Effectiveness of estetrol 15 mg combined with drospirenone 3 mg for symptom control in women with endometriosis: a systematic review

Leitão MO, Manuela Oliveira Leitão, Rodrigues de Sousa FT, Frederico Timm Rodrigues de Sousa, Cunha GR, Gabriela Reis Cunha, Tavares LV, Lara Vieira Tavares, Lunardi Rocha AL, Ana Luiza Lunardi Rocha, Fontes de Oliveira EC, Elaine Cristina Fontes de Oliveira
European journal of obstetrics, gynecology, and reproductive biology · 2026 · vol. 327 , pp. 115500 · doi:10.1016/j.ejogrb.2026.115500 · PMID:42892004 · W7221847817
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This systematic review evaluated the effectiveness of estetrol 15 mg combined with drospirenone 3 mg for controlling symptoms in women diagnosed with endometriosis.

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Abstract

OBJECTIVE: To systematically evaluate the effectiveness of estetrol (E4) combined with drospirenone (DRSP) in reducing endometriosis-related symptoms and improving quality of life (QoL). STUDY DESIGN: We conducted a systematic review in accordance with Cochrane Collaboration guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Two reviewers independently performed study selection, data extraction, and risk of bias assessment. A third author resolved disagreements between the reviewers. We conducted a comprehensive search across PubMed, Embase, and Cochrane Central Register of Controlled Trials, without language or date restrictions. MAIN FINDINGS: We included two RCTs and two observational cohorts, encompassing a total of 198 patients. Quantitative synthesis was not feasible for the outcomes due to the limited number of eligible studies and the lack of sufficient comparable data. E4/DRSP demonstrated a significant reduction in pelvic pain compared with placebo, whereas no significant differences were observed when compared with other active hormonal regimens. Treatment with E4/DRSP also was associated with clinically meaningful improvements in dysmenorrhea symptoms. Furthermore, E4/DRSP improved QoL in women with endometriosis, with improvements in sleep quality, patient- and clinician-reported global improvement and overall health status. The findings regarding dyspareunia were inconsistent. The most common adverse effect was intermenstrual bleeding/spotting. CONCLUSION: Based on the current evidence, E4/DRSP appears to be a promising option for the management of endometriosis-related symptoms, particularly improving pelvic pain, dysmenorrhea, and QoL. IMPLICATIONS: This systematic review, conducted according to Cochrane and PRISMA guidelines, indicated that E4/DRSP may be effective in reducing endometriosis-associated symptoms, although its superiority over other combined hormonal contraceptives remains uncertain.

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