Long-term treatment of transsexuals with cross-sex hormones: extensive personal experience

J Clin Endocrinol Metab. 2008 Jan;93(1):19-25. doi: 10.1210/jc.2007-1809. Epub 2007 Nov 6.


Context: Transsexuals receive cross-sex hormone treatment. Its short-term use appears reasonably safe. Little is known about its long-term use. This report offers some perspectives.

Setting: The setting was a university hospital serving as the national referral center for The Netherlands (16 million people).

Patients: From the start of the gender clinic in 1975 up to 2006, 2236 male-to-female and 876 female-to-male transsexuals have received cross-sex hormone treatment. In principle, subjects are followed up lifelong.

Interventions: Male-to-female transsexuals receive treatment with the antiandrogen cyproterone acetate 100 mg/d plus estrogens (previously 100 microg ethinyl estradiol, now 2-4 mg oral estradiol valerate/d or 100 microg transdermal estradiol/d). Female-to-male transsexuals receive parenteral testosterone esters 250 mg/2 wk. After 18-36 months, surgical sex reassignment including gonadectomy follows, inducing a profound hypogonadal state.

Main outcome measures: Outcome measures included morbidity and mortality data and data assessing risks of osteoporosis and cardiovascular disease.

Results: Mortality was not higher than in a comparison group. Regarding morbidity, with ethinyl estradiol, there was a 6-8% incidence of venous thrombosis, which is no longer the case with use of other types of estrogens. Continuous use of cross-sex hormones is required to prevent osteoporosis. Androgen deprivation plus an estrogen milieu in male-to-female transsexuals has a larger deleterious effect on cardiovascular risk factors than inducing an androgenic milieu in female-to-male transsexuals, but there is so far no elevated cardiovascular morbidity/mortality. Low numbers of endocrine-related cancers have been observed in male-to-female transsexuals.

Conclusions: Cross-sex hormone treatment of transsexuals seems acceptably safe over the short and medium term, but solid clinical data are lacking.

Publication types

  • Review

MeSH terms

  • Androgen Antagonists / administration & dosage*
  • Androgen Antagonists / adverse effects
  • Cardiovascular Diseases / chemically induced
  • Cyproterone Acetate / administration & dosage*
  • Cyproterone Acetate / adverse effects
  • Estradiol / administration & dosage
  • Estradiol / adverse effects
  • Estradiol / analogs & derivatives*
  • Female
  • Humans
  • Male
  • Osteoporosis / chemically induced
  • Testosterone / administration & dosage*
  • Testosterone / adverse effects
  • Transsexualism / drug therapy*


  • Androgen Antagonists
  • Testosterone
  • Cyproterone Acetate
  • Estradiol