Higher Rates of Certain Autoimmune Diseases in Transgender and Gender Diverse Youth

Background Inflammatory bowel disease (IBD) is a global healthcare problem that affects around 3 million people in the United States. Although the impact of gender-affirming hormone therapy (GAHT) on IBD severity has been studied in cisgender patients, there is currently no literature on the impact of exogenous hormone therapy (HT) in transgender and nonbinary (TGNB) individuals. Methods We conducted a retrospective chart review of TGNB adults diagnosed with IBD and treated with HT for gender dysphoria at Johns Hopkins Hospital (2015-2022). We aimed to determine whether the use of GAHT was associated with subsequent increase in IBD severity. We compared the incidence of flares before vs after GAHT. Results Twenty-two patients were analyzed. More than half (59%) of them were assigned female at birth, identified as transmen, and underwent masculinizing HT. Their median (interquartile range) age was 30 (25-36) years. More patients had Crohn’s disease compared with ulcerative colitis (13 [59.1%] vs 9 [40.9%], P = .23) with a median IBD duration of 6.2 (1.8-12.3) years. Nine (41%) patients were on biologics. Of 15 patients on HT, 8 (36.3%) experienced at least one flare. Most of them were treated with steroids (66.7%), and 6 (40%) required hospital or emergency room admission. The proportion of patients who flared after GAHT was similar to that before GAHT: 9 (60%) vs 8 (53.3%), P = 1.0. Conclusions GAHT was not associated with increased incidence of flares. Larger prospective randomized studies are needed to confirm our findings and understand the interaction between GAHT and IBD in TGNB individuals.

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Independent effects of testosterone, estradiol, and sex chromosomes on gene expression in immune cells of trans- and cisgender individuals

Harris,

Whitfield,

Blanton

et al. 2024

Preprint

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The origins of sex differences in human disease are elusive, in part because of difficulties in separating the effects of sex hormones and sex chromosomes. To separate these variables, we examined gene expression in four groups of trans- or cisgender individuals: XX individuals treated with exogenous testosterone (n=21), XY treated with exogenous estradiol (n=13), untreated XX (n=20), and untreated XY (n=15). We performed single-cell RNA-sequencing of 358,426 peripheral blood mononuclear cells. Across the autosomes, 8 genes responded with a significant change in expression to testosterone, 34 to estradiol, and 32 to sex chromosome complement with no overlap between the groups. No sex-chromosomal genes responded significantly to testosterone or estradiol, but X-linked genes responded to sex chromosome complement in a remarkably stable manner across cell types. Through leveraging a four-state study design, we successfully separated the independent actions of testosterone, estradiol, and sex chromosome complement on genome-wide gene expression in humans.

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Higher Rates of Certain Autoimmune Diseases in Transgender and Gender Diverse Youth

Cited by 3 publications

References 98 publications

A developmental framework for understanding the influence of sex and gender on health: Pediatric pain as an exemplar

A developmental framework for understanding the influence of sex and gender on health: Pediatric pain as an exemplar

The Impact of Hormone Therapy on Inflammatory Bowel Disease in Transgender and Nonbinary Individuals

Independent effects of testosterone, estradiol, and sex chromosomes on gene expression in immune cells of trans- and cisgender individuals

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