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 e xogenous sex hormones. As part of a multicenter evaluation of a permeation- enhanced testosterone transdermal system (TTD), the interrelationships amon g serum lipoproteins, hormone levels, anthropometric parameters, and age we re 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 withdr awal resulting in a hypogonadal state (HG), and finally during a l-yr treat ment 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 i n 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 tr iglycerides (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 significa nce. Likewise, there were no significant differences between the IM-T and T TD treatments. Serum HDL levels showed a strong negative correlation with b ody mass index and other obesity parameters in all three study periods (r < -0.45; P < 0.02). During treatment with TTD, serum testosterone levels als o correlated negatively with body mass index (r = -0.621; P < 0.001). As a consequence of these relationships, a positive trend was observed between H DL and testosterone levels during TTD treatment (r = 0.336; P = 0.07). Inte restingly, the changes in lipoprotein levels during TTD treatment indicated a more favorable profile (decrease in cholesterol and low density lipoprot ein levels) with increasing age of the patients. In hypogonadal men the effects of transdermal testosterone replacement on s erum lipoproteins appear consistent with the physiological effects of testo sterone in eugonadal men.