Testosterone Replacement Decreases Mortality in a VA Cohort

From: The Endocrine Society

Abstract

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). No significant effect modification was found by age, diabetes, or coronary heart disease.

Conclusions: In an observational cohort of men with low testosterone levels, testosterone treatment was associated with decreased mortality compared with no testosterone treatment. These results should be interpreted cautiously because residual confounding may still be a source of bias. Large, randomized clinical trials are needed to better characterize the health effects of testosterone treatment in older men with low testosterone levels.

Endogenous Testosterone and Mortality in Men: A Systematic Review and Meta-Analysis

Men with low blood levels of testosterone had higher risk of mortality

From: The Journal of Clinical Endocrinology & Metabolism. August 3, 2011 jc.2011-1137

Clinical Review: Endogenous Testosterone and Mortality in Men: A Systematic Review and Meta-Analysis

1. Andre B. Araujo, 
2. Julia M. Dixon, 
3. Elizabeth A. Suarez, 
4. M. Hassan Murad, 
5. Lin T. Guey and
6. Gary A. Wittert

-Author Affiliations

1. Department of Epidemiology (A.B.A., J.M.D., E.A.S., L.T.G.), New England Research Institutes, Inc., Watertown, Massachusetts 02472; Division of Preventative Medicine (M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; and Department of Medicine (G.A.W.), University of Adelaide, Adelaide, South Australia 5005, Australia

1. Address all correspondence and requests for reprints to: Andre B. Araujo, Ph.D., Vice President, Epidemiology, New England Research Institutes, Inc., 9 Galen Street, Watertown, Massachusetts 02472. E-mail: aaraujo@neriscience.com.

Abstract

Context: Low testosterone levels have been associated with outcomes that reduce survival in men.

Objective: Our objective was to perform a systematic review and meta-analysis of published studies to evaluate the association between endogenous testosterone and mortality.

Data Sources: Data sources included MEDLINE (1966 to December 2010), EMBASE (1988 to December 2010), and reference lists.

Study Selection: Eligible studies were published English-language observational studies of men that reported the association between endogenous testosterone and all-cause or cardiovascular disease (CVD) mortality. A two-stage process was used for study selection. 1) Working independently and in duplicate, reviewers screened a subset (10%) of abstracts. Results indicated 96% agreement, and thereafter, abstract screening was conducted in singlicate. 2) All full-text publications were reviewed independently and in duplicate for eligibility.

Data Extraction: Reviewers working independently and in duplicate determined methodological quality of studies and extracted descriptive, quality, and outcome data.

Data Synthesis: Of 820 studies identified, 21 were included in the systematic review, and 12 were eligible for meta-analysis [n = 11 studies of all-cause mortality (16,184 subjects); n = 7 studies of CVD mortality (11,831 subjects)]. Subject mean age and testosterone level were 61 yr and 487 ng/dl, respectively, and mean follow-up time was 9.7 yr. Between-study heterogeneity was observed among studies of all-cause (P < .001) and CVD mortality (P = 0.06), limiting the ability to provide valid summary estimates. Heterogeneity in all-cause mortality (higher relative risks) was observed in studies that included older subjects (P = 0.020), reported lower testosterone levels (P = 0.018), followed subjects for a shorter time period (P = 0.010), and sampled blood throughout the day (P = 0.030).

Conclusion: Low endogenous testosterone levels are associated with increased risk of all-cause and CVD death in community-based studies of men, but considerable between-study heterogeneity, which was related to study and subject characteristics, suggests that effects are driven by differences between cohorts (e.g. in underlying health status).

Low testosterone predicts increased mortality and testosterone replacement therapy improves survival in men with type 2 diabetes

Endocrine Abstracts (2011) 25 P163

Low testosterone predicts increased mortality and testosterone replacement therapy improves survival in men with type 2 diabetes

Vakkat Muraleedharan^1,2, Hazel Marsh¹ & Hugh Jones^1,2

¹Barnsley Hospital NHS Foundation Trust, Barnley, UK; ²University of Sheffield, Sheffield, UK.

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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) ii) low TT (≤10.4 nmol/l) without TRT. 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.

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Endocrine Abstracts (2011) 25 P163