(010) Vulvar Tissue Changes in Non-diabetic Women Receiving GLP-1 Receptor Agonists: A Global Federated Cohort Analysis

Abstract Introduction Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have become increasingly popular for weight management in non-diabetic women, with widespread media and patient forum discussions raising concerns about possible soft-tissue deflation or “sagging” in various body regions following rapid weight loss. While anecdotal accounts and social media reports have described perceived changes in vulvar appearance or tissue volume, there is no population-level evidence examining whether such effects correspond to clinically recognized vulvar atrophy or hypertrophy. Objective This study sought to objectively assess the incidence of vulvar soft-tissue disorders among non-diabetic women receiving GLP-1RAs using a large, real-world federated. Methods A retrospective cohort analysis was conducted using the TriNetX Global Collaborative Network, encompassing data from 162 health-care organizations and over 84 million patients. The study population included non-diabetic females aged 18 years or older. The exposure cohort consisted of women prescribed GLP-1RAs, identified by semaglutide (RxNorm 1 991 382) or other GLP-1 analogues (ATC A10BJ), totaling 618 362 individuals. The control group comprised 84 711 992 non-diabetic females with no GLP-1RA exposure. Patients with any diagnosis of diabetes mellitus (ICD-10 E08–E13 or E11) were excluded from both groups. The primary outcomes were coded diagnoses of vulvar atrophy or hypertrophy, identified using the following ICD-10 codes: N90.5 (atrophy of vulva), N90.6 (hypertrophy of vulva), N90.68 (unspecified hypertrophy of vulva), and N90.69 (other specified hypertrophy of vulva). Patients with pre-existing diagnoses were excluded to ensure new-onset events were captured. Incidence proportions were calculated and compared between groups using z-tests for two independent proportions, with statistical significance defined at α = 0.05. Results After exclusion of patients with pre-existing outcomes, 617 407 GLP-1RA users with a mean follow-up of 680 ± 656 days and 84 711 992 non-users were included in the final analysis. Vulvar atrophy or hypertrophy was diagnosed in 375 GLP-1RA users (0.061%) and 51 157 non-users (0.060%). The absolute risk difference was 0.001% (95% CI –0.02 to 0.02), with a two-tailed p-value of 0.97, indicating no statistically significant difference between the two cohorts. Conclusions In this global federated cohort of non-diabetic women, the incidence of vulvar atrophy or hypertrophy was exceedingly low (0.1%) and did not differ between GLP-1RA users and non-users. Further research incorporating imaging, histologic, and patient-reported data is warranted to explore potential subclinical or aesthetic tissue alterations following rapid weight loss. Disclosure No.