DHEA Levels & ADT Failure.

[pjoshea13]

New Japanese study [1].

No Abstract, but title seems to say it all:

"Baseline low serum dehydroepiandrosterone sulfate can predict poor responsiveness to hormone therapy in patients with hormone-naïve prostate cancer with skeletal metastases".

Dehydroepiandrosterone [DHEA] is a steroid hormone. Looking at the Steroidogenesis chart [2], we see Pregnenolone-->DHEA-->Androstenedione/Androstenediol-->Testosterone. Zytiga inhibits that first conversion. Having low levels of DHEA during ADT would seem to be a good thing. But having low levels of testosterone at diagnosis does not correlate with a better prognosis. What might be going on?

At 20 we have massive amounts of DHEA. At 50 they have declined by 50%; & at 75 to 10% of their peak. As with testosterone levels, which also fall 'naturally' (from about age 32), one wonders what is lost - do the declines increase susceptibility for age-related diseases, such as PCa.

The half-life of DHEA is short - about 25 minutes. Most of our DHEA is sulphated to DHEA-S, which has a half-life of ~11 hours. DHEA-S is a better measure of DHEA status, because it can be converted back to DHEA as needed.

In 1993, Comstock (Johns Hopkins) reported [3] that "DHEA-S levels were 12% lower than among controls" "in sera collected and frozen in 1974", but concluded that: "It seems unlikely that serum levels of DHEA or DHEA-S are important risk factors for prostate cancer."

"Like most potential risk factors for prostate cancer, the

associations of DHEA and DHEA-S with this malignancy

appear to be weak at best and within the usually accepted

limits for chance occurrences. The only evidence

against the null hypothesis is the consistency of the weak

associations in several subgroup analyses and some degree

of biological plausibility. DHEA has been shown to

have a protective effect against tumors in animals."

In a Japanese study from last year [4]: "low serum DHEA levels in prostate cancer patients were significantly related to high Gleason score and advanced clinical stage." "High serum PSA and low serum DHEA levels were significantly associated with poor prognosis factors in men with hormone-naïve prostate cancer."

...

On a personal note: I used to take DHEA to boost age-declining levels. When I began boosting testosterone to high-normal, I found that DHEA-S rose too, & I stopped using DHEA. I am not aware of a backward path from T to DHEA. Unfortunately, the above studies seem not to have considered T levels.

-Patrick

[1] onlinelibrary.wiley.com/wol...

[2] en.wikipedia.org/wiki/Dehyd...

[3] cebp.aacrjournals.org/conte...

[4] ncbi.nlm.nih.gov/pubmed/266...

[pjoshea13]

Nala,

Since low T & low DHEA are now each associated with a poorer prognosis, & there is no pathway from T to DHEA, I'd like to know if men with PCa & low T also tend to have low DHEA. Perhaps DHEA is much more important than I have assumed?

-Patrick