The Myth of testosterone and prostate cancer
Hi Guys,
What about the widely quoted effects of Testosterone of Prostrate ? I read an article which states this is simply not true and another one that states, if there is a prostrate issue, do not take exogenous test. as it is similar to pouring oil into fire! Can anyone shed some light on this?
Shifting The Paradigm Of Testosterone And Prostate Cancer: The Saturation Model And The Limits Of Androgen-Dependent Growth
For >65 yr, it has been widely accepted that prostate cancer (PCa) growth is dependent on serum testosterone (T) concentrations, based on experiments by Huggins et al, and that castration caused PCa regression, whereas T administration caused more rapid PCa growth. Yet recent studies have shown little or no relationship between serum T concentrations and PCa, making the long-held belief in a T-dependent model of PCa problematic, if not untenable, and. We present here a simple yet critical refinement to the traditional view of T and PCa, namely, that there is a limit to the ability of T to stimulate PCa growth. The Saturation Model presented below is founded on basic biochemical principles of androgen action within the prostate, and it provides a robust framework for understanding the seemingly contradictory sets of results seen with T manipulation.
Defining the relationship between T and PCa is of considerable importance. Not only is androgen deprivation a mainstay of treatment for advanced PCa, but there is also growing interest in T therapy for hypogonadism. Although T therapy has been shown to improve sexual function, bone density, and body composition, none of these benefits might be worthwhile if T therapy increased the risk of PCa.
The Saturation Model has been introduced previously; in this paper, we present the model in full, together with supporting evidence from human and laboratory studies. In brief, the Saturation Model accounts for the key observation that PCa growth is exquisitely sensitive to variation in serum T concentrations at or below the near-castrate range and is insensitive to T variations above this concentration. This model postulates that physiologic concentrations of T provide an excess of T and its intracellular prostatic metabolite, 5***945;-dihydrotestosterone (DHT), for optimal prostatic growth requirements. However, reducing T concentration below a critical concentration threshold (the Saturation Point) creates an intracellular milieu in which the availability of androgen becomes the rate-limiting step governing prostate tissue growth. This model is based on evidence that binding of androgen to the androgen receptor (AR) follows a similar saturation curve. We believe this simple model has important ramifications for clinical medicine and basic science research.
Morgentaler A, Traish AM.
Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. Eur Urol 2009;55(2):310-20. Shifting the Paradigm of Testosterone and Prostate Cancer: The Saturation Model and the Limits of Androgen-Dependent Growth - European Urology
Shifting the Paradigm of Testosterone and Prostate Cancer: The Saturation Model and the Limits of Androgen-Dependent Growth - European Urology
CONTEXT: The traditional belief that prostate cancer (PCa) growth is dependent on serum testosterone (T) level has been challenged by recent negative studies in noncastrated men.
OBJECTIVE: To provide an improved framework for understanding the relationship of PCa to serum T level that is consistent with current evidence and is based on established biochemical principles of androgen action within the prostate.
EVIDENCE ACQUISITION: A literature search was performed of publications dating from 1941 to 2008 that addressed experimental and clinical effects of androgens on prostate growth. Review of studies investigating the prostatic effects of manipulation of androgen concentrations in human and animal studies, and in PCa cell lines.
EVIDENCE SYNTHESIS: Prostate growth is exquisitely sensitive to variations in androgen concentrations at very low concentrations, but becomes insensitive to changes in androgen concentrations at higher levels. This pattern is consistent with the observation that androgens exert their prostatic effects primarily via binding to the androgen receptor (AR), and that maximal androgen-AR binding is achieved at serum T concentrations well below the physiologic range. A Saturation Model is proposed that accounts for the seemingly contradictory results in human PCa studies. Changes in serum T concentrations below the point of maximal androgen-AR binding will elicit substantial changes in PCa growth, as seen with castration, or with T administration to previously castrated men. In contrast, once maximal androgen-AR binding is reached the presence of additional androgen produces little further effect.
CONCLUSIONS: The evidence clearly indicates that there is a limit to the ability of androgens to stimulate PCa growth. A Saturation Model based on androgen-AR binding provides a satisfactory conceptual framework to account for the dramatic effects seen with castration as well as the minor impact of T administration in noncastrated men.
Tombal B. Editorial comment on:
Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. Eur Urol 2009;55(2):321. Editorial Comment on: Shifting the Paradigm of Testosterone and Prostate Cancer: The Saturation Model and the Limits of Androgen-Dependent Growth - European Urology
Editorial Comment on: Shifting the Paradigm of Testosterone and Prostate Cancer: The Saturation Model and the Limits of Androgen-Dependent Growth - European Urology
In Roman mythology, Janus was the god of gates and doors. He was usually depicted with two heads looking in opposite directions and was frequently used to symbolize changes and transitions, such as the progression from one vision to another. This idea perfectly illustrates the saturation model proposed by Morgentaler and Traish in the current issue of European Urology.
Indeed, many of us still regard testosterone through Charles Huggins's eyes and consider it to be a key promoter of prostate cancer progression only because its abrupt suppression induces metastatic prostate cancer to shrink. But is this view enough to sustain our common-sense understanding that testosterone promotes or even causes prostate cancer?
Although urologists still diabolize testosterone, endocrinologists, rheumatologists, and cardiologists attract more and more of our attention to its virtues, especially with regard to metabolic and cardiovascular health.
This paradigm is an interesting one for the physician counseling a man who was successfully treated for localized prostate cancer and who suffers from late-onset hypogonadism. What puts him more at risk: a high-testosterone-promoting cancer or a low-testosterone-promoting cardiovascular disease? Considering the extensive use of hormone therapy in early prostate cancer, it seems that urologists have some difficulties seeing the man around the prostate, although they should be aware of the lack of efficacy in that setting.
Morgentaler and Traish's saturation model provides a nice rational background in which to move away from our unwarranted fear of testosterone in prostate cancer. This article should help urologists to understand that treating middle-age men with localized disease requires getting rid of those fears and developing a holistic view of men's health that encompasses balancing the risks and benefits of adjusting testosterone to normal values.
this is an article talking about the study Morgentaler did after his theory. I think the article is dated april 11th of this year.
Revisiting Testosterone Tx in Prostate Ca
Medical News: Revisiting Testosterone Tx in Prostate Ca - in Oncology, Prostate Cancer from MedPage Today
Medical News: Revisiting Testosterone Tx in Prostate Ca - in Oncology, Prostate Cancer from MedPage Today
Men with low-risk prostate cancer and symptomatic hypogonadism had no evidence of cancer progression during long-term testosterone therapy, results of a small clinical trial showed.
Neither the mean PSA level nor prostate volume changed significantly during testosterone treatment that continued for as long as eight years, according to Abraham Morgentaler, MD, of Beth Israel Deaconess Medical Center in Boston, and colleagues.
Cancer biopsies in two men suggested cancer upgrading, but subsequent biopsy in one patient and radical prostatectomy in the other showed no evidence of progression.
The findings support the saturation hypothesis, which postulates that maximal prostate cancer growth occurs with low-level androgen stimulation, and higher levels elicit little or no additional growth, the researchers wrote in the April issue of the Journal of Urology.
"There has been a scare about testosterone for about 70 years that somehow it is a fuel for the fire in prostate cancer," Morgentaler said in an interview. "It's clear that's not the case.
"This study, although it's small, is the first time anyone has ever bothered to give testosterone and see what's happening in a prostate that has cancer."
Testosterone therapy has several beneficial effects in men with testosterone deficiency, including improvement in fatigue, libido, and sexual function. However, concern about potential stimulatory effects on prostate cancer has limited use of the hormonal therapy, Morgentaler and co-authors noted in the introduction to their findings.
The concern has its origin in observations that androgen deprivation slows prostate cancer progression, as reflected in decreased serum PSA, and that normalization of testosterone in androgen-deprived men raises PSA levels.
Though modest and circumstantial, the evidence has supported a traditional ban on testosterone therapy in men with a history of prostate cancer. When asked to write a review of the issue several years ago, Morgentaler and his co-authors were stunned to find no published clinical data to support a prohibition of testosterone in men with prostate cancer.
Subsequently, Morgentaler found a single article, published in 1941 by future Nobel Prize winner Charles Huggins and colleague Clarence Hodges of the University of Chicago (Cancer Res. 1941; 1: 293-297). The article detailed the effects of various interventions on acid phosphatase levels in men with metastatic prostate cancer, including three men who received testosterone injections.
Huggins and Hodges reported data for two of the three men, one of whom had been surgically castrated before getting testosterone.
"The general idea -- that adding testosterone to an otherwise relatively normal guy with or without prostate cancer will make the cancer grow -- is based on one individual," said Morgentaler.
More recently, results from several small studies have called into question the traditional paradigm of testosterone prohibition in men with prostate cancer. The studies, which collectively involved about 100 men with definitively treated prostate cancer and testosterone deficiency, showed no evidence of biochemical recurrence during treatment with testosterone for as long as 12 years.
With that clinical and scientific background, Morgentaler and co-authors examined the effects of testosterone therapy in 13 men with untreated prostate cancer undergoing active surveillance. The men had a mean age of 59, mean PSA value of 5.5 ng/mL, mean testosterone concentration of 238 ng/mL, and all but one had a biopsy Gleason score of 6 (one patient with Gleason 7).
After a median treatment duration of 2.5 years, the group's testosterone values averaged 664 ng/dL (P<0.001).
Mean PSA level declined to 3.6 ng/mL, which did not differ significantly from baseline. Prostate volume also did not change.
The men had an average of two prostate biopsies during follow-up, and 54% of specimens had no evidence of cancer.
Limitations of the study included its small size, retrospective design, inclusion of some men who had prostate cancer diagnosed after the start of testosterone therapy, and lack of generalizability to those with higher grade or higher volume disease.
On the basis of the results, the longstanding prohibition against testosterone therapy in men with untreated or low-risk prostate cancer merits re-evaluation, the authors wrote in conclusion.
Use of testosterone therapy by prostate cancer patients should be guided by an individual patient's testosterone level and any associated symptoms, said Morgentaler.
"To be a candidate for testosterone therapy, one needs to have symptoms and a low level of testosterone confirmed by blood testing," he said.
"In terms of giving it to men with a history of prostate cancer, the main impediment at this point is that there still are no large, long-term studies that can give us the bounds of safety data on this."
Before starting testosterone therapy, each of his patients must sign a consent form that spells out the unknown risks associated with the hormonal therapy, Morgentaler added.
Prognosis: Testosterone and Prostate Cancer
http://www.nytimes.com/2011/04/26/he...er=rss&emc=rss
By NICHOLAS BAKALAR
Doctors have long held that men with prostate cancer should not be given testosterone because the hormone might fuel tumor growth. But a small study adds to evidence that the fear may be overblown, at least in patients without evidence of recurrent or metastatic disease.
Researchers studied 13 men with scores of 6 or 7 on the 10-point Gleason scale, indicating mildly to moderately aggressive prostate cancer. They all initially chose watchful waiting rather than treatment for their cancers. All the men had low testosterone.
The men received testosterone therapy for an average of two and a half years, and had periodic prostate biopsies. None of their cancers progressed or spread to other organs. One subject whose score had increased to 7 from 6 had his prostate removed, but the final pathological exam found no aggressive disease.
The authors acknowledge that the study, published in the April issue The Journal of Urology, was small and retrospective. Still, it is the first to use biopsies to monitor the effects of testosterone in men with untreated, localized prostate cancer.
The lead author, Dr. Abraham Morgentaler, an associate clinical professor of surgery at Harvard, said that the findings of this and other recent studies suggest that the risks of testosterone therapy may have been exaggerated
