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Peer-reviewedCC BY 4.0Frontiers in Endocrinology

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

  • Tianmeng Liu1
  • Yuhong Cai2
  • Mingyang Li3
  • Suqing Cai1
  • Leilei Wang1
  • Dongmei Tang1
  • Yiling Wu1
  • Nan Zhu1
  1. 1Department of Obstetrics and Gynecology, Xiamen Susong Hospital
  2. 2Women and Children’s Hospital Affiliated to Xiamen University, Xiamen Maternal and Child Health Hospital
  3. 3Graduate School of Dalian Medical University
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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.

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Cite

BibTeXRIS
BibTeX
@article{liu2026gonadotropinreleasing,
  title = {{Gonadotropin-releasing hormone antagonists versus agonists for endometriosis: a systematic review and meta-analysis of randomized controlled trials}},
  author = {Tianmeng Liu and Yuhong Cai and Mingyang Li and Suqing Cai and Leilei Wang and Dongmei Tang and Yiling Wu and Nan Zhu},
  journal = {Frontiers in Endocrinology},
  year = {2026},
  month = oct,
  doi = {10.3389/fendo.2026.1979544},
  url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1979544/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Gonadotropin-releasing hormone antagonists versus agonists for endometriosis: a systematic review and meta-analysis of randomized controlled trials
AU  - Tianmeng Liu
AU  - Yuhong Cai
AU  - Mingyang Li
AU  - Suqing Cai
AU  - Leilei Wang
AU  - Dongmei Tang
AU  - Yiling Wu
AU  - Nan Zhu
PY  - 2026
DA  - 2026/10/14
JO  - Frontiers in Endocrinology
DO  - 10.3389/fendo.2026.1979544
UR  - https://www.frontiersin.org/articles/10.3389/fendo.2026.1979544/full
AB  - 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.
SN  - 1664-2392
ER  -