Smith Matthew R
Rev Urol. 2005;7 Suppl 3(Suppl 3):S30-5.
The intended therapeutic effect of gonadotropin-releasing hormone (GnRH) agonists is hypogonadism, which is a leading cause of osteoporosis in men. Consistent with this observation, GnRH agonists decrease bone mineral density and increase fracture risk in men with prostate cancer. GnRH agonists markedly decrease serum levels of both testosterone and estrogen. Estrogens play a central role in homeostasis of the normal male skeleton, and the available evidence suggests that estrogen deficiency rather than testosterone deficiency accounts for the adverse skeletal effects of GnRH agonists. The central role of estrogens in male bone metabolism provides a strong rationale to evaluate selective estrogen receptor modulators for prevention of treatment-related osteoporosis in men with prostate cancer. Preliminary evidence suggests that both raloxifene and toremifene increase bone mineral density in GnRH agonist-treated men. An ongoing pivotal study will evaluate the effects of toremifene on fractures and other complications of GnRH agonists in men with prostate cancer.
促性腺激素释放激素（GnRH）激动剂的预期治疗效果是性腺功能减退，这是男性骨质疏松症的主要原因。与这一观察结果一致，GnRH激动剂会降低前列腺癌男性的骨矿物质密度并增加骨折风险。GnRH激动剂会显著降低睾酮和雌激素的血清水平。雌激素在正常男性骨骼的稳态中起核心作用，现有证据表明，GnRH激动剂对骨骼的不良影响是由雌激素缺乏而非睾酮缺乏所致。雌激素在男性骨代谢中的核心作用为评估选择性雌激素受体调节剂预防前列腺癌男性治疗相关骨质疏松症提供了有力依据。初步证据表明，雷洛昔芬和托瑞米芬均可增加接受GnRH激动剂治疗男性的骨矿物质密度。一项正在进行的关键研究将评估托瑞米芬对前列腺癌男性GnRH激动剂所致骨折及其他并发症的影响。
