Sex hormones, inflammation and the metabolic syndrome: a population-based study

Abstract

Objective: Mild hypoandrogenism in men is associated with features of the metabolic syndrome, but the association with the metabolic syndrome itself using an accepted definition has not been described. Design: Men with the metabolic syndrome were identified and testosterone and sex hormone-binding globulin (SHBG) levels were determined in a population-based cohort of 1896 non-diabetic middleaged Finnish men. Results: Calculated free testosterone and SHBG were 11% and 18% lower (P , 0.001) in men with the metabolic syndrome (n ¼ 345, World Health Organisation definition). After categorisation by tertiles and adjusting for age and body mass index, total and free testosterone and SHBG were inversely associated with concentrations of insulin, glucose, triglycerides, C-reactive protein (CRP) and CRP-adjusted ferritin and positively associated with high-density lipoprotein cholesterol. Men with free testosterone levels in the lowest third were 2.7 (95% confidence interval (CI) 2.0-3.7) times more likely to have the metabolic syndrome in age-adjusted analyses, and 1.7 (95% CI 1.2 -2.4) times more likely even after further adjusting for body mass index. Exclusion of men with cardiovascular disease did not alter the association. The inverse association of SHBG with the metabolic syndrome was somewhat stronger. Conclusions: Low testosterone and SHBG levels were strongly associated not only with components of the metabolic syndrome, but also with the metabolic syndrome itself, independently of body mass index. Furthermore, sex hormones were associated with inflammation and body iron stores. Even in the absence of late-stage consequences such as diabetes and cardiovascular disease, subtle derangements in sex hormones are present in the metabolic syndrome, and may contribute to its pathogenesis.

The Princeton III Consensus Recommendations for the Management of Erectile Dysfunction and Cardiovascular Disease

“…Consistent with this notion, androgen deficiency has been associated with insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and increased deposition of visceral fat. [62][63][64][65] In the TIMES2 (Testosterone Replacement In Hypogonadal Men With Either Metabolic Syndrome or Type 2 Diabetes) study, 6 to 12 months of transdermal TRT (vs placebo) significantly improved insulin resistance and glycemic control in a large randomized study of hypogonadal men with type 2 diabetes mellitus (ACCF/AHA class Ib). 66 A meta-analysis of 5 other randomized controlled trials (including 3 placebo-controlled trials) with mean follow-up of 58 weeks found that TRT was associated with a significant reduction in fasting plasma glucose levels, homeostasis model assessment of insulin resistance index, triglycerides, and WC.…”

Testosterone treatment improves metabolic syndrome-induced adipose tissue derangements

“…MetS is often associated with testosterone deficiency in males (Laaksonen et al 2003, Kapoor et al 2005. A recent meta-analysis of the available cross-sectional studies on the association between MetS and hypogonadism found that patients with MetS had significantly lower testosterone plasma levels (about 3 nmol/l), in comparison with agematched subjects (Corona et al 2011a).…”

Association between prostate-specific antigen and leptin, adiponectin, HbA1c or C-peptide among African-American and Caucasian men

“…[35][36][37] Indeed, PSA expression is under androgen receptor regulation, and obesity and hyperinsulinemia are also associated with lower testosterone levels. [38][39][40][41][42] However, a prior study found no association between leptin or adiponectin and PSA among prostate cancer patients, 43,44 and the component(s) of body adiposity as estimated by BMI that affect PSA levels and perhaps the ability to detect early-stage prostate cancer remain unclear.…”