What medical therapies can shrink uterine fibroids in a premenopausal woman with heavy menstrual bleeding and pelvic pain who is not pregnant and has no severe osteoporosis, active liver disease, or known drug hypersensitivity?

Medical Therapies to Shrink Uterine Fibroids

For premenopausal women with symptomatic fibroids, oral GnRH antagonists (relugolix, elagolix, or linzagolix) combined with low-dose estrogen/progestin add-back therapy represent the most effective medical option for reducing both fibroid volume and bleeding symptoms. 1

First-Line Medical Options

GnRH Antagonists with Add-Back Therapy (Most Effective)

• Initiate oral GnRH antagonist therapy (relugolix, elagolix, or linzagolix) as the primary medical treatment for fibroid volume reduction, as these agents are FDA-approved and significantly shrink fibroids while controlling heavy menstrual bleeding. 2, 1

• Always prescribe concurrent low-dose estrogen/progestin add-back therapy (such as estradiol/norethisterone acetate) to prevent severe hypoestrogenic side effects including hot flashes, headaches, hypertension, and bone mineral density loss. 1, 3

• GnRH antagonists can be used safely for up to 24 months with add-back therapy without clinically meaningful bone loss in most women. 1

• Expect significant fibroid volume reduction along with rapid control of bleeding symptoms when using this combination therapy. 1

GnRH Agonists (Alternative Option)

• GnRH agonists reduce fibroid volume by 18-30% and are effective second-line options, though they produce similar hypoestrogenic effects requiring add-back therapy for tolerability. 3

• Limit GnRH agonist monotherapy (without add-back) to a maximum of 3-6 months due to severe hypoestrogenic symptoms and significant bone density loss. 2, 3, 4

• A 3-month preoperative course of GnRH agonist therapy optimally balances fibroid volume reduction with minimizing side effects when surgery is planned. 3

Selective Progesterone Receptor Modulators (SPRMs)

Ulipristal Acetate

• Ulipristal acetate effectively reduces both bleeding and bulk symptoms, induces amenorrhea within approximately 7 days, and produces persistent fibroid volume reduction that continues after treatment cessation. 2, 5

• Randomized controlled trials demonstrate efficacy for both continuous use up to 3 months and intermittent use for 2 years, with superiority over placebo and comparable efficacy to GnRH agonists. 2

• Critical caveat: Ulipristal acetate is not approved in the United States due to reports of hepatotoxicity, limiting its use despite strong efficacy data. 2, 3

• This agent remains available in some countries outside the United States where it represents a viable SPRM option. 4

Adjunctive and Less Effective Options

Hormonal Contraceptives

• Combined oral contraceptives and levonorgestrel-releasing intrauterine devices are considered first-line therapy primarily for controlling bleeding symptoms in patients with small fibroids, but do not produce significant fibroid volume reduction. 1, 6

• The evidence for oral contraceptive pills in fibroid management is mixed and contradictory, with studies showing reduced, similar, or even increased risk of fibroid growth. 1

• Standard formulations containing 20-30 μg ethinyl estradiol with progestin are appropriate, though these agents address symptoms rather than shrinking fibroids. 6

Non-Hormonal Adjuncts

• Tranexamic acid reduces menstrual blood loss but does not shrink fibroids; it serves as a useful adjunct when breakthrough bleeding persists despite hormonal therapy. 2, 1

• NSAIDs provide analgesia and modestly decrease menstrual blood loss when used for 5-7 days during bleeding episodes, but have no effect on fibroid size. 1

• Iron supplementation should be initiated immediately in patients with anemia from chronic bleeding while definitive fibroid therapy takes effect. 1

Treatment Algorithm

Step 1: Assess Treatment Goals

• Determine whether the patient desires future fertility, as GnRH antagonists suppress fertility during treatment (though this is reversible after discontinuation). 1

• Consider the patient's age relative to menopause, as women in their mid-40s may achieve symptom control with medical therapy until natural menopause causes fibroid regression. 1, 6

Step 2: Initiate Primary Therapy

• Start oral GnRH antagonist with add-back therapy as first-line medical treatment for fibroid volume reduction, particularly when fibroids are large or causing significant bulk symptoms. 1

• For patients with contraindications to GnRH antagonists or those with small fibroids and primarily bleeding symptoms, consider levonorgestrel IUD or combined oral contraceptives as initial therapy. 1, 6

Step 3: Add Adjunctive Measures

• Prescribe iron supplementation for anemia correction. 1

• Add tranexamic acid if breakthrough bleeding persists despite adequate hormonal therapy. 1

• Recommend NSAIDs for pain control during bleeding episodes. 1

Step 4: Monitor Response and Adjust

• If medical management fails after 3-6 months (persistent symptoms or continued fibroid growth), transition to surgical or interventional options including uterine artery embolization, MR-guided focused ultrasound, myomectomy, or hysterectomy. 1

• Preoperative GnRH therapy for 3 months can reduce fibroid size and correct anemia before eventual surgery if medical management proves inadequate. 1, 3

Important Clinical Caveats

Fertility Considerations

• All GnRH agonists and antagonists suppress fertility during active treatment, and symptoms typically recur rapidly after medication discontinuation. 1, 3

• Patients desiring near-future pregnancy should not receive GnRH antagonist therapy due to reversible fertility suppression. 1

Bone Health Monitoring

• Never use GnRH agonist or antagonist monotherapy beyond a few months without add-back therapy, as this leads to severe hypoestrogenic symptoms and significant bone mineral density loss. 1, 3

• With appropriate add-back therapy, treatment can continue for up to 24 months without clinically meaningful bone loss in most patients. 1

Hepatotoxicity Risk

• While ulipristal acetate shows excellent efficacy, its hepatotoxicity risk has prevented FDA approval in the United States, making it unavailable for routine use despite favorable data from randomized trials. 2, 3

Natural History Considerations

• Fibroids naturally shrink after menopause due to decreased circulating estrogen, so medical therapy may successfully bridge perimenopausal women to menopause and avoid surgery entirely. 2, 1