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10-07-2024 | Metabolic Disease and Nutrition | News

Testosterone use may increase metabolic syndrome risk in transmasculine individuals

Author: Laura Cowen

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medwireNews: Gender-affirming hormone treatment (GAHT) with testosterone may be associated with development and progression of metabolic syndrome, suggests a longitudinal study of US veterans.

Writing in JAMA Network Open, Leila Hashemi (VA Greater Los Angeles Health Care System, California) and co-authors note that sex hormones are known to influence metabolic syndrome risk, but data regarding the longitudinal effects of GAHT are lacking.

To address this, Hashemi and team investigated whether estradiol or testosterone, given as GAHT, are associated with changes in metabolic syndrome z-scores. The study included 1290 participants (mean age 41.3 years) registered in the Veterans Health Administration national database between 2006 and 2019. Of these, 645 were transgender veterans receiving GAHT and 645 were cisgender veterans matched by age, race, ethnicity, and index visit who were not receiving exogenous sex hormone treatment.

Among the individual components of metabolic syndrome, the researchers found that transmasculine participants (n=151) had the greatest mean increase in BMI, from 27.7 kg/m2 in the 13-year period before GAHT initiation to 30.0 kg/m2 up to 15 years after this date, with the difference statistically significant.

Transmasculine participants also had significantly higher mean systolic blood pressure (SBP) after than before GAHT initiation (123.5 vs 117.5 mmHg), as well as higher blood glucose levels (117.5 vs 92.7 mg/dL; 6.52 vs 5.14 mmol/L) and log triglyceride levels (4.72 vs 4.44 mg/dL), and significantly lower mean high-density lipoprotein (HDL) levels (49.4 vs 53.1 mg/dL).

For transfeminine individuals (n=494), there was no significant change in mean BMI after GAHT compared with before (30.0 vs 29.6kg/m2) and no significant change in SBP (126.2 vs 127.2 mmHg). Mean blood glucose levels increased significantly (116.5 vs 103.8 mg/dL; 6.46 vs 5.76 mmol/L) as did mean HDL level (49.9 vs 42.6 mg/dL), whereas log triglyceride levels decreased significantly in this group (4.88 vs 4.97 mg/dL).

Among the cisgender males (n=365), BMI, SBP, blood glucose, and HDL levels all increased significantly from before to after the index date, while triglyceride levels remained stable. For cisgender females (n=280), BMI, blood glucose, and HDL levels all increased significantly, while SBP and log triglyceride levels were stable.

Together, these findings mean that transmasculine veterans had the greatest percentage increase in mean z-scores for metabolic syndrome.

Specifically, mean z-score increased by a significant 298% among transmasculine veterans after versus before beginning GAHT. Cisgender females had the second greatest increase, at a significant 108.3%, followed by a significant 49.3% increase for cisgender males, and a nonsignificant increase of 3.0% for transfeminine individuals.

Hashemi et al comment: “Our hypothesis that sex hormones are associated with metabolic syndrome appeared to be valid in this cohort with the exception of cisgender females.”

This is because the longitudinal change in cisgender females’ z-score was greater than that for transfeminine and cisgender male veterans, which “is not fully consistent with our hypothesis that ovarian sex hormones would be protective.” They note cisgender female veterans generally have more complex comorbidities than cisgender female civilians, which “may place them at a higher risk of worse clinical outcomes.”

Nonetheless, the researchers conclude: “Our data from this cohort study indicated that in both cisgender and transgender individuals, estradiol was associated with reduced metabolic syndrome risk, whereas testosterone was associated with increased risk.”

They add: “These findings are relevant for the management of metabolic syndrome risk factors in cisgender and transgender individuals. It is also important to note that exogenous sex hormones are not equivalent to endogenous sex hormones, nor is the body in which they operate the same as one never exposed to the opposing sex hormones.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group

JAMA Netw Open 2024; 7: e2419696

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