by Jeffrey Dach MD
After men reach fifty years of age, Testosterone levels decline gradually culminating in low levels called the male Andropause. At age 70, Testosterone levels may have declined by 30 to 50 percent.
Symptoms of Low Testosterone
Low testosterone symptoms include muscle weakness, reduced libido, depression and loss of mental acuity. Symptoms are reversible with testosterone therapy.
Testosterone Therapy is Increasing
About 2 million prescriptions for testosterone were written in 2002, representing a 30% increase from 2001, and a 170% increase from 1999. Testosterone prescriptions have increased 5 fold over the past 10 years, in part due to increasing recognition of the low testosterone condition in aging males.
Adverse Health Effects of Low Testosterone
Medical studies suggest an association of low testosterone with increased morbidity and mortality. For example, there is a higher prevalence of depression, coronary heart disease, osteoporosis, fracture rates, frailty and even dementia with low testosterone levels.
Low Testosterone Predicts Increased Mortality
Dr Khaw reported in Circulation 2007 that “In men, endogenous testosterone concentrations are inversely related to mortality due to cardiovascular disease and all causes.” (12)
Dr Gail A. Laughlin reports in 2008, that “Testosterone insufficiency in older men is associated with increased risk of death over the following 20 years”.(13)
Resistance to Use of Testosterone by Mainstream Medicine
Some doctors are resistant to the use of testosterone in males with low testosterone levels. One of the reasons for this resistance to testosterone therapy is the history of synthetic testosterone use in the 1940s and 1950s, with methyltestosterone, a chemically altered version of testosterone not found in nature, and later found to cause cancer and heart disease. Following these revelations, testosterone use declined.
Interest in testosterone use was renewed in the 1980s with availability of the human bio-identical testosterone as topical creams, gels and injections. This is the exact same testosterone molecule that exists in the human body naturally.
Reputation from Sports Abuse
Testosterone has a terrible reputation stemming from a history of abuse in professional sports. After all, it is an anabolic steroid, and overachieving athletes have been found to cheat by using illegal anabolic steroids to gain competitive advantage. Young males may also be tempted to follow their example. One study from the University of Minnesota estimated that 5.9 percent of male high school seniors have taken anabolic steroids.(14)
In response to problems with athletes and sports abuse, Congress ruled Testosterone a Controlled Substance in the same category with addictive drugs such as morphine and oxycontin. Penalties for illegal use are severe, with 5 years imprisonment for any doctor who prescribes testosterone improperly. No wonder doctors are reluctant to prescribe it.
Institutional Medicine is Opposed to the Idea
On November 12, 2002, an Institute of Medicine panel (IOM) convened in Washington DC and declared that, “Existing scientific evidence does not justify claims that testosterone treatments can relieve or prevent certain age-related problems in men.” (15)
I would disagree with this IOM statement. There are literally dozens of studies in the medical literature showing health benefits and safety of testosterone therapy. (15) I believe that a normal level of testosterone, sustained for a lifetime, is one of the most important ways for men to maintain good health.
Benefits of Testosterone:
Benefits include positive effects on mood, energy levels, verbal fluency, strength, increased muscle size, decreased body fat and increased bone density.(18) There is also an anti-depressant effect.(16-17)
Testosterone Benefits for Metabolic Syndrome and Diabetes
Low Testosterone has been linked to metabolic syndrome and diabetes, and testosterone treatment has been found beneficial.(19-20) In a 2011 study by Marsh and Jones from Sheffield England, testosterone treatment reduced the six year mortality in a Diabetic population by over fifty per cent.(21) This is an excellent reduction in mortality with a single intervention (Testosterone). For more on Testosterone and Mortality Reduction see my article here.
Benefits of Testosterone: Heart and Circulation
Dr. S. Dobrzycki studied men with known coronary artery disease and showed they had significantly lower levels of testosterone (J Med Invest 2003).(6) 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). This was published in the American Journal of Cardiology in 2003. (7) Dr CJ Malkin has published dozens of studies on the beneficial effects of testosterone for cardiovascular health. For example, Dr. Malkin reports that Testosterone acts a protective factor against atherosclerosis and plaque formation in our vascular tree. (J Endocrin Sept 2003).
Dr. Gerald Philips at Columbia University, and Dr. Joyce Tenover of the University of Washington have published many studies over the years on Testosterone therapy, showing that low testosterone is a health risk, and testosterone treatment beneficial for health.
Testosterone Improves Cognitive Abilities:
Dr. Cherrier has an impressive array of studies which show testosterone improves cognitive and verbal abilities in men. (8-11)
Safety Regarding the Prostate
Does Testosterone Therapy cause Prostate Cancer? The answer is NO and is clearly found in the medical literature. Dr. Rhoden, in the January 2004 issue of the New England Journal of Medicine, reviewed 72 medical studies and found no evidence that testosterone therapy causes prostate cancer. (2) In fact, they note that prostate cancer becomes more prevalent exactly at the time of a man’s life when testosterone levels decline.(2)
Does Testosterone Cause Prostate Trouble?
Dr. Perchersky published a study in the International Journal of Andrology (2002), which examined men with low testosterone levels. He looked at multiple parameters, including prostate volume, PSA, and lower urinary tract symptoms like frequency and urgency. Of the 207 men studied, 187 responded favorably to testosterone treatment.(3)
A 2006 study by Leonard Marks, MD in JAMA again shows safety of testosterone therapy. “No treatment-related change was observed in prostate histology, tissue biomarkers, gene expression, or cancer incidence or severity. Treatment-related changes in prostate volume, serum prostate-specific antigen, voiding symptoms, and urinary flow were slight.”(4)
Adverse Side Effects of Excess Testosterone.
Adverse side effects from excess Testosterone administration listed in the medical literature are: sleep apnea, breast enlargement, testicular atrophy, excess blood count (polycythemia), and acne. Prostate issues such as possible stimulation of benign growth of the prostate (BPH) and worsening of urinary symptoms and stimulation of pre-existing prostate cancer growth are also included in this list. With careful monitoring of clinical and laboratory parameters, and keeping Testosterone levels within the normal range, these side effects can be avoided or minimized.
Monitoring of Testosterone Therapy:
Initially, a careful history and physical examination is required, as well as a testing panel which includes not only free testosterone levels, but also many other important parameters. As usual, it is important to work closely with a knowledgeable physician who is readily accessible and who can monitor adverse side effects and adjust treatment.
Articles with related interest:
1) The Testosterone Syndrome by Eugene Shippen, M.D.
2) Maximize Your Vitality and Potency for Men Over 40, Wright Jonathan V, Lenard L., Smart Publications, Petaluma, California, 1999
3) Testosterone and Andropause: the feasibility of testosterone replacement therapy in elderly men. Lund BC, Bever-Stille KA, Perry PJ.Pharmacotherapy. 1999 Aug;19(8):951-6. link
4) Case Scenarios in Androgen Deficiency. McCullough, Andrew MD, Rev Urol. 2003; 5 (Suppl 1): S41–S48.
Jeffrey Dach MD
7450 Griffin Road Suite 190
Davie, Florida 33314
Salazar, J, Risks of testosterone replacement therapy in aging men. Summary Expert Opinion on Drug Safety. November 2004, Vol. 3, No. 6, Pages 599-606
(2) Rhoden_Risks of Testosterone-Replacement Therapy
Rhoden, E.L, Risks of Testosterone-Replacement Therapy and Recommendations for Monitoring Ernani Luis Rhoden, M.D., and Abraham Morgentaler, M.D. NEJM Volume 350:482-492 Jan 29, 2004.
Perchersky AV et al. “Androgen administration in middle-aged and aging men: effects of oral testosterone undecanoate on di-hydrotestosterone, oestradiol, and prostate volume.” International J Androl 2002; 25(2): 119
(4) Effect of Testosterone Replacement Therapy_Testosterone_JAMA
Marks, Leonard S., Effect of Testosterone Replacement Therapy on Prostate Tissue in Men With Late-Onset Hypogonadism A Randomized Controlled Trial. , MD JAMA. 2006;296:2351-2361.
(5) Press Release for JAMA , Leonard Marks MD article
Dobrzycki S et al. “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.” J Med Invest 2003; 50(3-4):162-169.
Malkin CJ et al. “Effect of testosterone therapy on QT dispersion in men with heart failure.” Am J Cardiol 2003; 92(10): 1,241-1,243
Cherrier MM et al. “Testosterone supplementation improves spatial and verbal memory in healthy older men.” Neurology 2001; 57(1): 80-88.
(9)http://jcem.endojournals.org/content/87/7/3090.long Cherrier MM et al. “Cognitive effects of short-term manipulation of serum sex steroids in healthy young men.” J Clin Endocrinol Metab 2002; 87(7): 3,090-3,096.
(10) http://www.ncbi.nlm.nih.gov/pubmed/12826696 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(4): 568-576.
(11) http://www.ncbi.nlm.nih.gov/pubmed/14575730 Cherrier MM et al. “Relationship between testosterone supplementation and insulin-like growth factor-I levels and cognition in healthy older men.” Psychoneuroendocrinology 2004; 29(1): 65-82.
Khaw K., et al. “Endogenous Testosterone and Mortality Due to All Causes, Cardiovascular Disease, and Cancer in Men.”Circulation. 2007;116:2694-2701.
Conclusions— In men, endogenous testosterone concentrations are inversely related to mortality due to cardiovascular disease and all causes. Low testosterone may be a predictive marker for those at high risk of cardiovascular disease.
J Clin Endocrinol Metab. 2008 January; 93(1): 68–75. Low Serum Testosterone and Mortality in Older Men by Gail A. Laughlin, Elizabeth Barrett-Connor, and Jaclyn Bergstrom , Testosterone insufficiency in older men is associated with increased risk of death over the following 20 yr, independent of multiple risk factors and several preexisting health conditions.
Muscle-enhancing behaviors among adolescent girls and boys. by Marla E. Eisenberg; Melanie Wall; Dianne Neumark-Sztainer Pediatrics. 2012;130(6):1019-1026.
International Journal of Clinical Practice
Testosterone and Ageing: What Have We Learned Since the Institute of Medicine Report and What Lies Ahead? M. M. Miner, A. D. Seftel
Testosterone Gel Supplementation for Men With Refractory Depression: A Randomized, Placebo-Controlled Trial Harrison G. Pope, Jr., M.D.; Geoffrey H. Cohane, B.A.; Gen Kanayama, M.D., Ph.D.; Arthur J. Siegel, M.D.; James I. Hudson, M.D., Sc.D.
Am J Psychiatry 2003;160:105-111
CONCLUSIONS: These preliminary findings suggest that testosterone gel may produce antidepressant effects in the large and probably underrecognized population of depressed men with low testosterone levels.
J Affect Disord. 1998 Mar;48(2-3):157-61.
Testosterone replacement therapy for hypogonadal men with SSRI-refractory depression.Seidman SN, Rabkin JG.Testosterone replacement therapy may be an effective treatment of depressive symptoms in some men, and warrants further research.
International Journal of Impotence Research
Body Composition, Metabolic Syndrome and Testosterone in Aging Men C A Allan, B J G Strauss, R I McLachlan Int J Impot Res. 2007;19(5):448-457.
J Obes. 2011;2011. pii: 471584.
The role of testosterone in the etiology and treatment of obesity, the metabolic syndrome, and diabetes mellitus type 2. Saad F, Gooren LJ.
Bayer Schering Pharma AG, Scientific Affairs Men’s Healthcare, D-13342 Berlin, Germany.
Cross-sectional epidemiological studies have reported a direct correlation between plasma testosterone and insulin sensitivity, and low testosterone levels are associated with an increased risk of type 2 diabetes mellitus, dramatically illustrated by androgen deprivation in men with prostate carcinoma. Lower total testosterone and sex hormone-binding globulin (SHBG) predict a higher incidence of the metabolic syndrome. Administration of testosterone to hypogonadal men reverses part of the unfavorable risk profile for the development of diabetes and atherosclerosis.
Ther Adv Endocrinol Metab. 2010 Oct;1(5):207-23. doi: 10.1177/2042018810390258.
Testosterone and the metabolic syndrome. Muraleedharan V, Jones TH.
Vakkat Muraleedharan, MBBS, MD, MRCP Robert Hague Centre for Diabetes and Endocrinology, Barnsley Hospital NHS Foundation Trust, Barnsley and Department of Human Metabolism, University of Sheffield Medical School, Sheffield, UK.
Metabolic syndrome and testosterone deficiency in men are closely Linked.
Epidemiological studies have shown that Low testosterone Levels are associated with obesity, insulin resistance and an adverse Lipid profile in men. Conversely in men with metabolic syndrome and type 2 diabetes have a high prevalence of hypogonadism. Metabolic syndrome and Low testosterone status are both independently associated with increased all-cause and cardiovascular mortality. Observational and experimental data suggest that physiological replacement of testosterone produces improvement in insulin resistance, obesity, dyslipidae-mia and sexual dysfunction along with improved quality of Life.
Endocrine Abstracts (2011) 25 P163
Low testosterone predicts increased mortality and testosterone replacement therapy improves survival in men with type 2 diabetes by Vakkat Muraleedharan1,2, Hazel Marsh1 & Hugh Jones1,2 1 Barnsley Hospital NHS Foundation Trust, Barnley, UK; 2University of Sheffield, Sheffield, UK.
Aim: We report a 6 year follow-up study examining the effect of baseline testosterone and TRT in hypogonadal men with type 2 diabetes on all-cause mortality.Methods: Five hundred eighty-seven patients with type 2 diabetes had total testosterone (TT) performed between 2002 and 2005 and were followed up for 5.8±1.3 years. Deaths during the first 6 months were excluded.
Patients were then analysed in three groups.
i) normal TT (>10.4 nmol/l) (300 ng/dL)
ii) low TT (≤10.4 nmol/l) without TRT. (300 ng/dL)
iii) low TT receiving TRT for 2 years or more.
Results: Of 580 patients analysed, 338 had normal TT (58%) and 240 low TT (42%). In the low TT group 58 patients received TRT. Mean age 61±11 S.D. and similarly matched in all three groups. Total deaths 72 (12.4%).
Mortality rates –
low TT without treatment (36/182-20%),
normal TT (31/338-9%) and
low TT with TRT (5/58-8.6%).
Survival was significantly decreased in patients with low TT without TRT (P=0.001 log rank) compared to normal. The treated group had improved survival (P=0.049 log rank). In the Cox Regression model multi-variate (age, weight, HbA1c, pre existing cardiovascular disease, smoking, statin and ACEi/ARB use) adjusted hazard ratio for all-cause mortality was 2.2 (95% CI 1.3–3.7 P=0.001) for low TT.
Conclusions: This study shows that men with type 2 diabetes and low testosterone have a significant increased mortality. TRT improved survival compared to those untreated, recording a similar mortality rate to the normal TT group.
Brooke J. Poster 152. Muraleedharan V. Poster 163. Both presented at: Society for Endocrinology BES 2011; April 11-14, 2011; Birmingham, United Kingdom.
link to this article: http://wp.me/P3gFbV-q9
Jeffrey Dach MD
7450 Griffin Road Suite 190
Davie, Florida 33314
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