今日の臨床サポート

月経前症候群

著者: 五来逸雄 堀病院 産婦人科

監修: 小西郁生 独立行政法人国立病院機構 京都医療センター

著者校正/監修レビュー済:2021/05/26
参考ガイドライン:
  1. 日本産科婦人科学会:産婦人科診療ガイドライン婦人科外来編 2020
  1. 米国産婦人科学会(ACOG):米国産婦人科学会 第4版2014年
  1. 英国王立産婦人科医協会(RCOG):英国王立産婦人科医協会(Green-top Guideline No. 48) 2017年
患者向け説明資料

概要・推奨   

  1. 月経前症候群ではまず第一に発症時期、精神症状、身体症状の病歴を詳細に聴取することが勧められる。
  1. 治療薬剤を決めるときには患者自身よく話し合うことが重要である。
  1. 対症療法では鎮痛薬抗精神薬、抗不安薬利尿薬(スピロノラクトン)、漢方薬があり、ホルモン療法では低用量エストロゲン・プロゲスチン配合薬がある。漢方療法が長期間奏効する症例も存在する。
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:
五来逸雄 : 特に申告事項無し[2021年]
監修:小西郁生 : 未申告[2021年]

改訂のポイント:
  1. 婦人科診療ガイドライン婦人科外来編 2020、米国産婦人科学会第4版2014年に基づき確認を行うと同時に英国王立産婦人科医協会(Green-top Guideline No. 48) 2017年の内容を一部加えた。
  1. さらに病因では最新の知見を追加した。
  1. 経口避妊薬(OC)を低用量エストロゲン・プロゲスチン配合薬と記載した。精神安定薬は抗不安薬とした。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 月経前症候群(premenstrual syndrome、PMS)は、月経前3~10日間の黄体期後期に発症する多種多様な精神的あるいは身体的症状で月経発来とともに減弱あるいは消失するものをいう[1]
  1. 症状としては、精神症状(いらいら、のぼせ、怒りっぽくなる、落ち着きがない、憂うつの順で多い)、身体症状(下腹部膨満感、下腹痛、腰痛、頭重感、頭痛、乳房痛の順に多い)が観察される[1]
  1. 日本では生殖年齢女性の約70~80%が月経前に何らかの症状を有するといわれる。欧米と同じ基準を適応すると生殖年齢女性の約5.4%で社会生活困難を伴うPMSが認められる[2][3]。最近のメタ解析によると、人種差はあるものの平均すると47.8%が観察されている[4]。22~39歳の若年成人女性では、33~41%との報告もある[5]
  1. 精神症状が強い場合は月経前不快気分障害(premenstrual dysphoric disorder、PMDD)と呼び、その頻度は約1.2%であり[2][3]、欧米では3~8%である[6]
  1. PMS、PMDDの発症には年齢差、人種差は認めず、生活習慣や勤務の有無とは関係しない。
  1. 病因は多岐にわたり、卵胞ホルモンと黄体ホルモンの不均衡[7]、黄体期初期でのエストロゲン低値と黄体ホルモン高値[8]、黄体期後期の急峻な黄体ホルモン値の低下[9]、エストロゲン受容体の遺伝子多型[10]、黄体ホルモン代謝産物(allopregnanolone)に対するGABA-A受容体の感受性の異常[11][12][13]、セロトニン作動性ニューロンの異常[14][15]、レプチン[16]・μ-オピオイド受容体の増加とcAMP/ERKシグナル伝達経路の活性化[17]、α2アドレナリン作動性受容体の異常[18]、精神的葛藤、社会的不安[19]、カルシウム代謝ホルモンの異常 [20][21][22][23][24][25][26]、マグネシウム欠乏[27][28]、メラトニン日内変動異常[29][30]、喫煙[31]、アルコール摂取[32]などが考えられている。
  1. 月経周期の後半に類似の身体症状、精神症状が繰り返して出現することにより診断する。
  1. 日常生活、勤務などの社会生活に影響を与える中等度以上のPMS、PMDDのみが治療の対象になる[33]
  1. カウンセリング、生活指導、運動療法などを行う。
  1. 対症療法として鎮痛薬、抗精神薬、抗不安薬、利尿薬(スピロノラクトン)、漢方薬などがあり、ホルモン療法として低用量エストロゲン・プロゲスチン配合薬など[34][35][36]が用いられる[22][37]
  1. 精神症状が強度の場合には精神科あるいは心療内科に紹介する。
  1. PMSの既往と産後うつ発症との関連[38][39][40]、PMSとその後の高血圧症発症との関連[41]が示唆されている。
問診・診察のポイント  
問診:
  1. いらいら、怒りっぽくなる、のぼせ、憂うつ、下腹部膨満感、下腹部痛、腰痛、頭重感、頭痛、乳房痛、落ち着きがないなどの症状を聞きだし、精神症状と身体症状に分けて評価する。

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文献 

著者: M Steiner, M Macdougall, E Brown
雑誌名: Arch Womens Ment Health. 2003 Aug;6(3):203-9. doi: 10.1007/s00737-003-0018-4.
Abstract/Text A variety of instruments have been used in an attempt to operationalize DSM-IV criteria for premenstrual dysphoric disorder (PMDD) and to understand clinically significant premenstrual syndrome (PMS). The objectives of this research were to devise a simple user friendly screening tool to identify women who suffer from severe PMS/PMDD and who are likely to benefit from treatment. Five hundred and nineteen women, between the ages of 18 and 55 yrs, who were seen at a primary care facility completed "The Premenstrual Symptoms Screening tool" (PSST). The PSST reflects and 'translates' categorical DSM-IV criteria into a rating scale with degrees of severity. The results are in line with reported prevalence rates from several recent large prospective studies. We believe that the PSST applies a necessary degree of measure of severity and impact of premenstrual symptoms, establishes quickly if women qualify for PMDD, and is less time consuming and more practical than two cycles of prospective charting. This fast simple tool is an effective screening tool and an important starting point for further assessment.

PMID 12920618  Arch Womens Ment Health. 2003 Aug;6(3):203-9. doi: 10.1・・・
著者: T Takeda, K Tasaka, M Sakata, Y Murata
雑誌名: Arch Womens Ment Health. 2006 Jul;9(4):209-12. doi: 10.1007/s00737-006-0137-9. Epub 2006 Jun 9.
Abstract/Text To investigate the prevalence and impact of premenstrual symptoms in Japanese women, we developed the PSQ "The Premenstrual Symptoms Questionnaire" for the screening of premenstrual symptoms. The PSQ translates DSM-IV criteria into a rating scale with degrees of severity. One thousand one hundred and eighty-seven Japanese women between the ages of 20 and 49 yrs, who were seen at a clinic for uterine cancer screening, were assessed regarding their premenstrual symptoms using the PSQ. As many as 95% of these women were found to suffer from premenstrual symptoms. The rates of prevalence of moderate to severe PMS and PMDD in Japanese women were 5.3 and 1.2%, respectively, which are lower than those in Western women. Only 5.3% of women with moderate to severe PMS and PMDD were treated. The results of this study suggest that race and ethnicity influence the expression of premenstrual symptoms and that the current state of medical care for Japanese women with moderate to severe PMS and PMDD is not satisfactory.

PMID 16761114  Arch Womens Ment Health. 2006 Jul;9(4):209-12. doi: 10.・・・
著者: Direkvand-Moghadam A, Sayehmiri K, Delpisheh A, Kaikhavandi Sattar
雑誌名: J Clin Diagn Res. 2014 Feb;8(2):106-9. doi: 10.7860/JCDR/2014/8024.4021. Epub 2014 Feb 3.
Abstract/Text BACKGROUND AND OBJECTIVES: Premenstrual Syndrome (PMS) is a common health problem in women in reproductive age. The present study aimed to investigate the prevalence of PMS using meta-analysis method.
METHODS: This meta-analysis systematically reviewed the prevalence of PMS. A search was conducted using keywords Premenstrual Syndrome, PMS, prevalence PMS and symptom of PMS in reliable English articles. The initial search 53 articles were available. After review of full-text articles, 17 articles were selected for analysis. Data were combined using meta-analysis (random effects model). Data were analyzed using STATA software, Version 11.1 RESULTS: Overall, 17 studies met our inclusion criteria. The pooled prevalence of PMS was 47.8% (95% CI: 32.6-62.9). The lowest and highest prevalence were reported in France 12% (95% CI: 11-13) and Iran 98% (95% CI: 97-100) respectively. However, meta-regression scatter plot showed an increasing trend in the prevalence of PMS during 1996-2011 but correlation between prevalence of PMS and year of study was not significance (p= 0.797).
INTERPRETATION AND CONCLUSIONS: Considering that different tools have been used in studies and many studies have been designed based on a limited sample, therefore, future research needs to consider the prevalence of PMS in different countries of world.

PMID 24701496  J Clin Diagn Res. 2014 Feb;8(2):106-9. doi: 10.7860/JCD・・・
著者: Hong Ju, Mark Jones, Gita D Mishra
雑誌名: Maturitas. 2014 Jun;78(2):99-105. doi: 10.1016/j.maturitas.2014.03.008. Epub 2014 Apr 4.
Abstract/Text OBJECTIVES: To ascertain the prevalence of premenstrual syndrome (PMS) and dysmenorrhea in Australia women and to examine whether there is population subgroups with distinct symptom trajectories.
STUDY DESIGN: A prospective cohort study, including 9671 young women random sampled from national Medicare database and followed up for 13 years, examined the prevalence, the trend and the symptom trajectories of the conditions.
MAIN OUTCOME MEASURES: Prevalence of PMS and dysmenorrhea over time, their symptom trajectories, and the probability of symptom reporting at follow-up.
RESULTS: The prevalence of PMS varied between 33 and 41% and that of dysmenorrhea between 21 and 26%. The probabilities of reporting PMS and dysmenorrhea were 0.75 (95% CI, 0.73, 0.76) and 0.70 (95% CI, 0.68, 0.72), respectively, among women who reported them in three previous consecutive surveys. Four unique trajectories were identified for both conditions. PMS was experienced by 80% of women some time during the study period, with normative (22.1%), late onset (21.9%), recovering (26.5%) and chronic (29.5%) groups revealed. Dysmenorrhea occurred in 60% of women with normative (38.3%), low (28.0%), recovering (17.2%) and chronic (16.5%) groups identified.
CONCLUSIONS: PMS and dysmenorrhea are common among young women. Both have relatively stable prevalence over time, but exhibit considerable variation at the individual level. Four subgroups of women who followed similar symptom trajectories were identified. PMS was experienced by 80% of women during the study period and it tended to be a long-lasting problem in many. Although 60% of women experienced dysmenorrhea, only a small group continuously reported it. Smoking and illicit drugs use, and smoking and obesity were more common among women with persistent PMS and dysmenorrhea respectively.

Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
PMID 24750643  Maturitas. 2014 Jun;78(2):99-105. doi: 10.1016/j.maturi・・・
著者: Glenda MacQueen, Pratap Chokka
雑誌名: Can J Psychiatry. 2004 Mar;49(3 Suppl 1):27S-40S.
Abstract/Text Depression is more prevalent in women than in men, which may be related to biological, hormonal, and psychosocial factors. Four depressive conditions are specific to women: premenstrual dysphoric disorder (PMDD), depression in pregnancy, postpartum depression, and depression related to perimenopause or menopause. Antidepressant therapy with selective serotonin reuptake inhibitors and venlafaxine has demonstrated efficacy in PMDD. Both continuous and intermittent dosing regimens were effective at usual but not at low dosages. Despite reluctance of some women to take medication for depression during pregnancy and breastfeeding, substantial evidence suggests that antidepressants are safe and efficacious during these periods, while untreated depression has negative consequences for both mother and child. In peri- or postmenopausal women with depression, estrogen may enhance the effects of antidepressant medications, although a pooled analysis of data in women aged 50 years or over treated with venlafaxine found that remission rates were similar in those who were taking estrogen and those who were not. The management of women with depression can be done safely and effectively using antidepressants and alternative interventions throughout the life cycle.

PMID 15147034  Can J Psychiatry. 2004 Mar;49(3 Suppl 1):27S-40S.
著者: U Schweiger, R G Laessle, R J Tuschl, A Broocks, T Krusche, K M Pirke
雑誌名: J Clin Endocrinol Metab. 1989 May;68(5):888-92. doi: 10.1210/jcem-68-5-888.
Abstract/Text We tested the hypothesis that disturbed follicular development and disturbed luteal progesterone (P4) secretion are associated with reduced gonadotropin secretion in the early follicular phase by measuring pulsatile LH and FSH secretion at that time in 53 normally menstruating women. Three groups of women were identified on the basis of serum sex steroid concentrations (measured daily throughout the cycle) and luteal phase length. Group A (n = 27) had normal ovarian hormone secretion with peak serum estradiol (E2) concentrations of 440 pmol/L or more, peak serum P4 concentrations of 19 nmol/L or more, and luteal phase length of 9 days or more. Group B (n = 16) had normal peak serum E2 values, but peak serum P4 values less than 19 nmol/L and/or luteal phase length less than 9 days. Group C (n = 10) had peak serum E2 values below 440 pmol/L. Risk factors for the disturbances found in groups B and C were exercise and/or intermittent dieting. Compared to group A, both groups B and C had reduced mean serum LH concentrations (3.1 +/- 1.5 vs. 2.3 +/- 1.4 and 2.0 +/- 1.0 IU/L; P less than 0.05) and reduced LH pulse frequencies (5.2 +/- 2.1 vs. 3.5 +/- 1.8 and 3.3 +/- 2.3 pulses/12 h; P less than 0.02). LH amplitude was similar in all 3 groups. Mean serum FSH concentrations were slightly but not significantly lower in group C. We conclude that reduced gonadotropin secretion during the follicular phase may indeed affect E2 and P4 secretion at later stages of the menstrual cycle. The patterns of alteration associated with disturbed E2 and P4 secretion in normally menstruating women are similar to those that occur in women with hypothalamic amenorrhea.

PMID 2497129  J Clin Endocrinol Metab. 1989 May;68(5):888-92. doi: 10・・・
著者: Ju-Yu Yen, Huang-Chi Lin, Pai-Cheng Lin, Tai-Ling Liu, Cheng-Yu Long, Chih-Hung Ko
雑誌名: Int J Environ Res Public Health. 2019 Nov 7;16(22). doi: 10.3390/ijerph16224352. Epub 2019 Nov 7.
Abstract/Text : Objective/introduction: The dynamics of ovarian hormone fluctuations during the luteal phase of the menstruation cycle were previously suggested to contribute to the development of premenstrual dysphoric disorder (PMDD) symptoms, but adequate empirical evidence has not been obtained from hormone concentration studies. We prospectively evaluated estrogen and progesterone levels in the early luteal (EL) and late luteal (LL) phases in women with PMDD and the association of these levels with PMDD symptom severity. Methods: 63 women with PMDD and 53 controls without such severe symptoms were evaluated for the estrogen and progesterone levels, and PMDD severity in the EL and LL phases. Results: The results demonstrated that the women with PMDD had a lower EL-phase estrogen level than the controls. Covariant analysis demonstrated that the interaction term between EL-phase estrogen and EL-phase progesterone level was associated with PMDD severity. Among women with lower EL estrogen levels, higher EL-phase progesterone was observed among the women with PMDD versus controls. These results suggest that low EL-phase estrogen level could moderate the provoking effect of EL progesterone in women with PMDD. Overall, these data suggest a possible role of estrogen and progesterone in the development of PMDD symptoms.

PMID 31703451  Int J Environ Res Public Health. 2019 Nov 7;16(22). doi・・・
著者: Thelma A Lovick, Vinicius G Guapo, Janete A Anselmo-Franci, Camila M Loureiro, Maria Clara M Faleiros, Cristina M Del Ben, Marcus L Brandão
雑誌名: Psychoneuroendocrinology. 2017 Jan;75:83-90. doi: 10.1016/j.psyneuen.2016.10.024. Epub 2016 Oct 27.
Abstract/Text There is a consensus that the development of premenstrual dysphoric states is related to cyclical change in gonadal hormone secretion during the menstrual cycle. However, results from studies seeking to link symptom severity to luteal phase progesterone concentration have been equivocal. In the present study we evaluated not only the absolute concentrations of progesterone but also the kinetics of the change in progesterone concentration in relation to development of premenstrual symptoms during the last 10days of the luteal phase in a population of 46 healthy young adult Brazilian women aged 18-39 years, mean 26.5±6.7years. In participants who developed symptoms of premenstrual distress, daily saliva progesterone concentration remained stable during most of the mid-late luteal phase, before declining sharply during the last 3days prior to onset of menstruation. In contrast, progesterone concentration in asymptomatic women underwent a gradual decline over the last 8days prior to menstruation. Neither maximum nor minimum concentrations of progesterone in the two groups were related to the appearance or severity of premenstrual symptoms. We propose that individual differences in the kinetics of progesterone secretion and/or metabolism may confer differential susceptibility to the development of premenstrual syndrome.

Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.
PMID 27810707  Psychoneuroendocrinology. 2017 Jan;75:83-90. doi: 10.10・・・
著者: Ju-Yu Yen, Peng-Wei Wang, Chen-Hsiang Su, Tai-Ling Liu, Cheng-Yu Long, Chih-Hung Ko
雑誌名: Prog Neuropsychopharmacol Biol Psychiatry. 2018 Mar 2;82:216-223. doi: 10.1016/j.pnpbp.2017.11.013. Epub 2017 Nov 14.
Abstract/Text BACKGROUND: This study evaluated the association between estrogen levels, emotion regulation, depression, anxiety, and stress of women with premenstrual dysphoric disorder (PMDD). We also evaluated the moderating effect of estrogen receptor (ESR) α-Xbal polymorphism on the aforementioned association.
METHODS: A total of 100 women were diagnosed with PMDD based on psychiatric interviews and a prospective investigation of 3 menstrual cycles. A total of 96 normal individuals were recruited as controls. Their estrogen levels, depression, anxiety, stress, and ESR α-Xbal polymorphism in both premenstrual and follicular phases were assessed, and these data were included in the final analysis.
RESULTS: The PMDD group had high depression, anxiety, and stress and low emotional adjusting and tolerating in the premenstrual phase. Emotional adjustment was negatively associated with depression, anxiety and stress. No association was observed between PMDD and estrogen level. However, premenstrual estrogen level was negatively correlated with anxiety and stress in women with PMDD. The association was only significant in G carriers of ESR α-Xbal, as was the difference in premenstrual emotion regulation between the PMDD and control groups.
CONCLUSIONS: The results demonstrate the association between estrogen and anxiety in PMDD, supporting the claim that women with PMDD differ in their responses to normal estrogen levels. Furthermore, this association and dysfunctional emotional regulation in PMDD existed only among the G carriers of ESR α-Xbal polymorphism. Future studies should investigate the effect of estrogen on brain functions involving emotional regulation in women with PMDD, stratified by ESR α-Xbal polymorphism.

Copyright © 2017 Elsevier Inc. All rights reserved.
PMID 29146473  Prog Neuropsychopharmacol Biol Psychiatry. 2018 Mar 2;8・・・
著者: Marie Bixo, Karin Ekberg, Inger Sundström Poromaa, Angelica Lindén Hirschberg, Aino Fianu Jonasson, Lotta Andréen, Erika Timby, Marianne Wulff, Agneta Ehrenborg, Torbjörn Bäckström
雑誌名: Psychoneuroendocrinology. 2017 Jun;80:46-55. doi: 10.1016/j.psyneuen.2017.02.031. Epub 2017 Mar 1.
Abstract/Text CONTEXT: Allopregnanolone is a metabolite from progesterone and a positive modulator of the GABAA receptor. This endogenous steroid may induce negative mood in sensitive women when present in serum levels comparable to the premenstrual phase. Its endogenous isomer, isoallopregnanolone, has been shown to antagonize allopregnanolone effects in experimental animal and human models.
OBJECTIVE: The objective was to test whether inhibition of allopregnanolone by treatment with the GABAA modulating steroid antagonist (GAMSA) Sepranolone (UC1010) during the premenstrual phase could reduce symptoms of the premenstrual dysphoric disorder (PMDD). The pharmacokinetic parameters of UC1010 when given as a subcutaneous injection were measured in healthy women prior to the study in women with PMDD.
DESIGN: This was an explorative randomized, double-blind, placebo-controlled study.
SETTING: Swedish multicentre study with 10 centers.
PARTICIPANTS: Participants were 26 healthy women in a pharmacokinetic phase I study part, and 126 women with PMDD in a phase II study part. Diagnosis followed the criteria for PMDD in DSM-5 using Daily Record of Severity of Problems (DRSP) and Endicott's algorithm.
INTERVENTION: Subjects were randomized to treatment with UC1010 (10 or 16mg) subcutaneously every second day during the luteal phase or placebo during one menstrual cycle.
OUTCOME MEASURES: The primary outcome measure was the sum of all 21 items in DRSP (Total DRSP score). Secondary outcomes were Negative mood score i.e. the ratings of the 4 key symptoms in PMDD (anger/irritability, depression, anxiety and lability) and impairment (impact on daily life).
RESULTS: 26 healthy women completed the pharmacokinetic phase I study and the dosing in the following trial was adjusted according to the results. 106 of the 126 women completed the phase II study. Within this group, a significant treatment effect with UC1010 compared to placebo was obtained for the Total DRSP score (p=0.041) and borderline significance (p=0.051) for the sum of Negative mood score. Nineteen participants however showed symptoms during the follicular phase that might be signs of an underlying other conditions, and 27 participants had not received the medication as intended during the symptomatic phase. Hence, to secure that the significant result described above was not due to chance, a post hoc sub-group analysis was performed, including only women with pure PMDD who completed the trial as intended (n=60). In this group UC1010 reduced Total DRSP scores by 75% compared with 47% following placebo; the effect size 0.7 (p=0.006), and for sum of Negative mood score (p=0.003) and impairment (p=0.010) with the effect size 0.6. No severe adverse events were reported during the treatment and safety parameters (vital signs and blood chemistry) remained normal during the study.
CONCLUSIONS: This explorative study indicates promising results for UC1010 as a potential treatment for PMDD. The effect size was comparable to that of SSRIs and drospirenone containing oral contraceptives. UC1010 was well tolerated and deemed safe.

Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
PMID 28319848  Psychoneuroendocrinology. 2017 Jun;80:46-55. doi: 10.10・・・
著者: M Bixo, M Johansson, E Timby, L Michalski, T Bäckström
雑誌名: J Neuroendocrinol. 2018 Feb;30(2). doi: 10.1111/jne.12553.
Abstract/Text Premenstrual dysphoric disorder (PMDD) afflicts 3%-5% of women of childbearing age, and is characterised by recurrent negative mood symptoms (eg, irritability, depression, anxiety and emotional lability) during the luteal phase of the menstrual cycle. The aetiology of PMDD is unknown, although a temporal association with circulating ovarian steroids, in particular progesterone and its metabolite allopregnanolone, has been established during the luteal phase. Allopregnanolone is a positive modulator of the GABAA receptor: it is sedative in high concentrations but may precipitate paradoxical adverse effects on mood at levels corresponding to luteal phase concentrations in susceptible women. Saccadic eye velocity (SEV) is a measure of GABAA receptor sensitivity; in experimental studies of healthy women, i.v. allopregnanolone decreases SEV. Women with PMDD display an altered sensitivity to an i.v. injection of allopregnanolone compared to healthy controls in this model. In functional magnetic resonance imaging (fMRI) studies, women with PMDD react differently to emotional stimuli in contrast to controls. A consistent finding in PMDD patients is increased amygdala reactivity during the luteal phase. Post-mortem studies in humans have revealed that allopregnanolone concentrations vary across different brain regions, although mean levels in the brain also reflect variations in peripheral serum concentrations. The amygdala processes emotions such as anxiety and aggression. This is interesting because allopregnanolone is detected at high concentrations within the region into which marked increases in blood flow are measured with fMRI following progesterone/allopregnanolone administration. Allopregnanolone effects are antagonised by its isomer isoallopregnanolone (UC1010), which significantly reduces negative mood symptoms in women with PMDD when administered s.c. in the premenstrual phase. This was shown in a randomised, placebo-controlled clinical trial in which the primary outcome was change in symptom scoring on the Daily Rating of Severity of Problems (DRSP): the treatment reduced negative mood scores (P < .005), as well as total DRSP scores (P < .01), compared to placebo in women with PMDD. In conclusion, the underlying studies of this review provide evidence that allopregnanolone is the provoking factor behind the negative mood symptoms in PMDD and that isoallopregnanolone could ameliorate the symptoms as a result of its ability to antagonise the allopregnanolone effect on the GABAA receptor.

© 2017 British Society for Neuroendocrinology.
PMID 29072794  J Neuroendocrinol. 2018 Feb;30(2). doi: 10.1111/jne.125・・・
著者: Jane Marjoribanks, Julie Brown, Patrick Michael Shaughn O'Brien, Katrina Wyatt
雑誌名: Cochrane Database Syst Rev. 2013 Jun 7;6:CD001396. doi: 10.1002/14651858.CD001396.pub3. Epub 2013 Jun 7.
Abstract/Text BACKGROUND: Premenstrual syndrome (PMS) is a common cause of physical, psychological and social problems in women of reproductive age. The key characteristic of PMS is the timing of symptoms, which occur only during the two weeks leading up to menstruation (the luteal phase of the menstrual cycle). Selective serotonin reuptake inhibitors (SSRIs) are increasingly used as first line therapy for PMS. SSRIs can be taken either in the luteal phase or else continuously (every day). SSRIs are generally considered to be effective for reducing premenstrual symptoms but they can cause adverse effects.
OBJECTIVES: The objective of this review was to evaluate the effectiveness and safety of SSRIs for treating premenstrual syndrome.
SEARCH METHODS: Electronic searches for relevant randomised controlled trials (RCTs) were undertaken in the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, PsycINFO, and CINAHL (February 2013). Where insufficient data were presented in a report, attempts were made to contact the original authors for further details.
SELECTION CRITERIA: Studies were considered in which women with a prospective diagnosis of PMS, PMDD or late luteal phase dysphoric disorder (LPDD) were randomised to receive SSRIs or placebo for the treatment of premenstrual syndrome.
DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies, assessed eligible studies for risk of bias, and extracted data on premenstrual symptoms and adverse effects. Studies were pooled using random-effects models. Standardised mean differences (SMDs) with 95% confidence intervals (CIs) were calculated for premenstrual symptom scores, using separate analyses for different types of continuous data (that is end scores and change scores). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for dichotomous outcomes. Analyses were stratified by type of drug administration (luteal or continuous) and by drug dose (low, medium, or high). We calculated the number of women who would need to be taking a moderate dose of SSRI in order to cause one additional adverse event (number needed to harm: NNH). The overall quality of the evidence for the main findings was assessed using the GRADE working group methods.
MAIN RESULTS: Thirty-one RCTs were included in the review. They compared fluoxetine, paroxetine, sertraline, escitalopram and citalopram versus placebo. SSRIs reduced overall self-rated symptoms significantly more effectively than placebo. The effect size was moderate when studies reporting end scores were pooled (for moderate dose SSRIs: SMD -0.65, 95% CI -0.46 to -0.84, nine studies, 1276 women; moderate heterogeneity (I(2) = 58%), low quality evidence). The effect size was small when studies reporting change scores were pooled (for moderate dose SSRIs: SMD -0.36, 95% CI -0.20 to -0.51, four studies, 657 women; low heterogeneity (I(2)=29%), moderate quality evidence).SSRIs were effective for symptom relief whether taken only in the luteal phase or continuously, with no clear evidence of a difference in effectiveness between these modes of administration. However, few studies directly compared luteal and continuous regimens and more evidence is needed on this question.Withdrawals due to adverse effects were significantly more likely to occur in the SSRI group (moderate dose: OR 2.55, 95% CI 1.84 to 3.53, 15 studies, 2447 women; no heterogeneity (I(2) = 0%), moderate quality evidence). The most common side effects associated with a moderate dose of SSRIs were nausea (NNH = 7), asthenia or decreased energy (NNH = 9), somnolence (NNH = 13), fatigue (NNH = 14), decreased libido (NNH = 14) and sweating (NNH = 14). In secondary analyses, SSRIs were effective for treating specific types of symptoms (that is psychological, physical and functional symptoms, and irritability). Adverse effects were dose-related.The overall quality of the evidence was low to moderate, the main weakness in the included studies being poor reporting of methods. Heterogeneity was low or absent for most outcomes, though (as noted above) there was moderate heterogeneity for one of the primary analyses.
AUTHORS' CONCLUSIONS: SSRIs are effective in reducing the symptoms of PMS, whether taken in the luteal phase only or continuously. Adverse effects are relatively frequent, the most common being nausea and asthenia. Adverse effects are dose-dependent.

PMID 23744611  Cochrane Database Syst Rev. 2013 Jun 7;6:CD001396. doi:・・・
著者: Olle Eriksson, Anders Wall, Ulf Olsson, Ina Marteinsdottir, Maria Holstad, Hans Ågren, Per Hartvig, Bengt Långström, Tord Naessén
雑誌名: PLoS One. 2016;11(9):e0159538. doi: 10.1371/journal.pone.0159538. Epub 2016 Sep 12.
Abstract/Text STUDY OBJECTIVE: To investigate potential quantitative and qualitative differences in brain serotonergic activity between women with Premenstrual Dysphoria (PMD) and asymptomatic controls.
BACKGROUND: Serotonin-augmenting drugs alleviate premenstrual mood symptoms in the majority of women with PMD while serotonin-depleting diets worsen PMD symptoms, both indicating intrinsic differences in brain serotonergic activity in women with PMD compared to asymptomatic women.
METHODS: Positron-emission tomography with the immediate precursor of serotonin, 5-hydroxytryptophan (5-HTP), radiolabelled by 11C in the beta-3 position, was performed in the follicular and luteal phases for 12 women with PMD and 8 control women. Brain radioactivity-a proxy for serotonin precursor uptake and synthesis-was measured in 9 regions of interest (ROIs): the right and left sides of the medial prefrontal cortex, dorsolateral prefrontal cortex, putamen and caudate nucleus, and the single "whole brain".
RESULTS: There were no significant quantitative differences in brain 5-HTP-derived activity between the groups in either of the menstrual phases for any of the 9 ROIs. However, multivariate analysis revealed a significant quantitative and qualitative difference between the groups. Asymptomatic control women showed a premenstrual right sided relative increase in dorsolateral prefrontal cortex 5-HTP derived activity, whereas PMD women displayed the opposite (p = 0.0001). Menstrual phase changes in this asymmetry (premenstrual-follicular) correlated with changes in self ratings of 'irritability' for the entire group (rs = -0.595, p = 0.006). The PMD group showed a strong inverse correlation between phase changes (premenstrual-follicular) in plasma levels of estradiol and phase changes in the laterality (dx/sin) of radiotracer activity in the dorsolateral prefrontal ROI (rs = -0.635; 0.027). The control group showed no such correlation.
CONCLUSION: Absence of increased premenstrual right-sided relative 5-HTP-derived activity of the dorsolateral prefrontal cortices was found to strongly correlate to premenstrual irritability. A causal relationship here seems plausible, and the findings give further support to an underlying frontal brain disturbance in hormonally influenced serotonergic activity in women with PMD. Because of the small number of subjects in the study, these results should be considered preliminary, requiring verification in larger studies.

PMID 27617751  PLoS One. 2016;11(9):e0159538. doi: 10.1371/journal.pon・・・
著者: Zaira Fernanda Martinho Nicolau, Andréia Gomes Bezerra, Daniel Ninello Polesel, Monica Levy Andersen, Sergio Tufik, Helena Hachul
雑誌名: Obstet Gynecol Surv. 2017 Nov;72(11):659-662. doi: 10.1097/OGX.0000000000000502.
Abstract/Text Importance: Premenstrual syndrome (PMS) is characterized by physical and psychological symptoms in the luteal phase. Leptin can influence PMS as it acts on the hypothalamic-pituitary-gonadal axis.
Objective: The aim of this study was to evaluate data in the literature about the profile of plasma leptin in women with PMS.
Evidence Acquisition: We performed a search of databases using both descriptors. Three studies were identified. They included 181 participants. Two of these studies found higher leptin levels in women with PMS.
Results: Conflicting results were found regarding the leptin levels in the luteal phase and the correlation between leptin, estradiol, and progesterone levels.
Conclusions and Relevance: Leptin could have a role in the pathophysiology of PMS and indicate degree of severity of PMS. Future studies on the role of leptin in PMS are needed.

PMID 29164263  Obstet Gynecol Surv. 2017 Nov;72(11):659-662. doi: 10.1・・・
著者: G N Gurguis, K A Yonkers, S P Phan, J E Blakeley, A Williams, A J Rush
雑誌名: Biol Psychiatry. 1998 Oct 1;44(7):600-9.
Abstract/Text BACKGROUND: Abnormal alpha 2-adrenergic receptor (AR) function is implicated in anxiety and depressive disorders. Premenstrual dysphoric disorder (PMDD) is characterized by anxiety and depressive symptoms, which may be associated with changes in alpha 2AR function. Previous studies on alpha 2AR function during phases of the menstrual cycle in controls and PMDD patients are inconsistent.
METHODS: alpha 2AR function was examined in 16 PMDD patients and 15 controls during the follicular phase, and in 10 PMDD patients during late luteal phase. Antagonist-measured maximum binding capacity, agonist-measured receptor density in high- and low-conformational states, and agonist affinity to both states were measured. Coupling efficiency to Gi protein was estimated.
RESULTS: There were no significant differences in coupling efficiency. PMDD patients had significantly low antagonist affinity; there were no differences in other binding parameters. There were no changes in alpha 2AR binding parameters between phases of menstrual cycle in PMDD women. alpha 2AR density and symptom severity were inversely related during the follicular phase in controls and patients. During luteal phase, alpha 2AR density correlated positively with symptom severity in patients. High follicular alpha 2AR density predicted more severe luteal symptoms in PMDD patients.
CONCLUSIONS: These findings are discussed in view of the molecular biology of alpha 2AR, and their role in PMDD, anxiety, and depressive disorders.

PMID 9787884  Biol Psychiatry. 1998 Oct 1;44(7):600-9.
著者: Michelle Vichnin, Ellen W Freeman, Hui Lin, Janice Hillman, Stephanie Bui
雑誌名: J Pediatr Adolesc Gynecol. 2006 Dec;19(6):397-402. doi: 10.1016/j.jpag.2006.06.015.
Abstract/Text OBJECTIVES: Identify the presence of patients with premenstrual syndrome (PMS) in an adolescent gynecology practice, and evaluate the reported severity, impairment and timing of the symptoms in the menstrual cycle.
METHODS: Adolescents ages 13-18 years completed a symptom questionnaire, functional impairment ratings, and a brief medical history questionnaire during an office visit. Teens who responded that they had PMS and reported a premenstrual symptom score at least 50% greater than the postmenstrual score and rated moderate to severe impairment in one or more domains comprised the "PMS" group. Teens who responded that they had PMS but did not meet the symptom and impairment criteria were termed "PMS not supported." Teens who responded that they did not have PMS and did not meet the PMS symptom and impairment criteria were termed "No PMS."
RESULTS: Study participants (n = 94) had a mean age of 16.5 years (+/-1.3 SD); 31% met the criteria for the PMS group, 54% said they had PMS but did not meet criteria, and 15% clearly had no PMS. In the PMS group, the most severe symptoms were mood swings, anxiety, and irritability, with the greatest impairment in the home/family domain. Dysmenorrhea and the duration of PMS were significantly associated (P < 0.01) with PMS in univariate and multivariate analyses.
CONCLUSIONS: The reports of premenstrual symptoms, their severity, timing and impairment suggest that PMS is common in adolescents. Further study is warranted to confirm these results with prospective assessment of PMS and to evaluate treatments for adolescents who have clinically significant PMS.

PMID 17174829  J Pediatr Adolesc Gynecol. 2006 Dec;19(6):397-402. doi:・・・
著者: S Thys-Jacobs, M J Alvir
雑誌名: J Clin Endocrinol Metab. 1995 Jul;80(7):2227-32. doi: 10.1210/jcem.80.7.7608284.
Abstract/Text Calcium metabolism across one menstrual cycle was studied in 12 healthy, premenopausal women. Seven women had documented premenstrual syndrome (PMS), and five were asymptomatic controls. Fasting blood samples were drawn at six points throughout the ovulatory cycle. In both the asymptomatic and the PMS groups, total and ionized calcium declined significantly at midcycle with the increase of estradiol. In the PMS group only, peak midcycle intact PTH was significantly elevated by approximately 30% compared with early follicular levels (49 +/- 25 vs. 37 +/- 22 ng/L, t = 3.79, P = 0.009). In the asymptomatic group, iPTH did not vary during the menstrual cycle. Midcycle iPTH was significantly higher in the PMS group compared with that of the control group (49 +/- 25 vs. 26 +/- 7 ng/L, Wilcoxon Z = 2.28, P = 0.02). Multivariate analysis showed that total and ionized calcium both varied significantly across the menstrual cycle. Significant differences between groups were found for total calcium, 25OHD, and 1,25-(OH)2D. One woman with PMS was treated with oral elemental calcium and cholecalciferol daily for 3 months, with amelioration of her symptoms. Midcycle iPTH and 1,25-(OH)2D declined after repletion of 25OHD. In conclusion, we found that concentrations of total and ionized calcium significantly fluctuate during the menstrual cycle both in symptomatic and in asymptomatic women. We also found that concentrations of iPTH, 25OHD, and 1,25-(OH)2D differed between groups during specific phases of the menstrual cycle. Our data suggest that women with PMS have midcycle elevations of iPTH with a transient, secondary hyperparathyroidism.

PMID 7608284  J Clin Endocrinol Metab. 1995 Jul;80(7):2227-32. doi: 1・・・
著者: Elizabeth R Bertone-Johnson, Susan E Hankinson, Nancy G Forger, Sally I Powers, Walter C Willett, Susan R Johnson, JoAnn E Manson
雑誌名: BMC Womens Health. 2014 Apr 12;14:56. doi: 10.1186/1472-6874-14-56. Epub 2014 Apr 12.
Abstract/Text BACKGROUND: Moderate to severe premenstrual syndrome (PMS) affects 8-20 percent of premenopausal women. Previous studies suggest that high dietary vitamin D intake may reduce risk. However, vitamin D status is influenced by both dietary vitamin D intake and sunlight exposure and the association of vitamin D status with PMS remains unclear.
METHODS: We assessed the relation of plasma 25-hydroxyvitamin D (25OHD), total calcium and parathyroid hormone levels with risk of PMS and specific menstrual symptoms in a case-control study nested within the prospective Nurses' Health Study II. Cases were 401 women free from PMS at baseline who developed PMS during follow-up (1991-2005). Controls were women not experiencing PMS (1991-2005), matched 1:1 with cases on age and other factors. Timed luteal phase blood samples were collected between 1996 and 1999 from cases and controls. We used conditional logistic regression to model the relation of 25OHD levels with risk of PMS and individual menstrual symptoms.
RESULTS: In analyses of all cases and controls, 25OHD levels were not associated with risk of PMS. However, results differed when the timing of blood collection vs. PMS diagnosis was considered. Among cases who had already been diagnosed with PMS at the time of blood collection (n = 279), 25OHD levels were positively associated with PMS, with each 10 nmol/L change in 25OHD associated with a 13% higher risk. Among cases who developed PMS after blood collection (n = 123), 25OHD levels were unrelated to risk of PMS overall, but inversely related to risk of specific menstrual symptoms. For example, each 10 nmol/L increase was associated with a significant 21% lower risk of breast tenderness (P = 0.02). Total calcium or parathyroid hormone levels were unrelated to PMS.
CONCLUSIONS: 25OHD levels were not associated with overall risk of PMS. The positive association observed among women already experiencing PMS at the time of 25OHD measurement is likely due to confounding by indication related to use of dietary supplements to treat menstrual symptoms. Results from prospective analyses, which were less likely influenced by this bias, suggest that higher 25OHD levels may be inversely related to the development of specific menstrual symptoms.

PMID 24725979  BMC Womens Health. 2014 Apr 12;14:56. doi: 10.1186/1472・・・
著者: Massimo Tartagni, Maria Vittoria Cicinelli, Mario Valerio Tartagni, Hala Alrasheed, Maria Matteo, Domenico Baldini, Maria De Salvia, Giuseppe Loverro, Monica Montagnani
雑誌名: J Pediatr Adolesc Gynecol. 2016 Aug;29(4):357-61. doi: 10.1016/j.jpag.2015.12.006. Epub 2015 Dec 24.
Abstract/Text STUDY OBJECTIVE: Premenstrual syndrome (PMS) might become severe enough to interfere with normal interpersonal relationships. This study was planned to assess whether administration of vitamin D (200,000 IU at first, followed by 25,000 IU every 2 weeks) for a 4-month period might lessen the appearance and the intensity of mood disorders associated with PMS in young girls with severe hypovitaminosis D. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: One hundred fifty-eight young girls (15-21 years old) with PMS-related severe symptoms of the emotional and cognitive domains and low serum 25-hydroxycholecalciferol (25-OH-D) levels (≤10 ng/mL) were randomly assigned to two treatment groups and treated for 4 months with vitamin D (group 1; n = 80) or placebo (group 2; n = 78). Clinical and hormonal effects were compared between the two groups.
RESULTS: In patients from group 1, levels of vitamin D reached the normal range (35-60 ng/mL) after the first month and remained stable throughout the whole study. At the end of treatment, anxiety score decreased from 51 to 20 (P < .001 vs baseline); irritability score declined from 130 to 70 (P < .001 vs baseline). Crying easily and sadness decreased by a score of 41 and 51 to a score of 30 and 31, respectively (P < .001). For disturbed relationships, the score decreased from 150 to 70 (P < .001). Conversely, no appreciable changes were noted in symptom intensity from patients of group 2. The frequency of adverse events (nausea and constipation) was not different between participants of group 1 and group 2.
CONCLUSION: On the basis of the present findings, vitamin D therapy can be proposed as a safe, effective, and convenient method for improving the quality of life in young women with severe hypovitaminosis D and concomitant mood disorders associated with PMS.

Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.
PMID 26724745  J Pediatr Adolesc Gynecol. 2016 Aug;29(4):357-61. doi: ・・・
著者: Nesreen A A Shehata
雑誌名: Eur J Obstet Gynecol Reprod Biol. 2016 Mar;198:100-4. doi: 10.1016/j.ejogrb.2016.01.015. Epub 2016 Jan 13.
Abstract/Text OBJECTIVE: To compare the efficacy of calcium supplements versus combined oral contraceptive pills (COC) containing drospirenone in treating mild to moderate premenstrual syndrome.
STUDY DESIGN: This was a double-blind, randomized placebo controlled trial conducted in Beni-Suef University Hospital. Premenstrual syndrome (PMS) was prospectively diagnosed using the Daily Record of Severity of Problems (DRSP). In total, 210 women with mild to moderate PMS were randomly divided into three equal groups. Group 1 received COC daily for 21 days starting on the third day of menstruation and a daily oral placebo similar to calcium and vitamin D. Group 2 received calcium 400mg+vitamin D 400IU once daily and an oral placebo similar to COC for 21 days starting on the third day of menstruation. Group 3 received a daily placebo similar to calcium and vitamin D in addition to an oral placebo similar to COC for 21 days starting on the third day of menstruation. Treatment was continued for 3 months.
RESULTS: The proportion of women with improved PMS decreased progressively from the COC group to the calcium group and the placebo group (81%, 62.3% and 16.3%, respectively; p<0.001). Similarly, mean DRSP scores 5 days before menstruation decreased progressively from the COC group, the calcium group and the placebo group (45.51±16.97, 55±15.71 and 74.98±19.12, respectively; p<0.001).
CONCLUSION: Both COC and calcium supplements improved DRSP scores in women with mild to moderate PMS, but the improvement was more evident with COC.

Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
PMID 26808666  Eur J Obstet Gynecol Reprod Biol. 2016 Mar;198:100-4. d・・・
著者: Arman Arab, Sahar Golpour-Hamedani, Nahid Rafie
雑誌名: J Am Coll Nutr. 2019 Sep-Oct;38(7):648-656. doi: 10.1080/07315724.2019.1566036. Epub 2019 May 10.
Abstract/Text A number of studies have assessed the association between vitamin D and premenstrual syndrome (PMS) in different populations, but the findings have been inconclusive. Herein, we systematically reviewed available observational and interventional evidence to elucidate the overall relationship between vitamin D and PMS. PubMed, Cochrane Library, ScienceDirect, Scopus, Google Scholar, and ISI Web of Science databases were searched for all available articles until September 2018. The Newcastle-Ottawa quality assessment scale and Jadad scale were used to assess the quality of the observational and interventional studies, respectively. A total of 16 studies out of 196 met our inclusion criteria and were included in the final analysis. Although no significant association between serum 25(OH)D and PMS (weighted mean difference (WMD) = 3.35; 95% confidence interval, -7.80 to 1.11; p = 0.14) was indicated in observational studies, vitamin D supplementation was effective in ameliorating PMS symptoms based upon findings from interventional studies. These results add to the existing literature supporting the fact that nutrition, especially vitamin D, plays an important role in women's health. Additional well-designed clinical trials should be considered in future research to develop firm conclusions on the efficacy of vitamin D on PMS. KEY TEACHING POINTS 5-8% of women experience severe PMS. Nutrition especially vitamin D plays an important role in the women's health. Vitamin D could exert significant clinical effects on PMS symptoms. This is a systematic review and meta-analysis in this regard.

PMID 31074708  J Am Coll Nutr. 2019 Sep-Oct;38(7):648-656. doi: 10.108・・・
著者: Afsane Bahrami, Amir Avan, Hamid Reza Sadeghnia, Habibollah Esmaeili, Maryam Tayefi, Faezeh Ghasemi, Fatemeh Nejati Salehkhani, Mahla Arabpour-Dahoue, Azam Rastgar-Moghadam, Gordon A Ferns, Hamidreza Bahrami-Taghanaki, Majid Ghayour-Mobarhan
雑誌名: Gynecol Endocrinol. 2018 Aug;34(8):659-663. doi: 10.1080/09513590.2017.1423466. Epub 2018 Feb 15.
Abstract/Text Vitamin D has a crucial role in female reproduction, possibly through its effects on calcium homeostasis, cyclic sex steroid hormone fluctuations, or neurotransmitter function. We have assessed the effects of vitamin D supplementation on dysmenorrhea and premenstrual syndrome (PMS) in adolescents. In this study, 897 adolescent girls living in Mashhad and Sabzevar, Iran, received nine high-dose vitamin D supplements (as 50,000 IU/week of cholecalciferol) and were followed up over 9 weeks. We evaluated the effect of vitamin D supplementation on individuals in four categories: those with only PMS; individuals with only dysmenorrhea; subjects with both PMS and dysmenorrhea and normal subjects. The prevalence of PMS after the intervention fell from 14.9% to 4.8% (p < .001). Similar results were also found for the prevalence of subjects with dysmenorrhea (35.9% reduced to 32.4%), and in subjects with both PMS and dysmenorrhea (32.7% reduced 25.7%). Vitamin D supplementation was associated with a reduction in the incidence of several symptoms of PMS such as backache and tendency to cry easily as well as decrement in pain severity of dysmenorrhea (p < .05). High dose vitamin D supplementation can reduce the prevalence of PMS and dysmenorrhea as well as has positive effects on the physical and psychological symptoms of PMS.

PMID 29447494  Gynecol Endocrinol. 2018 Aug;34(8):659-663. doi: 10.108・・・
著者: Fabio Parazzini, Mirella Di Martino, Paolo Pellegrino
雑誌名: Magnes Res. 2017 Feb 1;30(1):1-7. doi: 10.1684/mrh.2017.0419.
Abstract/Text A growing amount of evidence suggests that magnesium deficiency may play an important role in several clinical conditions concerning women health such as premenstrual syndrome, dysmenorrhea, and postmenopausal symptoms. A number of studies highlighted a positive correlation between magnesium administration and relief or prevention of these symptoms, thus suggesting that magnesium supplementation may represent a viable treatment for these conditions. Despite this amount of evidence describing the efficacy of magnesium, few and un-systematize data are available about the pharmacological mechanism of this ion for these conditions. Herein, we review and systematize the available evidence about the use of oral magnesium supplementation in several gynecological conditions and discuss the pharmacological mechanisms that characterize these interventions. The picture that emerges indicates that magnesium supplementation is effective in the prevention of dysmenorrhea, premenstrual syndrome, and menstrual migraine and in the prevention of climacteric symptoms.

PMID 28392498  Magnes Res. 2017 Feb 1;30(1):1-7. doi: 10.1684/mrh.2017・・・
著者: Mohsen Moslehi, Arman Arab, Mahdi Shadnoush, Hossein Hajianfar
雑誌名: Biol Trace Elem Res. 2019 Dec;192(2):145-152. doi: 10.1007/s12011-019-01672-z. Epub 2019 Mar 18.
Abstract/Text A number of studies have assessed the association between serum magnesium (Mg) and premenstrual syndrome (PMS) in different population, but the findings have been inconclusive. Herein, we systematically reviewed available observational studies to elucidate the overall relationship between Mg and PMS. PubMed, Cochrane's library, ScienceDirect, Scopus, Google Scholar, and ISI web of science databases were searched for all available literature until January 2019 for studies evaluating the association between Mg and PMS. The Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of observational studies. A total of 13 studies out of 196 met our inclusion criteria and were included in our systematic review and meta-analysis. There were no associations between serum magnesium and PMS (WMD - 0.04; 95% CI, - 0.14 to 0.06; P = 0.46) during follicular or serum/erythrocyte magnesium (WMD - 0.37; 95% CI, - 1.01 to 0.27; P = 0.25)/(WMD - 0.04; 95% CI, - 0.10 to 0.03; P = 0.26) and during luteal phase except for the sub-group of studies done outside of the US in which recent association became significant and means that serum Mg is lower in PMS subjects. According to what have been discussed, although our study did not show any significant association between serum/erythrocyte Mg and PMS except for serum Mg in luteal phase in the sub-group of studies done outside of the USA, heterogeneity between studies should be taken into accounts when interpreting these results. Additional well-designed clinical trials should be considered in future research to develop firm conclusions on the efficacy of magnesium on PMS.Registration number: CRD42018114473 .

PMID 30880352  Biol Trace Elem Res. 2019 Dec;192(2):145-152. doi: 10.1・・・
著者: Ari Shechter, Paul Lespérance, N M K Ng Ying Kin, Diane B Boivin
雑誌名: PLoS One. 2012;7(12):e51929. doi: 10.1371/journal.pone.0051929. Epub 2012 Dec 19.
Abstract/Text Women with premenstrual dysphoric disorder (PMDD) experience mood deterioration and altered circadian rhythms during the luteal phase (LP) of their menstrual cycles. Disturbed circadian rhythms may be involved in the development of clinical mood states, though this relationship is not fully characterized in PMDD. We therefore conducted an extensive chronobiological characterization of the melatonin rhythm in a small group of PMDD women and female controls. In this pilot study, participants included five women with PMDD and five age-matched controls with no evidence of menstrual-related mood disorders. Participants underwent two 24-hour laboratory visits, during the follicular phase (FP) and LP of the menstrual cycle, consisting of intensive physiological monitoring under "unmasked", time-isolation conditions. Measures included visual analogue scale for mood, ovarian hormones, and 24-hour plasma melatonin. Mood significantly (P≤.03) worsened during LP in PMDD compared to FP and controls. Progesterone was significantly (P = .025) increased during LP compared to FP, with no between-group differences. Compared to controls, PMDD women had significantly (P<.05) decreased melatonin at circadian phases spanning the biological night during both menstrual phases and reduced amplitude of its circadian rhythm during LP. PMDD women also had reduced area under the curve of melatonin during LP compared to FP. PMDD women showed affected circadian melatonin rhythms, with reduced nocturnal secretion and amplitude during the symptomatic phase compared to controls. Despite our small sample size, these pilot findings support a role for disturbed circadian rhythms in affective disorders. Possible associations with disrupted serotonergic transmission are proposed.

PMID 23284821  PLoS One. 2012;7(12):e51929. doi: 10.1371/journal.pone.・・・
著者: Shazia Jehan, Evan Auguste, Mahjabeen Hussain, Seithikurippu R Pandi-Perumal, Amon Brzezinski, Ravi Gupta, Hrayr Attarian, Giradin Jean-Louis, Samy I McFarlane
雑誌名: J Sleep Med Disord. 2016;3(5). Epub 2016 Aug 3.
Abstract/Text The etiology of premenstrual syndrome (PMS) is unknown; it may be due to the normal effect of hormones during the menstrual cycle as it occurs in the late luteal phase of the menstrual cycle.PMS affects women of childbearing age and remits with the onset of menstruation. The menstrual phase is known to influence stage 2 and REM sleep in women, irrespective of premenstrual dysphoric disorder (PMDD). Women with PMDD showed a decreased response to melatonin in their luteal phase as compared to the follicular phase of the menstrual cycle. However, melatonin duration or timing of offset in the morning has not been reported to correlate with the mood. Rather, improvement in mood-related symptoms of PMDD has been found to be influenced by sleep deprivation, be it sleep restrictions in early or late night. Sleep disturbance and decreased melatonin secretions due to hormonal fluctuations during the luteal phase of the menstrual cycle could explain the sleep complaints of PMDD.

PMID 28239684  J Sleep Med Disord. 2016;3(5). Epub 2016 Aug 3.
著者: María Del Mar Fernández, Agustín Montes-Martínez, María Piñeiro-Lamas, Carlos Regueira-Méndez, Bahi Takkouche
雑誌名: PLoS One. 2019;14(6):e0218794. doi: 10.1371/journal.pone.0218794. Epub 2019 Jun 21.
Abstract/Text OBJECTIVE: To assess whether tobacco smoking is associated with Premenstrual Syndrome (PMS) and its most severe form, Premenstrual Dysphoric Disorder (PMDD).
DESIGN: Case-control study with incident cases using the Spanish public healthcare system.
SETTING: 3 major public hospitals and one family counseling and planning center.
POPULATION: Women consulting for troubles related to menstruation and for other motives such as screening for uterine cancer, contraception counseling or desire for pregnancy.
METHODS: Logistic regression.
MAIN OUTCOME MEASURES: Odds Ratios of PMS and PMDD.
RESULTS: 285 incident PMS cases and 285 age-matched controls on the one hand, and 88 incident PMDD cases and 176 controls on the other hand participated in the study. The odds of premenstrual disorders was higher in current smokers compared with never smokers: Odds Ratio (OR) = 1.78, 95% Confidence Interval (CI): 1.20-2.63 for PMS and OR = 2.92, 95%CI: 1.55-5.50 for PMDD. For PMS, women who smoke 1 to 5 cigarettes/day presented an OR = 2.82, 95%CI: 1.57-5.06 and those who smoke more than 15 cigarettes/day an OR = 2.52, 95%CI: 0.99-6.40. Compared to non-smokers, current and ex-smokers who smoked < 3 pack-years presented an OR = 1.79, 95%CI: 1.04-3.08 for PMS, and an OR = 3.06, 95%CI: 1.27-7.35 for PMDD. Smokers of 3 to 8 pack-years presented an OR = 2.34, 95%CI: 1.33-4.13 for PMS and OR = 3.56, 95%CI: 1.55-8.17 for PMDD. These results were confirmed by the exposure-effect curve obtained from a cubic spline model.
CONCLUSIONS: This study shows that smokers are more likely to develop PMS and PMDD.

PMID 31226148  PLoS One. 2019;14(6):e0218794. doi: 10.1371/journal.pon・・・
著者: María Del Mar Fernández, Jurgita Saulyte, Hazel M Inskip, Bahi Takkouche
雑誌名: BMJ Open. 2018 Apr 16;8(3):e019490. doi: 10.1136/bmjopen-2017-019490. Epub 2018 Apr 16.
Abstract/Text OBJECTIVE: Premenstrual syndrome (PMS) is a very common disorder worldwide which carries an important economic burden. We conducted a systematic review and a meta-analysis to assess the role of alcohol in the occurrence of PMS.
METHODS: We searched MEDLINE, EMBASE, the five regional bibliographic databases of the WHO, the Proceedings database and the Open Access Thesis and Dissertations (OATD) from inception to May 2017. We also reviewed the references of every article retrieved and established personal contact with researchers to trace further publications or reports. We did not include any language limitations. Studies were included if: (1) they presented original data from cohort, case-control or cross-sectional studies, (2) PMS was clearly defined as the outcome of interest, (3) one of the exposure factors was alcohol consumption, (4) they provided estimates of odds ratios, relative risks, or any other effect measure and their confidence intervals, or enough data to calculate them.
RESULTS: We identified 39 studies of which 19 were eligible. Intake of alcohol was associated with a moderate increase in the risk of PMS (OR=1.45, 95% CI: 1.17 to 1.79). Heavy drinking yielded a larger increase in the risk than any drinking (OR=1.79, 95% CI: 1.39 to 2.32).
DISCUSSION: Our results suggest that alcohol intake presents a moderate association with PMS risk. Future studies should avoid cross-sectional designs and focus on determining whether there is a threshold of alcohol intake under which the harmful effect on PMS is non-existent.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
PMID 29661913  BMJ Open. 2018 Apr 16;8(3):e019490. doi: 10.1136/bmjope・・・
著者: Ellen W. Freeman, Steven J. Sondheimer
雑誌名: Prim Care Companion J Clin Psychiatry. 2003 Feb;5(1):30-39.
Abstract/Text Premenstrual dysphoric disorder (PMDD) represents the more severe and disabling end of the spectrum of premenstrual syndrome and occurs in an estimated 2% to 9% of menstruating women. The most frequent PMDD symptoms among women seeking treatment consist of anger/irritability, anxiety/tension, feeling tired or lethargic, mood swings, feeling sad or depressed, and increased interpersonal conflicts. Women who develop PMDD appear to have serotonergic dysregulation that may be triggered by cyclic changes in gonadal steroids. The marked increase in the number of well-designed placebo-controlled studies in the past decade has established several selective serotonin reuptake- inhibiting antidepressants as effective first-line treatments for this disorder. Both continuous dosing and intermittent luteal dosing strategies lead to rapid improvement in symptoms and functioning. The present article provides a brief review of current information on the epidemiology, clinical presentation, neurobiology, and treatment of PMDD.

PMID 15156244  Prim Care Companion J Clin Psychiatry. 2003 Feb;5(1):30・・・
著者: Rohit Kumar Verma, Dinesh Kumar Chellappan, Awanish Kumar Pandey
雑誌名: J Basic Clin Physiol Pharmacol. 2014 Mar 12;. doi: 10.1515/jbcpp-2013-0072. Epub 2014 Mar 12.
Abstract/Text Abstract Premenstrual syndrome (PMS) is the most common problem associated with women's health. Most women take alternative therapies for the treatment of PMS along with conventional therapies. A literature search was conducted which investigated various conventional and alternative therapies for the treatment of PMS. Web- and manual-based literature surveys were conducted to assess the information available on conventional and alternative treatment of PMS. Pubmed, Scopus, and Google scholar databases were screened, using the terms 'PMS and its management', 'pharmacotherapy of PMS', 'Alternative therapies for the treatment of PMS'. Publications with abstract/full articles and books were reviewed. Based on the available literature, there have been randomized clinical trials (RCTs) and high levels of evidence studies. The review addressed that drosperinone with ethinylestradiol has shown great improvement in symptoms of PMS in various RCTs. Among the alternative therapies use of micronutrients and herbs were found effective in treatment for symptoms of PMS.

PMID 24620013  J Basic Clin Physiol Pharmacol. 2014 Mar 12;. doi: 10.1・・・
著者: Irene Kwan, Joseph Loze Onwude
雑誌名: BMJ Clin Evid. 2015 Aug 25;2015. Epub 2015 Aug 25.
Abstract/Text INTRODUCTION: A woman has premenstrual syndrome (PMS) if she complains of recurrent psychological and/or physical symptoms occurring during the luteal phase of the menstrual cycle, and often resolving by the end of menstruation. Symptom severity can vary between women. Premenstrual symptoms occur in 95% of women of reproductive age. Severe, debilitating symptoms occur in about 5% of those women. There is no consensus on how symptom severity should be assessed for PMS, which has led to the use of a wide variety of symptom scores and scales, thus making it difficult to synthesise data on treatment efficacy. The cyclical nature of the condition also makes it difficult to conduct RCTs.
METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of continuous hormonal treatments in women with premenstrual syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview).
RESULTS: At this update, searching of electronic databases retrieved 132 studies. After deduplication and removal of conference abstracts, 132 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 102 studies and the further review of 30 full publications. Of the 30 full articles evaluated, one systematic review and three RCTs were added to this overview. We performed a GRADE evaluation for three PICO combinations.
CONCLUSIONS: In this systematic overview, we categorised the efficacy for three interventions based on information relating to the effectiveness and safety of continuous combined oral contraceptives, continuous transdermal estradiol, and continuous subcutaneous estradiol implants.

PMID 26303988  BMJ Clin Evid. 2015 Aug 25;2015. Epub 2015 Aug 25.
著者: Takashi Takeda, Akiko Kondo, Shoko Koga, Jun Hayakawa, Kenichi Hayakawa, Keizo Hiramatsu, Nobuo Yaegashi
雑誌名: J Obstet Gynaecol Res. 2015 Oct;41(10):1584-90. doi: 10.1111/jog.12774. Epub 2015 Aug 26.
Abstract/Text AIM: A combined oral contraceptive containing ethinylestradiol 20 µg plus drospirenone 3 mg (EE20 + DRSP) in a 24/4 regimen has been shown to alleviate the symptoms of premenstrual syndrome and premenstrual dysphoric disorder. This study was conducted to evaluate the efficacy of EE20 + DRSP in Japanese patients with premenstrual symptoms.
MATERIAL AND METHODS: A multicenter, prospective, open-label, single-arm, phase IV study was performed in Japanese women with dysmenorrhea and premenstrual symptoms. They were treated with EE20 + DRSP to alleviate the symptoms of dysmenorrhea for six treatment cycles. Premenstrual symptoms were evaluated using a Premenstrual Symptoms Questionnaire at baseline and after three and six cycles of EE20 + DRSP. The degree of dysmenorrhea was also evaluated using a visual analog scale at baseline and after one, three, and six cycles of EE20 + DRSP.
RESULTS: Forty-eight patients were treated with EE20 + DRSP. Most of the premenstrual symptoms were alleviated significantly by three and six cycles of EE20 + DRSP treatment. EE20 + DRSP treatment significantly improved the severity of premenstrual symptoms. We also confirmed the effectiveness of EE20 + DRSP for the treatment for dysmenorrhea.
CONCLUSION: This study showed that EE20 + DRSP could be a useful treatment strategy for premenstrual symptoms in Japanese women.

© 2015 Japan Society of Obstetrics and Gynecology.
PMID 26310836  J Obstet Gynaecol Res. 2015 Oct;41(10):1584-90. doi: 10・・・
著者: Shalini Maharaj, Kenneth Trevino
雑誌名: J Psychiatr Pract. 2015 Sep;21(5):334-50. doi: 10.1097/PRA.0000000000000099.
Abstract/Text Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome that involves a combination of emotional and physical symptoms that result in significant functional impairment. Because of the debilitating nature of PMDD, multiple treatment options have been considered. This review provides a comprehensive overview of these therapeutic regimens to help health care professionals provide adequate treatment for PMDD and premenstrual syndrome. The treatments that are reviewed are organized into the following categories: psychiatric, anovulatory, supplements, herbal, nonpharmacological, and other. Selective serotonin reuptake inhibitors have been established as the first-line treatment for PMDD. Although luteal phase or continuous dosing can be used, additional research is needed to more thoroughly compare the efficacies and differential symptom response of continuous, semi-intermittent, luteal phase, and symptoms-onset dosing. The psychiatric medications venlafaxine, duloxetine, alprazolam, and buspirone have also been found to be useful treatments for PMDD. Various anovulatory-related treatments have demonstrated efficacy; however, the use of some of these treatments remains limited due to potential side effects and/or the availability of cheaper alternatives. Although a variety of supplement and herbal-related treatments have been proposed, with some warranting further research, at this time only calcium supplementation has demonstrated a consistent therapeutic benefit. In conclusion, serotoninergic antidepressants have been established as the first-line treatment option for PMDD; however, there are a variety of additional treatment options that should be considered if a patient fails to achieve an adequate therapeutic response with a selective serotonin reuptake inhibitor.

PMID 26352222  J Psychiatr Pract. 2015 Sep;21(5):334-50. doi: 10.1097/・・・
著者: Rebecca Stoner, Victoria Camilleri, Jean Calleja-Agius, Pierre Schembri-Wismayer
雑誌名: Gynecol Endocrinol. 2017 Aug;33(8):588-592. doi: 10.1080/09513590.2017.1318367. Epub 2017 Apr 26.
Abstract/Text Premenstrual syndrome (PMS) and related disorders, and postpartum depression (PPD) can affect women to the extent that their quality of life and that of their near ones can be severely impaired. This review focuses on the different theories regarding the etiologies of PMS and PPD, and attempts to draw a link between the two. Theories focus mainly on hormonal and cytokine factors throughout different phases in the female reproductive cycle. Changes in this symptomatology during pregnancy are also reviewed, as are changes in hormones and cytokine levels. Hypotheses are thus developed as to why the symptoms experienced in PMS often subside during pregnancy yet may recur and be exacerbated after birth, giving rise to the symptoms experienced in PPD.

PMID 28443697  Gynecol Endocrinol. 2017 Aug;33(8):588-592. doi: 10.108・・・
著者: R T Amiel Castro, E A Pataky, U Ehlert
雑誌名: Biol Psychol. 2019 Oct;147:107612. doi: 10.1016/j.biopsycho.2018.10.014. Epub 2018 Nov 16.
Abstract/Text Overlapping symptoms between premenstrual syndrome (PMS) and postpartum depression (PPD) suggest that these disorders may share a common etiology and pathology. Moreover, PMS is a risk factor for the development of PPD. This review aims to synthesize the evidence regarding associations between PMS and PPD. Studies were systematically reviewed through identification in PubMed, ISI web of knowledge, PsycINFO and JSTOR databases. A total of 16 studies met inclusion criteria. Three studies revealed an initial significant association between both variables, but it did not remain significant after the inclusion of confounders (e.g. personality, socio-demographic factors) into the analyses. Eleven papers found a positive association between PMS and PPD beyond the effects of biopsychosocial confounders (p < .05). Finally, two studies did not find any significant association between both variables. This review demonstrated that there is a positive association - potentially a mechanism - between PMS and PPD, which may depend on specific confounders.

Copyright © 2018 Elsevier B.V. All rights reserved.
PMID 30452945  Biol Psychol. 2019 Oct;147:107612. doi: 10.1016/j.biops・・・
著者: Sifan Cao, Mark Jones, Leigh Tooth, Gita D Mishra
雑誌名: J Psychiatr Res. 2020 Feb;121:82-90. doi: 10.1016/j.jpsychires.2019.11.010. Epub 2019 Nov 17.
Abstract/Text BACKGROUND: Premenstrual syndrome (PMS) is thought to be a risk factor for postpartum depression (PPD), but results from studies examining the association have been mixed.
OBJECTIVES: To estimate the association between pre-pregnancy history of PMS and development of PPD and evaluate the risk of bias of included evidence.
SEARCH STRATEGY: PubMed, EMBASE, CINAHL, PsycINFO, Cochrane Library, CNKI, Wanfang Data, and reference lists of relevant papers were searched.
SELECTION CRITERIA: Observational studies that collected pre-pregnancy history of PMS and measured PPD status between one week and one year after delivery were included.
DATA COLLECTION AND ANALYSIS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Random-effect models were used to calculate pooled odds ratios (ORs) with 95% confidence interval (CI). Small study effect was analysed by funnel plot. Risk of bias was assessed using the Risk of Bias Instrument for Non-Randomized Studies of Exposures (ROBINS-E).
MAIN RESULTS: Our meta-analysis included 19 studies. Overall, women with a pre-pregnancy history of PMS had more than double the odds of PPD compared to those without PMS (OR: 2.20, 95% CI: 1.81-2.68). However, the quality of evidence was low: five studies had moderate risk, eleven studies had serious risk, and three studies had critical risk of bias.
CONCLUSIONS: Current evidence supports a significant association between history of PMS and development of PPD. Well-designed prospective studies are needed to further investigate this relationship.

Copyright © 2019 Elsevier Ltd. All rights reserved.
PMID 31783236  J Psychiatr Res. 2020 Feb;121:82-90. doi: 10.1016/j.jps・・・
著者: Elizabeth R Bertone-Johnson, Brian W Whitcomb, Janet W Rich-Edwards, Susan E Hankinson, JoAnn E Manson
雑誌名: Am J Epidemiol. 2015 Dec 15;182(12):1000-9. doi: 10.1093/aje/kwv159. Epub 2015 Nov 24.
Abstract/Text The prevalence of hypertension is increasing among younger women, and new strategies are needed to identify high-risk women who should be targets for early intervention. Several mechanisms underlying hypertension might also contribute to premenstrual syndrome (PMS), but whether women with PMS have a higher risk of subsequently developing hypertension has not been assessed. We prospectively evaluated this possibility in a substudy of the Nurses' Health Study II. Participants were 1,257 women with clinically significant PMS (1991-2005) and 2,463 age-matched comparison women with few menstrual symptoms. Participants were followed for incident hypertension until 2011. Over 6-20 years, hypertension was reported by 342 women with PMS and 541 women without. After adjustment for age, smoking, body mass index, and other risk factors for hypertension, women with PMS had a hazard ratio for hypertension of 1.4 (95% confidence interval: 1.2, 1.6) compared with women without PMS. Risk was highest for hypertension that occurred before 40 years of age (hazard ratio = 3.3; 95% confidence interval: 1.7, 6.5; P for interaction = 0.0002). The risk associated with PMS was not modified by use of oral contraceptives or antidepressants but was attenuated among women with high intakes of thiamine and riboflavin (P < 0.05). These results suggest that PMS might be associated with future development of hypertension and that this risk may be modifiable.

© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PMID 26601989  Am J Epidemiol. 2015 Dec 15;182(12):1000-9. doi: 10.109・・・
著者: E W Freeman, R J DeRubeis, K Rickels
雑誌名: Psychiatry Res. 1996 Nov 15;65(2):97-106.
Abstract/Text Daily ratings of symptoms are essential to confirm a diagnosis of premenstrual syndrome (PMS). The 17-item Daily Symptom Report (DSR) is relatively brief and appropriate for clinical and primary care settings. We report the reliability, factor structure and relationships with other standard mood measures of the DSR as a measure of PMS. The sample includes 170 women who sought medical treatment for severe PMS and a non-clinical comparison group of 54 healthy women in the same age range. Cronbach's coefficient alpha was 0.92 for the premenstrual DSR scores, indicating very high internal consistency for the 17 symptoms. Factor analysis yielded four factors describing mood, behavioral items, pain, and physical symptoms. In the PMS sample, there were moderate correlations between the DSR and the Hamilton Rating Scale for Depression, the Profile of Mood States, and the Premenstrual Assessment Form. The moderate correlations of the DSR with other standard symptom measures add to the evidence that PMS overlaps with other mood disorders at the premenstrual time but is not simply a brief depression or a truncated anxiety disorder.

PMID 9122290  Psychiatry Res. 1996 Nov 15;65(2):97-106.
著者: J F Mortola, L Girton, L Beck, S S Yen
雑誌名: Obstet Gynecol. 1990 Aug;76(2):302-7.
Abstract/Text To establish a quantitative method for the diagnosis of premenstrual syndrome (PMS), a simple prospective inventory, the calendar of premenstrual experiences, was constructed. The validity and reliability of this instrument were assessed by administering it throughout two consecutive ovulatory cycles to 36 rigidly screened women with PMS and to 18 controls. To establish concurrent validity, scores on behavioral items were correlated with simultaneously obtained scores on lengthier, well-validated psychiatric inventories designed to measure depression rather than PMS, the Beck Depression Inventory and the Profile of Mood States. The results showed that the calendar of premenstrual experiences luteal phase score distinguished PMS women from controls correctly in 104 of 108 cycles, with a 2.8% false-negative rate and no false positives when used for two consecutive cycles. An upper limit follicular phase score was observed beneath which all PMS and normal control subjects fell, suggesting that a higher score is not consistent with PMS. Correlation coefficients of calendar item scores with Profile of Mood States scale scores were 0.58 for tension, 0.51 for depression, 0.46 for anger, 0.61 for fatigue, and 0.57 for confusion (P less than .0001 for all correlations). The correlation of the calendar depression item with the Beck Depression Inventory score was 0.56 (P less than .0001). The test-retest reliability of the calendar given in the same phase of two consecutive menstrual cycles was high (r = 0.78, P less than .0001). We conclude that this instrument is a valid, reliable, and practical PMS inventory, applicable to clinical and some research settings.

PMID 2371035  Obstet Gynecol. 1990 Aug;76(2):302-7.
著者: ACOG Committee on Practice Bulletins--Gynecology
雑誌名: Obstet Gynecol. 2000 Apr;95(4):suppl 1-9.
Abstract/Text
PMID 24829972  Obstet Gynecol. 2000 Apr;95(4):suppl 1-9.
著者: Susan R Johnson
雑誌名: Obstet Gynecol. 2004 Oct;104(4):845-59. doi: 10.1097/01.AOG.0000140686.66212.1e.
Abstract/Text The management of adverse premenstrual symptoms has presented a difficult challenge for clinicians. However, based on numerous well-designed research studies over the last decade, we now have diagnostic criteria for the severe form of the syndrome, premenstrual dysphoric disorder, and a variety of evidence-based therapeutic strategies. This review presents a comprehensive, practical description of what the clinician needs to know to diagnose and treat adverse premenstrual symptoms at all levels of severity. Diagnostic criteria are described in detail, including a discussion of the distinction between premenstrual dysphoric disorder and premenstrual syndrome (PMS). The rationale for including prospective symptom calendars as a routine part of the diagnostic evaluation of severe symptoms is presented. The differential diagnosis of cyclic symptoms, including depression and anxiety disorders, menstrual migraine, and mastalgia, and an approach for the management of each of these problems are presented. A treatment approach is recommended that matches the treatment to the degree of problems the woman is experiencing. Serotonin reuptake inhibitors are the treatment of choice for severe symptoms, and most women with PMS/premenstrual dysphoric disorder will respond to intermittent, luteal phase-only therapy. Ovulation suppression should be reserved for women who do not respond to other forms of therapy. The role of oophorectomy is limited, and guidelines for its use are presented.

PMID 15458909  Obstet Gynecol. 2004 Oct;104(4):845-59. doi: 10.1097/01・・・
著者: Anna Maria Paoletti, Stefano Lello, Stefania Fratta, Marisa Orrù, Francesca Ranuzzi, Cristiana Sogliano, Alessandra Concas, Giovanni Biggio, Gian Benedetto Melis
雑誌名: Fertil Steril. 2004 Mar;81(3):645-51. doi: 10.1016/j.fertnstert.2003.08.030.
Abstract/Text OBJECTIVE: To investigate in healthy eumenorrheic young women whether an oral contraceptive (OC) containing drospirenone (DRSP) (3 mg) + ethinyl estradiol (EE) (30 microg) (DRSP + EE) could modify psychological symptoms and whether it could modify steroids interfering with the gamma-aminobutyric acid (GABA)-A receptors.
DESIGN: Clinical study of treated subjects and nontreated controls.
SETTING: Healthy volunteers in the Department of Obstetrics and Gynecology at Cagliari University.
PATIENT(S): Control group (n = 12) and OC group (n = 10) women with similar age, body mass index, and main outcome measures.
INTERVENTION(S): The control group was studied during the first menstrual cycle at the follicular phase (FP) and at the luteal phase (LP) and during the third cycle at the LP; the OC group was studied during the first cycle, as described above, and on day 16-18 of the third cycle of treatment with DRSP + EE.
MAIN OUTCOME MEASURE(S): Psychometric scale (SCL-90), DHEAS, P, allopregnanolone (AP), and allotetrahydrodeoxy-corticosterone (THDOC).
RESULT(S): SCL-90 and DHEAS did not vary throughout the menstrual cycle. P, AP, and THDOC values were higher during the LP than the FP. At the third cycle, in the control group the main outcome measures were similar to those at LP. In the OC group, the SCL-90 global score, the intensity of anxiety and phobic anxiety, the levels of anxiolytic steroids (P, AP, THDOC) and the anxiety-inducing steroid DHEAS were reduced.
CONCLUSION(S): The results suggest beneficial effects of DRSP + EE on psychological symptoms by decreasing DHEAS.

PMID 15037415  Fertil Steril. 2004 Mar;81(3):645-51. doi: 10.1016/j.fe・・・
著者: Andrea L Coffee, Thomas J Kuehl, Sherilyn Willis, Patricia J Sulak
雑誌名: Am J Obstet Gynecol. 2006 Nov;195(5):1311-9. doi: 10.1016/j.ajog.2006.05.012. Epub 2006 Jun 21.
Abstract/Text OBJECTIVE: The purpose of this study was to assess the incidence and severity of premenstrual-type symptoms in patients converted from a 21/7 oral contraceptive (OC) regimen to an extended regimen.
STUDY DESIGN: This was a single center prospective analysis of the single item Scott and White (S&W) Mood Scale and the Penn State Daily Symptom Report (DSR17) during a 21/7-day followed by a 168-day extended regimen of an OC containing 3 mg of drosperinone and 30 microg of ethinyl estradiol (DRSP/EE).
RESULTS: Of the 114 patients who began the study, 111 completed the preextension 21/7 phase of the study. There were significant differences in severity in the DSR17 and the S&W mood scale among days of the cycle. (P < .0001) The highest values in both scales occurred during the 7-day hormone free interval (HFI) of the 21/7 cycles (P < .001). Of the 111 patients who completed the 21/7 phase of the study, 102 (92%) completed the 168-day extended regimen. During the extended phase of the study, subjects were divided into 2 groups: those with a 100% increase in symptoms from the first half to the second half of the last 21/7 cycle were labeled as high cyclic variability, whereas those with lesser or no cyclic change were labeled as low cyclic variability. There were 55 (54%) with increased cyclic variability in mood scores peaking during the 7-day HFI. Premenstrual-type symptoms measured by both the S&W mood scale and the DSR17 instrument decreased during the extended DRSP/EE OC regimen (P < .0001) compared with the preceding 21/7 cycle, with the greatest improvement detected in the sixth month of continuous OCs (P < .003). The patient group with greatest cyclic variability during the 21/7 regimen demonstrated the most improvement during the 168-day regimen (P < .0001). The single item S&W mood scale was significantly (P < .05) correlated to each of 17 elements of the DSR17 with Spearman R correlation coefficients of 0.25 to 0.57. The greatest correlation coefficient (Spearman's R = 0.66) is with the sum of all 17 items.
CONCLUSION: A 168-day extended regimen of DRSP/EE led to a decrease in premenstrual-type symptoms compared with the 21/7-day regimen.

PMID 16796986  Am J Obstet Gynecol. 2006 Nov;195(5):1311-9. doi: 10.10・・・
著者: Teri B Pearlstein, Gloria A Bachmann, Howard A Zacur, Kimberly A Yonkers
雑誌名: Contraception. 2005 Dec;72(6):414-21. doi: 10.1016/j.contraception.2005.08.021. Epub 2005 Nov 2.
Abstract/Text PURPOSE: This multicenter, double-blind, placebo-controlled crossover study evaluated the efficacy of a new oral contraceptive (OC) formulation containing drospirenone 3 mg and ethinyl estradiol (EE) 20 mug in treating symptoms of premenstrual dysphoric disorder (PMDD).
METHOD: The OC formulation or placebo was administered for 24 days in a 28-day cycle (24/4), rather than the usual 21-day active treatment, 7-day inert-pill regimen. Participants (N=64) were randomized to either study treatment for three cycles and then after a washout period of one treatment-free cycle switched to the alternate treatment.
RESULTS: The mean decrease from baseline for total Daily Record of Severity of Problems (DRSP) scores while using drospirenone/EE was significantly greater than for placebo (-12.47, 95% CI=-18.28, -6.66; p<.001). A positive response (i.e., a score of 1 or 2 in the Clinical Global Impressions-Improvement scale) occurred in 61.7% and 31.8% of subjects while taking drospirenone/EE and placebo, respectively (p=.009).
CONCLUSION: Drospirenone/EE, given in a 24/4 regimen, was superior to placebo for improving symptoms associated with PMDD.

PMID 16307962  Contraception. 2005 Dec;72(6):414-21. doi: 10.1016/j.co・・・
著者: Joachim Marr, Minoo Niknian, Lee P Shulman, Richard Lynen
雑誌名: Contraception. 2011 Jul;84(1):81-6. doi: 10.1016/j.contraception.2010.10.010. Epub 2010 Dec 17.
Abstract/Text BACKGROUND: A combined oral contraceptive comprising ethinylestradiol (EE) 20 mcg/drospirenone 3 mg in a 24/4 regimen has been clinically shown to alleviate the symptoms associated with premenstrual dysphoric disorder (PMDD). However, previous studies did not report data according to cycle-by-cycle improvement.
STUDY DESIGN: This was a subanalysis of a Phase III, double-blind, multicenter, United States-based study. Women with confirmed PMDD were randomized to EE 20 mcg/drospirenone 3 mg 24/4 or placebo for three treatment cycles. Ten of the 21 emotional and physical items on the Daily Record of Severity of Problems scale were grouped to define three symptom clusters: (a) negative emotions, (b) food cravings and (c) water retention-related symptoms. The change from baseline at each treatment cycle was compared between groups using a weighted analysis of covariance model.
RESULTS: The full analysis set comprised 449 women. Daily Record of Severity of Problems scores for each symptom cluster were significantly reduced from baseline with both EE 20 mcg/drospirenone 3 mg 24/4 and placebo (p<.0001 for all). The greatest symptom improvements were achieved within the first cycle of treatment and continued throughout cycles 2 to 3. The mean between-treatment difference was significant in favor of EE 20 mcg/drospirenone 3 mg 24/4 for all three symptom clusters in all three treatment cycles (p≤.0001 vs. placebo in percent change from baseline).
CONCLUSION: Ethinylestradiol 20 mcg/drospirenone 3 mg 24/4 improved commonly recognizable PMDD symptom clusters relating to negative emotions, food cravings and water retention-related symptoms to a significantly greater extent than placebo during all three cycles of treatment.

Copyright © 2011 Elsevier Inc. All rights reserved.
PMID 21664515  Contraception. 2011 Jul;84(1):81-6. doi: 10.1016/j.cont・・・
著者: Kelli Kelderhouse, Julie Smith Taylor
雑誌名: Nurs Womens Health. 2013 Aug-Sep;17(4):294-305. doi: 10.1111/1751-486X.12048.
Abstract/Text Premenstrual dysphoric disorder (PMDD) affects 5 to 8 percent of women and can significantly decrease their quality of life. Symptoms generally present during the late luteal phase of the menstrual cycle and can affect women emotionally, behaviorally, cognitively and physiologically. This article reviews the clinical literature on PMDD and the evidence behind various methods of symptom management. Evidence suggests that a holistic approach, including lifestyle modifications, pharmacotherapy and cognitive behavioral therapy, is most beneficial for symptom reduction and improvement in daily functioning and quality of life.

© 2013 AWHONN.
PMID 23957795  Nurs Womens Health. 2013 Aug-Sep;17(4):294-305. doi: 10・・・
著者: Laureen M Lopez, Adrian A Kaptein, Frans M Helmerhorst
雑誌名: Cochrane Database Syst Rev. 2012 Feb 15;2:CD006586. doi: 10.1002/14651858.CD006586.pub4. Epub 2012 Feb 15.
Abstract/Text BACKGROUND: Premenstrual syndrome (PMS) is a common problem. Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome. Combined oral contraceptives, which provide both progestin and estrogen, have been examined for their ability to relieve premenstrual symptoms. An oral contraceptive containing drospirenone and a low estrogen dose has been approved for treating PMDD in women who choose oral contraceptives for contraception.
OBJECTIVES: To review all randomized controlled trials comparing a combined oral contraceptive containing drospirenone to a placebo or another combined oral contraceptive for effect on premenstrual symptoms.
SEARCH METHODS: We searched for studies of drospirenone and premenstrual syndrome in the following databases: Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, and POPLINE (20 Dec 2011); EMBASE, LILACS, PsycINFO, ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP) of the World Health Organization (02 Mar 2011). We also examined references lists of relevant articles and wrote to known investigators to find other trials.
SELECTION CRITERIA: We included randomized controlled trials in any language that compared a combined oral contraceptive (COC) containing drospirenone with a placebo or with another COC for effect on premenstrual symptoms. The primary outcome included affective and physical premenstrual symptoms that were prospectively recorded. Adverse events related to combined oral contraceptive use were examined.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed study quality. For continuous variables, the mean difference (MD) was computed with 95% confidence interval (CI). For dichotomous outcomes, the Peto odds ratio (OR) with 95% CI was calculated.
MAIN RESULTS: We included five trials with a total of 1920 women. Two placebo-controlled trials of women with PMDD showed less severe premenstrual symptoms after three months with drospirenone 3 mg plus ethinyl estradiol 20 μg than with placebo (MD -7.92; 95% CI -11.16 to -4.67). The drospirenone group had greater mean decreases in impairment of productivity (MD -0.31; 95% CI -0.55 to -0.08), social activities (MD -0.29; 95% CI -0.54 to -0.04), and relationships (MD -0.30; 95% CI -0.54 to -0.06). Side effects more common with the use of the drospirenone COC contraceptive were nausea, intermenstrual bleeding, and breast pain. The respective odds ratios were 3.15 (95% CI 1.90 to 5.22), 4.92 (95% CI 3.03 to 7.96), and 2.67 (95% CI 1.50 to 4.78). Total adverse events related to the study drug were more likely for the drospirenone COC group (OR 2.36; 95% CI 1.62 to 3.44). Three trials studied the effect of drospirenone 3 mg plus ethinyl estradiol 30 μg on less severe symptoms. A placebo-controlled six-month trial had insufficient data for primary outcome analysis. Another six-month study used levonorgestrel 150 µg plus ethinyl estradiol 30 µg for the comparison group but did not provide enough data on premenstrual symptoms. In a two-year trial, the drospirenone COC group had similar premenstrual symptoms to the comparison group given desogestrel 150 µg plus ethinyl estradiol 30 µg (OR 0.87; 95% CI 0.63 to 1.22). The groups were also similar for adverse events related to treatment (OR 1.02; 95% CI 0.78 to 1.33).
AUTHORS' CONCLUSIONS: Drospirenone 3 mg plus ethinyl estradiol 20 μg may help treat premenstrual symptoms in women with severe symptoms, that is, premenstrual dysphoric disorder. The placebo also had a large effect. We do not know whether the combined oral contraceptive works after three cycles, helps women with less severe symptoms, or is better than other oral contraceptives. Larger and longer trials of higher quality are needed to address these issues. Trials should follow CONSORT guidelines.

PMID 22336820  Cochrane Database Syst Rev. 2012 Feb 15;2:CD006586. doi・・・
著者: Kimberly A Yonkers, Candace Brown, Teri B Pearlstein, Marie Foegh, Carole Sampson-Landers, Andrea Rapkin
雑誌名: Obstet Gynecol. 2005 Sep;106(3):492-501. doi: 10.1097/01.AOG.0000175834.77215.2e.
Abstract/Text OBJECTIVE: To compare the efficacy of a new low-dose oral contraceptive pill (OCP) formulation with placebo in reducing symptoms of premenstrual dysphoric disorder.
METHODS: This multicenter, double-blind, randomized clinical trial consisted of 2 run-in and 3 treatment cycles with daily symptom charting; 450 women with symptoms of premenstrual dysphoric disorder were randomized to either placebo or an OCP formulation containing drospirenone 3 mg and ethinyl estradiol 20 microg. Hormones were administered for 24 days, followed by 4 days of inactive pills (24/4).
RESULTS: Scores on the total Daily Record of Severity of Problems decreased by -37.49 in the drospirenone/ethinyl estradiol group and by -29.99 in the placebo group (adjusted mean difference -7.5, 95% confidence interval [CI] -11.2 to -3.8; P < .001 by rank analysis of covariance). Mood symptom scores were reduced by -19.2 and -15.3 in active-treatment and placebo groups, respectively (adjusted mean difference -3.9, 95% CI -5.84 to -2.01; P = .003); physical symptom scores were reduced by -10.7 and -8.6 in active-treatment and placebo groups, respectively (adjusted mean difference -2.1, 95% CI -3.3 to -0.95; P < .001); and behavioral symptom scores were reduced by -7.7 and -6.2 in active-treatment and placebo groups, respectively (adjusted mean difference -1.5, 95% CI -2.251 to -0.727; P < .001). Response, defined as a 50% decrease in daily symptom scores, occurred in 48% of the active-treatment group and 36% of the placebo group (relative risk 1.7, 95% CI 1.1 to 2.6; P = .015) and corresponds to a number-needed-to-treat of 8 patients.
CONCLUSION: A 24/4 regimen of drospirenone 3 mg and ethinyl estradiol 20 mug improves symptoms associated with premenstrual dysphoric disorder.
LEVEL OF EVIDENCE: I.

PMID 16135578  Obstet Gynecol. 2005 Sep;106(3):492-501. doi: 10.1097/0・・・

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