Objective: The optimum steroid hormone treatment regimes for transsexual subjects has not yet been established. We have investigated the mortality and morbidity figures in a large group of transsexual subjects receiving cross-sex hormone treatment.

Design: A retrospective, descriptive study in a university teaching hospital.

Subjects: Eight hundred and sixteen male-to-female (M-->F) and 293 female-to-male (F-->M) transsexuals.

Interventions: Subjects had been treated with cross-sex hormones for a total of 10,152 patient-years.

Outcome measures: Standardized mortality and incidence ratios were calculated from the general Dutch population (age- and gender-adjusted) and were also compared to side effects of cross-sex hormones in transsexuals reported in the literature.

Results: In both the M-->F and F-->M transsexuals, total mortality was not higher than in the general population and, largely, the observed mortality could not be related to hormone treatment. Venous thromboembolism was the major complication in M-->F transsexuals treated with oral oestrogens and anti-androgens, but fewer cases were observed since the introduction of transdermal oestradiol in the treatment of transsexuals over 40 years of age. No cases of breast carcinoma but one case of prostatic carcinoma were encountered in our population. No serious morbidity was observed which could be related to androgen treatment in the F-->M transsexuals.

Conclusion: Mortality in male-to-female and female-to-male transsexuals is not increased during cross-sex hormone treatment. Transdermal oestradiol administration is recommended in male-to-female transsexuals, particularly in the population over 40 years in whom a high incidence of venous thromboembolism was observed with oral oestrogens. It seems that in view of the deep psychological needs of transsexuals to undergo sex reassignment, our treatment schedule of cross-sex hormone administration is acceptably safe.