Research Needed to Assess CV Risks of Transgender Hormone Therapy

Veronica Hackethal, MD

August 01, 2017

More research is needed on the long-term cardiovascular effects of hormone therapy used for transitioning in transgender adults, according to a new review

"Current research regarding CVD among transgender adults receiving hormone therapy is greatly limited by a lack of large cohort studies in transgender persons, a lack of appropriate control populations, and inadequate collection of gender-identity information in clinics and national surveys," write Carl Streed Jr, MD, of Brigham and Women's Hospital, Boston, Massachusetts, and colleagues in the Annals of Internal Medicine

"Research findings have been based largely on retrospective studies, and the sample size of current studies remains small," they add.

According to recent reports, about 1.4 million people in the United States identify as transgender. Although transgender individuals have recently made strides in civil-rights issues, health disparities remain. A contributing factor may be the dearth of research and evidence-based guidelines on transgender health, which may limit appropriate care, say the researchers.

In particular, hormone therapy is an important part of transgender care. While some research in transgender individuals suggests hormone therapy may worsen CVD risk factors, whether this translates to increased illness and death is unclear. That's because studies have focused on younger people, making it difficult to get a clear picture of the long-term health effects of hormone therapy.  

The new review covers 13 studies about hormone therapy and CVD in transgender individuals. The authors also provide a review of relevant studies in cisgender adults (whose sex at birth matches their gender identity).

The review identified several key issues:

  • In transgender women, estrogen therapy may increase the risk for blood clots, so lower-dose transdermal and oral bioidentical formulations are preferred over high-dose oral ethinyl estradiol formulations.

  • In older transgender men, testosterone therapy may worsen CV risk factors, such as high blood pressure, insulin resistance, and lipid abnormalities. This higher risk, though, does not appear to increase the risk for CV events or mortality. However, larger, longer-term studies in older individuals are needed, the authors emphasize.

The review also stresses the importance of trying to reduce cardiovascular risk factors in both transgender women and men.

This is particularly true of older transgender women, who may have increased CVD risk factors. One study found a smoking prevalence of almost 50% among transgender women, for example.

Other studies have suggested the risk for CVD mortality is greater in transgender women compared with cisgender women and that long-term oral estrogen may play a role.

Because of the potential risks of hormone therapy, the authors emphasize shared decision making. However, they also stress the psychosocial benefits of hormone therapy. For this reason, a randomized controlled trial of hormone therapy in transgender individuals would be unethical, because it would deny proven benefits to the placebo group.

"Future research ideally should be based on large prospective cohort studies that include cisgender men and women, transgender men and women receiving cross-sex hormone therapy (CSHT), and transgender men and women not receiving CSHT.

"Such studies should be powered to evaluate differences among various CSHT regimens and should have sufficient follow-up to adequately assess cardiovascular outcomes, such as myocardial infarction and stroke, which often require more than a decade for adequate power to be generated," they conclude.

They also emphasize that research should address minority stress, or chronically elevated stress hormones experienced by stigmatized groups.

Dr Streed reports funding from an institutional National Research Service Award, the Ryoichi Sasakawa Fellowship Fund, and Brigham and Women's Hospital. Disclosures for the coauthors are listed in the paper.

Ann Intern Med. Published online July 24, 2017. Abstract

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