Rethinking Depression in Perimenopause: Why Menopause Hormone Therapy Should Come Before Antidepressants

Written and edited by Sarah Bonza MD, MPH, FAAFP, MSCP, DipABLM, NBC-HWC

Emerging research and expert consensus recommend considering hormone therapy as a first-line treatment for psychological symptoms in perimenopausal women.

A recent wave of studies and updated guidelines now recommend considering menopausal hormone therapy (MHT)—rather than antidepressants—as the preferred initial treatment for psychological symptoms in perimenopausal women who do not have a diagnosis of major depressive disorder.

This recommendation reflects new evidence on the efficacy of hormone therapy for mood stabilization, reduction in depression risk, and overall improvements in quality of life during the menopausal transition[1].

Key Findings From Recent Research

Research published and presented in 2025, including a UK-based cross-sectional study of over 1,000 women, found that 39% of those taking antidepressants or anxiolytics prior to starting hormone therapy reduced or discontinued their psychiatric medications after initiating MHT.

Women treated with estrogen combination therapy and testosterone saw an even greater rate of antidepressant discontinuation, suggesting added benefit when androgen is included. Hormone therapy demonstrated significant benefits both for physical symptoms (hot flashes) and for alleviating depressive symptoms in this population [2].

Estrogen and testosterone therapy may reduce depressive symptoms in perimenopause.

Guideline Updates and Expert Consensus

New position statements from The Menopause Society and recent FDA expert panels highlight that hormone therapy should be the first-line intervention for perimenopausal women experiencing mood symptoms if they do not meet criteria for a primary depressive disorder[2,3]. SSRIs and SNRIs remain recommended only for those with true major depressive disorder or when co-occurring vasomotor symptoms and depression/anxiety are present[2,4].

Clinical Implications

• Mood Improvement: MHT improves vasomotor instability and has neuromodulatory effects via estrogen pathways that impact mood-regulating neurotransmitters[5].

• Reduced Antidepressant Use: Initiating MHT can often allow for deprescribing or dose-reduction of antidepressants, which may reduce side effect burden and improve adherence[6].

• Quality of Life: Treating menopausal symptoms holistically, rather than just focusing on vasomotor complaints, leads to better overall well-being.

How to choose between menopause hormone therapy and antidepressants for perimenopausal mood changes.

Recommendations for Practice and Patient Care

• Assess whether mood changes in perimenopausal women are driven by hormonal fluctuations. If so, consider MHT before antidepressants, unless major depression is present.

• Monitor mental health alongside physiologic symptoms and adjust therapy as needed, individualizing care for each woman.

• Educate patients about the interplay between hormones and mood as part of a comprehensive menopause management strategy.

Emerging clinical evidence and expert consensus now recommend considering hormone therapy first for psychological symptoms in perimenopausal women, reserving antidepressants for those with major depressive disorder or refractory symptoms.

Hormone therapy tailored to your unique needs.

References

[1]  “HRT may reduce antidepressant need in menopausal women,” Contemporary OB/Gyn, Mar. 2025, [Online]. Available: https://www.contemporaryobgyn.net/view/hrt-may-reduce-antidepressant-need-in-menopausal-women

[2]  L. Brown et al., “Promoting good mental health over the menopause transition,” The Lancet, Mar. 2024, https://doi.org/10.1016/s0140-6736(23)02801-5

[3]  C. Shufelt et al., “The 2023 nonhormone therapy position statement of The North American Menopause Society,” Menopause The Journal of The North American Menopause Society, vol. 30, no. 6. Lippincott Williams & Wilkins, p. 573, May 30, 2023. https://doi.org/10.1097/gme.0000000000002200

[4]  “Time for a balanced conversation about menopause,” The Lancet, Mar. 2024, https://doi.org/10.1016/s0140-6736(24)00462-8

[5]  P. C. Bendis, S. Zimmerman, A. Onisiforou, P. Zanos, and P. Georgiou, “The impact of estradiol on serotonin, glutamate, and dopamine systems,” Frontiers in Neuroscience, vol. 18, Mar. 2024, https://doi.org/10.3389/fnins.2024.1348551

[6]  E. Mu, L. Chiu, and J. Kulkarni, “Using estrogen and progesterone to treat premenstrual dysphoric disorder, postnatal depression and menopausal depression,” Frontiers in Pharmacology, vol. 16. Frontiers Media, Feb. 20, 2025. https://doi.org/10.3389/fphar.2025.1528544