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