The effect of combined oral contraceptives and Nexplanon on gastroesophageal reflux disease in premenopausal women: A nationwide database analysis

Abstract

Background: Pregnancy, combined oral contraceptives (COC), and hormone replacement therapy have been reported to increase the risk of gastroesophageal reflux disease (GERD). To date, no study has evaluated the effect of Nexplanon, a commonly used progesterone-based contraceptive, on GERD. We aimed to determine the effect of Nexplanon and COC on GERD.

Methods: We performed a population-based analysis using the IBM Explorys national database (1999-2021). The study group included premenopausal women, defined as women less than 50 years of age while excluding the diagnosis of menopause. The effect of Nexplanon and COC on GERD (at least 30 days after Nexplanon/COC was initiated) was assessed by comparing it to premenopausal women who were not on contraceptives. Foregut surgery, esophageal dysmotility disorders, hiatal hernia, and delayed gastric emptying were excluded. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. A multivariate logistic regression analysis was conducted.

Key results: A total of 23,299,470 patients were identified as being premenopausal, of which 47,260 were on Nexplanon and 5480 on COCs. As compared to premenopausal women with GERD on no contraceptives (n = 565,880), 690 patients developed GERD at least 30 days after being on Nexplanon (OR = 0.55, 95% CI [0.51-0.59], p < 0.001) and 280 developed GERD after COC (1.93, [1.71-2.18], p < 0.001). A multivariate analysis accounting for Caucasian race, obesity, smoking, alcohol use, and NSAIDs revealed that COC is an independent risk factor for GERD (1.16, [1.12-1.20], p < 0.001), and Nexplanon was protective against GERD (0.90, [0.89-0.92], p < 0.001). Hydralazine was used as a control medication for data reliability. A total of 8420 patients developed GERD after initiating hydralazine, which was not statistically nor clinically significant (OR = 1.02, 95% CI [0.99-1.04], p = 0.08) when compared to those not on contraceptives.

Conclusions & inferences: Combined oral contraceptives is an independent risk factor for GERD, while Nexplanon has a limited protective effect. Further studies are needed to confirm the different effects on GERD of these two contraceptives.

Keywords: Nexplanon; combined oral contraceptives; estrogen; gastroesophageal reflux disease; progesterone.