Low Testosterone Levels Linked to Statin Therapy for Men With Type 2 Diabetes

In diabetic men treated with statins, particularly atorvastatin, evaluating androgen status using total testosterone may cause diagnostic error, according to the results of a cross-sectional study.

Roger D. Stanworth, BMEDSCI, from Barnsley Hospital National Health Service Foundation Trust in Barnsley, United Kingdom, writes, “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.”

The investigators evaluated the association of testosterone levels and hypogonadal symptoms with statin use in a study sample of 355 men with Type 2 diabetes. Enzyme-linked immunosorbent assays measured total testosterone, sex hormone-binding globulin (SHBG), and estradiol, and the modified ammonium sulfate precipitation method measured bioavailable testosterone.

The Androgen Deficiency in the Aging Male (ADAM) questionnaire was administered to evaluate symptoms of hypogonadism.

Compared with no treatment, statin therapy was associated with reduced total testosterone (11.9 vs 13.4 nmol/L; P = .006) and a trend toward lower SHBG (29.4 vs 35.3 nmol/L; P = .034). However, statin therapy did not appear to affect bioavailable testosterone, free testosterone, estradiol, or hypogonadal symptoms.

Compared with no treatment, use of atorvastatin was associated with lower total testosterone (11.4 vs 13.4 nmol/L; P = .006) and a trend toward reduced SHBG (27.6 vs 35.3 nmol/L; P = .022). The lowest levels of total testosterone were observed in men receiving 20 mg atorvastatin or more (9.6 nmol/L; P = .017), suggesting a dose-response effect. Testosterone or SHBG levels were not significantly lowered with simvastatin use.

“Assessing androgen status using total testosterone in men with Type 2 diabetes treated with statins, particularly atorvastatin, may potentially lead to diagnostic error,” the study authors write.

“Levels of bioavailable testosterone or free testosterone are recommended for the assessment of hypogonadism in this group if total testosterone levels are borderline.”

“This large data set is the first to suggest a significant effect of statins in lowering total testosterone and SHBG levels in a population of men with Type 2 diabetes,” the study authors conclude. “The findings have important implications for the diagnosis of hypogonadism in men receiving statin treatment. The opportunity to conduct similar studies of men with Type 2 diabetes, comparing men treated with statins to untreated men, has now probably passed owing to the almost ubiquitous use of statins in this group.”

Diabetes Care. April, 2009;32:541-546.