haidut

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I posted a few times about the steroidal characteristics of aging. Many people think there is a drop in testosterone (T) in aging and that is what drives the frailty of aging both in men and women. However, numerous studies show that that total T does not decrease with aging. What does seem to happen is that there is progressive rise of adrenal activity with advancing age. Initially, in the years between puberty and mid-30, there is a rise of DHEA concurrent with the rising cortisol and that protects humans from many of the cortisol's detrimental effects by being a direct cortisol antagonist and also by serving as precursor for androgens. However, with continued cortisol exposure eventually the adrenal layers responsible for DHEA synthesis atrophy and what remains is only the layer that synthesizes cortisol. A number of studies showed that ability to synthesize cortisol does NOT decline with age. Cortisol inhibits gonadal synthesis of steroids, prevents the recovery of the adrenal layers that synthesize DHEA, and activates the aromatase enzyme. Thus, old people end up with the cortisol levels of a 20 year old but with no DHEA and suppressed gonads (or failed ovaries) so they cannot synthesize protective steroids. Whatever small amount of DHEA remains in their blood gets shuttled to estrogen synthesis due to the high activity (and high expression as well due to increased adiposity) of aromatase .
The study below agrees with the description above. So, one possible approach would be to provide sufficient amount of the precursors pregnenolone, progesterone, and maybe some DHEA to at least balance the activity of cortisol and estrogen. Pregnenolone, progesterone and DHEA also help lower cortisol directly and thus should not only oppose cortisol's effects but also allow for the adrenal layers to recover and the gonads to resume synthesis of the protective steroids.

[Age-dependent changes in the concentration of active sex steroids, their precursors, metabolites, and regulating agents in male blood]. - PubMed - NCBI
"...Blood concentrations of hormone-inactive and active sex-steroid metabolites and their precursors were measured, taking into account changes in protein-peptide hormones that control the reproductive axis (in a total of 14 parameters) in men in the 18- to 72-year-old age interval. A significant decrease in the blood concentration of unutilized precursors of active sex steroids (pregnenolone, progesterone, dehydroepiandrosterone, and its sulfate), unbound testosterone, androstenedione (an inactive metabolite of testosterone), and an active metabolite, 5alpha-dihydrotestosterone was determined after the age of 35. However, the level of total testosterone and of estradiol (another active metabolite of testosterone) remained constant. The systems regulating the production of active sex steroids resisted a higher load, causing the luteinizing and follicle-stimulating hypophyseal hormones and activin of steroidogenic glands to increase and correlate positively with age; these hormones correlated negatively with certain sex steroids that realize negative feedback. A decrease in the level of adrenocorticotropic hypophyseal hormone with age suggests a more substantial role for adrenal glands as compared to that of testicles in reducing the blood concentration of active sex steroids. In general, despite the reduced activity of steroidogenic glands in 60- to 70-year-old men, their testosterone and estradiol concentrations remain unchanged, due to coordinated growth in the concentration of luteinizing and follicle-stimulating hypophyseal hormones, and to the activin of steroidogenic glands, which stimulated sex steroid biosynthesis. At the same time, the androgen effect was inhibited as a result of reduced levels of unbound testosterone and 5alpha-dihydrotestosterone."


[Age-related changes in blood concentration of hypothalamic-pituitary-adrenal axis hormones, their central and peripheral regulators in healthy men]. - PubMed - NCBI
"...We studied concentrations of cortisol, its precursors and active form in human blood and relation to the changes in concentration of central and peripheral hormonal regulators (total 36 parameters) in healthy male volunteers aged 18-72 y.o. The study demonstrated a significant decrease in blood concentrations of unutilazed cortisol precursors (pregnenolone and progesterone) with advanced age accompanied by maintenance of total and free cortisol concentrations. We found age-related decrease in ACTH level that is a known hypophysial stimulant of cortisol and cortisol precursor synthesis in adrenal glands. Cortisol and ACTH levels in study population had different correlation behavior in relation to central and peripheral regulators for hormonal axes.

"...CONCLUSION: cortisol level remains stable with advanced age in males despite the decrease in steroidogenic activity and blood ACTH level. This may be due to the imbalance in the regulation of cortisol and ACTH production by central and peripheral regulators especially by hormones of reproductive and somatotrophic axes."


Changes in serum concentrations of conjugated and unconjugated steroids in 40- to 80-year-old men. - PubMed - NCBI
"...The serum concentrations of 26 conjugated and unconjugated C21-, C19-, and C18-steroids were measured in 2423 men aged 40-80 yr. The serum concentrations of the major circulating adrenal C19-steroids, namely dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S), androst-5-ene-3 beta, 17 beta-diol and its sulfate, and androstenedione, decreased by about 60% between the ages of 40-80 yr. The small decrease in the serum concentrations of progesterone and pregnenolone in the presence of increased levels of cortisol and markedly decreased levels of DHEA, androst-5-ene-3 beta, 17 beta-diol, and their polar metabolites suggests that adrenal 17,20-lyase is particularly affected by aging. In addition to a marked decline in the serum concentrations of adrenal C19-steroids, a smaller, but significant, decrease occurred in serum testosterone. However, serum dihydrotestosterone levels remained constant, but the glucuronidated derivatives of dihydrotestosterone metabolites (androstane-3 alpha, 17 beta-diol glucuronide, androstane-3 beta, 17 beta-diol glucuronide, and androsterone glucuronide) were reduced by 45-50%, suggesting that 5 alpha-reductase activity in peripheral tissues may show a compensatory increase during aging. Analysis of the fatty acid esters of DHEA (DHEA-FA) also revealed that these nonpolar steroids markedly decrease between 40-80 yr of age, although such a decrease in DHEA-FA levels was smaller than that in DHEA and DHEA-S, suggesting that the formation of DHEA-FA may be specifically increased during aging. In summary, the present study suggests that in contrast to the marked decline in activity of steroidogenic enzymes in the adrenals and the small decrease in the testis, the activity of the steroid-converting enzymes present in peripheral tissues does not decrease during aging. In fact, the marked decrease in DHEA formation by the adrenals leads to a decrease of about 50% in total androgens in men between the ages of 40-80 yr. Such a decrease probably affects many physiological processes during aging."
 
Last edited:

Orion

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Thoughts on why 1 drop of pansterone will give older male night sweats, and a full dose will make it so I cannot sleep at all (feels like being on cortef, sleep is extremely light and un-restful).

I always suspected that it was estrogen/cortisol was actually being raised instead of dropping for me, when supp'ing preg, dhea or progesterone.

Still working on depleting PUFA stores, as I suspect this causes issues as well.
 

haidut

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Thoughts on why 1 drop of pansterone will give older male night sweats, and a full dose will make it so I cannot sleep at all (feels like being on cortef, sleep is extremely light and un-restful).

I always suspected that it was estrogen/cortisol was actually being raised instead of dropping for me, when supp'ing preg, dhea or progesterone.

Still working on depleting PUFA stores, as I suspect this causes issues as well.

It could be due to high FFA in the blood, so I would try taking with or a little after some niacinamide or aspirin or vitamin E, all of which lower lipolysis.
 

Orion

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I do take full Tocovit dose everyday with no adverse reaction, but B3 and aspirin give me the same symptoms, night wakings and sweats. B3 at even tiny amounts - 10 mg.

Will continue to focus on PUFA depletion.
 

johnwester130

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Thoughts on why 1 drop of pansterone will give older male night sweats, and a full dose will make it so I cannot sleep at all (feels like being on cortef, sleep is extremely light and un-restful).

I always suspected that it was estrogen/cortisol was actually being raised instead of dropping for me, when supp'ing preg, dhea or progesterone.

Still working on depleting PUFA stores, as I suspect this causes issues as well.

The DMSO potentiates the DHEA too much. It's much more like 5mg of DHEA, which is too much.
 

Drareg

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If an individual has some level of adiposity does this imply it might not be wise to use DHEA ?
Something like DHT or androsterone that cannot be converted via adipose expressed aromatase would be wiser?
 

Orion

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If an individual has some level of adiposity does this imply it might not be wise to use DHEA ?
Something like DHT or androsterone that cannot be converted via adipose expressed aromatase would be wiser?

Tried 11-keto, andro and 5a-DHP, they all seem to drive metabolism greatly at 1 drop (not used together), so night sweats and wakings occur with adequate calories.

PUFA depletion is probably the core issue I have, sleep and skin are improving with zero fat approach for me. Just need to commit more time to it I think.
 

haidut

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If an individual has some level of adiposity does this imply it might not be wise to use DHEA ?
Something like DHT or androsterone that cannot be converted via adipose expressed aromatase would be wiser?

Pregnenolone/progesterone alone or together, and some androsterone should do the trick.
 

Drareg

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Pregnenolone/progesterone alone or together, and some androsterone should do the trick.

Safer then when some level of adiposity is present to use pregnenolone instead of DHEA until fat levels are down?
Or using pregnenolone,progesterone,androsterone with dhea to insure no conversion to estrogen?

I'm guessing under 50 mg of pregnenolone is more than enough along with androsterone 1-2 drops.
 

Grouble

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I posted a few times about the steroidal characteristics of aging. Many people think there is a drop in testosterone (T) in aging and that is what drives the frailty of aging both in men and women. However, numerous studies show that that total T does not decrease with aging. What does seem to happen is that there is progressive rise of adrenal activity with advancing age. Initially, in the years between puberty and mid-30, there is a rise of DHEA concurrent with the rising cortisol and that protects humans from many of the cortisol's detrimental effects by being a direct cortisol antagonist and also by serving as precursor for androgens. However, with continued cortisol exposure eventually the adrenal layers responsible for DHEA synthesis atrophy and what remains is only the layer that synthesizes cortisol. A number of studies showed that ability to synthesize cortisol does NOT decline with age. Cortisol inhibits gonadal synthesis of steroids, prevents the recovery of the adrenal layers that synthesize DHEA, and activates the aromatase enzyme. Thus, old people end up with the cortisol levels of a 20 year old but with no DHEA and suppressed gonads (or failed ovaries) so they cannot synthesize protective steroids. Whatever small amount of DHEA remains in their blood gets shuttled to estrogen synthesis due to the high activity (and high expression as well due to increased adiposity) of aromatase .
The study below agrees with the description above. So, one possible approach would be to provide sufficient amount of the precursors pregnenolone, progesterone, and maybe some DHEA to at least balance the activity of cortisol and estrogen. Pregnenolone, progesterone and DHEA also help lower cortisol directly and thus should not only oppose cortisol's effects but also allow for the adrenal layers to recover and the gonads to resume synthesis of the protective steroids.

[Age-dependent changes in the concentration of active sex steroids, their precursors, metabolites, and regulating agents in male blood]. - PubMed - NCBI
"...Blood concentrations of hormone-inactive and active sex-steroid metabolites and their precursors were measured, taking into account changes in protein-peptide hormones that control the reproductive axis (in a total of 14 parameters) in men in the 18- to 72-year-old age interval. A significant decrease in the blood concentration of unutilized precursors of active sex steroids (pregnenolone, progesterone, dehydroepiandrosterone, and its sulfate), unbound testosterone, androstenedione (an inactive metabolite of testosterone), and an active metabolite, 5alpha-dihydrotestosterone was determined after the age of 35. However, the level of total testosterone and of estradiol (another active metabolite of testosterone) remained constant. The systems regulating the production of active sex steroids resisted a higher load, causing the luteinizing and follicle-stimulating hypophyseal hormones and activin of steroidogenic glands to increase and correlate positively with age; these hormones correlated negatively with certain sex steroids that realize negative feedback. A decrease in the level of adrenocorticotropic hypophyseal hormone with age suggests a more substantial role for adrenal glands as compared to that of testicles in reducing the blood concentration of active sex steroids. In general, despite the reduced activity of steroidogenic glands in 60- to 70-year-old men, their testosterone and estradiol concentrations remain unchanged, due to coordinated growth in the concentration of luteinizing and follicle-stimulating hypophyseal hormones, and to the activin of steroidogenic glands, which stimulated sex steroid biosynthesis. At the same time, the androgen effect was inhibited as a result of reduced levels of unbound testosterone and 5alpha-dihydrotestosterone."


[Age-related changes in blood concentration of hypothalamic-pituitary-adrenal axis hormones, their central and peripheral regulators in healthy men]. - PubMed - NCBI
"...We studied concentrations of cortisol, its precursors and active form in human blood and relation to the changes in concentration of central and peripheral hormonal regulators (total 36 parameters) in healthy male volunteers aged 18-72 y.o. The study demonstrated a significant decrease in blood concentrations of unutilazed cortisol precursors (pregnenolone and progesterone) with advanced age accompanied by maintenance of total and free cortisol concentrations. We found age-related decrease in ACTH level that is a known hypophysial stimulant of cortisol and cortisol precursor synthesis in adrenal glands. Cortisol and ACTH levels in study population had different correlation behavior in relation to central and peripheral regulators for hormonal axes.

"...CONCLUSION: cortisol level remains stable with advanced age in males despite the decrease in steroidogenic activity and blood ACTH level. This may be due to the imbalance in the regulation of cortisol and ACTH production by central and peripheral regulators especially by hormones of reproductive and somatotrophic axes."


Changes in serum concentrations of conjugated and unconjugated steroids in 40- to 80-year-old men. - PubMed - NCBI
"...The serum concentrations of 26 conjugated and unconjugated C21-, C19-, and C18-steroids were measured in 2423 men aged 40-80 yr. The serum concentrations of the major circulating adrenal C19-steroids, namely dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S), androst-5-ene-3 beta, 17 beta-diol and its sulfate, and androstenedione, decreased by about 60% between the ages of 40-80 yr. The small decrease in the serum concentrations of progesterone and pregnenolone in the presence of increased levels of cortisol and markedly decreased levels of DHEA, androst-5-ene-3 beta, 17 beta-diol, and their polar metabolites suggests that adrenal 17,20-lyase is particularly affected by aging. In addition to a marked decline in the serum concentrations of adrenal C19-steroids, a smaller, but significant, decrease occurred in serum testosterone. However, serum dihydrotestosterone levels remained constant, but the glucuronidated derivatives of dihydrotestosterone metabolites (androstane-3 alpha, 17 beta-diol glucuronide, androstane-3 beta, 17 beta-diol glucuronide, and androsterone glucuronide) were reduced by 45-50%, suggesting that 5 alpha-reductase activity in peripheral tissues may show a compensatory increase during aging. Analysis of the fatty acid esters of DHEA (DHEA-FA) also revealed that these nonpolar steroids markedly decrease between 40-80 yr of age, although such a decrease in DHEA-FA levels was smaller than that in DHEA and DHEA-S, suggesting that the formation of DHEA-FA may be specifically increased during aging. In summary, the present study suggests that in contrast to the marked decline in activity of steroidogenic enzymes in the adrenals and the small decrease in the testis, the activity of the steroid-converting enzymes present in peripheral tissues does not decrease during aging. In fact, the marked decrease in DHEA formation by the adrenals leads to a decrease of about 50% in total androgens in men between the ages of 40-80 yr. Such a decrease probably affects many physiological processes during aging."
Hi, new to this forum, been following you for a while; great info!. Menopause caused me serious health issues, of which the heat flushes was even welcome to the rest of it. Been reading ray peat articles for a few years. So finally I went to the doctor as progesterone is on the drug list in my country. My resting puls was 100, high blood pressure, heart was about to jump out of my chest. Couldn't sleep, though dead tired at all times. Temperature went from feeling ising cold to fever`ish. Anxiety, very low stress tolerance. (I have PTSD.) Lost weight as my appetite was non existent + a host of other symptoms. The doctor suspected hyper thyroid, took all the tests but came out normal.. Got hold of a bio-identical progesterone product; capsules. They were ment to take orally, but I ripped them apart mixed with aloe vera gel (+vit E) The effect has been close to a miracle. 14 days only, resting pulse down to the 60`s, blood pressure normal. I can sleep again; the waking up at 3-5 am is gone! (cortisol?) Now looking into pregnenolone for my PSTD. I just have to convince my doc.
 

Brave Heart

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Pregnenolone/progesterone alone or together, and some androsterone should do the trick.

"some level of adiposity" ??....means? I am probably 20lbs overweight fat around waist, chest , back....should I drop Pansterone for a while and try the above suggestion? I'm afraid I don't understand...
 

haidut

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"some level of adiposity" ??....means? I am probably 20lbs overweight fat around waist, chest , back....should I drop Pansterone for a while and try the above suggestion? I'm afraid I don't understand...

It means carrying extra fat tissue, which has a lot of aromatase in it and tends to convert DHEA into estrogen. Lower doses Pansterone should be OK but of course only blood/saliva tests would show for sure.
 

Brave Heart

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It means carrying extra fat tissue, which has a lot of aromatase in it and tends to convert DHEA into estrogen. Lower doses Pansterone should be OK but of course only blood/saliva tests would show for sure.

forgive me, I remember reading a little about this, but totally forgot about it...simply put, if I'm carrying a little extra fat still (lost 70# on Peat and gained back 10#...now top end of my ideal weight range) but looks like am still carrying 20# fat...I should forgo the DHEA (PANST.) for a while and do like DAGREG above?

"Safer then when some level of adiposity is present to use pregnenolone instead of DHEA until fat levels are down?
Or using pregnenolone,progesterone,androsterone with dhea to insure no conversion to estrogen?

I'm guessing under 50 mg of pregnenolone is more than enough along with androsterone 1-2 drops."
*********************
Currently using low Pan/Andro..2/1 ...Progestene arriving this week...no testing avail here.....what you think?
 

LeeLemonoil

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" The small decrease in the serum concentrations of progesterone and pregnenolone in the presence of increased levels of cortisol and markedly decreased levels of DHEA, androst-5-ene-3 beta, 17 beta-diol, and their polar metabolites suggests that adrenal 17,20-lyase is particularly affected by aging."

Taurine stimulates 17-Hydroxylase as far as I know
@haidut
 

LeeLemonoil

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@Dante

Pls read Haidut's opening posts and the study about Changes in serum concentrations of conjugated and unconjugated steroids in 40- to 80-year-old men.

Unfortunately only the abstract still exists - but it seems in aging peripheral tissue (hairloss) glucoronides of both 3a - and 3ß-diol decrease drastically.
Given that 3ß-HSD is expressed strongly in hairloss (the study we discussed), what does it mean - that hairloss is a condition where the scalp is unable to glucronidate DHT-metabolites like 3ß-diol - maybe this is a missing link
 

haidut

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" The small decrease in the serum concentrations of progesterone and pregnenolone in the presence of increased levels of cortisol and markedly decreased levels of DHEA, androst-5-ene-3 beta, 17 beta-diol, and their polar metabolites suggests that adrenal 17,20-lyase is particularly affected by aging."

Taurine stimulates 17-Hydroxylase as far as I know
@haidut

Yep, taurine upregulates that enzyme but the important one is the 17,20-lyase (of which 17-hydroxylase is a part) which converts C-21 steroids into C-19 steroids. Insulin and cortisol both suppress 17,20-lyase and cortisol/estrogen suppress the side chain-cleavage enzyme AND Leydig cell functionality in the gonads. So, in aging, there is decreased synthesis of pregnenolone (due to the side chain cleavage suppression), less conversion of the remaining pregnenolone into DHEA (due to the 17,20-lyase suppression), and finally less synthesis of androgens by Leydig cells. It seems that 17,20-lyase is the master break on androgen synthesis. If there was a way to boost its effects to suprephysiological levels then taking pregnenolone could replace AAS almost entirely. If you know of something that can stimulate 17,20-lyase please share. So far, I have only been able to find that aldosterone and ethanol stimulate it as well as boosting activity of cytochrome b5. Lowering insulin/cortisol would be the other method but it would be nice to get a few more substances that can boost 17,20-lyase independently.
It would be a good question for Peat I think.
 

chispas

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Tried 11-keto, andro and 5a-DHP, they all seem to drive metabolism greatly at 1 drop (not used together), so night sweats and wakings occur with adequate calories.

PUFA depletion is probably the core issue I have, sleep and skin are improving with zero fat approach for me. Just need to commit more time to it I think.

This happened to me when I took 1 drop orally. Try applying it in the morning, 2 hours after both waking, and consuming a good amount of orange juice or similar sugary food.
 

Agent207

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Cortisol rises because sentivity declines with aging, as happens with insulin.

What can be done to improve sensivity, other than fix inflammation sources and avoid excess stress?
 

Orion

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This happened to me when I took 1 drop orally. Try applying it in the morning, 2 hours after both waking, and consuming a good amount of orange juice or similar sugary food.

I am finding now the further I go on zero fat and using drops(stressnon and andro or DHP) on my feet, I am starting to see improvements in sleep, libido, etc. Still consuming lots of sucrose.
 

haidut

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Cortisol rises because sentivity declines with aging, as happens with insulin.

What can be done to improve sensivity, other than fix inflammation sources and avoid excess stress?

Lower lipolysis, which is mostly driven by estrogen and PUFA. So, the short answer would be niacinamide, aspirin and tocopherol. The long one would be improve thyroid function as it controls androgen synthesis, aromatase activity, and insulin sensitivity. Another study I posted said low-ish dose glycine restored glucose metabolism in 90-year old cells back to normal.
 
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