Abstract
INTRODUCTION: Women with endometriosis frequently experience psychological and sexual concerns. Combined oral contraceptives (COCs) and progestin-only pills (POPs) represent first-line treatments for the disease, yet their potential negative impact on mood and sexuality remains debated. MATERIAL AND METHODS: We conducted a systematic review of PubMed, Embase, and Scopus up to August 1st, 2025, to assess whether COCs or POPs adversely affect psychological well-being or sexual function in this population. Eligible studies included randomized controlled trials (RCTs) and non-randomized studies comparing COCs or POPs with no treatment in women with endometriosis. Outcomes of interest were adverse event rates and patient-reported measures of mood and sexual health. Risk of bias was assessed with RoB 2 and ROBINS-I. Given heterogeneity in outcome measures, we applied vote counting by direction of effect and harvest plots, with confidence intervals (CIs) calculated using the Wilson method, in line with Cochrane guidance. The study protocol was prospectively registered on PROSPERO (CRD420250656420). RESULTS: Of 1424 records screened, seven studies (four RCTs, three observational) met the inclusion criteria. Risk of bias was low in RCTs and moderate-to-serious in observational studies. Six of seven (pooled proportion: 86%; 95% CI: 49%-97%) reported no increased risk of psychological dysfunction in users. None reported increased sexual dysfunction (100%; 95% CI: 65%-100%). Most studies reported significant pain reduction with treatment. Six studies specifically reported on dyspareunia, all of which showed a benefit of treatment over placebo (100%; 95% CI: 61%-100%). No discontinuations for psychological or sexual adverse events were observed when pain remission was achieved. DISCUSSION: Despite the small number of studies, variability in measurement tools, and short follow-up (mean 6 months), the evidence suggests that COCs and POPs are generally well tolerated regarding psychological and sexual health, supporting their continued use for long-term management provided pain remission is achieved. CONCLUSIONS: In women with endometriosis, current evidence does not support a consistent increase in negative psychological or sexual outcomes among COCs or POPs users compared with non-users.