Unraveling the Cycle: A Scoping Review Exploring the Impact of Antidepressants on the Female Reproductive Cycle

Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are widely prescribed for mood disorders, including in individuals of reproductive age. While their psychiatric effects are well-documented, emerging evidence suggests these medications may influence hormonal regulation, ovulation, and menstrual cycle patterns. Potential mechanisms include disruption of the hypothalamic-pituitary-ovarian (HPO) axis, alterations in serotonergic signaling, and medication-specific hormonal fluctuations. These interactions raise important questions about the understudied reproductive impact of commonly prescribed antidepressants. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines, a comprehensive search of Ovid MEDLINE, Excerpta Medica Database (EMBASE), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases were performed to identify studies examining the effects of antidepressants on ovarian function, menstrual regularity, ovulation, or hormone levels. Eligible studies included those involving individuals assigned female at birth (AFAB) of reproductive age, as well as animal models with comparable reproductive physiology. Both human and preclinical studies were considered, covering a range of antidepressant classes: SSRIs, SNRIs, atypical antidepressants, tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), and newer agents such as vortioxetine and vilazodone.  Out of 34 eligible studies, 16 were included in the final synthesis. SSRIs, especially fluoxetine, sertraline, paroxetine, escitalopram, and citalopram, were most frequently studied. Observational studies reported increased rates of menstrual irregularity and sexual dysfunction, particularly with chronic SSRI use. Antidepressant use was associated with reduced fecundability, even after adjusting for depression severity. Bupropion, venlafaxine, and other SNRIs showed cycle-phase-dependent pharmacokinetics and variable hormonal interactions. Antidepressant use was associated with changes in menstrual cycle length and increased cardiometabolic risk; however, they may normalize low testosterone levels in depressed women, with improvements in sexual function post-treatment. Clinical and preclinical findings indicate that SSRIs may impair ovulation through serotonergic inhibition of gonadotropin-releasing hormone (GnRH) as well as downstream suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), with some studies also noting elevated prolactin and follicular atresia. Taken together, these findings suggest a biologic basis for the observed menstrual irregularities and reduced fecundability reported in observational and cohort studies. Across studies, reproductive effects varied by antidepressant class, duration of use, and underlying mood pathology. Observed trends support a drug- and class-dependent impact on estrogen, progesterone, prolactin, and reproductive function, with additional implications for systemic health.