Review of Studies of Androgen Treatment of Female-to-Male Transsexuals: Effects and Risks of Administration of Androgens to Females

INTRODUCTION: Testosterone supplementation in ovariectomized or elderly women may improve their sense of well-being and libido, muscle mass and strength, and bone mineral density. Naturally, androgens may have virilizing effects in women. It is often believed that androgens have deleterious effects on cardiovascular risks. AIM: To obtain an inventory of the effects of administration of testosterone on female biological functions. METHODS: We reviewed here our publications on the effects of high-dose androgen administration to female-to-male transsexuals treated between 1975 and 2004 (N = 712). Annual accrual was at a steady rate of 22-30 persons. Dosages administered were far above those suited for women. MAIN OUTCOME MEASURES: There was special focus on the potential negative effects on cardiovascular risk markers. RESULTS: The standard treatment was administration of testosterone esters, 250 mg/2-3 weeks, parenterally). With this dose, virilizing effects on the skin and clitoris were prominent. Spatial ability improved, while verbal fluency deteriorated. The ovaries developed polycystic characteristics. Adequate dosages of testosterone preserved bone mass in females. Androgens increased kallikreins, such as prostate-specific antigen, in female reproductive tissues. High-dose testosterone administration appeared to increase weight, visceral fat, and hematocrit, decrease high-density lipoprotein cholesterol, increase endothelin-1, increase C-reactive protein, and increase total homocysteine. But blood pressure, insulin sensitivity, fibrinolytic markers, arterial stiffness, and levels of von Willebrand factor, fibrinogen, and interleukin-6 remained largely unchanged. CONCLUSIONS: Our studies demonstrated that, while some markers of cardiovascular risk factors showed a shift to a more negative risk profile, others were not affected. Androgen effects on cardiovascular risk markers are therefore not universally negative, and it is reasonable to assume that the latter effects will not be negative with the much lower doses suited for administration to women.