 |
 | Home | Contact Us | FAQ | Search & Site Map | Link to Us |
 | Sign In | Join | Other 45 Sites in Network |
Medical Forum / Diseases and Disorders / Prostate Cancer / August 2006new study and Testosterone PCa relationship
Testosterone and Prostate Cancer: An Historical Perspective on a Modern Myth.Morgentaler A. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. OBJECTIVES: To review the historical origins and current evidence for the belief that testosterone (T) causes prostate cancer (pCA) growth. METHODS: Review of the historical literature regarding T administration and pCA, as well as more recent studies investigating the relationship of T and pCA. RESULTS: In 1941 Huggins and Hodges reported that marked reductions in T by castration or estrogen treatment caused metastatic pCA to regress, and administration of exogenous T caused pCA to grow. Remarkably, this latter conclusion was based on results from only one patient. Multiple subsequent reports revealed no pCA progression with T administration, and some men even experienced subjective improvement, such as resolution of bone pain. More recent data have shown no apparent increase in pCA rates in clinical trials of T supplementation in normal men or men at increased risk for pCA, no relationship of pCA risk with serum T levels in multiple longitudinal studies, and no reduced risk of pCA in men with low T. The apparent paradox in which castration causes pCA to regress yet higher T fails to cause pCA to grow is resolved by a saturation model, in which maximal stimulation of pCA is reached at relatively low levels of T. CONCLUSIONS: This historical perspective reveals that there is not now-nor has there ever been-a scientific basis for the belief that T causes pCA to grow. Discarding this modern myth will allow exploration of alternative hypotheses regarding the relationship of T and pCA that may be clinically and scientifically rewarding. If true, this is an astounding piece of news. Is it possible that the worldwide medical establishment has based treatment of millions of men on the case of a single patient in 1941, without ever verifying the results? Alan > If true, this is an astounding piece of news. > [quoted text clipped - 3 lines] > > Alan Alan, please . . . what are you talking about? Please quote the post you're addressing. I.P. >> If true, this is an astounding piece of news. >> [quoted text clipped - 6 lines] > > I.P. It was in the article Rich posted, specifically: > In 1941 Huggins and Hodges reported that marked reductions in T > by castration or estrogen treatment caused metastatic pCA to [quoted text clipped - 4 lines] > experienced subjective improvement, such as resolution of bone > pain. ... > there is not now-nor has there ever been-a scientific basis for > the belief that T causes pCA to grow. Discarding this modern > myth will allow exploration of alternative hypotheses regarding > the relationship of T and pCA that may be clinically and > scientifically rewarding. However, the question I raised was not properly phrased. The treatment of reducing testosterone to castrate level isn't questioned by the quoted article. What was questioned was that additional testosterone above some fairly low threshold promotes cancer growth. This question came up on this group some time ago when a poster who had had RP wanted to resume testosterone supplementation on the theory that his cancer was cured. We mostly advised against it and perhaps his doctor did too. But if this article is right, supplementing his low T level would do him no harm at all and might even do him good. From the middle of the abstract: > More recent data have shown no apparent increase in pCA rates > in clinical trials of T supplementation in normal men or men at [quoted text clipped - 4 lines] > pCA to grow is resolved by a saturation model, in which maximal > stimulation of pCA is reached at relatively low levels of T. Alan Ed Friedman, where are you? "The apparent paradox in which CASTRATION CAUSES PCA TO REGRESS yet higher T fails to cause pCA to grow is resolved by a saturation model, in which MAXIMAL STIMULATION OF PCA is reached at relatively low levels of T. CONCLUSIONS: This historical perspective reveals that there is not now-nor has there ever been-a scientific basis for the belief that T causes pCA to grow." (emphasis added) I'm not sure, given their acknowledgement that PCa regresses in a T-deprived atmosphere and is stimulated by a low level of T, that the conclusion necessarily follows as stated. It may not have been shown in the lab but it seems to me that if you reduce T to a castrate level and PCa regresses, then the other side of the coin is that T is necessary for PCa to survive. It's not much of a stretch to extrapolate from that that T up to some level does cause PCa to grow. It's just that heaping more on after that point will not make it grow faster. (Apparently it does make you able to pedal up the French Alps faster. :-) ) Off the bat I see 2 things of significance: 1. If you aren't willing to reduce T to castrate level, or somewhere close to it, you might as well pump yourself up all you want. 2. It is vital to ADT to monitor not only PSA but T and make sure you are below that low level, whatever it is, the only assurance of which is to be castrate. This supports Strum's focus on T level. I have always heard that it was more DHT than T that was the culprit but that cannot be the case if they found that the elimination of T alone caused PCa regression. However, perhaps PCa (and perhaps normal prostate tissue) needs T up to a "saturation" point to survive but also needs DHT to grow. That would explain why simply adding more T did not cause growth. But in the body that extra T is converted into DHT by 5-alpha reductase and PCa grows. This would also explain why a 5-aR inhibitor like finasteride (Proscar) shrinks the prostate but does not cure PCa. The experiment that needs to be done is to add different levels of T, T + DHT, and DHT alone to cultures of PCa and see what happens. Bill Denton RP 2/12/02 PSA ? Memphis Bill...A couple of comments inserted within your text...ron Bill wrote...snip... > I have always heard that it was more DHT than T that was the culprit > but that cannot be the case if they found that the elimination of T > alone caused PCa regression. I don't follow, DHT is a metabolic byproduct of T; reduce T and you reduce DHT (sometimes the relationship breaks down at low T levels, that's why some docs monitor DHT and T) > However, perhaps PCa (and perhaps normal > prostate tissue) needs T up to a "saturation" point to survive but also [quoted text clipped - 5 lines] > levels of T, T + DHT, and DHT alone to cultures of PCa and see what > happens. It has been demonstrated that DHT is more important than T for prostate growth. A real-world version of your experiment has been performed. There are certain groups/clans in some relatively remote areas that have a genetic mutation that precludes their body converting T to DHT (they lack the ability to produce the 5-AR isoenzymes that convert T to DHT). The Guevedoces in the Dominican republic are one such group. Merck studied them and found that they don't suffer from male pattern baldness, their prostates are under-developed and apparently they do not suffer from PCa. This study led to Propecia to treat baldness and ultimately finasteride (Proscar) and dutasteride (Avodart). It would be interesting to see a study comparing PCa incidence and severity between men with high / low T levels. The data must certainly exist by now/ > Ed Friedman, where are you? > [quoted text clipped - 38 lines] > PSA ? > Memphis Bill, OK, since you asked, I'll try to clear up the confusion here. First of all, the reason that doctors demonize T is not because of the 1941 Huggins and Hodges article, but because of a pair of articles published in the early 80's by Fowler and Whitmore. In one of those articles, they summarized all previously published results using T for PCa in a neat table form, with headings for various bad progression of the disease listed (e.g., increased bone pain or increased weight loss - since they didn't have PSA back then), with no headers being used for anything good happening. If you look at the articles that they cited, most of the patients did do poorly when given T, but there were two patients with almost total remission and one with significant improvement - but no mention was made of this in that particular Fowler and Whitmore paper. As a result, doctors have essentially demonized T since that paper was published. If you keep the level of T high enough, then PCa cannot start up (which is why teenagers never get it). As T levels drop with age, PCa can now start. The lower the T level drops, the worse off the PCa patient is. E.g., low endogenous T levels have been shown to be one of the best indicators of who will fail to be cured following RP. Basically, once you are above the castrate level of T, the higher the T the better. There are two androgen receptors that pretty much work in opposition to each other. Initially, high levels of T should eliminate the PCa, but as mutations develop, high levels of T can cause PCa to thrive. If you maximize the inbalance between the two androgen receptors, then you maximize the killing of the PCa. This can be done right now by high T coupled with low DHT (and possibly Casodex as well for good measure). Eventually, if drug companies develop a drug that only inhibits the membrane androgen receptor, then we should be seeing new systemic treatments that are much more powerful than anything being used today. Ed Friedman I recently read an article that I find a little hard to understand regarding DHT. It said DHT could be used to treat BHP. The article said: "DHT is a strong androgen that will signal the pituitary to decrease the production of gonadotropins. The decrease in gonadotropins will then cause less testosterone to be produced which will in turn cause the estrogen levels to drop. The resulting change in the hormonal milieu (high DHT, low estrogen) then apparently results in a regression of BPH." Details can be seen at http://www.bodybuilding.com/fun/reform8.htm. I love to hear someone explain this one. > I recently read an article that I find a little hard to understand > regarding DHT. It said DHT could be used to treat BHP. The article [quoted text clipped - 10 lines] > > I love to hear someone explain this one. John, The action of hormones on hormone receptors is quite fascinating, and I've often wondered if the hormone receptors involved in BPH are the same as those involved in PCa. Basically, in PCa, you get continual telomerase activity because the Aromatase (Aro) gene is permanently turned on. The Aro converts T to E2, and E2 has been shown to cause telomerase activity in prostate epithelial cells (as well as in PCa). Telomerase activity has been shown to force cell division. Now if BPH acts along similar lines, then you are getting telomerase activity occasionally instead of continually, due to high E2 levels in the blood. If this is all true, then DHT just might reduce BPH, but I would be very curious to see what the long term results are in diagnosed PCa cases. While it might prevent PCa in young men, for the typical middle-aged man with BPH, you must assume that there are some PCa cells present, in which case DHT should increase the rate of PCa population growth and thus increase the number of PCa cases diagnosed. Ed Friedman I recently read an article that I find a little hard to understand regarding DHT. It said DHT could be used to treat BHP. The article said: "DHT is a strong androgen that will signal the pituitary to decrease the production of gonadotropins. The decrease in gonadotropins will then cause less testosterone to be produced which will in turn cause the estrogen levels to drop. The resulting change in the hormonal milieu (high DHT, low estrogen) then apparently results in a regression of BPH." Details can be seen at http://www.bodybuilding.com/fun/reform8.htm. I love to hear someone explain this one. > I recently read an article that I find a little hard to understand > regarding DHT. It said DHT could be used to treat BHP. The article [quoted text clipped - 10 lines] > > I love to hear someone explain this one. John...USP 5,648,350 is a 1996 patent awarded to a French company. They administer massive amounts of DHT. The body "thinks" there is way too much T present, so it reacts by reducing the production of T (the bodiy's normal source of DHT). Since T is also the biochemical precursor to estrogen, the E level falls as well when the body slows T production. The science behind some patents is pretty flimsy and even incorrect. That will not necessarily stop the patent from being awarded. So patent results must be taken with a grain of salt, or at least read very closely. The patent claims something on the order of a 15.4% reduction in prostate volume after 1.8 years of the treatment. It says that the prostate volume was measured by ultrasound and PSA, so I'm not sure just how the volume was determined. Many substances can reduce PSA without affecting prostate volume. If PSA was somehow used to figure volume, and if large doses of DHT would cause PSA to decrease, then the already small 15.4% reduction in volume may actually be even smaller. It also seems that this claimed treatment for BPH, where excessive amounts of DHT are administered to older men whose T is out on the low side of normal, has not taken the world by storm, Again, this makes you wonder about the true usefulness of the patent. Finally, the normal DHT range for men >50 (the age guideline for the men studied in the patent) is 4.5-21 ng/dL. The patent increased the DHT level of the men they studied to 250-600 ng/dL. That's something like a 30-50 fold increase over the normal level. The body can do strange things under such extreme circumstances. I suspect not all of these "strange" things were recorded in the patent...Best wishes and good health, ron |
Reply to this Message |
 Sign In
 Join
 My Latest Posts My Monitored Threads My Blog My Photo Gallery My Profile My Homepage Start New Thread Enable EMail Alerts Rate this Thread
|
©2008 Advenet LLC Privacy Policy - Terms of Use
This website includes both content owned or controlled by Advenet as well as content owned or controlled by third parties.