I don't think I was tested against this gene, so I think it could be important for me as well.
A common genetic variation called the adrenal-permissive allele in the hsd3b1 gene can lead to more aggressive prostate cancer. This allele increases the activity of the 3βHSD1 enzyme, leading to higher production of androgens, even when androgen deprivation therapy (ADT) is used.
This can lead to castration-resistant prostate cancer and increased mortality in men who carry this allele. Germline testing for the hsd3b1 gene could identify men who may benefit from earlier and more aggressive treatment for prostate cancer.
Yes i have noticed that from time to time it comes back. The difference I see is mainly that now they added that they recommend adrenal glands blockade in first line for people with this mutation. I wonder why I was not tested for this gene 🤔
My error error KocoPr. And the 2024 link is too new for Sci-Hub to have it. Sans the use of newer, more thorough (and widely available) testing, we are all currently being treated withimprecision* medicine.
* imprecise: adjective
Example: the "witness" (substitute"doctor" here) could give only vague and imprecise descriptions. (and you have a rough description of the current SOC for mainstream PCa patients.)
I am trying to get more info about that article, I don't have access to such complete articles anymore but maybe I can find someone at my university that still has. My take is that while on ADT it allows enough testosterone to let the cancer progress and at a speed that leads sooner to CR due AR mutation, but that's what I get from reading also the older articles about it. I cannot find anywhere if they mean that the adrenal glands produce enough testosterone to avoid castration levels.
Max - Overnight, Patrick sent me the following comment re: your post on HSD3B1:
* * *
Perhaps those who test positive for HSD3B1 & are put on ADT, should also start Abiraterone at the same time? This might eliminate any adrenal hormone influence.
But, from 2020 [1], re Abi:
"An early metabolite, Δ4-abiraterone (D4A), strongly inhibits steroidogenic enzymes (CYP17A1, 3βHSD) and even AR itself. However, further metabolites of D4A have pro-androgenic activity. Work by Alyamani et al has demonstrated that presence of adrenal permissive alleles is associated with significantly more generation of the pro-androgenic abiraterone metabolites.40,41 Thus, while abiraterone itself may be beneficial in inhibiting adrenal androgen synthesis in patients with adrenal permissive alleles, increased metabolism of abiraterone by those same adrenal permissive enzymes to pro-androgenic metabolites may limit or blunt the efficacy of the drug."
Seems that HSD3B1 is common & everyone about to begin ADT should be tested. But, perhaps Dutasteride as a safety play would be sufficient?
{""Dihydrotestosterone synthesis in prostate cancer from adrenal DHEA/DHEA-sulfate requires enzymatic conversion in tumor tissues. 3β-hydroxysteroid dehydrogenase-1 is an absolutely necessary enzyme for such dihydrotestosterone synthesis and is encoded by the gene HSD3B1 which comes in 2 functional inherited forms described in 2013. The adrenal-permissive HSD3B1(1245C) allele allows for rapid dihydrotestosterone synthesis."}
As usual, we continue to be deprived of his invaluable insights by restrictions on his privileges that originate from a non-affiliated forum. Get real, Mr. D & bethishere.
No, but I'm on an anti-androgen (bical @ 50 mg daily) + a 5ARi (dutasteride or finasteride @ 3 x per wk.) + a SERM (low-dose tamoxifen @ 5 mg daily.) This combo has kept my PSA stable at 0.2 -0.4 ng/mL over the past 2 years. Since T is not blocked by this combo (just the conversion by 5 ARi of T to the more powerful DHT) and bical can actually boost T by as much as 80 %; the QOL issues related to SOC ADT are essentially absent. Since I have been able to return to a fully-active lifestyle post-COVID, my QOL is currently excellent. As I have an openly stated priority of QOL over longevity, I will use some variation of this combo until I see signs of waning efficacy or access to something better. Definitely a case of different strokes for different folks - and, thus, not recommended as a mainstream treatment approach.
Note that there is much speculative chatter these days about the presence of a "post-finasteride syndrome". As with most "syndromes", the evidence for this "condition" is mostly correlative vs evidentiary. Due to changes in my drug insurance this year, I switched from dutasteride to finasteride about six months back. I have noticed no discernible difference since making the switch.
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