Related Experiment Video
Updated: Apr 5, 2026

Developing a Rat Model for Bipolar Disorder
Published on: May 2, 2025
Symptom severity of bipolar disorder during the menopausal transition
Wendy K Marsh1, Bernice Gershenson, Anthony J Rothschild
1Department of Psychiatry, School of Medicine, University of Massachusetts, 55 Lake Ave North, S3-314, Worcester, MA, 01655, USA, Wendy.Marsh@umassmemorial.org.
Background:
Little is known about the mood symptom experience of women with bipolar disorder during the menopausal transition (MT). Yet times of rapid hormonal decline, such as the postpartum, are associated with increased risk of severe mood episodes in bipolar disorder, and the MT is a time of increased risk for unipolar depression in women with or without a history of depression.
Methods:
Enrollment included 56 women 40-60 years old diagnosed in the bipolar spectrum who were experiencing menopausal symptoms or were up to 5 years since their final menstrual period. Menopausal stages included early menopause, late menopause, or early postmenopause based on standardized criteria. Observational, prospective standardized mood symptom and reproductive hormone assessments were completed periodically. Concurrent menopausal symptoms as well as history of mood exacerbation during past reproductive events were assessed.
Results:
Forty-four women were included in the main analysis. The average Montgomery-Asberg Depression Rating Scale (MADRS) score was 4.43 points higher in the late transition/early postmenopausal stage women (n = 29) compared to the early menopausal stage women (n = 15) (±SE 2.14; p = 0.039), corresponding to a roughly 10 % higher score (range 0-40) in the late/post stage across all study visits. Results were similar for the Young Mania Rating Scale (YMRS), where the average score was 2.54 points higher in the late/early postmenopausal stage women compared to the early menopausal stage women (±SE 1.15; p = 0.027), also roughly 10 % higher (range 0-26). Estradiol and follicle-stimulating hormone (FSH) absolute levels as well as between-visit change in levels were not notably associated with YMRS or MADRS during study observation. Total Greene Climacteric Symptom (menopausal symptom) score was significantly associated with MADRS but not YMRS. History of mood exacerbation premenstrually and/or postpartum was not significantly associated with YMRS or MADRS severity during the MT.
Conclusions:
These results support the theory that times of increased reproductive hormonal changes, such as the late MT and early postmenopause, here compared to early MT, are associated with greater mood symptom severity in bipolar spectrum women. Nonetheless, absolute or change in FSH and estradiol levels were not significantly associated with depression or mood elevation severity.
Related Concept Videos
Bipolar Disorder
Menopause
Mania and Antimanic Drugs: Overview
Disorders of the Female Reproductive System
Depressive Disorders: MDD and Dysthymia
Hormonal Regulation of the Menstrual Cycle
At puberty, GnRH begins a pulsatile release pattern, which triggers the anterior pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The frequency and amplitude of GnRH pulses vary across the menstrual cycle, with faster pulses favoring LH release and slower pulses favoring FSH...

