Abstract
Most studies reporting on the association of circulating testosterone levels with type 2 diabetes in men are of cross-sectional design. Reports on the relevance of altered testosterone levels in women are scarce. Here, we evaluate the role of low serum testosterone levels for incident diabetes in men and women in a population setting of 7706 subjects (3896 females). During a mean follow up time of 13.8 years, 7.8% developed type 2 diabetes. Significant correlations of testosterone with high density lipoprotein (HDL)-cholesterol (R = 0.21, p < 0.001), body-mass-index (R = −0.23, p < 0.001), and waist-to-hip-ratio (R = −0.21, p < 0.001) were found in men. No correlation was found with age in men; in women, the correlation was negligible (R = 0.04, p = 0.012). In men, low testosterone levels predicted high risk of type 2 diabetes, while in women this relationship was opposite. Men with low testosterone levels showed increased risk of future diabetes (hazard ratio (HR) 2.66, 95% confidence interval (CI) 1.91–3.72, p < 0.001 in basic model; HR 1.56 95%, CI 1.10–2.21, p = 0.003). In women, low testosterone levels indicated lower risk with (HR 0.53, 95% CI 0.37–0.77, p = 0.003), while the association lost significance in the fully adjusted model (HR 0.72, 95% CI 0.49–1.05, p = 0.09). Low levels of testosterone predicted future diabetes in men. A borderline opposite association was found in women.
Highlights
Testosterone is the primary male sex hormone and an anabolic steroid, and it seems widely accepted that men experience a gradual decline in testosterone levels with increasing age [1,2,3,4].The potential association of circulating testosterone with diabetes is of utmost clinical interest: Since the Endocrine Society addressed the high prevalence of low serum testosterone levels in patients with type 2 diabetes in its Clinical Practical Guidelines of 2010, testosterone has moved into the focus of cardiometabolic therapy, and its prescription escalated at startling rates creating a $2 billion annual market in the U.S [5,6]
Since most studies reporting on the association of low circulating testosterone levels with type 2 diabetes in men are of cross-sectional design, and since reports on the relevance of altered testosterone levels in women are scarce, the clinical relevance of low testosterone levels remains unclear [15,16,17,18]
In crude Pearson analyses, no correlation was found with age in men (R = 0.02; p = 0.19), while correlation was negligible in women (R = 0.04; p = 0.012)
Summary
Testosterone is the primary male sex hormone and an anabolic steroid, and it seems widely accepted that men experience a gradual decline in testosterone levels with increasing age [1,2,3,4].The potential association of circulating testosterone with diabetes is of utmost clinical interest: Since the Endocrine Society addressed the high prevalence of low serum testosterone levels in patients with type 2 diabetes in its Clinical Practical Guidelines of 2010, testosterone has moved into the focus of cardiometabolic therapy, and its prescription escalated at startling rates creating a $2 billion annual market in the U.S [5,6]. Testosterone is the primary male sex hormone and an anabolic steroid, and it seems widely accepted that men experience a gradual decline in testosterone levels with increasing age [1,2,3,4]. No randomized clinical trial has provided proof of the benefit of testosterone therapy. The testosterone lowering properties of statins have come. Large meta-analyses of randomized clinical trials have demonstrated an increased risk of new-onset diabetes with statin therapy [8,9,10,11]. Statins lower testosterone levels by their very own property, as cholesterol is a precursor of the testosterone biosynthesis pathway, and by a selective inhibitory effect on 17-ketosteroid-oxidoreductase enzyme activity [12,13].
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