Questions Re Absorbability of testosterone Gels

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http://david-zava.blogspot.com/2010/07/testosterone-elixir-or-dangerous-drug.htm\

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Let's look at some assumptions made about using conventional venous serum to

monitor how much testosterone is entering the body following topical

testosterone therapy. It is " assumed " that when testosterone is delivered as a

topical gel only 10% is absorbed and utilized by the body. This is based on

measuring the total amount of testosterone that can be detected in venous serum

over a specific time frame, usually about 12-24 hours, after the testosterone

has been applied to the skin. With this conventional wisdom of 10% absorption,

topical testosterone gel has been FDA-approved at a pharmacological dose about

10 times higher (50-100 mg) than the amount a healthy young male's testes will

manufacture in a day, which is about 5-10 mg of testosterone.

What evidence do we have that the pharmacological dose (50-150 mg) of topical

testosterone used in the NEJM study was actually " delivering " a physiological

dose of testosterone into the tissues of these older men? The correct answer is

none. This would require measuring the levels of testosterone in different

tissue biopsies, which for obvious reasons is not practical and such studies

would not likely find many volunteers.

However, there are other means to look a little closer at " tissue " exposure to

testosterone, which is to measure the level in the fluid of tissues bathed by

capillary beds (blood flowing to tissues and delivering nutrients and hormones)

as opposed to blood flowing away from tissues (i.e. venous blood). Capillary

blood and saliva provide the next-best alternative as they are easily accessible

body fluids that are more representative of the direct interaction of capillary

beds with tissues (6,7).

In mining this extensive database, we find that when steroid hormones are

produced endogenously by the ovaries and testes and released into the

bloodstream the levels in venous blood serum are quantitatively equivalent to

whole capillary blood drawn from the finger (7). Under the same conditions,

salivary hormones are about 2-3% of venous serum or capillary blood hormone

levels, as reported extensively in the literature (6).

In contrast to what we see with endogenously produced hormones, when

testosterone, or any other steroid hormone, is applied topically as a cream,

gel, or spray, levels in capillary blood (finger) are remarkably higher, by

10-20 fold, than venous blood levels. Moreover, salivary hormones are often

>100% of venous serum levels, which ordinarily are only 2-3%. This remarkable

increase in capillary blood and salivary testosterone is NOT seen when it, or

other hormones, are delivered orally, or as im-injections or sc-pellet implants.

With these delivery systems capillary blood and venous serum levels are about

the same.

This discrepancy in venous serum vs capillary blood and salivary hormone levels

following topical hormone delivery has created enormous confusion among

physicians attempting to interpret hormone test results. Those using venous

serum are often frustrated that pharmacological dosing, as seen in the NEJM

article, only leads to lower to mid-physiological serum testosterone levels, but

side effects such as excessive buildup of red blood cells associated with

pharmacological dosing. On the other side, those using saliva and capillary

blood testing are shocked to see that pharmacological dosing leads to

pharmacological levels much higher than expected.

Specifically, with reference to the use of topical testosterone gels in men at

the 50-150 mg dosage, we find mean capillary (finger tip) blood levels of

testosterone to be about 5000 ng/dL, approximately 10 x higher than the

venipuncture serum blood levels reported in the NEJM study (574 +/- 403 ng/dL).

Of further relevance to the NEJM study, we find that men using the higher

pharmacological topical testosterone gel have capillary blood levels of

estradiol that usually exceed 100 pg/ml, which is very high for males. While

physiological levels of estrogens are beneficial to the male cardiovascular

system, higher levels can be harmful (8). Unfortunately, estrogens were not

monitored in the NEJM study so it is not possible to know if levels, even in

venous serum, were higher than physiological range. It is very possible that

some of the cardiovascular events observed in the older high risk men

participating in the NEJM study were precipitated by excess estrogens derived

from excess testosterone.

houghts and opinions are appreciated as I am confused.