For a study, researchers sought to evaluate once-daily relugolix combination treatment (relugolix-CT: relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg) to placebo in women with uterine leiomyomas and significant monthly bleeding. LIBERTY 1 and 2 were two duplicate, global, double-blind, 24-week, randomized phase 3 trials in premenopausal women with uterine leiomyoma–associated excessive menstrual bleeding (80 mL or greater per cycle for two cycles or 160 mL or greater during one cycle). A secondary goal was to see how relugolix-CT affected moderate-to-severe uterine leiomyoma related pain in the pain subpopulation (women with maximum pain ratings of 4 or higher on the 0–10 numerical rating scale at baseline and pain score reporting compliance of 80%) (i.e., 28 days or more over the last 35 days of treatment). This primary, the secondary endpoint was defined as the proportion of women who experienced minimal-to-no uterine leiomyoma–associated pain (maximum numerical rating scale score 1 or below) at week 24; menstrual and nonmenstrual pain was assessed in separate secondary analyses. The Cochran-Mantel-Haenszel test was used to compare treatments in the pooled LIBERTY 1 and 2 pain subpopulations stratified by baseline menstrual blood loss volume.
About 509 women were assigned to relugolix-CT or placebo in both studies (April 2017–December 2018). Around 277 (54.4%) of them satisfied the pain subpopulation criterion. About 45.2% (95% CI 36.4–54.3) of women experienced minimal-to-no discomfort with relugolix-CT, compared to 13.9% (95% CI 8.8–20.5) with placebo (nominal P<.001). The proportions of women experiencing minimal-to-no pain on menstrual and nonmenstrual days were significantly higher with relugolix-CT (65.0% [95% CI 55.6–73.5] and 44.6% [95% CI 32.3–57.5], respectively) compared to placebo (19.3% [95% CI 13.2–26.7], nominal P<.001, and 21.6% [95% CI 12.9–32.7], nominal P=.004). Relugolix-CT substantially decreased moderate-to-severe uterine leiomyoma–associated pain over 24 weeks, with a stronger impact on monthly pain. The findings supported that relugolix-CT had a clinically significant impact on women’s uterine leiomyoma–associated discomfort.