Background Autoimmune diseases are more common in women than in men. Generally, estrogen has an immunoenhancing effect, while testosterone has an immunosuppressive effect. However, it is not known whether gender-affirming hormone therapy in transgender people affects the risk of developing autoimmune diseases.

Methods All people initiating gender-affirming hormone therapy at the gender identity clinic in Amsterdam (1972-2018) without an autoimmune disease at start of hormone therapy, were included. The medical records were screened for the occurrence of autoimmune diseases during hormone therapy. In addition, the cohort was linked to a nationwide registry with diagnoses based on Diagnosis-Treatment-Combination codes (2012-2017), as not all people received check-ups at our clinic, and to compare with a control population. Standardized incidence ratios (SIR) were computed compared with the general population.

Results 2830 trans women and 1854 trans men were included. Median age at start of hormone therapy was 29 years (IQR 22-40) in trans women and 22 years (IQR 18-29) in trans men. Median follow-up time was 10 years (IQR 3-22, max 59) in trans women and 4 years (IQR 1-13, max 48) in trans men. 55 trans women and 48 trans men developed an autoimmune disease, after a median duration of hormone therapy of 7 years (IQR 2-17) and 5 years (IQR 1-12), respectively.

In the analyses with first autoimmune disease between 2012-2017, 25 trans women had an event, while 31 cases (SIR 0.81, 95%CI 0.52-1.16) were expected compared to cis men and 47 cases (SIR 0.54, 95%CI 0.35-0.77) compared to cis women. In trans men, 27 people had an event, while 15 cases were expected compared to cis men (SIR 1.81, 95%CI 1.19-2.55) and 23 cases compared to cis women (SIR 1.16, 95%CI 0.77-1.64).

Conclusion The risk of developing autoimmune diseases in trans women using gender affirming hormones was similar to the risk in cis men, whereas trans men had a similar risk as cis women. This implies that gender-affirming hormone therapy does not influence the risk of developing autoimmune diseases.