Wow, thanks for the comments guys. A lot of really good points, and corrections too.
Oscar, you are right, it’s DHT, I was being careless and using DHT and T interchangeably. I’m a little rusty on my hormone pathways.
In terms of your questions about it being strange that similar findings have not been observed post androgen ablation, I don’t think so as much. Complete androgen ablation is used relatively rarely, typically only in situations where the prostate cancer has become metastatic. I wouldn’t be suprised if the number of men taking propecia is 100x higher than those who have undergone AA. Thus if the incidence of our symptoms is as low as people think it is, there would be much fewer men who had AA with similar symptoms post AA to even report such symptoms. Furthermore, most men who have stage III-IV prostate cancer and get AA would be in the age range of 60-70, so probably had diminished androgen levels and libido to begin with and honestly libido is the least of their worries.
martinM, thanks for the data, it looks like the doses are not going up linearly and instead in multiples of 5 so i think the curve may look a little more flat and the drop off more drastic then it really it is. I would imagine it would be possible to titrate dose by splitting pills (probably still a challenge though)
spstriken, i would like to answer your quesitons but i’d like to stay more anonymous for now if that’s ok. My dept was pretty small at the university i went to, as well as the research hospital i worked at so it would be pretty easy to triangulate and find me if i said anything. One disclaimer, I haven’t been activiely researching for a good 4 years now, I’ve been working in the pharma industry (not Merck haha) more on the business side (hope this doesn’t invalidate my opinions!).
To answer your second question. I haven’t personally used finasteride in the research setting, but at the doses we are talking about I would be fairly certain that it’s not enough to induce apoptosis. When you block androgen signaling (e.g., DHT) the primary effect is presumed to be on slowing growth and proliferation, not causing cell death. If there were some kind of apoptosis, I would expect it to be reversed and cells to continue growing as normal once you stopped taking the drug.
Dubya. You are absolutely right. You caught a mistake. Thanks. Bical binds to AR and essentially blocks androgen from binding to cells and signaling. What I should say is “what if we were to dramatically lower the level of AR gene activity/signaling using AR antagonists like bicalutimide” Still the same concept.
You are right in pointing out that it cause an increase in T because your system starts pumping out more T in response to the shutdown in androgen activity/signaling by bicalutimide. That is why LHRH agonists are used which then shut down the T production leading to a TOTAL androgen ablation, which I am not sure we would need to go to that extent.
I was also thinking about the rise in estrogen levels which could be risky because it could lead to gyno and that’s a really good point. My initial thought was it may not be as much of an issue since we are talkiing about a really short term use but it still is risky. It would probably be best to use an aromatase inh or some other estrogen blocking molecule. The one thing is, if you are blocking both types of androgen (test & est) it would probably make you feel like complete s*** (esp if you are also using the LHRH agonist). I would want to more research into whether there could be any other side effects we should worry about.
Oscar, in the paper that Dubya was referencing I don’t think they were talking about literal castration, just chemical castration wher eyou temporarily mimic the effects of castration with drugs.
Thanks for all the comments and sorry in advance if I am slow in responding. I have a full-time job as well like the rest of you and I’ve been researching this in my spare time. Keep the comments coming and glad to hear more feedback. I will try to contact Awor and other suggested members when I have more time and after conducting a bit more research.