cvictorg
New Member
http://david-zava.blogspot.com/2010/07/testosterone-elixir-or-dangerous-drug.html
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.
The NEJM study (1), and many others preceding it (4,5), confirmed that the daily topical dosage of 50-150 mg testosterone results in a level of serum testosterone (mean 574 ng/dL) that would be considered healthy in young men.
It is “assumed” that when testosterone is delivered into the body using a topical gel that serum testosterone measurements, derived from a venous blood draw, actually reflect how much testosterone is entering tissues throughout the body.
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).
Over the past 10 years ZRT Laboratory has measured the levels of steroid hormones (estradiol, progesterone, testosterone, DHEAS, cortisol) in saliva and capillary blood (finger stick) from men and women who have used a plethora of different hormone doses and delivery systems (topical creams and alcoholic gels, oral, im-injections, sc-pellets, sublingual drops, and troches). Information on hormone type, dosage, delivery, and timing on well over a million people has been recorded in our database.
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.
We believe these differences in conventional venipuncture serum vs capillary blood and saliva testosterone provide a rational explanation for the unexpected adverse clinical events seen in the NEJM study.
Thoughts and opinions are appreciated as I am confused. Are the measurements taken via blood providing an accurate measurement of our testosterone levels??
http://www.testosteroneupdate.org/20...calConsult.php
Also - The US Food and Drug Administration (FDA) recently recommended that testosterone supplements in development achieve average serum concentrations (Cavg) of testosterone within the normal range (300-1000 ng/dL) for ?75% of subjects and maximum serum concentrations (Cmax) of testosterone <1500 ng/dL in more than 85% of patients, with <5% at 1800 to 2500 ng/dL and none ?2500 ng/dL (US Food and Drug Administration, oral communication, 2008).
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.
The NEJM study (1), and many others preceding it (4,5), confirmed that the daily topical dosage of 50-150 mg testosterone results in a level of serum testosterone (mean 574 ng/dL) that would be considered healthy in young men.
It is “assumed” that when testosterone is delivered into the body using a topical gel that serum testosterone measurements, derived from a venous blood draw, actually reflect how much testosterone is entering tissues throughout the body.
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).
Over the past 10 years ZRT Laboratory has measured the levels of steroid hormones (estradiol, progesterone, testosterone, DHEAS, cortisol) in saliva and capillary blood (finger stick) from men and women who have used a plethora of different hormone doses and delivery systems (topical creams and alcoholic gels, oral, im-injections, sc-pellets, sublingual drops, and troches). Information on hormone type, dosage, delivery, and timing on well over a million people has been recorded in our database.
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.
We believe these differences in conventional venipuncture serum vs capillary blood and saliva testosterone provide a rational explanation for the unexpected adverse clinical events seen in the NEJM study.
Thoughts and opinions are appreciated as I am confused. Are the measurements taken via blood providing an accurate measurement of our testosterone levels??
http://www.testosteroneupdate.org/20...calConsult.php
Also - The US Food and Drug Administration (FDA) recently recommended that testosterone supplements in development achieve average serum concentrations (Cavg) of testosterone within the normal range (300-1000 ng/dL) for ?75% of subjects and maximum serum concentrations (Cmax) of testosterone <1500 ng/dL in more than 85% of patients, with <5% at 1800 to 2500 ng/dL and none ?2500 ng/dL (US Food and Drug Administration, oral communication, 2008).
