Effects of combined estrogen and bazedoxifene (CEB) on depressive symptoms in perimenopause

Perimenopause is characterized by ovarian hormone fluctuation and associated with elevated risk for depression. Perimenopausal-onset major depression (PO-MDD) can be alleviated with estrogen treatment. However, due to potential risk for breast and uterine cancer, traditional hormone treatments may not be suitable for some. Conjugated estrogen combined with the selective estrogen receptor modulator (SERM) bazedoxifene (CEB) is a tissue selective estrogen complex (TSEC) used to target hot flashes and postmenopausal osteoporosis. CEB's effect on mood during perimenopause remains understudied.

In this open-label pilot clinical trial, CEB was administered to perimenopausal women (N = 10) for three weeks with weekly symptom assessments and estradiol measurements. Mixed effects models were used to examine changes in affective and menopausal symptoms.

Menopausal symptoms were significantly reduced over the course of treatment, and several depression symptom domains were also reduced (e.g., dysphoria, anhedonia, ill temper, insomnia; all p_FDRs < 0.05).

The current findings suggest that CEB reduces mood and menopausal symptoms without the concurrent risk profile of standard hormonal treatments. Further research is needed to understand potential links with estradiol variability and implications for the further development of treatments.