What are the management options for a 44-year-old woman with one month of heavy menstrual bleeding, multiple large intramural fibroids involving the anterior and posterior myometrium on ultrasound, and dysmenorrhea treated with dienazest 2 mg daily?

Management of Heavy Menstrual Bleeding with Multiple Large Intramural Fibroids on Failed Dienogest Therapy

Given that dienogest has failed to control bleeding after one month, you should immediately switch to an oral GnRH antagonist (relugolix, elagolix, or linzagolix) with estrogen-progestin add-back therapy while simultaneously correcting anemia with iron supplementation. 1, 2, 3

Immediate Medical Management Algorithm

Step 1: Initiate GnRH Antagonist Therapy with Add-Back

• Start an oral GnRH antagonist (relugolix, elagolix, or linzagolix) as these agents are the most effective medical option when first-line therapies like dienogest fail, significantly reducing both bleeding symptoms and fibroid volume. 1, 2
• Simultaneously add low-dose estrogen/progestin add-back therapy (such as estradiol/norethisterone acetate) to mitigate hypoestrogenic side effects including hot flushes, headaches, and bone mineral density loss. 4, 1, 2
• This combination is FDA-approved specifically for fibroid-related heavy menstrual bleeding and can be used for up to 2 years without clinically meaningful bone loss in most women. 4, 2

Step 2: Correct Anemia and Add Adjunctive Therapies

• Begin iron supplementation immediately to correct anemia from chronic bleeding while the GnRH antagonist takes effect. 2, 3, 5
• Add tranexamic acid as a nonhormonal adjunct if breakthrough bleeding persists, as it effectively reduces menstrual blood loss in patients with fibroids. 4, 1, 2
• Consider NSAIDs for 5-7 days during bleeding episodes for pain control and modest reduction in menstrual blood loss. 4, 1, 2

Why Dienogest Failed and What This Means

The evidence for progestin-only therapies like dienogest in fibroid management is mixed, with studies showing variable efficacy and no clear patterns of effectiveness. 2 Combined hormonal contraceptives and progestin-only options are considered first-line therapy primarily for patients with small fibroids and mild bleeding symptoms, not for multiple large intramural fibroids. 2 Your patient's failure on dienogest after one month indicates the need for more aggressive medical therapy.

Timeline and Monitoring Strategy

• Reassess response at 3 months: GnRH antagonists typically show significant improvement in bleeding symptoms and fibroid volume reduction by this timepoint. 2, 3
• If medical management fails after 3-6 months, or if fibroids continue to grow despite therapy, surgical options must be reconsidered. 2, 3
• Fertility is suppressed during GnRH antagonist treatment, and symptoms typically recur rapidly after cessation of therapy. 4, 1

Surgical Options if Medical Management Fails

For Women Desiring Uterine Preservation

• Laparoscopic or open myomectomy is the preferred surgical approach for multiple large intramural fibroids when fertility preservation or uterine preservation is desired, though it carries potential for further intervention. 3, 5, 6
• Uterine artery embolization (UAE) can be considered if medical management fails, with an average decrease in fibroid size of >50% at 5 years, though patients should be counseled that fecundity and pregnancy may be impacted. 3, 5
• MR-guided focused ultrasound (MRgFUS) is another non-surgical option showing significant improvement in quality of life and 18% decrease in fibroid diameter, though long-term data are lacking. 3, 7

For Women Not Desiring Future Fertility

• Hysterectomy by the least invasive approach possible provides definitive treatment and is associated with high levels of patient satisfaction, accounting for three-quarters of fibroid treatment in the United States. 4, 5, 6

Critical Pitfalls to Avoid

• Do not continue ineffective therapy: One month of persistent bleeding on dienogest is sufficient evidence of treatment failure; prolonging ineffective therapy worsens anemia and quality of life. 8, 7
• Do not use GnRH antagonists without add-back therapy long-term: This leads to significant bone mineral density loss and severe hypoestrogenic symptoms. 4, 1
• Do not delay iron supplementation: Anemia correction should begin immediately, not after bleeding is controlled. 2, 3, 5
• Counsel about fertility suppression: If the patient desires pregnancy in the near future, GnRH antagonists may not be appropriate as fertility is suppressed during treatment. 4, 1

Special Consideration for This 44-Year-Old Patient

At age 44, this patient is approaching menopause when fibroids naturally shrink due to decreased circulating estrogen. 4 If she can achieve symptom control with GnRH antagonist therapy for the next few years, she may avoid surgery entirely as fibroids will likely regress after menopause. 4, 9 However, if she has completed childbearing and desires definitive treatment, hysterectomy offers permanent cure with high satisfaction rates. 4, 5, 6