Soup To Nuts of Testosterone Replacement - An Endocrine Disruptor That Should Give Every Man Pause

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Evidence-based medicine provides guidance for the responsible practice of medicine and this is always in a state of flux as new data are added to the current body of knowledge.  Very few topics in medicine are without controversy — partly because data are not always clearcut.

One such issue which has been a source of confusion and contention is hormone replacement therapy (HRT).  A recent paper, published in the Texas Heart Institute Journal, discusses important issues to consider in men who are treating age-related declines in testosterone levels.  Unlike menopause when estrogen levels drop precipitously, testosterone levels in men gradually decline about 1-2 percent per year after age 40.  This phase is cheekily referred to as “manopause,” and can be associated with symptoms such as fatigue, low energy, decreased libido, and depression.

In some men with hypogonadism, a condition of testosterone deficiency, HRT has been the well-established treatment of choice. The deficiency of testosterone in men with hypogonadism has been associated with cardiovascular disease, obesity, decreased HDL ("good") cholesterol, increased LDL ("bad") cholesterol, high blood pressure, increased incidence of diabetes, and increased markers of inflammation -  testosterone replacement decreases these risks as well as the risk of cardiovascular events and possibly death attributable to CV disease. Whereas testosterone replacement therapy (TRT) was once reserved for young men suffering from testosterone deficiency (whatever the etiology), in the last decade, there has been an exponential increase in the use of TRT for anyone with low testosterone - or symptoms attributed to it.

What happens when testosterone is taken surreptitiously or for reasons not medically warranted? Replacing what the body makes naturally will cause a disruption in the “pituitary-testicular axis,” which is a feedback communication pathway of the endocrine system.  Under normal physiological conditions, this feedback loop maintains the appropriate hormonal milieu. When the body’s burden to produce a hormone is removed, that gland will subsequently atrophy - testosterone replacement shrinks the testes and reduces sperm count - one need only look at bodybuilders for verification.  

Aside from the physical manifestations, several studies and a warning from the Food and Drug Administration (FDA), indicate that there is an increased risk of heart attack and stroke in men who use TRT.  These findings are similar in post-menopausal women taking estrogen replacement therapy.  A study, published in the NEJM in 2009 had to be abruptly halted when a pattern of adverse cardiovascular events was observed in men receiving HRT.  While treating young men is appropriate, exogenous testosterone administration to aging men and men who have pre-existing cardiovascular disease would appear to be grossly negligent.

Despite the countless studies and FDA warning of these troubling findings, it has not stopped the persistent calls to question whether these findings are real and it certainly has not stopped marketers from capitalizing on the short-term benefits of TRT, which include improved libido and body composition.

Aside from the barrage of viagra commercials depicting handsome, older gentlemen playing golf whilst displaying trophy girlfriends, there has been no shortage of marketing the normal aging process in men as a condition to be treated - a condition popularly referred to as “low t” (low testosterone levels). With promises of increased sexual vigor, the sudden ability to operate a speedboat and having many attractive friends, what is downplayed in these commercials is not only the increased risk of heart attacks and strokes, but also risks of accidental exposure of testosterone to close contacts - such as partners, children, and even pets.  In children exposure to testosterone can cause premature puberty, enlargement of sexual organs, increased sexual and aggressive behavior.  Female partners who have been exposed can experience hirsutism and acne.  Exposure in pregnant women can cause masculinization of a female fetus.  

Not everything can or should be treated.  While there are instances that medically warrant the use of TRT, for the vast majority of the male population, there is no magic antidote.  There is no cure to reverse the process of aging nor the hormonal changes that accompany it.  Before turning your wife into the bearded lady, the best way to manage fatigue, depression and weight gain is to focus on exercise, weight loss, and a healthy diet.