A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones.
OBJECTIVE
Adverse effects of long-term cross-sex hormone administration to transsexuals are not well documented. We assessed mortality rates in transsexual subjects receiving long-term cross-sex hormones.


METHODS
A cohort study with a median follow-up of 18.5 years at a university gender clinic. Methods Mortality data and the standardized mortality rate were compared with the general population in 966 male-to-female (MtF) and 365 female-to-male (FtM) transsexuals, who started cross-sex hormones before July 1, 1997. Follow-up was at least 1 year. MtF transsexuals received treatment with different high-dose estrogen regimens and cyproterone acetate 100 mg/day. FtM transsexuals received parenteral/oral testosterone esters or testosterone gel. After surgical sex reassignment, hormonal treatment was continued with lower doses.


RESULTS
In the MtF group, total mortality was 51% higher than in the general population, mainly from increased mortality rates due to suicide, acquired immunodeficiency syndrome, cardiovascular disease, drug abuse, and unknown cause. No increase was observed in total cancer mortality, but lung and hematological cancer mortality rates were elevated. Current, but not past ethinyl estradiol use was associated with an independent threefold increased risk of cardiovascular death. In FtM transsexuals, total mortality and cause-specific mortality were not significantly different from those of the general population.


CONCLUSIONS
The increased mortality in hormone-treated MtF transsexuals was mainly due to non-hormone-related causes, but ethinyl estradiol may increase the risk of cardiovascular death. In the FtM transsexuals, use of testosterone in doses used for hypogonadal men seemed safe.
Endocrine Unit, Department of Internal Medicine Center of Expertise on Gender Dysphoria, VU University Medical Center, PO Box 7057, NL-1007 MB Amsterdam, The Netherlands.
Henk
H
Asscheman
Erik J
EJ
Giltay
Jos A J
JA
Megens
W Pim
WP
de Ronde
Michael A A
MA
van Trotsenburg
Louis J G
LJ
Gooren
D000293:Adolescent; D000328:Adult; D000368:Aged; D003534:Cyproterone / Q000009:adverse effects / Q000627:therapeutic use; D017373:Cyproterone Acetate / Q000009:adverse effects / Q000627:therapeutic use; D004997:Ethinyl Estradiol / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D012739:Gonadal Steroid Hormones / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013739:Testosterone / Q000009:adverse effects / Q000627:therapeutic use; D014189:Transsexualism / Q000188:drug therapy* / Q000401:mortality*; D055815:Young Adult
D012739:Gonadal Steroid Hormones; D013739:Testosterone; D004997:Ethinyl Estradiol; D017373:Cyproterone Acetate; D003534:Cyproterone