Reproductive life stages and female sex-specific patterns in uveitis activity: data from the AIDA Network Uveitis registry

Objective or purpose: To investigate whether non-infectious uveitis (NIU) activity varies across reproductive life stages (RLS) according to sex. Design: Observational, retrospective, cross-sectional registry-based study. Subjects, participants, and/or controls: The study recruited female patients with NIU (regardless of anatomical location or underlying etiology) as the main study group and male patients as controls to allow sex-based comparisons. They were enrolled in the AIDA Network Uveitis Registry between 2020 and 2025. Methods, intervention, or testing: RLS (pre-puberal, early puberty, late puberty, reproductive, perimenopause, and post-menopausal) were approximated using age intervals derived from epidemiological data. Study outcomes were flare frequency, anterior chamber cells (ACC), anterior chamber flare, vitreous haze, new posterior segment inflammatory signs, and immunosuppressive treatment (IST) exposure. Results: 425 female and 275 male patients were included. Median (IQR) relapse number in 12 months was 0.8 (1.3) [min 0.0 - max 2.0] in pre-puberty, 1.0 (2.0) [0.0 - 5.0] in early puberty, 0.0 (1.0) [0.0 - 5.0] in late puberty, 0.5 (1.0) [0.0 - 8.0] in reproductive age, 1.0 (1.0) [0.0 - 10.0] in perimenopause, and 0.5 (1.0) [0.0 - 7.5] in post-menopause (p= 0.014). There was a statistically significant interaction between RLS and sex (p= 0.044), with a perimenopausal peak retained only in women. In subjects with active anterior involvement, differences in the distribution of ACC grades among RLS were observed, with a peak in pre-puberty and early puberty (p= 0.004). Proportions of subjects receiving IST were higher in pre-puberty and puberty than in the remaining RLS (p= 0.012). Conclusions: RLS are clinically relevant modifiers of uveitis activity and should guide patient education, risk stratification, and therapy. Early puberty and perimenopause increase relapse risk; pediatric cases show more severe anterior inflammation and require more systemic IST.