The retrospective study evaluated 700 patients (425 women, 275 men) with NIU enrolled from 22 centers between 2020 and 2025, applying age-based proxies for reproductive life stages (pre-pubertal, early puberty, late puberty, reproductive, perimenopausal, and post-menopausal).
Across the cohort, flare frequency peaked in early puberty, showing both increased relapse numbers and higher exposure to conventional and biologic DMARDs. Pediatric patients demonstrated more severe anterior segment inflammation, reflected in higher anterior chamber cell (ACC) grades and a greater need for systemic immunosuppression. These findings mirror prior evidence that puberty is a period of heightened immune instability in conditions such as JIA-associated uveitis.
A second, female-specific rise in inflammatory activity emerged during perimenopause. When analyzed by sex, a statistically significant interaction indicated that this relapse peak occurred exclusively in women. This aligns with established immunological changes linked to fluctuating estrogen, progesterone, and cortisol levels during the menopausal transition — periods known to promote inflammatory rebounds in other autoimmune diseases.
Differences across reproductive stages were seen primarily in the anterior segment. ACC and flare grades varied significantly across life stages, while vitreous haze and new posterior signs did not. These findings suggest that anterior uveitis may be more sensitive to hormonal modulation, whereas intermediate/posterior disease may follow more stable or slower-evolving inflammatory pathways.
The investigators highlight several takeaways from their findings:
Adolescents require intensified monitoring – early puberty should trigger closer follow-up intervals and careful therapeutic planning, as rapid hormonal shifts may destabilize disease previously controlled in late childhood.
Women in their mid-40s to mid-50s may benefit from proactive counseling – perimenopause appears to carry a measurable relapse risk that may justify anticipatory adjustments in therapy or follow-up frequency.
Pregnancy and postpartum patterns remain complex – although data were limited, trends echoed prior studies that indicate reduced activity in late pregnancy and increased risk postpartum.
This registry-based analysis provides a lifespan perspective on uveitis behavior in women, and supports the incorporation of the reproductive life stage into routine patient counseling and risk stratification. While prospective studies with hormonal measurements are still needed, the message is clear: endocrine transitions represent critical inflection points in the uveitis course, and clinicians may improve outcomes by anticipating these physiologic shifts.
