The use of conjugated estrogens and bazedoxifene for the management of vasomotor symptoms in premenopausal and menopausal patients with endometriosis: a systematic review.

OBJECTIVE: This systematic review investigated the impact of conjugated estrogens/bazedoxifene (CE/BZA) for treating perimenopausal and menopausal symptoms in patients with a history of endometriosis. METHOD: The review followed PRISMA guidelines and was prospectively registered with PROSPERO (CRD42024617174). Without randomized controlled trials (RCTs), the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports and Case Series assessed methodology and risk of bias. An information specialist completed the search in June 2025 using Ovid MEDLINE, PubMed, Ovid EMBASE, and Web of Science, combining controlled vocabularies and keywords for dysmenorrhea, dyspareunia, endometriosis, perimenopausal, postmenopausal, menopause hormone therapy, Duavive, and CE/BZA. Eligible studies included RCTs, cohort studies, case reports, and case-control studies evaluating CE/BZA for vasomotor symptoms in premenopausal and menopausal endometriosis patients. RESULTS: Of 1540 retrieved studies, two coauthors (J.C.M.-G., E.S.) independently screened titles and abstracts, selecting 20 for full-text review. Only two publications met inclusion criteria, one case report and one case series, representing nine patients (four detailed, five additional). No RCTs, cohort, or case-control studies directly addressed CE/BZA in endometriosis. Preliminary narrative evidence suggests pain and vasomotor symptom relief, though findings carry high risk of bias. CONCLUSION: Because bazedoxifene antagonizes estrogen receptors and endometriosis is estrogen-dependent, CE/BZA may alter systemic inflammation or endothelial function. Although preclinical models show reduced lesion size, human evidence remains extremely limited and biased, insufficient to assess lesion recurrence or vascular safety. CE/BZA is currently indicated only for postmenopausal vasomotor symptoms; preliminary anecdotal evidence suggests symptom improvement, but large-scale comparative trials are urgently needed to establish safety and efficacy in endometriosis. Our systematic review investigated the potential use of conjugated estrogens and bazedoxifene (CE/BZA) to manage hot flashes in premenopausal and menopausal patients with a history of endometriosis. Endometriosis is a common condition where uterine-like tissue grows outside the uterus, causing pain and other symptoms. Managing menopausal symptoms in these patients is challenging because standard hormone therapies can sometimes worsen endometriosis symptoms.CE/BZA is a progesterone-free hormone therapy that combines estrogen with bazedoxifene, a selective estrogen receptor modulator (SERM). While bazedoxifene blocks estrogen’s effects in the uterus and breast, its effect on endometriosis lesions is not yet proven in humans. Our review found that there is a significant lack of strong clinical data. We found only one case report and one small case series (nine patients in total). These case-based publications were small, lacked control groups, and did not use objective measures, meaning their findings are very preliminary and carry a high risk of bias.While these few reports suggested that some patients experienced relief from pain and hot flashes, the findings are very preliminary and cannot be generalized. Currently, the medication is strictly indicated for postmenopausal vasomotor symptoms, not specifically for endometriosis. Well-designed, large-scale randomized controlled trials are needed to confirm the efficacy, safety and long-term impacts of CE/BZA for endometriosis patients experiencing vasomotor symptoms. We conclude that while this is an exciting possible treatment, more research is needed to ensure it does not cause endometriosis to return.