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Intramuscular testosterone esters and plasma lipids in hypogonadal men: a meta-analysis - 03/09/11

Doi : 10.1016/S0002-9343(01)00833-6 
Eric A Whitsel, MD, MPH , a, Edward J Boyko, MD, MPH b, e, Alvin M Matsumoto, MD c, e, Bradley D Anawalt, MD e, David S Siscovick, MD, MPH d, e, f
a Departments of Medicine and Epidemiology (EAW), Cardiovascular Disease Program, University of North Carolina Schools of Medicine and Public Health, Chapel Hill, North Carolina, USA 
b Epidemiologic Research and Information Center (EJB), Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA 
c Geriatric Research, Education and Clinical Center (AMM), Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA 
d Cardiovascular Health Research Unit (DSS), Seattle, Washington, USA 
e Department of Medicine (EJB, AMM, BDA, DSS), University of Washington Schools of Medicine and Public Health, Seattle, Washington, USA, 
f Department of Epidemiology (DSS), University of Washington Schools of Medicine and Public Health, Seattle, Washington, USA 

*Requests for reprints should be addressed to Eric A. Whitsel, MD, MPH, UNC-CH School of Public Health, Department of Epidemiology, Cardiovascular Disease Program, Bank of America Center, Suite 306, 137 East Franklin Street, Chapel Hill, North Carolina 27514

Abstract

Purpose

It is unclear whether intramuscular administration of testosterone esters to hypogonadal men is associated with changes in plasma lipids. We therefore analyzed 19 studies published between 1987 and 1999 that focused on male subjects with nonexperimental hypogonadism, treated subjects with an intramuscular testosterone ester and reported pretreatment and post-treatment concentrations of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) cholesterol, or total triglyceride.

Methods

We calculated study-specific, post-treatment minus pretreatment differences in each plasma lipid concentration (mean [95% confidence interval]). After testing of between-study homogeneity, we combined the study-specific differences. We then determined whether heterogeneity of differences could be explained in models of the differences on study and patient characteristics (mean ± SE) before and after excluding extreme values using a multiple outlier procedure.

Results

The studies represented 272 hypogonadal men (age 44 ± 4 years; 20% with hypergonadotropic hypogonadism; total testosterone 0.5 ± 0.2 ng/mL) who received, on average, 179 ± 13 mg intramuscular testosterone ester every 16 ± 1 days for 6 ± 1 months. Fixed-effects estimates of post-treatment minus pretreatment differences were −14 [−17 to −11] mg/dL (total cholesterol), −5 [−8 to −1] mg/dL (LDL cholesterol), −4 [−5 to −2] mg/dL (HDL cholesterol), and −1 [−6 to + 4] mg/dL (triglyceride). Decreases in HDL cholesterol were larger at lower dosages of testosterone ester (r = −0.54, P = 0.055), but were not explained by attrition, regression to the mean, dosing frequency or duration, concomitant elevation of plasma total testosterone, aromatization of testosterone to estradiol, or other study and patient characteristics.

Conclusion

Intramuscular administration of testosterone esters to hypogonadal men is associated with a small, dosage-dependent decrease in HDL cholesterol and concomitant declines in total cholesterol and LDL cholesterol. The aggregate effect of these changes on cardiovascular risk remains unknown but deserves further study.

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Keywords : Lipids, Testosterone, Hypogonadism, Men, Meta-analysis


Esquema


 Dr. Whitsel conducted this research under the sponsorship of a National Research Service Award (Contract 5-T32-HL07055) from the National Heart, Lung and Blood Institute and the Veterans Affairs Puget Sound Health Care System Health Services Research and Development Postdoctoral Fellowship Program. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs.


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Vol 111 - N° 4

P. 261-269 - septembre 2001 Regresar al número
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