I posted this over at Cutting Edge Muscle, but since that forum is kind of dead, I thought I would repost over here and see if I can get an answer. Basically, I'm trying to figure out how nandrolone converts to estrogen, what rate it converts it, does it convert through aromatase and how, and does it also convert through Cytochrome P450 how often and what is the % (if these figures are even available).
I'm doing some research on nandrolone for an article I'm writing and I'm getting conflicting information on how nandrolone interacts with the aromatase enzyme and how it may convert to estrogen in the liver via P450.
There is a study referenced in many articles having to do with this titled: Can 19-nortestosterone derivatives be aromatized in the liver of adult humans?. However, it many references two progesterone based birth control formulas called tibolone and norethisterone.
Further, in a book titled Doping in Sports (Handbook of Experimental Pharmacology, Vol. 195) 1st Edition
by Detlef Thieme (Editor), Peter Hemmersbach (Editor)
Also, over on Ergo-Log's steroid handbook, they have the following quote:
21. The Real Anabolic Steroids
which speculated that nandrolone completely suppresses testosterone and might fully cause estrogen production to cease, which I'm a bit skeptical about.
Theories, speculation, conjecture and confusion are welcome. Thanks in advance,
pogue
I'm doing some research on nandrolone for an article I'm writing and I'm getting conflicting information on how nandrolone interacts with the aromatase enzyme and how it may convert to estrogen in the liver via P450.
There is a study referenced in many articles having to do with this titled: Can 19-nortestosterone derivatives be aromatized in the liver of adult humans?. However, it many references two progesterone based birth control formulas called tibolone and norethisterone.
Here are some quotes from the full text:Climacteric. 2007 Aug;10(4):344-53.
Can 19-nortestosterone derivatives be aromatized in the liver of adult humans? Are there clinical implications?
Kuhl H1, Wiegratz I.
Author information
1Department of Obstetrics & Gynecology, J.W. Goethe University Frankfurt, Frankfurt am Main, Germany.
Abstract
CONTEXT:
Previous studies in postmenopausal women have demonstrated that, after oral administration of norethisterone, a small proportion of the compound is rapidly converted into ethinylestradiol. The shape of the concentration - time curve suggested that this occurred in the liver. The results were confirmed by in vitro investigations with adult human liver tissue. In 2002, it was shown that, after oral treatment of women with tibolone, aromatization of the compound occurred, resulting in the formation of a potent estrogen, 7 alpha-methyl-ethinylestradiol. The result has been called into question, because the adult human liver does not express cytochrome P450 aromatase, which is encoded by the CYP 19 gene. Moreover, it has been claimed that the serum level of 7 alpha-methyl-ethinylestradiol measured by gas chromatography/mass spectrometry was an artifact.
REPLY:
Aromatization of steroids is a complex process of consecutive oxidation reactions which are catalyzed by cytochrome P450 enzymes. The conversion of the natural C19 steroids, testosterone and androstenedione, into estradiol-17beta and estrone is dependent on the oxidative elimination of the angular C19-methyl group. This complex key reaction is catalyzed by the cytochrome P450 aromatase, which is expressed in many tissues of the adult human (e.g. ovary, fat tissue), but not in the liver. However, 19-nortestosterone derivatives are characterized by the lack of the C19-methyl group. Therefore, for the aromatization of these synthetic steroids, the action of the cytochrome P450 aromatase is not necessary and the oxidative introduction of double bonds into the A-ring can be catalyzed by other hepatic cytochrome P450 enzymes. The final key process in the formation of a phenolic A-ring, both in natural androgens and 19-nortestosterone derivatives, is the enolization of a 3-keto group to the C2-C3-enol or the C3-C4-enol moiety, which occurs without the action of enzymes.
CONCLUSION:
19-nortestosterone derivatives (norethisterone, norethynodrel, tibolone) can readily be aromatized in the adult human liver. This leads to the formation of the potent estrogens ethinylestradiol from norethisterone or norethynodrel and 7 alpha-methyl-ethinylestradiol from tibolone. This may have clinical consequences, e.g. the elevated risk of venous thromboembolic disease in premenopausal women treated with high doses of norethisterone for bleeding disorders, or the elevated risk of stroke or endometrial disease in postmenopausal women treated with tibolone.
Aromatization of steroids is a complex process of consecutive oxidation reactions which are catalyzed by cytochrome P450 enzymes. The conversion of the natural C19 steroids, testosterone and androstenedione, into estradiol-17B and estrone is dependent on the oxidative elimination of the angular C19-methyl group. This complex key reaction is catalyzed by the cytochrome P450 aromatase, which is expressed in many tissues of the adult human (e.g. ovary, fat tissue), but not in the liver. However, 19-nortestosterone derivatives are characterized by the lack of the C19-methyl group. Therefore, for aromatization of these synthetic steroids, the action of the cytochrome P450 aromatase is not necessary and the oxidative introduction of double bonds into the A-ring can be catalyzed by the other hepatic cytochrome P450 enzymes. The final key process in the formation of a phenolic A-ring, both in natural androgens and 19-nortestosterone derivatives, is the enolization of a 3-keto group to the C2-C3-enol or the C3-C4-enol moiety, which occurs without the action of enzymes.
Conclusion 19-nortestosterone derivatives (norethisterone, norethynordrel, tibolone) can readily be aromatized in the adult human liver. This leads to the formation of the potent estrogens ethinylestradiol from norethisterone or norethynodrel and 7a-methyl-ethinylestradiol from tibolone. This may have clinical consequences, e.g. the elevated risk of venous thromboembolic disease in premenopausal women treated with high doses of norethisterone for bleeding disorders, or the elevated risk of stroke or endometrial disease in postmenopausal women treated with tribolone.
AROMATIZATION OF 19-NORTESTOSTERONE DERIVATIVES
The situation is completely different in the aromatization of 19-nortestosterone derivatives like norethynodrel or tibolone. The term ‘19-nor’ represents the lack of an angular C19 methyl group. Therefore, the action of the CYP arom, which eliminates the angular C19 methyl group of natural androgens, is not needed for the aromatization of 19-nortestosterone derivatives (Fig 2).
Tibolone, which is the 7a-methyl-derivative of norethynodrel (Fig3), contains a double bond between C5 and C10 and a keto group at C3.
But, my question is, does this unusual route of administration apply to actual 19nortestosterone (nandrolone) or just it's derivatives?CONCLUSIONS
The conversion of the natural androgens testosterone and androstenedione into estradiol and estrone, which is dependent on the oxidative elimination of the C19-methyl group, is catalyzed by the classical cytochrome P450 aromatase system. Contrary to this, 19-nortestosterone derivatives can be aromatized by other hepatic cytochrome P450 enzymes after simple oxidative introduction of double bonds. This mechanism allows the rapid conversion of a small proportion of norethisterone into ethynlestradiol and of tibolone into 7a-methyl-ethinylestradiol, which occrs rapidly in the liver after oral administration.
Further, in a book titled Doping in Sports (Handbook of Experimental Pharmacology, Vol. 195) 1st Edition
by Detlef Thieme (Editor), Peter Hemmersbach (Editor)
So, my main question is, by what pathway does nandrolone convert to estrogen? Is it through the normal aromatase pathway that testosterone converts? Or is there another pathway that converts via the liver to estrogen through Cytochrome P450. Does it convert through both of these pathways, and if so, what is the generally known rate of conversion?Another important difference between testosterone and nandrolone biotransformation is related to its ability to be aromatised into an oestrogen. Unlike testosterone, nandrolone is not a substrate for the cytochrome P450 aromatase enzyme catalysed transformation to an oestrogen (Behre et al. 2001), although nandrolone-
related substances may undergo aromatisation via a different pathway in the liver
(Kuhl and Wiegratz 2007).
Also, over on Ergo-Log's steroid handbook, they have the following quote:
21. The Real Anabolic Steroids
I was asking Anthony Roberts for his opinion about it, and he pointed me to the following study RheumatologyIn principle nandrolone can aromatize, but this happens only under special circumstances and in small amounts. The normal aromatization of androstanes with the enzyme aromatase can not take place in nandrolone because the 19-methyl group is absent. Other enzymes have to oxidize ring A (remove two hydrogen atoms at C1 and C10) and then, after enolization of the C3-carbonyl group, the aromatic ring A is obtained.
Reduction of the D4 double bond by the enzyme 5AR can take place in a similar way as in testosterone. The androgenic activity of dihydronandrolone and its analogs is lower then that of the corresponding testosterone steroids. This means that less side effects occur in tissues where 5AR is active and converts nandrolone in dihydronandrolone. This results in a better ratio between anabolic and androgenic effects for nandrolone, in comparison with testosterone.
which speculated that nandrolone completely suppresses testosterone and might fully cause estrogen production to cease, which I'm a bit skeptical about.
An RCT of the anabolic steroid nandrolone in 21 men with idiopathic osteoporosis showed an increase in bone density after 3 months of treatment, which decreased to basal levels after 1 yr of treatment [17]. The apparent lack of benefit with nandrolone may be related to suppression of endogenous testosterone production and the inability to aromatize anabolic steroids such as nandrolone to oestradiol.
Theories, speculation, conjecture and confusion are welcome. Thanks in advance,
pogue
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