According to a systematic review and network meta-analysis, oral gonadotropin-releasing hormone (GnRH) antagonists are efficacious for reducing endometriosis-related pain and dysmenorrhea and improving the patient global impression. Investigators sought to review the usage of oral GnRH antagonists and synthesize their effectiveness and safety parameters to treat premenopausal females with endometriosis who had experienced moderate to severe pain.

Databases like MEDLINE, Web of Science, Scopus, and Embase were explored. Only randomized controlled trials were incorporated. Using Cochrane Risk of Bias tool 2, the risk of bias in the incorporated studies was determined. For performing indirect comparisons, a Bayesian random-effects network meta-analysis was utilized. For assessing the global heterogeneity, I2 was utilized. Relative treatment estimates were carried out.  Ranking of treatment was done via surface under the cumulative ranking curve.

Utilizing the Grading of Recommendations, Assessment, Development and Evaluation framework, the evidence certainty was explored. Dyspareunia, Endometriosis-associated pain, dysmenorrhea, and noncyclic pelvic pain reduction were the main outcomes ascertained. For inclusion, 5 studies and 6 trials, encompassing 2,796 females and 10 distinct doses of oral GnRH antagonists were eligible. All studies had a low risk of biasness. Almost all findings relating to safety and efficacy revealed a dose-response connection.

Linzagolix 200 mg, Linzagolix 75 mg, and Elagolix 400 mg were the best 3 therapies for endometriosis-related pain, with mean differences of -0.98, -0.98, and -1.26 respectively. Relugolix 20 mg, Elagolix 400 mg, and Relugolix 40 mg were the top 3 therapies for alleviating dysmenorrhea, with mean differences of -1.10, -1.25, and -1.60 respectively. But, the majority of outcomes linked to the quality of life and negative effects were only considerably correlated with high-dose therapies.

With the odds ratios of 6.88, 1.60, and 1.85, Relugolix 40 and 20 mg and Elagolix 400 mg showed a considerably raised frequency of side effects. Thus, oral GnRH antagonists are useful for the management of endometriosis-associated pain. The occurrence of ovarian hypoestrogenic effects in the short-term duration was profound in the dose-effect response, specifically the highest dose.