Structural Requirements For An Optimal Anti-Catabolic Steroid

[Nokoni]

is androsterone easily converted to estrogen?

I don’t think it can – it’s 5a-reduced – but I’ll defer to the biochemists. What I can say is that it melts fat and grows muscle, no dieting or exercise needed.

The body can use any tissue as energy storage, not just fat. When there is excess energy input (calories), what tissue will the body use to store it? When there is an energy shortage, what tissue will the body use to pull it from? (I believe this is called “caloric partitioning”.)

Normally the body will store excess energy as fat and keep it there when there is a shortage, drawing it instead from muscle, connective tissue, and the organs. With androsterone this is reversed and excess energy is stored in muscle and organ tissue and, when there is a shortage, it is pulled from fat.

Does it affect hair? I haven’t noticed anything but maybe @Velve921 can chime in on that since he’s been doing it for more than 10 times as long as I have. But hair loss is an esthetic issue. Pete Rose once said about Mike Schmidt, “To have his body, I’d trade him mine and my wife’s, and I’d throw in some cash.” I feel the same way about androsterone. I’d give up every hair on my head and a few toes too. It’s muscle in a pill. Plus fat loss. And it’s cheap as dirt. And I feel great, my back is better (it actually feels cured but time will tell), and my knees are better.

Weight training also grows muscle, of course. What I suspect is that regularly working a muscle down-regulates the GR, which would make physiological sense, but it probably down-regulates it in that muscle only. From the body’s perspective, apparently that muscle must be pretty damn important, so take the energy from other places. But note that if you work only the upper body you’ll get a light bulb physique. With androsterone, every muscle – and tendon, and fascia, and organ, plus probably bone – is spared. Therefore it may be that you get the best proportions by NOT working out, but by just taking androsterone.

Maybe it doesn’t work this well for everyone. I also use a little DHP, pregnenolone, DHEA, and progesterone, and I supplement vitamins and minerals, and I eat sensibly. But all that stuff didn’t make this kind of difference. For me androsterone was the sine qua non, and I’d bet that virtually everyone would benefit from it.

 

[haidut]

I don’t think it can – it’s 5a-reduced – but I’ll defer to the biochemists. What I can say is that it melts fat and grows muscle, no dieting or exercise needed.

The body can use any tissue as energy storage, not just fat. When there is excess energy input (calories), what tissue will the body use to store it? When there is an energy shortage, what tissue will the body use to pull it from? (I believe this is called “caloric partitioning”.)

Normally the body will store excess energy as fat and keep it there when there is a shortage, drawing it instead from muscle, connective tissue, and the organs. With androsterone this is reversed and excess energy is stored in muscle and organ tissue and, when there is a shortage, it is pulled from fat.

Does it affect hair? I haven’t noticed anything but maybe @Velve921 can chime in on that since he’s been doing it for more than 10 times as long as I have. But hair loss is an esthetic issue. Pete Rose once said about Mike Schmidt, “To have his body, I’d trade him mine and my wife’s, and I’d throw in some cash.” I feel the same way about androsterone. I’d give up every hair on my head and a few toes too. It’s muscle in a pill. Plus fat loss. And it’s cheap as dirt. And I feel great, my back is better (it actually feels cured but time will tell), and my knees are better.

Weight training also grows muscle, of course. What I suspect is that regularly working a muscle down-regulates the GR, which would make physiological sense, but it probably down-regulates it in that muscle only. From the body’s perspective, apparently that muscle must be pretty damn important, so take the energy from other places. But note that if you work only the upper body you’ll get a light bulb physique. With androsterone, every muscle – and tendon, and fascia, and organ, plus probably bone – is spared. Therefore it may be that you get the best proportions by NOT working out, but by just taking androsterone.

Maybe it doesn’t work this well for everyone. I also use a little DHP, pregnenolone, DHEA, and progesterone, and I supplement vitamins and minerals, and I eat sensibly. But all that stuff didn’t make this kind of difference. For me androsterone was the sine qua non, and I’d bet that virtually everyone would benefit from it.

No, androsterone cannot be converted to estrogen and in fact is an aromatase inhibitor as well. So it goes well with aromtizable steroids like DHEA and pregnenolone (even though pregnenolone is not a substrate for aromatase and seems to also inhibit it, albeit weakly).

 

[Xisca]

Actually Ray says it's the opposite : supplemental preg makes you generate more endogenous preg.

Yes, and that is the reason why I did not hesitate to take progest-e.
Nobody answered your question, and mine is about progesterone: does taking it make you generate more? Or does it block endogenous production?
Thanks for bringing light to this!

 

[HDD]

Yes, and that is the reason why I did not hesitate to take progest-e.
Nobody answered your question, and mine is about progesterone: does taking it make you generate more? Or does it block endogenous production?
Thanks for bringing light to this!

Progesterone stimulates the ovaries and adrenals to produce progesterone, and it also activates the thyroid, so one dose can sometimes have prolonged effects. It shouldn't be necessary to keep using progesterone indefinitely, unless the ovaries have been removed. In slender post-menopausal women, 10 mg. per day is usually enough to prevent progesterone deficiency symptoms.
Progesterone Summaries - Progesterone Deceptions - Progesterone Supplementation - Dosage of Progesterone

 

[haidut]

Yes, and that is the reason why I did not hesitate to take progest-e.
Nobody answered your question, and mine is about progesterone: does taking it make you generate more? Or does it block endogenous production?
Thanks for bringing light to this!

It stimulates more progesterone production. Anything that stimulated thyroid function, including thyroid and progesterone stimulates steroid synthesis. Pregnenolone, progesterone and DHEA stimulate their own production which is probably one reason why Peat recommends using them and not downstream steroids which tend to inhibit steroid synthesis. For instance both T and DHT tend to block steroid metabolism through a negative feedback mechanism. The more downstream a hormone is the more specific its function and the higher the chance that it triggers negative feedback mechanisms.

 

[A.R]

I think I will release progesterone + DHEA as supplement. This way people can try either stack and if needed modulate it with either extra pregnenolone (StressNon) or progesterone (Progestene).

Sorry if this has been asked but,

Have you personally ever trialled only progesterone and dhea (dissolved in dmso for rapid absorbtion)?

If so, what were the differences with that combo and Pansterone

 

[Dhair]

It stimulates more progesterone production. Anything that stimulated thyroid function, including thyroid and progesterone stimulates steroid synthesis. Pregnenolone, progesterone and DHEA stimulate their own production which is probably one reason why Peat recommends using them and not downstream steroids which tend to inhibit steroid synthesis. For instance both T and DHT tend to block steroid metabolism through a negative feedback mechanism. The more downstream a hormone is the more specific its function and the higher the chance that it triggers negative feedback mechanisms.

I was under the impression that 11-keto-dht stimulated its on synthesis and didn't trigger negative feedback mechanisms

 

[Constatine]

I was under the impression that 11-keto-dht stimulated its on synthesis and didn't trigger negative feedback mechanisms

At really low doses.

 

[Velve921]

I don’t think it can – it’s 5a-reduced – but I’ll defer to the biochemists. What I can say is that it melts fat and grows muscle, no dieting or exercise needed.

The body can use any tissue as energy storage, not just fat. When there is excess energy input (calories), what tissue will the body use to store it? When there is an energy shortage, what tissue will the body use to pull it from? (I believe this is called “caloric partitioning”.)

Normally the body will store excess energy as fat and keep it there when there is a shortage, drawing it instead from muscle, connective tissue, and the organs. With androsterone this is reversed and excess energy is stored in muscle and organ tissue and, when there is a shortage, it is pulled from fat.

Does it affect hair? I haven’t noticed anything but maybe @Velve921 can chime in on that since he’s been doing it for more than 10 times as long as I have. But hair loss is an esthetic issue. Pete Rose once said about Mike Schmidt, “To have his body, I’d trade him mine and my wife’s, and I’d throw in some cash.” I feel the same way about androsterone. I’d give up every hair on my head and a few toes too. It’s muscle in a pill. Plus fat loss. And it’s cheap as dirt. And I feel great, my back is better (it actually feels cured but time will tell), and my knees are better.

Weight training also grows muscle, of course. What I suspect is that regularly working a muscle down-regulates the GR, which would make physiological sense, but it probably down-regulates it in that muscle only. From the body’s perspective, apparently that muscle must be pretty damn important, so take the energy from other places. But note that if you work only the upper body you’ll get a light bulb physique. With androsterone, every muscle – and tendon, and fascia, and organ, plus probably bone – is spared. Therefore it may be that you get the best proportions by NOT working out, but by just taking androsterone.

Maybe it doesn’t work this well for everyone. I also use a little DHP, pregnenolone, DHEA, and progesterone, and I supplement vitamins and minerals, and I eat sensibly. But all that stuff didn’t make this kind of difference. For me androsterone was the sine qua non, and I’d bet that virtually everyone would benefit from it.

I have come across nothing so far that has helped with hair growth. Therefore, I'm bald with a beard :)

 

[haidut]

I was under the impression that 11-keto-dht stimulated its on synthesis and didn't trigger negative feedback mechanisms

Depends on the dose. In high doses like the ones used in some human studies (80mg+ daily) it can trigger negative feedback.

 

[Lukas]

@Constatine What would you consider a really low dose?

Edit: Sorry, I didnt see Haiduts reply.

 

[sladerunner69]

This post will be a bit long, but I hope it is worth it. I think @Jsaute21 and @dand will find it highly interesting but the information here applies just as much to females wishing to preserve lean tissue and prevent the catabolism that often occurs with aging.
Here we go. Lately, I have been researching the effects of various steroids on the glucocorticoid, androgenic and estrogenic receptors. There has been a great deal of interest in identifying steroids with anabolic effects but despite the decades of research on many synthetic ones the exact mechanism through which steroids like T or AAS stimulate protein synthesis is not really known.
My own personal experimentation with glucocorticoid antagonists like pregnenolone-16a-carbonitrile, RU486, progesterone, pregnenolone and DHEA led me to the theory that there is no such as anabolic hormones, only anticatabolic ones, and the "anabolic" effects from T and AAS are actually the result of their antagonism to cortisol (and potentially estrogen). An old study I found makes the same claim, and highlights the well-known fact that muscle contains almost exclusively glucocorticoid receptors (GR), while androgen receptors (AR) are mostly expressed in tissues like prostate, gonads, brain and skin. Thus, if a steroid if a steroid is found to have an "anabolic" effect in muscle that is due almost exclusively to antagonism of GR. Steroids with strong androgenic effects would also have anabolic effects but those would be secondary to GR antagonism and reserved mostly for tissues with high expression of AR - i.e. prostate, gonads, sex organs, brian, etc. This matches quite well the common knowledge that strong androgens are weakly anabolic for muscle but are highly anabolic for those tissues that express the AR. The studies I posted on androsterone's anabolism in kidney, heart, spleen, and thymus corroborate this theory further.

Binding of glucocorticoid antagonists to androgen and glucocorticoid hormone receptors in rat skeletal muscle. - PubMed - NCBI
"...Although the anabolic activity of androgenic steroids has been recognized for a long time, the way in which these steroids act in muscle is ill-understood. It is also known that glucocorticoids exert a catabolic and anti-anabolic effect on protein metabolism in skeletal muscle [l-3]. Androgen and glucocorticoid receptors have been demonstrated in this tissue [4-6]. Since several steroids, including androgens, behave as glucocorticoid antagonists when binding to the glucocorticoid receptor in other tissues [7,8] such steroids could antagonise the catabolic action of endogenous glucocorticoids by preventing binding of the latter to their cytosolic receptors in muscle [9, lo]. Thus, muscle anabolism could result either from agonist steroid binding to the androgen receptor, or from antagonist binding to the glucocorticoid receptor, or both."

"...Table 1 shows that rat skeletal muscle contains about 40 times less androgen receptors than glucocorticoid receptors. Thus, one might speculate that differentiated muscle cells contain only the glucocorticoid receptor, while the androgen receptors are restricted to the satellite cells since the latter contribute about 2-5% of nuclei in muscle [15, 161. Moreover, treatment with thyroxine, which has anabolic activity at physiological doses, results in elevated incidence of satellite cells per muscle fiber and in percentage of all muscle nuclei [27].

"...As to the glucocorticoid receptor, it bound four steroids with an affinity higher than the androgen receptor, namely RU486, 2001, 415 and DXB. The data for R 1881, testosterone, and nortestosterone are consistent with earlier work [5,26]. Interestingly, the potent anabolic steroid trenbolone [36,37] bound to the glucocorticoid receptor with an affinity almost as high as that of corticosterone, the endogenous glucocorticoid in the rat [12]. With the only exception of AY 13615, it is remarkable that all the steroids tested bound to the glucocorticoid receptor with an affinity that ranked in the same order as their antiglucocorticoid activity in the HTC system (compare Tables 2 and 3). The three weakest antiglucocorticoids, namely the androgens methyltestosterone, nortestosterone, and testosterone were also the steroids that bound the muscle glucocorticoid receptor with the lowest affinity."

"...These restrictions notwithstanding, these indices (Table 3) show how the high concentration of glucocorticoid receptor sites compensates for their relatively lower affinity towards some of the steroids tested, as compared to the androgen receptor. For instance, providing RU486 and R1881 both are anabolic agents, RU486 is expected, despite its 50-fold lower affinity for the androgen receptor, to be much more potent than R1881 if anabolism can result from antiglucocorticoid activity as well as from androgenic action proper. The latter possibility is supported by the observation that the anabolic action of androgens results from inhibition of protein catabolism rather than from stimulation of anabolism [37,39]. Indeed, antiglucocorticoid activity is expected to counteract protein catabolism, while androgenic activity would stimulate anabolism."


Thus, if one would like to combine the best of both worlds, one would need a steroid which is a strong antagonist at GR and a strong agonist at AR. This present a possible issue as the binding requirements for both receptors differ. Strong GR antagonists are usually pregnane derivatives, which also have at least one unsaturated (double) bond in the A-ring of the steroid core. Such steroids do not have great affinity for the AR.
On the other hand, strong AR agonists are usually fully saturated androstane steroids like DHT, and androsterone as well as synthetic derivatives like mesterolone and oxandrolone (among many others). However, fully reduced androstane steroids do not bind well to the GR even though they are antagonist to it. Thus, DHT is expected to be a relatively weak anabolic steroid in muscle and highly anabolic in AR-rich tissues, which has been confirmed in practice countless times.
In support of these assertions please see the attached study listing GR antagonism requirements and 50 steroids with various agonist or antagonist effects on GR. As can be immediately seen, progesterone is one of the most potent antagonists of GR as it satisfies all the requirements. Known "anabolic" steroids like testosterone and other AAS are also GR antagonists, but as the study above noted, relatively weak ones. In fact, as per the study, the only steroid stronger than progesterone is 1-dehydro-progesterone (delta-1-progesterone) - i.e another progestogen - but the differences are minuscule.

Btw, the study above lists RU486 as one steroid that satisfies the strong anticatabolism requirement but, as the study says, it is an AR antagonist. So while it may be anticatabolic a still better alternative is possible - i.e. combining a strong glucocorticoid antagonist with a strong androgen agonist. Be that as it may, given its opposition to cortisol and estrogen, RU486 has highly trophic effects on the brain which may explain some of its positive effects on the brain and in people with PFS. Its partial antagonism/agonism to progesterone likely has very little to do with its beneficial effects, and we can do better than that. But how?
Some people may have noticed that testosterone (T) is both an antagonist at GR and an agonist at AR. Unfortunately, as the study above shows, T is weak GR antagonist. Well, another thing we can try is a steroid stack. Progesterone would be my choice for a GR antagonist as per the attached study on structure/activity relationship and the other thread I posted on its antagonism to GR (The Anti-cortisol Mechanism Of Progesterone). In addition, as I posted in another thread, progesterone has proven anabolic effects at least in animal studies (The Anabolic Effects Of Progesterone). Needless to say, Peat has also written a ton on progesterone, of its opposition to cortisol and estrogen, and its role in protecting from tissue destruction.
As an androgen agonist I would of course pick DHT, especially given its own antagonism to GR and estrogen. However, given that is it not available OTC it is probably not an option for most people. That leaves androsterone and DHEA as legal substitutes, and in fact a combination of both may be even more powerful than either one alone, as shown by another study I posted in the past (Remarkable Synergistic Anabolic / Androgenic Effect Of Androsterone With DHEA). The doses for each steroid are based largely on Peat's recommendations and studies I have seen. We know that DHEA should not be used in daily doses over 15mg if we want estrogen to stay as is. Androsterone is likely optimal in a ratio 1:1 up to 1:4 in combination with DHEA. So, that means 5mg - 15mg androsterone. How about progesterone? Well, Peat mentioned it a few times in emails to people who asked him about melanoma treatment. He said progesterone in a ratio of least 2:1 to DHEA would be best. He gave an example of using 40mg progesterone and 25mg DHEA. So, that comes down to a stack where a single dose would have 5mg DHEA, 1mg-5mg androsterone and 10mg+ progesterone.

Btw, in confirmation of everything written above, this very recent human study found that progesterone was just as anabolic as testosterone in postmenopausal women, while estrogen had no effect! So, at least half of the theory seems confirmed by evidence in humans.
Progesterone Is As Anabolic For Muscle As Testosterone (in Women)



Thought, comments? Has anybody else experimented with something similar?

You've actually experimented with ru486 and found positive results? Primarily it functions as an anti-progestin, correct? I am not clear on the glucocorticoid antagonism effects, but guys tend to get fairly high libido and energy on it, it sure seems.

 

[sladerunner69]

Brilliant obfuscation. Well played.
Hopefully nobody actually uses that page as a reference for the effects of progesterone.

Why wouldn't they, precisely?

 

[Constatine]

@Constatine What would you consider a really low dose?

Edit: Sorry, I didnt see Haiduts reply.

Under 5mg should be safe.

 

[Nokoni]

Why wouldn't they, precisely?

Idealabs Progestene is what made my post-menopausal mother recover her sleep, in that site they are clearly talking about the side effects of progestins not actual progesterone

 

[haidut]

You've actually experimented with ru486 and found positive results? Primarily it functions as an anti-progestin, correct? I am not clear on the glucocorticoid antagonism effects, but guys tend to get fairly high libido and energy on it, it sure seems.

Yes, I tried it for a few days but it was pregnenolone-16a-carbonitrile (PCN) that I liked more. The RU486 made me jittery and ruined my sleep. I think progesterone, emodin and DHT are much safer than either RU486 or PCN as glucocorticoid antagonists. A recent study found that emodin is also an adrenergic (receptor) antagonist so it seems like it is the perfect anti-stress chemical. The effective concentration of pure emodin adrenaline antagonism was just 2.5mg/L, which means a dose of 15mg - 20mg should suffice and at that dose emodin also powerfully inhibits cortisol synthesis.

Purgative components in rhubarbs: adrenergic receptor inhibitors linked with glucose carriers. - PubMed - NCBI
"...Rhubarbs and their extractives have been used as cathartic for many years. There have been numerous breakthroughs in the pharmacological research of the drug. However, as the key point of the mechanism, the targets of the effective components still remain unclear. In this paper, with an in vitro system of isolated intestine, we found that both the rhubarb extractives and the anthraquinone derivatives can antagonize the adrenaline effectively. Furthermore, computer based docking provided the binding model of the anthraquinone derivatives and adrenergic receptor. Then, based on the results of the small intestinal promotion and purgative effect experiments in vivo, we built an "inhibitor-carrier" hypothesis to elucidate the mechanism of rhubarb. This work provided key massages for the pharmacological research of rhubarb, such a common and active medicinal plant, and might be of help for the development of new purgative drugs."

 

[Lyall]

Which could be part of the reason trenbolone contributes to neurodegeneration.

Could you elaborate on this point of neurodegenerarion?

 

[Dotdash]

Quote from RP interview with Lana Burman, Your Own Health & Fitness Talk Show:

"On the way up the scale towards protecting everything progesterone is also protective against salt imbalance and imbalance of the sex steroids. That means it protects your thymus and immune system against destruction by stress hormones or the sex hormones. So it’s extremely important in the sense of being protective but it also neutralizes the male hormone. At a very low level in men it begins to neutralize the testosterone, so a man needs to be conscious there is this deadly rising protective function and if they don’t want to be protected against having whiskers and other typically male traits they don’t want to take more than just a very few milligrams a day. Two or three milligrams a day is about enough to offer general protection without neutralizing them sexually.

Men can still function with their testosterone highly neutralized – they feel like they have just come out of a cold shower but the brain still knows how to make everything function. It doesn’t really prevent potency. At a very moderate dose it will shrink an enlarged prostrate." RP

 

[Braveheart]

Quote from RP interview with Lana Burman, Your Own Health & Fitness Talk Show:

"On the way up the scale towards protecting everything progesterone is also protective against salt imbalance and imbalance of the sex steroids. That means it protects your thymus and immune system against destruction by stress hormones or the sex hormones. So it’s extremely important in the sense of being protective but it also neutralizes the male hormone. At a very low level in men it begins to neutralize the testosterone, so a man needs to be conscious there is this deadly rising protective function and if they don’t want to be protected against having whiskers and other typically male traits they don’t want to take more than just a very few milligrams a day. Two or three milligrams a day is about enough to offer general protection without neutralizing them sexually.

Men can still function with their testosterone highly neutralized – they feel like they have just come out of a cold shower but the brain still knows how to make everything function. It doesn’t really prevent potency. At a very moderate dose it will shrink an enlarged prostrate." RP

Thank you...

 

[Frankdee20]

Adding smiley faces to your posts doesn’t make them funny,you need to have witty content,you clearly have no capacity for this.
You seem desperate for Haidut’s attention.
Dont bother responding,this is a good thread and haidut has put time into it,you have derailed enough threads with your clear examples of mania,adding bullet points to manic ranting doesn’t make it any less of a rant.

Wow, you went in !