Endometriosis—Endometriosis is defined as the presence of estrogen-sensitive endometrium outside the uterus that results in cyclical abdominal pain in premenopausal women. The pain of endometriosis is often reduced by abolishing exposure to the cyclical changes in the concentrations of estrogen and progesterone that are a normal part of the menstrual cycle. The ovarian suppression induced by continuous treatment with a GnRH agonist greatly reduces estrogen and progesterone concentrations and prevents cyclical changes. The preferred duration of treatment with a GnRH agonist is limited to 6 months because ovarian suppression beyond this period can result in decreased bone mineral density. When relief of pain from treatment with a GnRH agonist supports continued therapy for more than 6 months, the addition of add-back therapy (estrogen or progestins) reduces or eliminates GnRH agonistinduced bone mineral loss and provides symptomatic relief without reducing the efficacy of pain relief. Leuprolide and goserelin are administered as depot preparations that provide 1 or 3 months of continuous GnRH agonist activity. Nafarelin is administered twice daily as a nasal spray at a dose of 0.2 mg per spray.
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Uterine leiomyomata (uterine fibroids)—Uterine leiomyomata are benign, estrogen-sensitive, smooth muscle tumors in the uterus that can cause menorrhagia, with associated anemia and pelvic pain. Treatment for 3–6 months with a GnRH agonist reduces fibroid size and, when combined with supplemental iron, improves anemia. The effects of GnRH agonists are temporary, with gradual recurrent growth of leiomyomas to previous size within several months after cessation of treatment. GnRH agonists have been used widely for preoperative treatment of uterine leiomyomas, both for myomectomy and hysterectomy. GnRH agonists have been shown to improve hematologic parameters, shorten hospital stay, and decrease blood loss, operating time, and postoperative pain when given for 3 months preoperatively.
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Prostate cancer—Androgen deprivation therapy is the primary medical therapy for prostate cancer. Combined antiandrogen therapy with continuous GnRH agonist and an androgen receptor antagonist is as effective as surgical castration in reducing serum testosterone concentrations and effects. Leuprolide, goserelin, histrelin, buserelin, and triptorelin are approved for this indication. The preferred formulation is one of the long-acting depot forms that provide 1, 3, 4, 6, or 12 months of active drug therapy. During the first 7–10 days of GnRH analog therapy, serum testosterone levels increase because of the agonist action of the drug; this can precipitate pain in patients with bone metastases, and tumor growth and neurologic symptoms in patients with vertebral metastases. It can also temporarily worsen symptoms of urinary obstruction. Such tumor flares can usually be avoided with the concomitant administration of an androgen receptor antagonist (flutamide, bicalutamide, or nilutamide) (see Chapter 40). Within about 2 weeks, serum testosterone levels fall to the hypogonadal range.
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