Department of Medicine Austin Health, University of Melbourne, Heidelberg, Vic, Australia.
Department of Endocrinology, Austin Health, Heidelberg, Vic, Australia.
Clin Endocrinol (Oxf). 2018 Jul;89(1):11-21. doi: 10.1111/cen.13723. Epub 2018 May 16.
Obesity, increasing in prevalence globally, is the clinical condition most strongly associated with lowered testosterone concentrations in men and presents as one of the strongest predictors of receiving testosterone treatment. While low circulating total testosterone concentrations in modest obesity primarily reflect reduced concentrations of sex hormone binding globulin, more marked obesity can lead to genuine hypothalamic-pituitary-testicular axis (HPT) suppression. HPT axis suppression is likely mediated via pro-inflammatory cytokine and dysregulated leptin signalling and aggravated by associated comorbidities. Whether oestradiol-mediated negative hypothalamic-pituitary feedback plays a pathogenic role requires further study. Although the obesity-hypogonadism relationship is bidirectional, the effects of obesity on testosterone concentrations are more substantial than the effects of testosterone on adiposity. In markedly obese men submitted to bariatric surgery, substantial weight loss is very effective in reactivating the HPT axis. In contrast, lifestyle measures are less effective in reducing weight and generally only associated with modest increases in circulating testosterone. In randomized controlled clinical trials (RCTs), testosterone treatment does not reduce body weight, but modestly reduces fat mass and increases muscle mass. Short-term studies have shown that testosterone treatment in carefully selected obese men may have modest benefits on symptoms of androgen deficiency and body composition even additive to diet alone. However, longer term, larger RCTs designed for patient-important outcomes and potential risks are required. Until such trials are available, testosterone treatment cannot be routinely recommended for men with obesity-associated nonclassical hypogonadism. Lifestyle measures or where indicated bariatric surgery to achieve weight loss, and optimization of comorbidities remain first line.
肥胖症在全球范围内的发病率不断上升，是与男性睾丸酮浓度降低关系最密切的临床病症，也是接受睾丸酮治疗的最强预测因素之一。虽然适度肥胖症中循环总睾丸酮浓度降低主要反映了性激素结合球蛋白浓度降低，但更为明显的肥胖症可能导致真正的下丘脑-垂体-睾丸轴（HPT）抑制。HPT 轴抑制可能是通过促炎细胞因子和失调的瘦素信号传导介导的，并因相关合并症而加重。雌激素介导的负反馈下丘脑-垂体是否在发病机制中起作用还需要进一步研究。尽管肥胖症与性腺功能减退症之间存在双向关系，但肥胖症对睾丸酮浓度的影响大于睾丸酮对肥胖的影响。在接受减肥手术的明显肥胖症男性中，大量体重减轻非常有效地使 HPT 轴重新活跃。相比之下，生活方式措施在减轻体重方面效果较差，通常仅与循环睾丸酮的适度增加相关。在随机对照临床试验（RCT）中，睾丸酮治疗不会减轻体重，但会适度减少脂肪量并增加肌肉量。短期研究表明，在精心挑选的肥胖男性中，睾丸酮治疗即使单独饮食，也可能对雄激素缺乏症和身体成分的症状有适度的益处。然而，需要进行设计用于患者重要结局和潜在风险的更长期、更大规模的 RCT。在这些试验可用之前，不能常规推荐睾丸酮治疗用于与肥胖相关的非典型性腺功能减退症患者。生活方式措施或在有指征的情况下进行减肥手术以实现体重减轻，以及优化合并症仍然是第一线治疗方法。
