Androsterone - An Andidepressant Neurosteroid

haidut

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The neurosteroid DHEA has a well-known and studied anti-depressant effect. Several studies have been done in humans using relative high doses of DHEA (50mg - 450mg daily) and they all found positive effects of DHEA on depression.

Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression. - PubMed - NCBI
Neurosteroids in depression: a review. - PubMed - NCBI

However, there mechanism behind the anti-depressant effect of DHEA is not well known. What is known is that administering an anti-androgen together with DHEA blocks the anti-depressant effect. This suggest that one of the DHEA androgenic metabolites is the actual "active ingredient". Human studies using DHT and allopregnanolone all found benefit, further suggesting that it is steroids derived through the 5-AR enzyme that are likely behind the positive effect. Finally, administering DHT together with a chemical that blocks downstream DHT metabolism also largely eliminates the anti-depressant effect. This narrows down the list of possible "suspects" to just a few steroids and one of them is androsterone. Given that androsterone is also a potent GABA agonist just like allopregnanolone virtually points the finger straight at that steroid as the main mechanism of DHEA's antidepressant action. And a recent human study seems to confirm that hypothesis. In women with depression being treated with DHEA, the response rate was directly correlated with androsterone levels.

Altered levels of circulating GABAergic 5α/β-reduced pregnane and androstane steroids in schizophrenic men. - PubMed - NCBI
Relevance of endogenous 3alpha-reduced neurosteroids to depression and antidepressant action. - PubMed - NCBI
DHEA metabolism to the neurosteroid androsterone: a possible mechanism of DHEA's antidepressant action. - PubMed - NCBI

"...RESULTS: ADT levels (but not allopregnanolone, pregnanolone, and pregnenolone) increased after DHEA but not after placebo (F 2,42 = 3.3, p < 0.05). Post-DHEA ADT levels were higher in women than men [t 63 = 2.9, p < 0.05]. However, in both men and women who met criteria for clinical response on the CES-D, baseline ADT levels significantly increased post-DHEA, and the magnitude of the ADT increase post-DHEA treatment was similar in men and women. Consequently, it was the non-responders who accounted for the sex difference in post-DHEA plasma ADT levels, a difference that was driven by values in two women (the only female non-responders).

"...CONCLUSIONS: The small sample size notwithstanding, these data emphasize the potential behavioral relevance of ADT in humans, which may include contribution to the antidepressant effects of DHEA."
 
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chispas

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This is interesting. Do you think androsterone could work to help people with dementia or Alzheimers?
 

haidut

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This is interesting. Do you think androsterone could work to help people with dementia or Alzheimers?

Possibly, given that Alzheimer is simply brain-specific hypometabolism and fatty acid overload. In another post I showed that androsterone increases BDNF synthesis, which is another promising treatment for dementia. Thyroid also treats dementia and androsterone is probably one of the most pro-thyroid steroids.
 
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