harold
Established Member
- Reaction score
- 11
Hey all,
Some of you might have noticed that I am interested in the effect of dual inhibition of aromatase and 5ar and whether in doing so it may help to overcome some/all of the sides experienced by some who use dutasteride/finasteride and whether some who have had to give up due to those sides can subsequently use these products again by keeping estrogen under contrrol. I have also been worried as to whether it is possible to do this without overwhelming the beneficial effects of DHT inhibition on hairloss since estrogen and DHT are often antagonistic.
Found this on the web and since looked it up in the journals. It is an article that seems to be by an aging GP with a growing prostate and a dwindling sex drive who prescribed himself testosterone replacement therapy, some kind of 5ar inhibitor (probably finasteride) and an aromatase inhibitor. After 9 months his test levels were much higher, his estrogen was pretty much undetectable, sexual function had improved and - he noted that hair growth was improved. HE didnt get any more specific that "hair: growth" but I assume he is not talking about chest hair. No prostate cancer either.
Anyway I think thi is interesting stuff especially since there are so few reports of anyone following such a regimen for any length of time. This guy had been doing it with tweaks for a couple of years by the time he wrote in. He has other stuff about antioxidants and so forth but it was the dual inhibition of %ar and aromatase that got me interested. Anyway check it out.
hh
Antioxidants for safer testosterone supplementation - Letters to the Editor
Townsend Letter for Doctors and Patients, Feb-March, 2002
Editor:
The intent of this letter is provide additional empirical knowledge to the recent advances in the biochemistry of testosterone metabolism. Within the last few years, it has it become increasingly probable that certain oxidized metabolites of estrone and estradiol are sources of carcinogens that lead to cancers of the breast, prostate, endometrium and probably others not yet known. Although unfavorable metabolic processes can convert testosterone to the estrogens and then to carcinogenic metabolites, testosterone itself has not been found to be carcinogenic. To the contrary, testosterone has been found to be protective against cancer. Further complicating the understanding of how estrogens are metabolized to carcinogens is the unintentional intake of environmental chemicals that mimic the estrogens and are carcinogenic.
Biochemistry of Testosterone Metabolism
Advertisement
The following simplified diagram is intended to be helpful in understanding the sequence of chemical reactions that can make testosterone supplementation safe or dangerous.
Testosterone can be converted to: (1) dihydrotestosterone (DHT) by reduction catalyzed by the 5 alpha reductase enzyme, (2) androstenedione by oxidation, and (3) estradiol by oxidation and aromatization catalyzed by the aromatase enzyme.
Androstenedione can be converted to: (1) testosterone by reduction, and (2) estrone by oxidation and aromatization catalyzed by the aromatase enzyme.
Estradiol can be converted to: (1) estrone by oxidation, (2) estratriol by oxidation, (3) 2-hydroxyestradiol (protective) by oxidation, (4) 4-hydroxyestradiol (carcinogenic) by oxidation.)
Estrone can be converted to: (1) estradiol by reduction, (2) 2-hydroxyestrone (protective) by oxidation, (3) 4-hydroxyestrone (carcinogenic) by oxidation, and (4) 16 alpha-hydroxyestrone (carcinogenic) by oxidation.
The current primary strategy, for testosterone supplementation is to use 5 alpha reductase inhibitors to minimize dihydrotestosterone (to prevent enlargement of the prostate) and to use aromatase inhibitors to minimze estradiol. and estrone (to minimize carcinogenic metabolites).
A Personal Episode
1995 (age 66), I had my first PSA (prostate specific antigen) test which came in at 5.6 ng/ml. At the HMO anything over 4.0 shunted me to the urologist for a biopsy of the prostate. He took six slivers of flesh. (each about 3/4" long and a pencil point in diameter) out of the prostate without anesthesia. It was not only extremely painful, but it was also terrifying. Because three slivers on each side of the prostate is like stabbing in the dark for accuracy, current practice is to take up to eighteen shots at the prostate. I saw blood in the ejaculate for about a month.
After keeping me waiting for over a month for the results of the biopsy (during which time the sympathetic nervous system carried my blood pressure to a persistent 190/110 [normally 120/70]), I was told that I did not have cancer in the six slivers of tissue. I did have a prostate that was 50% larger (60cc) than normal (40cc). I swore I would never have another prostate biopsy.
In mid-1998 (age 69), a saliva test showed my testosterone was 60 pg/ml which was about normal for' an 80 year-old man. My diminished sexual function had already told me that I really longed for the pleasures of the past.
I began to supplement with testosterone cream (5% testosterone) by rubbing a small amount under my arm where it could spend all day being absorbed. I did not use the palms of my hands because I washed my hands frequently during the day. I was well aware of the dangers of enlarging the prostate further or getting prostate cancer by the conversion of testosterone to the estrogens. Those threats caused me to supplement with an array of antioxidants and inhibitors of aromatization and an inhibitor of testosterone to DHT. The program also included a wide array of supplemental nutrients for metabolic support and detoxication.
In early 1999, about nine months after beginning testosterone supplementation, a saliva test (measures "free" [immediately active] hormones) showed testosterone at 880 pg/ml (pg/ml=parts per trillion) and estradiol at 0.5 pg/ml (the low limit of the test). This saliva test indicated that the testosterone supplementation worked well -- perhaps too well, and the efforts to prevent conversion to estradiol were successful. The beneficial physiological effects of testosterone were evident not only in sexual function, but also in strength, hair: growth and especially in a feeling of well-being. Nevertheless, I decided to use much less testosterone in the coming months because of the dangers of high concentrations. I estimated that testosterone in the saliva of a 20 year-old would be about 600 pg/ml. My aim was to reduce the '880 to the 400-600 range.
In late 1999, another saliva test showed testosterone at only 100 pg/ml. I then a djusted the amount of testosterone applied to 1-2 mg every other day. The saliva level then rose to 550 pg/mi. Estradiol continued at 0.5 pg/ ml (the lowest measurable level). Estrone was reported at 1.1 pg/ml.
In 2000, I had an MRI (magnetic resonance imaging) with spectroscopic analysis of the prostate. It 'showed no detectable cancer throughout the entire prostate (much better than a biopsy!). This gave me courage for my next action. I decided to experiment with my regimen to limit estradiol and estrone. I stopped taking the aromatase and 5 alpha reductase inhibitors, but I continued the full set of antioxidants.
After about four months (November 2000), the saliva test showed testosterone at 550 pg/mi, estracliol at 0.5 pg/ml and estrone at 1.9 pg/ml. I was pleasantly surprised that estradiol had not risen at all, and that estrone had risen by only a small amount. This experiment indicated that the oxidation reactions of testosterone to estradiol and androstenedione to estrone were inhibited by the array of antioxidants. Furthermore, since the testosterone level remained high, it was probable that the oxidation of testosterone to androstenedione was also inhibited by the antioxidants.
My current protocol emphasizes antioxidants, but to be more secure, I also take the aromatization inhibitors and the 5 alpha reductase inhibitor. In addition, I have stepped up the use of detoxication nutrients because of the unprecedented dangers of environmental estrogen mimics.
Advertisement
Controlling Eicosanoids is a Prime Requisite for Safe Testosterone Supplementation
Hypothalamic sensitivity (necessary for all hormone production) is powered by cyclic adenosine monophosphate (cyclic AMP) which is under eicosanoid control. The hormone glucagon promotes positive eicosanoids, while excess insulin produces negative eicosanoids. The control of glucagon and insulin is in the diet. Based on what Barry Sears, PhD teaches us in his book The Antiaging Zone, implementing the production of positive eicosanoids is a prime requisite for a beneficial testosterone supplementation program. The main factors that promote glucagon dominance are:
* Hypocaloric diet (eat slightly less calories than used -- calorie restriction)
* Diet should be 30% protein (mainly cold water ocean fish), 30% fat (cod liver oil and olive oil), and 40% complex carbohydrates -- no sugar or high glycemic foods -- no hydrogenated oils including margarine -- lots of fiber to slow the digestion process and to promote detoxication.
The main factors that promote insulin dominance are:
* Hypercaloric diet (eating more calories than used -- gaining weight)
* Diet that is high in carbohydrates, high in sugar, high in other high glycemic foods (simple carbohydrates), and low in fiber.
Stanford Field
20730 Celeste Circle
Cupertino, California 95014 USA
Some of you might have noticed that I am interested in the effect of dual inhibition of aromatase and 5ar and whether in doing so it may help to overcome some/all of the sides experienced by some who use dutasteride/finasteride and whether some who have had to give up due to those sides can subsequently use these products again by keeping estrogen under contrrol. I have also been worried as to whether it is possible to do this without overwhelming the beneficial effects of DHT inhibition on hairloss since estrogen and DHT are often antagonistic.
Found this on the web and since looked it up in the journals. It is an article that seems to be by an aging GP with a growing prostate and a dwindling sex drive who prescribed himself testosterone replacement therapy, some kind of 5ar inhibitor (probably finasteride) and an aromatase inhibitor. After 9 months his test levels were much higher, his estrogen was pretty much undetectable, sexual function had improved and - he noted that hair growth was improved. HE didnt get any more specific that "hair: growth" but I assume he is not talking about chest hair. No prostate cancer either.
Anyway I think thi is interesting stuff especially since there are so few reports of anyone following such a regimen for any length of time. This guy had been doing it with tweaks for a couple of years by the time he wrote in. He has other stuff about antioxidants and so forth but it was the dual inhibition of %ar and aromatase that got me interested. Anyway check it out.
hh
Antioxidants for safer testosterone supplementation - Letters to the Editor
Townsend Letter for Doctors and Patients, Feb-March, 2002
Editor:
The intent of this letter is provide additional empirical knowledge to the recent advances in the biochemistry of testosterone metabolism. Within the last few years, it has it become increasingly probable that certain oxidized metabolites of estrone and estradiol are sources of carcinogens that lead to cancers of the breast, prostate, endometrium and probably others not yet known. Although unfavorable metabolic processes can convert testosterone to the estrogens and then to carcinogenic metabolites, testosterone itself has not been found to be carcinogenic. To the contrary, testosterone has been found to be protective against cancer. Further complicating the understanding of how estrogens are metabolized to carcinogens is the unintentional intake of environmental chemicals that mimic the estrogens and are carcinogenic.
Biochemistry of Testosterone Metabolism
Advertisement
The following simplified diagram is intended to be helpful in understanding the sequence of chemical reactions that can make testosterone supplementation safe or dangerous.
Testosterone can be converted to: (1) dihydrotestosterone (DHT) by reduction catalyzed by the 5 alpha reductase enzyme, (2) androstenedione by oxidation, and (3) estradiol by oxidation and aromatization catalyzed by the aromatase enzyme.
Androstenedione can be converted to: (1) testosterone by reduction, and (2) estrone by oxidation and aromatization catalyzed by the aromatase enzyme.
Estradiol can be converted to: (1) estrone by oxidation, (2) estratriol by oxidation, (3) 2-hydroxyestradiol (protective) by oxidation, (4) 4-hydroxyestradiol (carcinogenic) by oxidation.)
Estrone can be converted to: (1) estradiol by reduction, (2) 2-hydroxyestrone (protective) by oxidation, (3) 4-hydroxyestrone (carcinogenic) by oxidation, and (4) 16 alpha-hydroxyestrone (carcinogenic) by oxidation.
The current primary strategy, for testosterone supplementation is to use 5 alpha reductase inhibitors to minimize dihydrotestosterone (to prevent enlargement of the prostate) and to use aromatase inhibitors to minimze estradiol. and estrone (to minimize carcinogenic metabolites).
A Personal Episode
1995 (age 66), I had my first PSA (prostate specific antigen) test which came in at 5.6 ng/ml. At the HMO anything over 4.0 shunted me to the urologist for a biopsy of the prostate. He took six slivers of flesh. (each about 3/4" long and a pencil point in diameter) out of the prostate without anesthesia. It was not only extremely painful, but it was also terrifying. Because three slivers on each side of the prostate is like stabbing in the dark for accuracy, current practice is to take up to eighteen shots at the prostate. I saw blood in the ejaculate for about a month.
After keeping me waiting for over a month for the results of the biopsy (during which time the sympathetic nervous system carried my blood pressure to a persistent 190/110 [normally 120/70]), I was told that I did not have cancer in the six slivers of tissue. I did have a prostate that was 50% larger (60cc) than normal (40cc). I swore I would never have another prostate biopsy.
In mid-1998 (age 69), a saliva test showed my testosterone was 60 pg/ml which was about normal for' an 80 year-old man. My diminished sexual function had already told me that I really longed for the pleasures of the past.
I began to supplement with testosterone cream (5% testosterone) by rubbing a small amount under my arm where it could spend all day being absorbed. I did not use the palms of my hands because I washed my hands frequently during the day. I was well aware of the dangers of enlarging the prostate further or getting prostate cancer by the conversion of testosterone to the estrogens. Those threats caused me to supplement with an array of antioxidants and inhibitors of aromatization and an inhibitor of testosterone to DHT. The program also included a wide array of supplemental nutrients for metabolic support and detoxication.
In early 1999, about nine months after beginning testosterone supplementation, a saliva test (measures "free" [immediately active] hormones) showed testosterone at 880 pg/ml (pg/ml=parts per trillion) and estradiol at 0.5 pg/ml (the low limit of the test). This saliva test indicated that the testosterone supplementation worked well -- perhaps too well, and the efforts to prevent conversion to estradiol were successful. The beneficial physiological effects of testosterone were evident not only in sexual function, but also in strength, hair: growth and especially in a feeling of well-being. Nevertheless, I decided to use much less testosterone in the coming months because of the dangers of high concentrations. I estimated that testosterone in the saliva of a 20 year-old would be about 600 pg/ml. My aim was to reduce the '880 to the 400-600 range.
In late 1999, another saliva test showed testosterone at only 100 pg/ml. I then a djusted the amount of testosterone applied to 1-2 mg every other day. The saliva level then rose to 550 pg/mi. Estradiol continued at 0.5 pg/ ml (the lowest measurable level). Estrone was reported at 1.1 pg/ml.
In 2000, I had an MRI (magnetic resonance imaging) with spectroscopic analysis of the prostate. It 'showed no detectable cancer throughout the entire prostate (much better than a biopsy!). This gave me courage for my next action. I decided to experiment with my regimen to limit estradiol and estrone. I stopped taking the aromatase and 5 alpha reductase inhibitors, but I continued the full set of antioxidants.
After about four months (November 2000), the saliva test showed testosterone at 550 pg/mi, estracliol at 0.5 pg/ml and estrone at 1.9 pg/ml. I was pleasantly surprised that estradiol had not risen at all, and that estrone had risen by only a small amount. This experiment indicated that the oxidation reactions of testosterone to estradiol and androstenedione to estrone were inhibited by the array of antioxidants. Furthermore, since the testosterone level remained high, it was probable that the oxidation of testosterone to androstenedione was also inhibited by the antioxidants.
My current protocol emphasizes antioxidants, but to be more secure, I also take the aromatization inhibitors and the 5 alpha reductase inhibitor. In addition, I have stepped up the use of detoxication nutrients because of the unprecedented dangers of environmental estrogen mimics.
Advertisement
Controlling Eicosanoids is a Prime Requisite for Safe Testosterone Supplementation
Hypothalamic sensitivity (necessary for all hormone production) is powered by cyclic adenosine monophosphate (cyclic AMP) which is under eicosanoid control. The hormone glucagon promotes positive eicosanoids, while excess insulin produces negative eicosanoids. The control of glucagon and insulin is in the diet. Based on what Barry Sears, PhD teaches us in his book The Antiaging Zone, implementing the production of positive eicosanoids is a prime requisite for a beneficial testosterone supplementation program. The main factors that promote glucagon dominance are:
* Hypocaloric diet (eat slightly less calories than used -- calorie restriction)
* Diet should be 30% protein (mainly cold water ocean fish), 30% fat (cod liver oil and olive oil), and 40% complex carbohydrates -- no sugar or high glycemic foods -- no hydrogenated oils including margarine -- lots of fiber to slow the digestion process and to promote detoxication.
The main factors that promote insulin dominance are:
* Hypercaloric diet (eating more calories than used -- gaining weight)
* Diet that is high in carbohydrates, high in sugar, high in other high glycemic foods (simple carbohydrates), and low in fiber.
Stanford Field
20730 Celeste Circle
Cupertino, California 95014 USA
