Context: The most common treatment regimen in female-to-male transsexuals is administration of short-acting testosterone esters intramuscularly every 2 weeks.

Objective: To report the effects of administering long-acting testosterone undecanoate every 3 months on hormonal and clinical changes, mortality, morbidity, and safety during the first year of treatment in female-to-male transsexuals.

Design: One-year observational study.

Setting: Outpatient department at a university hospital.

Patients: Thirty-five female-to-male transsexuals completed the first year of observation, while two patients discontinued the treatment regimen due to serious hypertension.

Intervention: One year of intramuscular treatment with long-acting testosterone undecanoate every 3 months.

Main outcome measure(s): Gonadotropins, steroid hormones, liver enzymes, lipids, blood and coagulation parameter, body mass index, blood pressure, bone mineral density and endometrium thickness were measured at the beginning of cross-sex hormone treatment and after 12 months. The mortality, morbidity, adverse effects, and desired clinical changes were recorded.

Results: There was a significant decrease in LH, PRL, SHBG, HDL levels and endometrium thickness and a significant increase in BMI, systolic and diastolic blood pressure, TT and calculated androgens, TG, Hb, and Hct levels. No mortality was observed. Two cases of hypertension were noted. The patients reported a desirable increase in libido and clitoral growth. Acne was observed in five patients (14.3%).

Conclusions: The treatment of female-to-male transsexuals with long-acting testosterone undecanoate may be a feasible and safe option for testosterone augmentation in these subjects. However, monitoring of blood pressure should not be ignored during the treatment, in order to identify patients liable to develop hypertension.