Orr Rhonda, Fiatarone Singh Maria
School of Exercise and Sport Science, Faculty of Health Sciences, The University of Sydney, Sydney, Australia.
Drugs. 2004;64(7):725-50. doi: 10.2165/00003495-200464070-00004.
There has been increasing interest in the development of effective agents that can be safely used to promote anabolism in the clinical setting for patients with chronic wasting conditions as well as in the prevention and treatment of frailty associated with loss of muscle tissue in aging (sarcopenia). One such agent is the anabolic androgenic steroid (AAS) oxandrolone, which has been used in such clinical situations as HIV-related muscle wasting, severe burn injury, trauma following major surgery, neuromuscular disorders and alcoholic hepatitis for over 30 years. In the US, oxandrolone is the only AAS that is US FDA-approved for restitution of weight loss after severe trauma, major surgery or infections, malnutrition due to alcoholic cirrhosis, and Duchenne's or Becker's muscular dystrophy. Our review of the use of oxandrolone in the treatment of catabolic disorders, HIV and AIDS-related wasting, neuromuscular and other disorders provides strong evidence of its clinical efficacy. Improvements in body composition, muscle strength and function, status of underlying disease or recovery from acute catabolic injury and nutritional status are significant in the vast majority of well designed trials. However, oxandrolone has not yet been studied in sarcopenia.Unlike other orally administered C17alpha-alkylated AASs, the novel chemical configuration of oxandrolone confers a resistance to liver metabolism as well as marked anabolic activity. In addition, oxandrolone appears not to exhibit the serious hepatotoxic effects (jaundice, cholestatic hepatitis, peliosis hepatis, hyperplasias and neoplasms) attributed to the C17alpha-alkylated AASs. Oxandrolone is reported to be generally well tolerated and the most commonly documented adverse effects are transient elevations in transaminase levels and reductions in high density lipoprotein cholesterol level.However, optimal risk:benefit ratios for oxandrolone and other agents in its class will need to be refined before widespread clinical acceptance of AASs as a therapeutic option in sarcopenia and other chronic wasting conditions.
对于开发有效的药物，人们的兴趣与日俱增。这些药物可安全用于促进患有慢性消耗性疾病患者的合成代谢，以及预防和治疗与衰老过程中肌肉组织流失相关的虚弱症（肌肉减少症）。其中一种药物是合成代谢雄激素类固醇（AAS）氧雄龙，它已在诸如与HIV相关的肌肉消耗、严重烧伤、大手术后的创伤、神经肌肉疾病和酒精性肝炎等临床情况中使用了30多年。在美国，氧雄龙是唯一一种经美国食品药品监督管理局（FDA）批准用于严重创伤、大手术或感染后体重恢复、酒精性肝硬化所致营养不良以及杜氏或贝克氏肌营养不良症的AAS。我们对氧雄龙在治疗分解代谢紊乱、HIV和艾滋病相关消瘦、神经肌肉及其他疾病方面的应用进行的综述，为其临床疗效提供了有力证据。在绝大多数精心设计的试验中，身体成分、肌肉力量和功能、基础疾病状况或从急性分解代谢损伤中的恢复以及营养状况都有显著改善。然而，氧雄龙尚未在肌肉减少症中进行研究。与其他口服的C17α-烷基化AAS不同，氧雄龙的新型化学结构使其具有抗肝脏代谢能力以及显著的合成代谢活性。此外，氧雄龙似乎不会表现出归因于C17α-烷基化AAS的严重肝毒性作用（黄疸、胆汁淤积性肝炎、肝紫癜、增生和肿瘤）。据报道，氧雄龙总体耐受性良好，最常见的不良反应是转氨酶水平短暂升高和高密度脂蛋白胆固醇水平降低。然而，在AAS作为肌肉减少症和其他慢性消耗性疾病的治疗选择被广泛临床接受之前，需要进一步明确氧雄龙及同类其他药物的最佳风险效益比。
