英国剑桥大学John R. B. Perry、埃克塞特大学Timothy M Frayling等研究人员合作利用人类遗传学剖析了睾丸酮对男性和女性的疾病影响。2020年2月10日，《自然—医学》杂志在线发表了这项成果。

研究人员表示，睾丸酮补充因其对性功能、骨骼健康和身体成分的作用而被普遍使用，但对疾病结果的作用尚不清楚。

为了更好地理解这一点，研究人员在425097名英国生物银行研究参与者中确定了睾丸酮水平和相关性激素性状的遗传决定因素。使用2571个全基因组的显著关联，研究人员证明了睾丸酮水平的遗传决定因素在性别之间存在显著差异，而遗传上较高的睾丸酮对女性的代谢性疾病有害而对男性有益。例如，遗传上睾丸酮升高一个标准差的会增加2型糖尿病的风险（比值比（OR）= 1.37（95％置信区间（95％CI）：1.22-1.53??））和多囊卵巢综合征（OR = 1.51（95％CI：1.33-1.72） ），但降低了男性的2型糖尿病风险（OR = 0.86（95％CI：0.76-0.98））。研究人员还发现较高的睾丸酮对女性乳腺癌和子宫内膜癌以及男性前列腺癌具有不利影响。这些发现解析了睾丸酮的疾病影响，并强调了性别特异性遗传分析的重要性。

附：英文原文

Title: Using human genetics to understand the disease impacts of testosterone in men and women

Author: Katherine S Ruth, Felix R Day, Jessica Tyrrell, Deborah J Thompson, Andrew R Wood, Anubha Mahajan, Robin N Beaumont, Laura Wittemans, Susan Martin, Alexander S. Busch, A. Mesut Erzurumluoglu, Benjamin Hollis, Tracy A. OMara, Mark I McCarthy, Claudia Langenberg, Douglas F Easton, Nicholas J Wareham, Stephen Burgess, Anna Murray, Ken K Ong, Timothy M Frayling, John R. B. Perry

Issue&Volume: 2020-02-10

Abstract: Testosterone supplementation is commonly used for its effects on sexual function, bone health and body composition, yet its effects on disease outcomes are unknown. To better understand this, we identified genetic determinants of testosterone levels and related sex hormone traits in 425,097 UK Biobank study participants. Using 2,571 genome-wide significant associations, we demonstrate that the genetic determinants of testosterone levels are substantially different between sexes and that genetically higher testosterone is harmful for metabolic diseases in women but beneficial in men. For example, a genetically determined 1s.d. higher testosterone increases the risks of type 2 diabetes (odds ratio (OR)=1.37 (95% confidence interval (95% CI): 1.22–1.53)) and polycystic ovary syndrome (OR=1.51 (95% CI: 1.33–1.72)) in women, but reduces type 2 diabetes risk in men (OR=0.86 (95% CI: 0.76–0.98)). We also show adverse effects of higher testosterone on breast and endometrial cancers in women and prostate cancer in men. Our findings provide insights into the disease impacts of testosterone and highlight the importance of sex-specific genetic analyses.

DOI: 10.1038/s41591-020-0751-5

Source: https://www.nature.com/articles/s41591-020-0751-5