BAT, dutasteride, and my search for truth, Part 1 of 2

[cigafred]

I have received many helpful comments on my queries about BAT and dutasteride. Overall, the evidence favors continuing dutasteride during BAT (Nalakrats opined “I would use to defend against DHT, which would be increased. And I would watch E2, and not let it get out of the 20's.”)

But I have trouble getting beyond the comment from MateoBeach:

“. . . models show that finasteride reverses the effects of SRT [I think he means SPT=supra-physiological T] on LNCaP exografts.

Human prostate tumor growth in athymic mice: inhibition by androgens and stimulation by finasteride” pubmed.ncbi.nlm.nih.gov/887... [my reference]

Here are some of the other comments:

Medical Oncologists: I have asked several, some connected with BAT trials and my own MO who has been a principal investigator in dutasteride trials. No answer that I trusted, one said no impact from dutasteride so continue it, but I do not think he really had thought about this..

Dutasteride ok arguments (IMO):

The following are excerpts from a much longer conversation.

George71 in reply to kaptank

neither Avodart or finasteride are blocking the cells from getting testosterone -- nor are they blocking you from making testosterone -- they only keep you from converting testosterone to DHT.

Kaptank: I don't know the answer and cannot find it in the literature. If you are trying to expose your cancer cells to levels of T that are toxic to it (and many mechanisms may be involved) then it seems you are just working against that aim by having androgen blockers running through you body whose main aim and purpose is to deny the cell access to any T that may be floating around.

George 71: Neither one blocks androgen receptors on cancer cells or any other cell.

It simply lowers my DHT level.

We concluded that dutasteride was effective when combined with testosterone therapy in preventing premalignant histopathological changes in prostate tissue. Further evidence is needed to confirm our findings.

Andrologia

The effect of dutasteride on microscopic and macroscopic changes of testosterone replacement treatment on prostate tissue. onlinelibrary.wiley.com/doi...

The Prostate Cancer Warrior includes dutasteride and finasteride in his BAT.

Dutasteride (.5 mg daily) and/or finasteride (2.5-5 mg daily) to keep DHT moderately low (perhaps 25-50 ng/dl).

I plan to cycle dutasteride and finasteride. Duta has a long half-life and fina has a short one. So my cycling plan is the following:

Months 1-4: Duta every day and fina every day.

Month 5: Nothing

Month 6: Fina every day (no duta).

Month 7: Nothing

Month 8 Fina every day (no duta).

Month 9: Nothing

Repeat from step 1.

prostatecancer.health.blog/...

Dutasteride should be avoided argument:

MateoBeach BTW I agree with your comment about Dr. Leibowitz. His program including 5ARIs along with SRT makes no sense to me since models show that finasteride reverses the effects of SRT [I think he means SPT=supra-physiological T] on LNCaP exografts.

Human prostate tumor growth in athymic mice: inhibition by androgens and stimulation by finasteride pubmed.ncbi.nlm.nih.gov/887... [my reference]

Inconclusive argument:

“Several groups have reproducibly demonstrated a biphasic proliferative response to

androgen, with minimal proliferation in the absence of any androgen, high rates of proliferation at concentrations of dihydrotestosterone (DHT) or the non-metabolizable androgen (R1881) of 0.1 nM, and cell cycle arrest with concentrations of DHT/R1881 exceeding 1.0 nM (equivalent to ~5–10 nM T) [7,8,57]. This effect has been observed in other PCa lines that natively express the AR as well as cells engineered to express the AR (summarized in Appendix Table A1).”

PMCID: PMC5742814 PMID: 29210989

Supraphysiologic Testosterone Therapy in the Treatment of Prostate Cancer: Models,

Mechanisms and Questions

Or maybe forget BAT and plan for Erleada or Nubiqa, since, as Tall Allen has suggested,

“Erleada and Nubiqa - also prevent androgen receptor amplification, which is thought to be the primary mechanism for BAT when it works.”

And the fun continues in Part 2.

[cigafred]

The replies by direct messaging are appreciated, they favor continuing dutasteride, but no one who is of that school has tried to explain why the finasteride example can be discarded. But thanks for those replies, and I will spend some time considering them before replying further.

[MateoBeach]

Yes I did mean SPT (sorry). If high dose T (as in BAT) works in part by initiating irreparable double-stranded DNA breaks, then the mechanism involves a nuclear translocated AR and two molecules of DHT. This could be part of the mechanism anyway. So my bias (opinion) would be to hold the 5aReductase meds while on active cycling on BAT. But would consider resuming them on periods off of BAT. My choice would be dutasteride for its higher potency BTW. PSA levels should indicate whether or not it seems to be working or if it should be stopped as it does not work for all.

Supraphysiologic Testosterone Therapy

in the Treatment of Prostate Cancer:

Models, Mechanisms and Questions

duckduckgo.com/?q=Supraphys...

Transcription-induced DNA double strand breaks: both

oncogenic force and potential therapeutic target?

clincancerres.aacrjournals....

[MateoBeach]

Can't wait to read your part 2. Thanks for carrying the ball forward on this topic. I could not get my MO to approve TRT for me (yet). But I am currently in Mexico for a few months and stocked up on OTC topical T for future use. Very inexpensive here. But I will wait until I am COVID vaccinated by next Spring and reassess my situation. PSAs are low and steady off treatment currently so no rush. I am also inclined towards slower and less frequent cycling of BAT to hopefully ward off progression to CRPC. This is unexplored territory. But PC is slow growing so two week on/ two weeks off with BAT doesn't make sense to me. Perhaps a month of T every 6 months on ADT. Or something corresponding more to one's PSADT?

[cigafred in reply to MateoBeach]

Part 2 was posted simultaneously.