From menarche to menopause, the female reproductive lifespan is characterized by shifts in hormones that can influence mental health and lead to gender-based differences in prevalence, presentation and treatment considerations including in mental health care. For example, there is a clear increase in the incidence of depression in females beginning in puberty, which lasts throughout the lifespan. It is important to remember that while fluctuating reproductive hormones do contribute to increased rates of depression in women, it is driven by a complex interplay of biological and sociocultural factors.
In this article, we will review the mental health implications of fluctuations in reproductive hormones within a single menstrual cycle, and at physiological milestones such as menarche, pregnancy and perimenopause.
Menstrual cycles and mental health
Premenstrual syndrome (PMS) affects approximately 20% of menstruating individuals during the luteal phase (second half of the menstrual cycle from ovulation till onset of menses), and can be diagnosed by the presence of somatic (breast tenderness, bloating, headache, joint/muscle pain, weight gain, extremity swelling) or behavioral (fatigue, insomnia, food cravings, changes in sexual interest) symptoms with or without affective symptoms. 80 – 95% of reproductive-aged women experience at least one premenstrual symptom during the luteal phase.
Premenstrual dysphoric disorder (PMDD) affects a subgroup of women (prevalence 2 – 4%) who experience severe mood lability, irritability, dysphoria, anxiety and suicidal ideation during the luteal phase. Symptoms cause clinically significant distress and marked impairment in functioning and resolve within a few days of onset of menses.
Premenstrual exacerbation (PME) is the worsening of symptoms of an existing psychiatric condition during the luteal phase – symptoms are present throughout the cycle but become significantly more severe during the premenstrual and perimenstrual phases. About 60% of women with mood disorders experience PME, with a distinct pattern in bipolar disorder (where exacerbations may also occur around ovulation). PME also occurs in psychotic disorders, panic disorders, eating disorders, attention-deficit/hyperactivity disorder and borderline personality disorder. PME predicts a more severe course of illness and increased burden of illness as well.
In your practice, prospective daily symptom charting using the Daily Record of Severity of Problems (DRSP) can confirm whether symptoms are confined to the premenstrual window (PMDD) or represent a premenstrual worsening of a continuous disorder (PME). Consider providing this tool to patients presenting with cyclic mood symptoms.
Approximately one in five women of reproductive age is affected by either PMS or PMDD, yet these disorders are frequently undertreated. Treatment for PMDD includes SSRIs – continuous or intermittent (starting 1 week before menses and ending 3 days after onset) and combined oral contraceptives (COCs).
Treatment of PME involves optimizing treatment of the underlying condition and augmentation of the dosage of the existing treatment during the luteal phase. For example, for PME of unipolar depression, increasing the antidepressant dose during the luteal phase and returning to the baseline dose after menses can help. For bipolar disorder, the first step would be to optimize mood stabilizer dosing, and then address any remaining premenstrual symptoms with COCs, using SSRIs if needed with caution. Lamotrigine appears to specifically stabilize fluctuation of mood across the menstrual cycle. Preliminary studies indicate that individualized stimulant dose increases 3 – 10 days prior to menstruation can significantly improve focus in women with PME of ADHD.
Hormonal contraception (HC) and mental health
This is a topic of long-standing debate. Approximately 16% of women experience mood worsening with hormonal contraception. Danish cohort studies examined this issue and found
- Higher relative risk of antidepressant initiation among HC users, particularly adolescents aged 15-19 compared to non-users.
- Higher risk for suicide attempts and completed suicide among HC users compared to non-users.
While these data are sobering, mood disorders are not necessarily a contraindication to HC. Individuals with a history of depression should be attentive to potential mood changes after starting a hormonal contraceptive, with closer monitoring in adolescents. COCs with anti-androgenic progestagens, such as drospirenone and desogestrel, appear more favorable in terms of mood symptoms.
Managing interactions
Ethinyl estradiol can significantly reduce serum levels of lamotrigine and valproate by inducing the glucuronidation pathway. Women who are stable on lamotrigine and then start a COC may need their dose increased, and those who stop a COC while on lamotrigine will need to be monitored as their lamotrigine levels may suddenly rise.
Perinatal mental health
The perinatal period of course is a period of profound hormonal change and subsequent vulnerability to psychiatric illness. Most extensively studied are the hormonal underpinnings of postpartum depression (PPD). A subset of women appears to be sensitive to changes in the levels of estradiol and progesterone and following the acute hormonal withdrawal in the postpartum period, mood disturbance is triggered. Particularly important is the neuroactive progesterone metabolite allopregnanolone, a positive allosteric modulator of GABA-A receptors. Zuranolone is a formulation of allopregnanolone that is FDA approved specifically for the treatment of PPD.
Perinatal hormonal shifts may also influence the onset and course of other psychiatric conditions, including obsessive-compulsive disorder, post-traumatic stress disorder, and, rarely, postpartum psychosis although these are less studied.
Perimenopause and mental health
Perimenopause can last 4 – 8 years and is another period of intense hormonal flux. The risk of depression more than doubles at this time, again driven not only by rapid fluctuations in estradiol, but also by physical symptoms of perimenopause such as severe hot flashes, night sweats and subsequent sleep disturbance, and sociocultural stresses of caregiving, role transition and cultural attitudes toward aging. The risk of perimenopausal depression is higher in those with a history of postpartum depression or PMDD.
Treatment strategies include SSRIS, SNRIS, hormone replacement therapy or menopausal hormone therapy (MHT) – estrogen (combined with progesterone for those with an intact uterus) – and Cognitive Behavior Therapy for Insomnia. Although MHT is not considered a first-line treatment, estradiol may have antidepressant and anxiolytic effects in some perimenopausal women, and MHT may be useful in women who have a partial response to traditional antidepressants and those with significant vasomotor symptoms. Collaboration between psychiatrists, gynecologists and primary care providers can help create a comprehensive treatment plan. In 2025 the broad black box warning about cardiovascular disease and breast cancer associated with MHT was removed. MHT has several benefits when applied to appropriately selected women (e.g., under the age of 60 if they are within 10 years of their last menstrual period), including treatment of vasomotor symptoms and prevention of bone loss and fractures.
Ideally, our approach to women’s mental health would be informed by the shifting hormonal landscape across the lifespan — from puberty and the menstrual cycle, through pregnancy and the postpartum, to the menopausal transition — and interventions would be tailored based on the biopsychosocial context of each stage.
Resources:
For providers with questions about caring for patients in the perinatal period, please call the Perinatal PCL at 877-725-4666, Monday – Friday, 9 am to 5 pm (excluding holidays)
UW PERC Center Hormones and Mood Care Guide
The 20203 Practitioners Care Guide for Managing Menopause
Menopause Society Patient Education
References:
Arnold, M. J. (2024). Premenstrual Disorders: Guidelines From the American College of Obstetricians and Gynecologists. American Family Physician, 110(6), 647-650.
Faubion, S. S., Crandall, C. J., Davis, L., El Khoudary, S. R., Hodis, H. N., Lobo, R. A., … & Wolfman, W. (2022). The 2022 hormone therapy position statement of the North American Menopause Society. Menopause, 29(7), 767-794.
Jespersen, C., Lauritsen, M. P., Frokjaer, V. G., & Schroll, J. B. (2024). Selective serotonin reuptake inhibitors for premenstrual syndrome and premenstrual dysphoric disorder. Cochrane Database of Systematic Reviews, (8).
Kuehner, C., & Nayman, S. (2021). Premenstrual exacerbations of mood disorders: findings and knowledge gaps. Current psychiatry reports, 23(11), 78.
Wieczorek, K., Targonskaya, A., & Maslowski, K. (2023). Reproductive hormones and female mental wellbeing. Women, 3(3), 432-444.
Dr. Bhat is a perinatal psychiatrist and Associate Professor in the UW School of Medicine Department of Psychiatry and Behavioral Sciences where she serves as co-director of the Perinatal Mental Health & Substance Use Education, Research & Clinical Consultation (PERC) Center and the Perinatal Psychiatry Consultation Line (Perinatal PCL). Dr. Bhat earned her medical degree from Bangalore Medical College, India, and completed a psychiatry residency in St. John’s Medical College, India. She completed a second residency in Psychiatry with a focus on women’s mental health and integrated care from the University of Washington, and a fellowship in Primary Care in Psychiatry. Dr. Bhat also earned a master’s in public health from the University of Washington School of Public Health and is board certified with the American Board of Psychiatry and Neurology.
