Efficacy and safety of menopausal hormone therapy for depressive symptoms in perimenopausal women: A systematic review and meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 42061517 · doi:10.1016/j.jad.2026.121892
What was done
A systematic review and meta-analysis was performed searching PubMed, Embase, the Cochrane Library, Web of Science, and ClinicalTrials.gov through December 23, 2025. The authors included randomized controlled trials evaluating hormone replacement therapy (HRT) versus placebo, HRT versus HRT combined with antidepressants, and comparisons between different HRT regimens in perimenopausal women with depressive symptoms. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using random-effects models. Risk of bias was assessed with RoB 2 and certainty with GRADE.
What was found
Twelve randomized controlled trials were included. Compared to placebo, HRT was associated with a small reduction in depressive symptom severity (SMD = -0.23, 95% CI -0.43 to -0.03). Tests for subgroup differences by hormone type (such as tibolone or selective tissue estrogenic activity regulators) and administration route were not statistically significant, with limited study numbers per subgroup. Active-treatment comparisons were sparse, and reported adverse events were generally mild to moderate.
Why it matters
This review shows that while HRT yields a statistically significant reduction in perimenopausal depressive symptoms versus placebo, the clinical effect size is small and certainty is limited.
Limits
The total number of randomized participants is not reported in the abstract. Subgroup analyses were limited by small trial counts, comparative active-treatment data were insufficient, and long-term safety was not determined.
Cited by
- supports Declining estrogen levels can contribute to or cause depression in women.