Ovarian steroid sensitivity and candidate neural mechanisms of premenstrual dysphoric disorder

Premenstrual dysphoric disorder (PMDD) is a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) diagnosis defined by affective lability, irritability or anger, depressed mood or hopelessness, and anxiety or tension, with additional cognitive, somatic, or behavioral symptoms that recur in the late luteal phase and remit after menses.These symptoms cause marked functional impairment; a 2024 systematic review estimated the pooled prevalence of prospectively confirmed PMDD at 3.2% (95% confidence interval: 1.7-5.9).Although traditionally attributed to abnormal ovarian hormone concentrations, the available evidence suggests that symptom expression may be more closely related to altered central sensitivity to physiological ovarian steroid transitions.This altered sensitivity has been associated with changes in corticolimbic network activity and in serotonergic and gamma-aminobutyric acid neurotransmission.Hypothalamicpituitary-adrenal axis reactivity and neuroactive steroids may also contribute.Diagnosis requires prospective daily ratings across at least two symptomatic cycles.Selective serotonin reuptake inhibitors, hormonal interventions, neurosteroidtargeted agents, and psychological approaches show variable efficacy, reflecting the heterogeneity of underlying mechanisms.This review summarizes the evidence linking ovarian steroid sensitivity to candidate neural mechanisms of emotional and behavioral dysregulation in PMDD; the proposed model is hypothesis-generating and awaits prospective validation, while the underlying evidence is constrained by small samples, inconsistent cycle staging, and peripheral surrogate measures.