Eriksson Joel, Haring Robin, Grarup Niels, Vandenput Liesbeth, Wallaschofski Henri, Lorentzen Erik, Hansen Torben, Mellström Dan, Pedersen Oluf, Nauck Matthias, Lorentzon Mattias, Nystrup Husemoen Lise Lotte, Völzke Henry, Karlsson Magnus, Baumeister Sebastian E, Linneberg Allan, Ohlsson Claes
Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
University Medicine Greifswald, Institute of Clinical Chemistry and Laboratory Medicine, Greifswald, Germany.
PLoS One. 2017 Apr 27;12(4):e0176277. doi: 10.1371/journal.pone.0176277. eCollection 2017.
Obesity in men is associated with low serum testosterone and both are associated with several diseases and increased mortality.
Examine the direction and causality of the relationship between body mass index (BMI) and serum testosterone.
Bi-directional Mendelian randomization (MR) analysis on prospective cohorts.
Five cohorts from Denmark, Germany and Sweden (Inter99, SHIP, SHIP Trend, GOOD and MrOS Sweden).
7446 Caucasian men, genotyped for 97 BMI-associated SNPs and three testosterone-associated SNPs.
BMI and serum testosterone adjusted for age, smoking, time of blood sampling and site.
1 SD genetically instrumented increase in BMI was associated with a 0.25 SD decrease in serum testosterone (IV ratio: -0.25, 95% CI: -0.42--0.09, p = 2.8*10-3). For a body weight reduction altering the BMI from 30 to 25 kg/m2, the effect would equal a 13% increase in serum testosterone. No association was seen for genetically instrumented testosterone with BMI, a finding that was confirmed using large-scale data from the GIANT consortium (n = 104349).
Our results suggest that there is a causal effect of BMI on serum testosterone in men. Population level interventions to reduce BMI are expected to increase serum testosterone in men.
男性肥胖与血清睾酮水平低有关，且二者均与多种疾病及死亡率增加相关。
研究体重指数（BMI）与血清睾酮之间关系的方向及因果关系。
对前瞻性队列进行双向孟德尔随机化（MR）分析。
来自丹麦、德国和瑞典的5个队列（Inter99、SHIP、SHIP Trend、GOOD和瑞典MrOS）。
7446名白人男性，对97个与BMI相关的单核苷酸多态性（SNP）和3个与睾酮相关的SNP进行基因分型。
校正年龄、吸烟、采血时间和采血部位后的BMI和血清睾酮。
经基因检测，BMI每增加1个标准差，血清睾酮水平降低0.25个标准差（IV比值：-0.25，95%置信区间：-0.42--0.09，p = 2.8×10⁻³）。对于体重减轻使BMI从30降至25 kg/m²的情况，其效果相当于血清睾酮水平增加13%。经基因检测，未发现睾酮与BMI之间存在关联，这一结果在GIANT联盟的大规模数据（n = 104349）中得到证实。
我们的结果表明，BMI对男性血清睾酮有因果效应。预计在人群层面采取降低BMI的干预措施会使男性血清睾酮水平升高。
