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

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.