anti androgren monotherapy and testosterone levels

[joeguy]

As some of you know that have read my past posts, I am experimenting with Nubeqa monotherapy, which has brought on a bout of the man boobs. I was successful in convincing my doc to prescribe Tamoxifen, but have not yet started taking it, as I am waiting on blood tests to see where my estrogen/testosterone levels are. Apparently the E2 / testosterone ratio is important, but I am curious if anyone knows what a testosterone level actually means for someone taking anti androgens? The last time I had blood work, my testosterone was 450, but does the body even know you have testosterone with the AR blocking action of Nubeqa?

[Tall_Allen]

With nowhere to go, testosterone levels keep rising when you use antiandrogens. It isn't indefinite because negative feedback causes your hypothalamus to stop generating GnRH. When the GnRH stops because of the high testosterone, the pituitary signals the testicles to stop making more testosterone. Meanwhile, the high T levels are metabolized primarily into two "waste products" - DHT and estrogen. It is the accumulating estrogen that is responsible for the gynecomastia.

[joeguy in reply to Tall_Allen]

Thanks TA...... in the little bit of reading I have done, there seems to be some debate about if high estrogen alone is the culprit, or is it the ratio between testosterone and estrogen levels. I am curious not only as it relates to gynecomastia, but also for heart problems, and other issues. Once I have my E2 numbers I can calculate the ratio, but if my testosterone is measuring 450, and as you say, it has nowhere to go, is the number in reality much closer to zero ? I am starting to learn that doctors using hormone therapy to treat prostate cancer seem to have little concern for how the manipulated hormone levels impact things other than just the cancer.

[Tall_Allen in reply to joeguy]

There is a normal ratio of E2/T in healthy males, and when E2 gets too high absolutely or in the ratio, the excess causes gynecomastia. I think you're overthinking this. It doesn't matter - if your E2 is high enough to cause gynecomastia in YOU, you can prevent it with tamoxifen.

[joeguy in reply to Tall_Allen]

I probably am overthinking it. I’m just wondering if in this crazy world of hormone therapy, is there a way to maintain some sort of balance that doesn’t cause the development of heart problems, gynecomastia, cognitive issues, and all the other lovely SEs that come with it.

[Tall_Allen in reply to joeguy]

Castration doesn't usually cause gynecomastia.

[joeguy in reply to Tall_Allen]

No, but at least in my case, it caused a variety of heart and cognitive problems. That’s why I’m no longer on the castration drugs like Firmagon. Like I said, hormone therapy may be good for prostate cancer, but left unchecked, it’s bad for just about everything else.

[MateoBeach in reply to Tall_Allen]

However, the hypothalamus does not even know the testosterone is even there as its own receptors are blocked. Feedback control is absent which is why the testosterone levels go so high, get converted to estrogen. And voila man boobs. No?

[Tall_Allen in reply to MateoBeach]

No - the hypothalamus isn't blocked - that's why T doesn't rise indefinitely.

[noahware]

Even though T to E2 ratio is probably important in gynecomastia, I don't think there is any magic number to be discovered or to shoot for. It is going to be highly individual, and as well as differences between men there will be the variations YOU experience in any measured E2 at one given time versus another.

I did bicalutamide therapy before any chemical castration, and my high-normal T shot up to nearly 1400. It was still over 1100 a month after discontinuing the med! Unfortunately, I did not think this through regarding the washout period, and I stopped taking tamoxifen at the same time. I definitely got some breast tissue in that month or so of high T with no tamoxifen.

Now that I have started high-dose E2 as ADT, I am back on tamoxifen 10 mg. The ratio of T to E2 is going to be very different than with my last med!

[joeguy in reply to noahware]

It’s basically like we are all on our own personal clinical trial.... just one big experiment. Did you have any issues with Tamoxifen? Guess I will be starting 10 mg dose.

[noahware in reply to joeguy]

No issues. I think maybe most concern with Tamoxifen in men with PC is that it hasn't been studied deeply enough to know what the true concerns really are? We know it is another drug screwing with our natural hormone functions. It wouldn't surprise if it eventually is discovered that it contributes to some men's PC progression while contributing to other men's PC regression, but could be it doesn't matter a damn except in growing boobies.

[Graham49 in reply to noahware]

There are studies, mostly in vitro, see latest below which shows favorable effect of Tamoxifen against PCa. There was 1999 phase II trial which showed limited effect against PCa. I guess it was thought that the effect was not great enough for a phase III trial.

In Vitro Evaluation of the Effects of Tamoxifen on Prostate Cancer Cells

Gh Shafiee * , I Khodadadi , R Abbasalipourkabir

Department of Clinical Biochemistry, Hamedan University of Medical Scinces, Hamedan, I.R.Iran , [e-mail]

Abstract: (2636 Views)

BACKGROUND AND OBJECTIVE: Considering the high prevalence of prostate cancer and the effect of androgens on its progression, this study was conducted to investigate the inhibitory effects of tamoxifen as an anti-androgen on prostate cancer.

METHODS: In this experimental study, the human cell line (PC3) was purchased from the Pasteur Institute. The effect of tamoxifen at concentrations of 0, 3.25, 7.5, 15, 30 and 60 μM on cells was evaluated, and the tests of viability, migration, colonization and cell morphological changes were respectively performed using MTT, wound healing, colonization, and giemsa staining methods.

FINDINGS: IC50 dosage of tamoxifen of 15 μM with a regression coefficient of 0.90 was obtained within 24 hours. The results showed that tamoxifen significantly inhibited proliferation with 7.3±0.6 colonies compared with 100 colonies of control (p<0.03) and migration with 278.4±1.5 μm groove diameter compared with 89.68 ± 0.9 μm of control (p<0.01) at the dose of 15 μM. Treatment of cells with a dose of 15 μM also causes changes in the nucleus and cytoplasm and causes apoptosis in comparison with the control group.

CONCLUSION: The results of this study showed that tamoxifen has significant inhibitory effects on PC3 prostate cell and can be considered as an appropriate way for the treatment of prostate cancer.

[joeguy in reply to Graham49]

Interesting....... hopefully the combination of Nubequa and Tamoxifen will really piss it off !

[MateoBeach in reply to Graham49]

Thanks for finding and posting this. Reassuring support for use of tamoxifen for those with high estradiol from whatever source.

[j-o-h-n]

Worse than growing man boobs is growing just one man boob......

Good Luck, Good Health and Good Humor.

j-o-h-n Saturday 05/22/2021 10:22 AM DST

[Hidden in reply to j-o-h-n]

Unless it's between the legs, then let it grow.

[j-o-h-n in reply to Hidden]

I agree with TomTom1111 but with one caveat, "whatever's between your legs make sure it's yours first"........

Good Luck, Good Health and Good Humor.

j-o-h-n Saturday 05/22/2021 6:47 PM DST

[joeguy in reply to j-o-h-n]

Now that you mention it, they are kinda lopsided

[j-o-h-n in reply to joeguy]

Just tug on the crooked one until you hear it pop and then both of them will be popsided....Game over- you win.....

Good Luck, Good Health and God Humor.

j-o-h-n Sunday 05/23/2021 12:30 AM DST