Serum testosterone level is the major determinant of the male-female differences in serum levels of high-density lipoprotein (HDL) cholesterol and HDL2 cholesterol.

We studied prospectively the effect of exogenous testosterone (testosterone undecanoate [TU] 160 mg/d orally) on lipoprotein profiles in eight hypogonadal males and 10 females (female-to-male transsexuals). Testosterone administration to androgen-deficient men and to eugonadal women produced similar serum levels of testosterone (7.67 +/- 5.47 nmol/L v 8.45 +/- 3.81 nmol/L) and 5 alpha-dihydrotestosterone (DHT) (3.27 +/- 3.52 nmol/L v 3.97 +/- 2.35 nmol/L) in the two groups, while serum estradiol levels were three to four times higher in the females (90 +/- 24 pmol/Lv 376 +/- 315 pmol/L). After testosterone treatment serum high-density lipoprotein (HDL) cholesterol levels decreased from 1.41 +/- 0.27 mmol/L to 1.27 +/- 0.22 mmol/L after 3 months and 1.17 +/- 0.23 mmol/L after 6 months (P < .01) in female-to-male transsexuals and from 1.31 +/- 0.39 mmol/L to 1.09 +/- 0.31 mmol/L after 3 months and 1.10 +/- 0.32 mmol/L (P < .05) after 6 months in hypogonadal males. In particular, serum HDL2 cholesterol levels decreased from 0.71 +/- 0.44 mmol/L to 0.45 +/- 0.20 mmol/L after 3 months and 0.49 +/- 0.39 mmol/L after 6 months (P < .01) in female-to-male transsexuals and from 0.52 +/- 0.12 mmol/L to 0.38 +/- 0.18 mmol/L after 3 months and 0.34 +/- 0.19 mmol/L after 6 months (P < .05) in hypogonadal males. Serum apolipoprotein (apo) A1 levels decreased concomitantly. In both sexes, serum levels of HDL cholesterol and HDL2 cholesterol decreased by approximately 15% and 35%, respectively, whereas serum levels of total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, apo A2, and apo B were not affected.(ABSTRACT TRUNCATED AT 250 WORDS)