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LHRH agonists such as leuprolide, goserelin, and buserelin will lower testosterone to castrate levels. Like orchiectomy and estrogens, LHRH agonists cause impotence, hot flashes, and loss of libido. Tumor flare reactions may occur transiently but can be prevented by antiandrogens or by short-term estrogens at low dose for several weeks. There is conflicting evidence regarding whether LHRH agonists are associated with increased risk of cardiovascular morbidity or mortality.[78]

The pure antiandrogen flutamide may cause diarrhea, breast tenderness, and nausea. Case reports show fatal and nonfatal liver toxic effects.[79] Bicalutamide may cause nausea, breast tenderness, hot flashes, loss of libido, and impotence.[80] (For information on diarrhea, refer to the Gastrointestinal Complications summary; refer to the Nausea and Vomiting and the Fever, Sweats, and Hot Flashes summaries; and for information on loss of libido and impotence, refer to the Sexuality and Reproductive Issues summary.) The steroidal antiandrogen megestrol acetate suppresses androgen production incompletely and is generally not used as initial therapy.

Long-term use of ketoconazole can result in impotence, pruritus, nail changes, and adrenal insufficiency. (Refer to the PDQ summary on Pruritus for more information.) Aminoglutethimide commonly causes sedation and skin rashes. A national Medicare survey of men who had undergone radical prostatectomy for prostate cancer showed a decrease in all seven health-related quality-of-life measures (impact of cancer and treatment, concern regarding body image, mental health, general health, activity, worries about cancer and dying, and energy) in men who had received androgen-depletion therapy (either medically or surgically induced) versus those who had not.[81][Level of evidence: 3iC] Additional studies that evaluate the effects of various hormone therapies on quality of life are required.[82]

Androgen-deprivation therapy also can cause osteoporosis and bone fractures. In a population-based sample of 50,613 Medicare patients aged 66 years or older followed for a median of 5.1 years, men who had been treated with either a gonadotropin-releasing hormone (GnRH) or orchiectomy had a 19.4% bone fracture rate compared to 12.6% in men who had not received hormone-deprivation therapy. The effect was similar in men whether or not they had metastatic bone disease.[83] A small nonblinded study with short follow-up suggests that the bisphosphonate pamidronate can prevent bone loss in men receiving a GnRH agonist for prostate cancer.[84] Forty-seven prostate cancer patients (41 evaluable) with locally advanced prostate cancer, but with no known bone metastases, were randomly assigned to receive 3-monthly depot leuprolide with or without pamidronate (60 mg intravenously). No bone fractures were reported in either group. The use of surrogate endpoints and unblinded assessment of endpoints makes it difficult to know with certainty whether pamidronate use would prevent fractures.[84][Level of evidence: 1iiDiii]

The use of androgen deprivation therapy has also been associated with an increased risk of colorectal cancer. Using the SEER Medicare database, investigators assessed the risk of subsequent colorectal cancer in 107,859 men aged 67 years and older after an initial diagnosis of prostate cancer.[85] The rates of colorectal cancer per 1,000 person-years were 6.3 (95% CI, 5.3-7.5) in men who had orchiectomy, 4.4 (95% CI, 4.0-4.9) in men treated with GnRH agonists, and 3.7 (95% CI, 3.5-3.9) in men who had no androgen deprivation. In men treated with GnRH agonists, the risk increased with increasing duration of treatment (P for trend = .01).


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Last Updated: May 16, 2012
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