I met with a new oncologist yesterday. I asked a question of him that I have been thinking about. I am on monotherapy enzalutamide and have been for some time. My T is 600+. Enza prohibits the uptake of androgens everywhere in the body, not just the tumor cells, so no T in muscles and elsewhere while it circulates in serum. He noted I had not had a bone density test in several years. I asked if enza prohibited the uptake of E2 (estradiol-estrogen) produced by testes and integral in bone strength. He said he did not know.
Any takers on an answer for the doctor?
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The androgen receptor antagonist enzalutamide induces apoptosis, dysregulates the heat shock protein system, and diminishes the androgen receptor and estrogen receptor β1 expression in prostate cancer cells
Alexander Abazid 1 , Benedikt Martin 1 , Anja Choinowski 1 , Rhiannon V McNeill 2 , Lars-Ove Brandenburg 3 , Patrick Ziegler 4 , Uwe Zimmermann 1 , Martin Burchardt 1 , Holger Erb 5 , Matthias B Stope 1
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PMID: 31297844 DOI: 10.1002/jcb.28929
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Abstract
Enzalutamide's accepted mode of action is by targeting the androgen receptor's (AR) activity. In clinical practice, enzalutamide demonstrates a good benefit-risk profile for the treatment of advanced prostate cancer (PC), even after poor response to standard antihormonal treatment. However, since both, well-established antiandrogens and enzalutamide, target AR functionality, we hypothesized that additional unknown mechanisms might be responsible for enzalutamide's superior anticancer activity. In the current study, PC cells were incubated with enzalutamide and enzalutamide-dependent modulation of apoptotic mechanisms were assessed via Western blot analysis, TDT-mediated dUTP-biotin nick end-labeling assay, and nuclear morphology assay. Alterations of heat shock protein (HSP), AR, and estrogen receptor (ER) expression were examined by Western blot analysis. Enzalutamide attenuated the proliferation of PC cells in a time- and dose-dependent manner. In the presence of enzalutamide, apoptosis occurred which was shown by increased BAX expression, decreased Bcl-2 expression, nuclear pyknosis, and genomic DNA fragmentation. Moreover, enzalutamide inhibited the expression of HSPs primarily involved in steroid receptor stabilization and suppressed AR and ERβ1 expression. This study demonstrates for the first time that enzalutamide treatment of PC cells triggers varying molecular mechanisms resulting in antiproliferative effects of the drug. In addition to the well-characterized antagonistic inhibition of AR functionality, we have shown that enzalutamide also affects the intracellular synthesis of steroid receptor-associated HSPs, thereby diminishing the expression of AR and ERβ1 proteins and inducing apoptotic pathways. According to an indirect attenuation of HSP-associated factors such as steroid receptors, endometrial carcinoma, uterine leiomyosarcoma, and mamma carcinoma cells also demonstrated inhibited cell growth in the presence of enzalutamide. Our data, therefore, suggest that enzalutamide's high efficacy is at least partially independent of AR and p53 protein expression, which are frequently lost in advanced PC.”
So estrogen receptor ERb1 is affected according to this clinical article
I'd guess E2 still protects bone naturally when one is taking enzalutamide (Xtandi). Enzalutamide blocks the androgen receptor (AR) but not the estrogen receptor (ER). Estrogen increases bone mineral density (BMD) by activating the ERα in bone. Xtandi raises serum T levels by blocking thee AR sites where T would ordinarily be used up. Excess T is metabolized into E2, so you probably already have a lot of E2, without supplementing.
Incidentally, toremifene, a selective estrogen receptor modulator (SERM), also protects bone by activating the ERα.
Have you had any side effects from Xtandi monotherapy? I was on Xtandi with Firmagon for a while, and it kicked my ass with side effects (although it did an amazing job on the cancer and got me to undetectable). I am currently on monotherapy with Nubeqa, and the only real side effect has been the development of breasts.......Tamoxifen seems to be helping keep the man boobs in check.
Thats good to hear. If my Nubeqa mono-theraphy doesnt work out, I will probably be falling back on Xtandi as a monotherapy. So no trouble with breast development with the Xtandi ?
He is. He's a double D and knows I won't be borrowing his bras unless I really need to. The slingshot fight was great. Other fool came with a jock strap.
J-o-h-n has retired from the HU site. TomTom1111 knows more than I. I keep thinking that he may still read the posts, and he may get annoyed enough with some of the comments that are made, that he comes back to grace us with his wit. I know almost all of us miss him, and wish him well.
Looks like a very nice place to hide out in. Implied fool was Goliath. Monte and Goliath. That has a nice ring to it. It certainly wasn't Kaliber. He looks like the type who would bring a gun to a slingshot fight. Or a hammer.
Oh, yes. Blocking androgens creates aromitisation and conversion of T to Estrogen. After the first few months the endocrine system settled into a new stability and the breast growth stopped. I sometimes wear a compression undershirt in summer, otherwise it is of no consequence. To forestall cancer this is the mildest of side effects.
We’ve talked several times in the past…shoot me an email sometime…jlenington@comcast.net…perhaps we can have a short call to compare notes…I can’t remember…what was your psa when you went to Xtandi only? Are you still with Dr. Drake?
We’ve talked several times in the past…shoot me an email sometime…jlenington@comcast.net…perhaps we can have a short call to compare notes…I can’t remember…what was your psa when you went to Xtandi only? Are you still with Dr. Drake?
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