Kastelan Darko, Giljevic Zlatko, Kraljevic Ivana, Korsic Mirko
Division of Endocrinology, Department of Internal Medicine, University Hospital Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia.
Med Hypotheses. 2006;67(5):1052-3. doi: 10.1016/j.mehy.2006.04.040. Epub 2006 Jun 21.
More recently, osteoporosis in men has been recognized as an important public health problem. Bone loss begins in mid life and is associated with the decline of the sex steroids production. Although there is no equivalent of the menopause, gonadal function in men is affected in a slow progressive way leading to hypogonadism. Testosterone, the major androgen in men, exerts its effect on bone by local conversion to 5alpha-dihydrotestosterone or by aromatization to estrogens. Several studies have found that estrogen, rather than testosterone, levels are more closely correlated with BMD in elderly men. Selective estrogen receptor modulator (SERM) raloxifene binds to estrogen receptors and exhibit estrogenic effect in bone, but, contrary to estrogen, without feminizing effect. There are limited numbers of studies investigating the effects of SERMs in males. Animal studies demonstrated that SERMs inhibit bone turnover and prevent bone loss in orchidectomised adult male rats. Raloxifene has been shown to increase bone mineral density of the hip in men receiving androgen deprivation therapy for prostate cancer. Moreover, experimental data demonstrated dramatic increase in cell death in human prostate cancer cell lines after the treatment with raloxifene. All these observations suggest that SERMs may be useful for the prevention and treatment of osteoporosis not only in postmenopausal women but also in elderly men. However, our hypothesis should be tested in a proper designed clinical trial. Several important issues have to be addressed. Does the same drug dose that has been shown to be effective in postmenopausal women should be used in men, too? Does treatment with SERMs reduce the fracture risk in men and is it comparable to that observed in women? Does treatment with SERMs have any beneficial effect on cardiovascular system and prostate cancer? And finally, do men experience adverse events other than women treated with SERMs? Answering to these questions will have great impact in getting the decision of possible SERMs usage in the treatment of osteoporosis in elderly males.
近年来，男性骨质疏松症已被公认为一个重要的公共卫生问题。骨质流失始于中年，与性类固醇分泌减少有关。虽然男性没有相当于女性绝经的情况，但其性腺功能会以缓慢渐进的方式受到影响，导致性腺功能减退。睾酮是男性主要的雄激素，它通过局部转化为5α - 双氢睾酮或芳香化转化为雌激素对骨骼发挥作用。多项研究发现，在老年男性中，雌激素水平而非睾酮水平与骨密度的相关性更强。选择性雌激素受体调节剂（SERM）雷洛昔芬与雌激素受体结合，在骨骼中表现出雌激素样作用，但与雌激素不同的是，它没有女性化作用。研究SERM对男性影响的研究数量有限。动物研究表明，SERM可抑制去势成年雄性大鼠的骨转换并预防骨质流失。雷洛昔芬已被证明可增加接受前列腺癌雄激素剥夺治疗的男性的髋部骨矿物质密度。此外，实验数据表明，用雷洛昔芬治疗后，人类前列腺癌细胞系中的细胞死亡显著增加。所有这些观察结果表明，SERM不仅对绝经后女性，而且对老年男性的骨质疏松症预防和治疗可能都有用。然而，我们的假设应在一项设计合理的临床试验中进行检验。有几个重要问题必须解决。在男性中是否也应使用已证明对绝经后女性有效的相同药物剂量？SERM治疗是否能降低男性的骨折风险，其效果与女性相比如何？SERM治疗对心血管系统和前列腺癌是否有任何有益作用？最后，男性使用SERM后是否会出现与女性不同的不良事件？回答这些问题将对决定是否可能使用SERM治疗老年男性骨质疏松症产生重大影响。
