{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T17:30:59Z","timestamp":1784309459766,"version":"3.55.0"},"reference-count":63,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T00:00:00Z","timestamp":1585094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Oral contraceptives (OCs) containing estrogen and progesterone analogues are widely used amongst reproductive-aged women, but their neurocognitive impact is poorly understood. Preliminary studies suggest that OCs improve verbal memory and that OCs with greater androgenic activity may improve visuospatial ability. We sought to explore the cognitive impact of OCs by assessing performance of OC users at different stages of the OC cycle, and comparing this performance between users of different OC formulations according to known androgenic activity. We conducted a prospective, observational trial of OC users, evaluating cognitive performance with CogState software on two occasions: days 7\u201310 of active hormonal pill phase, and days 3\u20135 of the inactive pill phase (coinciding with the withdrawal bleed resembling menstruation). Thirty-five OC users (18 taking androgenic formulations, 17 taking anti-androgenic) were assessed. Analysis by androgenic activity showed superior performance by users of androgenic OCs, as compared to anti-androgenic OCs, in visuospatial ability and facial affect discrimination tasks. A growing understanding of cognitive effects of OC progestin androgenicity may have implications in choice of OC formulation for individuals and in future OC development.<\/jats:p>","DOI":"10.3390\/brainsci10040194","type":"journal-article","created":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T13:10:47Z","timestamp":1585141847000},"page":"194","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Effects of Oral Contraceptive Androgenicity on Visuospatial and Social-Emotional Cognition: A Prospective Observational Trial"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5663-3419","authenticated-orcid":false,"given":"Caroline","family":"Gurvich","sequence":"first","affiliation":[{"name":"Monash Alfred Psychiatry Research Centre, Central Clinical School, Monash University and The Alfred Hospital, Melbourne, VIC 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabelle M.","family":"Warren","sequence":"additional","affiliation":[{"name":"Monash Alfred Psychiatry Research Centre, Central Clinical School, Monash University and The Alfred Hospital, Melbourne, VIC 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roisin","family":"Worsley","sequence":"additional","affiliation":[{"name":"Monash Alfred Psychiatry Research Centre, Central Clinical School, Monash University and The Alfred Hospital, Melbourne, VIC 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2604-2463","authenticated-orcid":false,"given":"Abdul-Rahman","family":"Hudaib","sequence":"additional","affiliation":[{"name":"Monash Alfred Psychiatry Research Centre, Central Clinical School, Monash University and The Alfred Hospital, Melbourne, VIC 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3388-7408","authenticated-orcid":false,"given":"Natalie","family":"Thomas","sequence":"additional","affiliation":[{"name":"Monash Alfred Psychiatry Research Centre, Central Clinical School, Monash University and The Alfred Hospital, Melbourne, VIC 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayashri","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"Monash Alfred Psychiatry Research Centre, Central Clinical School, Monash University and The Alfred Hospital, Melbourne, VIC 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"110","DOI":"10.5694\/mja11.11599","article-title":"Current contraceptive management in Australian general practice: An analysis of BEACH data","volume":"197","author":"Mazza","year":"2012","journal-title":"Med. J. Aust."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1001\/jamapsychiatry.2016.2387","article-title":"Association of hormonal contraception with depression","volume":"73","author":"Skovlund","year":"2016","journal-title":"JAMA Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.contraception.2014.03.015","article-title":"A systematic review of the impact of oral contraceptives on cognition","volume":"90","author":"Warren","year":"2014","journal-title":"Contraception"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1210\/er.2001-0016","article-title":"Estrogen and cognitive functioning in women","volume":"24","author":"Sherwin","year":"2003","journal-title":"Endocr. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1586\/eem.09.30","article-title":"Estrogen and cognitive functions","volume":"4","author":"Gasbarri","year":"2009","journal-title":"Expert Rev. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.yhbeh.2012.06.003","article-title":"Progesterone and neuroprotection","volume":"63","author":"Singh","year":"2013","journal-title":"Horm. Behav."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.cobeha.2018.03.002","article-title":"Regulation of cognitive function by androgens and estrogens","volume":"23","author":"Hampson","year":"2018","journal-title":"Curr. Opin. Behav. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"104711","DOI":"10.1016\/j.yhbeh.2020.104711","article-title":"Estrogenic regulation of memory: The first 50 years","volume":"121","author":"Luine","year":"2020","journal-title":"Horm. Behav."},{"key":"ref_9","unstructured":"Lezak, M.D. (2012). Neuropsychological Assessment, Oxford University Press. [5th ed.]."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1037\/a0025539","article-title":"Estrogen and cognitive functioning in women: Lessons we have learned","volume":"126","author":"Sherwin","year":"2012","journal-title":"Behav. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1101\/lm.918309","article-title":"Sex influences on the neurobiology of learning and memory","volume":"16","author":"Andreano","year":"2009","journal-title":"Learn. Mem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.actpsy.2010.07.012","article-title":"Expression intensity, gender and facial emotion recognition: Women recognize only subtle facial emotions better than men","volume":"135","author":"Hoffmann","year":"2010","journal-title":"Acta Psychol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.conb.2016.02.007","article-title":"Sex and cognition: Gender and cognitive functions","volume":"38","author":"Hyde","year":"2016","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0306-4530(98)00044-4","article-title":"Pregnancy, the postpartum, and steroid hormones: Effects on cognition and mood","volume":"24","author":"Buckwalter","year":"1999","journal-title":"Psychoneuroendocrinology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1080\/13803390701612209","article-title":"A review of the impact of pregnancy on memory function","volume":"29","author":"Henry","year":"2007","journal-title":"J. Clin. Exp. Neuropsychol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.maturitas.2010.02.005","article-title":"Sex steroids to maintain cognitive function in women after the menopause: A meta-analyses of treatment trials","volume":"66","author":"Hogervorst","year":"2010","journal-title":"Maturitas"},{"key":"ref_17","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":"Hampson","year":"1990","journal-title":"Brain Cogn."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1037\/0735-7044.114.6.1245","article-title":"Sex hormones affect spatial abilities during the menstrual cycle","volume":"114","author":"Hausmann","year":"2000","journal-title":"Behav. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.yhbeh.2007.09.006","article-title":"Emotion recognition accuracy in healthy young females is associated with cycle phase","volume":"53","author":"Derntl","year":"2008","journal-title":"Horm. Behav."},{"key":"ref_20","first-page":"380","article-title":"Menstrual cycle influence on cognitive function and emotion processing-from a reproductive perspective","volume":"8","author":"Gingnell","year":"2014","journal-title":"Front. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.neuroscience.2005.10.058","article-title":"From structural biochemistry to expression profiling: Neuroprotective activities of estrogen","volume":"138","author":"Manthey","year":"2006","journal-title":"Neuroscience"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1152\/physrev.00036.2014","article-title":"Estrogen effects on cognitive and synaptic health over the lifecourse","volume":"95","author":"Hara","year":"2015","journal-title":"Physiol. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1152\/advan.00086.2006","article-title":"Sex steroid effects at target tissues: Mechanisms of action","volume":"31","author":"Wierman","year":"2007","journal-title":"Adv. Physiol. Educ."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/B978-0-444-53630-3.00008-7","article-title":"Neurosteroids: Endogenous role in the human brain and therapeutic potentials","volume":"186","author":"Reddy","year":"2010","journal-title":"Prog. Brain Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1016\/j.ajog.2011.06.057","article-title":"The state of hormonal contraception today: Benefits and risks of hormonal contraceptives: Combined estrogen and progestin contraceptives","volume":"205","author":"Shulman","year":"2011","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.maturitas.2003.09.014","article-title":"Classification and pharmacology of progestins","volume":"46","author":"Schindler","year":"2003","journal-title":"Maturitas"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jecm.2013.02.007","article-title":"Progestins in combined contraceptives","volume":"5","author":"Guerra","year":"2013","journal-title":"J. Exp. Clin. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.tics.2016.11.005","article-title":"How oral contraceptives impact social-emotional behavior and brain function","volume":"21","author":"Montoya","year":"2017","journal-title":"Trends Cogn. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.biopsycho.2013.02.001","article-title":"Natural and synthetic sex hormones: Effects on higher-order cognitive function and prepulse inhibition","volume":"93","author":"Gogos","year":"2013","journal-title":"Biol. Psychol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.yhbeh.2008.03.006","article-title":"Effects of menstrual cycle phase and oral contraceptive use on verbal memory","volume":"54","author":"Mordecai","year":"2008","journal-title":"Horm. Behav."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/S0028-3932(01)00126-9","article-title":"Implicit memory varies across the menstrual cycle: Estrogen effects in young women","volume":"40","author":"Maki","year":"2002","journal-title":"Neuropsychologia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.yhbeh.2015.06.012","article-title":"Oral contraceptives and cognition: A role for ethinyl estradiol","volume":"74","author":"Beltz","year":"2015","journal-title":"Horm. Behav."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1179\/147683008X301612","article-title":"Short-term changes in endogenous estrogen levels and consumption of soy isoflavones affect working and verbal memory in young adult females","volume":"11","author":"Islam","year":"2008","journal-title":"Nutr. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.jsams.2008.05.003","article-title":"The effects of menstrual cycle phase on clinical measures of concussion in healthy college-aged females","volume":"12","author":"Mihalik","year":"2009","journal-title":"J. Sci. Med. Sport\/Sports Med. Aust."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/S0306-4530(01)00083-X","article-title":"Verbal and spatial functions across the menstrual cycle in healthy young women","volume":"27","author":"Rosenberg","year":"2002","journal-title":"Psychoneuroendocrinology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/j.psyneuen.2011.03.001","article-title":"Effects of hormonal contraceptives on mental rotation and verbal fluency","volume":"36","author":"Griksiene","year":"2011","journal-title":"Psychoneuroendocrinology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1037\/1064-1297.16.2.156","article-title":"Oral contraceptives and androgenicity: Influences on visuospatial task performance in younger individuals","volume":"16","author":"Wharton","year":"2008","journal-title":"Exp. Clin. Psychopharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1097\/00006842-199903000-00006","article-title":"Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis","volume":"61","author":"Kirschbaum","year":"1999","journal-title":"Psychosom. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S0306-4530(02)00019-7","article-title":"Impact of oral contraceptive use on glucocorticoid sensitivity of pro-inflammatory cytokine production after psychosocial stress","volume":"28","author":"Rohleder","year":"2003","journal-title":"Psychoneuroendocrinology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1002\/jnr.23904","article-title":"Cortisol reactivity and emotional memory after psychosocial stress in oral contraceptive users","volume":"95","author":"Mordecai","year":"2017","journal-title":"J. Neurosci. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1016\/j.euroneuro.2014.08.015","article-title":"Oral contraceptives may alter the detection of emotions in facial expressions","volume":"24","author":"Hamstra","year":"2014","journal-title":"Eur. Neuropsychopharmacol. J. Eur. Coll. Neuropsychopharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.neuroscience.2014.12.004","article-title":"Mineralocorticoid receptor haplotype, oral contraceptives and emotional information processing","volume":"286","author":"Hamstra","year":"2015","journal-title":"Neuroscience"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.3389\/fnins.2018.01041","article-title":"Oral contraceptives impair complex emotion recognition in healthy women","volume":"12","author":"Pahnke","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1016\/j.euroneuro.2016.03.004","article-title":"Affective responsiveness is influenced by intake of oral contraceptives","volume":"26","author":"Radke","year":"2016","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1097\/00006842-196811000-00006","article-title":"The development of a menstrual distress questionnaire","volume":"30","author":"Moos","year":"1968","journal-title":"Psychosom. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1001\/archpsyc.1961.01710120031004","article-title":"An inventory for measuring depression","volume":"4","author":"Beck","year":"1961","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Maruish, M.E. (2004). Centre for Epidemiological Studies Depression Scale: Review and Revision (CESD and CESD-R). The Use of Psychological Testing for Treatment Planning and Outcomes Assessment: Instruments for Adults, Lawrence Erlbaum Associates. [3rd ed.].","DOI":"10.4324\/9781410610638"},{"key":"ref_48","unstructured":"McNair, D.M., Lorr, M., and Droppelman, L.F. (1981). Profile of Mood States, Educational and Industrial Testing Service."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.acn.2008.03.002","article-title":"An examination of the construct validity and factor structure of the groton maze learning test, a new measure of spatial working memory, learning efficiency, and error monitoring","volume":"23","author":"Pietrzak","year":"2008","journal-title":"Arch. Clin. Neuropsychol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.cct.2006.10.010","article-title":"Cognitive testing in early-phase clinical trials: Development of a rapid computerized test battery and application in a simulated Phase I study","volume":"28","author":"Collie","year":"2007","journal-title":"Contemp. Clin. Trials"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1080\/13803390500205718","article-title":"Practice effects associated with the repeated assessment of cognitive function using the CogState battery at 10-minute, one week and one month test-retest intervals","volume":"28","author":"Falleti","year":"2006","journal-title":"J. Clin. Exp. Neuropsychol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.contraception.2010.04.004","article-title":"The use of newer progestins for contraception","volume":"82","author":"Nath","year":"2010","journal-title":"Contraception"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/0306-4530(95)00051-8","article-title":"A curvilinear relationship between testosterone and spatial cognition in humans: Possible influence of hand preference","volume":"21","author":"Moffat","year":"1996","journal-title":"Psychoneuroendocrinology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1097\/WNN.0000000000000104","article-title":"Effects of testosterone therapy on cognitive function in aging: A systematic review","volume":"29","author":"Hua","year":"2016","journal-title":"Cogn. Behav. Neurol. Off. J. Soc. Behav. Cogn. Neurol."},{"key":"ref_55","first-page":"150","article-title":"Evaluation of high-dose estrogen and high-dose estrogen plus methyltestosterone treatment on cognitive task performance in postmenopausal women","volume":"58","author":"Wisniewski","year":"2002","journal-title":"Horm. Res."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Picot, M., Billard, J.M., Dombret, C., Albac, C., Karameh, N., Daumas, S., Hardin-Pouzet, H., and Mhaouty-Kodja, S. (2016). Neural androgen receptor deletion impairs the temporal processing of objects and hippocampal CA1-dependent mechanisms. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0148328"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.evolhumbehav.2006.05.002","article-title":"A female advantage in the recognition of emotional facial expressions: Test of an evolutionary hypothesis","volume":"27","author":"Hampson","year":"2006","journal-title":"Evol. Hum. Behav."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"529","DOI":"10.3389\/fpsyg.2018.00529","article-title":"Sex hormones and processing of facial expressions of emotion: A systematic literature review","volume":"9","year":"2018","journal-title":"Front. Psychol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1093\/scan\/nss128","article-title":"Hormonal contraceptives, menstrual cycle and brain response to faces","volume":"9","author":"Perrin","year":"2014","journal-title":"Soc. Cogn. Affect. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.brainres.2014.11.025","article-title":"Differential effects of androgenic and anti-androgenic progestins on fusiform and frontal gray matter volume and face recognition performance","volume":"1596","author":"Pletzer","year":"2015","journal-title":"Brain Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.biopsych.2007.05.013","article-title":"Exogenous testosterone enhances responsiveness to social threat in the neural circuitry of social aggression in humans","volume":"63","author":"Hermans","year":"2008","journal-title":"Biol. Psychiatry"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/npp.2008.2","article-title":"Testosterone increases amygdala reactivity in middle-aged women to a young adulthood level","volume":"34","author":"Zylicz","year":"2009","journal-title":"Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.psyneuen.2012.09.005","article-title":"Testosterone administration in women increases amygdala responses to fearful and happy faces","volume":"38","author":"Bos","year":"2013","journal-title":"Psychoneuroendocrinology"}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/10\/4\/194\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:11:25Z","timestamp":1760173885000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/10\/4\/194"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,25]]},"references-count":63,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["brainsci10040194"],"URL":"https:\/\/doi.org\/10.3390\/brainsci10040194","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,25]]}}}