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      Psychiatric Symptoms Across the Menstrual Cycle in Adult Women: A Comprehensive Review

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          Abstract

          Learning objective

          After participating in this activity, learners should be better able to:

          • Discuss and outline the general and overlapping effects of the menstrual cycle on women’s mental health

          Abstract

          A growing body of research demonstrates menstrual cycle–dependent fluctuations in psychiatric symptoms; these fluctuations can therefore be considered as prevalent phenomena. Possible mechanisms underlying these fluctuations posit behavioral, psychological, and neuroendocrine influences. Recent reviews document cyclic exacerbation of symptoms and explore these mechanisms in the context of specific and often single disorders. The question remains, however, as to whether there are general and overlapping effects of the menstrual cycle on women’s mental health. To address this gap, we synthesized the literature examining the exacerbation of a variety of psychiatric symptoms across the menstrual cycle in adult women. Results show that the premenstrual and menstrual phases are most consistently implicated in transdiagnostic symptom exacerbation. Specifically, strong evidence indicates increases in psychosis, mania, depression, suicide/suicide attempts, and alcohol use during these phases. Anxiety, stress, and binge eating appear to be elevated more generally throughout the luteal phase. The subjective effects of smoking and cocaine use are reduced during the luteal phase, but fewer data are available for other substances. Less consistent patterns are demonstrated for panic disorder, symptoms of posttraumatic stress disorder, and borderline personality disorder, and it is difficult to draw conclusions for symptoms of generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, and trichotillomania because of the limited data. Future research should focus on developing standardized approaches to identifying menstrual cycle phases and adapting pharmacological and behavioral interventions for managing fluctuations in psychiatric symptoms across the menstrual cycle.

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          Most cited references232

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          Effects of gonadal steroids in women with a history of postpartum depression.

          Endocrine factors are purported to play a role in the etiology of postpartum depression, but direct evidence for this role is lacking. The authors investigated the possible role of changes in gonadal steroid levels in postpartum depression by simulating two hormonal conditions related to pregnancy and parturition in euthymic women with and without a history of postpartum depression. The supraphysiologic gonadal steroid levels of pregnancy and withdrawal from these high levels to a hypogonadal state were simulated by inducing hypogonadism in euthymic women-eight with and eight without a history of postpartum depression-with the gonadotropin-releasing hormone agonist leuprolide acetate, adding back supraphysiologic doses of estradiol and progesterone for 8 weeks, and then withdrawing both steroids under double-blind conditions. Outcome measures were daily symptom self-ratings and standardized subjective and objective cross-sectional mood rating scales. Five of the eight women with a history of postpartum depression (62.5%) and none of the eight women in the comparison group developed significant mood symptoms during the withdrawal period. Analysis of variance with repeated measures of daily and cross-sectional ratings of mood showed significant phase-by-group effects. These effects reflected significant increases in depressive symptoms in women with a history of postpartum depression but not in the comparison group after hormone withdrawal (and during the end of the hormone replacement phase), compared with baseline. The data provide direct evidence in support of the involvement of the reproductive hormones estrogen and progesterone in the development of postpartum depression in a subgroup of women. Further, they suggest that women with a history of postpartum depression are differentially sensitive to mood-destabilizing effects of gonadal steroids.
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            Menstrual cycle phase modulates reward-related neural function in women.

            There is considerable evidence from animal studies that the mesolimbic and mesocortical dopamine systems are sensitive to circulating gonadal steroid hormones. Less is known about the influence of estrogen and progesterone on the human reward system. To investigate this directly, we used functional MRI and an event-related monetary reward paradigm to study women with a repeated-measures, counterbalanced design across the menstrual cycle. Here we show that during the midfollicular phase (days 4-8 after onset of menses) women anticipating uncertain rewards activated the orbitofrontal cortex and amygdala more than during the luteal phase (6-10 days after luteinizing hormone surge). At the time of reward delivery, women in the follicular phase activated the midbrain, striatum, and left fronto-polar cortex more than during the luteal phase. These data demonstrate augmented reactivity of the reward system in women during the midfollicular phase when estrogen is unopposed by progesterone. Moreover, investigation of between-sex differences revealed that men activated ventral putamen more than women during anticipation of uncertain rewards, whereas women more strongly activated the anterior medial prefrontal cortex at the time of reward delivery. Correlation between brain activity and gonadal steroid levels also revealed that the amygdalo-hippocampal complex was positively correlated with estradiol level, regardless of menstrual cycle phase. Together, our findings provide evidence of neurofunctional modulation of the reward system by gonadal steroid hormones in humans and establish a neurobiological foundation for understanding their impact on vulnerability to drug abuse, neuropsychiatric diseases with differential expression across males and females, and hormonally mediated mood disorders.
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              Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome.

              The symptoms of women with premenstrual syndrome improve in response to suppression of ovarian function, although these women have no evidence of ovarian dysfunction. We undertook a study to determine the role of estrogen and progesterone in this syndrome. We first studied the effect of ovarian suppression with leuprolide, an agonist analogue of gonadotropin-releasing hormone, or placebo on symptoms in 20 women with the premenstrual syndrome. Ten women whose symptoms improved during leuprolide treatment were given estradiol and progesterone in a double-blind, crossover design, each for four weeks, during continued leuprolide administration. Women without premenstrual syndrome (normal women) participated in a similar protocol. Outcomes were assessed on the basis of daily self-reports by the patients and biweekly rater-administered symptom-rating scales. The 10 women with premenstrual syndrome who were given leuprolide had a significant decrease in symptoms as compared with base-line values and with values for the 10 women who were given placebo. The 10 women with premenstrual syndrome who were given leuprolide plus estradiol or progesterone had a significant recurrence of symptoms, but no changes in mood occurred in 15 normal women who received the same regimen or in 5 women with premenstrual syndrome who were given placebo hormone during continued leuprolide administration. In women with premenstrual syndrome, the occurrence of symptoms represents an abnormal response to normal hormonal changes.
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                Author and article information

                Contributors
                Journal
                Harv Rev Psychiatry
                Harv Rev Psychiatry
                HRP
                Harvard Review of Psychiatry
                Lippincott Williams & Wilkins
                1067-3229
                1465-7309
                Mar-Apr 2022
                9 March 2022
                : 30
                : 2
                : 100-117
                Affiliations
                From Harvard Medical School (Drs. Handy, Greenfield, and Payne); McLean Hospital, Belmont, MA (Drs. Handy, Greenfield, and Payne); University of Massachusetts Medical School/UMass Memorial Medical Center, Worcester, MA (Dr. Yonkers).
                Author notes
                [*] Correspondence: Laura A. Payne, PhD, McLean Hospital, 115 Mill St., Belmont, MA. Email: lpayne@ 123456mclean.harvard.edu
                Article
                HRP_220047 00002
                10.1097/HRP.0000000000000329
                8906247
                35267252
                4aa64aaa-38b2-4405-9989-0c89ef4f6ce4
                Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the President and Fellows of Harvard College.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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                Review
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                CME
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                Clinical Psychology & Psychiatry
                estrogen,progesterone,menstrual cycle,mental health,women’s health

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