A phase 3, randomized, active-controlled study published in Fertility and Sterility demonstrated noninferiority of 40 mg relugolix (gonadotropin-releasing hormone antagonist) when compared to leuprorelin (gonadotropin-releasing hormone agonist) in females with endometriosis-associated pain. Tasuku Harada et al. aimed to examine the safety and effectiveness of relugolix in comparison with leuprorelin (as the active comparator) for the management of endometriosis-linked pelvic pain.

This double-dummy, double-blind, multicenter study enrolled females (age >20 years) with regular menstrual cycles (25–38 days) and suffering from endometriosis or ovarian endometrioma and reporting pelvic pain. Participants were randomly segregated into two groups:  (i) Relugolix group: Received oral administration of 40 mg relugolix once a day for twenty-four weeks, and (ii) Leuprorelin group: Received subcutaneous injection of 3.75 or 1.88 mg of leuprorelin every four weeks for twenty-four weeks.

An alteration in the maximum visual analog scale (VAS) score for pelvic pain from the baseline until twenty-eight days prior to therapy end was the major outcome ascertained. Alteration in maximum VAS score, a decline in ovarian endometrioma, and discontinuations from treatment-emergent adverse events (TEAEs) are shown in Table 1:

Headache, hot flush, genital hemorrhage, and metrorrhagia were drug-related TEAEs with an incidence of >10% for both groups. The safety profile of both relugolix and leuprorelin were comparable. However, menses were reported to return earlier in women taking relugolix, a tremendous advantage for females who wish to conceive after therapy. Thus, relugolix exhibits a promising potential of becoming a new therapeutic choice to mitigate pain symptoms linked with endometriosis.