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

Department of Endocrinology, Division of Andrology (E.J.G., J.M.H.E., L.J.G.G., H.A.), the Institute for Research in Extramural Medicine (E.K.H., C.D.A.S.), the Department of Internal Medicine (C.D.A.S.), and the Institute for Cardiovascular Research (C.D.A.S.), Hospital Vrije Universiteit and Vrije Universiteit, 1007 MB, Amsterdam, The Netherlands

Address all correspondence and requests for reprints to: Prof. Dr. Louis J. G. Gooren, M.D., Department of Endocrinology, Division of Andrology, Hospital Vrije Universiteit, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.

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 (MF) transsexuals treated with ethinyl estradiol (100 µg/day), in combination with the antiandrogen, cyproterone acetate (100 mg/day), and in 17 female-to-male (FM) transsexuals treated with testosterone esters (250 mg/2 weeks, im).

In MF transsexuals, the plasma tHcy level decreased from geometric mean 8.2 µmol/L to 5.7 µmol/L (P < 0.001); and in FM transsexuals, it increased from 7.7 µmol/L to 9.0 µmol/L (P = 0.005). In MF 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 FM transsexuals, changes in serum 17ß-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.

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