What is the best treatment option for a 34-year-old female with symptomatic uterine leiomyoma (uterine fibroids), experiencing heavy menstrual flow and severe abdominal cramping, currently taking a birth control pill with minimal improvement?

Treatment Recommendation for Symptomatic Uterine Fibroids with Failed Oral Contraceptive Therapy

For this 34-year-old woman with symptomatic uterine fibroids who has failed oral contraceptive therapy, initiating Myfembree (relugolix/estradiol/norethindrone acetate) 40-1-0.5 mg daily is an appropriate next-step medical therapy, combined with tranexamic acid for breakthrough bleeding, while awaiting pelvic ultrasound to guide definitive management decisions. 1, 2

Rationale for GnRH Antagonist Combination Therapy

• Myfembree represents the first-line oral medical option after failed hormonal contraceptives for heavy menstrual bleeding associated with uterine fibroids, as it substantially decreases menstrual bleeding and improves fibroid-related symptoms through competitive GnRH receptor antagonism. 2

• The fixed-dose combination of relugolix 40 mg with estradiol 1 mg and norethindrone acetate 0.5 mg achieves therapeutic estradiol concentrations that mitigate hypoestrogenic side effects (bone loss, vasomotor symptoms) while maintaining efficacy, enabling treatment duration up to 2 years without clinically meaningful bone density loss in most women. 3, 2

• GnRH antagonists reduce fibroid volume by approximately 35% and effectively control bleeding symptoms, making them superior to continued oral contraceptive therapy when initial hormonal management fails. 4, 5

Adjunctive Tranexamic Acid Protocol

• Tranexamic acid 1300 mg three times daily for 5 days during menstruation is appropriate for managing breakthrough bleeding episodes until amenorrhea is achieved with Myfembree. 4

• While tranexamic acid's role in fibroid-related bleeding remains somewhat unclear, it may help reduce menorrhagia through enhanced clot formation, though adverse effects including pelvic pain and fever can occur. 4

• Tranexamic acid should only be used during active bleeding days, not continuously, and must be discontinued if thromboembolic warning signs develop (leg pain, chest pain, shortness of breath, severe headache). 4

Critical Pre-Treatment Requirements

• Pelvic ultrasound must be completed before initiating Myfembree to evaluate fibroid size, location, number, and endometrial thickness, as this imaging will determine whether medical management is appropriate or if surgical intervention should be prioritized. 1

• The ultrasound is essential to rule out structural pathology and malignancy before starting hormonal treatment, particularly given her last imaging was 2 years ago. 1

• Pregnancy must be excluded before initiating GnRH antagonist therapy, as relugolix suppresses ovulation and prevents corpus luteum formation. 3

Expected Clinical Course and Monitoring

• Patients should expect irregular spotting for 1-2 months with likely amenorrhea by month 3, which represents the therapeutic goal for controlling heavy menstrual bleeding. 2

• Common side effects include hot flashes, headaches, and fatigue, though the add-back estrogen/progestin component minimizes these hypoestrogenic symptoms compared to GnRH agonist monotherapy. 3, 2

• Myfembree provides contraceptive effect through ovulation suppression, eliminating the need for separate birth control; the current oral contraceptive should be discontinued immediately before starting therapy. 3

Limitations and Alternative Considerations

• This medical approach serves as bridge therapy or long-term management for women not desiring immediate surgery, particularly useful for perimenopausal women transitioning to menopause while avoiding surgical intervention. 4

• GnRH antagonists have a significant drawback: once discontinued, fibroids typically return to their previous volume and symptoms recur, making this a temporizing rather than definitive treatment. 4

• If symptoms persist despite 3-6 months of Myfembree therapy, or if ultrasound reveals large fibroids (>5 cm) or concerning features, surgical options should be reconsidered, as medical management may be insufficient for significant fibroid burden. 4, 5

Surgical Alternatives if Medical Management Fails

• Hysterectomy remains the gold standard definitive treatment with satisfaction rates exceeding 90%, elimination of symptoms, and zero recurrence risk, though this is not appropriate for women desiring future fertility. 5

• Myomectomy should be offered as first therapeutic choice for women planning future pregnancy, with recurrence rates of 23-33% but preservation of reproductive potential; women should wait 2-3 months after myomectomy before attempting conception. 4, 5

• Uterine artery embolization (UAE) achieves 40-50% decrease in uterine volume with symptom control in approximately 80% of patients, but should not be first-line for women seeking pregnancy due to increased risks of miscarriage, cesarean sections, and postpartum hemorrhage. 5

Key Safety Monitoring

• Immediate medical attention is required for thromboembolic warning signs: severe headache, chest pain, leg pain, or shortness of breath, as GnRH antagonist therapy carries thrombotic risk. 3

• Follow-up assessment in 2-3 months is essential to evaluate symptom response, medication tolerance, and determine whether continued medical management is appropriate or if surgical intervention should be pursued. 4

• NSAIDs (ibuprofen 800 mg every 6-8 hours as needed) can be continued for breakthrough cramping and also provide additional menstrual blood flow reduction through prostaglandin inhibition. 4