index of Erectile Function (IIEF) questionnaire that includes questions on achieving (Q3) and maintaining (Q4) an erection as well as a global efficacy question (GEQ). QoL was also assessed.
RESULTS: After 12 weeks, patients receiving sildenafil had higher mean scores for IIEF Q3 and Q4 compared with those receiving placebo (p<0.0001), and 89% (92/103) reported improved erections compared with 24% (27/112) of patients receiving placebo (p<0.0001). At the end of the OLE phase, 95% of men reported improved erections. Patients receiving placebo during the DB phase showed a nearly fourfold increase in improved erections (97% v 26%). Men receiving sildenafil also showed improvements in five of the eight general QoL questions compared with men receiving placebo (p<0.05). The total mean score for the QoL questionnaire improved by 43% for the sildenafil group versus 13% for the placebo group (p<0.0001). Treatment related AEs were predominantly mild in nature, and no patient discontinued due to an AE.
CONCLUSION: Sildenafil treatment for ED in men with MS was effective and well tolerated, and resulted in significant improvements in both general and disease specific QoL variables.

PMID 15834030
Giuseppe Lombardi, Angelo Macchiarella, Giulio Del Popolo
Efficacy and safety of tadalafil for erectile dysfunction in patients with multiple sclerosis.
J Sex Med. 2010 Jun;7(6):2192-200. doi: 10.1111/j.1743-6109.2010.01797.x. Epub 2010 Apr 1.
Abstract/Text INTRODUCTION: Data are sparse concerning the effects of phosphodiesterase type 5 (PDE5) inhibitors for erectile dysfunction (ED) in subjects with multiple sclerosis (MS).
AIM: To evaluate the efficacy and safety of tadalafil use in subjects with ED because of MS.
METHODS: Ninety-six MS patients with ED after a 4-week treatment-free period were given tadalafil 10 mg. All patients were re-evaluated after 4 weeks. Those with a score lower than 26 on the International Index of Erectile Function (IIEF-15) and with less than 75% of total successful sexual attempts assessed by the Sexual Encounter Profile Questions 2 and 3 (SEP2-3) had their dosage of tadalafil increased to 20 mg, whereas responding subjects continued with 10 mg. Subsequently, all patients had a final follow-up visit after 8 weeks.
MAIN OUTCOME MEASURES: SEP2-3, IIEF-15 questionnaire. The Life Satisfaction Checklist (LSC) questionnaire composed of eight questions was used prior to starting tadalafil and at the end of the 12-week treatment.
RESULTS: Ninety-two subjects completed the study. Seventy-two responded, 30 of whom used 10 mg. Two subjects discontinued the therapy because of moderate side effects: one suffered from headache and one from tachycardia. Responding patients reached a significant statistical improvement in all follow-ups compared with baseline on the erectile domain and overall sexual satisfaction scores of the IIEF-15 using the Wilcoxon test P < 0.01. Furthermore, they showed statistical improvement through the Wilcoxon test P < 0.01 on the sexual life, family life, and partner relationship questions of the LSC compared with baseline.
CONCLUSION: Tadalafil is an effective and safe treatment for males with MS suffering from ED. Further studies are needed on MS patients to evaluate the efficacy and safety of long-term use, and to detect predictable parameters for the success of PDE5 inhibitors.

PMID 20384939
Abdulbari Bener, Abdulla O A A Al-Hamaq, Saadat Kamran, Abdullah Al-Ansari
Prevalence of erectile dysfunction in male stroke patients, and associated co-morbidities and risk factors.
Int Urol Nephrol. 2008;40(3):701-8. doi: 10.1007/s11255-008-9334-y. Epub 2008 Feb 2.
Abstract/Text BACKGROUND: Sexual problems have been a common finding in chronically ill and physically disabled patients such as those with cerebrovascular accidents. Previous studies have supported the association between stroke and erectile dysfunction (ED).
OBJECTIVES: The aim of this study was to investigate the prevalence of ED and its severity in male stroke patients in Qatar and to assess the co-morbidities and risk factors associated with ED.
DESIGN: This was a cross-sectional study.
SETTING: The study was conducted from January to December 2006 at the Hamad General Hospital, Hamad Medical Corporation (HMC).
SUBJECTS: Eight hundred Qatari and non-Qatari patients 35-75 years of age were invited to participate in this study; 605 patients gave their consent, which was a response rate of 75.6%.
METHODS: Face-to-face interviews were based on a questionnaire that included socio-demographic factors. The classification of the type of stroke was made according to the criteria of stroke by the World Health Organization (WHO). All patients completed a second questionnaire addressing their general medical history, type of treatment and co-morbidity with other diseases or risk factors. Sexual function was evaluated with the International Index of Erectile Function (IIEF).
RESULTS: The mean age of subjects was 56.1+/-9.8 years. Approximately 48.3% of the studied population reported some degree of erectile dysfunction. Of the stroke patients with ED, 36% had severe ED, 32.9% had moderate ED and 31.2% had mild ED. More than half of the stroke patients (59.6%) with ED were in the age group 60-75 years. The prevalence of ED increased with increasing age. The co-morbidities and risk factors were significantly more prominent in ED patients than in those without ED for hypercholesterolemia (P<0.001), diabetes (P=0.002), and hypertension (P=0.031). Medication taken for these diseases also had a significant association with ED.
CONCLUSIONS: Our study findings revealed a greater prevalence of ED in stroke patients in the population of Qatar. The most important co-morbid factors for ED in stroke patients were diabetes, hypertension and hypercholesterolemia, and the risk factors were smoking and obesity.

PMID 18246439
Ian Eardley, Peter Ellis, Mitradev Boolell, Maria Wulff
Onset and duration of action of sildenafil for the treatment of erectile dysfunction.
Br J Clin Pharmacol. 2002;53 Suppl 1:61S-65S.
Abstract/Text AIMS: To determine the onset and duration of action of sildenafil in patients with erectile dysfunction (ED).
METHODS: Two randomised, double-blind, placebo-controlled, two-way crossover studies were conducted in men with ED of no known organic cause. Study I: The time to onset of erections after sildenafil (50 mg) or placebo dosing following visual sexual stimulation (VSS) was assessed in 17 patients. Patients not achieving >60% penile rigidity by 70 min postdose as measured by a RigiScan(R) monitoring device were assigned an onset time of 70 min. Study II: The duration of grade 3 (hard enough for penetration) and grade 4 (fully hard) erections, determined by self-assessment during 60 min of VSS starting 2 and 4 h after sildenafil (100 mg) or placebo dosing, was measured in 16 patients.
RESULTS: Study I: The median time (range) to onset of erections was 27 min (in a range of 12--70) after receiving sildenafil 50 mg. In the sildenafil group, 71% of patients experienced onset of erections within 30 min of dosing, and 82% responded within 45 min. Of the patients who achieved >60% penile rigidity after sildenafil, 86% had done so by 30 min after dosing. Study II: When VSS began 2 h postdose, the median duration of grade 3 or 4 erections was 19.5 min (0--55) for sildenafil vs 0 min (0--23) for placebo. When VSS began 4 h postdose, the median duration was 5 min (0--45) for sildenafil compared with 0 min for placebo (0--27).
CONCLUSIONS: Sildenafil is an effective oral treatment for ED that produces a penetrative erection as early as 12 min and for most patients, within 30 min after dosing, and a duration of action lasting at least 4 h.

PMID 11879261
Culley C Carson, Arthur L Burnett, Laurence A Levine, Ajay Nehra
The efficacy of sildenafil citrate (Viagra) in clinical populations: an update.
Urology. 2002 Sep;60(2 Suppl 2):12-27.
Abstract/Text Although certain risk factors are known to be associated with erectile dysfunction (ED), the demographic and ED characteristics of the population of men with ED are quite diverse. We examined results from randomized trials of sildenafil citrate (Viagra) to ascertain if efficacy differed across various subgroups of men with ED. In addition, we reviewed findings from long-term extension studies and published accounts of sildenafil use in clinical practice to determine if effectiveness is maintained with long-term sildenafil treatment and to determine if effectiveness in the clinic practice setting is consistent with that reported in clinical trials. Data were pooled from 11 double-blind, placebo-controlled, flexible-dose (taken as needed) studies to assess efficacy (N = 2667) of sildenafil in men (aged 23 to 89 years) with ED of broad-spectrum etiology who were not receiving concomitant nitrate therapy. Efficacy evaluations included the International Index of Erectile Function, a global efficacy question ("Did treatment improve your erections?"), and a patient-recorded event log of sexual activity. Significantly improved erectile function was demonstrated for sildenafil compared with placebo for all efficacy parameters analyzed (P <0.02 to 0.0001), regardless of patient age, race, body mass index, ED etiology, ED severity, ED duration, or the presence of various comorbidities. Long-term effectiveness was assessed in 3 open-label extension studies. Of those who continued long-term therapy (1 to 3 years) with sildenafil, >95% of patients reported that they were satisfied with the effect of treatment on their erections, and that treatment had improved their ability to engage in sexual activity. Findings from published accounts of sildenafil use in the clinical practice setting further demonstrated that sildenafil is an effective treatment for a wide range of patients with ED.

PMID 12414330
Harin Padma-nathan, Ian Eardley, Robert A Kloner, Alan M Laties, Francesco Montorsi
A 4-year update on the safety of sildenafil citrate (Viagra).
Urology. 2002 Sep;60(2 Suppl 2):67-90.
Abstract/Text Clinical studies have demonstrated that sildenafil citrate (Viagra) is an effective and well-tolerated oral treatment for erectile dysfunction. Despite its established safety profile, concern about its cardiovascular safety persists among some physicians and the general public. This concern has stemmed primarily from sporadic reports of adverse events published in the literature and sensationalized by the media. However, the only absolute contraindication for sildenafil is concurrent use of nitrates. Because sildenafil has been on the market for 4 years and under clinical investigation for even longer, we can now evaluate its long-term safety in men who have been taking the drug for several years. We review this issue from 3 perspectives. First, we reassess the overall safety profile of sildenafil by reviewing the initial controlled clinical trials and open-label studies. We present new data from patients who have been exposed to sildenafil for up to 4.5 years. We also evaluate the results from independent postmarketing studies. Second, we review the cardiovascular-specific results from the clinical trials, long-term extension, and postmarketing studies. Lastly, we review the specific effects on the visual system based on findings from studies conducted during drug development and post marketing.

PMID 12414335
John P Mulhall
Understanding erectile dysfunction medication preference studies.
Curr Opin Urol. 2004 Nov;14(6):367-73.
Abstract/Text PURPOSE OF REVIEW: The existence of three phosphodiesterase 5 inhibitors has resulted in an increase in the marketing of the drugs. This has led to a shift in focus from scientifically rigorous endpoints such as efficacy and adverse event profiles to patient preference.
RECENT FINDINGS: Although no consensus currently exists as to the correct methodology for preference studies, some basic guidelines should be adhered to, including: (1) the double-blinding of drug administration; (2) non-biased drug administration instructions; (3) an adequately conducted crossover study; (4) comparison of equivalent doses; (5) standardized preference assessment; (6) declaration of patient demographics; and (7) rigorous statistical analysis. These factors are discussed in the light of the three published preference studies.
SUMMARY: In the final analysis, it is unclear to this author how preference studies impact upon clinician decision-making when confronted by a patient with erectile dysfunction.

PMID 15626881
Humphrey O Atiemo, Michael J Szostak, Geoffrey N Sklar
Salvage of sildenafil failures referred from primary care physicians.
J Urol. 2003 Dec;170(6 Pt 1):2356-8. doi: 10.1097/01.ju.0000096221.67967.ae.
Abstract/Text PURPOSE: Sildenafil citrate is an effective first line agent for most causes of erectile dysfunction. Primary care providers (PCPs) write the majority of these prescriptions and most failures of sildenafil therapy are subsequently referred to urologists for alternative therapies. Often it is concluded that the drug is ineffective when in actuality the failure is do to inadequate patient education. We examined patients referred from PCPs who were nonresponders to sildenafil therapy and attempted to convert them to responders through reeducation.
MATERIALS AND METHODS: In a 2-year period 253 sildenafil nonresponders were evaluated by the same urologist (GNS). Patient reeducation consisted of viewing a brief videotape, personal instruction and detailed instruction sheets for the patient and his partner. Outcome measures were obtained through patient self-reporting of the Sexual Health Inventory for Men and a global assessment question. Responders were identified as those who answered positively latter or had a statistical improvement in the score of the former.
RESULTS: Of the 253 patients reeducated 17 were excluded due to contraindications. Of the remaining nonresponders 41.5% achieved salvage with reeducation. Incorrect administration accounted for 81% of the failures. Average time with the physician was 12 minutes and 94% of the patients continued to respond at 26 months.
CONCLUSIONS: Approximately 40% of patients with sildenafil failures referred from PCPs can be converted to responders through reeducation. Incorrect drug administration was the most common reason for correctable failure. Reeducation can be done in an efficient manner. New package materials may improve sildenafil outcomes and compliance.

PMID 14634415
Andrew R McCullough, James H Barada, Ahmed Fawzy, Andre T Guay, Dimitrios Hatzichristou
Achieving treatment optimization with sildenafil citrate (Viagra) in patients with erectile dysfunction.
Urology. 2002 Sep;60(2 Suppl 2):28-38.
Abstract/Text Since its approval in 1998, sildenafil citrate (Viagra) has been shown to be efficacious in >100 clinical trials involving >8000 men with erectile dysfunction (ED). In clinical practice, however, many men do not continue long-term use of sildenafil for a variety of reasons; thus, 6 different aspects of optimizing treatment with sildenafil are described here. (1) Intercourse success rates, considered a reflection of real-world effectiveness, were assessed in 1276 patients with ED. Results indicated that the cumulative probability of achieving intercourse success with sildenafil increased with the number of attempts, reaching a plateau after approximately 8 attempts. (2) A comprehensive disease management approach that included a medical history, physical examination, educational material about ED, modifications of risk factors/lifestyle changes, and counseling resulted in successful intercourse in 74% of 111 patients taking sildenafil. (3) A survey conducted among primary care physicians revealed that almost 50% did not routinely question their patients about ED symptoms, although it is known that most patients would prefer their physician to take the initiative. (4) Overall, 55% of 137 men who were previously not successful with sildenafil became successful after reeducation and counseling, which included information on patient and partner expectations, how to properly take the drug, titration to maximum dose, and a minimum trial of 8 attempts for efficacy assessment. (5) Many men with ED have underlying comorbidities or take multiple medications that are risk factors for ED. Controlling these risk factors in 521 men from a multispecialty clinic led to an overall intercourse success rate of 82%; patients with multiple risk factors were less likely to have intercourse success than men with only 1 risk factor. (6) Finally, treatment satisfaction is a pivotal factor in maintaining long-term ED therapy. In an open-label trial, 82% of 443 subjects reported treatment satisfaction with sildenafil. In summary, these findings highlight how important it is for physicians to take a more comprehensive, proactive approach when treating men with ED, including control of risk factors, instructions on how to properly take the drug, partner involvement, and follow-up visits. Using these recommended measures, most men with ED, including those whose treatment was previously unsuccessful, can be treated successfully with sildenafil.

PMID 12414331
B-P Jiann, C-C Yu, C-C Su, J-K Huang
Rechallenge prior sildenafil nonresponders.
Int J Impot Res. 2004 Feb;16(1):64-8. doi: 10.1038/sj.ijir.3901143.
Abstract/Text To assess inappropriate use as a cause of sildenafil (Viagra ) failure and the feasibility of successfully rechallenging nonresponding patients, a total of 60 consecutive erectile dysfunction (ED) patients who first presented to our hospital and claimed poor response to sildenafil were enrolled into the study. The International Index of Erectile Function-5 (IIEF-5) was used to evaluate their baseline ED status and a self-administered sildenafil-use questionnaire composed of nine questions (SUQ-9) to assess how they had used sildenafil. A total of 44 subjects consent to rechallenge with sildenafil and were given thorough instruction based on individual answers to SUQ-9 and four doses of sildenafil 100 mg. After a 4-week follow-up, end point efficacy of rechallenge was evaluated using the IIEF-5 and the global assessment question (GAQ), 'After the treatment, did you have successful sexual intercourse?' Of the 60 subjects, 44 (77.3%) had one or more areas of major suboptimal use of sildenafil: 18 (30.0%) did not know that sexual stimulation was necessary for sildenafil to work, 36 (60.0%) attempted to use sildenafil less than four times, and 27 (45.0%) took a maximal dose less than 100 mg. Of the 44 patients undergoing sildenafil rechallenge, 34 (77.3%) completed the follow-up, while seven (15.9%) received only GAQ assessment by telephone interview and three (6.8%) were lost to follow-up. The total follow-up rate was 93.2% (41/44). Based on answers to the GAQ, the response rate to rechallenge was 58.5% (24/41). The mean improvement in the IIEF-5 score was 8.4+/-5.5 in responders (P <0.05). With individualized thorough instruction based on answers to SUQ-9 and scheduled follow-up, a high success rate was achieved by rechallenge with sildenafil in prior failures. The efficacy of sildenafil could be improved to a great extent by adequate education of patients and continuing medical education given to primary-care physicians.

PMID 14963473
Dimitrios Hatzichristou, Kyriakos Moysidis, Apostolos Apostolidis, Athanasios Bekos, Vasilios Tzortzis, Konstantinos Hatzimouratidis, Evangelos Ioannidis
Sildenafil failures may be due to inadequate patient instructions and follow-up: a study on 100 non-responders.
Eur Urol. 2005 Apr;47(4):518-22; discussion 522-3. doi: 10.1016/j.eururo.2004.12.005. Epub 2005 Jan 20.
Abstract/Text OBJECTIVE: The objective of this study was to identify factors that affect efficacy response rate to sildenafil in the clinical practice.
MATERIAL AND METHOD: The study comprised 100 consecutive sildenafil non-responders. Mean patient age was 59+/-14.4 years and mean duration of ED 5.5+/-6.4 years. All patients underwent detailed medical and sexual history and completed the IIEF and a questionnaire regarding the previous use of sildenafil. When inadequate instructions were reported, information on the appropriate use of sildenafil was given and patients were asked to use at least 4 tablets at home. Pharmacologic efficacy was re-evaluated in a scheduled follow-up visit.
RESULTS: Mean Erectile Function Domain (ED) of the IIEF score was 14+/-9.9. In 56 patients inappropriate use of sildenafil was recognized; 45 had never used the highest recommended dose (100 mg), 32 had taken the pill with a full stomach right after a meal, 22 had taken the pill just before the initiation of sexual activity and 12 were not aware that sexual stimulation was mandatory to achieve an erection. Furthermore, 8 patients had tried the 100mg dose, despite the presence of factors associated with sildenafil clearance reduction (renal insufficiency, cimetidine treatment). Only 34 patients reported that their physician had scheduled a follow-up visit. Following adequate dose titration and time adjustment, 31 patients responded to sildenafil; 10 patients used the 50 mg dose and 21 the 100 mg. Second and third-line treatment options were offered to the rest of the patients.
CONCLUSIONS: ED patients may receive inadequate instructions with their prescriptions. Response rate to sildenafil may be maximized after receiving appropriate dose titration and instructions on administration. ED should be treated in the same way as other chronic conditions; follow-up is necessary to evaluate the appropriate application and pharmacologic efficacy of the proposed treatment.

PMID 15774252
Konstantinos Hatzimouratidis, Kyriakos Moysidis, Athanasios Bekos, Zoi Tsimtsiou, Evangelos Ioannidis, Dimitrios Hatzichristou
Treatment strategy for "non-responders" to tadalafil and vardenafil: a real-life study.
Eur Urol. 2006 Jul;50(1):126-32; discussion 132-3. doi: 10.1016/j.eururo.2006.02.060. Epub 2006 Mar 10.
Abstract/Text OBJECTIVES: To develop and test step-wise treatment strategy for erectile dysfunction "non-responders" to tadalafil and vardenafil.
MATERIAL AND METHODS: Two groups [tadalafil-treated (TG); vardenafil-treated (VG)] of 100 consecutive patients complaining of non-response to treatments were enrolled in three-phase study. Phase 1: inadequate use was identified and patients were rechallenged, after receiving detailed usage information. Phase 2: true non-responders were given new instructions based on drugs' pharmacologic profiles: TGs were dosed at least 2 h before intercourse; VGs were dosed only in fasted state. Remaining non-responders entered phase 3: continuous administration of 20 mg tadalafil every other day, or 20 mg vardenafil every day for 2 weeks. Efficacy was based on positive (yes) response to two questions: "Were your erections rigid, and did they last long enough to have successful intercourse?" and "Do you want to repeat your prescription?"
RESULTS: Tadalafil group: Inappropriate use was recognized in 32 patients; 14 (43.75%) responded after adequate instruction. Phase 2: 32 of 86 (37.2%) had intercourse at least 2 h after dose intake. Phase 3: 6 of 86 (11.1%) responded to continuous administration. Overall salvage rate was 52 of 100 (52%). Vardenafil group: Inappropriate use was recognized in 38 patients; 12 (31.58%) responded after adequate instruction. Phase 2, 22 of 88 (25%) responded to dosing in a fasted state. Phase 3: 12 of 66 (18.2%) responded to daily dosing. Overall salvage rate was 46 of 100 (46%).
CONCLUSIONS: Following proposed treatment strategy may maximize response rate to phosphodiesterase 5 inhibitors; appropriate usage instructions may play significant role in response rate.

PMID 16564127
Konstantinos Hatzimouratidis, Edouard Amar, Ian Eardley, Francois Giuliano, Dimitrios Hatzichristou, Francesco Montorsi, Yoram Vardi, Eric Wespes, European Association of Urology
Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation.
Eur Urol. 2010 May;57(5):804-14. doi: 10.1016/j.eururo.2010.02.020. Epub 2010 Feb 20.
Abstract/Text CONTEXT: Erectile dysfunction (ED) and premature ejaculation (PE) are the two most prevalent male sexual dysfunctions.
OBJECTIVE: To present the updated version of 2009 European Association of Urology (EAU) guidelines on ED and PE.
EVIDENCE ACQUISITION: A systematic review of the recent literature on the epidemiology, diagnosis, and treatment of ED and PE was performed. Levels of evidence and grades of recommendation were assigned.
EVIDENCE SYNTHESIS: ED is highly prevalent, and 5-20% of men have moderate to severe ED. ED shares common risk factors with cardiovascular disease. Diagnosis is based on medical and sexual history, including validated questionnaires. Physical examination and laboratory testing must be tailored to the patient's complaints and risk factors. Treatment is based on phosphodiesterase type 5 inhibitors (PDE5-Is), including sildenafil, tadalafil, and vardenafil. PDE5-Is have high efficacy and safety rates, even in difficult-to-treat populations such as patients with diabetes mellitus. Treatment options for patients who do not respond to PDE5-Is or for whom PDE5-Is are contraindicated include intracavernous injections, intraurethral alprostadil, vacuum constriction devices, or implantation of a penile prosthesis. PE has prevalence rates of 20-30%. PE may be classified as lifelong (primary) or acquired (secondary). Diagnosis is based on medical and sexual history assessing intravaginal ejaculatory latency time, perceived control, distress, and interpersonal difficulty related to the ejaculatory dysfunction. Physical examination and laboratory testing may be needed in selected patients only. Pharmacotherapy is the basis of treatment in lifelong PE, including daily dosing of selective serotonin reuptake inhibitors and topical anaesthetics. Dapoxetine is the only drug approved for the on-demand treatment of PE in Europe. Behavioural techniques may be efficacious as a monotherapy or in combination with pharmacotherapy. Recurrence is likely to occur after treatment withdrawal.
CONCLUSIONS: These EAU guidelines summarise the present information on ED and PE. The extended version of the guidelines is available at the EAU Web site (http://www.uroweb.org/nc/professional-resources/guidelines/online/).

Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.
PMID 20189712
Abstract/Text CONTEXT: Erectile dysfunction is common in men with diabetes.
OBJECTIVE: To assess the efficacy and safety of oral sildenafil citrate in the treatment of erectile dysfunction in men with diabetes.
DESIGN: A multicenter, randomized, double-blind, placebo-controlled, flexible dose-escalation study conducted May through November 1996.
SETTING: Patients' homes and 19 clinical practice centers in the United States.
PATIENTS: A total of 268 men (mean age, 57 years) with erectile dysfunction (mean duration, 5.6 years) and diabetes (mean duration, 12 years).
INTERVENTIONS: Patients were randomized to receive sildenafil (n = 136) or placebo (n = 132) as needed, but not more than once daily, for 12 weeks. Patients took the study drug or placebo 1 hour before anticipated sexual activity. The starting dose of sildenafil citrate was 50 mg, with the option to adjust the dose to 100 mg or 25 mg based on efficacy and tolerability, to be taken as needed.
MAIN OUTCOME MEASURES: Self-reported ability to achieve and maintain an erection for sexual intercourse according to the International Index of Erectile Function and adverse events.
RESULTS: Two hundred fifty-two patients (94%) completed the study (131/136 in the sildenafil group, 121/132 in the placebo group). By intention-to-treat analysis, at 12 weeks, 74 (56%) of 131 patients in the sildenafil group reported improved erections compared with 13 (10%) of 127 patients in the placebo group (P<.001). The proportion of men with at least 1 successful attempt at sexual intercourse was 61 % (71/ 117) for the sildenafil group vs 22% (25/114) for the placebo group (P<.001). Adverse events related to treatment were reported for 22 (16%) of 136 patients taking sildenafil and 1 (1%) of 132 patients receiving placebo. The most common adverse events were headache (11% sildenafil, 2% placebo), dyspepsia (9% sildenafil, 0% placebo), and respiratory tract disorder (6% sildenafil, 2% placebo), predominantly sinus congestion or drainage. The incidence of cardiovascular adverse events was comparable for both groups (3% sildenafil, 5% placebo).
CONCLUSION: Oral sildenafil is an effective and well-tolerated treatment for erectile dysfunction in men with diabetes.

PMID 9952201
Howard A Fink, Roderick Mac Donald, Indulis R Rutks, David B Nelson, Timothy J Wilt
Sildenafil for male erectile dysfunction: a systematic review and meta-analysis.
Arch Intern Med. 2002 Jun 24;162(12):1349-60.
Abstract/Text OBJECTIVE: To determine the efficacy and safety of sildenafil citrate in the treatment of male erectile dysfunction.
DATA SOURCES: The MEDLINE, HealthSTAR, Current Contents, and Cochrane Library databases (January 1, 1995, through December 31, 2000); bibliographies of retrieved articles and review articles; conference proceedings abstracts; the Food and Drug Administration Web site; and the manufacturer.
STUDY SELECTION: Trials were eligible if they included men with erectile dysfunction, compared sildenafil with control, were randomized, were of at least 7 days' duration, and assessed clinically relevant outcomes.
DATA EXTRACTION: Two reviewers independently evaluated study quality and extracted data in a standardized fashion.
DATA SYNTHESIS: Twenty-seven trials (6659 men) met the inclusion criteria. In results pooled from 14 parallel-group, flexible as-needed dosing trials, sildenafil was more likely than placebo to lead to successful sexual intercourse, with a higher percentage of successful intercourse attempts (57% vs 21%; weighted mean difference, 33.7; 95% confidence interval [CI], 29.2-38.2; 2283 men) and a greater percentage of men experiencing at least 1 intercourse success during treatment (83% vs 45%; relative benefit increase, 1.8; 95% CI, 1.7-1.9; 2205 men). In data pooled from 6 parallel-group, fixed-dose trials, efficacy appeared slightly greater at higher doses. Treatment response appeared to vary between patient subgroups, although relative to placebo, sildenafil significantly improved erectile function in all evaluated subgroups. In trials with parallel-group design and flexible dosing, men randomized to receive sildenafil were less likely than those receiving placebo to drop out for any reason and no more likely to drop out due to an adverse event or laboratory abnormality. Specific adverse events with sildenafil included flushing (12%), headache (11%), dyspepsia (5%), and visual disturbances (3%); all adverse events were significantly less likely to occur with placebo. Sildenafil was not significantly associated with serious cardiovascular events or death.
CONCLUSIONS: Sildenafil improves erectile function and is generally well tolerated. Treatment response seems to vary between patient subgroups, although sildenafil has greater efficacy than placebo in all evaluated subgroups.

PMID 12076233
H Porst, R Rosen, H Padma-Nathan, I Goldstein, F Giuliano, E Ulbrich, T Bandel
The efficacy and tolerability of vardenafil, a new, oral, selective phosphodiesterase type 5 inhibitor, in patients with erectile dysfunction: the first at-home clinical trial.
Int J Impot Res. 2001 Aug;13(4):192-9. doi: 10.1038/sj.ijir.3900713.
Abstract/Text Vardenafil, a novel selective phosphodiesterase type 5 inhibitor, was evaluated in its first large-scale at-home trial. A total of 601 men with mild to severe erectile dysfunction (ED) were enrolled in this multi-centre, randomized, double-blind, placebo-controlled trial of 12 weeks of treatment with either placebo or 5, 10 and 20 mg of vardenafil. Primary endpoints were Q3 (vaginal penetration) and Q4 (maintenance of erection) of the International Index of Erectile Function (IIEF). In the intent-to-treat population (n=580), the changes from baseline for 5, 10 and 20 mg vardenafil (1.2, 1.3 and 1.5, respectively) were all improved (P<0.001) over placebo (0.2) for Q3 and were similarly improved for Q4 (1.4, 1.5 and 1.7) compared to placebo (0.5) (P<0.001). All vardenafil doses improved all IIEF domains compared to placebo (P<0.001). The percentage of successful intercourses was between 71 and 75% for the three vardenafil doses. For the 20 mg dose, 80% of the patients experienced improved erections (GAQ) compared to 30% for placebo. Most frequent treatment-emergent adverse events were headache (7-15%), flushing (10-11%) and up to 7% for dyspepsia or rhinitis. Vardenafil treatment resulted in a high efficacy and low adverse-event profile in a population with mixed ED etiologies.

PMID 11494074
T Klotz, R Sachse, A Heidrich, F Jockenhövel, G Rohde, G Wensing, R Horstmann, R Engelmann
Vardenafil increases penile rigidity and tumescence in erectile dysfunction patients: a RigiScan and pharmacokinetic study.
World J Urol. 2001 Feb;19(1):32-9.
Abstract/Text The pharmacodynamic effect on penile rigidity and tumescence and the pharmacokinetic properties of single oral doses of 10 and 20 mg vardenafil, a new PDE5-inhibitor, were investigated in 21 erectile dysfunction patients. Patients were evaluated with RigiScan on three occasions in a randomized, placebo-controlled, double-blind crossover fashion, while receiving visual sexual stimulation. Relative to placebo, a single dose of 10 mg vardenafil led to a mean increase in the duration of >60% penile rigidity of 24.4 min (95% CI: 7.4 to 41.3) at the base and of 24.8 min (8.5 to 41.1) at the tip. For the 20-mg dose, the increase in duration of > 60% penile rigidity relative to placebo was 37.2 min (20.2 to 54.1) at the base and 28.7 min (12.7 to 44.7) at the tip. Single doses of 10 and 20 mg vardenafil led to a rapid rise in the plasma concentrations of vardenafil, with a median tmax of 0.9 h and 0.7 h and a geometric mean Cmax of 9.1 microg/l (geometric SD = 1.63) and 20.9 microg/l (geometric SD = 1.83), respectively. In the post-absorptive phase, the concentrations declined with an average terminal t 1/2 of 4.2 h (geometric SD = 1.27) and 3.9 h (geometric SD = 1.31). The systemic exposure of vardenafil expressed as AUC normalized for dose and body weight was dose-proportional (associated 90% CI: -4 to 30%) as well as Cmax (associated 90% CI: -12 to 33%). The treatments were well tolerated. There was a small, clinically irrelevant reduction in blood pressure with a small compensatory rise in heart rate. There were no electrocardiographic effects or relevant changes of the safety laboratory screens. The observed pro-erectile properties, pharmacokinetic characteristics and safety profile make vardenafil a suitable candidate for further evaluation in the treatment of erectile dysfunction.

PMID 11289568
Wayne J G Hellstrom, Marc Gittelman, Gary Karlin, Thomas Segerson, Marc Thibonnier, Terry Taylor, Harin Padma-Nathan, Vardenafil Study Group
Sustained efficacy and tolerability of vardenafil, a highly potent selective phosphodiesterase type 5 inhibitor, in men with erectile dysfunction: results of a randomized, double-blind, 26-week placebo-controlled pivotal trial.
Urology. 2003 Apr;61(4 Suppl 1):8-14.
Abstract/Text The durability of key efficacy response parameters and safety of vardenafil was evaluated in a pivotal trial conducted in a broad population of men with erectile dysfunction (ED) in North America. In this randomized, double-blind, placebo-controlled, multicenter, fixed-dose, parallel-group, 6-month comparison study, men >18 years of age with ED for >6 months received 5-mg, 10-mg, and 20-mg doses of vardenafil as needed for up to 26 weeks. The primary efficacy variables were the International Index of Erectile Function (IIEF)-Erectile Function (EF) domain scores, and the Sexual Encounter Profile (SEP) mean per-patient success rates for penetration (SEP question 2) and maintenance of erections (SEP question 3). Safety data were also collected over time. Improvement in all primary efficacy variables was observed in all vardenafil groups versus placebo. These improvements occurred early and were either sustained or increased through week 26. Vardenafil in 10-mg and 20-mg doses was significantly superior to placebo at all time points for all efficacy variables (P <0.01), and all doses were superior to placebo at endpoint (P <0.001). Most treatment-emergent adverse events (headache, flushing, dyspepsia, and rhinitis) were mild or moderate in intensity, and incidence generally decreased over time. All 3 doses of vardenafil were superior to placebo across all primary efficacy variables and all study time points in a broad range of patients with ED, regardless of etiology or severity. Vardenafil was well tolerated. These results demonstrate that vardenafil provides sustained efficacy with reduced incidence of nuisance side effects over time. High resolution video, medium resolution video, low resolution video.

PMID 12657355
Hartmut Porst, Harin Padma-Nathan, François Giuliano, Greg Anglin, Lucio Varanese, Raymond Rosen
Efficacy of tadalafil for the treatment of erectile dysfunction at 24 and 36 hours after dosing: a randomized controlled trial.
Urology. 2003 Jul;62(1):121-5; discussion 125-6.
Abstract/Text OBJECTIVES: To examine the therapeutic effects of tadalafil on erectile dysfunction (ED) at 24 and 36 hours after dosing.
METHODS: A multicenter, randomized, double-blind, placebo-controlled, parallel-group study of 348 men (mean age 57 years) with ED was conducted in Europe and the United States. Patients were stratified by baseline severity of ED using the Erectile Function domain score of the International Index of Erectile Function and then randomly allocated within the severity group to receive tadalafil 20 mg (n = 175) or placebo (n = 173). Subsequently, participants were randomly assigned to two 4-week treatment intervals, during which they were requested to attempt sexual intercourse approximately 24 or 36 hours after tadalafil or placebo dosing. The primary outcome measure was the proportion of successful sexual intercourse attempts (completed to ejaculation) according to patient self-report using the Sexual Encounter Profile diary.
RESULTS: Of the 348 patients, 327 (94%) completed the trial (163 of 175 in the tadalafil group and 164 of 173 in the placebo group). Thirty-six hours after tadalafil dosing, 59.2% of intercourse attempts were successful versus 28.3% in the placebo group (P <0.001). The proportion of successful intercourse attempts at approximately 24 hours after treatment was also significantly greater with tadalafil (52.9%) than with placebo (29.1%; P <0.001). Tadalafil was well tolerated. The incidences of four treatment-emergent adverse events were significantly greater in the tadalafil group than in the placebo group (all P <0.05): headache, flushing, dyspepsia, and myalgia.
CONCLUSIONS: Tadalafil 20 mg is an effective and well-tolerated treatment for ED that has a period of responsiveness of up to 36 hours.

PMID 12837435
H Porst
IC351 (tadalafil, Cialis): update on clinical experience.
Int J Impot Res. 2002 Feb;14 Suppl 1:S57-64. doi: 10.1038/sj.ijir.3900807.
Abstract/Text IC351 (tadalafil, trade name Cialis) is a new representative compound of the second generation of selective phosphodiesterase 5 (PDE-5) inhibitors. The selectivity ratio vs PDE-5 is more than 10 000 for PDE-1 through PDE-4 and PDE-7 through PDE-10 and 780 for PDE-6. In the European daily-dosing trial, the efficacy rates were up to 93% for successful intercourses with completion in the 50-mg dose in patients with mild to moderate erectile dysfunction (ED). In two different dose-ranging studies with 2-25 mg taken as needed, efficacy rates of up to 88% improvement in erections and up to 73% successful intercourses with completion were achieved. In a placebo-controlled, fixed-dose (10- and 20-mg) trial in diabetic patients, improved erections of 56% and 64% were reported compared with 25% after placebo. Drug-related adverse effects, with headache in up to 23% of patients (placebo, up to 17%), dyspepsia in up to 11% (placebo, up to 7%), back pain in up to 4.7% (placebo, 0%), and myalgia in up to 4.1% (placebo, up to 2.4%), were mostly mild to moderate. Neither drug-related serious cardiovascular adverse events nor color vision disturbances were encountered. The long half-life (>17 h), with a comfortably long window of opportunity, releases couples from the need to plan sexual activities and therefore provides the highest amount of spontaneity for sexual activities.

PMID 11850737
Fred Govier, Axel-Juerg Potempa, Joel Kaufman, Jonathan Denne, Pavel Kovalenko, Sanjeev Ahuja
A multicenter, randomized, double-blind, crossover study of patient preference for tadalafil 20 mg or sildenafil citrate 50 mg during initiation of treatment for erectile dysfunction.
Clin Ther. 2003 Nov;25(11):2709-23.
Abstract/Text BACKGROUND: Tadalafil is a phosphodiesterase 5 (PDE5) inhibitor approved in >30 countries for the treatment of erectile dysfunction (ED). It has been shown to improve erectile function compared with placebo in Phase III studies, but clinical experience comparing tadalafil with the PDE5 inhibitor sildenafil citrate is lacking.
OBJECTIVE: This study compared patient preference for tadalafil 20 mg or sildenafil 50 mg during initial treatment for ED. It also compared the tolerability of the 2 agents at these doses.
METHODS: This randomized, double-blind, fixed-dose, 2-period crossover trial took place at 13 sites in the United States and Germany. Patients were randomized 1:1 to receive 4 weeks of treatment with tadalafil 20 mg or sildenafil 50 mg, followed by the alternative treatment, to be taken as needed up to once daily before sexual activity.
RESULTS: The study enrolled 215 men with ED, 109 randomized to the tadalafil-sildenafil sequence and 106 to the sildenafil-tadalafil sequence. Their mean age was 49.8 years; 84.7% were sildenafil naive and 15.3% had undergone a previous inadequate trial of sildenafil. Most patients had moderate ED (60.5%) of >or=1 year's duration (74.9%). Of 190 evaluable patients, 126 (66.3%) preferred to initiate treatment with tadalafil, compared with 64 (33.7%) with sildenafil (P < 0.001). Patients' preference did not differ by age, duration of ED, treatment sequence, or previous sildenafil exposure. Both medications were well tolerated, with no significant differences in the incidence of treatment-emergent adverse events. Headache (11.2% tadalafil, 8.8% sildenafil), dyspepsia (6.0% and 4.2%, respectively), nasopharyngitis (4.7% and 2.8%), and flushing (2.8% and 4.7%) were the most common adverse events. The rate of ocular disturbances was low: 1 patient experienced intermittent bilateral reduction in visual acuity with tadalafil, and 2 exhibited conjunctival hyperemia or eyelid edema with sildenafil.
CONCLUSIONS: Tadalafil 20 mg was preferred to sildenafil 50 mg for the initiation of ED therapy in this study population. Both medications were well tolerated.

PMID 14693299
Shin-Ichi Hisasue, Toshiyuki China, Akira Horiuchi, Masaki Kimura, Keisuke Saito, Shuji Isotani, Hisamitsu Ide, Satoru Muto, Raizo Yamaguchi, Shigeo Horie
Impact of aging and comorbidity on the efficacy of low-intensity shock wave therapy for erectile dysfunction.
Int J Urol. 2016 Jan;23(1):80-4. doi: 10.1111/iju.12955. Epub 2015 Oct 26.
Abstract/Text OBJECTIVES: To evaluate the efficacy of low-intensity shock wave therapy and to identify the predictive factors of its efficacy in Japanese patients with erectile dysfunction.
METHODS: The present study included 57 patients with erectile dysfunction who satisfied all the following conditions: more than 6-months history of erectile dysfunction, sexual health inventory for men score of ≤12 without phosphodiesterase type-5 inhibitor, erection hardness score grade 1 or 2, mean penile circumferential change by erectometer assessing sleep related erection of <25 mm and non-neurological pathology. Patients were treated by a low-energy shock waves generator (ED1000; Medispec, Gaithersburg, MD, USA). A total of 12 shock wave treatments were applied. Sexual health inventory for men score, erection hardness score with or without phosphodiesterase type-5 inhibitor, and mean penile circumferential change were assessed at baseline, 1, 3 and 6 months after the termination of low-intensity shock wave therapy.
RESULTS: Of 57 patients who were assigned for the low-intensity shock wave therapy trial, 56 patients were analyzed. Patients had a median age of 64 years. The sexual health inventory for men and erection hardness score (with and without phosphodiesterase type-5 inhibitor) were significantly increased (P < 0.001) at each time-point. The mean penile circumferential change was also increased from 13.1 to 20.2 mm after low-intensity shock wave therapy (P < 0.001). In the multivariate analysis, age and the number of concomitant comorbidities were statistically significant predictors for the efficacy.
CONCLUSIONS: Low-intensity shock wave therapy seems to be an effective physical therapy for erectile dysfunction. Age and comorbidities are negative predictive factors of therapeutic response.

© 2015 The Japanese Urological Association.
PMID 26501992
Noam D Kitrey, Ilan Gruenwald, Boaz Appel, Arik Shechter, Omar Massarwa, Yoram Vardi
Penile Low Intensity Shock Wave Treatment is Able to Shift PDE5i Nonresponders to Responders: A Double-Blind, Sham Controlled Study.
J Urol. 2015 Dec 13;. doi: 10.1016/j.juro.2015.12.049. Epub 2015 Dec 13.
Abstract/Text PURPOSE: We performed sham controlled evaluation of penile low intensity shock wave treatment effect in patients unable to achieve sexual intercourse using PDE5i (phosphodiesterase type 5 inhibitor).
MATERIALS AND METHODS: This prospective, randomized, double-blind, sham controlled study was done in patients with vasculogenic erectile dysfunction who stopped using PDE5i due to no efficacy. All patients had an erection hardness score of 2 or less with PDE5i. A total of 58 patients were randomized, including 37 treated with low intensity shock waves (12 sessions of 1,500 pulses of 0.09 mJ/mm(2) at 120 shock waves per minute) and 18 treated with a sham probe. In the sham group 16 patients underwent low intensity shock wave treatment 1 month after sham treatment. All patients were evaluated at baseline and 1 month after the end of treatment using validated erectile dysfunction questionnaires and the flow mediated dilatation technique for penile endothelial function. Erectile function was evaluated while patients were receiving PDE5i.
RESULTS: In the low intensity shock wave treatment group and the sham group 54.1% and 0% of patients, respectively, achieved erection hard enough for vaginal penetration, that is an EHS (Erection Hardness Score) of 3 (p <0.0001). According to changes in the IIEF-EF (International Index of Erectile Function-Erectile Function) score treatment was effective in 40.5% of men who received low intensity shock wave treatment but in none in the sham group (p = 0.001). Of patients treated with shock waves after sham treatment 56.3% achieved erection hard enough for penetration (p <0.005).
CONCLUSIONS: Low intensity shock wave treatment is effective even in patients with severe erectile dysfunction who are PDE5i nonresponders. After treatment about half of them were able to achieve erection hard enough for penetration with PDE5i. Longer followup is needed to establish the place of low intensity shock wave treatment in these challenging cases.

Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
PMID 26694904
Zhihua Lu, Guiting Lin, Amanda Reed-Maldonado, Chunxi Wang, Yung-Chin Lee, Tom F Lue
Low-intensity Extracorporeal Shock Wave Treatment Improves Erectile Function: A Systematic Review and Meta-analysis.
Eur Urol. 2017 Feb;71(2):223-233. doi: 10.1016/j.eururo.2016.05.050. Epub 2016 Jun 16.
Abstract/Text CONTEXT: As a novel therapeutic method for erectile dysfunction (ED), low-intensity extracorporeal shock wave treatment (LI-ESWT) has been applied recently in the clinical setting. We feel that a summary of the current literature and a systematic review to evaluate the therapeutic efficacy of LI-ESWT for ED would be helpful for physicians who are interested in using this modality to treat patients with ED.
OBJECTIVE: A systematic review of the evidence regarding LI-ESWT for patients with ED was undertaken with a meta-analysis to identify the efficacy of the treatment modality.
EVIDENCE ACQUISITION: A comprehensive search of the PubMed and Embase databases to November 2015 was performed. Studies reporting on patients with ED treated with LI-ESWT were included. The International Index of Erectile Function (IIEF) and the Erection Hardness Score (EHS) were the most commonly used tools to evaluate the therapeutic efficacy of LI-ESWT.
EVIDENCE SYNTHESIS: There were 14 studies including 833 patients from 2005 to 2015. Seven studies were randomized controlled trials (RCTs); however, in these studies, the setup parameters of LI-ESWT and the protocols of treatment were variable. The meta-analysis revealed that LI-ESWT could significantly improve IIEF (mean difference: 2.00; 95% confidence interval [CI], 0.99-3.00; p<0.0001) and EHS (risk difference: 0.16; 95% CI, 0.04-0.29; p=0.01). Therapeutic efficacy could last at least 3 mo. The patients with mild-moderate ED had better therapeutic efficacy after treatment than patients with more severe ED or comorbidities. Energy flux density, number of shock waves per treatment, and duration of LI-ESWT treatment were closely related to clinical outcome, especially regarding IIEF improvement.
CONCLUSIONS: The number of studies of LI-ESWT for ED have increased dramatically in recent years. Most of these studies presented encouraging results, regardless of variation in LI-ESWT setup parameters or treatment protocols. These studies suggest that LI-ESWT could significantly improve the IIEF and EHS of ED patients. The publication of robust evidence from additional RCTs and longer-term follow-up would provide more confidence regarding use of LI-ESWT for ED patients.
PATIENT SUMMARY: We reviewed 14 studies of men who received low-intensity extracorporeal shock wave treatment (LI-ESWT) for erectile dysfunction (ED). There was evidence that these men experienced improvements in their ED following LI-ESWT.

Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.
PMID 27321373

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