Testosterone and Metabolic Syndrome

Metabolic syndrome (MetS) is a cluster of conditions including high blood pressure and blood sugar level, abnormal cholesterol levels, and excess body fat around the waist. This medical condition is one of the main threats for public health in the 21st century. According to the International Diabetes Federation (IDF), 20-25% of the adult population worldwide has MetS. [448] Having MetS increases one’s risk of developing chronic medical conditions such as diabetes and cardiovascular disease.
An overwhelming body of clinical evidence has shown a higher prevalence of MetS in subjects with low testosterone. [449-455] This may be due to the fact that low testosterone also increases one’s risk for high blood pressure, high blood sugar, abnormal cholesterol, and obesity. This constellation of risk factors, constitute MetS.
Restoring low testosterone levels through testosterone replacement therapy may help improve symptoms of MetS. One of the earliest studies reporting the effect of testosterone replacement therapy on risk of factor of Mets was by Rebuffescrive et al. in 1991 where they found that the therapy decreased waist-hip ratio in 9 out of 11 men after 6 weeks. [456] Recently, there have been a number of studies published assessing the therapeutic benefits of testosterone replacement therapy in patients with MetS.
Heufelder et al. investigated the effects of supervised diet and exercise with or without testosterone administration among 32 hypogonadal men for a period of 52 weeks. [457] The study resulted in greater therapeutic improvements of blood sugar levels.
A related study conducted by Jones et al. among 220 hypogonadal men with type 2 diabetes and/or MetS who are on testosterone replacement therapy (TRT) over a 6-month period, has shown beneficial effects on insulin resistance, total and LDL-cholesterol (Low Density Lipoprotein), and sexual health. [458]
A single-blind randomized study of testosterone administration in men with MetS and recent onset of diabetes mellitus also resulted in significant improvements on blood pressure over and above the effects of diet and exercise. [459] The men treated with testosterone also reported increased well-being and energy.
In a study by Saad et al., they found that testosterone administration among elderly men with late-onset hypogonadism had beneficial effect on sexual dysfunction and symptoms of MetS. [460] In addition, they also observed that the higher plasma levels of testosterone generated with long-acting testosterone undecanoate were clearly more effective in achieving therapeutic effect than testosterone gel.
In a large multicenter study undertaken in eight European countries, the TIMES2 (Testosterone replacement In men with Metabolic Syndrome or type 2 diabetes), Jones et al. reported that the treatment improved insulin resistance and cholesterol levels, and reduced body fat percentage after 6 and 12 months of therapy. [461] Researchers concluded that testosterone replacement therapy in men with MetS is superior to placebo treatment and does not have any adverse side effects.
In another study, Francomano et al. treated 20 hypogonadal men with testosterone undecanoate injections every 12 weeks for 60 months. [462] After testosterone treatment, study participants experienced significant reductions in MetS parameters such as waist circumference, body weight and blood sugar level, and improvements in insulin sensitivity, lipid profile, systolic and diastolic blood pressure.
A 5-year study by Yassin et al. involving two hundred sixty-one patients diagnosed with late-onset-hypogonadism and erectile dysfunction, has shown that treatment with injectable testosterone undecanoate significantly decreased weight, waist circumference, blood pressure, HbA1c (a measure of blood sugar level), triglycerides and low density lipoprotein cholesterol (bad cholesterol). [463] In addition to this, there was a significant increase in high-density lipoprotein cholesterol (good cholesterol) observed after the treatment period.
A registry of 255 men, aged between 33 and 69 years with abnormally low blood levels of total testosterone and the MetS assessed the effects of testosterone treatment in these medical conditions. [464] All men were treated with injectable testosterone undecanoate 1000 mg at baseline and 6 weeks and thereafter every 12 weeks for up to 5 years. Interestingly, researchers observed that testosterone therapy restored physiological testosterone levels and resulted in reductions in total cholesterol, low-density lipoprotein cholesterol and triglycerides, and increased high density lipoprotein cholesterol levels. There were also marked reductions in systolic and diastolic blood pressure, as well as blood sugar levels.
Finally, a study by Bhattacharya et al. evaluated the effects of testosterone gel in men with and without the MetS for 1 year. [465] They observed that only patients with the MetS demonstrated decreases in waist circumference, blood sugar levels, and blood pressure. Significant decreases in these parameters were seen in patients in the lowest total testosterone quartile, suggesting that testosterone treatment has beneficial effects in patients suffering from MetS.