Females are disproportionately affected by gastroparesis. Sex hormones play a significant role. The aim of this study was to investigate the effects of combined oral contraceptives (COC) on the development of gastroparesis and its related symptoms, medication use, and diagnostic testing in pre-menopausal women. A population-based cohort study was conducted utilizing the TriNetX platform. The study group included pre-menopausal women. The effect of developing gastroparesis at least 30 days after initiating COC was assessed by comparing it to pre-menopausal women not on contraceptive therapy. A 1:1 propensity score matching was performed to adjust for age, race, ethnicity, body mass index, and diabetes mellitus. Exclusion criteria included upper gut and bariatric surgery, functional dyspepsia, cyclic vomiting syndrome, gastro-esophageal reflux disease, irritable bowel syndrome, cannabis dependence and opiate use. Odds ratios with 95 % confidence intervals were calculated. P-value <0.05 was considered statistically significant. After propensity matching, 1,370,274 patients were included in the study for each cohort. A total of 1,050 pre-menopausal women developed gastroparesis at least 30 days after being prescribed COC compared to 815 pre-menopausal women not prescribed COC (OR 1.29 [1.176-1.412] p-value<0.0001). These associations persisted in sensitivity analysis over 5 years (OR 1.31 [1.097-1.575] p-value=0.0029). COC were associated with increased gastrointestinal symptoms including early satiety (OR 2.31 [2.08-2.577] p-value<0.0001) and prokinetic medications including metoclopramide (OR 1.30 [1.285-1.316] p-value<0.0001). Gastrointestinal diagnostic tests including esophagogastroduodenoscopy (OR 1.611 [1.561-1.663] p-value<0.0001) and gastric emptying scintigraphy (OR 1.89 [1.717-2.085] p-value<0.0001) were more likely to be performed in pre-menopausal women who were prescribed COC. COC is associated with an increased risk of developing gastroparesis, which persists over time. Furthermore, COC is associated with developing gastrointestinal symptoms, increased prokinetic usage, and diagnostic testing.
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