Relugolix/Estradiol/Norethisterone (Norethindrone) Acetate: A Review in Symptomatic Uterine Fibroids

An oral fixed-dose combination of relugolix/estradiol/norethisterone (also known as norethindrone) acetate (Ryeqo(®); Myfembree(®)) has been approved for the management of heavy menstrual bleeding associated with uterine fibroids in the USA and management of moderate to severe symptoms of uterine fibroids in the EU. Relugolix is a gonadotropin releasing hormone (GnRH) receptor antagonist that decreases serum estradiol and progesterone concentrations to postmenopausal levels. The addition of estradiol/norethisterone acetate to relugolix ameliorates relugolix-induced bone loss and hot flush. In the two phase 3 LIBERTY trials, relugolix + estradiol/norethisterone substantially decreased menstrual bleeding and improved a range of other uterine fibroid symptoms in women with uterine fibroids-associated heavy menstrual bleeding. The combination was generally well tolerated, with vasomotor symptoms being the most common adverse reaction. Treatment with this combination for over up to 2 years did not induce a clinically meaningful bone loss in the majority of women. Relugolix/estradiol/norethisterone acetate, with its convenient once-daily administration, is a useful addition to current pharmacological treatment options for premenopausal women with symptomatic uterine fibroids. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40265-022-01790-4.