Metformin use linked to decreased risk of pelvic organ prolapse: insights from NHANES data

Preclinical evidence suggests that metformin may mitigate pelvic organ prolapse (POP) by altering the gene expression of human vaginal fibroblasts in a beneficial direction, but clinical validation is lacking. This study aimed to explore the association between metformin use and POP risk.

A cross-sectional analysis was conducted using the National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2012. POP was defined by self-reported vaginal bulging. Multivariable logistic regression models were used to assess associations between metformin use and POP in high-risk subgroups (hypertension or smoking), with adjustments for demographic, comorbidity, and obstetric/gynecologic factors. Associations between inflammatory and oxidative stress biomarkers and POP were also analyzed.

Three hundred and thirty of 9344 included women reported POP. Among 668 metformin users (630 with diabetes, 36 with prediabetes), 37 had POP. (Pre)diabetes was a risk factor for POP (OR = 1.52, P = 0.007). POP prevalence was lower in metformin-treated (pre)diabetes subgroups with hypertension (OR = 0.32, P = 0.045) or smoking (OR = 0.09, P = 0.022), independent of glycemic control, while thiazolidinediones, sulfonylureas, and insulin did not show the effect. C-reactive protein was higher in POP individuals (0.56 ± 0.98 mg/dL vs. 0.44 ± 0.73 mg/dL) and associated with POP (OR = 1.30, P = 0.020), especially in smokers (OR = 1.50, P = 0.002), but not in metformin users. Other biomarkers (systemic immune-inflammation index, ferritin, alkaline phosphatase, bilirubin, albumin, iron, γ-glutamyl transferase, and uric acid) showed no significant associations.

This is the first clinical study that suggests metformin may reduce POP risk in specific high-inflammatory subgroups, potentially via anti-inflammatory pathways. The findings warrant further prospective studies and mechanistic validation.