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Gonadotropin-releasing hormone (GnRH) agonists and dienogest are widely recognized as valuable medical therapies for endometriosis-associated pain.
Oral GnRH antagonists provide the greatest improvement in dysmenorrhea and non-menstrual pelvic pain, while dienogest offers superior dyspareunia relief with the best overall safety profile in endometriosis management.
Gonadotropin-releasing hormone (GnRH) agonists and dienogest are widely recognized as valuable medical therapies for endometriosis-associated pain. More recently, oral GnRH antagonists have emerged as a promising treatment option; however, clear evidence regarding the superiority of one therapy over another remains limited. Hence, this study explored the clinical efficacy and safety profiles of GnRH analogues and dienogest for pain due to endometriosis.
A systematic literature search of Cochrane Library, Embase, and MEDLINE was conducted to identify trials exploring the effects of dienogest and GnRH analogues on non-menstrual pelvic pain, dysmenorrhea, and dyspareunia. Safety outcomes included hot flashes, headaches, amenorrhea, irregular vaginal bleeding, and changes in bone mineral density. Treatment effects were calculated via standardized mean differences based on pre- and post-treatment outcomes. A network meta-analysis integrating direct and indirect comparisons was performed, while risk ratios with 95% confidence intervals were used to evaluate adverse events.
Overall, 8 randomized controlled trials involving 3,259 patients fulfilled the inclusion criteria. Both low- and high-dose oral GnRH antagonists and dienogest exhibited markedly greater potency than placebo in minimizing non-menstrual pelvic pain. High-dose GnRH antagonist ranked highest for non-menstrual pelvic pain improvement. For dyspareunia, both doses of GnRH antagonists and dienogest outperformed placebo, with leuprolide showing the strongest overall effect.
Notably, dienogest offered greater benefit than GnRH antagonists for dyspareunia relief. In the management of dysmenorrhea, high-dose GnRH antagonist attained the most pronounced symptom reduction. Dienogest showed the most favorable safety profile, with the lowest occurrence of adverse effects.
Oral GnRH antagonists offered the strongest therapeutic benefit for dysmenorrhea and non-menstrual pelvic pain in women with endometriosis. However, dienogest remained the preferred option for dyspareunia management and overall safety. These findings support individualized treatment selection based on symptom profile and tolerability, helping clinicians optimize medical therapy for endometriosis-associated pain.
European Journal of Obstetrics & Gynecology and Reproductive Biology
GnRH analogues and dienogest for second line treatment of endometriosis-associated pain: a systematic review, meta-analysis, and network meta-analysis
Aharon Dick et al.
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