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Clinical Trial
. 2025 Dec 1:390:119853.
doi: 10.1016/j.jad.2025.119853. Epub 2025 Jul 7.

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

Erin Bondy  1 , Julianna Prim  2 , David Rubinow  2 , Lauren Schiff  3 , Gabriel S Dichter  4 , Crystal E Schiller  2
Affiliations
Clinical Trial

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

Erin Bondy et al. J Affect Disord. .

Abstract

Background: 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.

Methods: 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.

Results: 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 pFDRs < 0.05).

Discussion: 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.

Keywords: Depression; Estrogen; Perimenopause.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Crystal E. Schiller reports financial support was provided by Foundation of Hope for Research and Treatment of Mental Illness. David Rubinow reports a relationship with SAGE Therapeutics Inc. that includes: funding grants. David Rubinow reports a relationship with Brii Biosciences that includes: consulting or advisory. David Rubinow reports a relationship with GH Research-Ireland that includes: consulting or advisory. David Rubinow reports a relationship with National Institutes of Health that includes: funding grants. David Rubinow reports a relationship with Buszucki Foundation that includes: funding grants. David Rubinow reports a relationship with SAGE Therapeutics Inc. that includes: board membership. David Rubinow reports a relationship with Foundation of Hope for Research and Treatment of Mental Illness that includes: board membership. David Rubinow reports a relationship with Sensorium Therapeutics that includes: board membership. David Rubinow reports a relationship with Felicitypharma that includes: board membership. Crystal E. Schiller reports a relationship with National Institutes of Health that includes: funding grants. Gabriel Dichter reports a relationship with National Institutes of Health that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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