M Steiner, M Macdougall, E Brown
The premenstrual symptoms screening tool (PSST) for clinicians.
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.
T Takeda, K Tasaka, M Sakata, Y Murata
Prevalence of premenstrual syndrome and premenstrual dysphoric disorder in Japanese women.
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.
Direkvand-Moghadam A, Sayehmiri K, Delpisheh A, Kaikhavandi Sattar
Epidemiology of Premenstrual Syndrome (PMS)-A Systematic Review and Meta-Analysis Study.
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.
Hong Ju, Mark Jones, Gita D Mishra
Premenstrual syndrome and dysmenorrhea: symptom trajectories over 13 years in young adults.
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.
Glenda MacQueen, Pratap Chokka
Special issues in the management of depression in women.
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.
Wyatt KM, Dimmock PW, Jones PW, Shaughn O'Brien PM.
Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: systematic review.
BMJ. 1999 May 22;318(7195):1375-81. doi: 10.1136/bmj.318.7195.1375.
Abstract/Text
OBJECTIVE: To evaluate the efficacy of vitamin B-6 in the treatment of premenstrual syndrome.
DESIGN: Systematic review of published and unpublished randomised placebo controlled trials of the effectiveness of vitamin B-6 in the management of premenstrual syndrome.
SUBJECTS: Nine published trials representing 940 patients with premenstrual syndrome.
MAIN OUTCOME MEASURES: Proportion of women whose overall premenstrual symptoms showed an improvement over placebo. A secondary analysis was performed on the proportion of women whose premenstrual depressive symptoms showed an improvement over placebo.
RESULTS: Odds ratio relative to placebo for an improvement in overall premenstrual symptoms was 2.32 (95% confidence interval 1.95 to 2.54). Odds ratio relative to placebo for an improvement in depressive symptoms was 1.69 (1.39 to 2.06) from four trials representing 541 patients.
CONCLUSION: Conclusions are limited by the low quality of most of the trials included. Results suggest that doses of vitamin B-6 up to 100 mg/day are likely to be of benefit in treating premenstrual symptoms and premenstrual depression.
Takeda T.
Premenstrual disorders: Premenstrual syndrome and premenstrual dysphoric disorder.
J Obstet Gynaecol Res. 2023 Feb;49(2):510-518. doi: 10.1111/jog.15484. Epub 2022 Nov 1.
Abstract/Text
Recently, the term premenstrual disorders (PMDs), which includes premenstrual syndrome and premenstrual dysphoric disorder as a continuum, has been proposed. Although the precise etiology of PMDs remains unknown, the involvement of hormonal fluctuations is clear. The brain transmitters, serotonin and γ-amino butyric acid, also seem to be involved. Serotonin reuptake inhibitors and oral contraceptives are the current mainstay of treatment, but these are insufficient. Even the currently used prospective two-period symptom diary is not widely used in actual clinical practice, creating a major problem of discrepancy between research and clinical practice. In this review, I would like to outline the latest information and problems in the etiology, diagnosis, and treatment of PMDs, with an emphasis on promising new therapies.
© 2022 Japan Society of Obstetrics and Gynecology.
U Schweiger, R G Laessle, R J Tuschl, A Broocks, T Krusche, K M Pirke
Decreased follicular phase gonadotropin secretion is associated with impaired estradiol and progesterone secretion during the follicular and luteal phases in normally menstruating women.
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.
Yen JY, Lin HC, Lin PC, Liu TL, Long CY, Ko CH.
Early- and Late-Luteal-Phase Estrogen and Progesterone Levels of Women with Premenstrual Dysphoric Disorder.
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.
Lovick TA, Guapo VG, Anselmo-Franci JA, Loureiro CM, Faleiros MCM, Del Ben CM, Brandão ML.
A specific profile of luteal phase progesterone is associated with the development of premenstrual symptoms.
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.
Yen JY, Wang PW, Su CH, Liu TL, Long CY, Ko CH.
Estrogen levels, emotion regulation, and emotional symptoms of women with premenstrual dysphoric disorder: The moderating effect of estrogen receptor 1α polymorphism.
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.
Bixo M, Ekberg K, Poromaa IS, Hirschberg AL, Jonasson AF, Andréen L, Timby E, Wulff M, Ehrenborg A, Bäckström T.
Treatment of premenstrual dysphoric disorder with the GABAA receptor modulating steroid antagonist Sepranolone (UC1010)-A randomized controlled trial.
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.
Hantsoo L, Epperson CN.
Allopregnanolone in premenstrual dysphoric disorder (PMDD): Evidence for dysregulated sensitivity to GABA-A receptor modulating neuroactive steroids across the menstrual cycle.
Neurobiol Stress. 2020 May;12:100213. doi: 10.1016/j.ynstr.2020.100213. Epub 2020 Feb 4.
Abstract/Text
Premenstrual dysphoric disorder (PMDD) is a severe mood disorder with core symptoms (affective lability, irritability, depressed mood, anxiety) and increased sensitivity to stress occurring in the luteal phase of the menstrual cycle. PMDD can be conceptualized as a disorder of suboptimal sensitivity to neuroactive steroid hormones (NASs). In this review, we describe the role of the NAS allopregnanolone (ALLO), a positive allosteric modulator of the GABAA receptor (GABAA-R), in PMDD's pathophysiology. We review evidence of impaired interaction between ALLO and GABAA-Rs in terms of affective symptom expression, with evidence from rodent and human studies. We discuss evidence of increased luteal phase stress sensitivity as a result of poor ALLO-GABA control of the HPA axis. Finally, we describe how treatments such as selective serotonin reuptake inhibitors (SSRIs) and new drugs targeting GABAA-Rs provide evidence for impaired ALLO-GABA function in PMDD. In sum, the literature supports the hypothesis that PMDD pathophysiology is rooted in impaired GABAA-R response to dynamic ALLO fluctuations across the menstrual cycle, manifesting in affective symptoms and poor regulation of physiologic stress response.
© 2020 Published by Elsevier Inc.
Bixo M, Johansson M, Timby E, Michalski L, Bäckström T.
Effects of GABA active steroids in the female brain with a focus on the premenstrual dysphoric disorder.
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.
Jane Marjoribanks, Julie Brown, Patrick Michael Shaughn O'Brien, Katrina Wyatt
Selective serotonin reuptake inhibitors for premenstrual syndrome.
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.
Eriksson O, Wall A, Olsson U, Marteinsdottir I, Holstad M, Ågren H, Hartvig P, Långström B, Naessén T.
Women with Premenstrual Dysphoria Lack the Seemingly Normal Premenstrual Right-Sided Relative Dominance of 5-HTP-Derived Serotonergic Activity in the Dorsolateral Prefrontal Cortices - A Possible Cause of Disabling Mood Symptoms.
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.
Nicolau ZFM, Bezerra AG, Polesel DN, Andersen ML, Tufik S, Hachul H.
Plasma Leptin and Premenstrual Syndrome: A Review.
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.
Song C, Xue L.
Roles of the µ-opioid receptor and its related signaling pathways in the pathogenesis of premenstrual syndrome liver-qi stagnation.
Exp Ther Med. 2017 Jun;13(6):3130-3136. doi: 10.3892/etm.2017.4374. Epub 2017 Apr 21.
Abstract/Text
The present study aimed to investigate the roles of the µ-opioid receptor (MOR) and its related signaling pathways in the pathogenesis of premenstrual syndrome (PMS) liver-qi stagnation, along with the therapeutic effects of the Shu-Yu capsule in treating the condition. A PMS liver-qi stagnation rat model was established using a chronic restraint stress method. The protein expression level of MOR within rat hippocampal tissue was detected via western blot analysis and cyclic adenosine monophosphate (cAMP) levels within the supernatant of a rat hippocampal cell culture were determined by ELISA. The western blot analysis indicated that the hippocampal expression level of MOR was significantly elevated in the PMS liver-qi stagnation model group. However, subsequent treatment with a Shu-Yu capsule was found to significantly decrease the level of MOR expression. In addition, in vitro experiments were performed, whereby primary hippocampal neurons were treated with model rat serum. It was observed that the level of MOR expression was significantly elevated, while brain-derived neurotrophic factor (BDNF) and cAMP levels in the culture supernatant were significantly decreased. These effects were reversed by treatment with serum from the Shu-Yu capsule-treated rats. Furthermore, when treated with the MOR activator DAMGO, the following were significantly decreased in the primary neurons: Phosphorylation levels of cAMP response element binding protein and extracellular signal-regulated protein kinases (ERK); BDNF expression; and cAMP content in the culture supernatant. These effects were reversed in primary neurons treated with DAMGO and Shu-Yu-containing rat serum. Collectively, the data suggest that increased MOR expression and activation of the cAMP/ERK signaling pathway in the hippocampus may be involved in the pathogenesis of PMS liver-qi stagnation. Furthermore, the efficacy of the Shu-Yu capsule in treating the condition may be via its regulation of MOR receptor signaling.
G N Gurguis, K A Yonkers, S P Phan, J E Blakeley, A Williams, A J Rush
Adrenergic receptors in premenstrual dysphoric disorder: I. Platelet alpha 2 receptors: Gi protein coupling, phase of menstrual cycle, and prediction of luteal phase symptom severity.
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.
Michelle Vichnin, Ellen W Freeman, Hui Lin, Janice Hillman, Stephanie Bui
Premenstrual syndrome (PMS) in adolescents: severity and impairment.
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.
Hou L, Chen L, Zhou R.
Premenstrual syndrome is associated with an altered spontaneous electroencephalographic delta/beta power ratio across the menstrual cycle.
Int J Psychophysiol. 2022 Nov;181:64-72. doi: 10.1016/j.ijpsycho.2022.08.007. Epub 2022 Aug 24.
Abstract/Text
Premenstrual syndrome is associated with altered spontaneous brain activity in the late luteal phase, but the fluctuation patterns of brain activity throughout the menstrual cycle have not been revealed. Furthermore, it is also unknown whether the altered spontaneous brain activity during the whole menstrual cycle is further associated with their habitual use of maladaptive emotion regulation strategies. Based on the two reasons, electroencephalogram data and cognitive emotion regulation questionnaire from 32 women with high premenstrual symptoms (HPMS) and 33 women with low premenstrual symptoms (LPMS) were measured in the late luteal and follicular phases. Delta power, theta power, beta power, and the slow/fast wave ratios (SW/FW, including theta/beta power ratio [TBR] and delta/beta power ratio [DBR]) were calculated using both fixed frequency bands and individually adjusted frequency bands (based on the individual alpha peak frequency). The results showed that for the frontal and central DBR, as assessed both with fixed and individualized frequency bands, there was no difference between the two phases of the LPMS group, whereas there was a difference between the two phases of the HPMS group with a higher DBR in the late luteal phase than in the follicular phase. Further correlation results revealed that for women with HPMS in the late luteal phase, the frontal and central DBR values, as assessed both with fixed and individualized frequency bands, were positively correlated with self-blame and rumination. Consequently, HPMS was characterized by a fluctuation across the menstrual cycle in the DBR, which was further associated with maladaptive emotion regulation.
Copyright © 2022 Elsevier B.V. All rights reserved.
S Thys-Jacobs, M J Alvir
Calcium-regulating hormones across the menstrual cycle: evidence of a secondary hyperparathyroidism in women with PMS.
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.
Elizabeth R Bertone-Johnson, Susan E Hankinson, Nancy G Forger, Sally I Powers, Walter C Willett, Susan R Johnson, JoAnn E Manson
Plasma 25-hydroxyvitamin D and risk of premenstrual syndrome in a prospective cohort study.
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.
Tartagni M, Cicinelli MV, Tartagni MV, Alrasheed H, Matteo M, Baldini D, De Salvia M, Loverro G, Montagnani M.
Vitamin D Supplementation for Premenstrual Syndrome-Related Mood Disorders in Adolescents with Severe Hypovitaminosis D.
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.
Nesreen A A Shehata
Calcium versus oral contraceptive pills containing drospirenone for the treatment of mild to moderate premenstrual syndrome: a double blind randomized placebo controlled trial.
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.
Abdi F, Ozgoli G, Rahnemaie FS.
A systematic review of the role of vitamin D and calcium in premenstrual syndrome.
Obstet Gynecol Sci. 2019 Mar;62(2):73-86. doi: 10.5468/ogs.2019.62.2.73. Epub 2019 Feb 25.
Abstract/Text
Premenstrual syndrome (PMS) is a common disorder that affects millions of women of reproductive age worldwide. In recent years, there has been a focus on finding accessible, acceptable, and cost-effective therapeutic approaches with minimal side effects to treat the symptoms of PMS. This systematic review aimed to investigate the role of calcium and vitamin D in Premenstrual syndrome. The PubMed, EMBASE, Web of Science, Scopus, Science Direct, and Google Scholar databases were systematically searched for relevant articles from clinical trial, case-control, and cross-sectional studies. The Strengthening the Reporting of Observational Studies in Epidemiology checklist was used to assess the quality of the selected papers. A total of 28 eligible high-quality papers were reviewed. Low serum levels of calcium and vitamin D during the luteal phase of the menstrual cycle were found to cause or exacerbate the symptoms of PMS. Therefore, the administration of calcium and vitamin D supplements or the use of a diet rich in these two substances can restore serum levels and eliminate or reduce the symptoms of PMS. Calcium and vitamin D supplementation are recommended as an inexpensive, low-risk, acceptable, and accessible approach to eliminate or reduce the symptoms of PMS.
Arab A, Golpour-Hamedani S, Rafie N.
The Association Between Vitamin D and Premenstrual Syndrome: A Systematic Review and Meta-Analysis of Current Literature.
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.
Bahrami A, Avan A, Sadeghnia HR, Esmaeili H, Tayefi M, Ghasemi F, Nejati Salehkhani F, Arabpour-Dahoue M, Rastgar-Moghadam A, Ferns GA, Bahrami-Taghanaki H, Ghayour-Mobarhan M.
High dose vitamin D supplementation can improve menstrual problems, dysmenorrhea, and premenstrual syndrome in adolescents.
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.
Parazzini F, Di Martino M, Pellegrino P.
Magnesium in the gynecological practice: a literature review.
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.
Moslehi M, Arab A, Shadnoush M, Hajianfar H.
The Association Between Serum Magnesium and Premenstrual Syndrome: a Systematic Review and Meta-Analysis of Observational Studies.
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 .
Ari Shechter, Paul Lespérance, N M K Ng Ying Kin, Diane B Boivin
Pilot investigation of the circadian plasma melatonin rhythm across the menstrual cycle in a small group of women with premenstrual dysphoric disorder.
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.
Jehan S, Auguste E, Hussain M, Pandi-Perumal SR, Brzezinski A, Gupta R, Attarian H, Jean-Louis G, McFarlane SI.
Sleep and Premenstrual Syndrome.
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.
Yin W, Zhang J, Guo Y, Wu Z, Diao C, Sun J.
Melatonin for premenstrual syndrome: A potential remedy but not ready.
Front Endocrinol (Lausanne). 2022;13:1084249. doi: 10.3389/fendo.2022.1084249. Epub 2023 Jan 9.
Abstract/Text
Premenstrual syndrome (PMS), a recurrent and moderate disorder that occurs during the luteal phase of the menstrual cycle and quickly resolves after menstruation, is characterized by somatic and emotional discomfort that can be severe enough to impair daily activities. Current therapeutic drugs for PMS such as selective serotonin reuptake inhibitors are not very satisfying. As a critical pineal hormone, melatonin has increasingly been suggested to modulate PMS symptoms. In this review, we update the latest progress on PMS-induced sleep disturbance, mood changes, and cognitive impairment and provide possible pathways by which melatonin attenuates these symptoms. Moreover, we focus on the role of melatonin in PMS molecular mechanisms. Herein, we show that melatonin can regulate ovarian estrogen and progesterone, of which cyclic fluctuations contribute to PMS pathogenesis. Melatonin also modulates gamma-aminobutyric acid and the brain-derived neurotrophic factor system in PMS. Interpreting the role of melatonin in PMS is not only informative to clarify PMS etiology but also instructive to melatonin and its receptor agonist application to promote female health. As a safe interaction, melatonin treatment can be effective in alleviating symptoms of PMS. However, symptoms such as sleep disturbance, depressive mood, cognitive impairment are not specific and can be easily misdiagnosed. Connections between melatonin receptor, ovarian steroid dysfunction, and PMS are not consistent among past studies. Before final conclusions are drawn, more well-organized and rigorous studies are recommended.
Copyright © 2023 Yin, Zhang, Guo, Wu, Diao and Sun.
Fernández MDM, Montes-Martínez A, Piñeiro-Lamas M, Regueira-Méndez C, Takkouche B.
Tobacco consumption and premenstrual syndrome: A case-control study.
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.
Fernández MDM, Saulyte J, Inskip HM, Takkouche B.
Premenstrual syndrome and alcohol consumption: a systematic review and meta-analysis.
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.
Ellen W. Freeman, Steven J. Sondheimer
Premenstrual Dysphoric Disorder: Recognition and Treatment.
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.
Rohit Kumar Verma, Dinesh Kumar Chellappan, Awanish Kumar Pandey
Review on treatment of premenstrual syndrome: from conventional to alternative approach.
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.
Irene Kwan, Joseph Loze Onwude
Premenstrual syndrome.
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.
Takashi Takeda, Akiko Kondo, Shoko Koga, Jun Hayakawa, Kenichi Hayakawa, Keizo Hiramatsu, Nobuo Yaegashi
Effectiveness of ethinylestradiol/drospirenone for premenstrual symptoms in Japanese patients with dysmenorrhea: Open-label pilot study.
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.
Maharaj S, Trevino K.
A Comprehensive Review of Treatment Options for Premenstrual Syndrome and Premenstrual Dysphoric Disorder.
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.
Ciccone N, Kovacheff MB, Frey BN.
The pharmacotherapeutic management of premenstrual dysphoric disorder.
Expert Opin Pharmacother. 2023 Jan;24(1):145-151. doi: 10.1080/14656566.2022.2114345. Epub 2022 Aug 22.
Abstract/Text
INTRODUCTION: Premenstrual dysphoric disorder (PMDD) is a prevalent psychiatric condition associated with substantial mental distress, impaired psychosocial functioning, high rates of co-morbid psychiatric conditions, and elevated risk of suicide.
AREAS COVERED: We provide an update on epidemiology, pathophysiology, clinical presentation, and diagnosis of PMDD, with a focus on the pharmacological management of this condition.
EXPERT OPINION: Given the high rates of false positives from retrospective assessments, prospective daily symptom monitoring for a minimal of two symptomatic menstrual cycles is critical to accurately confirm (or rule out) the diagnosis of PMDD. Serotonin-based antidepressants are well-established first-line treatments of PMDD. Second-line treatment includes the use of combined, monophasic oral contraceptives. In mild to moderate cases, independent meta-analyses have shown efficacy of Chasteberry extract (Vitex agnus cactus). Preliminary results with compounds blocking the synthesis of allopregnanolone are promising.
Kenda M, Glavač NK, Nagy M, Sollner Dolenc M, On Behalf Of The Oemonom.
Herbal Products Used in Menopause and for Gynecological Disorders.
Molecules. 2021 Dec 8;26(24). doi: 10.3390/molecules26247421. Epub 2021 Dec 8.
Abstract/Text
Herbal products are often used as an alternative to pharmacological therapy. Menopausal symptoms and gynecological disorders (such as premenstrual syndrome and dysmenorrhea) are the indications where pharmacological therapy may have serious adverse events, hence many women prefer to use herbal products to help with these symptoms. Here, we reviewed plants and derived products, which are commonly used for the abovementioned indications, focusing on clinical data, safely profile and whether or not their use is justified. We noted that limited data are available on the use of some plants for alleviating the symptoms of menopause and gynecological disorders. While black cohosh (Cimicifuga racemose) and red clover (Trifolium pretense) were consistently shown to help reduce menopausal symptoms in clinical studies, currently available data do not fully support the use of fenugreek (Trigonella foenum-graecum), hops (Humulus lupulus), valerian (Valeriana officinalis), and soybean (Glycine max and Glycine soja) for this indication. For premenstrual syndrome and premenstrual dysphoric disorder, chaste tree (Vitex agnus-castus) shows effectiveness, but more clinical studies are needed to confirm such effect upon the use of evening primrose (Oenothera biennis).
van Die MD, Burger HG, Teede HJ, Bone KM.
Vitex agnus-castus extracts for female reproductive disorders: a systematic review of clinical trials.
Planta Med. 2013 May;79(7):562-75. doi: 10.1055/s-0032-1327831. Epub 2012 Nov 7.
Abstract/Text
Vitex agnus-castus L. (chaste tree; chasteberry) is a popular herbal treatment, predominantly used for a range of female reproductive conditions in Anglo-American and European practice. The objective of this systematic review was to evaluate the evidence for the efficacy and safety of Vitex extracts from randomised, controlled trials investigating women's health.Eight databases were searched using Latin and common names for Vitex and phytotherapeutic preparations of the herb as a sole agent, together with filters for randomised, controlled trials or clinical trials. Methodological quality was assessed according to the Cochrane risk of bias and Jadad scales, as well as the proposed elaboration of CONSORT for reporting trials on herbal interventions.Thirteen randomised, controlled trials were identified and twelve are included in this review, of which eight investigated premenstrual syndrome, two premenstrual dysphoric disorder, and two latent hyperprolactinaemia. For premenstrual syndrome, seven of eight trials found Vitex extracts to be superior to placebo (5 of 6 studies), pyridoxine (1), and magnesium oxide (1). In premenstrual dysphoric disorder, one study reported Vitex to be equivalent to fluoxetine, while in the other, fluoxetine outperformed Vitex. In latent hyperprolactinaemia, one trial reported it to be superior to placebo for reducing TRH-stimulated prolactin secretion, normalising a shortened luteal phase, increasing mid-luteal progesterone and 17β-oestradiol levels, while the other found Vitex comparable to bromocriptine for reducing serum prolactin levels and ameliorating cyclic mastalgia. Adverse events with Vitex were mild and generally infrequent. The methodological quality of the included studies varied, but was generally moderate-to-high. Limitations include small sample sizes in some studies, heterogeneity of conditions being treated, and a range of reference treatments.Despite some methodological limitations, the results from randomised, controlled trials to date suggest benefits for Vitex extracts in the treatment of premenstrual syndrome, premenstrual dysphoric disorder and latent hyperprolactinaemia. Further research is recommended, and greater transparency in reporting for future trials.
Georg Thieme Verlag KG Stuttgart · New York.
Cerqueira RO, Frey BN, Leclerc E, Brietzke E.
Vitex agnus castus for premenstrual syndrome and premenstrual dysphoric disorder: a systematic review.
Arch Womens Ment Health. 2017 Dec;20(6):713-719. doi: 10.1007/s00737-017-0791-0. Epub 2017 Oct 23.
Abstract/Text
The objective of this study was to evaluate whether Vitex agnus castus is a safe and effective treatment for PMS and premenstrual dysphoric disorder (PMDD) and to discuss the implications of these findings for clinical practice. A systematic review of literature was conducted using PubMed and Scielo databases. The inclusion criteria were randomized controlled trials (RCT) using V. agnus castus in individuals with PMS or PMDD that compared this intervention with placebo or an active comparator and included a description of blinding and dropouts/withdrawals. The search was conducted by two independent investigators who reached consensus on the included trials. A total of eight RCTs were included in this study. Most studies focused on PMS, and the diagnostic criteria of PMS and PMDD changed over the years. Three different preparations of V. agnus castus (VAC) were tested, and there was significant variability in the measurement of treatment outcomes between the studies. Nevertheless, all eight studies were positive for VAC in the treatment of PMS or PMDD and VAC was overall well tolerated. Main limitations were differences in definition of diagnostic criteria, the instruments used as main outcome measures, and different preparations of VAC extracts limit the comparison of results between studies. In conclusion, the RCTs using VAC for treatment of PMS/PMDD suggested that the VAC extract is a safe and efficacious alternative to be considered for the treatment of PMS/PMDD symptoms.
Takeda T, Shiina M, Chiba Y.
Effectiveness of natural S-equol supplement for premenstrual symptoms: protocol of a randomised, double-blind, placebo-controlled trial.
BMJ Open. 2018 Jul 18;8(7):e023314. doi: 10.1136/bmjopen-2018-023314. Epub 2018 Jul 18.
Abstract/Text
INTRODUCTION: Premenstrual syndrome (PMS) comprises a range of mood, behavioural and physical symptoms, and impairs many women's quality of life. Isoflavones are expected to stabilise the natural fluctuation of the oestrogen cycle through their selective oestrogen receptor modulator-like activities that alleviate PMS symptoms. Equol, a metabolite of a soy isoflavone converted from daidzein by specific gut bacteria, has a greater bioavailability compared with other soy isoflavones. We aim to examine the effect of natural S-equol supplements on premenstrual symptoms.
METHODS AND ANALYSIS: This study will enrol 124 women (aged 20-45 years) who have PMS symptoms and are non-equol producers in a double-blind, parallel, randomised, placebo-controlled trial, in which they will receive natural S-equol supplement (equol 10 mg a day) or placebo, orally, twice daily, for three menstrual cycles. The primary outcome measure (Daily Record of Severity of Problems total score) will be assessed during intervention cycles. To compare the primary outcomes between the S-equol group and the placebo group, the mean differences in the Daily Record of Severity of Problems total score between the two groups will be determined. The p values will be determined using Student's t-test, where the significance level is 5% (two-sided).
ETHICS AND DISSEMINATION: The institutional review board at Kindai University approved the study. The findings of this trial will be submitted to an international peer-reviewed journal. Abstracts will be submitted to national and international conferences.
TRIAL REGISTRATION NUMBER: UMIN000031815.
© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Takeda T, Chiba Y.
Evaluation of a natural S-equol supplement in treating premenstrual symptoms and the effect of the gut microbiota: An open-label pilot study.
Neuropsychopharmacol Rep. 2022 Jun;42(2):127-134. doi: 10.1002/npr2.12234. Epub 2022 Feb 6.
Abstract/Text
AIM: Premenstrual syndrome causes disturbances in many women's daily activities. Isoflavones might cause changes in the estrogen cycle by their selective estrogen receptor modulator-like activities. Equol, which is a metabolite of a soy isoflavone, has greater biological activity than other soy isoflavones. In this preliminary study, we aimed to examine the effect of a natural S-equol supplement (SE5-OH) on premenstrual symptoms. The gut microbiota has recently been suggested to play an important role in brain function in psychiatric disease, such as depression. Therefore, we further aimed to evaluate the relationship of the effect of SE5-OH and the gut microbiota at preintervention.
METHODS: Twenty women who showed premenstrual symptoms and were nonequol producers were enrolled in an open-label, single-arm, clinical study in which they received oral SE5-OH for two period cycles. The Daily Record of Severity of Problems (DRSP) total score was evaluated during the intervention cycles. Before taking SE5-OH, fecal samples were obtained and subjected to terminal restriction fragment length polymorphism analysis.
RESULTS: The response rate to treatment (≥50% reduction from baseline in the DRSP total score) was 10.5%. Post hoc analysis showed a significant improvement in the change in the DRSP total score (P = .008) and DRSP scores for four core premenstrual dysphoric disorder symptoms. Multiple regression analysis showed that the percentage improvement of the DRSP total score was positively related to Bifidobacterium and negatively related to Clostridium cluster IV.
CONCLUSION: SE5-OH supplementation may be an acceptable treatment for premenstrual symptoms. The intestinal microbiota may have an effect on SE5-OH.
© 2022 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.
Stoner R, Camilleri V, Calleja-Agius J, Schembri-Wismayer P.
The cytokine-hormone axis - the link between premenstrual syndrome and postpartum depression.
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.
Amiel Castro RT, Pataky EA, Ehlert U.
Associations between premenstrual syndrome and postpartum depression: A systematic literature review.
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.
Cao S, Jones M, Tooth L, Mishra GD.
History of premenstrual syndrome and development of postpartum depression: A systematic review and meta-analysis.
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.
Bertone-Johnson ER, Whitcomb BW, Rich-Edwards JW, Hankinson SE, Manson JE.
Premenstrual Syndrome and Subsequent Risk of Hypertension in a Prospective Study.
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.
Prasad D, Wollenhaupt-Aguiar B, Kidd KN, de Azevedo Cardoso T, Frey BN.
Suicidal Risk in Women with Premenstrual Syndrome and Premenstrual Dysphoric Disorder: A Systematic Review and Meta-Analysis.
J Womens Health (Larchmt). 2021 Dec;30(12):1693-1707. doi: 10.1089/jwh.2021.0185. Epub 2021 Aug 20.
Abstract/Text
Purpose: Women with premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS) experience substantial functional impairment and decreased quality of life. While previous research has highlighted a relationship between premenstrual disturbances and suicide risk, no meta-analysis has been conducted to quantitatively assess the findings. Methods: A systematic review and meta-analysis was conducted by searching the literature in three databases (Pubmed, PsycINFO, and EMBASE) on July 15, 2020. Studies that assessed the relationship between suicidality (attempt, ideation, and/or plan) and premenstrual disturbance (PMDD, PMS, and/or premenstrual symptoms) were included. Results: Thirteen studies were included in the qualitative review (n = 10 included in meta-analysis). Results revealed that women with PMDD are almost seven times at higher risk of suicide attempt (OR: 6.97; 95% CI: 2.98-16.29, p < 0.001) and almost four times as likely to exhibit suicidal ideation (OR: 3.95; 95% CI: 2.97-5.24, p < 0.001). Similarly, women with PMS are also at increased risk of suicidal ideation (OR: 10.06; 95% CI: 1.32 to -76.67, p = 0.03), but not for suicide attempt (OR: 1.85; 95% CI: 0.77 to -4.46, p = 0.17). Conclusions: Women with PMDD and PMS are at higher risk of suicidality compared with women without premenstrual disturbances. These findings support routine suicidal risk assessments for women who suffer from moderate-to-severe premenstrual disturbance. Furthermore, psychosocial treatments for women diagnosed with PMS/PMDD should consider and target suicidality to minimize risk and improve well-being.
E W Freeman, R J DeRubeis, K Rickels
Reliability and validity of a daily diary for premenstrual syndrome.
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.
J F Mortola, L Girton, L Beck, S S Yen
Diagnosis of premenstrual syndrome by a simple, prospective, and reliable instrument: the calendar of premenstrual experiences.
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.
ACOG Committee on Practice Bulletins--Gynecology.
ACOG Practice Bulletin: No 15: Premenstrual syndrome.
Obstet Gynecol. 2000 Apr;95(4):suppl 1-9.
Abstract/Text
American College of Obstetricians and Gynecologists: Practice Bulletin Premenstrual syndrome Compendium of Selected Publications. 2005; 701-713.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text Revision, Washington, DC, American Psychiatric Association 2000.
鎌田泰彦:よくわかる月経前症候群の診断と治療.日産婦誌 2012;94: 117-121.
武谷雄二. 性器・生殖機能に関連する症候、女性医学体系、金原出版、2002; p35-37.
Susan R Johnson
Premenstrual syndrome, premenstrual dysphoric disorder, and beyond: a clinical primer for practitioners.
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.
Anna Maria Paoletti, Stefano Lello, Stefania Fratta, Marisa Orrù, Francesca Ranuzzi, Cristiana Sogliano, Alessandra Concas, Giovanni Biggio, Gian Benedetto Melis
Psychological effect of the oral contraceptive formulation containing 3 mg of drospirenone plus 30 microg of ethinyl estradiol.
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.
Andrea L Coffee, Thomas J Kuehl, Sherilyn Willis, Patricia J Sulak
Oral contraceptives and premenstrual symptoms: comparison of a 21/7 and extended regimen.
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.
日本産科婦人科学会編集・監修低用量経口避妊薬、低用量エストロゲン・プロゲスチン配合薬ガイドライン（OC・LEPガイドライン）2015年版 p.39 日本産科婦人科学会2015、東京.
Teri B Pearlstein, Gloria A Bachmann, Howard A Zacur, Kimberly A Yonkers
Treatment of premenstrual dysphoric disorder with a new drospirenone-containing oral contraceptive formulation.
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.
Joachim Marr, Minoo Niknian, Lee P Shulman, Richard Lynen
Premenstrual dysphoric disorder symptom cluster improvement by cycle with the combined oral contraceptive ethinylestradiol 20 mcg plus drospirenone 3 mg administered in a 24/4 regimen.
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.
Kelli Kelderhouse, Julie Smith Taylor
A review of treatment and management modalities for premenstrual dysphoric disorder.
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.
Laureen M Lopez, Adrian A Kaptein, Frans M Helmerhorst
Oral contraceptives containing drospirenone for premenstrual syndrome.
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.
Kimberly A Yonkers, Candace Brown, Teri B Pearlstein, Marie Foegh, Carole Sampson-Landers, Andrea Rapkin
Efficacy of a new low-dose oral contraceptive with drospirenone in premenstrual dysphoric disorder.
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.
Batra P, Harper DM: Recognizing and treating premenstrual dysphoric disorder. JCOM 2002; 9: 87-98.
村田高明、木村裕幸：月経前症候群と漢方.産婦治療2011; 103: 467-471.
藤井絵里子：月経前症候群（premenstrual syndrome;PMS）産婦実際2014; 63: 337-341.
小川真里子、高松潔.：月経前症候群（PMS:premenstrual syndrome）、月経前不快気分障害（PMDD:premenstrual dysphoric disorder）.医学と薬学2014; 71:1541-1548.
