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In transgender women, estrogen therapy may raise risk for VTE

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July 9, 2018

Transgender women who initiated cross-sex estrogen therapy were at increased risk for acute cardiovascular events, including venous thromboembolism and stroke, compared with cisgender women who initiated similar hormone therapy, according to a health care database analysis published in the Annals of Internal Medicine.

“In the patterns of vascular events in relation to hormone therapy, generally, you expect to see an increase in risk early, and then flattening of the risk, the hazard ratio goes down,” Michael Goodman, MD, MPH, associate professor in the department of epidemiology at Emory University Rollins School of Public Health, told Endocrine Today. “But that’s not what we found. First, there is a modest increase in risk for vascular events in transgender women, and then risk really increases in the following years. My first desire is to make sure these results are confirmed with independent data. If so, that would be an important finding.”

Goodman and colleagues analyzed electronic medical records of 2,842 transgender women and 2,118 transgender men from Kaiser Permanente sites in Georgia, Northern California and Southern California with an index date (first evidence of transgender status) between 2006 and 2014. Transgender hormone treatment was determined through linked prescription data. Patients were matched by year of birth, race, study site and index date enrollment with 48,686 cisgender men and 48,775 cisgender women. Researchers assessed incidence of VTE, ischemic stroke and MI via diagnostic codes through 2016, and used Cox proportional hazard models to compare acute CV events in the overall transgender women and transgender men cohorts and among those initiating HT with those in the matched cisgender reference groups.

Within the cohort, transgender women were followed for a mean of 4 years and transgender men were followed for a mean of 3.6 years.

Among transgender women, researchers observed 148 acute CV events since the index date, including 61 incidents of VTE, 54 ischemic strokes and 33 MI events. In the transgender men cohort, researchers observed 23 incidents of VTE, 16 ischemic strokes and nine MI incidents.

Compared with cisgender men and cisgender women, transgender women experienced an increase in post-index date incident of VTE, with the difference increasing with follow-up, according to researchers. Relative to cisgender men, 2-year and 8-year risk differences for VTE were 4.1 per 1,000 person-years (95% CI, 1.6-6.7) and 16.7 per 1,000 person-years (95% CI, 6.4-27.5). Relative to cisgender women, 2-year and 8-year risk differences for VTE were 3.4 per 1,000 person-years (95% CI, 1.1-5.6) and 13.7 per 1,000 person-years (95% CI, 4.1-22.7).

Researchers observed that the incidence of MI in transgender women was greater vs. cisgender women; however, there was no difference in risk between transgender women and cisgender men. There were no between-group differences in ischemic stroke, according to researchers.

In separate analyses that followed transgender women who initiated HT during follow-up, researchers observed more pronounced differences in risk for VTE and ischemic stroke. Evidence was insufficient to allow for conclusions regarding any risk among transgender men.

“Vigilance, in terms of monitoring side effects, should continue with these patients over the years as they are being treated,” Goodman said. “It’s important not to relax after 2 or 3 years if you don’t see a vascular event. And that goes against the pattern we observe in cisgender women undergoing hormone replacement therapy. We really don’t have a good answer as to what drives this risk. For the next round of analysis, we will need more people with longer follow-up, looking at risk by dose and route of administration. There’s good a priori reason to think that route of administration may be important. There could also be a dose-escalation risk that explains this pattern.” – by Regina Schaffer

Disclosures: The Patient-Centered Outcomes Research Institute (PCORI) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development funded this study. The authors report no relevant financial disclosures.