relugolix-estradiol-norethisterone acetate for treating moderate to severe symptoms of uterine fibroids

Last edited 10/2022 and last reviewed 10/2022

Relugolix-estradiol-norethisterone acetate for treating moderate to severe symptoms of uterine fibroids

Relugolix

• is an orally active nonpeptide GnRH-receptor antagonist that is suitable for daily use
• competitively binds to pituitary GnRH receptors, blocking the binding and signaling of endogenous GnRH and thus leading to reversible, dose-dependent decreases in gonadotropin concentrations and subsequent suppression of ovarian estradiol and progesterone production
• to achieve efficacy, minimize hypoestrogenic side effects, and preserve bone mineral density, relugolix combination therapy (consisting of 40 mg of relugolix, 1 mg of estradiol, and 0.5 mg of norethindrone acetate) was developed as a once-daily treatment for maintaining estradiol levels within the physiologic range of the early follicular phase of the menstrual cycle, with the addition of a progestin to mitigate the unopposed estrogen action that could lead to endometrial hyperplasia (1)
• study evidence showed:
  • once-daily relugolix combination therapy resulted in a significant reduction in menstrual bleeding, as compared with placebo, and preserved bone mineral density in women with uterine fibroids (1)
  • significantly reduced moderate-to-severe uterine leiomyoma-associated pain with a more pronounced effect on menstrual pain (2)

NICE state:

• relugolix-estradiol-norethisterone acetate is recommended, within its marketing authorisation, as an option for treating moderate to severe symptoms of uterine fibroids in adults of reproductive age
• the NICE committee noted other advantages of using this treatment as:
  • it is an effective non-surgical treatment
  • it is taken orally
  • there is no restriction on treatment duration in the marketing authorisation (in contrast to GnRH agonists)
  • it is well tolerated
  • it preserves the uterus (in contrast to surgical options)

Reference:

• Al-Hendy A, Lukes AS, Poindexter AN 3rd, Venturella R, Villarroel C, Critchley HOD, Li Y, McKain L, Arjona Ferreira JC, Langenberg AGM, Wagman RB, Stewart EA. Treatment of Uterine Fibroid Symptoms with Relugolix Combination Therapy. N Engl J Med. 2021 Feb 18;384(7):630-642.
• Stewart EA, Lukes AS, Venturella R, Arjona Ferreira JC, Li Y, Hunsche E, Wagman RB, Al-Hendy A. Relugolix Combination Therapy for Uterine Leiomyoma-Associated Pain in the LIBERTY Randomized Trials. Obstet Gynecol. 2022 Jun 1;139(6):1070-1081.
• NICE (October 2022). Relugolix-estradiol-norethisterone acetate for treating moderate to severe symptoms of uterine fibroids