Bhasin Shalender, Calof Olga M, Storer Thomas W, Lee Martin L, Mazer Norman A, Jasuja Ravi, Montori Victor M, Gao Wenqing, Dalton James T
Boston University School of Medicine, Boston, MA 02118, USA.
Nat Clin Pract Endocrinol Metab. 2006 Mar;2(3):146-59. doi: 10.1038/ncpendmet0120.
Several regulatory concerns have hindered development of androgens as anabolic therapies, despite unequivocal evidence that testosterone supplementation increases muscle mass and strength in men; it induces hypertrophy of type I and II muscle fibers, and increases myonuclear and satellite cell number. Androgens promote differentiation of mesenchymal multipotent cells into the myogenic lineage and inhibit their adipogenic differentiation, by facilitating association of androgen receptors with beta-catenin and activating T-cell factor 4. Meta-analyses indicate that testosterone supplementation increases fat-free mass and muscle strength in HIV-positive men with weight loss, glucocorticoid-treated men, and older men with low or low-normal testosterone levels. The effects of testosterone on physical function and outcomes important to patients have not, however, been studied. In older men, increased hematocrit and increased risk of prostate biopsy and detection of prostate events are the most frequent, testosterone-related adverse events. Concerns about long-term risks have restrained enthusiasm for testosterone use as anabolic therapy. Selective androgen-receptor modulators that are preferentially anabolic and that spare the prostate hold promise as anabolic therapies. We need more studies to determine whether testosterone or selective androgen-receptor modulators can induce meaningful improvements in physical function and patient-important outcomes in patients with physical dysfunction associated with chronic illness or aging.
尽管有明确证据表明补充睾酮可增加男性的肌肉量和力量，能诱导I型和II型肌纤维肥大，并增加肌核及卫星细胞数量，但一些监管方面的担忧阻碍了雄激素作为合成代谢疗法的发展。雄激素通过促进雄激素受体与β-连环蛋白结合并激活T细胞因子4，促进间充质多能细胞向肌源性谱系分化，并抑制其脂肪形成分化。荟萃分析表明，补充睾酮可增加体重减轻的HIV阳性男性、接受糖皮质激素治疗的男性以及睾酮水平低或低正常的老年男性的去脂体重和肌肉力量。然而，睾酮对身体功能以及对患者重要的结局的影响尚未得到研究。在老年男性中，血细胞比容升高以及前列腺活检风险增加和前列腺事件检测是最常见的与睾酮相关的不良事件。对长期风险的担忧抑制了将睾酮用作合成代谢疗法的热情。优先具有合成代谢作用且对前列腺影响较小的选择性雄激素受体调节剂有望成为合成代谢疗法。我们需要更多研究来确定睾酮或选择性雄激素受体调节剂是否能在患有与慢性疾病或衰老相关的身体功能障碍的患者中诱导身体功能和对患者重要的结局有有意义的改善。
