Bioavailability, Androgenicity, And Estrogenicity Of DHEA

[2thecloudsabove]

Nobody knows that as it depends on many factors, such as stress and inflammation. In higher doses it is estrogenic as evidence by increased estrone and decreased androgen levels in 35+ year olds.

Dr.Peat says we decline dhea production with age at about 2mg/decade rate after 25, so that should be the amount to be restored. So if oral administration has 3% aprox bioavailability, we should aim for (i.e. for 1 decade) 2/.03= 66mg dose? then we'd absorve the 3% equaling to the 2mg target. Is this right?

 

[haidut]

Dr.Peat says we decline dhea production with age at about 2mg/decade rate after 25, so that should be the amount to be restored. So if oral administration has 3% aprox bioavailability, we should aim for (i.e. for 1 decade) 2/.03= 66mg dose? then we'd absorve the 3% equaling to the 2mg target. Is this right?

In theory yes, but in practice it has been shown that even 15mg DHEA as a single dose taken over time ends up raising estrogen. So, lower doses than that are needed. Peat also said, 5mg restores DHEA levels in most people to youthful levels and that dose happens to be pretty safe for most people, even when stressed.

 

[2thecloudsabove]

In theory yes, but in practice it has been shown that even 15mg DHEA as a single dose taken over time ends up raising estrogen. So, lower doses than that are needed. Peat also said, 5mg restores DHEA levels in most people to youthful levels and that dose happens to be pretty safe for most people, even when stressed.

When you say "in practice", may I know which concrete practice are you referring to? per reviewed studies showing a generalized concomitant estrogen rise? or, individual, symptoms based, guessing driven claims?

 

[haidut]

When you say "in practice", may I know which concrete practice are you referring to? per reviewed studies showing a concomitant generalized estrogen rise? or, individual, symptoms based, guessing driven claims?

I mean studies, human ones. There are several studies on men with 25mg oral DHEA daily doses raising all 3 types of etsrogens, and topical DHEA in women raising estrogens when used in doses above 18mg daily. Here is the study on women, which applied 9mg DHEA twice daily (18mg total) for 12 months. Look at Fig. 7 in that study for more specific info.
Changes in serum DHEA and eleven of its metabolites during 12-month percutaneous administration of DHEA. - PubMed - NCBI

The other studies are also posted on the forum but are spread across various threads so you'll have to search.

 

[2thecloudsabove]

I mean studies, human ones. There are several studies on men with 25mg oral DHEA daily doses raising all 3 types of etsrogens, and topical DHEA in women raising estrogens when used in doses above 18mg daily. Here is the study on women, which applied 9mg DHEA twice daily (18mg total) for 12 months. Look at Fig. 7 in that study for more specific info.
Changes in serum DHEA and eleven of its metabolites during 12-month percutaneous administration of DHEA. - PubMed - NCBI

The other studies are also posted on the forum but are spread across various threads so you'll have to search.

1. I ask you because I've already searched not just here on the forum but all over internet, and no trace of those misterious studies on normal, young or middle aged men. You mentioned "practice".. well lets talk practice then.

2. Sorry, but throwing a postmenopausal women study as response, supossing you understand the context of what we're talking about and its intrinsic traits, its a very poor movement and a scorn to the intelligence to say the least. A c.elegans study would have been less offensive.

 

[2thecloudsabove]

Woww, even after the nonsense of your refutal, I've been digging more into that postmenopausal study you threw, just for curiosity and fun and seriously can't believe how ingenuous you must be at assuming users ignorance on endocrinology or dont being able to read an study.

The study was not just done on menopausal women, but on top of that it used dhea TOPICAL form. Remember how this started, debating about oral/transdermal equivalence absorption rates? well so this by no means refutes what I said that higher oral doses should be required to equal a given transdermal 100% absortpion route.

But ok let that sit apart and take a look at the study. You said "look at figure 7" (your link to an abstract, so no figures to see, had to find the full text, maybe you thought I couldn't or I'll pass? well, I didnt) like saying... "look at how horrible estrogen rose at those poor women"... well, here you have:

LOL.. E2 was precisely the only one with a barely significan increase from all of them.

But wait!! this doesn't end here. Lets have a look at the resulting net estrogen levels on them...

Around 5-6 pg/mL? Hahahaha... you know how a fairly young women around 20s-30s ranges? 50-100 pg/mL (--> Menses, not follicular, not luteal phasing) Oh God.. those women must had counted days left to live for for such a dramatic increase in estrogen (and I repeat, not just postmenopausic scenario here, but transdermal administration, supposed 10x higher absorption over oral)

Well, it took my time but I guess anyone with 2 working neurons can see your extremely biased and forced arguments, and how bad you are at manipulating and exposing it. Maybe with the hope that most of the people that reads you to be completely novice on the subject and and believe the stance getting lost in a mumbo-jumbo gibberish bunch of words and technical argot. And that when you're not showing a sentence on a titles thread so to look a generalized statement and then you get in and find mice, elegans and extremely cherry picked scenarios. Poor grade clickbaiting is how we call it at our neighborhood.

 

[haidut]

1. I ask you because I've already searched not just here on the forum but all over internet, and no trace of those misterious studies on normal, young or middle aged men. You mentioned "practice".. well lets talk practice then.

2. Sorry, but throwing a postmenopausal women study as response, supossing you understand the context of what we're talking about and its intrinsic traits, its a very poor movement and a scorn to the intelligence to say the least. A c.elegans study would have been less offensive.

You are joking, right? I said there are studies and found one of the ones I had in mind with a quick search, which albeit in women, shows statistically significant elevations in estrogens. You don't think this elevation of estrogen in women, in whom DHEA has predominantly androgenic effects (especially when used topically) has any merit or reason for caution??
Then here is your male study, with 25mg daily dose. Do you see what I see - more than doubling of estrone and estradiol levels?
Long-term low-dose dehydroepiandrosterone replacement therapy in aging males with partial androgen deficiency. - PubMed - NCBI
"...Allopregnanolone levels (163.8+38.6 pg/ml) rose significantly at the 7th month (p50.05) and reached the steady state at the 9th month (269.8+49.3 pg/ml, p50.001). SHBG values (17.0+2.4 ng/ml) showed a significant decrease from the 7th month of therapy (14.94+1.34 ng/ml, p50.05). Estrone levels (34.17+12.19 pg/ml) increased progressively from the 4th month (p50.05) and reached the steady state at the 8th month of therapy (70.5+ 12.9 pg/ml). Estradiol levels (18.67+3.08 pg/ ml) rose significantly at the 3rd month of therapy (p50.05) and reached the steady state at the 9th month (43.5+8.09 pg/ml, p50.001)."

 

[haidut]

Woww, even after the nonsense of your refutal, I've been digging more into that postmenopausal study you threw, just for curiosity and fun and seriously can't believe how ingenuous you must be at assuming users ignorance on endocrinology or dont being able to read an study.

The study not just on menopausal women, but it used TOPICAL dhea. Remember how this started, debating about oral/transdermal equivalence absorption rates? well so this by no means refutes what I said that higher oral doses should be required to equal a given transdermal 100% absortpion route.

But ok let that sit apart and take a look at the study. You said "look at figure 7" (your link to an abstract, so no figures to see, had to find the full text, maybe you thought I couldn't or I'll pass? well, I didnt) like saying... "look at how horrible estrogen rose at those poor women"... well, here you have:

LOL.. E2 was just the only one with a barely significan increase from all of them.

But wait!! this doesn't end here. Lets have a look at the resulting net estrogen levels on them...

Around 5-6 pg/mL? Hahahaha... you know how a fairly young women around 20s-30s ranges? 50-100 pg/mL (--> Menses, not follicular, not luteal phasing) Oh God.. those women must had counted days left to live for for such dramatic increase in estrogen (and I repeat, not just postmenopausic scenario here, but transdermal administration, supposed 10x higher absorption over oral)

Well, it took my time but I guess anyone with 2 working neurons can see your extremely biased and forced arguments, and how bad you are at manipulating and exposing it. Maybe with the hope that most of the people that reads you to be completely novice on the subject and and believe the stance getting lost in a mumbo-jumbo gibberish bunch of words and technical argot. And that when you're not showing a sentence on a titles thread so to look a generalized statement and then you get in and find mice, elegans and extremely cherry picked scenarios. Poor grade clickbaiting is how we call it at our neighborhood.

Not sure why you think I am manipulating anybody or hiding data. It is customary to post only the PubMed link as not to violate copyright terms. Whoever wants to get the full study usually goes to Sci-Hub.
That being said - where exactly did I say that DHEA results in massive increases in estrogen? I said I have seen studies in both men and women showing DHEA in doses of higher than 15mg raises estrogen. Did I provide you with one study in my first response? I did. Did it show increases in E2, E1 and E1S from 18mg DHEA daily? It did. Whether you think this increase is big enough to be a reason for concern or not is your business, it has nothing to do with the veracity of what I said about DHEA raising estrogen. Did I provide you with the male study using 25mg DHEA daily in the second response? I did. Did it show more than doubling of E2 and E1. It did.

So, where exactly is the discrepancy between what I said and the evidence I provided??

 

[2thecloudsabove]

Yeah, Im havin a look at this last study you linked which sounds more convincing. Had you referred to this one earlier before posting that joke of the menopausal women, we'd save time and energy resources. I'll read this last one right now, I dont have problem at agreeing with coherence and proper criteria.

 

[Vinero]

Dr.Peat says we decline dhea production with age at about 2mg/decade rate after 25, so that should be the amount to be restored. So if oral administration has 3% aprox bioavailability, we should aim for (i.e. for 1 decade) 2/.03= 66mg dose? then we'd absorve the 3% equaling to the 2mg target. Is this right?

Good luck with that. Oral DHEA is estrogenic especially in such high doses. I get high estrogen symptoms even from a 5 mg oral dose of DHEA. I would only use DHEA topically.

 

[haidut]

Yeah, Im havin a look at this last study you linked which sounds more convincing. Had you referred to this one earlier before posting that joke of the menopausal women, we'd save time and energy resources. I'll read this last one right now, I dont have problem at agreeing with coherence and proper criteria.

Yes, I have. I think Peat was the first one mentioning it years ago and I also had trouble finding it on PubMed. He said that since 25mg DHEA in men is estrogenic and less than that is estrogenic in women (in whom DHEA favors the andogen pathway) than less than 15mg daily should probably be used. He also said the daily DHEA production in young people is about 12mg-14mg so the dose should probably not exceed that one. Finally, a rat study showed that a HED of 0.15mg/kg elevated DHT without much effects on estrogen. That would correspond to a 10mg - 14mg dose for most adults. Here is the study.
DHEA Provides Same Benefits Effects As Exercise By Increasing DHT

So, the combination of those studies, what Peat said, and the studies on men showing oral DHEA in 25mg dose being estrogenic (and 50mg / 100mg doses being highly estrogenic) is what led me to say several times on the forum that doses of 15mg or less are probably safest.

 

[haidut]

Yeah, Im havin a look at this last study you linked which sounds more convincing. Had you referred to this one earlier before posting that joke of the menopausal women, we'd save time and energy resources. I'll read this last one right now, I dont have problem at agreeing with coherence and proper criteria.

As per your other calculation of about 66mg daily dose - there are several studies with male humans showing 50mg was quite estrogenic, more so (expectedly) than the 25mg dose. I can post those studies as well.
The oral bioavailability of DHEA is likely higher than 3%. It just has a very short half life as it gets extensively metabolized into DHEA-S, and other downstream steroids, so studies looking at the bioavailability usually can't measure properly how much is absorbed/utilized. Better bioavailability studies have been done with animals since they can be given radioactive DHEA, and in them DHEA has close to 100% bioavailability. I don't know of any mechanism in humans that would reduce this high bioavailability of DHEA especially when taken with fat.
Finally, Peat has recommended many times to people doses of 5mg-10mg DHEA and said higher doses would be estrogenic (especially when under stress) and that the 5mg-10mg should be enough to restore DHEA levels back to normal. It just might take some times as DHEA is so extensively metabolized and it will take some time to fill the downstream pathways if there are any deficiencies. But within a few months, even 10mg DHEA have been shown to raise DHEA levels back within the normal range. Those 10mg studies were with women so not sure if you want to see them or not but I can dig them out if you want.

Here is one study with 100mg oral DHEA in men showing 70%+ increase in estradiol, no change in total T and 20% increase in free T. See Table 1 in the study for specific numbers.
Dehydroepiandrosterone replacement in aging humans. - PubMed - NCBI
"...During the use of the drug, blood DHEA, DHEAS, and estradiol showed a strong mean increase (P , 0.0005), as did free testosterone (P , 0.0013), but there was no statistical significance for total testosterone or PSA. Neither fasting blood insulin nor T4 changed."

Now, the real question is - can somebody take small DHEA doses repeatedly and get the androgenic effects without the estrogenic ones? I believe it may be possible, especially in people younger than 35, but you may need to use sub 5mg doses 8-10 times daily. If you want to try 3mg every 2 hours and do some blood work I would be very interested in seeing it.

 

[Wagner83]

Didn't Ray say that in individual with less than ideal metabolism even 2-3mg could enlarge the liver?
He also said this:
"One study has found that the only hormone abnormality in a group of Alzheimer's patients' brains was an excess of DHEA. In cell culture, DHEA can cause changes in glial cells resembling those seen in the aging brain. These observations suggest that DHEA should be used with caution. Supplements of pregnenolone and thyroid seem to be the safest way to optimize DHEA production. " -Ray Peat
So I think he is very cautious about dhea supplementation, even more than what the studies suggest, here are some quotes:
Ray Peat Email Advice Depository

For a young person, 5 mg DHEA orally is a very effective amount, very old people could use 10 to 15 mg. For a year I took an average of 3000 mg of pregnenolone daily, with nothing but good effects, but when I tried different brands (that was from Syntex), even 20 mg caused intestinal inflammation symptoms.
[...]It takes a larger dose on the skin than orally.

Ray Peat Email Advice Depository

but 5 mg of DHEA is safe, if your thyroid, vitamin D, and other tests are normal.

Ray Peat Email Advice Depository

A teenage male makes only about 12 mg of DHEA per day; when older men take 25 mg, they usually get very high estrogen."

If your thyroid is very low, you should be cautious with the DHEA, because stress hormones can cause it to turn to estrogen. 5 mg of DHEA taken with a little olive oil or butter can have a noticeable effect on your mood and muscle tone in a few hours.

If your thyroid is very low, you should be cautious with the DHEA, because stress hormones can cause it to turn to estrogen. 5 mg of DHEA taken with a little olive oil or butter can have a noticeable effect on your mood and muscle tone in a few hours.

 

[TheBeard]

As per your other calculation of about 66mg daily dose - there are several studies with male humans showing 50mg was quite estrogenic, more so (expectedly) than the 25mg dose. I can post those studies as well.
The oral bioavailability of DHEA is likely higher than 3%. It just has a very short half life as it gets extensively metabolized into DHEA-S, and other downstream steroids, so studies looking at the bioavailability usually can't measure properly how much is absorbed/utilized. Better bioavailability studies have been done with animals since they can be given radioactive DHEA, and in them DHEA has close to 100% bioavailability. I don't know of any mechanism in humans that would reduce this high bioavailability of DHEA especially when taken with fat.
Finally, Peat has recommended many times to people doses of 5mg-10mg DHEA and said higher doses would be estrogenic (especially when under stress) and that the 5mg-10mg should be enough to restore DHEA levels back to normal. It just might take some times as DHEA is so extensively metabolized and it will take some time to fill the downstream pathways if there are any deficiencies. But within a few months, even 10mg DHEA have been shown to raise DHEA levels back within the normal range. Those 10mg studies were with women so not sure if you want to see them or not but I can dig them out if you want.

Here is one study with 100mg oral DHEA in men showing 70%+ increase in estradiol, no change in total T and 20% increase in free T. See Table 1 in the study for specific numbers.
Dehydroepiandrosterone replacement in aging humans. - PubMed - NCBI
"...During the use of the drug, blood DHEA, DHEAS, and estradiol showed a strong mean increase (P , 0.0005), as did free testosterone (P , 0.0013), but there was no statistical significance for total testosterone or PSA. Neither fasting blood insulin nor T4 changed."

Now, the real question is - can somebody take small DHEA doses repeatedly and get the androgenic effects without the estrogenic ones? I believe it may be possible, especially in people younger than 35, but you may need to use sub 5mg doses 8-10 times daily. If you want to try 3mg every 2 hours and do some blood work I would be very interested in seeing it.

@haidut at which DHEA blood level would you advise someone to start supplementing? Are mid-range values normal as doctors say, or should we shoot for the high end of the range?

I would obviously take aromasin with the DHEA to avoid any estrogen sides

 

[haidut]

@haidut at which DHEA blood level would you advise someone to start supplementing? Are mid-range values normal as doctors say, or should we shoot for the high end of the range?

I would obviously take aromasin with the DHEA to avoid any estrogen sides

I think epidemiological studies have shown that optimal health is when DHEA levels are maintained in the top 25% range for young people. So, if your lab gives different "normal" ranges depending on age I would try to be in the top 25% of the age group 20-30. If youa re using aromasin then there may be no need to even take DHEA separately, as DHEA decline with age are mostly due to estrogen/cortisol elevations and aromasin has been shown to raise DHEA levels by at least 30%-40%.

 

[Spondive]

Copper, Coronary Heart Disease, and Dehydroepiandrosterone

Perhaps low DHEA in their subjects (1) was a subtle, indirect sign of copper deficiency. People who believe that high concentrations of DHEA are beneficial may find that copper supplements are less expensive and less hazardous than DHEA supplements. A supplement containing copper produced improvement in heart failure.

 

[TheBeard]

I think epidemiological studies have shown that optimal health is when DHEA levels are maintained in the top 25% range for young people. So, if your lab gives different "normal" ranges depending on age I would try to be in the top 25% of the age group 20-30. If youa re using aromasin then there may be no need to even take DHEA separately, as DHEA decline with age are mostly due to estrogen/cortisol elevations and aromasin has been shown to raise DHEA levels by at least 30%-40%.

Thank you.

I’ll stick to aromasin for now then

 

[Matestube]

****** NEW EXPERIMENT ******


I have made some DHEA in DMSO at 100mg/ml, applying 1ml on the scrotum and 1ml on the abdomen in the morning (so 200mg DHEA transdermally every day), and got off testosterone, in order to measure the testosterone and e2 conversion of high dose transdermal DHEA.

I'm tired of studies saying that it either works or doesn't for raising T, so I decided to try it.
I hope the results show in serum blood levels and that the conversion doesn't happen mostly peripherically.

I'm still not sure about how many days I should wait before drawing bloods, but I'm away for a month anyways, so I might wait for mid August before I do so.

If that works, one gets a more complete androgenic profile than just test base in DMSO.
If it doesn't, I'll have to keep applying test base and little DHEA to have a complete androgenic profile.

 

[AinmAnseo]

The study with humans using topical administration found no estrogen increase until the daily dose reached 18mg. Androgens kept increasing for all doses. So, it seems that by using DMSO we can get a much bigger percentage of DHEA to convert into androgens if we stay under 18mg daily. There is another study that I will post on Monday showing 40% - 60% of the topically applied DHEA converted into DHT. So, this means getting 7mg+ of DHT from 15mg DHEA daily. This is a LOT. I have seen several official sources claim that a healthy young male produces around 0.1mg DHT per day. Not bad for a steroid officially labelled as dead-end in terms of relevance to human aging.

So, based on this, it - seems - like:
A man (past 50?) should not take more than 1 mg of topical DHEA daily, since it looks like 1 mg of topical DHEA daily would convert to .5 mg of DHT, which is already much more than even a young man makes.
I assume that when Peat spoke about not needing more than 5 mg DHEA to restore youthful levels, he meant orally, but I am not sure.

 

[AinmAnseo]

Thank you.

I’ll stick to aromasin for now then

What is your source for aromasin?