POINT: Testosterone Therapy in Older Men: The Next Big Thing in Medicine?

Wed, 7/15/09 - 9:12am
1 Comments
3642 reads

Citation:

Pages 22 - 24

Authors:

Abraham Morgentaler, MD, FACS

Introduction

The Holy Grail for geriatric medicine would be a treatment or medication that allowed older individuals to feel younger and more robust, and that increased longevity. In the past, any treatment that purported to demonstrate such effects has been equated with snake oil. Yet, it is fair to say that there has been a reasonable expectation that medical science would one day find such a treatment, usually based on studies that will help delineate the biochemical basis of aging, and hence provide insight into avenues of modifying or reversing this biochemical process. Surprisingly, accumulating evidence indicates that an old treatment may already provide many of the benefits one associates with youthfulness and health: testosterone therapy for testosterone-deficient men.

Clinicians tend to have an immediate resistance to considering this possibility. Just the word “testosterone” brings to mind unsavory associations, such as cheating athletes, body building use of steroids, and endless Internet spam, or advertisements promoting incredible virility-enhancing supplements via stimulation of “natural” testosterone-like supplements. Anti-aging enthusiasts have in some cases asserted that testosterone is a solution to a variety of problems for which evidence is lacking. Apart from these affronts to the properly skeptical medical scientist, worrisome reports regarding testosterone therapy have appeared in the literature over several decades, including the potential for stimulating dormant prostate cancer, liver toxicity, hypertension, heart disease, and lipid abnormalities. Additional hurdles inhibiting the use of testosterone therapy include the perception that testosterone therapy is primarily indicated for sexual pleasure, as well as the viewpoint that testosterone deficiency represents a normal aging process that does not merit treatment.

Testosterone therapy thus suffers from the soft prejudice of familiarity. Yet, recent scientific information indicates that the treatment of testosterone deficiency may provide some of the most far-reaching benefits currently available for aging men in terms of overall health and metabolic changes, with a favorable side-effect profile, including reassuring new evidence regarding prostate cancer. It is time for clinicians to suspend old prejudices in order to more objectively evaluate testosterone therapy for their older male patients.

Case Vignette

SD was a 67-year-old man who was seen with his wife of 30 years for absent libido, fatigue, lack of energy, and frequent naps. “He’s never been like this,” reported his wife. “He was always someone who had a lot of energy.” The patient denied depression. His past medical history was notable for prostate cancer treated with radical prostatectomy 5 years previously, followed by external beam radiation therapy for biochemical recurrence. Despite having a penile prosthesis for prior treatment of erectile dysfunction, he and his wife no longer engaged in sexual activity due to SD’s lack of libido. Blood tests revealed undetectable prostate-specific antigen (PSA) and markedly reduced total and free testosterone. A DXA scan was normal. Body composition showed 39% body fat.

After discussion of risks, the patient began treatment with testosterone gel. At 6 months, libido had returned, and SD and his wife had resumed regular intercourse. He felt more energetic, and his wife reported that he no longer took naps. Body fat declined to 36%, lean mass increased by 1.5 kg, and fat mass declined by 2.0 kg. PSA remained undetectable.

References:

1. Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in adult men with androgen deficiency syndromes: An endocrine society clinical practice guideline [pubished correction appears in J Clin Endocrinol Metab 2006;91(7):2688]. J Clin Endocrinol Metab 2006;91(6):1995-2010. Published Online: May 23, 2006.

2. Wang C, Cunningham G, Dobs A, et al. Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab 2004;89:2085-2098.

3. Morgentaler A. Testosterone and prostate cancer: An historical perspective on a modern myth. Eur Urology 2006;50:935-939. Published Online: July 27, 2006.

4. Endogenous Hormones Prostate Cancer Collaborative Group, Roddam AW, Allen NE, Appleby P, Key TJ. Endogenous sex hormones and prostate cancer: A collaborative analysis of 18 prospective studies. J Natl Cancer Inst 2008;100:170-183. Published Online: January 29, 2008.

5. Morgentaler A. Testosterone replacement therapy and prostate cancer. Urol Clin North Am 2007;34:555-563, vii.

6. Mulligan T, Frick MF, Zuraw QC, et al. Prevalence of hypogonadism in males aged at least 45 years: The HIM study. Int J Clin Pract 2006;60:762-769.

7. Yialamas MA, Dwyer AA, Hanley E, et al. Acute sex steroid withdrawal reduces insulin sensitivity in healthy men with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab 2007;92:4254-4259. Published Online: August 28, 2007.

8. Laaksonen DE, Niskanen L, Punnonen K, et al. Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care 2004;27:1036-1041.

9. Kupelian V, Hayes FJ, Link CL, et al. Inverse association of testosterone and the metabolic syndrome in men is consistent across race and ethnic groups. J Clin Endocrinol Metab 2008;93:3403-3410. Published Online: June 17, 2008.

10. Hak AE, Witteman JC, de Jong FH, et al. Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: The Rotterdam Study. J Clin Endocrinol Metab 2002;87:3632-3639.

11. English KM, Steeds RP, Jones TH, et al. Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: A randomized, double-blind, placebo-controlled study. Circulation 2000;102:1906-1911.

12. Khaw KT, Dowsett M, Folkerd E, et al. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study. Circulation 2007;116:2694-2701. Published Online: November 26, 2007.

13. Madeo B, Zirilli L, Caffagni G, et al. The osteoporotic male: Overlooked and undermanaged? Clin Interv Aging 2007;2:305-312.

14. Amory JK, Watts NB, Easley KA, et al. Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. J Clin Endocrinol Metab 2004;89:503-510.

15. Meier C, Nguyen TV, Handelsman DJ, et al. Endogenous sex hormones and incident fracture risk in older men: The Dubbo Osteoporosis Epidemiology Study. Arch Intern Med 2008;168(1):47-54.

16. Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and mortality in older men. J Clin Endocrinol Metab 2008;93:68-75. Published Online: October 2, 2007.

17. Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR. Low serum testosterone and mortality in male veterans. Arch Intern Med 2006;14-28;166:1660-1665.

18. Morgentaler A, Traish AM. Shifting the paradigm of testosterone and prostate cancer: The Saturation Model and the limits of androgen-dependent growth. Eur Urol 2009;55(2):310-321. Published Online: September 25, 2008.

19. Ho SM, Damassa D, Kwan PW, et al. Androgen receptor levels and androgen contents in the prostate lobes of intact and testosterone-treated Noble rats. J Androl 1985;6:279-290.

20. Rhoden EL, Morgentaler A. Risks of testosterone-replacement therapy and recommendations for monitoring. N Engl J Med 2004;350:482-492.