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haidut

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So much for pregnenolone being an inactive steroid. The study below shows that even very low concentrations of pregnenolone are high anabolic for the bone and its effects are comparable to those of potent steroids like DHT or the well-known androgenic-anabolic steroid (AAS) commonly known as nandrolone. Remarkably, pregnenolone was effective even in very low concentrations, achievable with doses of just a few milligrams daily. While nandrolone was the most effective steroid, it is also the most toxic among the ones studies. As a result the study suggests using pregnenolone instead of other steroids given its lack of toxicity, or a alternatively combination of a progestin and a weak androgen. Pregnenolone/DHEA or progesterone/DHEA sounds especially appealing,considering their low risk and wide availability.

Effects of androgen and progestin on the proliferation and differentiation of osteoblasts
"...The proliferation effects of cells treated with drugs at concentrations of 0, 10‑10, 10‑8, 10‑6 and 10‑5 mol/l were analyzed using an MTS assay. The measured OD values for Preg, AD, Etio, An, NA and T with various concentrations were plotted and are presented in Figs. 2‑7, respectively. Cells treated with 10‑10 and 10‑8 mol/l Preg exhibited significantly increased proliferation rate compared with the blank control group (Fig. 2). This finding was consistent with the effective concentrations for AD and Etio, which also induced a significant increase in proliferation at 10‑10 and 10‑8 mol/l compared with the control (Figs. 3 and 4). An significantly increased cell proliferation at 10‑10 mol/l (Fig. 5). T was not as effective as expected for cell proliferation at these concentrations. Nevertheless, the results of T still indicated that proliferation was significantly increased in the 10‑10 and 10‑8 mol/l groups compared with the control group (Fig. 7)."

"...Among the androgens, T and DHT were the main steroids explored in these studies (33). The present study demonstrated that Preg, AD, Etio, and An could improve the proliferation and differentiation of bone cells in vitro. Although the effects of these steroids on bone health in vivo may not be an exact replication of those in vitro, their clinically active effects in treating osteoporosis are still worthy of consideration. Preg is a precursor of androgens and estrogens, and AD is a precursor of T, DHT and estrogens. An can be converted into DHT via 3α‑hydroxysteroid dehydrogenase and 17β‑hydroxysteroid dehydrogenase, and could be considered to be a metabolic intermediate in its own right (38,39). Therefore, androgens and progestin, and their metabolites, may promote bone regeneration."

"...In conclusion, the present study demonstrated for the first time that Preg, AD, Etio, and An improved the proliferation of osteoblasts in vitro. These steroids also significantly increased ALP activity and BGP secretion of hFOB cells. These findings may potentially represent novel therapeutic strategies for the treatment of osteoporosis. Therapy with these individual agents, in combination (e.g. estrogen plus the weak androgen or estrogen plus Preg), or the application of progestogen and the weak androgen during the ‘drug holiday’ of bisphosphonate may be more effective and safe treatment strategies."
 
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How do you calculate the proper dose to use? Doesn't it look like normal body concentrations of pregnenolone are already as high as what's used in the study?
 

haidut

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How do you calculate the proper dose to use? Doesn't it look like normal body concentrations of pregnenolone are already as high as what's used in the study?

The study used concentrations in the range 10 nM/L - 10 uM/L. These are achievable with just a few milligram doses and given that pregnenolone levels decline with age it could be one of the reasons behind osteoporosis. No pregnenolone also means no progesterone, DHEA or other steroids known to help bone health so the picture is quite consistent with what we have been seeing in aging people.
 

Logan-

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The study used concentrations in the range 10 nM/L - 10 uM/L. These are achievable with just a few milligram doses and given that pregnenolone levels decline with age it could be one of the reasons behind osteoporosis. No pregnenolone also means no progesterone, DHEA or other steroids known to help bone health so the picture is quite consistent with what we have been seeing in aging people.

I know this is dependent on the context, and every person has different physiological, environmental, pscyhological etc. states; but could you give a dose-range that is not going to yield estrogenic effects from pregnenolone supplementation? I remember you wrote just recently that lower doses can produce this (estrogenic) effect. What would be a good pregnenolone dosage for males who are 20-40 years old and are generally (more or less) healthy?

I want to learn your view on proper pregnenolone dosage more explicitly and specifically.
 

haidut

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I know this is dependent on the context, and every person has different physiological, environmental, pscyhological etc. states; but could you give a dose-range that is not going to yield estrogenic effects from pregnenolone supplementation? I remember you wrote just recently that lower doses can produce this (estrogenic) effect. What would be a good pregnenolone dosage for males who are 20-40 years old and are generally (more or less) healthy?

I want to learn your view on proper pregnenolone dosage more explicitly and specifically.

The estrogenic effects were temporary and then pregnenolone potently suppressed estrogen after the 3rd day of exposure. Same with progesterone.
As far as doses, I personally like doses below 50mg daily. One human study showed positive effects from 30mg and 50mg but no positive effects all the way up to 500mg and then benefit for some conditions was shown again. Lower doses feed into the androgen pathway better. So, either 30mg once waily or even 10mg several tmies daily. Adding 5mg DHEA would not hurt and would likely increase the bone anabolism as DHEA has been shown to do in every organism tested so far, including humans.
 
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Wasn't the effective dose 0.1 to 10nM? And what human studies do you use to decide with what dose that corresponds?

humanconc.png

prolif.png
 
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Logan-

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The estrogenic effects were temporary and then pregnenolone potently suppressed estrogen after the 3rd day of exposure. Same with progesterone.
As far as doses, I personally like doses below 50mg daily. One human study showed positive effects from 30mg and 50mg but no positive effects all the way up to 500mg and then benefit for some conditions was shown again. Lower doses feed into the androgen pathway better. So, either 30mg once waily or even 10mg several tmies daily. Adding 5mg DHEA would not hurt and would likely increase the bone anabolism as DHEA has been shown to do in every organism tested so far, including humans.

This is helpful, thank you.
 

Cameron

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Based on blood levels what would you say is below optimal my old lab showed I had low preg level of 30 I will check my referance range but even my doctor said I should consider preg I'm 25 23 at the time. seasoned weight lifter looking to increase androgens. My dhea-s was high in the 200s
 

haidut

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Wasn't the effective dose 0.1 to 10nM? And what human studies do you use to decide with what dose that corresponds?

View attachment 11436

View attachment 11437

Actually, it was 100 pM/L - 10 uM/L, but as the picture shows the effects were optimal for 10 nM/L. These concentrations can be achieved with tiny doses, probably a milligram or even less. There aren't many human studied with pregnenolone but its "volume of distribution" has been calculated before and a dose around 25mg achieves 500 nM/L concentrations, so I guess 0.5mg should be enough but since pregnenolone undergoes extensive metabolism in lower doses, a bit higher dose may be needed. The doses of 30mg and 50mg showing benefit but higher doses not showing benefit are based on human studied with depression and schizophrenia.
Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomiz... - PubMed - NCBI
Pregnenolone treatment reduces severity of negative symptoms in recent-onset schizophrenia: an 8-week, double-blind, randomized add-on two-center t... - PubMed - NCBI
Pregnenolone for cognition and mood in dual diagnosis patients. - PubMed - NCBI
 
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Yeah, so assuming matching the serum levels would have the same effect it looks like baseline concentrations were already close to the optimum in the study I shared and it tripled with a dose of 100->300mg (escalated over 6 weeks). One of your studies also saw a baseline serum concentration of about 10nM (others didn't measure serum concentrations?).

09m05031yelf4.gif
 

haidut

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Yeah, so assuming matching the serum levels would have the same effect it looks like baseline concentrations were already close to the optimum in the study I shared and it tripled with a dose of 100->300mg (escalated over 6 weeks). One of your studies also saw a baseline serum concentration of about 10nM (others didn't measure serum concentrations?).

View attachment 11447

One caveat - serum levels are not the same as tissue levels. Serum levels of pregnenolone reflect mostly adrenal and gonadal activity (not necessarily tissue levels) and decline strongly with age. The levels and graphs you listed were from studies with mostly young people. The anti-osteoporotic effects of exogenous pregnenolone would probably apply mostly to the 60+ crowd whose endogenous synthesis is very low (just like it is for DHEA, and progesterone). I did not suggest everybody should start loading up on pregnenolone. The study is mostly for people with osteoporosis due to aging or excess glucocorticoid activity causing osteopenia and premature osteoporosis.
Btw, what study is the table listing change in steroids in weeks 1-6 from? You included it in your previous post with 2 screenshots.
 

LeeLemonoil

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Could topical applie dPreg on the face be a good "anti-age" agent? Most think about wrinkles and such, but as we know an ageing face has many hallmarks.

Bone loss one of them? What are Pregs putative effects on other skin tissue like dermis and subconscious fat, facial muscle? It seems it could influence many parameters in a beneficial way, though local endocrine tissue has to be considered too.
 

haidut

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Could topical applie dPreg on the face be a good "anti-age" agent? Most think about wrinkles and such, but as we know an ageing face has many hallmarks.

Of course, there is even a commercial product with it.
Pregnenolone acetate - Wikipedia
"...Pregnenolone acetate (brand names Antofin, Previsone, Pregno-Pan), also known as pregn-5-en-3β-ol-20-one 3β-acetate, is a synthetic pregnane steroid and an ester of pregnenolone which is described as a glucocorticoid and as a skin-conditioning and skin anti-aging agent.[1][2] It has been found to significantly reduce wrinkles in elderly women when applied in the form of a 0.5% topical cream, effects which were suggested to be due to improved hydration of the skin.[2] Pregnenolone acetate has been marketed in France in a topical cream containing 1% pregnenolone acetate and 10% "sex hormone" for the treatment of premature skin aging but was withdrawn from the market in 1992.[2] Although the medication has been described by some sources as a glucocorticoid, other authors have stated that systemic pregnenolone acetate has no undesirable metabolic or toxic effects even at high dosages."

Progesterone works just as well, and testosterone is even better.
http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.575.1488&rep=rep1&type=pdf
"...Synopsis--The male hormone, testosterone, has a rejuvenating or ameliorative effect when applied to aging human skin. Clinically evident changes, such as eftacement of wrinkles, hair growth, and augmented sweating, are present but modest, particularly when compared to the improvement in the microscopic architecture of the skin. Progesterone and pregnenolone produce similar but more diminutive alterations. The female hormone, ethinyl estradiol, was without effect, while the corticosteroids accentuated the degradative changes of senescence."

The doses used in the above study were low - 0.5ml of a 1% steroid solution. Six months of treatment were needed with this once daily application in order to see results.
"...The following hormones, compounded either into hydrophilic ointment base or alcoholic solutions, were used: testosterone propionate 1.0%, progesterone1 .0%, pregnenolonea cetate* 0.5%, ethinyl estradiol 0.5% , triamcinolonea cetonide• 0.5% , and fluocinolonea cetonide 0.2% 11. Each unilateral test site received daily topical treatment with approximately 0.5 g of preparation while the contralateral side had the corresponding vehicle similarly applied."

"..Approximately six months of treatment are necessary before the hormonal effects become apparent."
 
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Seeweed65

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@haidut

The doses used in the above study were low - 0.5ml of a 1% steroid solution. Six months of treatment were needed with this once daily application in order to see results.
"...The following hormones, compounded either into hydrophilic ointment base or alcoholic solutions, were used: testosterone propionate 1.0%, progesterone1 .0%, pregnenolonea cetate* 0.5%, ethinyl estradiol 0.5% , triamcinolonea cetonide• 0.5% , and fluocinolonea cetonide 0.2% 11. Each unilateral test site received daily topical treatment with approximately 0.5 g of preparation while the contralateral side had the corresponding vehicle similarly applied."

Is there any harm in applying SressNon to the face straight from the bottle or is there a better or safer way of doing this. I have the SFA ester bottle.

Regards
 

haidut

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@haidut

The doses used in the above study were low - 0.5ml of a 1% steroid solution. Six months of treatment were needed with this once daily application in order to see results.
"...The following hormones, compounded either into hydrophilic ointment base or alcoholic solutions, were used: testosterone propionate 1.0%, progesterone1 .0%, pregnenolonea cetate* 0.5%, ethinyl estradiol 0.5% , triamcinolonea cetonide• 0.5% , and fluocinolonea cetonide 0.2% 11. Each unilateral test site received daily topical treatment with approximately 0.5 g of preparation while the contralateral side had the corresponding vehicle similarly applied."

Is there any harm in applying SressNon to the face straight from the bottle or is there a better or safer way of doing this. I have the SFA ester bottle.

Regards

I don't see an issue with applying to the face, just avoid getting it into the eyes.
 
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