Gonadotropin-releasing hormone antagonists versus agonists for endometriosis: a systematic review and meta-analysis of randomized controlled trials

Tianmeng Liu, Yuhong Cai, Mingyang Li, 蔡素卿, Leilei Wang, Dongmei Tang, Yiling Wu, Nan Zhu
In: Frontiers in Endocrinology · 2026 · vol. 17 · doi:10.3389/fendo.2026.1979544 · W7221750056
Systematic review / meta-analysis OA: gold CC0
🔓 Open OA copy View on OpenAlex View at publisher

Abstract

Background Endometriosis is a chronic estrogen-dependent inflammatory disease requiring individualized long-term hormonal management. Gonadotropin-releasing hormone agonists (GnRH-a) effectively suppress ovarian function but may induce hypoestrogenic adverse effects, whereas oral gonadotropin-releasing hormone antagonists (GnRH-ant) offer rapid, reversible suppression with reduced hormonal fluctuation. However, their comparative efficacy and safety remain unclear. Methods We performed a systematic review and meta-analysis of randomized controlled trials comparing GnRH-ant with leuprolide-based GnRH-a for the treatment of endometriosis, assessing symptom relief, pelvic signs, bone mineral density (BMD), quality of life, and hormonal outcomes. Results Five randomized controlled trials were included. Compared with GnRH-ant, GnRH-a yielded greater improvements in dysmenorrhea (standardized mean difference (SMD) = 0.69, 95% CI: 0.48–0.91), nonmenstrual pelvic pain (NMPP) (SMD = 0.33, 95% CI: 0.16–0.50), overall pelvic pain (OPP) (SMD = 0.25, 95% CI: 0.13–0.38), and dyspareunia (SMD = 0.14, 95% CI: 0.02–0.26). GnRH-a was also associated with better outcomes in pelvic tenderness, Douglas pouch induration scores, peak pain severity, analgesic requirements, and menstrual blood loss. Subgroup analysis suggested a more pronounced analgesic benefit of GnRH-a after 12 weeks of treatment. In contrast, GnRH-ant resulted in significantly less BMD reduction (SMD = 0.64, 95% CI: 0.39–0.89), a stronger bone-sparing effect at 24 weeks. No significant differences were observed in most quality-of-life domains. Conclusions Leuprolide-based GnRH-a provides superior symptom control, whereas GnRH-ant offers less decline in BMD and reversible ovarian suppression, but differences among individual antagonists should be considered. Treatment selection should be individualized based on symptom severity, bone health, and fertility goals. Long-term head-to-head trials are warranted. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420261289010 , identifier CRD420261289010.

My notes (saved in your browser only)

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (23)

Source provenance

openalex
last seen: 2026-10-16T06:01:16.192504+00:00
License: CC0 · commercial use OK