But first, the following is from a South African study (2016) [2].
"Dihydrotestosterone (DHT) is regarded as the most potent natural androgen and is implicated in the development and progression of castration resistant prostate cancer (CRPC). Under castrate conditions, DHT is produced from the metabolism of the adrenal androgen precursors, DHEA and androstenedione."
"Recent studies have shown that the adrenal steroid 11β-hydroxyandrostenedione ... serves as the precursor to the androgens 11-ketotestosterone (11KT) and 11-ketodihydrotestosterone (11KDHT)."
"This is the first study, to our knowledge, to show that 11KT and 11KDHT, like T and DHT, are potent and efficacious agonists of the human androgen receptor (AR) ..."
"... our data demonstrates that 11KT and 11KDHT likely play a vital, but overlooked, role in the development and progression of CRPC."
***
From the new study:
"Studies have identified 11-ketotestosterone (11KT) as a potent AR agonist, but it is unknown if 11KT is present at physiologically-relevant concentrations in CRPC patients to drive AR activation."
"The potent AR agonist 11KT is the predominant circulating active androgen in CRPC patients and, therefore, one of the potential drivers of AR activation in CRPC. Assessment of androgen status should be extended to include 11KT, as current clinical approaches likely underestimate androgen abundance in CRPC patients."
***
Abiraterone targets adrenal-related androgens, so presumably 11KT isn't a problem for CRPC men on Abi? From a 2020 U.S. study [3]:
"In CRPC patients, administration of {Abi & medical castration} lowered all four 11-oxygenated androgens to below the lower limits of quantitation ..."
***
... but 11KT remains of interest to those whose only AR-axis targeted therapy is castration.
So the studies are showing another pathway to create DHT besides usual pathway from T. DHT is DHT,..does not matter how and from which pathway it is being formed. Therefore, DHT blocking is very important even in CRPC. We know that 5 Alpha reductase inhibitors like Finasteride and Dutasterides inhibit formation of DHT. What substances or drugs can be utilized to block DHT generated from this other pathway ? Abiraterone seems one. What else ?
This is exactly what I am trying to understand. Finasteride and Dutasteride already block most of the DHT. While reading about DHT blocking by 5 ARIs..I found out that long term use of Finasteride and /or Dutasteride is likely to cause fat deposition in liver and gradual onset of type 2 diabetes and Dry eyes. By long term use the authors mean over 5 years. So these meds which are used freely by men to grow scalp hairs are not as safe as what thought in the past.
Any idea or speculation on what a "safe" DHT range would be? Zero? Ten? I suspect zero DHT would be best, but it does have some functions in the endocrine system so need to find a balance.
It basically will depend on aggressiveness of one's PCa. For milder types, more than zero DHT might be acceptable but for very aggressive types, I will aim for as low as I can get it to.
My ONE OFF (experimental) series of events following my dx that so far has provided a Quality of Life fairly problem free (i.e.--no side effects) age of 71 this 7/10 -- caveat--if still alive ;0) >>>
IMMEDIATE CASTRATION in April 2015
Begin taking Dutasteride and Metformin and have Right Half of prostate with GL10 CRYO'd
7 months later in situ a Keytruda + Opdivo + Yervoy injection
1 month later begin Cypionate biweekly injections
For 6+ years now have continued a plant based diet with sardines and Sockeye Salmon for animal protein source + copious amounts of spices AND EXERCISE via bicycling up to 10+ hours in a day. NOTE -- dry orgasms still happening even though castrated.
Your regimen is fantastic. .Cycling upto 10 hours...plant based diet, lots of spices and on top of it Metformin. Metformin and statin both do help prolong life in PCa men.
Interesting, Dr Myers considered controlling DHT important. Think his range was something like 3-4. He put me on Dutasteride. My body apparently metabolizes dutasteride too quickly, so he upped to 2 pills per day. After a while that wasn’t enough so he added grapefruit juice to slow it down. So have been on on 2 pills per day plus 16oz (up from original 8 oz ) grapefruit juice. Seems like body is slowly adapting to these levels.
I recall that he wanted DHT to be below 5 (I forget the units).
He was speaking (in a vlog post) of the rare DHT producer - while castrate. He was one himself.
However, we cannot use DHT<5 as a guarantee that PCa cells haven't learned the alternative pathway. That's why I use Dutasteride anyway.
Dutasteride has a lengthy half-life & it takes a long time for Dutasteride levels to plateau. Dr. Myers recommended starting out at a high dose in order to speed up the the time to acquiring therapeutic levels.
I have been on Proscar for 22 years after BCR from surgery 28 years ago and added Avodart 16 years ago to the Proscar. Now on both plus Casodex (3 1/2 yrs) metformin , doxycycline plus many antioxidants and antinflamatories. DHT went from 40 to less than 5 when first on Proscar. Now, PSA= 0.07 up from low of 0.015 from a high PSA of 12.2 with hip met and 7 lymph mets by Axumin scan 3 1/2 years ago . No sign of liver or eye effects. Life is GOOD, at 81. Best Pedro Pray you find answers to your cancer.
HA! Literally finishing some Blue Bunny chocolate ice cream thinking about next steps and ran into your post....kismet indeed! So I'm shruggin' off ta bed....
And, just for a cringe, a historical goodie from 1962 (partial cite) about "Adrenalectomy for Hopeless Carcinoma of the Prostate" that is pertinent to this discussion, since we are talking about androgens produced in the adrenal cortex:
Yikes. We've come a long way. The article summary even mentions "hypophysectomy" - that's the pituitary gland, folks! - as a means to "sometimes favorably" change "mammary and prostatic malignancies".... And I thought my life as biochemical robot couldn't get worse... I stand corrected.
This discussion has (somewhat) landed on the value of BHP treatments like Finasteride and Dutasteride to keep DHT in check. There is statistically-proven benefit to these, although their impact on survivability hasn't been determined:
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C-11 Choline Pet Scan
11 months of vacatión and going strong, I think
UCLA is expanding access to the Ga-68-PSMA-11 PET scan
Did 9.11 miles to honor those murdered on 9/11
