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

Abstract

Introduction: Hypogonadism 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 methods: A 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. Results: Mean 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/m(2)) 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. Conclusion: Low 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.