Zytiga during BAT

[PCaWarrior]

I'm testing this to verify but it appears that using Zytiga within 4-5 weeks of SPA is a big no-no. Zytiga's first metabolite is Δ4-Abiraterone. It inhibits 5-ar. So, inhibits T->DHT. Should be simple to test. I'll have the first half of the results this week. N of 1 but I'm the 1 so good on me

If it does inhibit as per multiple studies I've found, it should be very easy to tell.

It doesn't apply to me but I found this interesting: The 5α-reduced metabolite of D4A, 3-keto-5α-abiraterone, is an agonist of the AR. Dutasteride blocks the formation of that metabolite. So, adding dutasteride stops the formation of a metabolite that activates the ARs as well as stopping the 5-ar conversion of T to DHT. D4A inhibits the conversion, dutasteride inhibits it 90%.

But Zytiga blocks cyp17 biosynthesis of T.

So.... clinical trials are needed.

Lacking trials, we could get an idea of whether dutasteride stops the metabolite. But to measure the metabolite custom lab equipment would be needed. So.... clinical trials are needed.

If I were CRPC and was using Zytiga but progressing, barring liver breakdown or hypersensitivity to dutasteride, I wouldn't hesitate to add it to Zytiga.

[PCaWarrior]

Perplexity likes it:

"Your comment outlines an interesting hypothesis on the timing and sequencing of Zytiga administration relative to SPA, and the potential role of dutasteride in modulating its metabolic effects. The notion is that Zytiga's primary metabolite, Δ4-abiraterone, inhibits 5α-reductase (5-ar), thereby reducing the conversion of testosterone to DHT. However, its further metabolite—3-keto-5α-abiraterone—acts as an androgen receptor agonist. By introducing dutasteride, you aim to block the formation of this agonistic metabolite, which in theory could prevent unwanted AR activation and enhance the overall therapeutic effect.

This rationale is compelling given that while Zytiga already reduces testosterone production by inhibiting CYP17A1, combining it with dutasteride might further suppress the androgen pathway by both inhibiting the conversion of T to DHT and preventing formation of an AR agonist from D4A. Nonetheless, these mechanistic insights need validation through well-designed clinical trials. Your N-of-1 experiment may offer preliminary insights, but broader studies are essential to determine if the combination provides a significant clinical advantage over Zytiga alone.

It’s also crucial to monitor key biomarkers—such as serum levels of testosterone, DHT, Δ4-abiraterone, and 3-keto-5α-abiraterone—over time to assess the biochemical impact of the combination therapy. Ultimately, your approach highlights the need for clinical trials to determine whether the theoretical benefits translate into improved outcomes in patients."

[Bhraen2]

Weren’t you using Zytiga during the arsi phase of PBAT when you first stared doing PBAT?

[PCaWarrior in reply to Bhraen2]

Sometimes. I'm testing the DHT reduction. I am not convinced that it is a no-no for the ADT phase of BAT. Metabolite half-life is short and if only the 5-ar enzyme is inhibited, it should bounce back within a day or two.

[Bhraen2]

It also allows your androgen receptors to be open to receive the prostate cancer fighting capabilities and QOL benefits that some new sarms can help us with. And also would add another element of adaptive therapy if it could be alternated with Nubeqa

[PCaWarrior in reply to Bhraen2]

I was thinking more along the lines of doublet or triplet therapy. Orgovyx + Nubeqa + Zytiga or Nubeqa + Zytiga. In 2019 that would have wiped me out with sides (Zytiga, casodex, and dutasteride were hard enough) but on pBAT...

Zytiga shouldn't block the androgenic effects of SARMs. So, still need to be careful with the amounts used. Nubeqa will block but in so doing all of their anabolic properties go away.