Clinical Presentation and Diagnostic Pathways of Genital Graft-Versus-Host Disease by Prior Local Estrogen Exposure

Objectives: To investigate whether women with prior local estrogen therapy (LET) differ in the clinical presentation, diagnostic pathway, disease severity, and longitudinal course of genital chronic graft-versus-host disease (cGvHD). Secondary analyses explored associations between postdiagnosis treatments and disease severity. Methods: We conducted an ambispective cohort study of women diagnosed with genital cGvHD after allogeneic hematopoietic stem cell transplantation at a tertiary referral center (2013–2023). Women were categorized by prior LET exposure. Clinical presentation, anatomical involvement, diagnostic pathway, and disease severity (2005 NIH criteria) were assessed at diagnosis. Disease severity over 24 months was analyzed using generalized estimating equations. Treatment analyses were exploratory. Results: Thirty-six women were included: 18 (50%) had prior LET. Prior LET was not associated with lower disease severity at diagnosis. Women with prior LET were more frequently diagnosed during follow-up, whereas half of those without prior LET were referred because of genital symptoms or clinical suspicion ( p =.007), indicating distinct diagnostic pathways. Isolated vulvar involvement was more frequent without prior LET, whereas combined vulvovaginal involvement was more common with prior LET. Disease severity improved during follow-up, but exploratory analyses found no significant associations between postdiagnosis treatments and disease severity. Conclusions: Prior LET was not associated with lower genital cGvHD severity at diagnosis. Instead, differences between women with and without prior LET suggest distinct clinical care pathways and patterns of disease recognition rather than a biological effect of estrogen therapy. These findings support specialized gynecologic assessment and longitudinal multidisciplinary follow-up after allogeneic hematopoietic stem cell transplantation.