Low Testosterone Associated With Obesity and the Metabolic Syndrome Contributes to Sexual Dysfunction and Cardiovascular Disease Risk in Men With Type

1. Christina Wang, MD¹⇓,
2. Graham Jackson, MD²,
3. T. Hugh Jones, MD³,
4. Alvin M. Matsumoto, MD⁴,
5. Ajay Nehra, MD⁵,
6. Michael A. Perelman, PHD⁶,
7. Ronald S. Swerdloff, MD¹,
8. Abdul Traish, PHD⁷,
9. Michael Zitzmann, MD⁸ and
10. Glenn Cunningham, MD⁹

+ Author Affiliations

1. ¹Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, California
2. ²London Bridge Hospital, London, U.K.
3. ³Robert Hague Centre for Diabetes and Endocrinology, Barnsley Hospital, and the Department of Metabolism, University of Sheffield Medical School, Sheffield, U.K.
4. ⁴Geriatric Research, Education and Clinical Center, V.A. Puget Sound Health Care System, Department of Medicine, University of Washington School of Medicine, Seattle, Washington
5. ⁵Department of Urology, Mayo Clinic, Rochester, Minnesota
6. ⁶Departments of Psychiatry, Reproductive Medicine, and Urology, NY Weill Cornell College of Medicine, New York, New York
7. ⁷Department of Urology, Boston University School of Medicine, Boston, Massachusetts
8. ⁸Clinical Andrology/Centre for Reproductive Medicine and Andrology, University Clinics of Muenster, Muenster, Germany
9. ⁹Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, St. Luke’s–Baylor Diabetes Program, Houston, Texas

1. Corresponding author: Christina Wang, wang@labiomed.org.

Men with obesity, the metabolic syndrome, and type 2 diabetes have low total and free testosterone and low sex hormone–binding globulin (SHBG). Conversely, the presence of low testosterone and/or SHBG predicts the development of metabolic syndrome and type 2 diabetes. Visceral adiposity present in men with low testosterone, the metabolic syndrome, and/or type 2 diabetes acts through proinflammatory factors. These inflammatory markers contribute to vascular endothelial dysfunction with adverse sequelae such as increased cardiovascular disease (CVD) risk and erectile dysfunction. This review focuses on the multidirectional impact of low testosterone associated with obesity and the metabolic syndrome and its effects on erectile dysfunction and CVD risk in men with type 2 diabetes. Whenever possible in this review, we will cite recent reports (after 2005) and meta-analyses.

Epidemiological studies of low testosterone, obesity, metabolic status, and erectile dysfunction

Epidemiological studies support a bidirectional relationship between serum testosterone and obesity as well as between testosterone and the metabolic syndrome. Low serum total testosterone predicts the development of central obesity and accumulation of intra-abdominal fat ( 1– 3). Also, low total and free testosterone and SHBG levels are associated with an increased risk of developing the metabolic syndrome, independent of age and obesity ( 1– 3). Lowering serum T levels in older men with prostate cancer treated with androgen deprivation therapy increases body fat mass ( 4). Conversely, high BMI, central adiposity, and the metabolic syndrome are associated with and predict low serum total and to a lesser extent free testosterone and SHBG levels ( 1– 3, 5). Because obesity suppresses SHBG and as a result total testosterone concentrations, alterations in SHBG confound the relationship between testosterone and obesity.

Low total testosterone or SHBG levels are associated with type 2 diabetes, independent of age, race, obesity, and criteria for diagnosis of diabetes ( 6, 7). In longitudinal studies, low serum total and free testosterone …

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