Uro-gynecological disorders in women with non-celiac gluten/wheat sensitivity: a prospective study and response to a wheat-free diet

Background: Women with irritable bowel syndrome (IBS)-like symptoms frequently report uro-gynecological complaints without identifiable organic disease. A substantial proportion are diagnosed with non-celiac gluten/wheat sensitivity (NCGWS), a condition characterized by systemic manifestations. Aim: To prospectively assess the prevalence of uro-gynecological disorders in women with NCGWS and their evolution following a wheat-free diet (WFD). Methods: We enrolled 186 newly diagnosed NCGWS female patients and 403 age-matched healthy controls. A structured questionnaire evaluating menstrual, gynecological and urological symptoms was administered at baseline and repeated in NCGWS patients after 12 (T1) and 24 (T2) months of WFD. In a subgroup, cervical cytology was assessed before and after a 7-day open wheat challenge. Results: Uro-gynecological disorders were more prevalent in NCGWS patients than controls (54.3% vs 35.7%, P < 0.0001), across menstrual (41.9%vs 28.8%, P = 0.002), gynecological (46.8%vs 8.9%, P < 0.0001), and urological domains (39.2%vs 4.0%, P < 0.0001). Strict WFD adherence was associated with significant reduction in all symptom domains at 12 months (P < 0.0001), with further improvement at 24 months in adherent patients. Poor adherence was associated with symptom recurrence, particularly gynecological complaints (+88.9%, P = 0.008). Cytology showed mild-to-moderate inflammation with increased granulocytes, more evident after wheat reintroduction. Conclusions: Women with NCGWS reported more uro-gynecological complaints than controls. Long-term adherence to WFD was associated with clinical improvement, while wheat exposure might (re)trigger urogenital inflammation. Controlled studies are needed to establish the specificity of these associations and the therapeutic effect of wheat exclusion. Nevertheless, these findings highlight the relevance of dietary management and multidisciplinary approach in NCGWS patients.