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Tuesday, August 9, 2011

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).

Monday, August 1, 2011

Changes in Prostate Specific Antigen in Hypogonadal Men After 12 Months of Testosterone Replacement Therapy: Support for the Prostate Saturation Theory

Those who start at low baseline testosterone had the largest PSA increases. That makes sense since low levels of testosterone reduce prostate volume and prostatic specific antigen to levels under the expected median for a specific age. PSA levels normalized after the first month on the gel.


J Urol. 2011 Jul 23. [Epub ahead of print]

Changes in Prostate Specific Antigen in Hypogonadal Men After 12 Months of Testosterone Replacement Therapy: Support for the Prostate Saturation Theory.

Source

Scott Department of Urology, Baylor College of Medicine, Houston, Texas.

Abstract

PURPOSE:

We measured prostate specific antigen after 12 months of testosterone replacement therapy in hypogonadal men.

MATERIALS AND METHODS:

Data were collected from the TRiUS (Testim® Registry in the United States), an observational registry of hypogonadal men on testosterone replacement therapy (849). Participants were Testim naïve, had no prostate cancer and received 5 to 10 gm Testim 1% (testosterone gel) daily.

RESULTS:

A total of 451 patients with prostate specific antigen and total testosterone values were divided into group A (197 with total testosterone less than 250 ng/dl) and group B (254 with total testosterone 250 ng/dl or greater). The groups differed significantly in free testosterone and sex hormone-binding globulin, but not in age or prostate specific antigen. In group A but not group B prostate specific antigen correlated significantly with total testosterone (r = 0.20, p = 0.005), free testosterone (r = 0.22, p = 0.03) and sex hormone-binding globulin (r = 0.59, p = 0.002) at baseline. After 12 months of testosterone replacement therapy, increase in total testosterone (mean ± SD) was statistically significant in group A (+326 ± 295 ng/dl, p <0.001; final total testosterone 516 ± 28 ng/dl) and group B (+154 ± 217 ng/dl, p <0.001; final total testosterone 513 ± 20 ng/dl). After 12 months of testosterone replacement therapy, increase in prostate specific antigen was statistically significant in group A (+0.19 ± 0.61 ng/ml, p = 0.02; final prostate specific antigen 1.26 ± 0.96 ng/ml) but not in group B (+0.28 ± 1.18 ng/ml, p = 0.06; final prostate specific antigen 1.55 ± 1.72 ng/ml). The average percent prostate specific antigen increase from baseline was higher in group A (21.9%) than in group B (14.1%). Overall the greatest prostate specific antigen was observed after 1 month of treatment and decreased thereafter.

CONCLUSIONS:

Patients with baseline total testosterone less than 250 ng/dl were more likely to have an increased prostate specific antigen after testosterone replacement therapy than those with baseline total testosterone 250 ng/dl or greater, supporting the prostate saturation hypothesis. Clinicians should be aware that severely hypogonadal patients may experience increased prostate specific antigen after testosterone replacement therapy.
Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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