Hypogonadal obese men with and without diabetes mellitus type 2 lose weight and show improvement in cardiovascular risk factors when treated with testosterone, "Beyond the Abstract," by Farid Saad

BERKELEY, CA (UroToday.com) - In a recent paper, we could demonstrate that normalizing serum testosterone in obese hypogonadal men, and also in those with type 2 diabetes, reduced their body weight and improved their metabolic state. Studies confirming these effects of testosterone on body weight and metabolic variables are increasing, and for a number of reasons, they deserve the attention of the urological profession. Obesity has been linked to the severity of lower urinary tract symptoms and to erectile dysfunction, and inflammation associated with obesity is probably the link between these two conditions. Studies associating low testosterone to the metabolic syndrome and inflammation have been predominantly performed in elderly men. But in relatively young men, low serum testosterone concentrations (often associated with severe obesity) were significantly associated with elevated levels of the pro-inflammatory cytokine TNF-α as well as the pro-inflammatory chemokines. Also prostate cancer has been shown to be linked to obesity, and, again, inflammation might be a key player. In a study in Denmark, incidence, clinical stage, and survival of prostate cancer appeared to have a relationship to obesity. Obesity also increases the risk for high-grade prostate cancer. There are reasons to conceptualize benign prostate hyperplasia as a metabolic disease occurring in obese men. So, there is accumulating evidence that obesity is relevant for the urology clinic and that it is timely to take a more holistic approach and include the presence of obesity in the diagnostic work-up of patients.

It is relatively easy to include a measurement of serum testosterone in the work up of obese patients presenting with the above urological complaints. To avoid over diagnosis, blood must be sampled before 11.00 am when serum testosterone is at its highest level on the basis of its diurnal rhythm. To establish a diagnosis of testosterone deficiency, serum testosterone must be below the lower limit of reference values, and there must be clinical symptoms of testosterone deficiency as well. There is no international consensus as to the normal range of testosterone, but clinical data suggest that the normal range of testosterone in adult men is between 12 and 40 nmol/L. A threshold of 12.1 nmol/L (348.3 ng/dL) was confirmed by an international group of authors based on analyses of several well-known studies in which liquid chromatography tandem mass spectrometry as a gold standard had been used.

Many physicians are hesitant to prescribe testosterone. The traditional way of thinking is that use of testosterone, particularly in the elderly, increases the risk of cardiovascular disease and of prostate cancer. It has been largely the work of Dr. Abraham Morgentaler dispelling the historical fear that raising testosterone levels will result in more prostate cancer. Studies have failed to show an increased risk of prostate cancer in men with higher serum testosterone, and even supraphysiological testosterone levels do not appear to increase prostate volume or prostate-specific antigen in healthy men. This apparent paradox is explained by the ‘saturation model,’ which posits a finite capacity of androgen to stimulate growth of prostate cancer. Recent studies indicate no increased risk of prostate cancer among men with serum testosterone in the therapeutic range. Follow-up of elderly men receiving testosterone is evidently necessary because age is a strong prognosticator of prostate malignancy. Urologists are well placed to make a realistic assessment of the risk of prostate cancer in men using testosterone.

An important barrier to overcome is the fear that testosterone administration will increase cardiovascular disease. Studies showing a relationship between testosterone administration and cardiovascular disease in elderly men have been heavily criticized for methodological flaws and should invite a much needed critical analysis of pro and con arguments. As yet there is no convincing evidence that use of testosterone in the elderly increases the risk of cardiovascular disease.

Written by:
Farid Saad as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Bayer Pharma, Global Medical Affairs Andrology, Berlin, Germany; Gulf Medical University School of Medicine, Ajman, United Arab Emirates

Hypogonadal obese men with and without diabetes mellitus type 2 lose weight and show improvement in cardiovascular risk factors when treated with testosterone: An observational study - Abstract

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