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Does Testosterone Therapy Cause Prostate Cancer?

Another huge question in the minds of many men on TRT (testosterone therapy) such as myself is whether or not it will increase risk for prostate cancer.  Several large, well done studies - see below - have showed this not to be the case and that testosterone therapy does not appear to increase prostate cancer risk. Of course, since I am on HRT, this is what I want to believe, especially since I feel so much better with subQ cypionate injections.  However, nothing in this life is usually that clean cut and so I want to start out by issuing several cautions:

1. There are standard contraindications to TRT, such as liver problems and high RBC's/hematocrit/hemoglobin.  However, probably front and center would have to be prostate issues, including an enlarged prostate or past/existing prostate cancer that need to be discussed with your physician. 

2. Some of the pro-testosterone has been funded by those who have received money from testosterone manufacturers.

3. My urologist, who is a smart guy and graduated from an Ivy League university, absolutely insists that TRT (testosterone therapy) increases risk by 3-4% in men and that he has seen this in his practice.  Some urologists feel this way.

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4.  Furthermore, and as many men know, the standard treatment for serious cases of prostate cancer is to lower testosterone pharmaceutically to very low levels.  This is a miserable experience, of course, but does often help to regress the cancer.  This is one of the reasons that urologists for decades concluded that testosterone itself, therefore, caused prostate cancer.  In my opinion, there are many strong rebuttals to this argument, which I will discuss below.

There are many problems with the TRT-causes-prostate-cancer way of thinking and considerable research data began to cast doubts in the minds of many.  Let's look at some of the research that show the exact opposite of the testosterone-fuels-prostate-cancer theory

1. STUDY: Higher Testosterone = Lower Prostate Cancer.  A huge epidemiological study of 28,000+ men found that the higher the T-levels , the lower the incidence of prostate cancer. [18] John Hopkins researchers found men without prostate cancer had average T-levels of 636 ng/ml while prostate cancer patients average levels of 473. [19] Again, if increasing testosterone is dangerous to the prostate, one would not expect this result.

2. STUDY: Testosterone Therapy Does Not Increase the Risk of Aggressive Prostate Cancer.  What you really care about is avoiding the aggressive from of prostate cancer, which can spread easily and kill you in a matter of months. [40]  A recent (2015) study by the Journal of Urology showed no increase the nasty form of prostate cancer, again completely counterintuitive to the standard model. [41] By the way, this study looked over a fairly long time frame of five years.

NOTE:  You should also check out my page How to Lower Your PSA, which shows the latest research on how to lower your PSA, and my page that discusses the research on How to Prevent Prostate Cancer.

3. STUDIES: High Testosterone Increases Survival from PC.  Several studies have shown that the higher one’s testosterone, the better the chance of survival from prostate cancer. [22] Why would higher testosterone protect men from prostate cancer if testosterone is what causes and spreads it in the first place?  Again, that does not seem to add up.

4. STUDIES:  Low Testosterone Increases the Risk of Prostate Cancer.  A recent research summary pointed out that most studies show that low testosterone, and not high testosterone, increase the risk of more advanced forms of prostate cancer and the likelihood of developing cancer even after the prostate has been removed. [39] From this data, one can only argue that testosterone appears to be protective not harmful.

5. STUDY: Natural Testosterone Shrinks the Prostate.  The University of Utah studied 214 identical twins and found that the size of the prostate – one of the “curses” of middle and older aged males – was inversely related to T-levels. [20] Does somthing that decreases prostate size really increase prostate cancer risk?  I guess anything is possible, eh?  (Prostate size does NOT necessarily have anything to do with prostate cancer.  You can have a small prostate and nasty aggressive prostate cancer.  My point is that usually things that are natural and healthy for the body come in packages and improve health in many complementary ways.)

6. STUDY: Supplemental Testosterone Shrinks the Prostate.  Similar to #2, one study showed that men given supplemental testosterone actually shrank their prostates! [21] Again, testosterone seems generally prostate friendly and not the opposite.

NEW MODEL: The Saturation Model.  All of the above data lead a small group of researchers to come up with a completely different model relating testosterone to PC and dubbed it The Saturation Model.  The pioneers were Drs. Muller and Morgentaler, who point out that the data seems to point out that testosterone has a finite, limited ability to fuel prostate cancer.  Dr. Morgentaler, in my opinion, argues eloquently for this view and develops it fully in a landmark paper in the journal European Urology. [40] There he states that testosterone can stimulate prostate cancer growth at very low levels of testosterone and then additional testosterone makes no difference.  This is why the pharmaceutical lowering of testosterone to essentially castrate a man does help with prostate cancer:  Furthermore, this is why raising testosterone past, say, a 100 ng/dl makes no real difference in prostate cancer rates.  It simply does not matter any more, because testosterone has done all the prostate stimulation that it is going to do back at 100 (or whatever the very low T number is).

CAUTION:  Of course, I encourage you to talk to your doctor:  it is his job to stay up on the latest research and, of course, he will have experience in his own practice as well.  Perhaps some subpopulation of men is at risk for prostate cancer and he or she is aware of this link.  In general, though, the saturation model makes a lot of sense to me.  However, I do want to point out that some men go on testosterone therapy and increase their testosterone quite high and estradiol increases with it of course.  Furthermore, many men, at least here in the U.S., are overweight or obese and so their estradiol levels shoot up to unnaturally high levels, much greater than during their youth generally.  And most doctors ignore these high levels of estradiol and do not encourage their patients to lose weight, lower their dosage or perhaps manage their estradiol.  The reason that I bring this up is that there is some evidence that higher estradiol levels are linked to prostate cancer risk, something I outline in my page High Estradiol, Prostate Cancer and BPH (Enlarged Prostate), although it does not show up in the above studies as far as I know. Again, discuss with your doctor.

NOTE:   I have struggled with a mildly elevated PSA after going on TRT, but so far there is no evidence of prostate cancer but rather inflammation.  You can read about this in my pages High PSA But No Cancer and My Recent 4kScore Test Results.

REFERENCES:

18) Cancer, Epidemiology, Biomarkers Preview, v.6, 1997, p967-9

19) Prostate, v.27, 1995, p. 25-31

20) Journal of Clinical Endocrinology and Metabolism, v82, 1997, p571-5

21) Int’l Journal of Andrology, v.25,2002, p119-125

22) Cancer Research v.59,1999, p4161-4; Amer Journal of Clinical Oncology v20,1997,p605-8;Journal of urology, v163, 2000,p824-7; Prostate v47, 2001, p52-8; Journal of the American medical Assoc, v276, 1996, p1904-6

23) Am J Clin Nutr. 2007 Feb;85(2):523-9

24) UUrology,2007,70:672-676

25) Amer J of Epidem,2008,167(1):71-77

26) PLoS ONE, 2008, 3(7):e2568

27) Cancer Epidemiology, Biomarkers & Prev, Nov 1, 2007, 16:2213, "Cholesterol-Lowering Drugs and Advanced Prostate Cancer Incidence in a Large U.S. Cohort"

28) Cancer Epidemiol Biomarkers Prev 2009, 18:2807-2813, "Men with low serum cholesterol have a lower risk of high-grade prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial"

29) Cancer Epidemiol Biomarkers Prev 2009; 18:2814-2821, "Prediagnostic total and high-density lipoprotein cholesterol and risk of cancer"

Cancer Epidemiol Biomarkers Prev, 2009;18:2805-2806, 2807-2813, 2814-2821

31) Harvard Men's Health Watch, June 2007

32) CA Cancer J Clin, 2004, 54:68,"TOMATOES BEAT LYCOPENE ALONE FOR PROSTATE CANCER PROTECTION", http://caonline.amcancersoc.org/cgi/content/full/54/2/68

33) http://www.northwestern.edu/ newscenter/stories/2010/11/soy-prostate-cancer.html, Northwestern University Newscenter, Nov 8 2010, "Soy May Stop Prostate Cancer Spread: Experimental soy-based drug shows benefits in men with localized prostate cancer"

34) The Lancet, 1 January 2011, 377(9759):31-41,"Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials"

35) http://www.dailymail.co.uk/health/article-2359466/Taking-omega-3-fish-oil-supplements-increase-risk-aggressive-prostate-cancer-70.html

36) JAMA, 2011, 306(14):1549-1556, "Vitamin E and the Risk of Prostate Cancer The Selenium and Vitamin E Cancer Prevention Trial (SELECT)"

37) J Natl Cancer Inst, 2000 Dec 20, 92(24):2018-23, "Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer"

38) http://www.medicalnewstoday.com/articles/260338.php

39) European Urology, Jan 2015, 65(1):115-123,"A New Era of Testosterone and Prostate Cancer: From Physiology to Clinical Implications

40) EUROPEAN UROLOGY, 2012, 62:765–767, "Goodbye Androgen Hypothesis, Hello Saturation Model"

41) Journal of Urology, Accepted: May 29, 2015; Published Online: June 08, 2015, "Long-Term Exposure to Testosterone Therapy and the Risk of High Grade Prostate Cancer"

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