Efficacy and safety of relugolix therapy for symptomatic uterine fibroids: a systematic review and meta-analysis.

[INTRODUCTION] Uterine fibroids are the most common benign tumors in premenopausal women and often necessitate fertility-sparing treatments. Relugolix, an oral GnRh antagonist has emerged as a promising non-surgical option. This systematic review and meta-analysis evaluate the efficacy and safety of relugolix for symptomatic uterine fibroids.

[METHODS] We searched PubMed, Embase, Cochrane CENTRAL, Scopus, and ClinicalTrials.gov through March 2025. Six studies (n = 511) were included in accordance with the PRISMA guidelines. Data were analysed using random-effects models in R (v4.5.0). Risk of Bias was assessed using ROB 2 tool. Continuous outcomes were reported as mean differences (MDs), dichotomous outcomes as odds ratios (ORs) or proportions, and heterogeneity using I statistics, with sensitivity analyses for I ≥ 50 %.

[RESULTS] Pooled analysis revealed a myoma volume reduction (MVR) of -30.18 %, with similar findings when compared to placebo (-28.50 %; p-value = 0.0070). Uterine volume decreased by -27.22 %. When compared with placebo, uterine volume significantly reduced by -30.31 (p-value = 0.0028). Amenorrhea was achieved by 63 % of patients, with relugolix-treated patients showing 31-fold higher odds versus controls (31.07 %; p-value < 0.0001). Haemoglobin levels improved in 46.3 % patients, while relugolix-treated patients achieved significant pain relief compared to controls (OR 9.02; p = value < 0.0001). Subgroup analyses showed that relugolix monotherapy produced greater reductions in myoma and uterine volumes than combination therapy, although both regimens were effective. Treatment as generally well-tolerated, with hot flushes being the most common adverse event. A small proportion reported persistent menorrhagia without indicating treatment failure. Other adverse events, such as headache, were also reported, though discontinuation rates were comparable to controls.

[CONCLUSION] Relugolix significantly reduces fibroid burden and symptoms with favourable safety profile. It offers a well-tolerated, fertility-preserving alternative to surgery. Further large-scale RCTs are needed to confirm these findings and optimize treatment protocols.