Medical Management of Uterine Fibroids (Leiomyomas)

Note: Shaw's Textbook of Gynaecology is not available in the library. The following is drawn from Berek & Novak's Gynecology and Katzung's Basic & Clinical Pharmacology, which are the most authoritative available sources covering this topic in full detail.

Overview of Treatment Approach

1. Watchful waiting
2. Medical therapy
3. Surgical treatment (myomectomy, hysterectomy)
4. Minimally invasive procedures (UAE, focused ultrasound)

Watchful Waiting

• Not having treatment rarely results in harm, except in women with:
  • Severe anemia from heavy menstrual bleeding
  • Hydronephrosis from ureteric obstruction
• Average fibroid volume increases ~9% per year (range: −25% to +138%); 7% of fibroids regress spontaneously
• A nonrandomized study found that 77% of women who chose watchful waiting had no significant changes in bleeding, pain, or bothersome symptoms at 1 year
• Perimenopausal women: Short-term observation is reasonable because after menopause, bleeding stops and fibroids decrease in size

Medical Therapy

1. NSAIDs (Nonsteroidal Anti-Inflammatory Drugs)

• Not effective for heavy menstrual bleeding in fibroid patients
• A double-blind placebo-controlled study of 25 women (11 with fibroids) showed a 36% decrease in blood loss in idiopathic heavy menstrual bleeding, but no decrease in women with fibroids
• No further studies have examined this treatment

2. Tranexamic Acid

• A synthetic antifibrinolytic agent
• Dose: 1.3 g three times a day for 3–5 days during menstrual bleeds
• A pooled analysis of two randomized, double-blind, placebo-controlled studies found significantly reduced menstrual blood loss vs. placebo, maintained across three treatment cycles (p <0.001)
• Side effects: Headache (55%), nausea (15%)
• Note: Results may not generalize to women with markedly enlarged fibroids requiring surgery

3. Gonadotropin-Releasing Hormone Agonists (GnRH-a)

Effects

• Reduces fibroid volume by ~30% and total uterine volume by ~35% after 6 months of monthly injections
• Volume reduction occurs mostly within the first 3 months
• Heavy menstrual bleeding resolved in 37/38 women (97%) by 6 months

Limitations

• After discontinuation: menses returns in 4–8 weeks and uterine size returns to pretreatment levels within 4–6 months
• 64% of women remained asymptomatic 8–12 months after treatment

Side Effects (occur in 95% of women)

Add-back Therapy

• Low-dose estrogen + progestin added to reduce side effects, inhibit bone loss, and allow longer use
• Long-term use (6 years) showed a wide range of bone density reduction; no difference in bone loss between those given add-back vs. GnRH-a alone

Use in Perimenopausal Women

• In late perimenopause: short-term GnRH-a for 6 months is appropriate
• In one study of 34 women: 31/34 avoided surgery, 15 entered natural menopause

Urinary Symptoms

• GnRH-a with 55% reduction in uterine volume: urinary frequency, nocturia, and urgency all decreased (no change in stress/urge incontinence)

4. GnRH Antagonists

• Ganirelix (daily SC injection): produces an immediate antagonist effect
• Results in a 29% reduction in fibroid volume within 3 weeks — faster than GnRH agonists
• Accompanied by hypoestrogenic symptoms
• Elagolix (oral, non-peptide GnRH antagonist): FDA-approved in 2018 for moderate-to-severe pain of endometriosis; undergoing phase III trials for heavy menstrual bleeding and pain associated with uterine leiomyoma, with and without add-back therapy
• Side effects: hot flush, night sweats, headache, mood swings (mostly mild to moderate)
• When long-acting compounds become available, GnRH antagonists may be preferred for preoperative use

5. Mifepristone (Antiprogestin)

• A progesterone-blocking drug that reduces uterine size similarly to GnRH-a
• A prospective RCT found a 48% decrease in mean uterine volume after 6 months
• Risk: Unopposed estrogen exposure may lead to endometrial hyperplasia
  • A systematic review found hyperplasia in 10/36 (28%) women screened with endometrial biopsy

6. Ulipristal Acetate (UPA)

Mechanism

• Modulates progesterone signaling pathway
• Promotes remodeling of extracellular matrix and reduces collagen synthesis

Clinical Evidence

• Largest study: 451 women with symptomatic fibroids and heavy menstrual bleeding
• Four repeated 12-week courses of daily UPA 5 mg or 10 mg
• Amenorrhea achieved in ≥70% of women, usually within 1 week
• Bleeding controlled in ≥73%
• Hemoglobin levels increased and maintained
• By the 4th treatment course: ~80% had >25% reduction in volume of the three largest fibroids
• Significant improvement in pain and quality of life
• 6 cases of hyperplasia — all returned to normal endometrium during the study

Advantages

• E2 levels remain well above postmenopausal levels → bone mineral density not adversely affected
• Side effects: headache and hot flushes in 11% (mostly mild/moderate)

7. Levonorgestrel-Releasing Intrauterine System (LNG-IUS / Mirena)

• A reasonable treatment for selected women with fibroid-associated heavy menstrual bleeding
• A systematic review of 11 studies concluded:
  • Significantly reduced menstrual blood loss
  • Increased hemoglobin and ferritin levels
  • Did NOT decrease fibroid volume
• Expulsion rates:
  • 15.4% with fibroids >3 cm
  • Only 6.3% with fibroids <3 cm
  • Unrelated to fibroid location

8. Alternative Medicine

• A Chinese herbal medicine (kuei-chi-fu-ling-wan) for ≥12 weeks in 110 women with fibroids <10 cm:
  • Complete resolution in 19%, decrease in 43%, no change in 34%, increase in 4%
  • Heavy menstrual bleeding improved in 95%, dysmenorrhea improved in 94%
  • 14% ultimately required hysterectomy
• Evidence is weak (uncontrolled studies); selection bias likely

Preoperative Medical Treatment for Anemia

Summary Table