{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:02:33Z","timestamp":1790928153302,"version":"4.1.0"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T00:00:00Z","timestamp":1623283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wilfred and Joyce Posluns Chair in Women\u2019s Brain Health and Aging from the Posluns Family Foundation","award":["WJP-150643"],"award-info":[{"award-number":["WJP-150643"]}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008914","name":"Ontario Brain Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008914","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Alzheimer\u2019s Society of Canada","award":["WJP-150643"],"award-info":[{"award-number":["WJP-150643"]}]},{"name":"Canadian Institutes of Health Research (CA) Masters Award"},{"name":"Jacqueline Ford Gender and Health Fund"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Despite the widespread use of oral contraceptives (OCs), and the well-documented influence of estrogens, notably 17\u03b2-estradiol (E2), on cognition, research relating OCs to working memory is limited and mixed. Two factors may contribute to these mixed findings: 1) pharmacokinetics of oral contraceptives, which drive fluctuations in synthetic hormone levels; and 2) genetic polymorphisms related to dopamine degradation and working memory, which interact with E2. This research investigated whether the pharmacokinetics of oral contraceptives, in concert with the single nucleotide polymorphism (<jats:italic>Val<\/jats:italic><jats:sup><jats:italic>158<\/jats:italic><\/jats:sup><jats:italic>Met<\/jats:italic>; rs4680) of the catechol-o-methyltransferase gene (<jats:italic>COMT<\/jats:italic>), influence working memory performance.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>University-age women taking and not taking OCs were tested for working memory and genotyped for <jats:italic>COMT<\/jats:italic>. If they were not taking OCs (n = 62), sessions occurred in the early follicular (low E2) and late follicular (high E2) phase. If they were taking OCs (n = 52), sessions occurred 1\u20132 hours after (high ethinyl estradiol, EE) and ~24 hours after (low EE) pill ingestion. Working memory was tested using the N-back, AX-CPT, Digit Span, and Digit Ordering Tasks. Data were analyzed using multilevel models with estrogen condition, <jats:italic>COMT<\/jats:italic>, and group as predictors, controlling for mood and practice effects.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>For women taking OCs, time of pill ingestion did not influence performance. However, the subgroup with <jats:italic>COMT val\/val<\/jats:italic> (low dopamine) were less accurate on 2-back lure trials than those with <jats:italic>COMT met\/met<\/jats:italic> (high dopamine). For women not taking OCs, cycle phase moderated <jats:italic>COMT<\/jats:italic>\u2019s influence on lure accuracy. When compared, women taking OCs had higher AX-CPT proactive control indices than those not taking OCs.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>These findings suggest that oral contraceptives are not detrimental for young women\u2019s working memory and that they may increase proactive control. The more pronounced effects of <jats:italic>COMT<\/jats:italic> in women taking OCs suggests that, in women taking OCs, suppressed endogenous E2\u2013not fluctuating EE levels\u2013may be more relevant for working memory. Future studies are needed to differentiate effects of endogenous versus synthetic estrogens on working memory.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0252807","type":"journal-article","created":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T23:30:44Z","timestamp":1623367844000},"page":"e0252807","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["Do oral contraceptives affect young women\u2019s memory? Dopamine-dependent working memory is influenced by COMT genotype, but not time of pill ingestion"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9087-9199","authenticated-orcid":true,"given":"Laura","family":"Gravelsins","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Duncan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian","family":"Einstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,6,10]]},"reference":[{"key":"pone.0252807.ref001","first-page":"1","article-title":"Novel drug delivery methods for improving efficacy of endometriosis treatments","volume":"27","author":"S Garzon","year":"2020","journal-title":"Expert Opin Drug Deliv"},{"key":"pone.0252807.ref002","volume-title":"Beyond birth control: the overlooked benefits of oral contraceptive pills","author":"RK Jones","year":"2011"},{"key":"pone.0252807.ref003","volume-title":"Oral contraceptive use among women aged 15 to 49: results from the Canadian Health Measures Survey","author":"M Rotermann","year":"2015"},{"key":"pone.0252807.ref004","volume-title":"NCHS Data Brief, no. 327","author":"K Daniels","year":"2018"},{"key":"pone.0252807.ref005","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.neubiorev.2016.03.024","article-title":"Why estrogens matter for behavior and brain health","volume":"76","author":"LA Galea","year":"2017","journal-title":"Neuroscience & Biobehavioral Reviews"},{"issue":"1","key":"pone.0252807.ref006","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/0278-2626(90)90058-V","article-title":"Variations in sex-related cognitive abilities across the menstrual cycle","volume":"14","author":"E Hampson","year":"1990","journal-title":"Brain Cogn"},{"key":"pone.0252807.ref007","first-page":"104488","article-title":"Sex difference or hormonal difference in mental rotation?","author":"D Peragine","year":"2019","journal-title":"The influence of ovarian milieu. 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