Testosterone, PSA and the Prostate, Myths and Misconceptions 

Benefits of Testosterone Therapy

The Nobel Prize in Chemistry was awarded to Butenandt and Ruzicka in 1939 for the synthesis of testosterone (1) Since then, seventy years ago, thousands of medical studies have shown benefits of testosterone for improving health and prolonging life.(2-27)

Testosterone can prevent or reduce the likelihood of osteoporosis, type 2 diabetes, cardiovascular disease,  obesity, depression and anxiety and the risk of early mortality.(7)  Health benefits include positive effects on mood, energy levels, verbal fluency, strength, increased muscle size, decreased body fat and increased bone density.(2-27) Testosterone restores and enhances male libido, and is a treatment for male sexual dysfunction.(33) 

Low Testosterone Associated With Increased Mortality

The 2007 EPIC study concluded that testosterone level is inversely related to cardiovascular disease risk and all-cause mortality. Thus, low testosterone may be a marker for increased risk of cardiovascular disease.(35) Low Testosterone levels is also linked to reduced cognitive performance and onset of Alzheimers in elderly men. (36)(37)

Above Left Image: Adam by Albrecht Durer 1507 Courtesy of Del Prado, Madrid Courtesy Wikimedia

Testosterone Benefits the Heart

Here are a few studies showing testosterone benefits the heart and circulation. 

Dr. Dobrzycki studied men with known coronary artery disease and showed they had significantly lower levels of testosterone (J Med Invest 2003).(22) He also showed that lower testosterone levels was associated with reduced pumping ability of the heart.

Dr. C.J. Malkin showed that testosterone therapy reduced the risk of death from abnormal heart rhythms (arrhythmias).(23)   Dr. Malkin also reported that testosterone improves the pumping action of the heart in patients with Congestive Heart Failure,(24) and acts a protective factor against atherosclerosis and plaque formation in arteries. (J Endocrin 2003).

Dr. Eugene Shippen presented an impressive study at a medical meeting, in which testosterone therapy was used to successfully reverse diabetic gangrene of the lower legs and avoid amputation in many of the cases.

For more information on testosterone for aging males, see my web site testosterone information page.(25)

No Evidence of Adverse Effect on the Prostate

Regarding a hypothetical question of prostate cancer risk from testosterone administration, there is no evidence for this in the medical literature. Here are three of many medical studies reporting no adverse effect on the prostate, and no evidence that testosterone causes prostate cancer. 

Dr Morgentaler says: "It has been part of the conventional medical wisdom for six decades that higher testosterone in some way increases the risk of prostate cancer. This belief is derived largely from the well-documented regression of prostate cancer in the face of surgical or pharmacological castration. However, there is an absence of scientific data supporting the concept that higher testosterone levels are associated with an increased risk of prostate cancer. Specifically, no increased risk of prostate cancer was noted in 1) clinical trials of testosterone supplementation, 2) longitudinal population-based studies, or 3) in a high-risk population of hypogonadal men receiving testosterone treatment. Moreover, hypogonadal men have a substantial rate of biopsy-detectable prostate cancer, suggesting that low testosterone has no protective effect against development of prostate cancer. These results argue against an increased risk of prostate cancer with testosterone replacement therapy." Testosterone replacement therapy and prostate risks: where's the beef? Morgentaler A. Can J Urol. 2006 Feb;13 Suppl 1:40-3. (28)

Dr Morales says: "No evidence exists that appropriate androgen administration with knowledgeable monitoring carries significant or potentially serious adverse effects on the prostate gland." Monitoring androgen replacement therapy: testosterone and prostate safety by Morales A. J Endocrinol Invest. 2005;28(3 Suppl):122-7(29) 

Dr Rhoden says: “Despite decades of research, there is no compelling evidence that testosterone has a causative role in prostate cancer.” Risks of Testosterone-Replacement Therapy and recommendations for Monitoring. N Engl J Med 2004;350:482-92. Rhoden and Morgentaler.(30)


The ADAM Testosterone Questionnaire

This questionnaire is useful for detecting low testosterone levels.  ADAM is short for Androgen Deficiency in the Aging Male.(43)(44)

1. Do you have a decrease in libido (sex drive)? Yes No

2. Do you have a lack of energy? Yes No

3. Do you have a decrease in strength and/or endurance? Yes No

4. Have you lost height? Yes No

5. Have you noticed a decreased "enjoyment of life" Yes No

6. Are you sad and/or grumpy? Yes No

7. Are your erections less strong? Yes No

8. Have you noticed a recent deterioration in your ability to play sports? Yes No

9. Are you falling asleep after dinner? Yes No

10. Has there been a recent deterioration in your work performance? Yes No

If you answered YES to questions 1 or 7, or any 3 other questions, you may have low testosterone.  Next step is a testosterone blood test to determine your level. If low, then testosterone supplementation may be considered.  It is important to work closely with a knowledgeable physician who can do a full evaluation, order the appropriate tests, and prescribe treatment.

Testosterone for Dry Eyes in Women

Among other things, some post-menopausal women have a chronic dry eye problem with redness and irritation of the eyes.  This is called the evaporative dry eye and is usually a sign of testosterone deficiency, which can be confirmed by blood test for testosterone level, and rapidly resolves with topical testosterone cream in appropriate dosage.(31)(32)

Articles with Related Content:

Testosterone Safety and Benefits

Testosterone and PSA  Part Two

PSA Screening, the Failed Medical Experiment

More Articles on Testosterone

Testosterone and Dry Eye


Jeffrey Dach MD
7450 Griffin Rd Suite 180/190
Davie, FL 33314
Phone: 954-792-4663
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References:

(1) http://nobelprize.org/nobel_prizes/chemistry/laureates/1939/press.html
The Nobel Prize in Chemistry 1939 Presentation Speech The following account of Butenandt's work has been made.

Benefits of Testosterone

(2) http://mclean.harvard.edu/news/press/current.php?id=24

Study Suggests Depressed Men May Benefit from Testosterone Replacement Therapy Belmont--January 1, 2003, Harvard Medical School affiliate McLean Hospital -- A preliminary study published today in the American Journal of Psychiatry suggests that transdermal testosterone replacement gel, in conjunction with conventional antidepressants, may improve mood, anxiety, libido and other aspects of depression in difficult-to-treat men who fail to respond to antidepressants alone. Researchers from McLean Hospital in Belmont, MA, conducted the study in treatment-resistant depressed men with low testosterone levels.

(3) http://cgi.cnn.com/HEALTH/library/MC/00030.html
Testosterone therapy: The answer for aging men? Date updated: April 14, 2006   Content provided by MayoClinic.com Mayo Foundation for Medical Education and Research (MFMER)

(4) Testosterone Replacement_Therapy_Wayne_Hellstrom_2004.pdf
1.1 MB
2004 Testosterone Replacement Therapy. Wayne J.G. Hellstrom, M.D. Tulane University Medical Center New Orleans, LA

(5) http://www.medscape.com/viewarticle/556617


Testosterone and Ageing: What Have We Learned Since the Institute of Medicine Report and What Lies Ahead? M. M. Miner; A. D. Seftel Int J Clin Pract. 2007;61(4):622-632. 05/21/2007

The possible relationship of testosterone to risk of prostate cancer remains a concern; however, no new evidence has emerged to suggest that testosterone replacement therapy increases the risk. Recent studies have demonstrated that hypogonadism in men may be more prevalent than previously thought, is strongly associated with metabolic syndrome, and may be a risk factor for type 2 diabetes and cardiovascular disease. Clinical studies have shown that testosterone replacement therapy in hypogonadal men improves metabolic syndrome indicators and cardiovascular risk factors. Maintaining testosterone concentrations in the normal range has been shown to contribute to bone health, lean muscle mass, and physical and sexual function, suggesting that testosterone replacement therapy may help to prevent frailty in older men. Based on current knowledge, testosterone replacement therapy is unlikely to pose major health risks in patients without prostate cancer and may offer substantial health benefits.

(6) http://www.aafp.org/afp/20060501/1591.html
Testosterone Treatments: Why, When, and How? American Academy of Family Physicians.May 1, 2006 KATHERINE MARGO, M.D., University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania ROBERT WINN, M.D., Jefferson Medical College, Philadelphia, Pennsylvania

(7) http://www.sciencedaily.com/releases/2006/08/060816083120.htm
Science News Low Testosterone Levels Associated With Increased Risk Of Death In Men

ScienceDaily (Aug. 17, 2006) — Men who have a low testosterone level after age 40 may have a higher risk of death over a four-year period than those with normal levels of the hormone, according to a report in the August 14/28 issue of Archives of Internal Medicine, one of the JAMA/Archives journals (Arch Intern Med. 2006;166:1660-1665.

(8) http://www.sciencedaily.com/releases/2008/01/080109111320.htm
Testosterone May Improve Mental Function. ScienceDaily (Jan. 14, 2008) — When we think about the powers of testosterone, we usually do not consider mental processes. However, research suggests that testosterone levels may affect men’s cognitive performance, reports the January 2008 issue of Harvard Men’s Health Watch.

(9) http://www.worldhealth.net/pdf/bookstore/thera6_ch7.pdf
Chapter 7 Testosterone, The Male Hormone Connection: Treating Diabetes and Heart Disease
Michael Klentze, M.D., Ph.D. Medical Director, Klentze Institute of Anti-Aging, Munich,

(10) Lets_Talk_Testosterone_Steven F Hotze.pdf
2.0 MB
Testosterone By Steven F. Hotze, M.D., e-book.

(11) http://www.pharmacytimes.com/publications/issue/2004/2004-10/2004-10-4595

State-of-the-Art Update on Testosterone Replacement: A Clinical and Pharmacological Approach Narinder Duggal Pharmacy Times

(12) http://www.drmirkin.com/men/M227.html
TESTOSTERONE REPLACEMENT FOR OLDER MEN? Gabe Mirkin, M.D.

(13) Androgens_Testosterone_Endocrine_Society.pdf
4.5 MB
Treating With Testosterone: Endocrine Society


(14) patients_guide_low_testosterone_2003.pdf
458.1 KB

PATIENT’S GUIDE to Low Testosterone (2003 Edition)
Editors:Glenn R. Cunningham, MD,  Alvin M. Matsumoto, MD, Ronald Swerdloff, MD. From the Family Physicians Inquiries Network. Do testosterone injections increase libido for elderly hypogonadal patients? Krupa Shah, MD; Cathy Montoya, MLS Baylor College of Medicine, Houston, Texas. The Evidence-based answer, Yes, testosterone therapy is effective in improving libido for elderly hypogonadal males.

(15)http://www.harvardprostateknowledge.org/a-harvard-expert-shares-his-thoughts-on-testosterone-replacement-therapy

An interview with Abraham Morgentaler, M.D.A Harvard expert shares his thoughts on testosterone-replacement

(16) http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1502320
Rev Urol. 2003; 5(Suppl 1): S34–S40. New Advances in the Treatment of Hypogonadism in the Aging Male Christopher P Steidle, MD

(17) http://www.ncbi.nlm.nih.gov/pubmed/15799128
Aging Male. 2004 Dec;7(4):319-24. Testosterone therapy--what, when and to whom?Jockenhövel F.

(18) http://www.ncbi.nlm.nih.gov/pubmed/15329035
Drugs. 2004;64(17):1861-91. Androgen replacement therapy: present and future.Gooren LJ, Bunck MC.

(19) http://www.ncbi.nlm.nih.gov/pubmed/16918944
Clin Endocrinol (Oxf). 2006 Sep;65(3):275-81. Testosterone treatment comes of age: new options for hypogonadal men. Nieschlag E.

(20) Harrisons Aging Related Changes Male Reproductive Function.pdf
96.0 KB

Aging-Related Changes in Male Reproductive Function.pdf
Harrison's Internal Medicine Chapter 325. Disorders of the Testes and Male Reproductive System

(21) http://onlinelibrary.wiley.com/doi/10.2164/jandrol.05036/full

http://www.ncbi.nlm.nih.gov/pubmed/16474018

Journal of Andrology, Vol. 27, No. 2, March/April 2006
Review Testosterone Replacement Therapy for Older Men
MOSHE WALD*, RANDALL B. MEACHAM, LAWRENCE S. ROSS AND CRAIG S. NIEDERBERGER

Testosterone and the Heart

(22) http://www.ncbi.nlm.nih.gov/pubmed/13678385
J Med Invest. 2003 Aug;50(3-4):162-9.
An assessment of correlations between endogenous sex hormone levels and the extensiveness of coronary heart disease and the ejection fraction of the left ventricle in males.Dobrzycki S, Serwatka W, Nadlewski S, Korecki J, Jackowski R, Paruk J, Ladny JR, Hirnle T. 

(23) http://www.ncbi.nlm.nih.gov/pubmed/14609611
Am J Cardiol. 2003 Nov 15;92(10):1241-3. Links
Effect of testosterone therapy on QT dispersion in men with heart failure.Malkin CJ, Morris PD, Pugh PJ, English KM, Channer KS.
Department of Cardiology, Royal Hallamshire Hospital, Sheffield, United Kingdom.
The effects of testosterone on cardiac electrophysiology are poorly described. In this study we report the effect of physiologic testosterone therapy in 2 cohorts of men, the first with stable coronary disease and the second with congestive heart failure. Testosterone reduced QT dispersion in the heart failure cohort; no other effects were observed.

(24) http://www.ncbi.nlm.nih.gov/pubmed/16093267
Eur Heart J. 2006 Jan;27(1):57-64. Epub 2005 Aug 10. Links
Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial. Malkin CJ, Pugh PJ, West JN, van Beek EJ, Jones TH, Channer KS. Testosterone replacement therapy improves functional capacity and symptoms in men with moderately severe heart failure.

(25) Testosterone Information Page Jeffrey Dach MD

(26) http://drcranton.com/hrt/testosterone_replacement.htm
Testosterone Replacement: The Male Andropause, Taken from a chapter in the book, Resetting the Clock, by Elmer M. Cranton, M.D. and William Fryer

(27) http://archneur.ama-assn.org/cgi/content/abstract/59/11/1750
Beneficial Effects of Testosterone Replacement for the Nonmotor Symptoms of Parkinson Disease Michael S. Okun, MD; Benjamin L. Walter, MD; William M. McDonald, MD; Joyce L. Tenover, MD; Joanne Green, PhD; Jorge L. Juncos, MD; Mahlon R. DeLong, MD Arch Neurol. 2002;59:1750-1753.

Risks of Testosterone

(28) http://www.ncbi.nlm.nih.gov/pubmed/16526980
Can J Urol. 2006 Feb;13 Suppl 1:40-3. Testosterone replacement therapy and prostate risks: where's the beef? Morgentaler A. Division of Urology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

Specifically, no increased risk of prostate cancer was noted in 1) clinical trials of testosterone supplementation, 2) longitudinal population-based studies, or 3) in a high-risk population of hypogonadal men receiving testosterone treatment. Moreover, hypogonadal men have a substantial rate of biopsy-detectable prostate cancer, suggesting that low testosterone has no protective effect against development of prostate cancer. These results argue against an increased risk of prostate cancer with testosterone replacement therapy.

(29) http://www.ncbi.nlm.nih.gov/pubmed/16042371
J Endocrinol Invest. 2005;28(3 Suppl):122-7. Monitoring androgen replacement therapy: testosterone and prostate safety. Morales A. No evidence exists that appropriate androgen administration with knowledgeable monitoring carries significant or potentially serious adverse effects on the prostate gland.

(30) http:////img1.wsimg.com/blobby/go/cf110889-2dab-451b-855a-8addb7a314f4/downloads/testosterone_rhoden.pdf
Risks of Testosterone-Replacement Therapy and Recommendations for Monitoring
Ernani Luis Rhoden, M.D., and Abraham Morgentaler, M.D. N Engl J Med 2004;350:482-92.

(31) http://www.ncbi.nlm.nih.gov/pubmed/10415627
Androgens and dry eye in Sjögren's syndrome. Ann N Y Acad Sci. 1999 Jun 22;876:312-24. Sullivan DA et al.  Our results demonstrate that androgens regulate both lacrimal and meibomian gland function, and suggest that topical androgen administration may serve as a safe and effective therapy for the treatment of dry eye in Sjögren's syndrome.

(32) http://www.ncbi.nlm.nih.gov/pubmed/12114274
Androgen deficiency, Meibomian gland dysfunction, and evaporative dry eye. Sullivan DA et al. Ann N Y Acad Sci. 2002 Jun;966:211-22. Overall, these results support our hypothesis that androgen deficiency may be an important etiologic factor in the pathogenesis of evaporative dry eye in women with Sjögren's syndrome.

(33)

http://www.ncbi.nlm.nih.gov/pubmed/12917096

Male Sexual Dysfunction, Endocr Pract. 2003;9 (No. 1) January/February 2003 77
AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE EVALUATION AND TREATMENT OF MALE SEXUAL DYSFUNCTION: A COUPLE’S PROBLEM–2003 UPDATE AACE Male Sexual Dysfunction Task Force Andre T. Guay, MD, Richard F. Spark, MD, Sudhir Bansal, MD et al.

(34) http://www.fda.gov/safety/medwatch/safetyinformation/ucm186386.htm
Androgel FDA approved topical version of testosterone.

(35) http://www.ncbi.nlm.nih.gov/pubmed/18040028

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 2/6/2008  Khaw KT, Dowsett M, Folkerd E, et al. Circulation. 2007;116:2694-2701.The authors concluded that endogenous testosterone concentrations are inversely related to cardiovascular disease and all-cause mortality. Thus, low testosterone may be a marker for increased risk of cardiovascular disease.

(36) http://www.nih.gov/news/pr/jan2004/nia-26.htm
Low Free Testosterone Levels Linked to Alzheimer’s Disease in Older Men

(37) http://jcem.endojournals.org/cgi/content/full/87/11/5001
The Journal of Clinical Endocrinology & Metabolism Vol. 87, No. 11 5001-5007
Longitudinal Assessment of Serum Free Testosterone Concentration Predicts Memory Performance and Cognitive Status in Elderly Men
Scott D. Moffat, Alan B. Zonderman, E. Jeffrey Metter, Marc R. Blackman, S. Mitchell Harman and Susan M. Resnick. These results suggest a possible beneficial relationship between circulating free T concentrations and specific domains of cognitive performance in older men.

(38) http://www.mbschachter.com/male_andropause.htm
The Male Andropause, by Michael B. Schachter M.D., F.A.C.A.M.

(39) http://www.usdoctor.com/Chapter13.html
NATIONAL FEATURED ARTICLE TESTOSTERONE for MEN with DIABETES

(40)  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3064036/
Testosterone Replacemnent for Men with Type 2 Diabetes Mellitus. T Hugh Jones. Consultant Physician and Endocrinologist, Barnsley Hospital NHS Foundation Trust, and Honorary Professor of Andrology, Academic Unit of Diabetes, Endocrinology and Metabolism, University of Sheffield

(40) Androgen Deficiency in Men. Daniel S. Tung, MD, and Glenn R. Cunningham, MD  The Endocrinologist  Volume 17, Number 2, April 2007

(42) http://care.diabetesjournals.org/cgi/content/full/30/4/911
Diabetes Care 30:911-917, 2007 Clinical and Biochemical Assessment of Hypogonadism in Men With Type 2 Diabetes, Correlations with bioavailable testosterone and visceral adiposity. Dheeraj Kapoor, MD, et al. Testosterone levels are frequently low in men with type 2 diabetes, and the majority of these men have symptoms of hypogonadism.

(43) http://jcem.endojournals.org/cgi/content/full/89/12/5920#R4
The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 12 5920-5926
Prevalence and Incidence of Androgen Deficiency in Middle-Aged and Older Men: Estimates from the Massachusetts Male Aging Study. Andre B. Araujo et al.

(44) http://www.ncbi.nlm.nih.gov/pubmed/11016912
Metabolism. 2000 Sep;49(9):1239-42.Validation of a screening questionnaire for androgen deficiency in aging males. (ADAM) Morley JE, Charlton E et al.


Jeffrey Dach MD