by Jeffrey Dach MD
At the 2011 Society for Endocrinology Meeting, Dr. Jones presented data on men with low testosterone and type two diabetes (elevated blood sugar). (1,2)
The authors studied 587 diabetic men over 6 years. About 40% of the men had low testosterone (below 300 ng/DL), and in this group, 58 men received Testosterone Replacement. The men were followed for 6 years and mortality rates reported.
Above Left Image: Testing Blood Glucose Wikimedia Commons.
Group 1) Low Testosterone without treatment (36/182-20% mortality),
Group 2) Normal Testosterone Level (31/338-9% mortality)
Group 3) Low Testosterone Level with Testosterone Replacement (5/58-8.6% mortality).
Mortality in the testosterone treatment men was reduced from 20% mortality to 8.6% , an 11 % mortality reduction over 6 years. This is a 2% per year mortality reduction.
Compare this 2% per year mortality reduction with testosterone to the 0.5% annual mortality reduction with Statin Drug Treatment in the average secondary prevention trial such as the 4S or LIPID studies, which found a 0.5% per year reduction in mortality for statin treatment in men with known heart disease.(3,4,5)
The shocking conclusion is that testosterone replacement in diabetic men is a far better treatment with more robust reduction in mortality and fewer adverse effects when compared to statin drug treatment.
Take Home message: Testosterone is much more beneficial in diabetic men than a statin drug would ever be.
Links and References
Endocrine Abstracts (2011) 25 P163 Low testosterone predicts increased mortality and testosterone replacement therapy improves survival in men with type 2 diabetes Vakkat Muraleedharan1,2, Hazel Marsh1 & Hugh Jones1,2 1 Barnsley Hospital NHS Foundation Trust, Barnley, UK; 2University of Sheffield, Sheffield, UK.
Background: Low testosterone in men is associated with increase in all-cause and cardiovascular mortality. There is a high prevalence of hypogonadism in men with type 2 diabetes and testosterone replacement therapy (TRT) improves cardiovascular risk. However there is no published data regarding mortality in these patients in relation to testosterone levels, and the long term effect of TRT on mortality.
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.
1nmol/L = 28.843 ng/dL
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.
Society for Endocrinology – Media Release
Embargoed until 00:01 BST, Wednesday 13 April 2011
Increase in deaths in men with type 2 diabetes and testosterone deficiency may be prevented by testosterone replacement
4S Study Seconday Prevention
Am J Cardiol. 1995 Sep 28;76(9):64C-68C.
Reducing the risk of coronary events: evidence from the Scandinavian Simvastatin Survival Study (4S). Kjekshus J, Pedersen TR. National Hospital, Department of Medicine, Oslo, Norway.
The Scandinavian Simvastatin Survival Study (4S) was designed to evaluate the effects of cholesterol reduction with simvastatin on mortality and morbidity in patients with coronary artery disease (CAD). A total of 4,444 patients with angina pectoris or previous myocardial infarction and serum cholesterol levels of 213-310 mg/dl (5.5-8.0 mmol/liter) while treated with a lipid-lowering diet were randomly assigned to double-blind treatment with simvastatin or placebo. Over the 5.4 years of median follow-up, simvastatin produced changes in total cholesterol, low density lipoprotein (LDL) cholesterol, and high density lipoprotein (HDL) cholesterol of -25%, -35%, and +8%, respectively, with minimal adverse effects.
A total of 256 patients (12%) in the placebo group died compared with 182 (8%) in the simvastatin group, a risk reduction of 30% (p = 0.0003) attributable to a 42% reduction in the risk of coronary death.
Noncardiovascular causes accounted for 49 and 46 deaths in the placebo and simvastatin groups, respectively. Major coronary events were experienced by 622 patients (28%) in the placebo group and 431 patients (19%) in the simvastatin group, corresponding to a risk reduction of 34% (p < 0.00001).
Circulation. 1998 Apr 21;97(15):1453-60.
Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S)
Pedersen TR, Olsson AG, Faergeman O, Kjekshus J, Wedel H, Berg K, Wilhelmsen L, Haghfelt T, Thorgeirsson G, Pyörälä K, Miettinen T, Christophersen B, Tobert JA, Musliner TA, Cook TJ. Aker Hospital, Oslo, Norway.
5) LIPID STUDY
Prevention of Cardiovascular Events and Death with Pravastatin in Patients with Coronary Heart Disease and a Broad Range of Initial Cholesterol Levels
The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group
N Engl J Med 1998; 339:1349-1357November 5, 1998
Practical Diabetes International Volume 28, Issue 1,Article first published online: 4 FEB 2011 Every obese male with type 2 diabetes should be screened for hypogonadism’
FOR Professor T Hugh Jones Consultant Physician & Endocrinologist, Robert Hague Centre for Diabetes and Endocrinology, Barnsley Hospital NHS Foundation Trust, and Hon. Professor of Andrology, Academic Unit of Diabetes, Endocrinology and Metabolism, School of Medicine and Biomedical Sciences, University of Sheffield, UK
updated clinical practice guideline of the American Endocrine Society does say that they suggest measurement of testosterone in men with type 2 diabetes.22
The Journal of Clinical Endocrinology & Metabolism June 1, 2010 vol. 95
Testosterone Therapy in Men with Androgen Deficiency Syndromes:
An Endocrine Society Clinical Practice Guideline
Shalender Bhasin, Glenn R. Cunningham, Frances J. Hayes, Alvin M. Matsumoto, Peter J. Snyder, Ronald S. Swerdloff and Victor M. Montori Boston University School of Medicine (S.B.), Boston, Massachusetts 02118; Baylor College of Medicine/Veterans Affairs Medical Center (G.R.C.), Houston, Texas 77030; St. Vincent’s University Hospital (F.J.H.), Dublin 4, Ireland; University of Washington/Veterans Affairs Puget Sound Health Care System (A.M.M.), Seattle, Washington 98108; University of Pennsylvania School of Medicine (P.J.S.), Philadelphia, Pennsylvania 19104; Harbor University of California, Los Angeles Medical Center (R.S.S.), Torrance, California 90502; and Mayo Clinic (V.M.M.), Rochester, Minnesota 55905
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