Testosterone Therapy Safe for Men With Prostrate Cancer

[F.I.S.T. Senior Member Find all posts View Profile Close F.I.S.T.]

Testosterone Therapy Safe for Men With Prostrate Cancer

New research claims Testosterone therapy may be safe for men with prostate cancer.


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.

[F.I.S.T. Senior Member Find all posts View Profile Close F.I.S.T.]

A New Concern: Prostate Cancer and Low testosterone

I no longer fear that giving a man testosterone therapy will make a hidden prostate cancer grow or put him at increased risk of developing prostate cancer down the road. My real concern now is that men with low testosterone are at an increased risk of already having prostate cancer.

When my colleagues and I published our results in 1996 from prostate biopsies in men with low testosterone and PSA of 4.0 ng/mL or less, the 14 percent cancer rate was several times higher than any published series of men with normal PSA. In 2006, Dr. Rhoden and I published a larger study of prostate biopsies performed in 345 men. The cancer rate of 15 percent in this group was very similar to the first study. But whereas the cancer rate in 1996 was much higher than anything published to that date in men with PSA of 4.0 ng/mL or less, in 2006 the perspective had changed due to an important study called the Prostate Cancer Prevention Trial.




In that study, the cancer rate among men with a PSA of 4.0 ng/mL or less was also 15 percent. Because this value is identical to what we had found in our patients with low testosterone, it was suggested that the cancer rate in men with low testosterone is the same as the normal population—neither higher nor lower. However, the average age of men in our study was a decade younger than the men studied in the Prostate Cancer Prevention Trial (fifty-nine versus sixty-nine years). Almost half the men in the other study were seventy years or older, and age is the greatest risk factor we know for prostate cancer. The way I look at these numbers is that men with low testosterone have a cancer rate as high as men with normal T who are a decade older.
More importantly, in our study of 345 men, we found that the degree of testosterone deficiency correlated with the degree of cancer risk. Men whose testosterone levels were in the bottom third of the group were twice as likely to have cancer diagnosed on biopsy as men in the upper third. This finding adds to the concern that low testosterone is a risk factor for prostate cancer.
There is now additional data from around the world associating low testosterone and worrisome features of prostate cancer. For example, low testosterone is associated with more aggressive tumors. In addition, men with low testosterone appear to have a more advanced stage of disease at the time of surgical treatment.
Whereas I originally began to perform prostate biopsies in men with low testosterone because I was worried that treatment might cause a hidden cancer to grow, I now perform biopsies in these men because I am concerned they might have an increased risk of cancer. This risk is approximately one in seven for men with PSA values less than 4 ng/mL.
Because prostate cancer tends to be curable when caught early, I feel I’ve done these men a service by finding their cancers before they have an abnormal PSA or DRE. With today’s ability to monitor men with prostate cancer, not all of these men will necessarily require treatment. But the ones who have evidence of more aggressive tumors should definitely have an advantage by having their diagnosis made early.

The Evidence as it Now Stands

For over sixty-five years, there has been a fear that testosterone therapy will cause new prostate cancers to arise or hidden ones to grow. Although no large-scale studies have yet been performed to provide a definitive verdict on the safety of testosterone therapy, it is quite remarkable to discover that the long-standing fear about testosterone and prostate cancer has little scientific support. The old concepts, taken as gospel, do not stand up to critical examination. I believe the best summary about the risk of prostate cancer from testosterone therapy, based on published evidence at the time this book is written, is as follows:
Low blood levels of testosterone do not protect against prostate cancer and, indeed, may increase the risk.
High blood levels of testosterone do not increase the risk of prostate cancer.
Treatment with testosterone does not increase the risk of prostate cancer, even among men who are already at high risk for it.


In men who do have metastatic prostate cancer and who have been given treatment that drops their blood levels of testosterone to near zero, starting treatment with testosterone (or stopping treatment that has lowered their testosterone to near zero) might increase the risk that residual cancer will again start to grow.

One of the most important and reassuring studies regarding testosterone and prostate cancer was an article published in the Journal of the National Cancer Institute in 2008, in which the authors of eighteen separate studies from around the world pooled their data regarding the likelihood of developing prostate cancer based on concentrations of various hormones, including testosterone. This enormous study included more than 3,000 men with prostate cancer and more than 6,000 men without prostate cancer, who served as controls in the study. No relationship was found between prostate cancer and any of the hormones studied, including total testosterone, free testosterone, or other minor androgens. In an accompanying editorial, Dr. Carpenter and colleagues from the University of North Carolina School of Public Health suggest scientists finally move beyond the long-believed but unsupported view that high testosterone is a risk for prostate cancer.


More and more physicians are coming around to recognize that testosterone therapy is not a true risk for prostate cancer, but it can take many years to alter established beliefs. Don’t be surprised if your own doctor still raises this issue with you if you are considering testosterone therapy. If he objects to treating you for that reason, you should refer him to the article above, or one of the other review articles listed in the References at the back of this book. Even better, have him read this chapter!

Abraham Morgentaler, MD, is an associate clinical professor of urology at Harvard Medical School, and is the founder of Men’s Health Boston, a center focusing on sexual and reproductive health for men. He is the author of a number of popular books including The Male Body and The Viagra Myth.
Excerpted with permission from Testosterone for Life: Recharge Your Sex Drive, Muscle Mass, Energy and Overall Health by Abraham Morgentaler, MD, FACS. Published by McGraw-Hill.

[F.I.S.T. Senior Member Find all posts View Profile Close F.I.S.T.]

References

Agarwal PK, Oefelein MG. Testosterone replacemen testosterone therapy after primary treatment for prostate cancer. J Urol. 2005 Feb;173(2):533-6.

Araujo AB, Kupelian V, Page ST, et al. Sex steroids and all-cause and cause-specific mortality in men. Arch Intern Med. 2007;167:1252-60.
Bhasin S, Singh AB, Mac RP, Carter B, Lee MI, Cunningham GR. Managing the risks of prostate disease during testosterone replacement therapy in older men: recommendations for a standardized monitoring plan. J Androl. 2003;24:299-311.
Bhasin S, Storer TW, Berman N, et al. Testosterone replacement increases fat-free mass and muscle size in hypogonadal men. J Clin Endocrinol Metab. 1997;82:407-13.
Bremner WJ, Vitiello MV, Prinz PN. Loss of circadian rhythmicity in blood testosterone levels with aging in normal men. J Clin Endocrinol Metab. 1983;56:1278-81.
Carter HB, Pearson JD, Metter EJ, et al. Longitudinal evaluation of serum androgen levels in men with and without prostate cancer. Prostate. 1995;27(1):25-31.
Cherrier MM, Craft S, Matsumoto AH. Cognitive changes associated with supplementation of testosterone or dihydrotestosterone in mildly hypogonadal men: a preliminary report. J Androl. 2003;24:568-76.
Dobs AS, Meikle AW, Arver S, Sanders SW, Caramelli KE, Mazer NA. Pharmacokinetics, efficacy, and safety of a permeation-enhanced testosterone transdermal system in comparison with bi-weekly injections of testosterone enanthate for the treatment of hypogonadal men. J Clin Endocrinol Metab. 1999;84(10):3469-78.
English KM, Steeds RP, Jones TH, Diver MJ, Channer KS. Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina. Circulation. 2000;102(16):1906-11.
Gann PH, Hennekens CH, Ma J, et al. Prospective study of sex hormone levels and risk of prostate cancer. J Natl Cancer Inst. 1996;88(16): 1118-26.
Greenstein A, Mabjeesh NJ, Sofer M, Kaver I, Matzkin H, Chen J. Does sildenafil combined with testosterone gel improve erectile dysfunction in hypogonadal men in whom testosterone supplement therapy alone failed? J Urol. 2005 Feb;173(2):341.
Harman SM, Metter EJ, Tobin JD, et al. Longitudinal effects of aging on serum total and free testosterone levels in healthy men: Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metabol. 2001;86(2):724-31.
Hoffman MA, DeWolf WC, Morgentaler A. Is low serum free testosterone a marker for high grade prostate cancer? J Urol. 2000;163: 824-7.
Hsing AW. Hormones and prostate cancer: what’s next? Epidemiologic Rev. 2001;23(1):42-58.
Huggins CB, Stevens RB, Hodges CV. The effects of castration on advanced carcinoma of the prostate gland. Arch Surg. 1941;43:209.
Hwang TI, Chen HE, Tsai TF, Lin YC. Combined use of androgen and sildenafil for hypogonadal patients unresponsive to sildenafil alone. Int J Impot Res. 2006;18:400-4.
Kaufman JM, Graydon RJ. Androgen replacement after curative radical prostatectomy for prostate cancer in hypogonadal men. J Urol. 2004 Sep;172(3):920-2.
Kupelian V, Page ST, Araujo AB, Travison TG, Bremner WJ, McKinlay JB. Low sex hormone binding globulin, total testosterone, and symptomatic androgen deficiency are associated with development of the metabolic syndrome in non-obese men. J Clin Endocrinol Metab. 2006;91:843-50.
Lazarou S, Morgentaler A. Hypogonadism in the man with erectile dysfunction: what to look for and when to treat. Curr Urol Rep. 2005;6:476-81.
Lazarou S, Reyes-Vallejo L, Morgentaler A. Wide Variability in Laboratory Reference Values for Serum Testosterone. J Sex Med. 2006;3:1085-9.
Marin R, Escrig A, Abreu P, Mas M. Androgen-dependent nitric oxide release in rat penis correlates with levels of constitutive nitric oxide synthase isoenzymes. Biol Reprod. 1999;61:1012-6.
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;296:2351-61.
McNicholas TA, Dean JD, Mulder H, Carnegie C, Jones NA. A novel testosterone gel formulation normalizes androgen levels in hypogonadal men, with improvements in body composition and sexual function. Br J Urol. 2003;91:69-74.
Morgentaler A. The Viagra Myth: The Surprising Impact on Love and Relationships. San Francisco, CA: Jossey-Bass/Wiley, 2003.
Morgentaler A, Crews D. Role of the anterior hypothalamus-preoptic area in the regulation of reproductive behavior in the lizard, Anolis carolinensis: Implantation studies. Horm Behav. 1978;11:61.
Morgentaler A, Bruning CO, III, DeWolf WC. Incidence of occult prostate cancer among men with low total or free serum testosterone. JAMA. 1996;276:1904-6.
Morgentaler A. Male Impotence. Lancet. 1999;354:1713-8.
Morgentaler A. Testosterone and the prostate: is there really a problem? Contemporary Urol. 2006;18:26-33.
Morgentaler A. Testosterone replacement therapy and prostate risks: where’s the beef? Can J Urol. 2006;13:S40-3.
Morgentaler A. Testosterone therapy for men at risk for or with history of prostate cancer. Curr Treatment Options Oncol. 2006;7:363-9.
Morgentaler A. Testosterone and Prostate Cancer: An Historical Perspective On A Modern Myth. Eur Urol. 2006;50:935-9.
Morgentaler A, Rhoden EL. Prevalence of prostate cancer among hypogonadal men with prostate-specific antigen of 4.0 ng/ml or less. Urology. 2006;68:1263-7.
Morgentaler A. Testosterone and sexual function. Med Clin N Am. 2006;90:S32-4.
Morgentaler A. Cultural Biases and Scientific Squabbles: The Challenges to Acceptance of Testosterone Therapy As A Mainstream Medical Treatment. Aging Male. 2007;10:1-2.
Morgentaler A. Guideline for Male Testosterone Therapy: A Clinician’s Perspective. J Clin Endocrinol Metab. 2007;92:416-7.
Morgentaler A. Testosterone Deficiency and Prostate Cancer: Emerging Recognition of an Important and Troubling Relationship. Eur Urol. 2007;52:623-5.
Morgentaler A. Testosterone replacement therapy and prostate cancer. Urol Clin N Am. 2007;34:555-63.
Morley JE, Kaiser FE, Perry HM, et al. Longitudinal changes in testosterone, LH and FSH in healthy older men. Metabolism. 1997;46(4):410-3.
Nieschlag E, Swerdloff R, Behre HM, et al. Investigation, treatment and monitoring of late-onset hypogonadism in males. ISA, ISSAM, and EAU recommendations. Eur Urol. 2005;48:1-4.
Oh JY, Barrett-Connor E, Wedick NM, Wingard DL. Endogenous sex hormones and the development of type 2 diabetes in older men and women: the Rancho Bernardo study. Diabetes Care. 2002;25:55-60.
Pope HG Jr, Cohane GH, Kanayama G, Siegel AJ, Hudson JI. Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. Am J Psychiatry. 2003;160:105-11.
Rhoden EL, Estrada C, Levine L, Morgentaler A. The value of pituitary magnetic resonance imaging in men with hypogonadism. =J Urol. 2003;170:795-8.
Rhoden EL, Morgentaler A. Testosterone replacement therapy in hypogonadal men at high risk for prostate cancer: results of 1 year of treatment in men with prostatic intraepithelial neoplasia. J Urol. 2003;170:2348-51.
Rhoden EL, Morgentaler A. Treatment of testosterone-induced gynecomastia with the aromatase inhibitor, anastrozole. Int J Impot Res. 2004;16:95-7.
Rhoden EL, Morgentaler A. Influence of demographic factors and biochemical characteristics on the prostate-specific antigen (PSA) response to testosterone replacement therapy. Int J Impot Res. 2006;18:201-5.Shabsigh R. Testosterone therapy in erectile dysfunction. Aging Male. 2004;7:312-8.
Shores MM, Moceri VM, Gruenwals DA, et al. low testosterone is associated with decreased function and increased mortality risk: a preliminary study of men in a geriatric rehabilitation unit. J Am Geriatr Soc. 2004;52:2077-81.
Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR. Low serum testosterone and mortality in male veterans. Arch Intern Med. 2006;166:1660-5.Tenover JL. Testosterone replacement therapy in older adult men. Int J Androl. 1999 Oct;22(5):300-6.
Traish AM, Toselli P, Jeong SJ, Kim NN. Adipocyte accumulation in penile corpus cavernosum of the orchiectomized rabbit: a potential mechanism for veno-occlusive dysfunction in androgen deficiency. J Androl. 2005;26:242-8.
Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999;84:3666-72.
The Institute of Medicine Report. Testosterone and Aging: Clinical Research Directions. Washington, DC: The National Academies Press, 2004.
Wang C, Swerdloff RS, Iranmanesh A, et al. Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. J Endocrinol Metab. 2000;85(8):2839-53.
Whitsel EA, Boyko EJ, Matsumoto AM, Anawalt BD, Siscovick DS. Intramuscular testosterone esters and plasma lipids in hypogonadal men: a meta-analysis. Am J Med. 2001;111(4): 261-8.
Zvara P, Sioufi R, Schipper HM, Begin LR, Brock GB. Nitric oxide mediated erectile activity is a testosterone dependent event: a rat erection model. Int J Impot Res. 1995;7:209-19.

[F.I.S.T. Senior Member Find all posts View Profile Close F.I.S.T.]

Bump for Win All Day

[Win All Day Senior Member Find all posts View Profile Close Win All Day]

Previously, why would people shy away from utilizing Test therapy if they had prostate cancer? Did they believe that the Test would have negative side effects towards the cancer?

[F.I.S.T. Senior Member Find all posts View Profile Close F.I.S.T.]

Bump for Doc45