Treatment with testosterone improves cardiovascular risk factors in obese hypogonadal men, with or without type 2 diabetes mellitus
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 Haider A, Saad F, Doros G, and Gooren L. Obesity Research & Clinical Practice 2014;8:e339–49
Obesity is a well-known risk factor for the development of cardiovascular disorders. Globally, obese patients have a higher risk of morbidity1,2 and mortality3; risk of type 2 diabetes, cardiovascular mortality, and premature death is increased by ~30% in obese patients.4 In addition, obesity leads to a decrease in serum testosterone and vice versa. This summary discusses the effects of normalising testosterone levels in obese hypogonadal men, with and without type 2 diabetes mellitus (T2DM). Based on a registry of 255 hypogonadal men5 this was a long-term observational analysis of a subgroup of obese men (n=181).6
What is known
In obese and overweight patients, diet and exercise have been shown to reduce weight and improve obesity parameters, however, these patients have a higher risk of reverting back after an initial weight loss. It has been well documented that normalising circulating testosterone in obese hypogonadal patients is efficacious7,8 and well tolerated.9 Improvements in diet and exercise lead to improvements in the management of diabetes, but even further improvements may be achieved after the administration of testosterone.10
It is now recognised that waist circumference is a better identifier of weight loss than BMI.11 Indeed, waist circumference provides a better measure of (abdominal) body fat and is a better predictor of diabetes mellitus and cardiovascular risk in obese patients.11
What this study adds
In this population of hypogonadal obese men, in a real-life setting, treatment with TU was associated with a significant decrease in both anthropometric parameters and cardiovascular risk factors in patients both with and without T2DM.6
Throughout the study period patients did not experience low levels of testosterone; serum testosterone was maintained in a range >17–19 nmol/L over the 5 year treatment period. Normalising testosterone levels in obese hypogonadal men in this long-term study resulted in continuous and sustained decreases in waist circumference, body weight and BMI. Fasting blood glucose decreased over the first year and then remained steady. Total cholesterol, LDL, and triglycerides significantly decreased (p<0.0001 compared with baseline) following a similar pattern to fasting blood glucose. HDL cholesterol had a significant increase compared with baseline (p<0.0001).
Patients in the diabetic subgroup experienced similar reductions in anthropometric and cardiovascular parameters, however percent decrease in HbA1c was more pronounced in the diabetic subgroup than in the full study population, falling by a mean 2.01±0.07%. Blood pressure is a major risk factor for cardiovascular diseases; in this study both SBP and DBP decreased over the first two years of the study, before levelling off. Further decreases were seen in SBP after 4 years of treatment, falling to 139.04 mmHg.
One remarkable finding from this study is the continuous weight loss over the 5 year treatment period. Weight loss associated with pharmacological treatments usually reaches a plateau after 1–2 years of treatment, with a similar effect seen after bariatric surgery.6 However, in this study, treatment with TU was associated with a continuous and sustained decrease in weight over 5 years.
TU was found to be well tolerated; both haematocrit and haemoglobin increased but remained within normal ranges. Prostate volume increase slightly but prostate-specific antigen levels decreased and there was no indication for increased risk of prostate cancer in this population.
Despite the benefits shown, this study was associated with a number of limitations. As the study was performed in patients who sought treatment at an urologist’s office for a number of urological conditions, the study was not designed to monitor the effect of normalising serum testosterone levels on weight loss, and therefore the population of men were different to those enrolled to weight loss trials.
The promising results from this study need to be confirmed in larger, controlled studies, and future studies should consider the inclusion of free living, physical activity and exercise which have been shown to have clinical benefit in improvements of glucose control and HbA1c.
Figure 1. Percent decrease in mean waist circumference and mean weight in obese hypogonadal men over 60 months of treatment6