Interrelationships among lipoprotein levels, sex hormones, anthropometric parameters, and age in hypogonadal men treated for 1 year with a permeation-enhanced testosterone transdermal system

Serum lipoproteins and cardiovascular risk are affected by endogenous and exogenous sex hormones. As part of a multicenter evaluation 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 density lipoprotein [HDL; 12.0 ± 1.6% (±SEM); P < 0.001] and total cholesterol (4.2 ± 1.9%; P = 0.02) and a decrease in the cholesterol/HDL ratio (-9.7 ± 2.8%; P = 0.02). Compared with the HG period, TTD treatment produced decreases in HDL (-7.6 ± 2.5%; P = 0.002) and increases in the cholesterol/HDL ratio (9.0 ± 2.5%; P = 0.01) and triglycerides (20.7 ± 6.4%; P = 0.03). Small decreases in total cholesterol (-1.2 ± 1.8%; P = 0.1) and low density lipoprotein (-0.8 ± 2.6%; P = 0.07) were also observed during TTD, but did not reach statistical significance. Likewise, there were no significant differences 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 < -0.45; P < 0.02). During treatment with TTD, serum testosterone levels also correlated negatively with body mass index (r = -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 = 0.336; P = 0.07). Interestingly, the changes in lipoprotein levels during 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 replacement on serum lipoproteins appear consistent with the physiological effects of testosterone in eugonadal men.