Department of Medicine Austin Health, University of Melbourne, 145 Studley Road, Heidelberg, Victoria 3084, Australia Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia.
J Endocrinol. 2014 Jan 27;220(3):R37-55. doi: 10.1530/JOE-13-0393. Print 2014 Mar.
A wealth of observational studies show that low testosterone is associated with insulin resistance and with an increased risk of diabetes and the metabolic syndrome. Experimental studies have identified potential mechanisms by which low testosterone may lead to insulin resistance. Visceral adipose tissue is an important intermediate in this relationship. Actions of testosterone or its metabolite oestradiol on other tissues such as muscle, liver, bone or the brain, and body composition-independent effects may also play a role. However, definitive evidence from randomised controlled trials (RCTs) to clarify whether the association of low testosterone with disordered glucose metabolism is causative is currently lacking. It therefore remains possible that this association is due to reverse causation, or simply originates by association with common health and lifestyle factors. RCTs of testosterone therapy in men with or without diabetes consistently show modest metabolically favourable changes in body composition. Despite this, testosterone effects on glucose metabolism have been inconsistent. Recent evidence suggests that the hypothalamic-pituitary-testicular axis suppression in the majority of obese men with metabolic disorders is functional, and may be, at least in part, reversible with weight loss. Until further evidence is available, lifestyle measures with emphasis on weight reduction, treatment of comorbidities and optimisation of diabetic control should remain the first-line treatment in these men. Such measures, if successful, may be sufficient to normalise testosterone levels in men with metabolic disorders, who typically have only modest reductions in circulating testosterone levels.
大量观察性研究表明，低睾酮与胰岛素抵抗以及糖尿病和代谢综合征的风险增加有关。实验研究已经确定了低睾酮可能导致胰岛素抵抗的潜在机制。内脏脂肪组织是这种关系中的一个重要中间环节。睾酮或其代谢产物雌二醇对肌肉、肝脏、骨骼或大脑等其他组织的作用，以及与身体成分无关的作用，也可能发挥作用。然而，目前缺乏来自随机对照试验（RCT）的明确证据来澄清低睾酮与葡萄糖代谢紊乱之间的关联是否具有因果关系。因此，仍然有可能这种关联是由于反向因果关系，或者仅仅是由于与常见的健康和生活方式因素有关。在有或没有糖尿病的男性中进行的睾酮治疗 RCT 一致显示出适度的代谢有益的身体成分变化。尽管如此，睾酮对葡萄糖代谢的影响一直不一致。最近的证据表明，大多数患有代谢紊乱的肥胖男性的下丘脑-垂体-睾丸轴抑制是功能性的，并且至少部分可能随着体重减轻而逆转。在进一步的证据出现之前，生活方式措施应侧重于减肥、治疗合并症和优化糖尿病控制，这些措施仍然是这些男性的一线治疗方法。如果这些措施成功，可能足以使患有代谢紊乱的男性的睾酮水平正常化，这些男性通常只有循环睾酮水平适度降低。
