Statin therapy is associated with lower total but not bioavailable or free testosterone in men with type 2 diabetes.

Abstract

Objective- There is a high prevalence of hypogonadism in men with type 2 diabetes. This will lead to an increase in assessments of hypogonadism. Statins could potentially decrease testosterone levels by reducing the availability of cholesterol for androgen synthesis. We compared testosterone levels and hypogonadal symptoms with statin use in a cross-section of 355 men with type 2 diabetes.

Research design and methods- Total testosterone (TT), SHBG and estradiol were measured by ELISA. Bioavailable testosterone (BT) was measured by modified ammonium sulphate precipitation method. Free testosterone (FT) was calculated using Vermeulen's formula. Symptoms of hypogonadism were assessed using the ADAM questionnaire.

Results- Statins were associated with lower TT (11.9 nmol/l vs 13.4 nmol/l, p=0.006) and a trend to lower SHBG (29.4 nmol/l vs 35.3 nmol/l, p=0.034) compared with no treatment. BT, FT, estradiol and hypogonadal symptoms were not affected. Subanalysis showed that atorvastatin was associated with reduced TT (11.4 nmol/l vs 13.4 nmol/l, p=0.006) and a trend to reduced SHBG (27.6nmol/l vs 35.3 nmol/l, p=0.022) compared with no treatment and there was an apparent dose response effect with the lowest levels of TT seen in men treated with 20mg or more atorvastatin (9.6 nmol/l, p=0.017). Simvastatin use was not associated with significant reductions in testosterone or SHBG levels.

Conclusions- Assessing androgen status using TT in men with type 2 diabetes treated with statins, particularly atorvastatin, may potentially lead to diagnostic error. BT or FT are recommended for the assessment of hypogonadism in this group if TT levels are borderline.