<TABLE class=contentpaneopen><TBODY><TR><TD class=contentheading width="100%">Testosterone Unrelated To Prostate Cancer

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by Dan Gwartney, M.D.

As this article is being written, Roger Clemens is appearing before the House Committee on Oversight and Government Reform to testify as to whether or not he used anabolic steroids or human growth hormone. Interestingly, prior to this, a scathing commentary from a member of the Cato Institute (a libertarian think-tank based in Washington, DC) on CNBC (February 13, 2008) condemned Congress for becoming involved in regulating professional sports, spending extensive time and resources on a matter that is not within their purview and pales in comparison to the critical matters of national security and prosperity (Iraq, housing crisis anyone?) to serve their addiction for media exposure. The comment was made that were cameras not present, the Mitchell Report and related investigations would not exist. Some may have noticed that this was the treatment given to Barry Bonds, whose claim of the career home run record went relatively unnoticed and unheralded due to his (Bonds’) alleged use of numerous performance-enhancing drugs. It is a sad commentary on our elected officials, the media and the public. Frankly, there is a more critical need for all members of Congress, state and local legislatures, as well as teachers, to be subjected to random drug and alcohol testing.

For decades, there have been numerous different disincentive approaches taken to lessen the appeal of anabolic steroids to athletes and young people. Though the intent behind these approaches may have been charitable, they have served only to drive a wedge between professional and authoritative agencies and the audiences they are trying to reach. Similarly, disincentives against testosterone therapy for quality-of-life or aging-related treatment are current matters claiming headlines across the nation. While it is essential that patients be aware of potential risks involved with any medication or therapy, false allegations serve no one in the end. Since the publication of a paper in 1941 that reported that the growth of prostate cancer was slowed in one man who was castrated (surgical removal of testicles) after diagnosis, it has been assumed that not only can testosterone accelerate the growth of prostate cancer, but also cause the disease.1 This theory went unchallenged for decades until it was noted that prostate cancer is extremely rare in men under 40 and occurs with greater frequency in older men.2 This is counter to what one would expect, as testosterone levels are highest during a man’s teens and 20s; men in their 70s and 80s, when the prevalence of prostate cancer can be as high as 46 percent-80 percent, suffer from testosterone deficiency.3,4 Further eroding support for the assumption that testosterone causes prostate cancer is the observation that the prevalence of prostate cancer in men younger than 50 is on the increase, when average testosterone concentrations have been falling for the last several generations.3,5

Recently, direct challenges to the allegation that testosterone (in the physiologic range) has an adverse (negative) effect on a man’s prostate as it relates to prostate cancer have been published in the medical literature. Researchers have investigated the origins of the assumption and concluded that there is no association between testosterone concentrations and the incidence of prostate cancer.6,7 Expanding on the potentially misstated relationship between testosterone and health are numerous studies showing that men with low testosterone levels are at higher risk for several diseases or poor health conditions and may also be at risk of premature death!8,9 Yet, somehow, it is deemed unethical to explore the potential benefits of high-normal to slightly supraphysiologic testosterone therapy; rather, leading agencies such as the Endocrinology Society have recommended against screening for testosterone deficiency or providing more than the minimal amount of supplemental testosterone.10 Clearly, there is a discrepancy here that is not explained using any objective or rational argument.

In addition to testosterone, there are numerous other steroids that are considered sex steroids and capable of interacting with receptors in prostate tissue. These include: DHT (a potent androgenic metabolite of testosterone), DHEA, androstenedione, androstenediol and estradiol (a potent estrogenic metabolite of testosterone). As no study has looked globally at all these hormones collectively in a large group, there has been some uncertainty as to what factors may actually be impacting the findings in prostate studies. Fortunately, there is an accepted method of combining data from many studies to increase the accuracy and usefulness of the grouped results. This is called a meta-analysis.
In February of 2008, a meta-analysis of 18 peer-reviewed studies examining the relationship between sex hormones and prostate cancer was published in the Journal of the National Cancer Institute.11 In total, over 10,000 men were compared to determine the relationship between the sex hormones mentioned above (including testosterone) and prostate cancer. Additionally, free testosterone and free estradiol were calculated and SHBG (a protein that binds sex hormones in the bloodstream) was measured. After analyzing all the data and accounting for numerous factors known to affect hormone levels or the risk of prostate cancer, the statistics reached a definitive conclusion: “There were no statistically significant associations between serum concentrations of any of the androgens or estrogen and risk of prostate cancer…”11
Now, that may initially be mistaken to suggest that there is no increased risk of prostate cancer with any use of testosterone or other anabolic steroids, but that would be as incorrect as the long-standing premise that testosterone caused prostate cancer. Remember, this study looked at natural (endogenous) testosterone concentrations, not supplemental testosterone and no synthetic anabolic steroid was analyzed. There is no surety that supraphysiologic concentrations, such as are used by athletes and bodybuilders, are safe. Further, this study was limited somewhat by relying on a single measure of testosterone, rather than following testosterone concentrations over time. Also, it did not measure sex hormone levels in prostate tissue or exposure in utero (meaning while the person was still a fetus in his mother’s uterus).


Many other factors have been shown to be associated with an increased risk of prostate cancer, which are rarely, if ever, mentioned in the news or medical literature.12-14 Just this week, findings were reported linking 20 different genes to an increased risk of prostate cancer.15 Further, another study has reported that men with sedentary jobs were nearly twice as likely to develop prostate cancer when compared to men with active jobs.13,16 The intense focus on the unproven, possibly incorrect, position that testosterone therapy increases the risk of prostate cancer has robbed resources that could have been investigating and publicizing other more likely causes. This is a sad example of a protectionist attitude by several government and clinical agencies, manipulating public opinion to create a disincentive against male hormone replacement or anabolic therapy. The reporting bias against testosterone may have placed generations of men at higher risk of several disease processes, ranging from cardiovascular disease to premature death.8,9


One argument that has been cast against any position advocating testosterone therapy or even research into the benefits of testosterone therapy is the lack of a large study, as well as the lack of long-term data regarding the safety of such therapy. Certainly, there have been a number of studies, some extending to years in length, looking at the safety of various forms of testosterone.17,18 Perhaps the most promising involves the use of an extremely long-acting form of testosterone called testosterone undecanoate; an injectable ester that maintains steady concentrations for up to 14 weeks between injections.18 However, these long-term studies are derived primarily from individual clinics and are limited to a small number of subjects. Given that testosterone and other anabolic steroids have been available for decades and they represent an inexpensive treatment option that could alleviate many conditions that would promote independence and quality of life, it is shameful that more research into the benefits and therapeutic indications for testosterone have not been supported.


Clearly, many of the assumptions and disincentives against the clinical use of testosterone or related drugs need to be re-examined and re-evaluated. Measures to prevent abuse and sports doping should not include misinformation or punitive measures against physicians and the public.

References:

1. Huggins C, Hodges C. Studies on Prostatic Cancer: I. The Effect of Castration, of Estrogen and of Androgen Injection on Serum Phosphatases in Metastatic Carcinoma of the Prostate. Cancer Res, 1941;1:293-7.

2. Wilt T, Abrahamsson P, et al. Prostate Cancer: Epidemiology and Screening. Rev Urol, 2003;5(Suppl 6);S3-9.

3. Yin M, Bastacky S, et al. Prevalence of incidental prostate cancer in the general population: a study of healthy organ donors. J Urol, 2008 Jan 18 [Epub ahead of print].

4. Thompson IM, Lucia MS, et al. Commentary: The ubiquity of prostate cancer: echoes of the past, implications for the present. Int J Epidemiol, 2007;36:287-9.

5. Travison TG, Araujo AB, et al. A population-level decline in serum testosterone levels in American men. J Clin Endocrinol Metab, 2007;92:196-202.

6. Raynaud JP. Prostate cancer risk in testosterone-treated men. J Steroid Biochem Mol Biol, 2006;102:261-6.

7. Morgentaler A. Testosterone and prostate cancer: an historical perspective on a modern myth. Eur Urol, 2006;50:935-9.

8. Laughlin GHA, Barrett-Connor E, et al. Low serum testosterone and mortality in older men. J Clin Endocrinol Metab, 2008;93:68-75.

9. Saad F, Gooren L, et al. Effects of testosterone gel followed by parenteral testosterone undecanoate on sexual dysfunction and on features of the metabolic syndrome. Andrologia, 2008;40:44-48.

10. Bhasin S, Cunningham GR, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab, 2006;91:1995-2010.

11. Roddam AW, Allen NE, et al, (Endogenous Hormones, Prostate Cancer Collaborative Group). Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Instit, 2008;100:170-83.

12. Hsing AW, Sakoda LC, et al. Obesity, Metabolic Syndrome and prostate cancer. Am J Clin Nutr, 2007;86:s843-57.

13. Strom SS, Yamamura Y, et al. Prostate cancer in Mexican-Americans: Identification of risk factors. Prostate, 2008 Feb 4. [Epub ahead of print].

14. Colli JL, Colli A. International comparisons of prostate cancer mortality rates with dietary practices and sunlight levels. Urol Oncol, 2006;24:184-94.

15. Reinberg S. More gene variations found that raise prostate cancer risk. US News & World Report 2008 February 11. Available at https://health.usnews.com/usnews/heal...ancer-risk.htm, accessed February 14, 2008.

16. Bairati I, Larouche R, et al. Lifetime occupational physical activity and incidental prostate cancer (Canada). Cancer Cause Control, 2000;11:759-64.

17. Bhasin S, Woodhouse L, et al. Testosterone dose-response relationships in healthy young men. Am J Physiol Endocrinol Metab, 2001;281:E1172-81.

18. Minnemann T, Schubert M, et al. A four-year efficacy and safety study of the long-acting parenteral testosterone undecanoate. Aging Male, 2007;10:155-8.
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