Menopause Mondays: Testosterone Therapy & Prostate Cancer with Dr. Josh Trutt
If you find that the men in your life are exhausted, grumpy, getting thicker around the middle, experiencing a crashing libido and/or are unusually anxious, it might be time to suggest that they get a checkup. In addition to checking the normal blood tests, be sure to remind them to have their thyroid checked as well as their free and total testosterone levels. Hormone replacement therapy is not just a woman’s option. That’s right, men! Call it andropause, male menopause or “manopause,” men go through a similar depletion of hormones as they grow up, which can contribute to negative physical, psychological and sexual issues. Testosterone therapy is one option men can use to counteract these effects, though some hold that it increases a man’s risk of prostate cancer.
Feeling healthy is the best present you can give yourself and those you love! Men go through hormonal fluctuations, too. If you love the men in your life, help them become proactive about their health. Get the proper tests and understand the options available to them. We all deserve to feel great!
Happy Father’s Day! Remember: Reaching out is IN. Suffering in silence is OUT!
In celebration of Father’s Day and all the wonderful men in our lives, I asked Dr. Josh Trutt, MD, of PhysioAge Medical Group if testosterone therapy increases the risk of prostate cancer. Here is what he had to say:
No. The medical literature indicates that testosterone therapy does not increase the risk of prostate cancer. In fact, the literature increasingly supports the theory that testosterone therapy actually decreases the risk of prostate cancer! Read on for details…
(The following is adapted from an excellent lecture by urologist Kenneth Janson, MD, FACS, given at the November 2010 Age Management Medical Group conference, as well as a lecture by Harvard urologist Abe Morgentaler at the December 2011 A4M conference.)
Historical background: In the past it was accepted belief that raising testosterone would increase the risk of prostate cancer. This was largely because in 1941 Huggins, Hodges and Scott showed that orchiectomy (surgical castration) caused regression of prostate cancer.
In 1966 Huggins won the Nobel Prize for “fundamental discoveries concerning the hormone dependence of normal and neoplastic cells in animals, and their practical application to the treatment of human prostatic and breast cancer.”
This led to many years of unchallenged belief that raising testosterone would increase the risk of prostate cancer. What never made the news was that this belief was based on Huggins and Hodges work with… one single patient.
In 1981 Fowler and Whitmore re-opened the discussion: they did a study showing that in men with prostate cancer who were treated with chemical castration (i.e. given medicine to shut down all testosterone production), testosterone therapy caused disease progression, just like Huggins and Hodges had shown. However, testosterone therapy in non-castrated men did not cause progression. (In other words: in men that still had some testosterone of their own, adding more did not cause prostate cancer progression.) (1)
Because of that paper, some questions started to be asked about the assumption that testosterone therapy is always bad in prostate cancer:
In 2000, articles from the Massachusetts Male Aging Study were published showing no correlation between PSA and testosterone levels even with testosterone levels up to 2800ng/dL. (For perspective, Age Management Medicine protocols generally do not push levels past 1200ng/dL, so this study used more than double the typical maximum levels for HRT.) (2,3)
In 2002 the Mayo Clinic stated (4),
There is no clinical evidence that testosterone replacement causes prostate cancer.
In 2004, things started really getting interesting. Harvard urologists Morgentaler and Rhoden published an article in the New England Journal of Medicine.(5) The article stated:
None of the 12 longitudinal population based studies, such as the Physician’s Health Study, found any increased risk of prostate cancer in men with higher levels compared to men with lower levels of testosterone.
Despite decades of research, there is no compelling evidence that testosterone has a causative role in prostate cancer. There is no compelling evidence to suggest that high testosterone levels or testosterone administration increases the risk of cancer. Prostate cancer becomes more relevant at the time of a man’s life when testosterone levels decline. Experienced clinicians aim for the upper normal range, in order to optimize treatment.
In 2009, Dr. Morgentaler went a bold step further: he published a case report of an 84-year old attorney who was diagnosed with prostate cancer and decided to not treat it– and to remain on testosterone therapy. After 24 months his PSA decreased and his prostate cancer was deemed stable. (6)
Morgentaler proposed the Saturation Theory: in patients with no testosterone (chemically castrated or levels less than 70ng/dL), testosterone replacement may cause disease progression—that first little bit may stimulate receptors on the cancer. HOWEVER, those receptors quickly saturate; therefore if patients are NOT castrated, and have testosterone already circulating, then additional testosterone doesn’t stimulate the receptors any further. (7,8,9)
That same year (2008) Cornell, Baylor and University of Toronto published a study showing that Testosterone therapy in hypogonadal men after radical prostatectomy for prostate cancer resulted in no increase in PSA and no increase in prostate cancer progression. (10)
Also that year, Marks et al published a study showing that tissue levels of Testosterone in the prostate were tested before and after testosterone therapy, and even though blood levels of testosterone went up significantly, there was no change in testosterone levels in the prostate. (11)
In 2010 the American Urological Association published work by Morgentaler on 13 patients already diagnosed with Prostate Cancer, who were treated with testosterone replacement and followed for 30 months: they showed no progression of their prostate cancer on subsequent biopsies and no increase in PSA. (12)
Furthermore: there is significant evidence to suggest that LOW testosterone INCREASES the risk of prostate cancer:
In 2001 Schatzl showed that lower testosterone levels were associated with more aggressive prostate cancer. (13)
In 2006 Morgentaler and Rhodes published a paper (14) showing that low levels of testosterone actually increase the risk of prostate cancer:
Among 345 hypogonadal men with low levels of total or free testosterone, Prostate cancer was present in more than 1 of 7 of the men even though their PSA was less than 4.0.
An increased risk of prostate cancer was associated with more severe reductions in testosterone.
In the Baltimore Longitudinal Study of Aging, men with the highest levels of Testosterone were at the LOWEST risk of developing prostate cancer.(15)
A study in Korea looked at 568 patients who underwent prostate biopsy. Patients with lower levels of serum testosterone had a higher risk of prostate cancer than did patients with high serum testosterone.(16)
And even more recently(17), in 2011 Salonia et al found that in men with low testosterone compared with men with normal testosterone levels,
▪ The risk of high-grade prostate cancer was increased by >50% (33% vs 19.8%, p< .0009),
▪ local invasion nearly doubled (21% vs 11%, P < .003),
and for men with more severe T deficiency, the risk of high grade cancer tripled (59.5% vs 19.8%, P < .0001).
IT IS IMPORTANT TO UNDERSTAND that clinical tumor recurrence or increase in PSA DOES OCCUR in a small percentage of patients treated with testosterone— but the rate is not higher than previously published statistics in men not receiving testosterone. In other words: whether they get testosterone or not, some men will get (initial or recurrent) prostate cancer. The literature simply indicates that testosterone replacement is not the cause.
In any patient on long-term testosterone replacement therapy, it is important to carefully monitor PSA levels, and regular prostate exam is necessary. Referral to a Urologist is warranted for any concerns. At present, most Urologists who are also trained in Age Management Medicine (a small group, to be sure) would likely NOT stop testosterone therapy even if PSA went up, but that decision would of course be made by the patient after an informed discussion with his doctors.
In the interest of balance it should be noted that, as of this writing, the Endocrine Society Clinical Guidelines still state that testosterone therapy is contraindicated in patients with prostate cancer.
1. Fowler, J, Whitmore, W. The Response of Metastatic Adenocarcinoma of the Prostate to Exogenous Testosterone. J Urology 1981, 126:372-375
2. Massachusetts Male Aging Study, Diabetes Care 2000; 23: 490-494.
3. Hoffman, M, DeWolf, W, Morgentaler, A. Is Low Serum Free Testosterone a Marker for High Grade Prostate Cancer? J Urology 2000,163:824-827
4. Mayo Clin Proc 2002 Jan:75:583-87
5. Rhoden E, Morgentaler, A. Risks of Testosterone-Replacement Therapy and Recommendations for Monitoring. New England Journal of Medicine 2004,350:482-492
6. Morgentaler, A. Two years of Testosterone Therapy Associated with Decline in Prostate-specific Antigen in a man with Untreated Prostate Cancer. J Sexual Medicine 2009,6:574-577
7. Morgentaler, A. Guilt by Association: A Historical Perspective on Huggins, Testosterone Therapy and Prostate Cancer. J Sex Med 2008, 5:1834-1840
8. Morgentaler, A. Testosterone Therapy in Men with Prostate Cancer: Scientific and Ethical Considerations. J Urology 2009, 181:972-979
9. Morgentaler, A. Shifting the Paradigm of Testosterone and Prostate Cancer: the Saturation Model and the Limits of Androgen-Dependent Growth. European Urology 55 (2009) 310-321
10. Roddam, A and the Endogenous Hormones and Prostate Cancer Collaborative Group. J National Cancer Institute 2008, 100:170-183
11. Marks LS, Mazer NA, Mostaghel E. et al. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. JAMA 2006; 296: 2351
12. Morgentaler A, Morales A: Should hypogonadal men with prostate cancer receive testosterone? J Urology October 2010, 184; 1257-1260
13. Schatzl et al. High-grade prostate cancer is associated with low serum testosterone levels. Prostate 47:52-58, 2001
14. Morgentaler A, Rhoden E. Prevalence of Prostate Cancer Among Hypogonadal Medn with PSA levels of 4.0ng/mL or Less. Urology 68:1263-1267, 2006
15. Laughlin GA, Barrett-Connor E and Bergstrom J: Low serum testosterone and mortality in older men. J Clin Endocrinol Metab 2008; 93: 68
16. Bo Sung Shin, et al: Is a Decreased Serum Testosterone Level a Risk Factor for Prostate Cancer? A Cohort Study of Korean MenKorean J Urol 2010 December; 51(12): 819–823
17. Morgentaler A. Turning Conventional Wisdom Upside-Down: Low Serum Testosterone and High-Risk Prostate Cancer. Cancer Volume 117, Issue 17, pp 3885–3888, 1 September 2011
Thank you to Dr. Trutt for helping so many men and women get the help they need. For more words of wisdom from the magnificent Dr. Trutt, check out “Menopause Mondays: Understanding Hormone Replacement Therapy” and “Menopause Mondays: Does HRT Cause Cancer.”