Fulvestrant reduces AR

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#1

Came across this. Fulvestrant is known to down regulate AR and is being tested for androgen-resistant prostate cancer. This goes along with what NYScientist was thinking.

clinicaltrials.gov/show/NCT00244998

Principal Investigator: Donald L. Trump, MD Roswell Park Cancer Institute

“He leads the Institute’s strong clinical research program in vitamin D-based cancer prevention and treatment, and he cares for patients with prostate cancer and other urologic cancers. He is principal investigator or co-principal investigator on several grants funded by the National Cancer Institute. He holds European and U.S. patents for the use of vitamin D and vitamin D analogs in combination with high-dose chemotherapy.”

Sounds like an interesting guy to have on our case.

#2

Here is another interesting article. By the way, thanks for the comments guys. I love how all the melodramatic threads receive tons of replies, but the threads that discuss the science behind our problem are silent.

content.karger.com/ProdukteDB/pr … Doi=271605

#3

The article mentions other potential drugs that may help.

#4

Novel Agents for Castrate-Resistant Prostate Cancer Include Potent Androgen Blockers and Immunotherapies

www2.mdanderson.org/depts/oncolo … -11-1.html

#5

what this all has to do with us?

#6

I guess you’ll see when the research studies come out.

#7

This recent paper includes the results of many studies relating to AR modifications (its full text is available for free):

http://joe.endocrinology-journals.org/content/215/2/221.long

Regulation of the androgen receptor by post-translational modifications

Abstract

The androgen receptor (AR) is a key molecule in prostate cancer and Kennedy’s disease. Understanding the regulatory mechanisms of this steroid receptor is important in the development of potential therapies for these diseases. One layer of AR regulation is provided by post-translational modifications including phosphorylation, acetylation, sumoylation, ubiquitination and methylation. While these modifications have mostly been studied as individual events, it is becoming clear that these modifications can functionally interact with each other in a signalling pathway. In this review, the effects of all modifications are described with a focus on interplay between them and the functional consequences for the AR.

#8

Most of us know how hard Awor has been working to engage the scientific community and initiate research desperately needed for understanding the root cause of our problem. Here is another study showing the importance of regulatory proteins to AR function and includes a few examples of AR related pathologies (one being testes volume shrinkage - which sounds familiar!)

The more we contribute to the PFS Foundation and the sooner we do it, the easier will be to initiate such research and get results, i.e. treatment/cure.

Androgen Receptor (AR) Coregulators: A Diversity of Functions Converging on and Regulating the AR
Transcriptional Complex

http://edrv.endojournals.org/content/28/7/778.full
(free full text)

Abstract

Androgens, acting through the androgen receptor (AR), are
responsible for the development of the male phenotype during
embryogenesis, the achievement of sexual maturation at puberty,
and the maintenance of male reproductive function and
behavior in adulthood. In addition, androgens affect a wide
variety of nonreproductive tissues. Moreover, aberrant androgen
action plays a critical role in multiple pathologies,
including prostate cancer and androgen insensitivity syndromes.
The formation of a productive AR transcriptional
complex requires the functional and structural interaction of
theARwith its coregulators. In the last decade, an overwhelming
and ever increasing number of proteins have been proposed
to possess AR coactivating or corepressing characteristics.Intriguingly, a vast diversity of functions has been
ascribed to these proteins, indicating that a multitude of cellular
functions and signals converge on the AR to regulate its
function. The current review aims to provide an overview of
the AR coregulator proteins identified to date and to propose
a classification of these AR coregulator proteins according to
the function(s) ascribed to them. Taken together, this approach
will increase our understanding of the cellular pathways
that converge on the AR to ensure an appropriate transcriptional
response to androgens. (Endocrine Reviews 28:
778–808, 2007)

#9

Has still no one tried Fulvestrant? Its an anti-estrogen that also down-regulates the androgen receptor.

#10

I also think the meds that treat androgen resistant prostate cancer will save us

#11

Why don’t you try it yourself?

#12

JQD was working on getting some. I believe he said you have to take it in injection and it is very expensive…

#13

Oh Faslodex, ihatepropecia and I were going to try and get some and use it to solve our estrogen problems. We both are into building muscle with Pfs, though he considers himself recovered, he has residual issues dealing with water retention and muscles being softer. Then he discovered a supplement called Vitex, yet again another supplement. I bought it but didn’t think it would do anything, after he has been raving about it and been on it a month with great success. I really had my interest peaked when he told me it was increasing his response to test, increasing 5ar and making his muscles harder, increasing libido, making his dick bigger. Apparently it is a dopamine agonist, it regulates estrogen and progesterone, it raises endogenous testosterone, and is an anti prolactin. So I started it, and indeed it increased my response to testosterone, ihatepropecia said every week it is becoming more effective. So currently the faslodex experiment is on the shelf while we run this, it is giving me about an 80% response to test at 1600mg a day.

However, we did not know there was a chance faslodex could somehow reverse Pfs? Is this based on Awor’s theories? Im open to all, perhaps there are truths behind mine and awor’s together, we do seem to have 2 types of Pfs syndromes too.

If you are looking for guinea pigs, solvepfs is where you need to go. Im sure one of is will try it over there, it’s a once a month injection, or once every 2 months I think.

Here is the thread I started there

solvepfs.com/viewtopic.php?f … 3622#p3622

If enough info is given to me that’s convincing, then I might try it, but right now im on a working protocol. There are a couple guys at solvepfs that are suicidal and looking for experimental treatments. My view is that it is better for them to try an experimental treatment that has merit than blow their brains out, Slayo is one of them. Interesting though, I did not know faslodex has any potential at reversing Pfs, I was only interested in its anti estrogen effects.

Currently Vitex has solved my estrogen problems for now.

#14

Why do we want to decrease ARs? I thought out problem is that our AR are weak and / or reduced. Citations would be appreciated.

#15

AR gene expression is weak to non-existant. Actual AR levels are high. The question is: (1) are AR levels stuck high causing low AR gene expression OR (2) is AR gene expression stuck low, causing AR levels to be high…

Either way, the end goal is to get AR levels normalized and AR gene expression normalized. It can be theorized that attempting to lower AR levels could possibly fix problem (1) as stated above. Its a shot in the dark, but some research by Ashley Monks has shown it was effective in rats with a condition similar to PFS.

I dont have time for citations right now, but look at the study with PFS AR levels and also dig into some of Ashley Monk’s research in animal models.

#16

I am not sure if low AR expression as a cause is possible. I’ve lost some facial hair, but I’m still hairier than the overwhelming majority of men. My body hair seemed to be falling out like crazy, but it hasn’t been cosmetically significant. And at 5 months post-crash most of my body hairs have gone through a complete life cycle.

I remember being 13 with high libido and great erections… and I could maybe grow a moustache and had no body hair. I am magnitudes more androgenic now. Including base muscle and strength…

That theory still doesn’t make sense to me. Especially since I recovered from all of the symptoms I have now before the crash. I’m not saying it isn’t possible. It just doesn’t make sense in my case.

#17

So by using Fulvestrant the following would happen:

AR gene expression increases
AR genes become stronger / more responsive / more sensitive
Testosterone would become more efficient therefore less circulating testosterone is produced / needed.

Is this correct?

#18

bump