Statin Therapy Is Associated With Lower Total but Not Bioavailable or Free Testosterone in Men With Type 2 Diabetes
- Roger D. Stanworth, BMEDSCI1,2,
- Dheeraj Kapoor, MD1,
- Kevin S. Channer, MD3 and
- T. Hugh Jones, MD1,2
- 1Department of Diabetes and Endocrinology, Barnsley Hospital NHS Foundation Trust, Barnsley, U.K.;
- 2Academic Unit of Diabetes, Endocrinology and Metabolism, Division of Genomic Medicine, University of Sheffield, Sheffield, U.K.;
- 3Faculty of Health and Wellbeing, Sheffield Hallam University, and Department of Cardiology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, U.K.
- Corresponding author: T. Hugh Jones, hugh.jones{at}nhs.net.
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-sectional study of 355 men with type 2 diabetes.
RESEARCH DESIGN AND 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 ≥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.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Received June 30, 2008.
- Accepted December 17, 2008.
- © 2009 by the American Diabetes Association.
