Progesterone Is As Anabolic For Muscle As Testosterone (in Women)

haidut

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I am posting this in support of the recent thread on what constitutes an anabolic supplement steroid and how to properly combine various steroids to help prevent/limit catabolism and enhance anabolism in both men and women.
Quest For The Perfect Anticatabolic / Anabolic Supplement

This study shows that in a daily dose of 100mg (intravaginal gel) progesterone stimulated muscle protein synthesis by the same amount (50%+) as testosterone (1.2mg absorbed form topical gel).
Notably, estrogen had no effect on muscle protein synthesis, which the author cite as consistent with results from other groups.

Testosterone and Progesterone, But Not Estradiol, Stimulate Muscle Protein Synthesis in Postmenopausal Women
"...The average muscle protein FSR was unchanged in the control group (Figure 3), and the time between the two studies (31–78 d) did not correlate with the change in muscle protein FSR (r = 0.06, P = .91). Estradiol treatment did not affect the muscle protein FSR, whereas both T and progesterone treatment increased it by approximately 50% (both P < .01; Figure 3). T and estradiol treatment had no effect on skeletal muscle MYOD1, MSTN, FST, and FOXO3 mRNA expression; progesterone treatment significantly increased MYOD1 mRNA expression (P < .05) but had no effect on MSTN, FST, and FOXO3 mRNA expression (Figure 4)."

"...Our study confirms previous observations by our own and other research groups concerning the anabolic effect of T (3,7) and an age-related up-regulation of both stimulatory and inhibitory muscle growth regulatory genes and accelerated basal muscle protein turnover in women (14, 43, 44), which might be indicative of increased skeletal muscle remodeling in post- compared with premenopausal women. In addition, it provides several novel findings regarding female sex hormone action on muscle protein metabolism. We have demonstrated that estradiol has no effect on muscle protein synthesis or the expression of genes involved in the regulation of muscle mass, whereas progesterone has potent stimulatory effects on muscle protein synthesis and MYOD1 mRNA expression."
 

DaveFoster

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Notably, estrogen had no effect on muscle protein synthesis, which the author cite as consistent with results from other groups.
In before gbolduev.

@AretnaP
 

AretnaP

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In before gbolduev.

@AretnaP
I'm sure it has some creatine-like effect of putting more water in the muscles (and thus allowing for more work-load), but yeah I'm not surprised by this at all.

Gbold's claim that "bodybuilders should never inhibit estrogen" and that they will "lose all the effects of testosterone" is completely insane and unsupported.

They already do inhibit estrogen in preparation for shows to give the muscles a dryer, leaner look.

Not that bodybuilding has much, if any, relevance to health, but this is good to know.
 

haidut

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I'm sure it has some creatine-like effect of putting more water in the muscles (and thus allowing for more work-load), but yeah I'm not surprised by this at all.

Gbold's claim that "bodybuilders should never inhibit estrogen" and that they will "lose all the effects of testosterone" is completely insane and unsupported.

They already do inhibit estrogen in preparation for shows to give the muscles a dryer, leaner look.

Not that bodybuilding has much, if any, relevance to health, but this is good to know.

I think the main issue stems from misunderstanding on the difference between "wet" growth and "dry" growth. It is the latter that we should be after. Estrogen simply causes cells to accumulate water and start dividing. That is NOT the same as increasing protein synthesis. It is the latter that true bodybuilders and medicine is after, and the former is highly sought after only by farmers looking to fatten up and bulk their farm animals.
When steroids are compared based on "dry" weight muscle increase progesterone has the same effects as testosterone (see thread below), which is not surprising as the anabolism of both is simply the result of their anti-catabolic effetcs by opposing cortisol. Testosterone by itself is not very abdrogenic and it actually has some estrogenic effects, as the study below showed. So ideally progesterone (anti-catabolic) should be combined with a much stronger androgen agonist (anabolic) than T in order to achieve optimal results. Given that T is itself somewhat estrogenic having extra estrogen for (fake) anabolism is definitely not needed.
The Anabolic Effects Of Progesterone

As it seems, the Russians are quite aware of this line of thinking, which I posted in the other thread of anticatabolic/anabolic combinations. So, as a doping agent they administer a cocktail of a powerful anti-catabolic steroid (trenbolone) + powerful androgenic/anabolic steroid (oxandrolone). They also administered methenolone, which is another anti-catabolic steroid.
Oxandrolone - Wikipedia
"...Many bodybuilders and athletes use oxandrolone for its muscle-building properties. It is much less androgenic than anabolic, so women and those seeking less intense steroid regimens use it particularly often.[19] Many also value oxandrolone's low hepatotoxicity relative to most other orally active steroids.[19] The infamous "duchess" cocktail administered to Russian athletes at the Sochi Winter Olympics consisted of Oxandrolone, Methenolone and Trenbolone."

The reason methenolone was administered is likely because of its double bond at C-1, which also antagonizes GR. An "ideal" anti-catabolic steroid would be a 3-keto steroid with double bonds at C1, C-4, and C-11. Such a steroid probably has not been marketed or rumored to have been used yet, but I will not be surprised if work is under way to do it. The combination of trenbolone (C4, C11 double bonds) and methenolone (C1 double bond) achieves these effects of such an ideal anti-catabolic steroid, while the oxdandrolone is the strong androgen agonist needed for increasing protein synthesis. The methylation of both oxandrolone and methenolone is dangerous and will likely cause liver toxicity, especially in combination use. IMO, similar doping effects could have been achieved much more safely by combining boldenone + oxandrolone.
In the world of bioidentical steroids, the closest analogy would be a combination of progesterone + DHT, or even pregnenolone + progesterone + DHEA + DHT. The pregnenolone/progesterone/DHEA would be the anti-catabolic agent and DHT the androgenic/anabolic one. Of the legally available OTC steroids the closest combination would be pregnenolone + progesterone + DHEA + androsterone.
 
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DaveFoster

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I think the main issue stems from misunderstanding on the difference between "wet" growth and "dry" growth. It is the latter that we should be after. Estrogen simply causes cells to accumulate water and start dividing. That is NOT the same as increasing protein synthesis. It is the latter that true bodybuilders and medicine is after, and the former is highly sought after only by farmers looking to fatten up and bulk their farm animals.
When steroids are compared based on "dry" weight muscle increase progesterone has the same effects as testosterone (see thread below), which is not surprising as the anabolism of both is simply the result of their anti-catabolic effetcs by opposing cortisol. Testosterone by itself is not very abdrogenic and it actually has some estrogenic effects, as the study below showed. So ideally progesterone (anti-catabolic) should be combined with a much stronger androgen agonist (anabolic) than T in order to achieve optimal results. Given that T is itself somewhat estrogenic having extra estrogen for (fake) anabolism is definitely not needed.
The Anabolic Effects Of Progesterone

As it seems, the Russians are quite aware of this line of thinking, which I posted in the other thread of anticatabolic/anabolic combinations. So, as a doping agent they administer a cocktail of a powerful anti-catabolic steroid (trenbolone) + powerful androgenic/anabolic steroid (oxandrolone). They also administered methenolone, which is another anti-catabolic steroid.
Oxandrolone - Wikipedia
"...Many bodybuilders and athletes use oxandrolone for its muscle-building properties. It is much less androgenic than anabolic, so women and those seeking less intense steroid regimens use it particularly often.[19] Many also value oxandrolone's low hepatotoxicity relative to most other orally active steroids.[19] The infamous "duchess" cocktail administered to Russian athletes at the Sochi Winter Olympics consisted of Oxandrolone, Methenolone and Trenbolone."

The reason methenolone was administered is likely because of its double bond at C-1, which also antagonizes GR. An "ideal" anti-catabolic steroid would be a 3-keto steroid with double bonds at C1, C-4, and C-11. Such a steroid probably has not been marketed or rumored to have been used yet, but I will not be surprised if work is under way to do it. The combination of trenbolone (C4, C11 double bonds) and methenolone (C1 double bond) achieves these effects of such an ideal anti-catabolic steroid, while the oxdandrolone is the strong androgen agonist needed for increasing protein synthesis. The methylation of both oxandrolone and methenolone is dangerous and will likely cause liver toxicity, especially in combination use. IMO, similar doping effects could have been achieved much more safely by combining boldenone + oxandrolone.
In the world of bioidentical steroids, the closest analogy would be a combination of progesterone + DHT, or even pregnenolone + progesterone + DHEA + DHT. The pregnenolone/progesterone/DHEA would be the anti-catabolic agent and DHT the androgenic/anabolic one. Of the legally available OTC steroids the closest combination would be pregnenolone + progesterone + DHEA + androsterone.
That's interesting, haidut. People rarely mention that the testosterone molecule itself has estrogenic properties. They usually merely mention its aromatization.

This could offer a more direct, causal explanation of "roid rage" and hypersexuality brought on by AAS use (from the high levels of testosterone, and not merely its aromatization).
 

sladerunner69

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I'm sure it has some creatine-like effect of putting more water in the muscles (and thus allowing for more work-load), but yeah I'm not surprised by this at all.

Gbold's claim that "bodybuilders should never inhibit estrogen" and that they will "lose all the effects of testosterone" is completely insane and unsupported.

They already do inhibit estrogen in preparation for shows to give the muscles a dryer, leaner look.

Not that bodybuilding has much, if any, relevance to health, but this is good to know.

Yeah though the low estrogen symptoms bodybuilders are wary of include low libido, aching joints, listlessness, and inability to achieve "dat pump brah".
 

denise

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When steroids are compared based on "dry" weight muscle increase progesterone has the same effects as testosterone (see thread below), which is not surprising as the anabolism of both is simply the result of their anti-catabolic effetcs by opposing cortisol.
I just read through the study, and they mention this:

"...we chose to provide 17β-estradiol and micronized progesterone in replacement doses and delivered them to tissues through the systemic circulation [i.e., transdermally and transvaginally rather than orally] to avoid these confounding influences; in fact, none of our hormone treatments affected the concentrations of insulin, IGF-I, IGF-BP3, or cortisol or resulted in nonspecific sex hormone concentration changes."

Would this mean that progesterone's effects were not simply by opposing cortisol? Or am I missing something?
 

haidut

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I just read through the study, and they mention this:

"...we chose to provide 17β-estradiol and micronized progesterone in replacement doses and delivered them to tissues through the systemic circulation [i.e., transdermally and transvaginally rather than orally] to avoid these confounding influences; in fact, none of our hormone treatments affected the concentrations of insulin, IGF-I, IGF-BP3, or cortisol or resulted in nonspecific sex hormone concentration changes."

Would this mean that progesterone's effects were not simply by opposing cortisol? Or am I missing something?

Progesterone is a glucocorticoid (receptor) antagonist, so it can be anticatabolic without affecting basal cortisol levels much. I think these results are a very good thing because other glucocorticoid antagonists like RU486 are known to cause hypercortisolemia while taken. In theory, that hypercortisolemia should be harmless as RU486 is blocking the receptors but there are surface receptors on the cell that steroids affect and RU486 probably does nothing for that.
 

Koveras

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I think the main issue stems from misunderstanding on the difference between "wet" growth and "dry" growth. It is the latter that we should be after. Estrogen simply causes cells to accumulate water and start dividing. That is NOT the same as increasing protein synthesis. It is the latter that true bodybuilders and medicine is after, and the former is highly sought after only by farmers looking to fatten up and bulk their farm animals.
When steroids are compared based on "dry" weight muscle increase progesterone has the same effects as testosterone (see thread below), which is not surprising as the anabolism of both is simply the result of their anti-catabolic effetcs by opposing cortisol. Testosterone by itself is not very abdrogenic and it actually has some estrogenic effects, as the study below showed. So ideally progesterone (anti-catabolic) should be combined with a much stronger androgen agonist (anabolic) than T in order to achieve optimal results. Given that T is itself somewhat estrogenic having extra estrogen for (fake) anabolism is definitely not needed.
The Anabolic Effects Of Progesterone

As it seems, the Russians are quite aware of this line of thinking, which I posted in the other thread of anticatabolic/anabolic combinations. So, as a doping agent they administer a cocktail of a powerful anti-catabolic steroid (trenbolone) + powerful androgenic/anabolic steroid (oxandrolone). They also administered methenolone, which is another anti-catabolic steroid.
Oxandrolone - Wikipedia
"...Many bodybuilders and athletes use oxandrolone for its muscle-building properties. It is much less androgenic than anabolic, so women and those seeking less intense steroid regimens use it particularly often.[19] Many also value oxandrolone's low hepatotoxicity relative to most other orally active steroids.[19] The infamous "duchess" cocktail administered to Russian athletes at the Sochi Winter Olympics consisted of Oxandrolone, Methenolone and Trenbolone."

The reason methenolone was administered is likely because of its double bond at C-1, which also antagonizes GR. An "ideal" anti-catabolic steroid would be a 3-keto steroid with double bonds at C1, C-4, and C-11. Such a steroid probably has not been marketed or rumored to have been used yet, but I will not be surprised if work is under way to do it. The combination of trenbolone (C4, C11 double bonds) and methenolone (C1 double bond) achieves these effects of such an ideal anti-catabolic steroid, while the oxdandrolone is the strong androgen agonist needed for increasing protein synthesis. The methylation of both oxandrolone and methenolone is dangerous and will likely cause liver toxicity, especially in combination use. IMO, similar doping effects could have been achieved much more safely by combining boldenone + oxandrolone.
In the world of bioidentical steroids, the closest analogy would be a combination of progesterone + DHT, or even pregnenolone + progesterone + DHEA + DHT. The pregnenolone/progesterone/DHEA would be the anti-catabolic agent and DHT the androgenic/anabolic one. Of the legally available OTC steroids the closest combination would be pregnenolone + progesterone + DHEA + androsterone.

Oxandrolone blocks glucocorticoid signaling in an androgen receptor-dependent manner. - PubMed - NCBI

The anabolic steroid oxandrolone is increasingly used to preserve or restore muscle mass in those with HIV infection or serious burns. These effects are mediated, in part, by the androgen receptor (AR). Anti-glucocorticoid effects have also been reported for some anabolic steroids, and the goal of our studies was to determine whether oxandrolone had a similar mechanism of action. Studies with in vitro translated glucocorticoid receptor (GR), however, showed no inhibition of cortisol binding by oxandrolone. Conversely, experiments in cell culture systems demonstrated significant antagonism of cortisol-induced transcriptional activation by oxandrolone in cells expressing both the AR and GR. Inhibition was not overcome by increased cortisol concentration, and no inhibition by oxandrolone was observed in cells expressing GR alone, confirming that non-competitive mechanisms were involved. AR-dependent repression of transcriptional activation by oxandrolone was also observed with the synthetic glucocorticoids dexamethasone and methylprednisolone. Furthermore, the AR antagonists 2-hydroxyflutamide and DDE also repressed GR transactivation in an AR-dependent manner. A mutant AR lacking a functional nuclear localization signal (AR(4RKM)) was active in oxandrolone-mediated repression of GR even though oxandrolone-bound AR(4RKM) failed to enter the nucleus and did not affect nuclear import of GR. These data indicate a novel action of oxandrolone to suppress glucocorticoid action via crosstalk between AR and GR.
 

haidut

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Oxandrolone blocks glucocorticoid signaling in an androgen receptor-dependent manner. - PubMed - NCBI

The anabolic steroid oxandrolone is increasingly used to preserve or restore muscle mass in those with HIV infection or serious burns. These effects are mediated, in part, by the androgen receptor (AR). Anti-glucocorticoid effects have also been reported for some anabolic steroids, and the goal of our studies was to determine whether oxandrolone had a similar mechanism of action. Studies with in vitro translated glucocorticoid receptor (GR), however, showed no inhibition of cortisol binding by oxandrolone. Conversely, experiments in cell culture systems demonstrated significant antagonism of cortisol-induced transcriptional activation by oxandrolone in cells expressing both the AR and GR. Inhibition was not overcome by increased cortisol concentration, and no inhibition by oxandrolone was observed in cells expressing GR alone, confirming that non-competitive mechanisms were involved. AR-dependent repression of transcriptional activation by oxandrolone was also observed with the synthetic glucocorticoids dexamethasone and methylprednisolone. Furthermore, the AR antagonists 2-hydroxyflutamide and DDE also repressed GR transactivation in an AR-dependent manner. A mutant AR lacking a functional nuclear localization signal (AR(4RKM)) was active in oxandrolone-mediated repression of GR even though oxandrolone-bound AR(4RKM) failed to enter the nucleus and did not affect nuclear import of GR. These data indicate a novel action of oxandrolone to suppress glucocorticoid action via crosstalk between AR and GR.

Very interesting, thanks. So, based on the study both AR agonists and antagonists may be able to suppress glucocorticoid effects and without directly displacing cortisol from the receptor. Btw, pregnenolone does something similar in a receptor independent way - i.e. it does not block cortisol from binding to the receptor but blocks translocation of the bound steroid/receptor complex to the cell nucleus, which in effects prevents cortisol's genomic effects. Progesterone does both - displaces cortisol from the receptor and blocks translocation to the nucleus. DHEA is 11b-HSD1 inhibitor and 11b-HSD2 activator. I guess the androgen receptor crosstalk is yet another mechanism for opposing cortisol, which means that a progesterone + DHEA + strong androgen combo would be really good as it address all of these pathways.
 
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