In healthy women with normal ovulatory function, treatment with elagolix suppressed ovulation in a dose-dependent manner and reduced endometrial thickness at doses used to treat endometriosis pain, according to study results published in The Journal of Endocrinology & Metabolism. However, elagolix did not consistently inhibit ovulation and therefore may not be a contraceptive.
Elagolix, an orally active, nonpeptide gonadotropin-releasing hormone antagonist, was previously found to be well tolerated and produced rapid and dose-dependent suppression of gonadotropins and estradiol. The goal of the current study was to explore the effects of different doses of elagolix on ovulation, gonadotropins, ovarian hormones, and endometrial thickness during 3 continuous 28-day dosing intervals.
The phase 1 randomized, open-label, multicenter, sequential dose-escalation study was conducted at 20 sites and included 205 women between the age of 18 and 40 years with a history of regular menstrual cycles and without significant gynecologic disorders.
The primary outcomes were ovulation rates, progesterone levels, and hormone suppression.
The data show that elagolix suppressed ovulation in a dose-dependent fashion, as the rate of women who ovulated during the 3 intervals was highest at a dose of 100 mg once daily (78%); intermediate at 150 mg once daily, 200 mg once daily, and 100 mg twice daily (47%-57%); and lowest in women treated with 200 and 300 mg twice daily (32% and 27%, respectively). The combination of estradiol/norethindrone acetate and elagolix 300 mg twice daily further suppressed the percentage of women who ovulated to 10%.
With luteinizing hormone and estradiol, there was progressively increased suppression with higher doses of elagolix, whereas for follicle-stimulating hormone, suppression was observed with doses of 200 mg twice daily and higher. The addition of estradiol/norethindrone acetate resulted in further suppression of follicle-stimulating hormone and luteinizing hormone, but not estradiol.
Administration of elagolix had no effect on monthly concentrations of anti-mullerian hormone at any time point. Endometrial thickness was substantially lower while patients were receiving elagolix than during the screening period.
“Women being treated with elagolix may ovulate and should use effective methods of contraception,” concluded the researchers.
Disclosure: This clinical trial was supported by AbbVie. Please see the original reference for a full list of authors’ disclosures.
Archer DF, Ng J, Chwalisz K, et al. Elagolix suppresses ovulation in a dose-dependent manner: results from a 3-month, randomized study in ovulatory women [published online October 25, 2019]. J Clin Endocrinol Metab. doi:10.1210/clinem/dgz086