Effects of Sex Steroids on Plasma Total Homocysteine Levels: A Study in Transsexual Males and Females

Abstract

Plasma total homocysteine (tHcy) levels are higher in men vs. premenopausal women, but it is not known whether this difference is related to sex steroids. The effects of cross-sex hormone administration on plasma tHcy levels were therefore investigated. Plasma tHcy levels were measured at baseline and after 4 months of treatment in 17 male-to-female (M→F) transsexuals treated with ethinyl estradiol (100 μg/day), in combination with the antiandrogen, cyproterone acetate (100 mg/day), and in 17 female- to-male (F→M) transsexuals treated with testosterone esters (250 mg/2 weeks, im). In M→F transsexuals, the plasma tHcy level decreased from geometric mean 8.2 μmol/L to 5.7 μmol/L (P < 0.001); and in F→M transsexuals, it increased from 7.7 μmol/L to 9.0 μmol/L (P = 0.005). In M→F transsexuals, changes in serum sex hormone-binding globulin levels correlated negatively, and changes in plasma creatinine and albumin levels correlated positively, with changes in plasma tHcy levels. In F→M transsexuals, changes in serum 17β-estradiol levels correlated negatively, and changes in plasma creatinine levels correlated positively, with changes in plasma tHcy levels. We conclude that tHcy levels decrease after estrogen + antiandrogen administration to male (transsexual) subjects, and levels increase after androgen administration to female (transsexual) subjects. These changes may be both primary and secondary to the anabolic/catabolic effects, as reflected by changes of creatinine and albumin levels after cross-sex hormone administration.