Cardiovascular disease in transsexual persons treated with cross-sex hormones: reversal of the traditional sex difference in cardiovascular disease pattern

Eur J Endocrinol. 2014 Jun;170(6):809-19. doi: 10.1530/EJE-14-0011. Epub 2014 Mar 10.

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.

Subjects and 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cardiovascular Diseases / epidemiology*
  • Cardiovascular System / drug effects
  • Female
  • Gonadal Steroid Hormones / therapeutic use*
  • Humans
  • Male
  • Sex Characteristics*
  • Sex Reassignment Procedures / statistics & numerical data*
  • Transgender Persons / statistics & numerical data*

Substances

  • Gonadal Steroid Hormones