{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T13:22:36Z","timestamp":1771334556925,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,2,5]],"date-time":"2023-02-05T00:00:00Z","timestamp":1675555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>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\u2010based contraceptive, on GERD. We aimed to determine the effect of Nexplanon and COC on GERD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a population\u2010based analysis using the IBM Explorys national database (1999\u20132021). The study group included premenopausal women, defined as women less than 50\u2009years of age while excluding the diagnosis of menopause. The effect of Nexplanon and COC on GERD (at least 30\u2009days 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>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 (<jats:italic>n<\/jats:italic>\u00a0=\u00a0565,880), 690 patients developed GERD at least 30\u2009days after being on Nexplanon (OR\u00a0=\u00a00.55, 95% CI [0.51\u20130.59], <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and 280 developed GERD after COC (1.93, [1.71\u20132.18], <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). 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\u20131.20], <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), and Nexplanon was protective against GERD (0.90, [0.89\u20130.92], <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). 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\u00a0=\u00a01.02, 95% CI [0.99\u20131.04], <jats:italic>p<\/jats:italic>\u00a0=\u00a00.08) when compared to those not on contraceptives.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.14542","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T06:20:26Z","timestamp":1675664426000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The effect of combined oral contraceptives and Nexplanon on gastroesophageal reflux disease in premenopausal women: A nationwide database analysis"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1307-4837","authenticated-orcid":false,"given":"Sherif","family":"Saleh","sequence":"first","affiliation":[{"name":"Department of Internal Medicine MetroHealth Medical Center and Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2089-7607","authenticated-orcid":false,"given":"Benjamin D.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine MetroHealth Medical Center and Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Trujillo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine MetroHealth Medical Center and Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Thomas","sequence":"additional","affiliation":[{"name":"Center for Health Care Research and Policy MetroHealth Medical Center and Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4807-3052","authenticated-orcid":false,"given":"Ronnie","family":"Fass","sequence":"additional","affiliation":[{"name":"Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology MetroHealth Medical Center and Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,2,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-304269"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.32978"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.01.009"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(79)90797-x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2013.07.006"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(76)80193-X"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2007.05.006"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.1999.01128.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2022.01.058"},{"key":"e_1_2_9_11_1","unstructured":"IBM explorys\u2010accelerating insights from real\u2010world evidence.2022. 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