Intramuscular testosterone esters and plasma lipids in hypogonadal men: A meta-analysis

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 a n intramuscular testosterone ester and reported pretreatment and post-treat ment concentrations of total cholesterol, low-density lipoprotein (LDL), hi gh-density lipoprotein (HDL) cholesterol, or total triglyceride. METHODS: We calculated study-specific, post-treatment minus pretreatment di fferences in each plasma lipid concentration (mean [95% confidence interval ]). After testing of between-study homogeneity, we combined the study-speci fic differences. We then determined whether heterogeneity of differences co uld be explained in models of the differences on study and patient characte ristics (mean +/- SE) before and after excluding extreme values using a mul tiple outlier procedure. RESULTS: The studies represented 272 hypogonadal men (age 44 +/- 4 years; 2 0% with hypergonadotropic hypogonadism; total testosterone 0.5 0.2 ng/mL) w ho received, on average, 179 +/- 13 mg intramuscular testosterone ester eve ry 16 +/- 1 days for 6 +/- 1 months, Fixed-effects estimates of post-treatm ent minus pretreatment differences were -14 [ -17 to -11] mg/dL (total chol esterol), -1 [ - 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, d osing frequency or duration, concomitant elevation of plasma total testoste rone, aromatization of testosterone to estradiol, or other study and patien t characteristics. CONCLUSION: Intramuscular administration of testosterone esters to hypogona dal men is associated with a small, dosage dependent decrease in HDL choles terol and concomitant declines in total cholesterol and LDL cholesterol. Th e aggregate effect of these changes on cardiovascular risk remains unknown but deserves further study. (C) 2001 by Excerpta Medica, Inc.