SERUM TESTOSTERONE LEVEL IS THE MAJOR DETERMINANT OF THE MALE-FEMALE DIFFERENCES IN SERUM LEVELS OF HIGH-DENSITY-LIPOPROTEIN (HDL) CHOLESTEROL AND HDL(2) 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 5α-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/L v 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. We suggest that serum testosterone level is the major determinant of the male-female differences in serum HDL cholesterol and HDL2 cholesterol levels. © 1994.