{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:34:37Z","timestamp":1760060077400,"version":"build-2065373602"},"reference-count":58,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"IVI Foundation Research Department","award":["1706-FIVI-048-PD","CIGE 2023"],"award-info":[{"award-number":["1706-FIVI-048-PD","CIGE 2023"]}]},{"name":"Generalitat Valenciana","award":["1706-FIVI-048-PD","CIGE 2023"],"award-info":[{"award-number":["1706-FIVI-048-PD","CIGE 2023"]}]},{"name":"Subvenciones concedidas a grupos de investigaci\u00f3n emergentes","award":["1706-FIVI-048-PD","CIGE 2023"],"award-info":[{"award-number":["1706-FIVI-048-PD","CIGE 2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Drug\u2013drug interactions (DDIs) may occur when two or more drugs are taken together, leading to undesired side effects or potential synergistic effects. Most clinical effects of drug combinations have not been assessed in clinical trials. Therefore, predicting DDIs can provide better patient management, avoid drug combinations that can negatively affect patient care, and exploit potential synergistic combinations to improve current therapies in women\u2019s healthcare. Methods: A DDI prediction model was built to describe relevant drug combinations affecting reproductive treatments. Approved drug features (chemical structure of drugs, side effects, targets, enzymes, carriers and transporters, pathways, protein\u2013protein interactions, and interaction profile fingerprints) were obtained. A unified predictive score revealed unknown DDIs between reproductive and commonly used drugs and their associated clinical effects on reproductive health. The performance of the prediction model was validated using known DDIs. Results: This prediction model accurately predicted known interactions (AUROC = 0.9876) and identified 2991 new DDIs between 192 drugs used in different female reproductive conditions and other drugs used to treat unrelated conditions. These DDIs included 836 between drugs used for in vitro fertilization. Most new DDIs involved estradiol, acetaminophen, bupivacaine, risperidone, and follitropin. Follitropin, bupivacaine, and gonadorelin had the highest discovery rate (42%, 32%, and 25%, respectively). Some were expected to improve current therapies (n = 23), while others would cause harmful effects (n = 11). We also predicted twelve DDIs between oral contraceptives and HIV drugs that could compromise their efficacy. Conclusions: These results show the importance of DDI studies aimed at identifying those that might compromise or improve their efficacy, which could lead to personalizing female reproductive therapies.<\/jats:p>","DOI":"10.3390\/pharmaceutics17081020","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T10:13:51Z","timestamp":1754475231000},"page":"1020","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Are We Considering All the Potential Drug\u2013Drug Interactions in Women\u2019s Reproductive Health? A Predictive Model Approach"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5844-4892","authenticated-orcid":false,"given":"Pablo","family":"Garcia-Acero","sequence":"first","affiliation":[{"name":"IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigaci\u00f3n Sanitaria La Fe, Av. Fernando Abril Martorell 106, Torre A, Planta 1, 46026 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ismael","family":"Henarejos-Castillo","sequence":"additional","affiliation":[{"name":"IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigaci\u00f3n Sanitaria La Fe, Av. Fernando Abril Martorell 106, Torre A, Planta 1, 46026 Valencia, Spain"},{"name":"Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, Av. Blasco Ib\u00e1\u00f1ez 15, 46010 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco Jose","family":"Sanz","sequence":"additional","affiliation":[{"name":"IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigaci\u00f3n Sanitaria La Fe, Av. Fernando Abril Martorell 106, Torre A, Planta 1, 46026 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7299-3660","authenticated-orcid":false,"given":"Patricia","family":"Sebastian-Leon","sequence":"additional","affiliation":[{"name":"IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigaci\u00f3n Sanitaria La Fe, Av. Fernando Abril Martorell 106, Torre A, Planta 1, 46026 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9496-6989","authenticated-orcid":false,"given":"Antonio","family":"Parraga-Leo","sequence":"additional","affiliation":[{"name":"IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigaci\u00f3n Sanitaria La Fe, Av. Fernando Abril Martorell 106, Torre A, Planta 1, 46026 Valencia, Spain"},{"name":"Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, Av. Blasco Ib\u00e1\u00f1ez 15, 46010 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1005-8727","authenticated-orcid":false,"given":"Juan Antonio","family":"Garcia-Velasco","sequence":"additional","affiliation":[{"name":"IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigaci\u00f3n Sanitaria La Fe, Av. Fernando Abril Martorell 106, Torre A, Planta 1, 46026 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0031-7545","authenticated-orcid":false,"given":"Patricia","family":"Diaz-Gimeno","sequence":"additional","affiliation":[{"name":"IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigaci\u00f3n Sanitaria La Fe, Av. Fernando Abril Martorell 106, Torre A, Planta 1, 46026 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"key":"ref_1","first-page":"627","article-title":"A Comparison of the Effects of Chlorothiazide and of Metolazone in the Treatment of Hypertension","volume":"51","author":"Hua","year":"1976","journal-title":"Clin. Sci. Mol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1002\/pds.1351","article-title":"Hospitalisations and Emergency Department Visits Due to Drug-Drug Interactions: A Literature Review","volume":"16","author":"Becker","year":"2007","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1021\/acs.molpharmaceut.5b00762","article-title":"QSAR Modeling and Prediction of Drug-Drug Interactions","volume":"13","author":"Zakharov","year":"2016","journal-title":"Mol. 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