Prostate Cancer and the Testosterone �Myth�
Quote:
Prostate Cancer and the Testosterone �Myth�
Abraham Morgentaler, M.D.
1 Brookline Place, Suite #624
Brookline, MA 02445, USA
(617) 277-5000 / (617) 277-5444 (FAX)
[email protected]
www.menshealthboston.com
Eur Urol, 2006 Nov;50(5):935-9. Epub 2006 Jul 27 45529 (3/2007)
Kirk Hamilton: Can you please share with us your educational background and current position?
Abraham Morgentaler: I received my bachelor�s degree from Harvard College in 1978 and my MD from Harvard Medical School in 1982. I completed my urology residency at the Harvard Program in Urology in 1988.
KH: What got you interested in studying this perceived controversial topic regarding testosterone causing prostate cancer?
AB: My interest in testosterone began as an undergraduate, working on a research study on the sexual effects of testosterone on the brains of lizards. When I completed my urology training, my clinical and research interest was in reproductive and sexual medicine, and I found there was little work being done on the effect of testosterone in men. I was very pleased to discover that a substantial proportion of men with sexual symptoms, such as low libido or erectile dysfunction, had low testosterone levels at the time I saw them, and many responded nicely to testosterone therapy. However, everyone was worried about the potential for hidden prostate cancers to grow. So, I started doing prostate biopsies before beginning testosterone treatment, and was surprised to find a much higher prevalence of cancer in these men than would have been expected. At the time, the conventional wisdom was that high testosterone was associated with prostate cancer, and low testosterone should be protective against cancer. It made me re-think and re-examine the literature on the relationship between testosterone and prostate cancer.
KH: How did the concept that prostate cancer was caused by testosterone ever get started?
AB: In 1941 Huggins showed that near-total reductions in testosterone caused prostate cancer to regress. He accomplished this by castration or by treatment with estrogen. Reducing testosterone to castration levels, now usually performed with medications, remains a standard approach to the treatment of advanced prostate cancer to this day. It seemed logical that if lowering testosterone made prostate cancer shrink, then raising testosterone should make prostate cancer grow. Besides, Huggins, who later won the Nobel Prize for his work demonstrating that prostate cancer was hormonally-sensitive, also asserted that raising testosterone caused �enhanced growth� of prostate cancer, and he maintained this position at least until 1967, when he published a review article on the subject. Remarkably, Huggin�s conclusion that testosterone caused increased growth was based on only a single patient!
KH: Is there any data that males on physiologic testosterone replacement increase their prostate cancer risk? Or increase the spread or growth of an established prostate cancer?
AB: Numerous studies have attempted to show that higher testosterone levels increase the risk of prostate cancer, but the results have all been consistently negative. Unfortunately, we do not yet have any large-scale, long-term studies of testosterone treatment versus placebo, so it is impossible to say categorically that testosterone treatment does not involve any risk. But there has been no shortage of other studies, some of which are quite sophisticated, looking at this issue. So far, the data are all very reassuring. The best of these studies are the population-based, longitudinal studies. Medical histories are obtained on large numbers of individuals, blood is obtained and frozen, and these men are then followed for periods of time up to twenty years. At the end of the study, a group of men will have developed prostate cancer (or some other condition of interest) and some will not. The frozen blood can then be analyzed to determine whether the prostate cancer group had higher testosterone levels, or levels of other hormones, compared with the group without cancer. There are at least 16 such studies, involving hundreds of thousands of men in total- not one has shown a relationship with total testosterone. A few have found weak associations with minor androgens, but those results have not been reproducible in other studies. The largest study of this type, from Scandinavia, actually suggested that increased risk of prostate cancer was associated with LOW levels of testosterone. To some extent, the lack of an association between higher testosterone and prostate cancer makes sense when one looks at the effect of testosterone on the normal prostate. When normal men were injected with supraphysiologic doses of testosterone, no change in prostate volume or PSA was noted. It appears the system becomes saturated for testosterone at a relatively low testosterone concentration.
KH: Why does castration cause metastatic prostate cancer to regress?
AB: Testosterone is a growth requirement for most prostate cancers. Without it, prostate tumors shrink, as does the normal prostate. This relationship is without dispute. The error, however, is in thinking that cancer growth continues to grow and grow as testosterone levels increase. All the data indicate that at some relatively low level of testosterone, no further growth occurs despite raising testosterone further.
KH: Why does estrogen therapy cause metastatic prostate cancer to regress?
AB: Estrogen therapy lowers serum testosterone via feedback inhibition of the hypothalamus and pituitary. Once testosterone levels become very low, prostate cancer regresses. The mechanism by which testosterone is lowered appears not to matter.
KH: I thought a high serum estrogen to testosterone ratio increased the risk to BPH and prostate cancer? Can you comment?
AB: There is some interest in the ratio of estrogen to testosterone. In my opinion, these data are not compelling.
KH: Do men on testosterone therapy who get prostate cancer diagnosed have a reduce risk to metastasises and improved morbidity and mortality compared to those not on testosterone replacement? Is there any data on this?
AB: Multiple studies have failed to show any worse aspects of prostate cancer presentation or survival among men with higher levels of testosterone. Interestingly, there are now several papers showing a relationship between LOW testosterone and prostate cancer. Specifically, low testosterone has been associated with high-grade tumors, advanced stage of presentation, and worse prognosis.
KH: If the patient is testosterone deficient, is there a time or circumstance in which he should not receive physiologic testosterone replacement? Who is or who isn�t a candidate for testosterone replacement?
AB: At the present time, the only indications for testosterone treatment are in men who have signs or symptoms of low testosterone, with a confirmatory blood test. There is currently no basis to recommend treatment for men who are found to have low testosterone but are asymptomatic. The usual symptoms that prompt treatment are low libido, erectile dysfunction, and fatigue. There is also fairly solid evidence that low testosterone is a risk factor for reduced bone mineral density, which responds to testosterone treatment, and so the presence of osteopenia or osteoporosis in a man who is androgen-deficient is a relatively recent indication for testosterone treatment.
KH: Can you tell us the best way to assess for testosterone need? Serum, saliva or urine? If serum, should you get a total, free and/or bioavailable level? Should you get a SHBG level? How do you determine testosterone adequacy? Do you have cut off levels for deficiency, insufficiency, normal ranges and excessive levels? Can you share your thoughts on these questions?
AB: The standard test for low testosterone is the total testosterone assay. Levels less than 200 ng/dl are definitely low, levels between 200-400 may be low depending on clinical circumstances (eg, symptoms), and levels above 400 ng/dl are unlikely to be low. The FDA and practice guidelines from the Endocrine Society use a threshold below 300 ng/dl for the definition of androgen deficiency. I personally find the free testosterone assay available through most laboratories a more useful tool than total testosterone. Much of the total testosterone is bound to the carrier molecule SHBG, but is unavailable to the cells. Men with higher SHBG levels may have a normal-appearing total testosterone, but may be truly androgen-deficient. I consider free testosterone levels below 1.5 ng/dl or 15 pg/ml (analog assay) consistent with androgen deficiency in a symptomatic man.
KH: What levels of testosterone should physiologic replacement aim for? Mid normal ranges of "youthful" testosterone levels, or mid normal ranges of the "same age (aging)" levels? Can you comment on this somewhat confusing question?
AB: I am strongly opposed to the use of age-adjusted values for testosterone, used to determine if a man is androgen deficient. Since testosterone levels decline with age, older men need to have incredibly low testosterone values to �qualify� as androgen-deficient. Since the symptoms of low testosterone are the same at all ages, a standard threshold for men of all ages should be applied.
KH: Do you think many males do not receive needed testosterone replacement due to clinician concern about testosterone causing prostate cancer?
AB: There is no doubt that androgen deficiency is under-diagnosed and under-treated. The main reasons include lack of familiarity on the part of primary care physicians, confusion regarding how to make the diagnosis, and the fear of stimulating occult prostate cancer.
KH: How do you approach male subjects who are either on testosterone replacement who get prostate cancer, or those with prostate cancer who biochemically and symptomatically need testosterone replacement?
AB: Regrettably, prostate cancer is very common, regardless of whether a man is taking testosterone or not. There is no evidence that testosterone treatment causes prostate cancer, and I share this information with my patients. The conversation about starting testosterone treatment in men who already have prostate cancer is more complicated, largely because the conventional wisdom clearly states that a history of prostate cancer is a definite contraindication to testosterone treatment. This field is shifting rapidly, though, and many of my colleagues have begun to offer treatment to selected men, with careful monitoring for recurrence or progression of their cancer.
KH: Do you think the medical community is coming around to the understanding that testosterone doesn�t cause prostate cancer?
AB: It takes a while for longstanding beliefs to change. Eventually, evidence wins out.
KH: What are some of the benefits, if any, of testosterone replacement, especially in those with prostate cancer?
AB: The proven benefits of testosterone in men include improved libido, erectile function, increased bone and muscle mass, and decreased fat mass. There are interesting, but as yet unproven data regarding its value for depressed mood, cognition, and sense of energy and vitality. These benefits are unrelated to a prior history of prostate cancer, but clearly there is greater concern with starting treatment in a man with prostate cancer, for the reasons described above.
KH: How do you use the PSA value with testosterone replacement in males?
AB: Testosterone treatment is associated with a small rise in PSA in some men. This usually occurs within the first 3 months. Any subsequent yearly rise of 0.7 ng/ml or greater means the PSA gets repeated, and a biopsy is performed for a rise of 1.0 ng/ml or more.
KH: Do you have any other comment you would like to make on this very important and timely topic?
AB: Testosterone treatment can be enormously helpful for many men. Attitudes are shifting with regard to its relationship to prostate cancer, and interested readers may wish to review my article on this subject that appeared in European Urology, in which I argue that the relationship between higher testosterone and cancer is a myth. Additional information may also be found on the website for my practice, at www.menshealthboston.com.
Copyright � Vitasearch. All rights reserved.
https://www.vitasearch.com/CP/experts...AT02-25-07.htm
|
|
04-09-2007, 08:17 AM
Similar Threads
Linear Mode
