A 38-year-old woman with symptomatic uterine fibroids (heavy menstrual bleeding and dysmenorrhea) desires uterine-sparing treatment before considering hysterectomy. She has no contraindications to hormonal therapy. What is the drug of choice for medical management of her fibroids?

Explanation

## Medical Management of Symptomatic Uterine Fibroids **Key Point:** GnRH agonists (leuprolide, goserelin, nafarelin) are the gold-standard pharmacological agents for preoperative shrinkage and symptom relief in women with symptomatic fibroids awaiting surgery or desiring uterine preservation. ### Mechanism of Action GnRH agonists cause: 1. Initial FSH/LH surge (flare effect) 2. Downregulation of pituitary GnRH receptors 3. Profound hypogonadism → estrogen/progesterone withdrawal 4. Fibroid involution (20–40% volume reduction in 3 months) 5. Menstrual suppression and symptom relief ### Clinical Use in Fibroid Management | Indication | Benefit | |---|---| | Preoperative (3 months before myomectomy) | Reduces fibroid size, decreases operative blood loss, facilitates minimally invasive approach | | Preoperative (before hysterectomy) | Reduces bleeding, improves hemoglobin, reduces transfusion risk | | Bridge therapy | Symptom control while awaiting definitive surgery | | Perimenopausal women | Symptom relief until natural menopause | **High-Yield:** Standard dosing is leuprolide 3.75 mg IM monthly or 11.25 mg IM every 3 months. Duration is typically 3–6 months (limited by bone loss and hypogonadal side effects). ### Side Effects & Limitations - Hot flushes, vaginal dryness, mood changes (hypogonadism) - Bone loss (1–3% per month) — limit use to ≤6 months - Cost - Flare effect in first 1–2 weeks (can be mitigated with add-back therapy: norethisterone 5 mg daily or conjugated estrogens) **Clinical Pearl:** Add-back therapy (low-dose estrogen + progestin) is used in women on prolonged GnRH agonist therapy to reduce vasomotor and bone loss side effects without compromising fibroid shrinkage. ### Newer Agents (Selective Progesterone Receptor Modulators) Mifepristone and ulipristal acetate (SPRM) are emerging alternatives that: - Cause fibroid shrinkage without hypogonadal side effects - Preserve bone density - Are not yet first-line in most guidelines but are increasingly used off-label or in clinical trials [cite:Berek & Novak's Gynecology 16e Ch 18; ACOG Practice Bulletin 228]