Smith Matthew R
Harvard Medical School, Boston, MA, USA.
Nat Clin Pract Urol. 2005 Dec;2(12):608-15; quiz 628. doi: 10.1038/ncpuro0326.
The intended therapeutic effect of gonadotropin-releasing-hormone (GnRH) agonists is hypogonadism, which is a leading cause of osteoporosis in men. Observations are consistent with this effect: GnRH agonists decrease bone mineral density and increase fracture risk in men with prostate cancer. Estrogens play a central role in homeostasis of the normal male skeleton and evidence suggests that estrogen deficiency is primarily responsible for the adverse skeletal effects of GnRH agonists. The mechanism of treatment-related bone loss involves acceleration of physiologic bone turnover. In small, randomized, controlled trials, bisphosphonates (pamidronate, zoledronic acid) and selective estrogen-receptor modulators (raloxifene, toremifene) increased bone mineral density in GnRH-agonist-treated men. Two ongoing large, randomized, placebo-controlled studies will prospectively define fracture outcomes in men with prostate cancer and assess the efficacy of novel pharmacologic interventions (AMG 162, toremifene) in GnRH-agonist-treated men.
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。相关观察结果与这一效果相符：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。雌激素在正常男性骨骼的内环境稳定中起核心作用，有证据表明雌激素缺乏是GnRH激动剂产生不良骨骼影响的主要原因。与治疗相关的骨质流失机制涉及生理性骨转换加速。在小型随机对照试验中，双膦酸盐（帕米膦酸、唑来膦酸）和选择性雌激素受体调节剂（雷洛昔芬、托瑞米芬）可增加接受GnRH激动剂治疗男性的骨矿物质密度。两项正在进行的大型随机安慰剂对照研究将前瞻性地确定前列腺癌男性的骨折结局，并评估新型药物干预措施（AMG 162、托瑞米芬）对接受GnRH激动剂治疗男性的疗效。
