Interrelationships among Lipoprotein Levels, Sex Hormones, Anthropometric Parameters, and Age in Hypogonadal Men Treated for 1 Year with a Permeation-Enhanced Testosterone Transdermal System

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Abstract
Serum lipoproteins and cardiovascular risk are affected by endog- enous and exogenous sex hormones. As part of a multicenter evalu- ation of a permeation-enhanced testosterone transdermal system (TTD), the interrelationships among serum lipoproteins, hormone levels, anthropometric parameters, and age were investigated in 29 hypogonadal men. Subjects (aged 21- 65 yr) were first studied during prior treatment with im testosterone esters (IM-T), then during an 8-week period of androgen withdrawal resulting in a hypogonadal state (HG), and finally during a 1-yr treatment period with the TTD. Compared with treatment with IM-T, the HG period produced increases in high den- sity lipoprotein (HDL; 12.0 6 1.6% (6SEM); P , 0.001) and total cholesterol (4.2 6 1.9%; P 5 0.02) and a decrease in the cholesterol/ HDL ratio (29.7 6 2.8%; P 5 0.02). Compared with the HG period, TTD treatment produced decreases in HDL (-7.6 6 2.5%; P 5 0.002) and increases in the cholesterol/HDL ratio (9.0 6 2.5%; P 5 0.01) and triglycerides (20.7 6 6.4%; P 5 0.03). Small decreases in total cho- lesterol (21.2 6 1.8%; P 5 0.1) and low density lipoprotein (20.8 6 2.6%; P 5 0.07) were also observed during TTD, but did not reach statistical significance. Likewise, there were no significant differ- ences between the IM-T and TTD treatments. Serum HDL levels showed a strong negative correlation with body mass index and other obesity parameters in all three study periods (r ,2 0.45; P , 0.02). During treatment with TTD, serum testosterone levels also correlated negatively with body mass index (r 52 0.621; P , 0.001). As a consequence of these relationships, a positive trend was observed between HDL and testosterone levels during TTD treatment (r 5 0.336; P 5 0.07). Interestingly, the changes in lipoprotein levels dur- ing TTD treatment indicated a more favorable profile (decrease in cholesterol and low density lipoprotein levels) with increasing age of the patients. In hypogonadal men the effects of transdermal testosterone re- placement on serum lipoproteins appear consistent with the physi- ological effects of testosterone in eugonadal men. (J Clin Endocrinol Metab 86: 1026 -1033, 2001)

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