Long-term relugolix combo helps with heavy periods, anaemia in women with uterine fibroids

Treatment with relugolix combination for up to 52 weeks yields sustained reductions in heavy menstrual bleeding as well as subsequent increases in iron stores in women with uterine leiomyomas, as shown in a study.

At week 52, the women experienced a decrease of 89.9 percent in menstrual blood loss volume from baseline, with 70.6 percent of them achieving amenorrhea over the last 35 days of treatment. Moreover, 59.0 percent of the women with anaemia at baseline saw an increase of >2 g/dL in haemoglobin concentration. [Obstet Gynecol 2022;doi:10.1097/AOG.0000000000004988]

“Most of the reduction in menstrual blood loss volume was observed by week 4, and the full effect was observed by week 8 and sustained through week 52… These results indicate that treatment with relugolix combination therapy was associated with a rapid, clinically meaningful, and sustained improvement in bleeding for patients with heavy menstrual bleeding associated with uterine leiomyomas,” the investigators said.

“Treatment effect was independent [of] race, body mass index, and baseline menstrual blood loss volume, as well as uterine and uterine leiomyoma volumes,” they added.

The analysis included 476 women with uterine leiomyoma–associated heavy menstrual bleeding who completed their 24-week treatment in either the LIBERTY 1 or LIBERTY 2 trial. They received once-daily relugolix combination therapy (40 mg relugolix, estradiol 1 mg, norethindrone acetate 0.5 mg) in a 28-week, open-label extension study. A total of 363 (76.1 percent) women completed 52 weeks of treatment.

Other benefits

Aside from the mentioned improvements, Bleeding and Pelvic Discomfort (BPD) scale score also decreased by 51.3 points, reflecting improvement in the distress related to the key uterine leiomyoma symptoms of heavy menstrual bleeding, passing of blood clots, and pelvic pressure and tightness.

“Another potentially less obvious aspect of the benefit of relugolix combination therapy involves the effect on uterine and uterine leiomyoma volumes (ie, as assessed by imaging),” according to the investigators.

“A modest but continued reduction in uterine and uterine leiomyoma volumes was observed in this study, which is consistent with the oestrogen-threshold hypothesis proposing that maintenance of the oestradiol concentration between 20 and 50 pg/mL (70 and 180 pmol/L) may stop the progression of leiomyoma growth while minimizing hypoestrogenic adverse effects,” they said. [Am J Obstet Gynecol 1992;166:740-745]

This modest reduction in uterine and uterine leiomyoma volumes may be a boon for patients who have bulk symptoms or in the subgroup of patients who plan subsequent surgery, as the investigators pointed out.

Safety

Long-term relugolix combination therapy was tolerated well, with no unexpected safety issues identified through 52 weeks. The most frequent adverse events were headache and hot flush, with a higher cumulative frequency in women who initially received relugolix monotherapy in the LIBERTY trials.

Moreover, bone mineral density (BMD) was preserved over the course of the 52-week treatment period in most women in the relugolix combination therapy group.

In comparison, another drug used for the treatment of uterine fibroids and heavy menstrual bleeding in women, elagolix has been shown to be effective when administered with add-back therapy. However, unlike the once-daily relugolix combination, elagolix requires twice-daily dosing due to its short half-life, which may be a challenge for long-term treatment adherence. [N Engl J Med 2020;382:328-340; Obstet Gynecol 2020;135:1313-1326]

“Although not direct head-to-head studies, the reported rate of vasomotor symptoms and BMD loss [with elagolix] at 1 year was higher than observed in the LIBERTY Extension Study. Therefore, a therapeutic agent that is well tolerated and provides effective long-term management of the symptoms associated with uterine leiomyomas may help address a significant medical need as well as help support patient demands and choice for uterus-preserving treatment,” the investigators said. [Obstet Gynecol 2021;137:e100-e115]

“Relugolix combination therapy may represent an option for longer-term treatment in women with heavy menstrual bleeding associated with uterine leiomyomas,” they added.