A realization is dawning in clinical medicine that testosterone has a prominent role in maintaining good health. That is not to say that more is always better. Just like other readily understood areas of human existence, there is an optimum range, below and above which can be detrimental. Typically people enjoy environmental temperatures between 40 degrees and 90 degrees. Temperatures above and below this range cause some discomfort, injury and eventual death. Even within this “normal” range there exists a smaller range representing the optimal temperature. Although it may not be universal, people are most active, happy and productive around a temperature of 75 degrees. Similar ranges can be described for physiologic functions. A resting heart rate between 60-80 beats per minute is healthy, as is getting 7-9 hours of sleep per night or blood glucose of 60-100 mg/dl.
Testosterone levels are no different. There is a strong and growing body of evidence supporting the notion that low testosterone concentrations in men predisposes them to a higher risk of chronic degenerative diseases, poor physical and mental health and premature death.[1] [2] Although it has not been directly studied, there is ample anecdotal evidence from athletes and bodybuilders that supraphysiologic (above normal range) levels of testosterone confer little health benefit, and are probably harmful in the long term.
Low testosterone concentration in men is, however, clearly unhealthy. Men with low testosterone levels are at increased risk of cardiovascular disease (CVD), type-2 diabetes, obesity, and prostate cancer. Testosterone therapy in men with low testosterone produces changes that are associated with lower risk of CVD. These changes include reduced visceral (abdominal) obesity and insulin resistance, improved lipid profile, reduced blood inflammatory markers, and better exercise tolerance.[3] Bolstering the beneficial effects testosterone therapy can have on heart function, injections of long-acting testosterone was shown to increase the blood-pumping ability and heart muscle strength in men with heart failure. Improvements in functional exercise capacity and insulin resistance were also noted.[4]
Metabolic syndrome is a constellation of health problems and risk factors including abdominal obesity, high triglycerides, high LDL cholesterol, low HDL cholesterol, hypertension and high fasting blood glucose. It confers an increased risk for developing future CVD, stroke and type-2 diabetes. New research presented at The Endocrine Society’s 91st Annual meeting in Washington, DC earlier this year demonstrated that long term testosterone therapy in middle-aged and older men with low testosterone levels led to significant improvements in their fatty liver disease, risk factors for CVD and diabetes and features of the metabolic syndrome. Specifically, study participants were age 36 to 69 years and experienced:
- Decreased waist circumference in 6 months
- Decreased LDL in six months
- Increased HDL over two years
- Decreased total cholesterol and triglycerides in one year
- Decline in c-reactive protein (marker of inflammation)
- 77% of men with metabolic syndrome at baseline no longer had metabolic syndrome after 2 years.
Metabolic syndrome has become more common since it was first described in the early 1980’s. Along with increasing rates of obesity, it is largely attributed to lifestyle and dietary changes. Curiously, during the same period, the average testosterone concentration in men has also been falling.[5] Obesity is a major risk factor for cardiovascular disease. There is an inverse (opposite) relationship between testosterone level and obesity. In particular, numerous studies have shown that a low testosterone level correlates with increasing abdominal obesity, higher body fat percentage and higher insulin levels. High insulin levels promote fat storage and leads to insulin resistance. Low testosterone is frequently a precursor to type-2 diabetes.[6] Obesity, insulin resistance and type-2 diabetes are all factors contributing to the risk for having a heart attack.
As testosterone levels fall, body fat increases. Fat cells contain an enzyme, aromatase, which converts testosterone to estrogen. This leads to a vicious cycle, as estrogen not only promotes fat accumulation, it decreases the body’s sensitivity to low testosterone. This is believed to be mediated through a hormone called leptin and causes the body to fail to increase testosterone production as levels fall.
Testosterone therapy appears to have a multitude of beneficial effects: reduces insulin resistance by reducing visceral fat, which reduces inflammatory cytokines, reduces fatty acid delivery to the liver and improves lipid profiles, reduces risk for diabetes and cardiovascular disease, improves cardiovascular function, and has been shown to be an effective treatment for erectile dysfunction, even among some men that do not respond to Viagra-like drugs.[7]
What is the optimal testosterone concentration for men with regard to overall health? Although the definitive study has not been done, mounting scientific evidence supports maintaining testosterone in the upper third of the normal range rather than the lower third. While improving sexual desire and erectile function are important for quality of life, testosterone has a much wider therapeutic role in maintaining optimal health.
[1] Lauglin, et al. Low serum testosterone and morality in older men. J Clin Endo Metab, 2008 Jan
[2] Khaw, KT, Dowsett, M, et al. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men. Circulation, 2007 Dec
[3] Jones TH, Saad F. The effects of testosterone on risk factors associated with myocardial infarction in 52 countries (the INTERHEART study). Lancet, 2004 Sept
[4] Lellamo F, Jones TH. Testosterone therapy may help men with heart failure, J Amer Coll Card, 2009 Sept
[5] Tavison TG Araujo AB, et al. A population-level decline in serum testosterone levels in American men. J Clin Endocrinol Metab, 2007 Jan.
[6] Haffner SM, Shaten J, et al. Low levels of sex hormone binding globulin and testosterone predict the development of non-insulin dependent diabetes mellitus in men. Multiple risk Factor Intervention Trial. Am J Epidemiol, 1996 May.
[7] Greco EA, Spera G, et al. Combining testosterone andPDE5 inhibitors in erectile dysfunction: basic rationale and clinical evidences. Eur Urol, 2006 Nov.
