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.