Holmboe Stine A, Jensen Tina K, Linneberg Allan, Scheike Thomas, Thuesen Betina H, Skakkebaek Niels E, Juul Anders, Andersson Anna-Maria
Department of Growth and Reproduction (S.A.H., T.K.J., N.E.S., A.J., A.-M.A.) and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (S.A.H., T.K.J., N.E.S., A.J., A.-M.A.), Rigshospitalet, University of Copenhagen, Department of Clinical Experimental Research (A.L.), Rigshospitalet, and Department of Clinical Medicine (A.L., A.J.), Faculty of Health and Medical Sciences, and Department of Biostatistics (T.S.), University of Copenhagen, DK-2100 Copenhagen, Denmark; and Research Centre for Prevention and Health (A.L., B.H.T.), The Capital Region, DK-2600 Glostrup, Denmark.
J Clin Endocrinol Metab. 2016 Aug;101(8):3180-90. doi: 10.1210/jc.2016-1778. Epub 2016 Jun 10.
Low serum T levels have been associated with type 2 diabetes (T2D) and cardiovascular disease. However, it is unresolved whether low T is a risk factor or rather a risk marker for these conditions.
The objective of the study was to investigate serum levels of total T, SHBG, free T, estradiol, LH, and FSH and the subsequent risk of T2D and/or cardiovascular disease.
DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study consisting of 5350 men from the general population aged 30-70 years at baseline, examined between 1982 and 2001 and followed with complete registry follow-up until December 2011, ie, up to 29 years of follow-up.
T2D outcomes defined as the first diagnosis of T2D and cardiovascular outcomes defined as first diagnosis of either ischemic heart disease or stroke (ischemic and hemorrhagic stroke).
In Cox proportional hazards models, a significantly negative association between T quartile and the risk of T2D was seen. Similarly, men with SHBG in the highest quartile had a decreased risk of developing T2D (nonsmokers: hazard ratio 0.30, 95% confidence interval 0.14-0.63; smokers: hazard ratio 0.40, 95% confidence interval 0.20-0.78). Similar trends were seen for free T, however, insignificant in the fully adjusted analysis. No associations were seen for estradiol, LH, and FSH. A less consistent pattern was seen for the hormones in relation to CVD outcomes; nonsmoking men showed a pattern of higher levels of total T, SHBG, and LH being negatively associated with ischemic heart disease and less pronounced for stroke, whereas in smokers higher levels of total T, free T, and LH were positively associated with the two CVD outcomes.
The observed negative associations of T and SHBG with T2D, but no association to LH and free T, indicates that low T in men who develop T2D is a marker of the disease rather than primary hypogonadism being a causal risk factor.
血清睾酮（T）水平低与2型糖尿病（T2D）和心血管疾病相关。然而，低T是这些疾病的危险因素还是风险标志物尚未明确。
本研究的目的是调查血清总T、性激素结合球蛋白（SHBG）、游离T、雌二醇、促黄体生成素（LH）和促卵泡生成素（FSH）水平以及随后发生T2D和/或心血管疾病的风险。
设计、地点和参与者：一项前瞻性队列研究，由5350名基线年龄为30 - 70岁的普通男性组成，于1982年至2001年进行检查，并进行完整的登记随访直至2011年12月，即长达29年的随访。
T2D结局定义为首次诊断为T2D，心血管结局定义为首次诊断为缺血性心脏病或中风（缺血性和出血性中风）。
在Cox比例风险模型中，观察到T四分位数与T2D风险之间存在显著负相关。同样，SHBG处于最高四分位数的男性患T2D的风险降低（不吸烟者：风险比0.30，95%置信区间0.14 - 0.63；吸烟者：风险比0.40，95%置信区间0.20 - 0.78）。游离T也观察到类似趋势，但在完全调整分析中不显著。未观察到雌二醇、LH和FSH有相关性。激素与心血管疾病结局的关系模式不太一致；不吸烟男性中，总T、SHBG和LH水平较高与缺血性心脏病呈负相关，与中风的相关性较弱，而在吸烟者中，总T、游离T和LH水平较高与这两种心血管疾病结局呈正相关。
观察到T和SHBG与T2D呈负相关，但与LH和游离T无相关性，这表明患T2D男性的低T是该疾病的标志物，而非原发性性腺功能减退是因果风险因素。
