GAHT & IBD

July 28, 2025

Issue 15

Clinical Question

What is the risk of inflammatory bowel disease flare following initiation of gender-affirming hormone therapy in transgender and gender diverse adults?

Editor’s Bottom Line

These data associate use of testosterone by transgender and gender diverse adults with an increase risk of flare of inflammatory bowel disease. Clinicians may seek to initiate masculinizing hormone therapy when disease in in remission.

Reference

Bennett A, Field J, Newman KL, et al. Gender-Affirming Hormone Therapy and Risk of Inflammatory Bowel Disease Flare in Transgender and Gender Diverse Adults. Am J Gastroenterol. Epub ahead of print May 16, 2025. https://journals.lww.com/ajg/abstract.aspx

Synopsis

This multicenter retrospective study examined the impact of gender-affirming hormone therapy (GAHT) on IBD flare rates in transgender and gender diverse adults across five IBD centers in the United States.

The study included 85 transgender and gender diverse adults with IBD who initiated GAHT. The cohort comprised 42 (49.4%) transgender women, 28 (32.9%) transgender men, and 15 (17.6%) gender diverse individuals. Forty-seven patients (55.3%) had Crohn’s disease and 38 (44.7%) had ulcerative colitis. The median age at GAHT initiation was 23.5 years (range 18–60). Approximately 59% of individuals were receiving advanced IBD therapy at the time of GAHT initiation.

Forty-six individuals (54.1%) received feminizing therapy with estrogen and 39 (45.9%) received masculinizing therapy with testosterone. Among those receiving estrogen therapy, 58% received oral estradiol and of patients receiving testosterone therapy, 63% used injectable testosterone. At GAHT initiation, 53% of individuals were in clinical IBD remission, while 38.8% had active IBD and disease status was unknown in 8.2%.

In the year before GAHT initiation, 49.4% experienced an IBD flare—defined as need for corticosteroids, IBD-associated emergency department visit or hospitalization or IBD medication change for disease activity—compared to 37.6% in the year after GAHT (p=0.06).

While there was no statistically significant overall difference in flare rates before and after GAHT initiation, univariate analysis showed that factors associated with a flare in the year after GAHT start included active IBD symptoms at GAHT initiation (58% vs. 24% in remission; p=0.003) and use of testosterone therapy (53% for testosterone vs. 26% with estrogen; p=0.01).

Multivariable analysis adjusting for age and IBD type confirmed that individuals with active IBD at GAHT initiation were more likely to flare in the year after starting GAHT (adjusted Odds Ratio [aOR]: 5.1; 95% Confidence Interval [CI], 1.7–15.2; p=0.002) as were those who received testosterone vs. estrogen (aOR: 3.1; 95% CI, 1.2–8.1; p=0.015).

Analysis limited to only patients in clinical remission at GAHT initiation also confirmed that those receiving testosterone were significantly more likely to experience flare in the year after GAHT start compared to those receiving estrogen (38% vs. 14%; p=0.046). For patients with active IBD at GAHT start, there was a numerical trend toward increased flare rates with testosterone versus estrogen (73% vs. 44%; p=0.09).

There were no significant differences in C-reactive protein or fecal calprotectin levels before and after GAHT initiation and, among the 14 individuals who had colonoscopy before and after hormone start, only 14% had worsening endoscopic inflammation.

There were minimal complications related to GAHT, with 2.4% experiencing blood clots after starting GAHT, including one deep venous thrombosis in a transgender woman receiving estrogen and one pulmonary embolism in a transgender man receiving testosterone. Both patients had active IBD at hormone initiation and required steroids in the year before and after hormone start.

Details

Study Design: Multicenter retrospective cohort study
Funding: Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery
Allocation: Not applicable
Setting: Multicenter
Level of Evidence: 2b