The Pituitary-Gonadal Axis and Health in Elderly Men: A Study of Men Born in 1913

Abstract

The results of recent studies suggest that a relative hypogonadism in men is associated with several established risk factors for prevalent diseases. Therefore, we determined total and free testosterone, luteinizing hormone (LH), and sex-hormone binding globulin (SHBG) in a cohort of randomly selected men (n = 659) at 67 years of age. These data were analyzed cross-sectionally in relation to blood glucose and serum insulin, which were measured while fasting and after an oral glucose tolerance test, in addition to plasma lipids and blood pressure. The data were also analyzed in relation to impaired glucose tolerance (IGT) and diabetes, which were discovered at examination or earlier diagnosis. Risk factors for the development of diabetes up to 80 years of age were analyzed with univariate and multivariate statistics. Total and free testosterone and SHBG concentrations correlated negatively with glucose and insulin values; total testosterone and SHBG, with triglycerides; and SHBG, with blood pressure (from P < 0.05 to P < 0.01). Men with IGT or newly diagnosed diabetes had higher BMI values (26.2 +/- 0.31 and 27.0 +/- 0.59 [mean +/- SE], respectively) and waist circumference (99.0 +/- 1.03 and 100.5 +/- 1.57) than nondiabetic men (BMI, 25.1 +/- 0.14; waist circumference, 95.4 +/- 0.47; P < 0.05), indicating abdominal obesity. Such men and men with previously diagnosed diabetes had, in general, lower total and free testosterone and SHBG levels, while those for LH were not different. In multivariate analyses that included BMI, waist-to-hip ratio, total and free testosterone, and SHBG, the remaining independent predictors for the development of diabetes were low total testosterone (P = 0.015) and, on the borderline, low SHBG (P = 0.053). In relation to nondiabetic men, the risk ratio for mortality, myocardial infarction, and stroke increased gradually and significantly from 1.18 to 1.68, from 1.51 to 1.78, and from 1.72 to 2.46 in men with IGT, newly diagnosed diabetes, and previously known diabetes, respectively. It was concluded that low testosterone and SHBG concentrations in elderly men are associated with established risk factors for diabetes and in established diabetes. Moreover, low testosterone levels independently predict the risk of developing diabetes. In different degrees of expression, the diabetic state predicts strongly (and gradually mortality from) myocardial infarction and stroke. It has been suggested that a relative hypogonadism might be a primary event, because other studies have shown that testosterone deficiency is followed by insulin resistance, which is ameliorated by testosterone substitution. The data suggest that the relative hypogonadism involved might be of both central and peripheral origin.

Endogenous Sex Hormones, Metabolic Syndrome, and Diabetes in Men and Women

“…Diabetes was identified primarily by self-report [45–48] with confirmation by additional testing or record review [45], or by FPG levels and medication use [49–52]; several studies used 2-hour glucose levels as well [53–57]. It is possible that this variety in definitions contributed to inconsistent associations.…”

“…Five studies found an association between lower total T and incident diabetes [49, 55, 47, 58, 57], while 3 studies reported no association [46, 59, 48]. Two studies found an association between lower bioavailable or free T and incident diabetes [49, 57], while 3 studies reported no association [51, 46, 59]. One study examined total E2 and found an association [48], while another examined total and bioavailable E2 in men and diabetes and found no association [55].…”

“…One study examined total E2 and found an association [48], while another examined total and bioavailable E2 in men and diabetes and found no association [55]. Five studies examining SHBG found an association between lower SHBG and incident diabetes [49, 51, 46, 58, 57]; 4 did not [53, 56, 59, 48], particularly after adjustment for waist measures. Tibblin et al [57] examined IGT as well as diabetes as an outcome and also reported that lower total T was associated with incident IGT.…”

Would prostate cancer detected by screening withprostate‐specific antigen develop into clinical cancer if left undiagnosed? A comparison of two population‐based studies in Sweden

“…The study comprised two cohorts of men from Go Èteborg; both cohorts were population-based and in both the men were personally invited to participate. The cohort of men born in 1913 were randomly selected from the general population and has been extensively described elsewhere [13]. Altogether, 973 men were initially invited to a health screening examination in 1963, of whom 855 (88%) participated.…”

Sex differences in type 2 diabetes: focus on disease course and outcomes

“…Low testosterone levels are associated with abdominal obesity and insulin resistance in men,39 and are an independent risk factor for developing T2D 40. Insulin sensitivity, visceral fat mass, blood pressure, and plasma lipids improve with testosterone substitution 41,42.…”