{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T06:26:45Z","timestamp":1790922405384,"version":"4.1.0"},"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T00:00:00Z","timestamp":1618963200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS082432"],"award-info":[{"award-number":["R01NS082432"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001068","name":"Dana Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001068","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The effects of hormonal contraceptives on structural features of the hypothalamus and pituitary are incompletely understood. One prior study reported microstructural changes in the hypothalamus with oral contraceptive pill (OCP) use. However, effects on hypothalamic volume have not been reported. One prior study reported volumetric changes in the pituitary. However, this study was limited by including participants evaluated for neurological symptoms. We sought to determine if OCP use is associated with alteration of hypothalamic or pituitary volume. High-resolution 3T MRI was performed for a prospective cohort of 50 healthy women from 2016 to 2018, which comprised 21 OCP users (age, 19\u201329) and 29 naturally cycling women (age, 18\u201336). Participants were excluded if they were pregnant or had significant medical conditions including neurological, psychiatric, and endocrine disorders. After confirming reliability of the image analysis techniques, 5 raters independently performed manual segmentation of the hypothalamus and semi-automated intensity threshold-based segmentation of the pituitary using ITK-SNAP. Total intracranial volume was estimated using FreeSurfer. A general linear model tested the association of OCP use with hypothalamic and pituitary volumes. Hypothalamic (B = -81.2 \u00b1 24.9, p = 0.002) and pituitary (B = -81.2 \u00b1 38.7, p = 0.04) volumes in OCP users were smaller than in naturally cycling women. These findings may be related to interference with known trophic effects of sex hormones and suggest a structural correlate of central OCP effects.<\/jats:p>","DOI":"10.1371\/journal.pone.0249482","type":"journal-article","created":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T17:36:22Z","timestamp":1619026582000},"page":"e0249482","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":27,"title":["Oral contraceptive use is associated with smaller hypothalamic and pituitary gland volumes in healthy women: A structural MRI study"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2171-6641","authenticated-orcid":true,"given":"Ke Xun","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandie","family":"Worley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Foster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Edasery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shima","family":"Roknsharifi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe","family":"Ifrah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Lipton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,4,21]]},"reference":[{"key":"pone.0249482.ref001","article-title":"Combination estrogen-progestin oral contraceptives","author":"DB Petitti","year":"2003","journal-title":"New England Journal of Medicine"},{"key":"pone.0249482.ref002","author":"J Jones","year":"2013","journal-title":"Current contraceptive use in the united states, 2006\u20132010, and changes in patterns of use since 1995. Sexual Statistics: Select Reports from the National Center for Health Statistics"},{"key":"pone.0249482.ref003","article-title":"50 years of hormonal contraception\u2014time to find out, what it does to our brain","author":"BA Pletzer","year":"2014","journal-title":"Front Neurosci"},{"key":"pone.0249482.ref004","article-title":"Differential effects of androgenic and anti-androgenic progestins on fusiform and frontal gray matter volume and face recognition performance","author":"B Pletzer","year":"2015","journal-title":"Brain Res"},{"key":"pone.0249482.ref005","article-title":"Normal Sexual Dimorphism of the Adult Human Brain Assessed by In Vivo Magnetic Resonance Imaging","author":"JM Goldstein","year":"2001","journal-title":"Cereb Cortex"},{"key":"pone.0249482.ref006","article-title":"Regional sex differences in grey matter volume are associated with sex hormones in the young adult human brain","author":"AV Witte","year":"2010","journal-title":"Neuroimage"},{"key":"pone.0249482.ref007","article-title":"Hypothalamic Abnormalities in Schizophrenia: Sex Effects and Genetic Vulnerability","author":"JM Goldstein","year":"2007","journal-title":"Biol Psychiatry"},{"key":"pone.0249482.ref008","article-title":"Hypothalamus and pituitary volume in schizophrenia: A structural MRI study","author":"A Klomp","year":"2012","journal-title":"Int J Neuropsychopharmacol"},{"key":"pone.0249482.ref009","article-title":"Enlarged hypothalamic volumes in schizophrenia","author":"S Tognin","year":"2012","journal-title":"Psychiatry Res\u2014Neuroimaging"},{"key":"pone.0249482.ref010","article-title":"Menstrual cycle and hormonal contraceptive use modulate human brain structure","author":"B Pletzer","year":"2010","journal-title":"Brain Res"},{"key":"pone.0249482.ref011","article-title":"Regional gray matter volume differences and sex-hormone correlations as a function of menstrual cycle phase and hormonal contraceptives use","author":"T De Bondt","year":"2013","journal-title":"Brain Res"},{"key":"pone.0249482.ref012","article-title":"Oral contraceptive pill use is associated with localized decreases in cortical thickness","author":"N Petersen","year":"2015","journal-title":"Hum Brain Mapp"},{"key":"pone.0249482.ref013","article-title":"Reproducibility of hormone-driven regional grey matter volume changes in women using SPM8 and SPM12","author":"T De Bondt","year":"2016","journal-title":"Brain Struct Funct"},{"key":"pone.0249482.ref014","article-title":"Sex hormones and gender role relate to gray matter volumes in sexually dimorphic brain areas","author":"B. Pletzer","year":"2019","journal-title":"Front Neurosci"},{"key":"pone.0249482.ref015","article-title":"Sex steroid hormones-related structural plasticity in the human hypothalamus","author":"M Baroncini","year":"2010","journal-title":"Neuroimage"},{"key":"pone.0249482.ref016","article-title":"Volumetric analysis of the hypothalamus in huntington disease using 3T MRI: The IMAGE-HD study","author":"S Gabery","year":"2015","journal-title":"PLoS One"},{"key":"pone.0249482.ref017","article-title":"Detailed volumetric analysis of the hypothalamus in behavioral variant frontotemporal dementia","author":"M Bocchetta","year":"2015","journal-title":"J Neurol"},{"key":"pone.0249482.ref018","article-title":"Development and Evaluation of an Algorithm for the Computer-Assisted Segmentation of the Human Hypothalamus on 7-Tesla Magnetic Resonance Images","author":"S Schindler","year":"2013","journal-title":"PLoS One"},{"key":"pone.0249482.ref019","article-title":"Estrogen- and progesterone-mediated structural neuroplasticity in women: evidence from neuroimaging","author":"E Catenaccio","year":"2016","journal-title":"Brain Structure and Function"},{"key":"pone.0249482.ref020","article-title":"Female pituitary size in relation to age and hormonal factors","author":"AE Grams","year":"2010","journal-title":"Neuroendocrinology"},{"key":"pone.0249482.ref021","article-title":"Variability in the phases of the menstrual cycle","author":"RJ Fehring","year":"2006","journal-title":"JOGNN\u2014J Obstet Gynecol Neonatal Nurs"},{"key":"pone.0249482.ref022","article-title":"Volume deficits of subcortical nuclei in mood disorders: A postmortem study","author":"H Bielau","year":"2005","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"pone.0249482.ref023","article-title":"Changes in key hypothalamic neuropeptide populations in Huntington disease revealed by neuropathological analyses","author":"S Gabery","year":"2010","journal-title":"Acta Neuropathol"},{"key":"pone.0249482.ref024","article-title":"User-guided 3D active contour segmentation of anatomical structures: Significantly improved efficiency and reliability","author":"PA Yushkevich","year":"2006","journal-title":"Neuroimage"},{"key":"pone.0249482.ref025","article-title":"Serum estradiol in women ingesting combination oral contraceptive steroids","author":"DR Mishell","year":"1972","journal-title":"Am J Obstet Gynecol"},{"key":"pone.0249482.ref026","article-title":"Plasma hormone levels in women receiving new oral contraceptives containing ethinyl estradiol plus levonorgestrel or desogestrel","author":"UJ Gaspard","year":"1983","journal-title":"Contraception"},{"key":"pone.0249482.ref027","article-title":"The mechanism of action of hormonal contraceptives and intrauterine contraceptive devices","author":"R Rivera","year":"1999","journal-title":"American Journal of Obstetrics and Gynecology"},{"key":"pone.0249482.ref028","article-title":"Effects of progesterone and medroxyprogesterone on actin remodeling and neuronal spine formation","author":"AM Sanchez","year":"2013","journal-title":"Mol Endocrinol"},{"key":"pone.0249482.ref029","article-title":"Gonadal hormone modulation of dendrites in the mammalian CNS","author":"BM Cooke","year":"2005","journal-title":"Journal of Neurobiology"},{"key":"pone.0249482.ref030","article-title":"Membrane-initiated estradiol actions mediate structural plasticity and reproduction","author":"P Micevych","year":"2012","journal-title":"Frontiers in Neuroendocrinology"},{"key":"pone.0249482.ref031","article-title":"Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods","author":"C Barth","year":"2015","journal-title":"Frontiers in Neuroscience"},{"key":"pone.0249482.ref032","article-title":"Roles of estradiol and progesterone in regulation of hippocampal dendritic spine density during the estrous cycle in the rat","author":"CS Woolley","year":"1993","journal-title":"J Comp Neurol"},{"key":"pone.0249482.ref033","article-title":"Oral contraception: Mechanism of action","author":"RA Bronson","year":"1981","journal-title":"Clinical Obstetrics and Gynecology"},{"key":"pone.0249482.ref034","article-title":"To what extent do oral contraceptives influence mood and affect?","author":"KA Oinonen","year":"2002","journal-title":"Journal of Affective Disorders"},{"key":"pone.0249482.ref035","article-title":"Do the emotional side-effects of hormonal contraceptives come from pharmacologic or psychological mechanisms?","author":"SA Robinson","year":"2004","journal-title":"Med Hypotheses."},{"key":"pone.0249482.ref036","article-title":"Depression as a side effect of the contraceptive pill.","author":"J. Kulkarni","year":"2007","journal-title":"Expert Opinion on Drug Safety"},{"key":"pone.0249482.ref037","article-title":"Depression associated with combined oral contraceptives: A pilot study","author":"J Kulkarni","year":"2005","journal-title":"Australian Family Physician"},{"key":"pone.0249482.ref038","article-title":"Menstrual pain is associated with rapid structural alterations in the brain","author":"CH Tu","year":"2013","journal-title":"Pain"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0249482","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T17:36:23Z","timestamp":1619026583000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0249482"}},"subtitle":[],"editor":[{"given":"Niels","family":"Bergsland","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,4,21]]},"references-count":38,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0249482","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,21]]}}}