Hormone Receptors & Prostate Cancer: What Your Test Results Mean

•The more advanced the prostate cancer, the more likely there are mutations that protect it from testosterone. Also, the more advanced the prostate cancer, the more estrogen receptor alpha present, which makes estradiol more deadly.

•If you still have your prostate, then it’s important to keep estradiol at low normal levels for good health and discourage additional cancer initiation. High levels of estradiol cause cell division and mutations in prostate epithelial cells, ultimately leading to cancer. To monitor your estradiol and other hormones, you can get a hormone panel test, such as the Genova Diagnostics “One Day Hormone Check” . To keep your estradiol at low normal levels, you can take aromatase inhibitors or eat Brussel sprouts.

•If you don’t have a prostate, keep estradiol in normal range for good health. You should keep your estradiol at 13-20 pg/ml. Sometimes it will become undetectable. It is a moving target if you introduce exogenous testosterone.

•High levels of testosterone act to prevent epithelial prostate cell division and can kill your cancer cells. A better way to implement bipolar androgen therapy is to keep testosterone high and cycle DHT (dihydrotestosterone, the most potent hormone among the androgens, and considered a pure androgen as it cannot convert into estrogen.) What are possible future implications of this model? RU486, mifepristone, a drug which blocks progesterone, could be a game changer for prostate cancer. How do key hormones contribute to prostate cancer and how can they be controlled?

•Testosterone: The main male sex hormone. A messenger that tells the prostate cells to grow, divide, or die. We can decrease it or increase it as desired. Receptor(s): Membrane androgen Receptor(s) (mAR), Intracellular androgen Receptor(s) (iAR).

•DHT: dihydrotestosterone, the most potent hormone among the androgens, and considered a pure androgen as it cannot convert into estrogen. Almost all of it is derived from testosterone via 5AR. If we want to block it we can use 5AR inhibitors (e.g., finasteride, dutasteride). We can decrease it or increase it as desired. Usually this will also involve increasing testosterone. Receptor(s): Intracellular androgen Receptor(s) (iAR)

•Estrogen: Most of it is derived from testosterone via aromatase. If we want to block it we can use aromatase inhibitors (e.g., letrozole, anastrozole, exemestane). If we want to increase it we can use estrogen patches, gels, or creams. Receptor(s): Estrogen receptor alpha (ERa) – usually bad. Estrogen receptor beta (ERb) – usually good

•Prolactin: This hormone could be used as fuel by some castrate resistant prostate cancer tumors. If we want to block it we can use prolactin inhibitors (e.g. cabergoline). Receptor(s): PRLE.

•Progesterone: One of its functions is to assist in testosterone production. Receptor(s): PRa – usually bad, PRb – usually good. How can I learn more about Dr. Friedman’s theories? Please see his book and his website. The information and opinions expressed on this website or platform, or during discussions and presentations (both verbal and written) are not intended as health care recommendations or medical advice by Cancer Patient Lab/Prostate Cancer Lab, its principals, presenters, participants, or representatives for any medical treatment, product, or course of action. You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health. Meeting Notes The information and opinions expressed on this website or platform, or during discussions and presentations (both verbal and written) are not intended as health care recommendations or medical advice by Cancer Patient Lab/Prostate Cancer Lab, its principals, presenters, participants, or representatives for any medical treatment, product, or course of action. You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health. SUMMARY KEYWORDS receptor, testosterone, prostate cancer, cancer, intracellular, estriol, membrane, finasteride, cell, progesterone, estradiol, receptor alpha, showed, patients, give, amplified, paper, doctor, prostate, mutations SPEAKERS Ed Friedman (85%), Russ Hollyer (7%), Brian McCloskey (5%), John Sandiford (2%), Brad Power (<1%) Discussion Outline 1.Introduction to Dr. Ed Friedman. (0:00) 2.Ed’s background and research. (1:39) 3.How prostate cancer originates and the role of estrogen. (5:32) 4.Hormone testing and prostate cancer. (13:07) 5.Good and bad androgen receptors. (21:10) 6.How to treat prostate cancer? (28:03) 7.How safe is estriol for men and women? (34:55) 8.Hormone sensitivity and prostate cancer. (42:29) 9.The problem with finding a doctor to treat prostate cancer. (48:29) 10.The benefits of testosterone replacement therapy. (56:18) 11.Do you know i if functional testing has been done? (1:03:21) Russ Hollyer 1:03 We have today with us Edward Friedman, PhD. He's an expert on hormones. I was so excited when he agreed to present, even though it was on Sunday. I said any day, any time, I don't care if it's 2am, or 3am, at whatever the time, on whatever the day, I will be there. He is an expert. He was the reason why I abandoned ADT and went to high testosterone, which worked for me for two years. Ed Friedman 1:54 Let me talk a little bit about my background. I've been researching hormone receptors since 2004. My first article was published in 2005. It was on prostate cancer and the properties of the androgen and estrogen receptors. After doing that article, some people I knew came down with breast cancer. When I was doing the research for the article, there were so many papers talking about the receptors and saying that what they were seeing was exactly what they were seeing in breast cancer. So I started researching breast cancer as well. In 2007 I had my second article published, and I added progesterone receptors. Basically, all the receptors are almost identical in breast and prostate cancer. The only exception is the membrane antigen receptor, which in women decreases BCL2, and in men increases it. I'm not going to go into all the details, but it's pretty close to being the same. Some people urged me to write a book. I had that published in 2013. One of my fans happened to be a professional English teacher teaching people how to get a book published, and he volunteered his time and helped me to find a literary agent, and eventually became a co-author to make my book more readable in plain English. Since that time, I've had three more articles that I published in researchgate.net, one of which was expanding on the role of estradiol in prostate cancer, and the latest one was looking at the BAT treatment in terms of what they're overlooking and what they're doing right. Everything I tell you is pure theory. It's based on what I'm seeing in the literature. It's not something that I'm making a guess at. “I think this.” It's like, “There are articles out there.” Russ Hollyer 5:09 You're a theoretician, a researcher, versus a clinician. A clinician looks at clinical results. I think they're both vitally important. You're looking at the theory, you're not looking necessarily at the practical applications. Ed Friedman 5:31 That's correct. tate Cancer” You're a theoretician, a researcher, versus a clinician. A clinician looks at clinical results. I think they're both vitally important. You're looking at the theory, you're not looking necessarily at the practical applications. Ed Friedman 5:31 That's correct. And the other thing is that the clinicians will publish the results without giving a clear explanation of why they have what they have. I'll give you an example. In fact, Dr. Denmeade says, it works because of the wind cap on a 402 cell line (?) and what that does, but in that paper he doesn't answer the question. “Why do you have to have an amplified intracellular androgen receptor before high dose testosterone works?” “Why can't you just give even more testosterone if the only thing that matters is what's happening in the interest of the end of the receptor?” Those are the sorts of questions that I consider in theory, in which the clinicians are totally oblivious. So with that in mind, I basically look at what people published and ask why. “Why is this the result?” Often I look at their data, and their data tells me what's going on. So far, everything I've seen fits my model. But in some cases, the author of the paper will say these results are inexplicable or paradoxical. And that's because they conflict with what they were taught in medical school. I never went to medical school, so I never got indoctrinated in dogma, I just look at the actual data of what's been published, and work out logically what's going on. So let's start with how prostate cancer originates. To give you a quick background, for decades, doctors were convinced testosterone causes prostate cancer. Their proof was that by giving the noble rat high levels of testosterone, they could get around two thirds of them to develop prostate cancer. So you assume they have the answer. And plus the fact that androgen deprivation kills prostate cancer, they thought testosterone was the villain. For decades, we taught them that in medical school. They were going on that assumption. It turns out that in reality prostate cancer is caused by high local levels of estradiol, which acts on estrogen receptor alpha. They've shown that early prostate epithelial cells, which is where the cancer comes from, never divide. They're made from stem cells. They sit there. They die off. They get replaced. They never divide. The cancer is the dividing. They've shown you can take ordinary prostate epithelial cells, and with high local levels of estradiol, cause prostate cancer to arise. In 2008 researcher Gail Risbridger from Australia, who's done wonderful work on estrogen and prostate cancer, proved beyond a shadow of a doubt that estrogen receptor alpha is what causes prostate cancer. She used ordinary mice and when she knocked out their estrogen receptor alpha gene, she was unable to have them develop prostate cancer, no matter how much testosterone and no matter how much estradiol they were given, they simply could not develop prostate cancer. On the other hand, if you took normal mice, gave them enough testosterone so that you don't kill the prostate cells due to androgen deprivation, and then start raising the level of estradiol, she got a 100% rate of developing prostate cancer. This should be taught in all the medical schools. All the doctors should be aware of it. They're not. Part of the problem is this article was published in a biological Journal, the Facet Journal, which is one of the two best biological journals in the world. Doctors read medical journals; they don't read biological journals. The best you'll see is some doctor may say, “It's unclear what the role of testosterone and estradiol are in prostate cancer.” The reality is, if they read all the literature that's out there, it's very clear. There's no ambiguity. The high local levels of estradiol will cause cell division to start. That's not enough for cancer. You now need mutations, and it turns out the high local levels of estradiol also cause what's called “depurinating adducts”, which are a mild mutagen. But with enough of them heightened enough, with high level estradiol given a long enough time, even a mild mutagen will eventually lead to prostate cancer. And the way you get the high local level of estradiol is by a high local aromatase activity. In a separate paper Dr. Risbridger has shown that the prostate cancer cell line had local high aromatase activity on a par with what we've seen in breast cancer. Russ Hollyer 11:52 So if you simply look at testosterone, you could be easily fooled into thinking that it causes prostate cancer, if you ignore the fact that it actually produces DHT, and in this case, estrogen, so as you increase testosterone, you increase your estrogen. Is that correct? Ed Friedman 12:16 That's correct. And most people I should point out, ordinarily, the prostate epithelial cells do not express aromatase at all. That's why the first step in prostate cancer development is the activation of that gene. The gene is being silenced. The gene is part of the human genome. It's just silenced. So it's not expressed in prostate epithelial cells. But there are many billions of cells that are being created. One gets created with a mistake that it doesn't silence. It's not clear whether it's methylation silencing. There are various ways to silence a gene. But whatever it is, it's failing when you start to get prostate cancer. John Sandiford 13:16