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Transgender individuals on cross-sex hormones may have a higher risk for acute cardiovascular events (ACVEs) a large retrospective study found.

Transfeminine individuals -- transitioning from male to female on estrogen therapy -- saw a significantly higher incidence of venous thromboembolism (VTE) when compared to either cisgender men or cisgender women, according to Michael Goodman, MD, MPH, of Emory University School of Public Health in Atlanta, and colleagues.

This risk for VTE in the transfeminine population increased further as time went on, the group reported in .

Compared to cisgender men, transfeminine persons had a 2-year risk difference of 4.1 (95% CI 1.6-6.7) per 1,000 persons for incidence of VTE, which then jumped to an 8-year risk difference of 16.7 (95% CI 6.4-27.5). Compared to cisgender women, transfeminine persons similarly had significantly 2-year and 8-year risk differences for experiencing VTE of 3.4 (95% CI 1.1-5.6) and 13.7 (95% CI 4.1-22.7) per 1,000 persons, respectively.

During the study period, transfeminine persons experienced VTE at around twice the rate when compared to both cisgender men and women:

• Transfeminine versus cisgender men: adjusted HR 1.9 (95% CI 1.4-2.7)
• Transfeminine versus cisgender women: aHR 2.0 (95% CI 1.4-2.8)

There was no corresponding risk among so-called transmasculine individuals, however, and rates of non-VTE cardiovascular events were not as strongly increased in the transfeminine population.

Although additionally confirmatory research is needed, Goodman and colleagues said these findings suggest a need for "increasing vigilance" to assess more of the longer-term outcomes of estrogen therapy for this population, particularly in regards to the vascular effects. "In the meantime, it is critical to keep in mind that the risk for ACVEs in this population must be weighed against the benefits of treatment," they recommended.

Drawing upon electronic medical records, the analysis included 2,842 transfeminine persons and 2,118 transmasculine persons with an known index date reflecting the first evidence of their transgender status. These individuals were then matched to 48,686 cisgender men and 48,775 cisgender women. Individuals in the cohort identified as male at birth prescribed feminizing drugs, including estradiol and spironolactone, while individuals identified as female at birth prescribed masculinizing drugs like testosterone were considered to be actively on hormone therapy.

Transfeminine persons also saw a slightly higher rate of ischemic strokes compared to both cisgender men (aHR 1.2, 95% CI 0.9-1.7) and cisgender women (aHR 1.9, 95% CI 1.3-2.6), although wasn't quite to the same extent as VTE risk.

Risk of myocardial infarction were also higher among transfeminine persons compared to cisgender women (aHR 1.8, 95% CI 1.1-2.9), although was generally similar to cisgender men (aHR 0.9, 95% CI 0.6-1.5).

But transmasculine persons -- transitioning from female to male on testosterone therapy -- did not see any significant differences in the rate of ACVEs compared to cisgender persons:

• VTE risk: aHR 1.6 (95% CI 0.9-2.9) [versus men]; aHR 1.1 (95% CI 0.6-2.1) [versus women]
• Ischemic stroke: aHR 1.1 (95% CI 0.6-2.0); aHR 1.3 (95% CI 0.7-2.5)
• Myocardial infarction: aHR 0.7 (95% CI 0.3-1.8); aHR 1.3 (95% CI 0.5-3.9)

Despite the lack of data to firmly say there was an elevated risk for transmasculine individuals or for heart events other than VTE in transfeminine individuals, the researchers warned than "interpreting these data as conclusive evidence of no association would be premature."

"In particular, our analyses suggest that transmasculine persons receiving testosterone may be at higher risk for myocardial infarction, but the number of events was insufficient because of the relatively young age of the transmasculine cohort," the group explained.

In order to further assess these potential risks, Goodman's group recommended future studies include an extended follow-up including more specific information of various treatments, such as different combinations of estradiol, progesterone and anti-androgens.

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