Sex steroid treatment is associated with side effects. The number of deaths and morbidity cases in 425 transsexual patients treated with cross- gender hormones were evaluated retrospectively and compared with the expected number in a similar reference group of the population. The number of deaths in male-to-female transsexuals was five times the number expected, due to increased numbers of suicide and death of unknown cause. Combined treatment with estrogen and cyproterone acetate in 303 male-to-female transsexuals was associated with a 45-fold increase of thromboembolic events, hyperprolactinemia (400-fold), depressive mood changes (15-fold), and transient elevation of liver enzymes. Androgen treatment in 122 female-to- male transsexuals was associated with weight increase >10% (17.2%) and acne (12.3%). In both groups persistent liver enzyme abnormalities could be attributed to other causes than sex steroids (hepatitis B and alcohol abuse). Much of the morbidity was minor and reversible with appropriate treatment or temporary discontinuation of hormone treatment. Thus, the dilemma of prescribing cross gender hormones in view of the needs of these patients is not resolved. Explanation of possible side effects and careful clinical judgment remain the cornerstone of the clinical decision to prescribe cross- gender hormones. Furthermore, follow up of this relatively young population to disclose long-term side effects and to elucidate the association of sex steroids with coronary heart disease, as well as efforts to reduce the risk of thromboembolic events, are required. Transsexual seek to adapt their bodies to the opposite biologic sex to which they perceive themselves belonging. Hormonal treatment plays an important role in this process.1 Ideally, the given hormone treatment should suppress the secondary sex characteristics of the original sex, as well as induce those of the opposite sex to the fullest extent and in the shortest possible period of time. Therefore, there is an inclination to maximize hormone dosage, which may involve health hazards.

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Experimental and Clinical Observations

Marie Kwan, Ph.D.1 Judy
VanMaasdam, B.A.2 and Julian M. Davidson, Ph.D.1

The effects of oral estrogen treatment on sexual physiology and behavior were examined in seven presurgical male-to-female transsexuals engaged in cross-living. Subjects were studied prior to hormone treatment during long- term hormone treatment and during an experimental double-blind period in which the effects of their usual hormone regimen were compared to those of placebo during successive 4-week periods. Subjects maintained daily logs of their spontaneous erections, sexual activity (masturbation), and feelings throughout the study. Nocturnal penile tumescence was measured using home monitors in order to estimate estrogen-induced changes in erectile capacity. Erectile response to sexually arousing stimuli (erotic films and self-generated fantasy) was also assessed in the laboratory. Blood samples were taken at intervals for testosterone and sex-hormone-binding globulin measurements and free testosterone levels were calculated. Estrogen treatment inhibited sexual activity spontaneous erections and nocturnal penile tumescence. No significant effects on psychophysiological response to film and fantasy or frequency of sexual feelings were found, but the psychophysiological data were very variable. Testosterone levels were suppressed by estrogen, but not to the extent that free testosterone levels were. It appears that declining free testosterone level is associated with inhibition of spontaneous erections (during both sleep and waking) and of sexual activity, though the latter relationship is less clear. No evidence of an effect on film or fantasy-induced erections was obtained.

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