Influence of various modes of androgen substitution on serum lipids and lipoproteins in hypogonadal men.

We investigated whether the androgen type or application mode or testosterone (T) serum levels influence serum lipids and lipoprotein levels differentially in 55 hypogonadal men randomly assigned to the following treatment groups: mesterolone 100 mg orally daily ([MES] n = 12), testosterone undecanoate 160 mg orally daily ([TU] n = 13), testosterone enanthate 250 mg intramuscularly every 21 days ([TE] n = 15), or a single subcutaneous implantation of crystalline T 1,200 mg ([TPEL] n = 15). The dosages were based on standard treatment regimens. Previous androgen substitution was suspended for at least 3 months. Only metabolically healthy men with serum T less than 3.6 nmol/L and total cholesterol (TC) and triglyceride (TG) less than 200 mg/dL were included. After a screening period of 2 weeks, the study medication was taken from days 0 to 189, with follow-up visits on days 246 and 300. Before substitution, all men were clearly hypogonadal, with mean serum T less than 3 nmol/L in all groups. Androgen substitution led to no significant increase of serum T in the MES group, subnormal T in the TU group (5.7 +/- 0.3 nmol/L), normal T in the TE group (13.5 +/- 0.7 nmol/L), and high-normal T in the TPEL group (23.2 +/- 1.1 nmol/L). 5 alpha-Dihydrotestosterone significantly increased in all treatment groups compared with baseline. Compared with presubstitution levels, a significant increase of TC was observed in all treatment groups (TU, 14.4% +/- 3.0%; MES, 18.8% +/- 2.5%; TE, 20.4% +/- 3.0%; TPEL, 20.2% +/- 2.6%). Low-density lipoprotein cholesterol (LDL-C) also increased significantly by 34.3% +/- 5.5% (TU), 46.4% +/- 4.1% (MES), 65.2% +/- 5.7% (TE), and 47.5% +/- 4.3% (TPEL). High-density lipoprotein cholesterol (HDL-C) showed a significant decrease by -30.9% +/- 2.8% (TU), -34.9% +/- 2.5% (MES), -35.7% +/- 2.6% (TE), and -32.5% +/- 3.5% (TPEL). Serum TG significantly increased by 37.3% +/- 11.3% (TU), 46.4% +/- 10.3% (MES), 29.4% +/- 6.5% (TE), and 22.9% +/- 6.7% (TPEL). TU caused a smaller increase of TC than TE and TPEL, whereas the parenteral treatment modes showed a lower increase of TG. There was no correlation between serum T and lipid concentrations. Despite the return of serum T to pretreatment levels, serum lipid and lipoprotein levels did not return to baseline during follow-up evaluation. In summary, androgen substitution in hypogonadal men increases TC, LDL-C, and TG and decreases HDL-C independently of the androgen type and application made and the serum androgen levels achieved. Due to the extended washout period for previous androgen medication and the exclusion of men with preexisting hyperlipidemia, this investigation demonstrates more clearly than previous studies the impact of androgen effects on serum lipids and lipoproteins. It is concluded that preexisting low serum androgens induce a "male-type" serum lipid profile, and increasing serum androgens further within the male normal range does not exert any additional effects. The threshold appears to be above the normal female androgen serum levels and far below the lower limit of normal serum T levels in adult men. These findings may have considerable implications for the use of androgens as a male contraceptive and for androgen therapy in elderly men.