Statin therapy is associated with lower total but not bioavailable or free testosterone in men with type 2 diabetes.
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-sectional study of 355 men with type 2 diabetes.


METHODS
Total testosterone, sex hormone-binding globulin (SHBG), and estradiol were measured by an enzyme-linked immunosorbent assay. Bioavailable testosterone was measured by the modified ammonium sulfate precipitation method. Free testosterone was calculated using Vermeulen's formula. Symptoms of hypogonadism were assessed using the Androgen Deficiency in the Aging Male questionnaire.


RESULTS
Statins were associated with lower total testosterone (11.9 vs. 13.4 nmol/l, P = 0.006) and a trend toward lower SHBG (29.4 vs. 35.3 nmol/l, P = 0.034) compared with no treatment. Bioavailable testosterone, free testosterone, estradiol, and hypogonadal symptoms were not affected. Subanalysis showed that atorvastatin was associated with reduced total testosterone (11.4 vs. 13.4 nmol/l, P = 0.006) and a trend toward reduced SHBG (27.6 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 total testosterone seen in men treated with >or=20 mg 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 total testosterone in men with type 2 diabetes treated with statins, particularly atorvastatin, may potentially lead to diagnostic error. Levels of bioavailable testosterone or free testosterone are recommended for the assessment of hypogonadism in this group if total testosterone levels are borderline.
Stanworth
Roger D
RD
Department of Diabetes and Endocrinology, Barnsley Hospital NHS Foundation Trust, Barnsley, UK.
Kapoor
Dheeraj
D
Channer
Kevin S
KS
Jones
T Hugh
TH
D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D001682:Biological Availability; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004958:Estradiol / Q000097:blood; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000494:pharmacology; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology; D013739:Testosterone / Q000097:blood*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol; D000069059:Atorvastatin; D019821:Simvastatin