Testosterone Replacement Reduces Mortality
Testosterone Replacement
Reduces Mortality
by Jeffrey Dach MD
A study published in the Journal of Clinical Endocrinology & Metabolism by Molly Shores examined 1,031 men over 4 years. All 1,031 had low testosterone (below 250), and a subgroup of 398 of the men were treated with testosterone supplementation. At the end of the observation period the treated men had 10.3% mortality compared to 20.7% for the untreated men.(1) Testosterone supplementation reduced mortality in half. This is a rather impressive result.
For Post-menopausal Diabetic Women, Testosterone is Found to be Beneficial
A study published in 2011 Diabetes Care by Elisabeth Wehr from Graz, Austria looked at testosterone levels in 875 postmenopausal women referred for coronary angiography who were followed for 7 years. The Diabetic women with the highest quartile testosterone levels had a 60 percent reduction in all-cause and cardiovascular mortality compared to the lowest quartile.(2)
A similar study in older men referred for coronary angiography published by Dr Lerchblaumin in 2012 Clinical Endocrinology found that a combination of low free testosterone and low vitamin D predicts mortality.(3)
Endocrine Society Now Recommended Testosterone Testing and Replacement for All Diabetic Males (4,5)
About a quarter of diabetic men will have subnormal testosterone levels putting them at (200-300%) increased risk of cardiovascular mortality. The Endocrine Society now recommends that diabetic men have testosterone levels checked and given Testosterone replacement when found low. (4,5) Testosterone replacement is no longer controversial in the mainstream literature.(6,7,8)
Above Image: Testosterone chemical structure Courtesy of Wikimedia Commons
Articles with Related Interest:
Low Testosterone Diagnosis and Treatment
HCG in Males with Low Testosterone
Testosterone Benefits, PSA and Prostate Part One
Clomid for Men with Low Testosterone, Part One
Clomid For Men With Low Testosterone, Part Two
Hormone Disruption From Pain Pills
Testosterone Reduces Mortality
Increased Mortality from Testosterone Blockade
Testosterone Found Beneficial For Diabetes
Jeffrey Dach MD
7450 Griffin Road Suite 180/190
Davie, Florida 33314
954-792-4663
Links and References
1) http://jcem.endojournals.org/content/early/2012/04/11/jc.2011-2591.abstract
Testosterone Treatment and Mortality in Men with Low Testosterone Levels
by Molly M. Shores, Nicholas L. Smith, Christopher W.
Forsberg, Bradley D. nawalt and Alvin M. Matsumoto -
The Journal of Clinical Endocrinology & Metabolism April 11, 2012 jc.2011-2591
Context: Low testosterone levels in men have been associated with increased mortality. However, the influence of testosterone treatment on mortality in men with low testosterone levels is not known.
Objective: The objective of the study was to examine the association
between testosterone treatment and mortality in men with low
testosterone levels.
Design: This was an observational study of mortality in
testosterone-treated compared with untreated men, assessed with
time-varying, adjusted Cox proportional hazards regression models.
Effect modification by age, diabetes, and coronary heart disease was
tested a priori.
Setting: The study was conducted with a clinical database that included seven Northwest Veterans Affairs medical centers.
Patients: Patients included a cohort of 1031 male veterans, aged older than 40 yr, with low total testosterone [≤250 ng/dl
(8.7 nmol/liter)] and no history of prostate cancer, assessed between
January 2001 and December 2002 and followed up through the end of
2005.Main Outcome Measure: Total mortality in testosterone-treated
compared with untreated men was measured.Results: Testosterone
treatment was initiated in 398 men (39%) during routine clinical care.
The mortality in testosterone-treated men was 10.3% compared with 20.7%
in untreated men (P<0.0001) with a mortality rate of
3.4 deaths per 100 person-years for testosterone-treated men and 5.7
deaths per 100 person-years in men not treated with testosterone. After
multivariable adjustment including age, body mass index, testosterone
level, medical morbidity, diabetes, and coronary heart disease, testosterone
treatment was associated with decreased risk of death (hazard ratio
0.61; 95% confidence interval 0.42–0.88; P = 0.008).
Conclusions: In an observational cohort of men with low testosterone
levels, testosterone treatment was associated with decreased mortality
compared with no testosterone treatment.
Testosterone in AODM
2) care.diabetesjournals.org/content/34/8/1771.full
Diabetes Care August 2011 vol. 34 no. 8 1771-1777
Low Free Testosterone Levels Are Associated With All-Cause and
Cardiovascular Mortality in Postmenopausal Diabetic Women by Elisabeth
Wehr 1Department of Internal Medicine, Division of Endocrinology and
Metabolism, Medical University Graz, Graz, Austria
OBJECTIVE We aimed to evaluate whether total testosterone (TT), free testosterone (FT), and sex hormone–binding globulin (SHBG) are associated with all-cause and cardiovascular mortality in a cohort of postmenopausal women.
RESEARCH DESIGN AND METHODS We measured TT and SHBG levels in 875 postmenopausal women who were referred for coronary angiography (during 1997–2000). FT was calculated according to the Vermeulen method. The main outcome measures were Cox proportional hazard ratios (HRs) for mortality from all causes and from cardiovascular causes.
RESULTS After a median follow-up time of 7.7 years, 179 women (20.5%) had died. There were 101 deaths due to cardiovascular disease (56.4% of all deaths). We found no association of FT, TT, and SHBG levels with mortality in all postmenopausal women.
In postmenopausal diabetic women, multivariable-adjusted HRs (with 95% CIs) in the fourth compared with the first FT quartile for all-cause and cardiovascular mortality were 0.38 (0.08–0.90), P = 0.025, and 0.28 (0.08–0.90), P = 0.032, respectively. We found no association of TT and SHBG with mortality in diabetic postmenopausal women.
CONCLUSIONS In postmenopausal diabetic women referred for coronary angiography, low FT levels are independently associated with increased all-cause and cardiovascular mortality.
3) www.ncbi.nlm.nih.gov/pubmed/22356136
Clin Endocrinol (Oxf). 2012 Feb 22.Combination of low free
testosterone and low vitamin D predicts mortality in older men referred
for coronary angiography. Lerchbaum E, Pilz S, Boehm BO, Grammer TB,
Obermayer-Pietsch B, März W. Department of Internal Medicine, Division
of Endocrinology and Metabolism, Medical University of Graz, Graz,
Austria.
Low levels of 25-hydroxyvitamin D (25(OH)D) and free testosterone (FT) are both associated with increased mortality. Experimental
studies show a complex interplay of vitamin D and androgen metabolism
suggesting that a deficiency of both hormones may be associated with a
particularly adverse clinical outcome. OBJECTIVE: To evaluate the impact
of parallel FT and 25(OH)D deficiency in a large cohort of older men.
DESIGN:We measured total testosterone (TT), SHBG, and 25(OH)Dlevels in
2069 men who were routinely referred for coronary angiography
(1997-2000).
MAIN OUTCOME MEASURES:Cox proportional hazard ratios (HRs) (with 95%
confidence intervals) for mortality from all causes, cardiovascular, and
non-cardiovascular causes according to combined deficiency of FT and
25(OH)D.
RESULTS:In multivariate adjusted analyses, we found an increased risk
for all-cause mortality, cardiovascular and non-cardiovascular mortality
for men in the lowest FT (HR 1.26 [1.03-1.54], 1.24 [0.96-1.60], and
1.39 [1.00-1.93], respectively) and 25(OH)D quartile (HR 1.77
[1.47-2.13], 1.65 [1.29-2.10], and 1.89 [1.38-2.60] respectively)
compared to men in higher FT and 25(OH)D quartiles. There was no
independent association of TT levels with mortality. Multivariate
adjusted HRs progressively increased with the number of hormones (FT and
25(OH)D) in the lowest quartile (0 vs 2 hormone deficiencies:
2.11 [1.60-2.79] for all cause,
1.77 [1.23-2.55] for cardiovascular, and
2.33 [1.45-3.47] for non-cardiovascular mortality respectively).
CONCLUSION:A combined deficiency of FT and 25(OH)D is significantly associated with fatal events in a large cohort of men referred for coronary angiography.
——————————-
Endocrine society – measure testo in AODM Men
4) www.ncbi.nlm.nih.gov/pubmed/21896895
J Clin Endocrinol Metab. 2011 Sep;96(9):2643-51.
Update: Hypogonadotropic hypogonadism in type 2 diabetes and obesity.
Dandona P, Dhindsa S.Division of Endocrinology, State University of New
York at Buffalo and Kaleida Health, Buffalo, New York 14209, USA.
Studies over the last few years have clearly established that at least 25% of men with type 2 diabetes have subnormal free testosterone concentrations in association with inappropriately low LH and FSH concentrations. Another 4% have subnormal testosterone concentrations with elevated LH and FSH concentrations.
The Endocrine Society, therefore, now recommends the measurement of testosterone in patients with type 2 diabetes on a routine basis. The subnormal testosterone concentrations are not related to glycosylated hemoglobin or duration of diabetes, but are associated with obesity, very high C-reactive protein concentrations, and mild anemia.
In addition, subnormal testosterone concentrations in these men are associated with a two to three times elevated risk of cardiovascular events and death in two early studies. Short-term studies of testosterone therapy in hypogonadal men with type 2 diabetes have demonstrated an increase in insulin sensitivity and a decrease in waist circumference. However, the data on the effect of testosterone replacement on glycemic control and cardiovascular risk factors such as cholesterol and C-reactive protein concentrations are inconsistent. As far as sexual function is concerned, testosterone treatment increases libido but does not improve erectile dysfunction and thus, phosphodiesterase inhibitors may be required. Trials of a longer duration are clearly required to definitively establish the benefits and risks of testosterone replacement in patients with type 2 diabetes and low testosterone.
5) www.endo-society.org/guidelines/final/upload/final-androgens-in-men-standalone.pdf endocrine society Guidelines and testosterone recommendations in AODM Men
—————————————-
Two hormones testo and IGF-1 better predictors of increased mortality when low
6) www.ncbi.nlm.nih.gov/pubmed/22037276
Steroids. 2012 Jan;77(1-2):52-8. Epub 2011 Oct 20.
Improved prediction of all-cause mortality by a combination of serum total testosterone and insulin-like growth factor I in adult men.
Friedrich N, Schneider HJ, Haring R, Nauck M, Völzke H, Kroemer HK, Dörr
M, Klotsche J, Jung-Sievers C, Pittrow D, Lehnert H, März W, Pieper L,
Wittchen HU, Wallaschofski H, Stalla GK.Institute of Clinical Chemistry
and Laboratory Medicine, Ernst Moritz Arndt University, Greifswald,
Germany.
Lower levels of anabolic hormones in older age are well documented.
Several studies suggested that low insulin-like growth factor I (IGF-I)
or testosterone levels were related to increased mortality. The aim of
the present study was to investigate the combined influence of low IGF-I
and low testosterone on all-cause mortality in men.
METHODS AND RESULTS:From two German prospective cohort studies, the DETECT study and SHIP, 3942 men
were available for analyses. During 21,838 person-years of follow-up,
8.4% (n=330) of men died. Cox model analyses with age as timescale and
adjusted for potential confounders revealed that men with levels below
the 10th percentile of at least one hormone [hazard ratio (HR) 1.38 (95%
confidence-interval (CI) 1.06-1.78), p=0.02] and two hormones [HR 2.88
(95% CI 1.32-6.29), p<0.01] showed a higher risk of all-cause
mortality compared to men with non-low hormones. The associations became
non-significant by using the 20th percentile as cut-off showing that
the specificity increased with lower cut-offs for decreased hormone
levels. The inclusion of both IGF-I and total testosterone in a
mortality prediction model with common risk factors resulted in a
significant integrated discrimination improvement of 0.5% (95% CI
0.3-0.7%, p=0.03).
CONCLUSIONS:Our results prove that multiple anabolic deficiencies have a
higher impact on mortality than a single anabolic deficiency and
suggest that assessment of more than one anabolic hormone as a biomarker
improve the prediction of all-cause mortality.
————————–
7) jcem.endojournals.org/content/96/1/38.full
The Journal of Clinical Endocrinology & Metabolism January 1,
2011 vol. 96 no. 1 38-52 Why Is Androgen Replacement in Males
Controversial? Glenn R. Cunningham, M.D., Baylor College of Medicine
Houston, Texas 77030.
Until recently, it was thought that testosterone deficiency in middle-aged and older men mainly affected the quality of life, but it was unlikely to affect morbidity or mortality. However, population-based studies indicate that testosterone deficiency predicts future development of type 2 diabetes mellitus (6), metabolic syndrome (7), cardiovascular events (8, 9, 10, 11), mobility limitation (12), frailty (13), and mortality (8, 9, 10, 11). Whether testosterone treatment can improve health and prolong active lifestyles is unknown. No large, multicenter, long-term RPCTs have addressed these issues.
8) jcem.endojournals.org/content/96/1/62.full
The Journal of Clinical Endocrinology & Metabolism January 1, 2011
vol. 96 no. 1 62-65 Editorial Testosterone Treatment of Older Men—Why
Are Controversies Created? Ronald Swerdloff and Christina Wang
Ronald Swerdloff, M.D., Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center California
Jeffrey Dach MD
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