Male hypogonadism: 14-year prospective outcome in 550 men with type 2 diabetes.

Abstract

SummaryIntroductionHypogonadism is more prevalent in men with type 2 diabetes (T2DM) (25%‐40%) than in men without T2DM. Hypogonadism has been associated with poorer glycaemic outcomes and increased cardiovascular morbidity/mortality. We report a 14‐year follow‐up study to evaluate the influence of baseline testosterone level on T2DM outcomes.Research design and methodsA total of 550 men with T2DM underwent baseline total testosterone and dihydrotestosterone measurement by tandem mass spectrometry. Mean age of the men was 59.7 ± 12 (mean ± SD) years. Sex hormone‐binding globulin (SHBG) was measured and free testosterone estimated. Patients were followed up between 2002 and 2016. Mean follow‐up period was 12.2 ± 4 years using the Salford (UK) Integrated Health Records system.ResultsMean baseline total testosterone was 13.7 ± 5.8 nmol/L, and mean free testosterone was 245.7 ± 88.0 pmol/L. Mean for low total testosterone (<10 nmol/L) was 7.6 ± 2.0 nmol/L (n = 154) and 142 men had a free testosterone <190 pmol/L. During the 14‐year duration follow‐up, 22% of men experienced a myocardial infarction, 18% experienced a stroke, 11% developed angina, 14% underwent coronary revascularization. About 38% of the men initially recruited died. A lower total testosterone was associated with a higher body mass index (kg/m2) at follow‐up: regression coefficient −0.30 (95% CI −0.445 to −0.157), P = 0.0001. The mortality rate was higher in patients with lower total testosterone compared to normal baseline total testosterone (5.0% vs 2.8% per year, P < 0.0001). A similar phenomenon was seen for dihydrotestosterone (4.3% vs 2.9% per year, P = 0.002) for normal vs low dihydrotestosterone) and for lower SHBG. Over the whole follow‐up period 36.1% (143/396), men with normal baseline testosterone died vs 55.8% (86/154) of hypogonadal men at baseline. In Cox regression, the age‐adjusted hazard ratio (HR) for higher mortality associated with low total testosterone was 1.54 (95% CI: 1.2‐2.0, P < 0.002), corresponding to a 3.2 year reduced life expectancy for hypogonadal T2DM men.ConclusionLow testosterone and dihydrotestosterone levels are associated with higher all‐cause mortality in T2DM men. Hypogonadal men with T2DM should be considered as very high risk for cardiovascular events/death.