title: Cardiovascular disease in transsexual persons treated with cross-sex hormones: reversal of the traditional sex difference in cardiovascular disease pattern.
abstract: OBJECTIVE
  The incidence of heart disease increases with age, but is lower in women than in men up to 75 years. A protective effect of female sex hormones or, alternatively, acceleration in male heart disease by testosterone at younger ages, could explain this sex difference. In contrast with the above, male-to-female transsexual subjects (MtoF) treated with estrogens (+anti-androgens) show more cardiovascular pathology than female-to-male transsexual subjects (FtoM) receiving testosterone. Why MtoF suffer more frequently from cardiovascular disease than females is as yet unclear. The mode of cross-sex hormone treatment may be a factor, and, if so, it may need adaptations.
  
  
  METHODS
  Studies in transsexual people on the effects of cross-sex hormone treatment on surrogate cardiovascular risks and on clinical endpoints were reviewed. With regard to MtoF, a parallel was sought with men with prostate cancer, undergoing androgen deprivation and estrogen administration.
  
  
  RESULTS
  Exposure of FtoM to testosterone was not associated with a strong increase in cardiovascular events. Aging and pre-existing cardiovascular pathology contributed to the risk of cardiovascular disease in MtoF. Use of the synthetic biopotent compound ethinyl estradiol in a dose two to four times of oral contraceptives increased cardiovascular risk substantially. The route of administration of estrogens (oral vs transdermal) may have impacted on the risks.
  
  
  CONCLUSIONS
  MtoF should not be treated with oral ethinyl estradiol. Transdermal estrogens are probably safer than oral estrogens. Pre-existing cardiovascular risks should be taken into consideration when prescribing and choosing the type of estrogens in cross-sex hormone administration (oral vs transdermal). In addition, risk factors, as they emerge with aging, should be addressed.
authors.affiliation: EmeritusVU University Medical Center, PO Box 7057, NL-1007 MB Amsterdam, The NetherlandsDepartment of EndocrinologyUZ Gent, Gent, BelgiumDepartment of PsychiatryLeiden University Medical Center, Leiden, The Netherlands louisjgooren@gmail.com.
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Gooren
authors.affiliation: EmeritusVU University Medical Center, PO Box 7057, NL-1007 MB Amsterdam, The NetherlandsDepartment of EndocrinologyUZ Gent, Gent, BelgiumDepartment of PsychiatryLeiden University Medical Center, Leiden, The Netherlands.
authors.forename: Katrien
authors.initials: K
authors.lastname: Wierckx
authors.affiliation: EmeritusVU University Medical Center, PO Box 7057, NL-1007 MB Amsterdam, The NetherlandsDepartment of EndocrinologyUZ Gent, Gent, BelgiumDepartment of PsychiatryLeiden University Medical Center, Leiden, The Netherlands.
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Giltay
mesh_terms: D002318:Cardiovascular Diseases / Q000453:epidemiology*; D002319:Cardiovascular System / Q000187:drug effects; D005260:Female; D012739:Gonadal Steroid Hormones / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D012727:Sex Characteristics; D057829:Gender-Affirming Procedures / Q000706:statistics & numerical data*; D063106:Transgender Persons / Q000706:statistics & numerical data*
chemical_list: D012739:Gonadal Steroid Hormones