Oral and transdermal estrogens both lower plasma total homocysteine in male-to-female transsexuals

Plasma total homocysteine (tHcy) levels are on average lower in women versus men, indicating an estrogenic effect. Oral estrogens (absorbed via the liver) may be hypothesized to have stronger effects on hepatic homocysteine metabolism than transdermal estrogens. We randomly assigned 30 male-to-female transsexuals (20–44 years old) to 4 months’ administration of oral ethinyl estradiol (n=15) or transdermal 17β-estradiol (n=15), both with the antiandrogen cyproterone acetate (CA). Ten other male controls were treated with CA only. At baseline and after 2 and 4 months, plasma tHcy was analyzed in conjunction with plasma folate. Oral ethinyl estradiol and transdermal 17β-estradiol similarly reduced plasma tHcy (geometric mean 10.6 μmol/l [95% CI 8.2–13.9] to 7.5 [6.5; 8.8], and 11.3 [8.1; 16.4] to 8.4 [6.5; 11.1]; P<0.001 for both), whereas CA had no effects. No effects were found on folate levels. Thus, oral and transdermal estrogens decrease plasma tHcy to a similar degree (by geometric mean −26%), which suggests that a hepatic mechanism is unlikely to play an important role in the decline of tHcy levels.