Is Myfembree (Relugolix 40mg + Estradiol 1mg + Norethisterone 0.5mg) Appropriate to Start?
Yes, Myfembree is an excellent choice for this patient who has failed both levonorgestrel IUS and dienogest, as it represents FDA-approved second-line therapy specifically designed for heavy menstrual bleeding from uterine fibroids and will address both bleeding control and fibroid volume reduction. 1, 2
Why Myfembree Is the Right Choice Now
First-line therapies have clearly failed in this patient—the levonorgestrel IUS (considered the most effective first-line option) and two months of dienogest (a progestin) have not controlled bleeding that extends to day 25 of the cycle. 2, 3
GnRH antagonists with add-back therapy are the recommended next step after progestin failure, according to current guidelines, and Myfembree is specifically FDA-approved for this indication. 1, 2
The combination formulation prevents hypoestrogenic side effects that would occur with relugolix monotherapy—the estradiol 1mg and norethisterone 0.5mg components mitigate bone mineral density loss, hot flashes, headaches, and hypertension while maintaining efficacy for bleeding control. 1, 4, 5
Expected Clinical Benefits
Rapid and sustained bleeding reduction: Relugolix combination therapy achieves faster reduction in heavy menstrual bleeding compared to GnRH agonists, with most women responding within the first treatment cycle. 4, 6
Fibroid volume reduction: The medication significantly reduces both uterine volume and individual fibroid size, addressing the underlying pathology of large intramural fibroids. 1, 7, 6
Improved quality of life: Clinical trials demonstrate substantial improvements in fibroid-related symptoms and health-related quality of life measures. 4, 8, 7
Anemia correction: The dramatic reduction in menstrual blood loss allows hemoglobin recovery, especially when combined with iron supplementation. 2, 8
Treatment Duration and Safety Profile
Up to 2 years of continuous use is safe without clinically meaningful bone loss in the majority of women when the add-back hormones are included. 1, 4, 8
Most common side effects are manageable: Headaches and hot flushes are the most frequent adverse events, but these are significantly reduced compared to GnRH antagonist monotherapy due to the add-back component. 4, 8
Fertility is suppressed during treatment but returns after discontinuation; this is important counseling for patients who may desire future pregnancy. 1, 2
Concurrent Management Strategies
Start iron supplementation immediately to correct any existing anemia from chronic heavy bleeding while initiating Myfembree. 2, 3
Consider adding tranexamic acid as a nonhormonal adjunct if breakthrough bleeding persists in the first few cycles, though most patients will not require this. 1, 2, 3
NSAIDs for 5-7 days during any bleeding episodes provide additional pain control and modest reduction in menstrual blood loss. 2, 3
When to Reassess
Evaluate response at 3 months: If bleeding has not substantially improved or fibroids continue to grow despite therapy, surgical options (myomectomy, uterine artery embolization, or hysterectomy) should be reconsidered. 2, 9
Preoperative use is valuable: Even if surgery becomes necessary later, 3 months of Myfembree will reduce fibroid size and correct anemia, optimizing surgical outcomes. 2, 3, 9