Abrupt decrease in serum testosterone levels after an oral glucose load in men: implications for screening for hypogonadism

Objective This study examines the physiological impact of a glucose load on serum testosterone (T) levels in men with varying glucose tolerance (GT). Design Cross-sectional study. Patients and Methods 74 men (1974 years, mean 51.4 +/- 1.4 years) underwent a standard 75-g oral glucose tolerance test with blood sampling at 0, 30, 60, 90 and 120 min. Fasting serum glucose, insulin, total T (and calculated free T), LH, SHBG, leptin and cortisol were measured. Results 57% of the men had normal GT, 30% had impaired GT and 13% had newly diagnosed type 2 diabetes. Glucose ingestion was associated with a 25% decrease in mean T levels (delta = -4.2 +/- 0.3 nm, P < 0.0001). T levels remained suppressed at 120 min compared with baseline (13.7 +/- 0.6 vs 16.5 +/- 0.7 nm, P < 0.0001) and did not differ across GT or BMI. Of the 66 men with normal T levels at baseline, 10 (15%) had levels that decreased to the hypogonadal range (<9.7 nm) at one or more time points. SHBG, LH and cortisol levels were unchanged. Leptin levels decreased from baseline at all time points (P < 0.0001). Conclusions Glucose ingestion induces a significant reduction in total and free T levels in men, which is similar across the spectrum of glucose tolerance. This decrease in T appears to be because of a direct testicular defect, but the absence of compensatory changes in LH suggests an additional central component. Men found to have low nonfasting T levels should be re-evaluated in the fasting state.