Myfembree (Relugolix) for Uterine Fibroids
Myfembree (relugolix combination therapy) is an FDA-approved oral GnRH receptor antagonist combination therapy specifically indicated for the management of heavy menstrual bleeding associated with uterine fibroids. 1, 2
Mechanism of Action
- Relugolix is a nonpeptide GnRH receptor antagonist that competitively binds to pituitary GnRH receptors, reducing the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), consequently decreasing estrogen and progesterone levels 3
- Myfembree contains a fixed-dose combination of relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg in a single daily tablet 2, 4
- The addition of estradiol and norethindrone acetate (add-back therapy) mitigates the hypoestrogenic side effects of relugolix monotherapy, particularly bone mineral density loss and vasomotor symptoms 1, 4
Clinical Efficacy
- In the LIBERTY phase 3 trials, 71-73% of women treated with relugolix combination therapy achieved a significant reduction in menstrual blood loss (volume <80 ml and ≥50% reduction from baseline), compared to only 15-19% in the placebo group 4
- Treatment with Myfembree resulted in significant improvements in six of seven key secondary endpoints, including amenorrhea rates, pain reduction, decreased distress from bleeding and pelvic discomfort, improved anemia, and reduced uterine volume 4
- Long-term data from the LIBERTY randomized withdrawal study demonstrated that 78.4% of women maintained reduced menstrual blood loss through 76 weeks of treatment, compared to only 15.1% in the placebo group 5
- After 2 years of continuous treatment, 69.8% of women maintained reduced menstrual blood loss, showing durability of effect 5
Position in Treatment Algorithm
- The American College of Radiology recommends estrogen-progestin oral contraceptive pills and progestin-containing intrauterine devices (IUDs) as first-line medical management for reducing bleeding symptoms associated with uterine fibroids 6, 7
- GnRH antagonists like relugolix are considered effective second-line options that both reduce bleeding symptoms and significantly reduce fibroid volume by 18-30% 6, 8
- Myfembree is specifically FDA-approved for the management of heavy menstrual bleeding associated with uterine fibroids 2
Safety Profile
- Myfembree is generally well-tolerated with an adverse event profile similar to placebo in clinical trials 4
- The most common adverse reactions are vasomotor symptoms (hot flushes) 1
- Unlike GnRH agonists or antagonist monotherapy, relugolix combination therapy with estradiol/norethindrone preserves bone mineral density through 2 years of treatment 5
- Treatment with relugolix combination therapy for up to 2 years did not induce clinically meaningful bone loss in the majority of women 1
Clinical Considerations
- Fertility is suppressed during treatment with Myfembree, making it inappropriate for women actively seeking pregnancy 8
- Symptoms typically recur rapidly after cessation of therapy, with 88.3% of women experiencing return of heavy menstrual bleeding within a median of 5.9 weeks after stopping treatment 5
- Myfembree offers the convenience of once-daily oral administration, unlike injectable GnRH agonists such as leuprolide acetate 1, 9
- Myfembree can be used preoperatively to reduce fibroid size and correct anemia before surgical interventions 8, 9
Contraindications and Precautions
- Myfembree should not be used in women with a high risk of arterial, venous thrombotic, or thromboembolic disorders 8
- The medication is contraindicated in pregnancy, as relugolix may cause fetal harm based on animal studies 3
- Women should use effective non-hormonal contraception during treatment and for some time after discontinuation 3
Myfembree represents an important addition to the medical management options for women with symptomatic uterine fibroids, offering effective control of heavy menstrual bleeding while avoiding the hypoestrogenic effects associated with GnRH antagonist monotherapy.