No evidence for hepatic conversion of dehydroepiandrosterone (DHEA) sulfate to DHEA: in vivo and in vitro studies

[Gianluca]

Abstract​

Dehydroepiandrosterone (DHEA) sulfate (DHEAS) is the most abundant steroid in the human circulation and is thought to be the circulating hydrophilic storage form of DHEA. It is generally accepted that DHEA and DHEAS inter-convert freely and continuously via hydroxysteroid sulfotransferases and steroid sulfatase and that only desulfated DHEA can be converted downstream to sex steroids. Here we analyzed DHEA/DHEAS interconversion in vivo and in vitro. We administered oral DHEA (100 mg) and iv DHEAS (25 mg) to eight healthy young men, resulting in similar increases in serum DHEAS compared with baseline. However, although DHEA administration significantly increased serum DHEA (P < 0.05), no such increase was observed after DHEAS. Similarly, DHEA but not DHEAS was converted downstream to androstenedione, estrone, and androstanediol glucuronide. The striking absence of conversion of DHEAS to DHEA was mirrored by our in vitro findings in HepG2 cells, revealing dose-dependent conversion of DHEA (0.1-2 mum) to DHEAS but no conversion of DHEAS (0.1-2 mum). These results clearly illustrate a lack of hepatic conversion of DHEAS to DHEA, challenging the concept of free interconversion of DHEA and DHEAS. DHEAS does not seem to represent a circulating storage pool for DHEA regeneration, and therefore serum DHEAS is unlikely to reflect bioavailable DHEA.

No evidence for hepatic conversion of dehydroepiandrosterone (DHEA) sulfate to DHEA: in vivo and in vitro studies - PubMed

Dehydroepiandrosterone (DHEA) sulfate (DHEAS) is the most abundant steroid in the human circulation and is thought to be the circulating hydrophilic storage form of DHEA. It is generally accepted that DHEA and DHEAS inter-convert freely and continuously via hydroxysteroid sulfotransferases and...

pubmed.ncbi.nlm.nih.gov

 

[Gianluca]

I would like to hear the opinions on this study, which does explain why when i tested my Free DHEA in an adrenal stress profile, it came back low, despite my DHEA-S was at a good level.

 

[Dicky]

The way I am reading this, the only issue here is that we are measuring DHEA-S via bloodwork to see if our DHEA levels are good. The study is saying that it doesn't work like that...."and therefore serum DHEAS is unlikely to reflect bioavailable DHEA." Perhaps we need to be using an adrenal stress profile or something similar to what you did in order to directly measure DHEA instead of DHEA-S.

Your situation (low free DHEA yet good DHEA-S) should be easily remedied by taking oral DHEA, which should drive up your free DHEA level.

Was the adrenal stress profile a saliva test?

 

[Gianluca]

The way I am reading this, the only issue here is that we are measuring DHEA-S via bloodwork to see if our DHEA levels are good. The study is saying that it doesn't work like that...."and therefore serum DHEAS is unlikely to reflect bioavailable DHEA." Perhaps we need to be using an adrenal stress profile or something similar to what you did in order to directly measure DHEA instead of DHEA-S.

Your situation (low free DHEA yet good DHEA-S) should be easily remedied by taking oral DHEA, which should drive up your free DHEA level.

Was the adrenal stress profile a saliva test?

Yes it was a saliva test, so I think it was a free DHEA that was tested, and if I'm correct, all the free portion of the hormones are those that are actually important. Perhaps DHEA-S may not be the best way to determine good DHEA levels.

Probably best way to raise free DHEA is with a cream, injection or sublingual, like any other hormones.

By the way, my DHEA-s at the time of the test was at about 350, so the low bottom of what considered optimal.

 

[Dicky]

Yes it was a saliva test, so I think it was a free DHEA that was tested, and if I'm correct, all the free portion of the hormones are those that are actually important. Perhaps DHEA-S may not be the best way to determine good DHEA levels.

Probably best way to raise free DHEA is with a cream, injection or sublingual, like any other hormones.

By the way, my DHEA-s at the time of the test was at about 350, so the low bottom of what considered optimal.

FWIW In the USA, oral DHEA is very inexpensive as opposed to other forms. That would probably be the first item I would try.