Newish study below . The findings are interesting, albeit strange.
DHEA (dehydroepiandrosterone) is a precursor of T (testosterone). There are two paths:
a) cholesterol --> pregnenolone --> DHEA --> androstenedione --> T
b) cholesterol --> pregnenolone --> DHEA --> androstenediol --> T
Zytiga blocks the conversion of pregnenolone to DHEA.
We produce a ton of DHEA when we are young adults, but levels plummet with age. It's an extraordinary drop. Why did we need so much when young?
The sulphated form of DHEA (DHEA-S) represents our reservoir of DHEA.
"Baseline low serum dehydroepiandrosterone sulfate can predict poor responsiveness to hormone therapy in patients with hormone-naïve prostate cancer with skeletal metastases"
Why would that be?
DHEA is an over-the-counter supplement. I used it many years ago, but subsequently, when I began using T patches, DHEA-S rose to youthful levels without a supplement. That in itself is strange - why would increased T raise levels of its precursor?
Some experts advise against using DHEA, since it can also convert to estrogen. I always viewed that as a specious warning. At 18 my body was swimming in the stuff & I'm sure that my T:estrogen ratio was fine - better than at age 58, I'm sure. The body uses the DHEA-S reservoir judiciously IMO.
The following is from Labrie (2005) :
"Dehydroepiandrosterone (DHEA) is not a hormone but it is a very important prohormone secreted in large amounts by the adrenals in humans and other primates, but not in lower species. It is secreted in larger quantities than cortisol and is present in the blood at concentrations only second to cholesterol. All the enzymes required to transform DHEA into androgens and/or estrogens are expressed in a cell-specific manner in a large series of peripheral target tissues, thus permitting all androgen-sensitive and estrogen-sensitive tissues to make locally and control the intracellular levels of sex steroids according to local needs."
"In men, where the secretion of androgens by the testicles continues for life, the contribution of DHEA to androgens has been best evaluated in the prostate where about 50% of androgens are made locally from DHEA."
So a shortage of DHEA-S might indicate that PCa had already been enduring a shortage of androgen? And that the cancer is already primed to become CRPC., perhaps.
"The active androgens made locally in the prostate exert their action by interacting with the androgen receptor in the same cells where their synthesis takes place without being released in significant amounts in the extracellular environment or the general circulation. Contrary to the previous belief that the testes are responsible for 90–95% of total androgen production in men (as could be inferred from the 90–95% decrease in serum testosterone observed after castration), it is now well demonstrated that the prostatic tissue efficiently transforms the inactive steroid precursors DHEA-S, DHEA and 4-dione into the active androgens testosterone and DHT locally in peripheral tissues, including the prostate, without significant release of the active androgens in the circulation. In fact, the prostate makes its own androgens at a level comparable with the androgens of testicular origin."
Which suggests that Zytiga & Lupron be started together,
Inernational Journal of Urology. Urological Notes
Baseline low serum dehydroepiandrosterone sulfate can predict poor responsiveness to hormone therapy in patients with hormone-naïve prostate cancer with skeletal metastases
Akihiro Yano M.D., Ph.D.,
Makoto Kagawa M.D.,
Hideki Takeshita M.D., Ph.D.,
Yohei Okada M.D., Ph.D.,
Makoto Morozumi M.D., Ph.D.,
Satoru Kawakami M.D., Ph.D.
First published: 11 September 2017