Bazedoxifene plus conjugated estrogen to treat menopausal depression—A pilot study

Gonadal hormone fluctuations in the menopausal transition, particularly the decline in brain estrogen levels, significantly contribute to menopausal depression. Although hormone replacement therapy, known as "menopause hormone therapy," effectively manages physical symptoms, it is not routinely used for mental health disturbances due to limited large-scale clinical trial evidence comparing menopause hormone therapy with standard antidepressants. The recognition of menopausal mental illness as being different to major depressive disorder is currently lacking in research and clinical practice. Furthermore, concerns about the long-term safety of estrogen and progestins have prompted the exploration of alternative hormone therapies. Bazedoxifene, a selective estrogen receptor modulator, in combination with conjugated estrogens, is a newer, safe option for physical menopause symptoms. Our 12-week double-blind, randomized, placebo-controlled pilot study evaluated the effects of this combined hormone therapy on menopausal depression in 37 women. Twenty participants received bazedoxifene plus conjugated estrogen, and 17 received placebo. Results indicated that both groups had a decrease in the standard depression rating scale (Montgomery-Asberg Depression Rating Scale) scores from baseline to week 12. However, the decrease was not significantly different between groups. When we used our specific menopause depression rating scale-the Meno-D-we found that women receiving bazedoxifene plus conjugated estrogen improved significantly more compared with women taking the placebo. This suggests that the combined hormone therapy effectively targets the unique symptoms that constitute menopausal depression. Further research is needed to develop targeted treatments for menopausal depression, which appears to be a different type of depression that responds to hormone therapy. SIGNIFICANCE STATEMENT: This pilot study demonstrates that combined hormone therapy with bazedoxifene plus conjugated estrogen significantly improves symptoms of menopausal depression, a condition distinct from major depressive disorder. These findings highlight the potential of targeted hormone treatments for menopausal mental health, warranting further research to develop effective therapies.