今日の臨床サポート

更年期の不定愁訴

著者: 望月 善子 もちづき女性クリニック

監修: 小林裕明 鹿児島大学大学院医歯学総合研究科生殖病態生理学

著者校正/監修レビュー済:2022/01/12
参考ガイドライン:
  1. 日本産婦人科学会、日本産婦人科医会:産婦人科診療ガイドライン 婦人科外来編 2020年度版
患者向け説明資料

概要・推奨   

  1. 更年期障害患者における抑うつ傾向は約60%と決して低くないため、鑑別診断が必要である(推奨度1O)
  1. 更年期障害に対して、HRTは有効であり、国際閉経学会(IMS)のrecommendationでは「禁忌に該当しなければ、中等度から高度の更年期障害に対してはHRTをgold-standardとして勧めるべきである」と強く推奨している(推奨度2JGCS)
  1. 更年期障害に対しては漢方療法も考慮できる(推奨度2Rs)
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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。
※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、実際の保険適用の査定において保険適用及び保険適用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用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:
望月 善子 : 未申告[2022年]
監修:小林裕明 : 講演料(中外製薬株式会社,アストラゼネカ株式会社),研究費・助成金など(シスメックス株式会社),奨学(奨励)寄付など(中外製薬株式会社)[2022年]

改訂のポイント:
  1.  定期レビューを行った。

病態・疫学・診察

疫学情報・病態・注意事項  
  1. 更年期障害とは「更年期に現れる多種多様な症状のなかで、器質的変化に起因しない症状を更年期症状と呼び、これらの症状のなかで日常生活に支障を来す病態を更年期障害と定義する」とされている。
  1. 更年期女性の約50~80%が更年期に愁訴を訴えるといわれている。これらのうち、少なく見積もって30%が何らかの治療が必要であるとしても、更年期障害は400万人、総女性人口の6%もが治療対象となると推計される。産婦人科のみならず内科や整形外科を初診で受診する症例も少なくない。
  1. 更年期に現れる原因不明の種々の不定愁訴のうち、日常生活に差し障りのあるものが更年期障害であり、以下の点を満たすことが必要である。診断基準はない。
  1. 更年期に現れること
  1. 器質的疾患に起因しないこと
  1. 日常生活に支障を来すこと
  1. 症状は多彩である。のぼせ・ほてりといったホットフラッシュが有名であるが、これがあれば更年期障害といえる特徴的な症状はない。
  1. 閉経に伴うエストロゲンの消退が最も大きな要因であるが、対人関係や家族の問題などの社会的環境的要因や生来の性格や生育歴などの心理的・性格的要因も無視できない。
  1. 除外診断によって診断される疾患であるため、鑑別診断が重要であり、特に、うつ病などの精神疾患、不安障害、甲状腺機能異常(亢進症・低下症)などは常に念頭に置く。
問診・診察のポイント  
 
  1. 更年期とは閉経の前後10年間をいう。最終月経より1年間月経がない時点で閉経と診断される。日本人女性の閉経年齢は約50歳であるが、個人差が大きく、更年期障害は40歳から60歳ごろの女性にみられると考えてよい。したがって、70歳以降の女性や20歳代、30歳代の女性に生じる更年期障害類似の症状は更年期障害とはいえない。子宮摘出後の場合にはホルモン値(エストロゲン値は月経周期中でも変化の幅が大きいため、卵胞刺激ホルモン[FSH]値)を参考にする。特徴的な症状はないとされてはいるが、のぼせ・ほてり・発汗は頻度が高く、これらがまったくない症例は少ない。

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文献 

M H Birkhäuser, N Panay, D F Archer, D Barlow, H Burger, M Gambacciani, S Goldstein, J A Pinkerton, D W Sturdee
Updated practical recommendations for hormone replacement therapy in the peri- and postmenopause.
Climacteric. 2008 Apr;11(2):108-23. doi: 10.1080/13697130801983921.
Abstract/Text
PMID 18365854
A H Maclennan, J L Broadbent, S Lester, V Moore
Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes.
Cochrane Database Syst Rev. 2004 Oct 18;(4):CD002978. doi: 10.1002/14651858.CD002978.pub2. Epub 2004 Oct 18.
Abstract/Text BACKGROUND: Hot flushes and night sweats are common symptoms experienced by menopausal women. Hormone therapy (HT), containing oestrogens alone or oestrogens together with progestogens in a cyclic or continuous regimen, is often recommended for their alleviation.
OBJECTIVES: To examine the effect of oral HT compared to placebo on these vasomotor symptoms and the risk of early onset side-effects.
SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders Group and Subfertility Group trials register (searched May 2002). This register is based on regular searches of MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, the handsearching of 20 relevant journals and conference proceedings, and searches of several key grey literature sources. We also contacted all relevant pharmaceutical companies, The Journal of the International Menopause Society and Climacteric.
SELECTION CRITERIA: Double-blind, randomised, placebo-controlled trials of oral HT for at least three months duration.
DATA COLLECTION AND ANALYSIS: Study quality and outcome data were assessed independently. Random effects models were considered appropriate due to the variety of trial methodologies. The meta-analyses were explored for sensitivity to trial quality and therapy duration. Symptom frequency and severity were assessed separately, together with withdrawals and side-effects. Frequency data were analysed using the Weighted Mean Difference (WMD) between treatment and placebo outcomes. For severity data, odds ratios were estimated from the proportional odds model. From 115 references originally identified, 24 trials meeting the selection criteria were included in the review. Study participants totaled 3,329. Trial duration ranged from three months to three years.
MAIN RESULTS: There was a significant reduction in the weekly hot flush frequency for HT compared to placebo (WMD -17.92, 95% CI -22.86 to -12.99). This was equivalent to a 75% reduction in frequency (95% CI 64.3 to 82.3) for HT relative to placebo. Symptom severity was also significantly reduced compared to placebo (OR 0.13, 95% CI 0.07 to 0.23). Withdrawal for lack of efficacy occurred significantly more often on placebo therapy (OR 10.51, 95% CI 5.00 to 22.09). Withdrawal for adverse events, commonly breast tenderness, oedema, joint pain and psychological symptoms, was not significantly increased (OR 1.25, 95% CI 0.83 to 1.90), although the occurrence of any adverse events was significantly increased for HT (OR 1.41, 95% CI 1.00 to 1.99). In women who were randomised to placebo treatment, a 57.7% (95% CI 45.1 to 67.7) reduction in hot flushes was observed between baseline and end of study.
REVIEWERS' CONCLUSIONS: Oral HT is highly effective in alleviating hot flushes and night sweats. Therapies purported to reduce such symptoms must be assessed in blinded trials against a placebo or a validated therapy because of the large placebo effect seen in well conducted randomised controlled trials, and also because during menopause symptoms may fluctuate and after menopause symptoms often decline. Withdrawals due to side-effects were only marginally increased in the HT groups despite the inability to tailor HT in these fixed dose trials. Comparisons of hormonal doses, product types or regimens require analysis of trials with these specific "within study" comparisons.

PMID 15495039
Heidi D Nelson
Commonly used types of postmenopausal estrogen for treatment of hot flashes: scientific review.
JAMA. 2004 Apr 7;291(13):1610-20. doi: 10.1001/jama.291.13.1610.
Abstract/Text CONTEXT: Recommendations for postmenopausal hormone therapy have changed since the Women's Health Initiative indicated that estrogen was harmful for use in disease prevention; however, treatment of menopausal symptoms with low-dose estrogen remains an approved indication for use.
OBJECTIVE: To compare the short-term efficacy and adverse effects of 2 commonly used estrogens, conjugated equine estrogen (CEE) and 17beta-estradiol, for reducing menopausal hot flashes by systematically reviewing randomized controlled trials.
DATA SOURCES: MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, and Cochrane Controlled Trials Registry were searched from the database start dates to July 2003 using database-specific key words. Reference lists of published articles, experts, and pharmaceutical manufacturers were also consulted.
STUDY SELECTION: English-language abstracts of double-blind, randomized, placebo-controlled trials and systematic evidence reviews of oral CEE and oral and transdermal 17beta-estradiol, and treatment of menopausal hot flashes and their adverse effects.
DATA EXTRACTION: Study design, population characteristics, eligibility criteria, interventions, withdrawals, adverse effects, and results for each outcome. Study quality was assessed using predefined criteria based on parameters developed with the US Preventive Services Task Force and the UK National Health Services Centre.
DATA SYNTHESIS: A total of 32 trials including 4 head-to-head comparisons met inclusion criteria; 14 trials met criteria for meta-analysis. All estrogen agents significantly reduced the weekly number of hot flashes compared with placebo (CEE, 1 trial: mean change, -19.1; 95% confidence interval [CI], -33.0 to -5.1; oral 17beta-estradiol, 5 trials: pooled weighted mean difference, -16.8; 95% CI, -23.4 to -10.2; transdermal 17beta-estradiol, 6 trials: pooled weighted mean difference, -22.4; 95% CI, -35.9 to -10.4); differences between agents were not significant. Breast tenderness and atypical vaginal bleeding were the most frequently reported adverse effects among estrogen users. The influence of progestin or progesterone use, cyclic and continuous regimens, and differences in adverse effects could not be determined.
CONCLUSION: Conjugated equine estrogen and 17beta-estradiol have consistent and comparable effects on treatment of menopausal hot flashes and may have similar short-term adverse effects.

PMID 15069049
Jan L Shifren, Isaac Schiff
Role of hormone therapy in the management of menopause.
Obstet Gynecol. 2010 Apr;115(4):839-55. doi: 10.1097/AOG.0b013e3181d41191.
Abstract/Text There are many options available to address the quality of life and health concerns of menopausal women. The principal indication for hormone therapy (HT) is the treatment of vasomotor symptoms, and benefits generally outweigh risks for healthy women with bothersome symptoms who elect HT at the time of menopause. Although HT increases the risk of coronary heart disease, recent analyses confirm that this increased risk occurs principally in older women and those a number of years beyond menopause. These findings do not support a role for HT in the prevention of heart disease but provide reassurance regarding the safety of use for hot flushes and night sweats in otherwise healthy women at the menopausal transition. An increased risk of breast cancer with extended use is another reason short-term treatment is advised. Hormone therapy prevents and treats osteoporosis but is rarely used solely for this indication. If only vaginal symptoms are present, low-dose local estrogen therapy is preferred. Contraindications to HT use include breast or endometrial cancer, cardiovascular disease, thromboembolic disorders, and active liver disease. Alternatives to HT should be advised for women with or at increased risk for these disorders. The lowest effective estrogen dose should be provided for the shortest duration necessary because risks increase with increasing age, time since menopause, and duration of use. Women must be informed of the potential benefits and risks of all therapeutic options, and care should be individualized, based on a woman's medical history, needs, and preferences.

PMID 20308847
Jacques E Rossouw, Garnet L Anderson, Ross L Prentice, Andrea Z LaCroix, Charles Kooperberg, Marcia L Stefanick, Rebecca D Jackson, Shirley A A Beresford, Barbara V Howard, Karen C Johnson, Jane Morley Kotchen, Judith Ockene, Writing Group for the Women's Health Initiative Investigators
Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial.
JAMA. 2002 Jul 17;288(3):321-33.
Abstract/Text CONTEXT: Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain.
OBJECTIVE: To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States.
DESIGN: Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998.
INTERVENTIONS: Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102).
MAIN OUTCOMES MEASURES: The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes.
RESULTS: On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years.
CONCLUSIONS: Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.

PMID 12117397
Garnet L Anderson, Marian Limacher, Annlouise R Assaf, Tamsen Bassford, Shirley A A Beresford, Henry Black, Denise Bonds, Robert Brunner, Robert Brzyski, Bette Caan, Rowan Chlebowski, David Curb, Margery Gass, Jennifer Hays, Gerardo Heiss, Susan Hendrix, Barbara V Howard, Judith Hsia, Allan Hubbell, Rebecca Jackson, Karen C Johnson, Howard Judd, Jane Morley Kotchen, Lewis Kuller, Andrea Z LaCroix, Dorothy Lane, Robert D Langer, Norman Lasser, Cora E Lewis, JoAnn Manson, Karen Margolis, Judith Ockene, Mary Jo O'Sullivan, Lawrence Phillips, Ross L Prentice, Cheryl Ritenbaugh, John Robbins, Jacques E Rossouw, Gloria Sarto, Marcia L Stefanick, Linda Van Horn, Jean Wactawski-Wende, Robert Wallace, Sylvia Wassertheil-Smoller, Women's Health Initiative Steering Committee
Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial.
JAMA. 2004 Apr 14;291(14):1701-12. doi: 10.1001/jama.291.14.1701.
Abstract/Text CONTEXT: Despite decades of use and considerable research, the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain.
OBJECTIVE: To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States.
DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled disease prevention trial (the estrogen-alone component of the Women's Health Initiative [WHI]) conducted in 40 US clinical centers beginning in 1993. Enrolled were 10 739 postmenopausal women, aged 50-79 years, with prior hysterectomy, including 23% of minority race/ethnicity.
INTERVENTION: Women were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen (CEE) or placebo.
MAIN OUTCOME MEASURES: The primary outcome was coronary heart disease (CHD) incidence (nonfatal myocardial infarction or CHD death). Invasive breast cancer incidence was the primary safety outcome. A global index of risks and benefits, including these primary outcomes plus stroke, pulmonary embolism (PE), colorectal cancer, hip fracture, and deaths from other causes, was used for summarizing overall effects.
RESULTS: In February 2004, after reviewing data through November 30, 2003, the National Institutes of Health (NIH) decided to end the intervention phase of the trial early. Estimated hazard ratios (HRs) (95% confidence intervals [CIs]) for CEE vs placebo for the major clinical outcomes available through February 29, 2004 (average follow-up 6.8 years), were: CHD, 0.91 (0.75-1.12) with 376 cases; breast cancer, 0.77 (0.59-1.01) with 218 cases; stroke, 1.39 (1.10-1.77) with 276 cases; PE, 1.34 (0.87-2.06) with 85 cases; colorectal cancer, 1.08 (0.75-1.55) with 119 cases; and hip fracture, 0.61 (0.41-0.91) with 102 cases. Corresponding results for composite outcomes were: total cardiovascular disease, 1.12 (1.01-1.24); total cancer, 0.93 (0.81-1.07); total fractures, 0.70 (0.63-0.79); total mortality, 1.04 (0.88-1.22), and the global index, 1.01 (0.91-1.12). For the outcomes significantly affected by CEE, there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years. The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years.
CONCLUSIONS: The use of CEE increases the risk of stroke, decreases the risk of hip fracture, and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years. A possible reduction in breast cancer risk requires further investigation. The burden of incident disease events was equivalent in the CEE and placebo groups, indicating no overall benefit. Thus, CEE should not be recommended for chronic disease prevention in postmenopausal women.

PMID 15082697
Gerardo Heiss, Robert Wallace, Garnet L Anderson, Aaron Aragaki, Shirley A A Beresford, Robert Brzyski, Rowan T Chlebowski, Margery Gass, Andrea LaCroix, JoAnn E Manson, Ross L Prentice, Jacques Rossouw, Marcia L Stefanick, WHI Investigators
Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin.
JAMA. 2008 Mar 5;299(9):1036-45. doi: 10.1001/jama.299.9.1036.
Abstract/Text CONTEXT: The Women's Health Initiative (WHI) trial of estrogen plus progestin vs placebo was stopped early, after a mean 5.6 years of follow-up, because the overall health risks of hormone therapy exceeded its benefits.
OBJECTIVE: To report health outcomes at 3 years (mean 2.4 years of follow-up) after the intervention was stopped.
DESIGN, SETTING, AND PARTICIPANTS: The intervention phase was a double-blind, placebo-controlled, randomized trial of conjugated equine estrogens (CEE) 0.625 mg daily plus medroxyprogesterone acetate (MPA) 2.5 mg daily, in 16,608 women aged 50 through 79 years, recruited by 40 centers from 1993 to 1998. The postintervention phase commenced July 8, 2002, and included 15 730 women.
MAIN OUTCOME MEASURES: Semi-annual monitoring and outcomes ascertainment continued per trial protocol. The primary end points were coronary heart disease and invasive breast cancer. A global index summarizing the balance of risks and benefits included the 2 primary end points plus stroke, pulmonary embolism, endometrial cancer, colorectal cancer, hip fracture, and death due to other causes.
RESULTS: The risk of cardiovascular events after the intervention was comparable by initial randomized assignments, 1.97% (annualized rate) in the CEE plus MPA (343 events) and 1.91% in the placebo group (323 events). A greater risk of malignancies occurred in the CEE plus MPA than in the placebo group (1.56% [n = 281] vs 1.26% [n = 218]; hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.04-1.48). More breast cancers were diagnosed in women who had been randomly assigned to receive CEE plus MPA vs placebo (0.42% [n = 79] vs 0.33% [n = 60]; HR, 1.27; 95% CI, 0.91-1.78) with a modest trend toward a lower HR during the follow-up after the intervention. All-cause mortality was somewhat higher in the CEE plus MPA than in the placebo group (1.20% [n = 233] vs 1.06% [n = 196]; HR, 1.15; 95% CI, 0.95-1.39). The global index of risks and benefits was unchanged from randomization through March 31, 2005 (HR, 1.12; 95% CI, 1.03-1.21), indicating that the risks of CEE plus MPA exceed the benefits for chronic disease prevention.
CONCLUSIONS: The increased cardiovascular risks in the women assigned to CEE plus MPA during the intervention period were not observed after the intervention. A greater risk of fatal and nonfatal malignancies occurred after the intervention in the CEE plus MPA group and the global risk index was 12% higher in women randomly assigned to receive CEE plus MPA compared with placebo.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000611.

PMID 18319414
Gregory A Plotnikoff, Kenji Watanabe, Carolyn Torkelson, June La Valleur, David M Radosevich
The TU-025 keishibukuryogan clinical trial for hot flash management in postmenopausal women: results and lessons for future research.
Menopause. 2011 Aug;18(8):886-92. doi: 10.1097/gme.0b013e31821643d9.
Abstract/Text OBJECTIVE: The aim of this study was to assess the efficacy of TU-025, keishibukuryogan, a Japanese prescription herbal medicine used for hot flash management, in American women.
METHODS: This randomized, double-blind, placebo-controlled, phase II trial enrolled 178 postmenopausal women aged 45 to 58 years with a Mayo hot flash score greater than 28 per week who met other inclusion criteria. After a 1-week placebo run-in period, participants were randomly assigned placebo, or 7.5 g/day, or 12.5 g/day groups, for 12 weeks. Primary and secondary outcomes were measured using the Mayo Clinic Hot Flash Diary, the Greene Climacteric Index, and the Pittsburgh Sleep Quality Index.
RESULTS: At 3 months, hot flash scores, climacteric symptoms, and sleep quality improved by 34% in the placebo group, 40% in the 7.5 g/day group, and 38% in the 12.5 g/day group. (P < 0.001). However, the differences in changes between groups were not statistically significant (P = 0.990). Diarrhea unexpectedly developed in 20% of participants receiving active medication.
CONCLUSIONS: For American women, unlike the clinical experience for Japanese women, TU-025 did not significantly reduce the frequency and severity of hot flash symptoms, improve climacteric symptoms, or benefit sleep quality. This study identified several potentially significant methodological factors to be considered in future scientific assessments of traditional Asian medicines.

PMID 21738077
Hideaki Nagata, Masahiro Nozaki, Hitoo Nakano
Short-term combinational therapy of low-dose estrogen with selective serotonin re-uptake inhibitor (fluvoxamine) for oophorectomized women with hot flashes and depressive tendencies.
J Obstet Gynaecol Res. 2005 Apr;31(2):107-14. doi: 10.1111/j.1447-0756.2005.00254.x.
Abstract/Text AIM: To examine whether low-dose and short-term estrogen-replacement therapy (ERT) plus selective serotonin re-uptake inhibitor (SSRI) treatment is effective or not in the treatment of climacteric disorders, hot flashes and depressive symptoms, in oophorectomized women.
METHOD: Forty-two oophorectomized women with hot flashes and depressive symptoms were assigned randomly to two groups. We examined the efficacy rates of climacteric disorders, particularly hot flashes and depressive symptoms in 21 women on low-dose ERT (conjugated equine estrogens [CEE] 0.3125 mg/day) and 21 women on low-dose ERT (CEE 0.3125 mg/day) plus SSRI (fluvoxamine 50 mg/day) treated for 8 weeks. We used questionnaires to evaluate the efficacy for depression, namely the Self-rating Depression Scale (SDS) and the Self-rating Questionnaire for Depression (SRQ-D), and for anxiety with the State-Trait Anxiety Inventory (STAI). In the statistical analysis, in the mixed-effect model, for the score against time and adjusted with age, treatment and treatment as the fixed effects.
RESULTS: The average scores on the SDS in both groups were decreased by the treatment (P < 0.001). But the efficacy of the ERT + SSRI group in the time x treatment SDS and SRQ-D scores was significantly higher compared with those of ERT (P = 0.0025, 0.0162) and there was a significant difference in the decrease in the frequency of hot flashes by 8 weeks between the two groups (P = 0.036).
CONCLUSIONS: A combination of low-dose and short-term ERT + SSRI is more effective than low-dose estrogen alone in relieving the depressive symptoms and hot flashes of oophorectomized women.

PMID 15771635
Paul R Gordon, James P Kerwin, Kelly Green Boesen, Janet Senf
Sertraline to treat hot flashes: a randomized controlled, double-blind, crossover trial in a general population.
Menopause. 2006 Jul-Aug;13(4):568-75. doi: 10.1097/01.gme.0000196595.82452.ca.
Abstract/Text OBJECTIVE: To evaluate the effectiveness of a selective serotonin reuptake inhibitor (SSRI) (sertraline) in decreasing hot flashes in a general population of women.
DESIGN: A double-blind, placebo-controlled, crossover trial was conducted in a southwestern urban setting. A total of 102 women aged 40 to 65 who were experiencing hot flashes and not taking any hormone therapy were recruited. After 1 week of baseline hot flash data collection, study participants were randomized to receive placebo or active drug (sertraline 50 mg) for 4 weeks. This intervention was followed by a 1-week washout and cross over to the opposite treatment for 4 weeks. The number and severity of hot flashes were measured.
RESULTS: One hundred two women were enrolled in the study. Five dropped out before providing baseline data. Of the 97 remaining, 52 were randomized to active drug first and 45 to placebo first. Ten dropped out of the study before completing all 10 weeks, leaving 46 in the active drug-first arm and 41 in the placebo-first arm. At baseline, the mean number of hot flashes reported was 45.6 per week (SD = 29.6), ranging from 2 to 148. During the sertraline phase of the study, women experienced five fewer hot flashes per week than they did on the placebo (P = 0.002). The severity of hot flashes was not significantly different; however, the hot flash score (number x average severity) was significantly improved during the sertraline phase.
CONCLUSION: Sertraline reduced the number of hot flashes and improved the hot flash score relative to placebo and may be an acceptable alternative treatment for women experiencing hot flashes.

PMID 16837878
Ellen W Freeman, Katherine A Guthrie, Bette Caan, Barbara Sternfeld, Lee S Cohen, Hadine Joffe, Janet S Carpenter, Garnet L Anderson, Joseph C Larson, Kristine E Ensrud, Susan D Reed, Katherine M Newton, Sheryl Sherman, Mary D Sammel, Andrea Z LaCroix
Efficacy of escitalopram for hot flashes in healthy menopausal women: a randomized controlled trial.
JAMA. 2011 Jan 19;305(3):267-74. doi: 10.1001/jama.2010.2016.
Abstract/Text CONTEXT: Concerns regarding the risks associated with estrogen and progesterone to manage menopausal symptoms have resulted in its declining use and increased interest in nonhormonal treatments with demonstrated efficacy for hot flashes.
OBJECTIVE: To determine the efficacy and tolerability of 10 to 20 mg/d escitalopram, a selective serotonin reuptake inhibitor, in alleviating the frequency, severity, and bother of menopausal hot flashes.
DESIGN, SETTING, AND PATIENTS: A multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel group trial that enrolled 205 women (95 African American; 102 white; 8 other) between July 2009 and June 2010.
INTERVENTION: Women received 10 to 20 mg/d of escitalopram or a matching placebo for 8 weeks.
MAIN OUTCOME MEASURES: Primary outcomes were the frequency and severity of hot flashes assessed by prospective daily diaries at weeks 4 and 8. Secondary outcomes were hot flash bother, recorded on daily diaries, and clinical improvement (defined as hot flash frequency ≥50% decrease from baseline).
RESULTS: Mean (SD) daily hot flash frequency was 9.78 (5.60) at baseline. In a modified intent-to-treat analysis that included all randomized participants who provided hot flash diary data, the mean difference in hot flash frequency reduction was 1.41 (95% CI, 0.13-2.69) fewer hot flashes per day at week 8 among women taking escitalopram (P < .001), with mean reductions of 4.60 (95% CI, 3.74-5.47) and 3.20 (95% CI, 2.24-4.15) hot flashes per day in the escitalopram and placebo groups, respectively. Fifty-five percent of women in the escitalopram group vs 36% in the placebo group reported a decrease of at least 50% in hot flash frequency (P = .009) at the 8-week follow-up. Reductions in hot flash severity scores were significantly greater in the escitalopram group (-0.52; 95% CI, -0.64 to -0.40 vs -0.30; 95% CI, -0.42 to -0.17 for placebo; P < .001). Race did not significantly modify the treatment effect (P = .62). Overall discontinuation due to adverse events was 4% (7 in the active group, 2 in the placebo group). Three weeks after treatment ended, women in the escitalopram group reported a mean 1.59 (95% CI, 0.55-2.63; P = .02) more hot flashes per day than women in the placebo group.
CONCLUSION: Among healthy women, the use of escitalopram (10-20 mg/d) compared with placebo resulted in fewer and less severe menopausal hot flashes at 8 weeks of follow-up.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00894543.

PMID 21245182
Akira Oishi, Yoshiko Mochizuki, Reiko Otsu, Noriyuki Inaba
Pilot study of fluvoxamine treatment for climacteric symptoms in Japanese women.
Biopsychosoc Med. 2007 Jun 5;1:12. doi: 10.1186/1751-0759-1-12. Epub 2007 Jun 5.
Abstract/Text BACKGROUND: Selective serotonin-reuptake inhibitors (SSRIs) are commonly prescribed for the treatment of depression and can be used as nonhormonal alternatives to manage hot flashes for women with a history of breast cancer and unable to take hormone replacement therapy. There are, however, few reports on the efficacy of SSRIs for the treatment of natural postmenopausal climacteric symptoms. In this pilot study, we evaluate the SSRI, fluvoxamine, for controlling climacteric symptoms and vasomotor symptoms, in particular.
METHODS: Twenty-two patients were enrolled from our hospital. All were orally administered fluvoxamine (50 mg daily). Climacteric and depressive symptoms were assessed using simple menopausal index (SMI) and self-rating questionnaire for depression (SRQ-D), respectively, at baseline, and at 2 and 6 weeks post-treatment.
RESULTS: Six weeks following drug administration, neither the SRQ-D nor SMI scores significantly decreased compared to baseline. The mean levels of vasomotor symptoms and mental symptoms decreased significantly following fluvoxamine administration, while skeletal muscle symptom scores did not.
CONCLUSION: We were able to demonstrate that fluvoxamine was effective in treating not only depressive moods in climacteric symptoms but also the associated vasomotor symptoms. There are several limitations to this preliminary study. Future controlled studies are needed to further evaluate the efficacy of fluvoxamine for climacteric disturbances.

PMID 17547780
Anja Jacobs, Uta Wegewitz, Christine Sommerfeld, Rolf Grossklaus, Alfonso Lampen
Efficacy of isoflavones in relieving vasomotor menopausal symptoms - A systematic review.
Mol Nutr Food Res. 2009 Sep;53(9):1084-97. doi: 10.1002/mnfr.200800552.
Abstract/Text This review assessed the efficacy of isoflavone supplements to reduce vasomotor symptoms in menopausal women by reviewing all published randomized controlled trials. Systematic literature searches were carried out in 70 databases. Randomized and placebo controlled studies were included if they investigated the treatment of isoflavone supplements derived from soy or red clover on vasomotor symptoms in peri- or postmenopausal women for at least 12 wks. Data were analyzed concerning outcome and methodological quality of the study. Twenty-three trials met the inclusion criteria, thereof 17 investigated soy isoflavones and 6 red clover isoflavones. Without exception, selected trials examining the effect of red clover isoflavones were already assessed in several meta-analyses and were therefore excluded from this evaluation. As the soy isoflavone studies were very heterogeneous concerning interventions and outcome measures, meta-analysis could not be performed and trials were systematically assessed in a structured approach. Included soy isoflavone studies had numerous quality deficiencies and did not consistently show a reduction of flushes after treatment with soy isoflavones. Therefore, there is no conclusive evidence, but only some indication of a benefit of soy isoflavones on hot flush frequency or severity.

PMID 19653225
Kyoko Taku, Melissa K Melby, Fredi Kronenberg, Mindy S Kurzer, Mark Messina
Extracted or synthesized soybean isoflavones reduce menopausal hot flash frequency and severity: systematic review and meta-analysis of randomized controlled trials.
Menopause. 2012 Jul;19(7):776-90. doi: 10.1097/gme.0b013e3182410159.
Abstract/Text OBJECTIVE: This analysis was conducted to determine the efficacy of extracted or synthesized soybean isoflavones in the alleviation of hot flashes in perimenopausal and postmenopausal women.
METHODS: PubMed and The Cochrane Controlled Clinical Trials Register Database were searched for relevant articles reporting double-blinded randomized controlled trials through December 14, 2010. References within identified articles, as well as peer-reviewed articles that had come to the attention of the authors through other means, were also examined for suitability. This systematic review and meta-analysis, which evaluated the effects of isoflavones on the frequency, severity, or composite score (frequency × severity) of hot flashes compared with placebo was conducted according to Cochrane Handbook guidelines.
RESULTS: From 277 potentially relevant publications, 19 trials (reported in 20 articles) were included in the systematic review (13 included hot flash frequency; 10, severity; and 3, composite scores), and 17 trials were selected for meta-analyses to clarify the effect of soybean isoflavones on hot flash frequency (13 trials) and severity (9 trials). Meta-analysis revealed that ingestion of soy isoflavones (median, 54 mg; aglycone equivalents) for 6 weeks to 12 months significantly reduced the frequency (combined fixed-effect and random effects model) of hot flashes by 20.6% (95% CI, -28.38 to -12.86; P < 0.00001) compared with placebo (heterogeneity P = 0.0003, I = 67%; random effects model). Meta-analysis also revealed that isoflavones significantly reduced hot flash severity by 26.2% (95% CI: -42.23 to -10.15, P = 0.001) compared with placebo (heterogeneity, P < 0.00001, I = 86%; random effects model). Isoflavone supplements providing more than 18.8 mg of genistein (the median for all studies) were more than twice as potent at reducing hot flash frequency than lower genistein supplements.
CONCLUSIONS: Soy isoflavone supplements, derived by extraction or chemical synthesis, are significantly more effective than placebo in reducing the frequency and severity of hot flashes. Additional studies are needed to further address the complex array of factors that may affect efficacy, such as dose, isoflavone form, baseline hot flash frequency, and treatment duration.

PMID 22433977
Takeshi Aso, Shigeto Uchiyama, Yasuhiro Matsumura, Makoto Taguchi, Masahiro Nozaki, Kiyoshi Takamatsu, Bunpei Ishizuka, Toshiro Kubota, Hideki Mizunuma, Hiroaki Ohta
A natural S-equol supplement alleviates hot flushes and other menopausal symptoms in equol nonproducing postmenopausal Japanese women.
J Womens Health (Larchmt). 2012 Jan;21(1):92-100. doi: 10.1089/jwh.2011.2753. Epub 2011 Oct 12.
Abstract/Text OBJECTIVE: The objective of this clinical trial was to examine the efficacy of a supplement containing natural S-(-)equol, a daidzein metabolite, in reducing menopausal symptoms.
METHODS: In this multicenter, double-blind placebo-controlled trial, 160 equol nonproducing, postmenopausal Japanese women who experienced at least 1 hot flush/day were randomly assigned to consume 10 mg/day S-(-)equol (n=77 women) or placebo (n=83 women) for 12 weeks. Participants completed a standardized menopausal symptom checklist and rated five common menopause symptoms by a visual analog scale at baseline, week 12, and week 18 (6-week postintervention). Physical, blood, and urine examinations were conducted. One hundred twenty-six women completed the study.
RESULTS: At baseline, daily hot flush frequency was 2.9±2.1 for the S-(-)equol group and 3.2±2.4 for the placebo group. After the 12-week intervention, the S-(-)equol group had a greater decrease from baseline in hot flush frequency compared with the placebo group (-1.9±1.8/day, -58.7%, vs. -1.0±2.0/day, -34.5%, p=0.009). The severity of hot flushes and neck or shoulder muscle stiffness significantly decreased in the S-(-)equol group compared with the placebo group. No changes in clinical parameters or serious adverse effects were reported.
CONCLUSIONS: This is the first trial to show beneficial effects of a 10-mg natural S-(-)equol supplement consumed daily for 12 weeks on major menopausal symptoms, specifically, hot flushes and neck or shoulder muscle stiffness, in postmenopausal Japanese women. This supplement offers a promising alternative for management of menopausal symptoms.

PMID 21992596
Heidi D Nelson, Kimberly K Vesco, Elizabeth Haney, Rongwei Fu, Anne Nedrow, Jill Miller, Christina Nicolaidis, Miranda Walker, Linda Humphrey
Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis.
JAMA. 2006 May 3;295(17):2057-71. doi: 10.1001/jama.295.17.2057.
Abstract/Text CONTEXT: Concern regarding the adverse effects of estrogen and other hormones for treating menopausal symptoms has led to demand for other options; however, the efficacy and adverse effects of nonhormonal therapies are unclear.
OBJECTIVE: To assess the efficacy and adverse effects of nonhormonal therapies for menopausal hot flashes by reviewing published randomized controlled trials.
DATA SOURCES: MEDLINE (1966-October 2005), PsycINFO (1974-October 2005), and the Cochrane Controlled Clinical Trials Register Database (1966-October 2005) were searched for relevant trials that provided data on treatment of menopausal hot flashes using 1 or more nonhormonal therapies.
STUDY SELECTION: All English-language, published, randomized, double-blind, placebo-controlled trials of oral nonhormonal therapies for treating hot flashes in menopausal women measuring and reporting hot flash frequency or severity outcomes.
DATA EXTRACTION: Trials were identified, subjected to inclusion and exclusion criteria, and reviewed. Data on participants, interventions, and outcomes were extracted and trials were rated for quality based on established criteria. A meta-analysis was conducted for therapies with sufficient trials reporting hot flash frequency outcomes.
DATA SYNTHESIS: From 4249 abstracts, 43 trials met inclusion criteria, including 10 trials of antidepressants, 10 trials of clonidine, 6 trials of other prescribed medications, and 17 trials of isoflavone extracts. The number of daily hot flashes decreased compared with placebo in meta-analyses of 7 comparisons of selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) (mean difference, -1.13; 95% confidence interval [CI], -1.70 to -0.57), 4 trials of clonidine (-0.95; 95% CI, -1.44 to -0.47), and 2 trials of gabapentin (-2.05; 95% CI, -2.80 to -1.30). Frequency was not reduced in meta-analysis of trials of red clover isoflavone extracts and results were mixed for soy isoflavone extracts. Evidence of the efficacy of other therapies is limited due to the small number of trials and their deficiencies. Trials do not compare different therapies head-to-head and relative efficacy cannot be determined.
CONCLUSION: The SSRIs or SNRIs, clonidine, and gabapentin trials provide evidence for efficacy; however, effects are less than for estrogen, few trials have been published and most have methodological deficiencies, generalizability is limited, and adverse effects and cost may restrict use for many women. These therapies may be most useful for highly symptomatic women who cannot take estrogen but are not optimal choices for most women.

PMID 16670414
Abstract/Text Lack of confidence in the espoused benefits of hormone replacement therapy (HRT) coupled with a significant array of side effects of HRT, results in fewer than 1 in 3 women choosing to take HRT. The use of alternatives to conventional HRT has become more accessible and acceptable to many women. As more women choose these alternatives, physicians are confronted with the challenges of how to advise patients about alternative medicine and how to determine which therapies may be safe and effective. This document will examine available scientific information on alternative therapies for treatment of menopausal symptoms and provide recommendations on efficacy and potential adverse consequences.

PMID 11501568
Gabriel Rada, Daniel Capurro, Tomas Pantoja, Javiera Corbalán, Gladys Moreno, Luz M Letelier, Claudio Vera
Non-hormonal interventions for hot flushes in women with a history of breast cancer.
Cochrane Database Syst Rev. 2010 Sep 8;(9):CD004923. doi: 10.1002/14651858.CD004923.pub2. Epub 2010 Sep 8.
Abstract/Text BACKGROUND: Hot flushes are common in women with a history of breast cancer. Hormonal therapies are known to reduce these symptoms but are not recommended in women with a history of breast cancer due to their potential adverse effects. The efficacy of non-hormonal therapies is still uncertain.
OBJECTIVES: To assess the efficacy of non-hormonal therapies in reducing hot flushes in women with a history of breast cancer.
SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group Specialised Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE, LILACS, CINAHL, PsycINFO (August 2008) and WHO ICTRP Search Portal. We handsearched reference lists of reviews and included articles, reviewed conference proceedings and contacted experts.
SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing non-hormonal therapies with placebo or no therapy for reducing hot flushes in women with a history of breast cancer.
DATA COLLECTION AND ANALYSIS: Two authors independently selected potentially relevant studies, decided upon their inclusion and extracted data on participant characteristics, interventions, outcomes and the risk of bias of included studies.
MAIN RESULTS: Sixteen RCTs met our inclusion criteria. We included six studies on selective serotonin (SSRI) and serotonin-norepinephrine (SNRI) reuptake inhibitors, two on clonidine, one on gabapentin, two each on relaxation therapy and homeopathy, and one each on vitamin E, magnetic devices and acupuncture. The risk of bias of most studies was rated as low or moderate. Data on continuous outcomes were presented inconsistently among studies, which precluded the possibility of pooling the results. Three pharmacological treatments (SSRIs and SNRIs, clonidine and gabapentin) reduced the number and severity of hot flushes. One study assessing vitamin E did not show any beneficial effect. One of two studies on relaxation therapy showed a significant benefit. None of the other non-pharmacological therapies had a significant benefit. Side-effects were inconsistently reported.
AUTHORS' CONCLUSIONS: Clonidine, SSRIs and SNRIs, gabapentin and relaxation therapy showed a mild to moderate effect on reducing hot flushes in women with a history of breast cancer.

PMID 20824841
Cristina Larroy García, Sonia Gutiérrez Gómez-Calcerrada
Cognitive-behavioral intervention among women with slight menopausal symptoms: a pilot study.
Span J Psychol. 2011 May;14(1):344-55.
Abstract/Text Menopause is associated with a considerable variety of physical, psychological and social symptoms that can be treated using cognitive-behavioral techniques. In the present study, 21 women took part in an eight-week group intervention consisting of weekly two-hour sessions to address their slight symptoms related to the climacteric stage of life. The intervention included: psycho education on menopause, relaxation techniques, nutrition and fitness exercises, Kegel exercises, and problem-solving techniques. A control group was included that did not receive treatment and consisted of 28 women. The results revealed a significant reduction in most symptoms (including depression and anxiety) after intervention as compared to the baseline period. No changes appeared in the control group. The relevance of this work lies in the potential element of prevention this therapeutic package could offer to relieve various symptoms, slight and incipient, during the perimenopausal stage.

PMID 21568191
Laurie Keefer, Edward B Blanchard
Hot flash, hot topic: conceptualizing menopausal symptoms from a cognitive-behavioral perspective.
Appl Psychophysiol Biofeedback. 2005 Mar;30(1):75-82.
Abstract/Text While most healthy women report that the menopausal transition is nondistressing, a subset of women does report that symptoms significantly interfere in their lives. The most common reason that women seek treatment during this time is for vasomotor symptoms, namely, hot flashes and night sweats. Research has suggested that reports of distress during flashing are only weakly related to more objective measures of the flash, including duration and frequency and that differences in treatment-seeking during the menopausal transition may be better accounted for by differences in symptom awareness mediated by a variety of personality and stress factors. This paper discusses hot flashes and night sweats from a cognitive-behavioral perspective, taking into account individual difference variables that may also affect the experience of menopausal symptoms.

PMID 15889587
K Takamatsu, H Ohta, K Makita, F Horiguchi, S Nozawa
Effects of counseling on climacteric symptoms in Japanese postmenopausal women.
J Obstet Gynaecol Res. 2001 Jun;27(3):133-40.
Abstract/Text OBJECTIVES: We objectively assessed the effects of counseling on climacteric symptoms in Japanese postmenopausal women.
METHODS: Symptoms in 44 women (age, 51.4 +/- 3.4 years; period after menopause, 3.6 +/- 3.4 years) treated with counseling were evaluated according to the Keio modified menopause index. The response to counseling was compared with that to hormone replacement therapy (HRT).
RESULTS: Forty cases (90.9%) showed an improvement in index score. There were no significant relationships between improvement and age, the period after menopause, or the severity or type of symptoms before counseling. The most improved symptom was headache, followed by palpitation and insomnia. Physical symptoms accounted for most of the common symptoms. The pattern of improvement with counseling was markedly different from that with HRT.
CONCLUSIONS: We suggest that counseling is effective for treating climacteric symptoms, since it improves not only psychological symptoms, but also physical ones. Counseling may deserve evaluation as a complementary treatment to HRT.

PMID 11561829
Peter J Schmidt
Mood, depression, and reproductive hormones in the menopausal transition.
Am J Med. 2005 Dec 19;118 Suppl 12B:54-8. doi: 10.1016/j.amjmed.2005.09.033.
Abstract/Text This article focuses on a review of evidence related to the following 3 questions: (1) Does depression appear during the menopausal transition? (2) What factors influence the risk for depression during the menopausal transition? (3) Do age-related alterations in ovarian hormone secretion contribute to the development of depression in some middle-aged women? A brief background is provided on the importance of depressive disorders. Methodologic issues that have compromised previous studies investigating the possible relation between the menopausal transition and depression are discussed. Evidence is presented that suggests a relation between the perimenopause (the interval between the early menopausal transition and 1 year after the last menses), but not the postmenopause, and the onset of depressive illness. Finally, studies are reviewed that suggest an association between alterations in ovarian function and depression, including several randomized placebo-controlled trials examining the antidepressant efficacy of estradiol in depressed perimenopausal and postmenopausal women.

PMID 16414327
Toshiyuki Ikeda, Kazuya Makita, Ken Ishitani, Kiyoshi Takamatsu, Fumi Horiguchi, Shiro Nozawa
Status of climacteric symptoms among middle-aged to elderly Japanese women: comparison of general healthy women with women presenting at a menopausal clinic.
J Obstet Gynaecol Res. 2005 Apr;31(2):164-71. doi: 10.1111/j.1341-8076.2005.00268.x.
Abstract/Text AIM: To examine the status and characteristics of climacteric symptoms reported by generally healthy middle-aged to elderly women in Japan, those living in Saitama Prefecture were surveyed .
METHODS: The subjects comprised 398 women ranging in age from 40 to <60 years (mean age, 50.5 years). Climacteric symptoms were objectively assessed using the Keio questionnaire. The total scores obtained for the 40 symptoms were used to calculate symptom prevalence and severity.
RESULTS: (i) The most frequent symptom was poor memory, reported by 88.7% of the women. (ii) Lumbar-sacral back pain was rated as a severe symptom by the highest percentage of women (15.3%). (iii) The prevalence and severity of poor memory and lumbar-sacral back pain did not differ with menopausal status. (iv) Hot flashes and sweats were slightly higher in peri- and early postmenopausal women than in premenopausal women.
CONCLUSIONS: The present study showed that healthy women who do not consult physicians because of climacteric symptoms are primarily concerned with age-related symptoms, such as poor memory, loss of hair, and forgetfulness.

PMID 15771644
Kiyoshi Takamatsu, Michiko Kasuga, Kazuya Makita, Shiro Nozawa
Evaluation of depressive conditions among Japanese patients at a menopause clinic.
J Obstet Gynaecol Res. 2004 Feb;30(1):42-7.
Abstract/Text AIM: To examine current depressive tendencies among Japanese patients visiting a menopause clinic with complaints of climacteric symptoms.
METHODS: The subjects were 389 Japanese women (age range: 45-60 years; mean: 51.4 +/- 3.8 years) who visited the menopause clinic in Department of Obstetrics and Gynecology, Keio university hospital, reporting climacteric symptoms. Their depressive tendencies were examined with the SDS (Self-rating Depression Scale, filled out by the patient).
RESULTS: The SDS was computed to be 42.4 +/- 9.9. Ninety-three (23.9%) suffered from an intermediate or higher level depressive tendency; 132 (33.9%) had a mild depression; and 164 (42.2%) were free of any depressive tendency. It was concluded that more than one-half of the subjects suffered from some form of depression. Correlations between age, time after menopause/oophorectomy, and depressive tendency were ambiguous. In comparing the total scores of SDS for pre-, peri-, and postmenopause groups, the incidence of probable depression was higher in the second group, but no significant differences were noted among each group. When the parameters were compared in relation to their hormonal environments, the natural menopause group rated significantly higher in the scores related to sleep disturbance, hopelessness and dissatisfaction than the premenopause group. The number of those who probably exhibited mild or more exaggerated depression was significantly lower in the surgical menopause group in comparison with the natural menopause group.
CONCLUSION: A depressive tendency occurred frequently among Japanese patients with menopausal disorders. It is important to evaluate the mental status of these patients with the aid of an appropriate tool.

PMID 14718020

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