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April 29, 2020
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Gender-affirming HT poses no hypertension risk

Among a large cohort of transgender adults prescribed gender-affirming hormones, higher levels of cross-sex hormones did not increase the odds of hypertension, and hypertension diagnoses were fewer among transgender women who were ever prescribed progestins, according to data published in Transgender Health.

However, more recent use of progestins —particularly in the form of medroxyprogesterone acetate — may be associated with increased odds of thromboembolism among transgender women.

We were able to look at a fairly large cohort of transgender patients in the U.S. and found that, across a variety of regimens, gender-affirming hormones were not associated with increased cardiovascular risk for transmen, though the picture is a little more complicated for transwomen,” Maria Pyra, MPH, PhD, research assistant professor in the section of infectious diseases and global health at the University of Chicago and senior epidemiologist at Howard Brown Health in Chicago, told Healio. “We were reassured that there was no association between estrogens and thromboembolisms for transwomen; this suggests that safer regimens have been successfully adopted. However, the potential for recent progestin prescriptions to be associated with thromboembolisms is an important question that needs to be addressed.”

In a retrospective study, Pyra and colleagues assessed data on hormone levels from 2,509 transgender women (median age, 30 years; age range, 20-70 years; median time since first hormone prescription, 2.6 years) and 1,893 transgender men (median age, 26 years; age range, 20-67 years; median time since first hormone prescription, 2.2 years) collected between October 2006 and October 2018 from the electronic health records of patients at Howard Brown Health in Chicago. All patients with a history of HT had a first prescription at least 6 months before data analysis. The researchers used the most recent hormone levels within a year of a hypertension or thromboembolism diagnosis or the end of the study.

Among a large cohort of transgender adults prescribed gender-affirming hormones, higher levels of cross-sex hormones did not increase the odds of hypertension, and hypertension diagnoses were fewer among transgender women who were ever prescribed progestins.
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Among the transgender men, 99.6% had ever had a prescription for testosterone from the clinic, and 96% of these were recent. Researchers observed no statistically significant association between testosterone prescription and hypertension for the 1.5% of transgender men exposed to HT with a hypertension diagnosis.

Among the transgender women, 99% had ever had a prescription for estrogen, 94.2% had ever had a prescription for an androgen antagonist/finasteride, and 29.8% had ever had a prescription for progestin. Higher levels of endogenous testosterone were associated with increased risk for hypertension in models adjusted for BMI (adjusted OR = 1.16; 95% CI, 1.01-1.33). No statistically significant association was observed between estradiol level and hypertension for the 2.1% of transgender women exposed to HT with a hypertension diagnosis. A progestin prescription was associated with lower odds of hypertension (aOR = 0.36; 95% CI, 0.15-0.87).

Researchers observed no associations between estrogen or testosterone level or between a prescription for estradiol or an androgen antagonist and thromboembolism for the 0.8% of transgender women exposed to HT with a thromboembolism diagnosis. A recent prescription for progestin was associated with increased odds for thromboembolism in adjusted models (aOR = 2.95; 95% CI, 1.02-8.57) with a greater association for medroxyprogesterone acetate than for micronized progesterone, according to the researchers.

“However, the CIs were very wide and the sample size is too small to be conclusive,” the researchers wrote.

Current standard gender-affirming hormone therapy regimens estradiol and an anti-androgen for feminization or testosterone for masculinization appear to be safe,” Pyra said. “However, more research is needed about the short-term effects and safety profile of progestins, in particular medroxyprogesterone acetate in transwomen on hormone therapy.”