5Alpha Reductase Inhibitors in advanced Pca

[Tommyj2]

Reading an old post I noticed that 5ARI's are noted to artificially lower PSA numbers..... Often in men who are using them for BPH. I note also that they are frequently used IN advanced Pca.... Are they useful in lowering actual Testosterone Levels and subsequently PSA in a _ real_ way. I'm a little confused...

[FCoffey]

I read that a lot too: "artificially lower PSA." I'm not sure what that means. Does not Lupron artificially lower PSA? Chemo? RP? None of those is exactly natural.

5ARIs slow or stop the conversion of testosterone to the more potent androgen dihydrotestosterone (DHT). As such, they don't directly lower testosterone levels. They can raise serum testosterone because it is no longer being converted to DHT.

[Tall_Allen]

They do not lower testosterone (T) - they lower a metabolite of testosterone, called dihydrotestosterone (DHT). DHT is a more powerful androgen than T at activating the androgen receptor (AR). An activated AR causes the cancer to replicate. In theory, blocking DHT with a 5ARi should result in slower progression and lower PSA in men with advanced PC. But in actual practice, it is usually taken with a GnRH agonist (like Lupron), which prevents T from occurring in the first place, and the 5ARi probably has little if any, effect.

What you heard about is 5ARis used in a different situation - before biopsy. There, they lower the PSA due to BPH, but not the PSA due to prostate cancer.

[Tommyj2 in reply to Tall_Allen]

That was another question that I had Allen... Since DHT is a potent anti-adrogen is it ever used alone to treat advancing Pca?? I used to use low dose proscar to slow down my balding when I was young so I am aware that it affects DHT... but I thought that it ultimately did affect testosterone levels as well??

[Tall_Allen in reply to Tommyj2]

To repeat - it does not lower T, only DHT. In advanced PC, some doctors like to add a 5ARi, but evidence so far is that it adds little, as I said.

[Tommyj2 in reply to Tall_Allen]

Understood....

[George71]

Avadart alone slows cancer progression

youtube.com/watch?v=0g0m8AT...(Not working as expected?)

[pjoshea13]

Tommy,

I wouldn't use the word "artificially".

Dr. Myers has noted that some patients make DHT even at the lowest T levels. Before retirement he prescribed Avodart only in men with DHT above a certain level. He argues that T does not drive PCa - DHT does. Why then do doctors measure T but not DHT? Because they assume that if T=0, DHT=0. It isn't always the case.

Also, in some men, PCa cells can evolve to synthesize DHT via a pathway that does not involve T. Since the DHT is made within the cell for use in the cell, a blood test would not be useful, IMO, in this instance.

In treatments that target the AR axis, it seems to me to be prudent to add Avodart.

I would also suggest a statin for the same reason. Cholesterol is the starting point for steroidogenesis. Therefore, is is prudent to inhibit the uptake & synthesis in PCa cells.

One can argue that only x% CRPC cases have DHT synthesis involvement, & only y% have cholesterol synthesis, so why bother? I doubt that a study would find much benefit for the cohort, but a minority would benefit. Perhaps a few of us here.

-Patrick

[Tommyj2 in reply to pjoshea13]

It is not at ALL reassuring that there is so much that is not commonly agreed upon with Advanced Pca ( or even initial Pca for that matter)... the more I read on this forum the more educated AND confused I get!!!

[Kevinski65]

Has anyone ever heard of cimetidine slowing down prostate cancer ?

[Tommyj2 in reply to Kevinski65]

Hey Kevin...

You would probably get more replies if you posted this question as your own rather than in reply to my question re: 5ARI's