Risk Of Testosterone Replacement Therapy

Risks Of Testosterone Replacement Therapy In Men

What are the risks?

As we mentioned previously, there is extensive evidence that replacing testosterone in ‘hypogonadism’ is warranted and is FDA approved. At sometime during his life a man will begin to experience a decline in testosterone levels, both free and total. It may be in his mid thirties, forties, or not until his fifties; eventually, however, it will drop to a lower level than when he was twenty. If it drops below 300 (assuming he is lucky enough to get his doctor to check it), then there is no controversy—it should be treated. But what about the 50 year old otherwise healthy male with a total testosterone of 500 ng/dl and a free testosterone level of 90 ng/dl who may have had a level of 800 when he was in his early twenties? Should he wait until he reaches the “magic” number of 300 for his total testosterone level before he starts TRT? Or is it sufficient that his level has already dropped more than 30 percent, he notices he has been having trouble making progress at the gym, and he notices that it is tougher to keep the weight off of his waist? Herein lies the crux of the controversy.

Two questions immediately come to mind when pondering this controversy. First, Are there benefits to be had from raising a testosterone level from 500 to 800 ng/dl? If there are, Are there any significant risks—both short and long term—to maintaining this level of testosterone with therapy? The first is the “Where’s the beef?” question; the second is the “There’s no free lunch” healthy skepticism question.

A number of studies have been done in healthy young men in which doses of testosterone were given that raised their levels into the high adolescent range—1000 to 2000 ng/dl. In all of these studies, lean muscle mass has increased and fat mass has decreased. Similar studies with lower doses have been done in moderately obese men; again, lean mass increased and fat decreased even more. Moreover, insulin resistance (a pre-diabetic state) improved, triglycerides decreased, and energy increased. In case you’re wondering, none of these studies noted any increase in aggressive behavior that many people expect might happen with high doses of testosterone.

Many more studies have been published showing similar effects in older men (over 65) with mildly low testosterone levels. The NIA has published the results of studies of TRT on body composition (lean muscle and fat ratios) in 108 men which demonstrated a 6 lb. fat loss and 5 lb. lean muscle gain when the testosterone level was raised from an average of 370 to 640 ng/dl for 36 months. The same men had an increase in bone density if they started out with a low bone density. The accumulating evidence shows that whenever you raise the testosterone level—no matter what the starting level—you get benefits in body composition. We think that the dose of testosterone used in this study was too low and that if higher dose had been used even more impressive results would have been demonstrated, without any significant increase in adverse effects.

Short term risks

What about that free lunch question? Short term risks, what we call side effects, are few. If a man had a propensity to develop acne as a teenager, this may be reactivated when the testosterone levels get raised back to adolescent levels. This can be treated with topical or oral medications quite effectively. The tendency to lose scalp hair can be exacerbated as well, but this too can be effectively treated with a medication that inhibits the conversion of testosterone to dihydrotestosterone called finasteride or Propecia.

Prostate

The main concern that men have with regard to long term TRT is whether it will increase the risk of prostate cancer, BPH, and cardiovascular disease. At physiologic replacement levels—the range we keep our patients within—there is no evidence of any increase risk of prostate cancer or enlargement of the prostate to the point of symptoms. It is true that the longest prospective study is the three year NIA study—which didn’t show any prostate problems—but the overwhelming majority of case-controlled, retrospective, epidemiological studies following men for many years show no increased risk in men whose testosterone levels are higher than average. The concern about TRT increasing the risk of prostate cancer stems from the well documented fact that prostate cancers shrink if you deprive them of testosterone; however, as with breast cancer, this does not prove a causal or initiating role. If one does have an occult (as yet undetected ) cancer, then it may cause it to grow, but we screen all our patients with a total PSA and the newer free PSA ( a more specific test) before starting TRT and we continue to monitor it twice yearly.

Cardiovascular disease

The concern about a link between testosterone and heart disease comes from the following line of reasoning: men have a higher incidence of heart disease than women; men have higher testosterone levels than women; therefore, higher testosterone levels may cause a greater incidence of heart disease. This is another example of the fallacious reasoning that plagues the field of hormone replacement therapy. Because two conditions are found in the same population, it does not necessarily follow that the one causes the other. For these two conditions—testosterone levels and heart disease—we have, in fact, the results of many studies that show just the opposite. This has been studied extensively and there is a greater incidence of heart disease in men with low testosterone levels than those with high levels. More dramatic evidence comes from the fact that giving testosterone intravenously during angina results in improvement in symptoms. Other studies have looked at the effect of TRT on cholesterol levels and have universally found a decrease in total cholesterol, LDL, and triglycerides, and no change or only a slight decrease in HDL. And, as mentioned above, restoring youthful testosterone levels can reverse the metabolic syndrome that can increase the risk of cardiovascular disease. So much for the prevailing wisdom.

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