From Pages to Practice
Marcia, a 25-year-old nulliparous pharmacy graduate student, has been referred to your clinic for the management of uterine fibroids. She reports that the pain has improved with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), but she still struggles with heavy bleeding and fatigue, causing her to miss classes and work during the first three days of her menstrual period each month. In a discussion of treatment options, Marcia seems reluctant to undergo any surgical procedures and is eager to avoid injection hormone therapy. She asks about oral treatment options.
For women like Marcia, fibroids negatively affect quality of life, including physical, psychological, and social wellbeing. Missed work days due to menstrual discomfort and recurrent healthcare visits both contribute to a significant economic burden. Surgical intervention remains the primary management for these benign tumors of the uterus; however, nonsurgical alternatives that take advantage of fibroid responsiveness to hormone manipulation have shown promise.
In two identical randomized placebo-controlled studies published in NEJM, investigators examined the efficacy of elagolix, an oral gonadotropin-releasing hormone antagonist, for the treatment of uterine fibroid-related menorrhagia in premenopausal women. Elagolix significantly reduced heavy menstrual bleeding associated with fibroids and now offers a new oral treatment for patients such as Marcia.
The following NEJM Journal Watch summary explains the study in more detail.
Robert L. Barbieri, MD reviewing Schlaff WD et al. N Engl J Med 2020 Jan 23
Uterine fibroids often cause heavy menstrual bleeding. Elagolix is an oral gonadotropin-releasing hormone (GnRH) antagonist approved by the FDA for management of pelvic pain caused by endometriosis. To study the efficacy of elagolix (alone or with estrogen-progestin add-back therapy) in the setting of uterine fibroids, two identical industry-supported trials were performed. A total of 790 women in both trials (mean age, 42) with heavy menstrual bleeding (>80 mL blood loss per cycle), and ultrasound-diagnosed uterine fibroids were randomized to elagolix (300 mg twice daily) plus add-back (1 mg estradiol and 0.5 mg norethindrone acetate once daily), elagolix alone, or placebo for 6 months. Menstrual blood loss was quantified on collected sanitary products. The primary endpoint was menstrual blood loss <80 mL as well as a ≥50% reduction in blood loss from baseline during the final month of treatment.
At 6 months, the percentages of women achieving the primary endpoint in the first trial were 84% (elagolix alone), 68% (elagolix plus add-back), and 9% (placebo). Mean changes from baseline in lumbar spine bone density were −2.95% (elagolix alone), −0.76% (elagolix plus add-back), and −0.21% (placebo). Results were similar in the second trial. Hot flashes were reported by a mean 54% of the elagolix alone group, 20% of the elagolix plus add-back group, and 7% of the placebo group.
Comment: In these studies, elagolix alone or with estrogen-progestin add-back therapy effectively reduced menstrual bleeding associated with fibroids. Unlike elagolix alone, which was associated with significant loss of bone mineral density, elagolix plus hormonal add-back was associated with more-modest loss. One weakness is that the effect of estradiol plus norethindrone acetate treatment on menstrual bleeding was not addressed. The benefits and risks of elagolix in the long-term management (beyond 6 months) of heavy menstrual bleeding caused by uterine fibroids remain to be determined.