Controversies of Testosterone Replacement Therapy (TRT) - Dr Zakany

[trikydik]

Traditional physicians who have not received advanced training in Anti-Aging Medicine typically believe that hormone levels should not be optimized or corrected unless they fall outside the "normal range". The problem is that the "normal range" is typically not age specific and dependent on the lab. It usually includes the range of what 90% of all tested fall into. This would mean that only 5% of all people tested would be considered either high or low.

Both total and free testosterone studies should be measured to adequately evaluate testosterone levels . Depending on the lab used, approximately 300-900 ng/dL are given as a normal laboratory range, for men ages 20-70. For females, this range is 15-70 ng/dL. Free testosterone levels average approximately 2% of the total, 55-200 pg/ml for men and 1-10 pg/ml for women. Free testosterone is the more valuable of the two, reflecting the amount of hormone available to perform useful work.

Relying on a 50-year age span (from ages 20 to 70) for a "normal range" is not useful. A decline of 70% from more youthful levels can produce numerous clinical problems, yet is declared "within normal range". A more accurate approach is using the upper end of normal range," adjusted for age-then maintain these levels over time, rather than letting them continually decline. This is the healthy or optimal range.

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 thirties, forties, or not until his fifties; however, it will drop eventually to a lower level than when he was twenty. If it drops below 300, 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 100 pg/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 over 35%, and he notices he has been having trouble building muscles at the gym, and having a tougher time keeping the weight off of his waist? This is the center of the controversy.

Two questions come to mind when considering this controversy. First, are there benefits to raising a testosterone level from 500 to 800 ng/dl? If so, are there any significant risks, both short and long term, in maintaining this level of testosterone with therapy?

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. 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 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 effectively treated with topical or oral medications. The tendency to lose scalp hair can be exacerbated as well, but this also can be effectively treated with a medication that inhibits the conversion of testosterone to dihydrotestosterone called finasteride or Propecia.

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 before starting TRT and we continue to monitor it twice yearly.

The concern about a link between testosterone and heart disease comes from the following line of thinking: 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 (bad cholesterol), and triglycerides, and no change or only a slight decrease in HDL (good cholesterol). And, as mentioned above, restoring youthful testosterone levels can reverse the metabolic syndrome that can increase the risk of cardiovascular disease.

Before moving on, we want to clarify some misconceptions about what testosterone is and is not. While testosterone is a member of the group of compounds known as 'anabolic steroids ,' the muscle and bone building molecules, it is different from the kind this term often refers to, such as those that have been abused by body builders and professional athletes. These include decadurabolin, oxandrolone, and methyltestosterone which are different from testosterone in their molecular structure and not normally found in the human body. These are potent anabolic hormones, but they can have adverse effects on other organ systems, such as the brain and liver, due to this changed structure; therefore, while they have similar muscle building effects, the side effect profiles are not comparable. Because unscrupulous doctors and black marketers sold these drugs in high doses to young men and professional athletes, they, and testosterone along with them, became regulated as schedule II substances like morphine and other narcotics. This has tarnished testosterone's image amongst doctors and the public to the detriment of many who would benefit from responsible well-monitored TRT.

[Beethoven]

Very good read. Most Doctors today, like the one I had shoot not for an optimal level but the middle of the scale. Some may need a higher level to feel optimal.

[dreadnok89]

My question is: why even let them drop? Losing hair is natural in men but they try their dam nest to get it back.

[2Sox]

The concern about a link between testosterone and heart disease comes from the following line of thinking: 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 (bad cholesterol), and triglycerides, and no change or only a slight decrease in HDL (good cholesterol). And, as mentioned above, restoring youthful testosterone levels can reverse the metabolic syndrome that can increase the risk of cardiovascular disease.

Great piece, Triky. Although it's not footnoted, it does cite available research, and does so very clearly. Actually, it's a great rebuttal that could be posted on this thread:
http://forums.steroid.com/hormone-re...rt-attack.html