{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T21:14:27Z","timestamp":1793481267056,"version":"4.5.0"},"reference-count":112,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007306","name":"Arizona Department of Health Services","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010407","name":"College of Liberal Arts and Sciences, Arizona State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>Oral contraceptives and hormone therapies require a progestogen component to prevent ovulation, curtail uterine hyperplasia, and reduce gynecological cancer risk. Diverse classes of synthetic progestogens, called progestins, are used as natural progesterone alternatives due to progesterone\u2019s low oral bioavailability. Progesterone and several synthetic analogs can negatively impact cognition and reverse some neuroprotective estrogen effects. Here, we investigate drospirenone, a spironolactone-derived progestin, which has unique pharmacological properties compared to other clinically-available progestins and natural progesterone, for its impact on spatial memory, anxiety-like behavior, and brain regions crucial to these cognitive tasks. Experiment 1 assessed three drospirenone doses in young adult, ovariectomized rats, and found that a moderate drospirenone dose benefited spatial memory. Experiment 2 investigated this moderate drospirenone dose with and without concomitant ethinyl estradiol (EE) treatment, the most common synthetic estrogen in oral contraceptives. Results demonstrate that the addition of EE to drospirenone administration reversed the beneficial working memory effects of drospirenone. The hippocampus, entorhinal cortex, and perirhinal cortex were then probed for proteins known to elicit estrogen- and progestin- mediated effects on learning and memory, including glutamate decarboxylase (GAD)65, GAD67, and insulin-like growth factor receptor protein expression, using western blot. EE increased GAD expression in the perirhinal cortex. Taken together, results underscore the necessity to consider the distinct cognitive and neural impacts of clinically-available synthetic estrogen and progesterone analogs, and why they produce unique cognitive profiles when administered together compared to those observed when each hormone is administered separately.<\/jats:p>","DOI":"10.3389\/fnins.2022.885321","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T04:59:01Z","timestamp":1653454741000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Evaluating the Cognitive Impacts of Drospirenone, a Spironolactone-Derived Progestin, Independently and in Combination With Ethinyl Estradiol in Ovariectomized Adult Rats"],"prefix":"10.3389","volume":"16","author":[{"given":"Stephanie V.","family":"Koebele","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mallori L.","family":"Poisson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin M.","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Berns-Leone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven N.","family":"Northup-Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica L.","family":"Pe\u00f1a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel M.","family":"Strouse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haidyn L.","family":"Bulen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruti","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corissa","family":"Croft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather A.","family":"Bimonte-Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4248","DOI":"10.1210\/en.2008-1802","article-title":"Transitional versus surgical menopause in a rodent model: etiology of ovarian hormone loss impacts memory and the acetylcholine system.","volume":"150","author":"Acosta","year":"2009","journal-title":"Endocrinology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1515\/jbcpp-2018-0184","article-title":"Drospirenone-containing oral contraceptives do not affect glucose regulation and circulating corticosterone.","volume":"30","author":"Adeyanju","year":"2019","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1016\/j.psyneuen.2009.02.003","article-title":"Sex steroid induced negative mood may be explained by the paradoxical effect mediated by GABAA modulators.","volume":"34","author":"Andr\u00e9en","year":"2009","journal-title":"Psychoneuroendocrinology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/j.contraception.2015.07.014","article-title":"Drospirenone-only oral contraceptive: results from a multicenter noncomparative trial of efficacy, safety and tolerability.","volume":"92","author":"Archer","year":"2015","journal-title":"Contraception"},{"key":"B5","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1007\/s11920-015-0627-4","article-title":"GABAA receptor-modulating steroids in relation to women\u2019s behavioral health.","volume":"17","author":"B\u00e4ckstr\u00f6m","year":"2015","journal-title":"Curr. Psychiatry Rep."},{"key":"B6","doi-asserted-by":"publisher","first-page":"379","DOI":"10.3758\/BF03192707","article-title":"Recommended effect size statistics for repeated measures designs.","volume":"37","author":"Bakeman","year":"2005","journal-title":"Behav. Res. Methods"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1016\/j.bbagen.2010.01.006","article-title":"Influence of different estrogens on neuroplasticity and cognition in the hippocampus.","volume":"1800","author":"Barha","year":"2010","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"B8","doi-asserted-by":"publisher","first-page":"37","DOI":"10.3389\/fnins.2015.00037","article-title":"Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods.","volume":"9","author":"Barth","year":"2015","journal-title":"Front. Neurosci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1002\/hipo.23383","article-title":"G protein-coupled estrogen receptor-1 enhances excitatory synaptic responses in the entorhinal cortex.","volume":"31","author":"Batall\u00e1n Burrowes","year":"2021","journal-title":"Hippocampus"},{"key":"B10","doi-asserted-by":"publisher","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":"B11","doi-asserted-by":"publisher","first-page":"777911","DOI":"10.3389\/fnbeh.2021.777911","article-title":"The link between masculinity and spatial skills is moderated by the estrogenic and progestational activity of oral contraceptives.","volume":"15","author":"Beltz","year":"2022","journal-title":"Front. Behav. Neurosci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing.","volume":"57","author":"Benjamini","year":"1995","journal-title":"R. Stat. Soc."},{"key":"B13","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/S0306-4530(98)00068-7","article-title":"Estradiol facilitates performance as working memory load increases.","volume":"24","author":"Bimonte","year":"1999","journal-title":"Psychoneuroendocrinology"},{"key":"B14","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/s0031-9384(00)00259-6","article-title":"In two species, females exhibit superior working memory and inferior reference memory on the water radial-arm maze.","volume":"70","author":"Bimonte","year":"2000","journal-title":"Physiol. Behav."},{"key":"B15","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/978-1-4939-2159-1_2","article-title":"The Mazes","author":"Bimonte-Nelson","year":"2015","journal-title":"The Maze Book: Theories, Practice, and Protocols for Testing Rodent Cognition"},{"key":"B16","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1111\/j.1460-9568.2006.04867.x","article-title":"Progesterone reverses the spatial memory enhancements initiated by tonic and cyclic oestrogen therapy in middle-aged ovariectomized female rats.","volume":"24","author":"Bimonte-Nelson","year":"2006","journal-title":"Eur. J. Neurosci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1037\/0735-7044.118.4.707","article-title":"Ovarian hormones and cognition in the aged female rat: II. progesterone supplementation reverses the cognitive enhancing effects of ovariectomy.","volume":"118","author":"Bimonte-Nelson","year":"","journal-title":"Behav. Neurosci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2659","DOI":"10.1097\/00001756-200412030-00021","article-title":"Progesterone counteracts estrogen-induced increases in neurotrophins in the aged female rat brain.","volume":"15","author":"Bimonte-Nelson","year":"","journal-title":"Neuroreport"},{"key":"B19","doi-asserted-by":"publisher","first-page":"73","DOI":"10.2165\/0044011-200929020-00001","article-title":"Added benefits and user satisfaction with a low-dose oral contraceptive containing drospirenone.","volume":"29","author":"Bitzer","year":"2009","journal-title":"Clin. Drug Investig."},{"key":"B20","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/0031-9384(75)90188-2","article-title":"Sex differences in open field behavior in the rat: the inductive and activational role of gonadal hormones.","volume":"14","author":"Blizard","year":"1975","journal-title":"Physiol. Behav."},{"key":"B21","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/j.bbr.2016.06.053","article-title":"A comparison of progestins within three classes: differential effects on learning and memory in the aging surgically menopausal rat.","volume":"322","author":"Braden","year":"2017","journal-title":"Behav. Brain Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1007\/s00213-011-2322-4","article-title":"Cognitive-impairing effects of medroxyprogesterone acetate in the rat: independent and interactive effects across time.","volume":"218","author":"Braden","year":"2011","journal-title":"Psychopharmacology"},{"key":"B23","doi-asserted-by":"publisher","first-page":"149","DOI":"10.3389\/fnagi.2015.00149","article-title":"The GABA-A antagonist bicuculline attenuates progesterone-induced memory impairments in middle-aged ovariectomized rats.","volume":"7","author":"Braden","year":"2015","journal-title":"Front. Aging Neurosci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1016\/j.nlm.2010.01.002","article-title":"Medroxyprogesterone acetate impairs memory and alters the GABAergic system in aged surgically menopausal rats.","volume":"93","author":"Braden","year":"2010","journal-title":"Neurobiol. Learn. Mem."},{"key":"B25","year":"2019","journal-title":"Key Statistics from the National Survey of Family Growth: Contraception."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1097\/GME.0000000000001135","article-title":"Therapeutic progestin segesterone acetate promotes neurogenesis: implications for sustaining regeneration in female brain.","volume":"25","author":"Chen","year":"2018","journal-title":"Menopause"},{"key":"B27","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1006\/hbeh.2000.1626","article-title":"Acute administration of estrogen and progesterone impairs the acquisition of the spatial morris water maze in ovariectomized rats.","volume":"38","author":"Chesler","year":"2000","journal-title":"Horm. Behav."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/23293691.2022.2054670","article-title":"Current contraceptive status Among Women Aged 15\u201349: United States, 2015-2017.","volume":"327","author":"Daniels","year":"2018","journal-title":"NCHS Data Brief."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1097\/gme.0b013e318287474f","article-title":"Continuous-combined oral estradiol\/drospirenone has no detrimental effect on cognitive performance and improves estrogen deficiency symptoms in early postmenopausal women: a randomized placebo-controlled trial.","volume":"20","author":"Davison","year":"2013","journal-title":"Menopause"},{"key":"B30","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1055\/s-2001-18637","article-title":"Noncontraceptive benefits and therapeutic uses of the oral contraceptive pill.","volume":"19","author":"Dayal","year":"2001","journal-title":"Semin. Reprod. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.exger.2011.10.008","article-title":"Behavioral effects of estradiol therapy in ovariectomized rats depend on the age when the treatment is initiated.","volume":"47","author":"Diz-Chaves","year":"2012","journal-title":"Exp. Gerontol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1089\/jwh.2012.3522","article-title":"Longer duration of hormonal contraceptive use predicts better cognitive outcomes later in life.","volume":"21","author":"Egan","year":"2012","journal-title":"J. Womens Health"},{"key":"B33","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1093\/cvr\/cvy248","article-title":"Contraceptive drugs mitigate experimental stroke-induced brain injury.","volume":"115","author":"El Amki","year":"2019","journal-title":"Cardiovasc. Res."},{"key":"B34","first-page":"67120","article-title":"Drugs: Drospirenone\/Ethinylestradiol 3mg\/20 \u03bcg (24\/4 Day Regimen): A Review of Its Use in Contraception. Premenstrual Dysphoric Disorder and Moderate Acne Vulgaris.","volume":"67","author":"Fenton","year":"2007","journal-title":"Drugs"},{"key":"B35","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1080\/13697130500330309","article-title":"Added benefits of drospirenone for compliance.","volume":"8","author":"Foidart","year":"2005","journal-title":"Climacteric"},{"key":"B36","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1002\/hipo.20935","article-title":"Role of estrogen receptor alpha and beta expression and signaling on cognitive function during aging.","volume":"22","author":"Foster","year":"2012","journal-title":"Hippocampus"},{"key":"B37","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.yhbeh.2015.05.004","article-title":"The evolving role of dendritic spines and memory: interaction(s) with estradiol.","volume":"74","author":"Frankfurt","year":"2015","journal-title":"Horm. Behav."},{"key":"B38","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/s0010-7824(96)00195-3","article-title":"The novel progestin drospirenone and its natural counterpart progesterone: biochemical profile and antiandrogenic protential.","volume":"7824","author":"Fuhrmann","year":"1996","journal-title":"Contraception"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jim.2018.03.004","article-title":"A new background subtraction method for Western blot densitometry band quantification through image analysis software.","volume":"457","author":"Gallo-Oller","year":"2018","journal-title":"J. Immunol. Methods"},{"key":"B40","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1159\/000097485","article-title":"Cross-talk between IGF-I and estradiol in the brain: focus on neuroprotection.","volume":"84","author":"Garcia-Segura","year":"2007","journal-title":"Neuroendocrinology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.nlm.2016.06.012","article-title":"Intra-perirhinal cortex administration of estradiol, but not an ER\u03b2 agonist, modulates object-recognition memory in ovariectomized rats.","volume":"133","author":"Gervais","year":"2016","journal-title":"Neurobiol. Learn. Mem."},{"key":"B42","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1016\/j.yhbeh.2013.08.010","article-title":"Systemic and intra-rhinal-cortical 17-\u03b2 estradiol administration modulate object-recognition memory in ovariectomized female rats.","volume":"64","author":"Gervais","year":"2013","journal-title":"Horm. Behav."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1002\/hipo.22479","article-title":"Attenuation of dendritic spine density in the perirhinal cortex following 17\u03b2-Estradiol replacement in the rat.","volume":"25","author":"Gervais","year":"2015","journal-title":"Hippocampus"},{"key":"B44","doi-asserted-by":"publisher","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":"B45","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1002\/bdrb.20106","article-title":"The rodent estrous cycle: characterization of vaginal cytology and its utility in toxicological studies.","volume":"80","author":"Goldman","year":"2007","journal-title":"Birth Defects Res. B"},{"key":"B46","doi-asserted-by":"publisher","first-page":"e0252807","DOI":"10.1371\/journal.pone.0252807","article-title":"Do oral contraceptives affect young women\u2019s memory? Dopamine-dependent working memory is influenced by COMT genotype, but not time of pill ingestion.","volume":"16","author":"Gravelsins","year":"2021","journal-title":"PLoS One"},{"key":"B47","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1016\/j.contraception.2012.05.017","article-title":"Types of combined oral contraceptives used by U.S. women.","volume":"86","author":"Hall","year":"2012","journal-title":"Contraception"},{"key":"B48","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1016\/j.neurobiolaging.2006.02.019","article-title":"Effects of estrogen and progesterone on spatial memory consolidation in aged females.","volume":"28","author":"Harburger","year":"2007","journal-title":"Neurobiol. Aging"},{"key":"B49","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.neuroscience.2009.02.024","article-title":"Dose-dependent effects of post-training estradiol plus progesterone treatment on object memory consolidation and hippocampal extracellular signal-regulated kinase activation in young ovariectomized mice.","volume":"160","author":"Harburger","year":"2009","journal-title":"Neuroscience"},{"key":"B50","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.biopsych.2005.10.019","article-title":"Estrogen selectively increases tryptophan hydroxylase-2 mRNA expression in distinct subregions of rat midbrain raphe nucleus: association between gene expression and anxiety behavior in the open field.","volume":"60","author":"Hiroi","year":"2006","journal-title":"Biol. Psychiatry"},{"key":"B51","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.bbr.2005.07.021","article-title":"Differential effects of ovarian steroids on anxiety versus fear as measured by open field test and fear-potentiated startle.","volume":"166","author":"Hiroi","year":"2006","journal-title":"Behav. Brain Res."},{"key":"B52","doi-asserted-by":"publisher","first-page":"517","DOI":"10.3389\/fnins.2016.00517","article-title":"Benefits of hormone therapy estrogens depend on estrogen type: 17\u03b2-estradiol and conjugated equine estrogens have differential effects on cognitive, anxiety-like, and depressive-like behaviors and increase tryptophan hydroxylase-2 mRNA levels in dorsal.","volume":"10","author":"Hiroi","year":"2016","journal-title":"Front. Neurosci."},{"key":"B53","first-page":"236","article-title":"Premenstrual syndrome and premenstrual dysphoric disorder.","volume":"94","author":"Hofmeister","year":"2016","journal-title":"Am. Fam. Physician"},{"key":"B54","first-page":"1","article-title":"What are the options for providing contraception to perimenopausal women?","volume":"10","author":"Ikhena","year":"2012","journal-title":"Sex. Reprod. Menopause"},{"key":"B55","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1038\/sj.jcbfm.9600211","article-title":"Estradiol alters only GAD67 mRNA levels in ischemic rat brain with no consequent effects on GABA.","volume":"26","author":"Joh","year":"2006","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B56","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1101\/lm.038687.115","article-title":"Entorhinal-hippocampal neuronal circuits bridge temporally discontiguous events.","volume":"22","author":"Kitamura","year":"2015","journal-title":"Learn. Mem."},{"key":"B57","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.maturitas.2016.01.015","article-title":"Modeling menopause: the utility of rodents in translational behavioral endocrinology research.","volume":"87","author":"Koebele","year":"2016","journal-title":"Maturitas"},{"key":"B58","doi-asserted-by":"publisher","first-page":"696838","DOI":"10.3389\/fnbeh.2021.696838","article-title":"Clinically used hormone formulations differentially impact memory, anxiety-like, and depressive-like behaviors in a rat model of transitional menopause.","volume":"15","author":"Koebele","year":"","journal-title":"Front. Behav. Neurosci."},{"key":"B59","doi-asserted-by":"publisher","first-page":"e13002","DOI":"10.1111\/jne.13002","article-title":"Oestrogen treatment modulates the impact of cognitive experience and task complexity on memory in middle-aged surgically menopausal rats.","volume":"33","author":"Koebele","year":"","journal-title":"J. Neuroendocrinol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.yhbeh.2016.10.010","article-title":"Cognitive changes across the menopause transition: a longitudinal evaluation of the impact of age and ovarian status on spatial memory.","volume":"87","author":"Koebele","year":"2017","journal-title":"Horm. Behav."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1210\/en.2018-00709","article-title":"Hysterectomy uniquely impacts spatial memory in a rat model: a role for the non-pregnant uterus in cognitive processes.","volume":"160","author":"Koebele","year":"2019","journal-title":"Endocrinology"},{"key":"B62","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S0010-7824(00)00133-5","article-title":"Drospirenone: pharmacology and pharmacokinetics of a unique progestogen.","volume":"62","author":"Krattenmacher","year":"2000","journal-title":"Contraception"},{"key":"B63","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1080\/13697130500148875","article-title":"Pharmacology of estrogens and progestogens: influence of different routes of administration.","volume":"8","author":"Kuhl","year":"2005","journal-title":"Climacteric"},{"key":"B64","doi-asserted-by":"publisher","first-page":"1672","DOI":"10.1111\/1471-0528.14358","article-title":"Drospirenone-containing combined oral contraceptives and the risk of arterial thrombosis: a population-based nested case-control study.","volume":"124","author":"Lariv\u00e9e","year":"2016","journal-title":"BJOG"},{"key":"B65","doi-asserted-by":"publisher","first-page":"817825","DOI":"10.3389\/fendo.2022.817825","article-title":"No differences in value-based decision-making due to use of oral contraceptives.","volume":"13","author":"Lewis","year":"2022","journal-title":"Front. Endocrinol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1097\/GRF.0000000000000657","article-title":"The role of progestogens in menopausal hormone therapy.","volume":"64","author":"Liu","year":"2021","journal-title":"Clin. Obstet. Gynecol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.yhbeh.2010.03.018","article-title":"Effects of long-term treatment with 17 \u03b2-estradiol and medroxyprogesterone acetate on water maze performance in middle aged female rats.","volume":"58","author":"Lowry","year":"2010","journal-title":"Horm. Behav."},{"key":"B68","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1210\/en.2004-1158","article-title":"Novel actions of estrogen receptor-\u03b2 on anxiety-related behaviors.","volume":"146","author":"Lund","year":"2005","journal-title":"Endocrinology"},{"key":"B69","first-page":"254","author":"McDonald","year":"2014","journal-title":"Handbook of Biological Statistics."},{"key":"B70","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1016\/j.yhbeh.2008.04.010","article-title":"Assessment of estradiol influence on spatial tasks and hippocampal CA1 spines: evidence that the duration of hormone deprivation after ovariectomy compromises 17\u03b2-estradiol effectiveness in altering CA1 spines.","volume":"54","author":"McLaughlin","year":"2008","journal-title":"Horm. Behav."},{"key":"B71","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.psyneuen.2015.01.002","article-title":"Understanding the cognitive impact of the contraceptive estrogen Ethinyl Estradiol: tonic and cyclic administration impairs memory, and performance correlates with basal forebrain cholinergic system integrity.","volume":"54","author":"Mennenga","year":"","journal-title":"Psychoneuroendocrinology"},{"key":"B72","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.steroids.2014.08.010","article-title":"Pharmacological blockade of the aromatase enzyme, but not the androgen receptor, reverses androstenedione-induced cognitive impairments in young surgically menopausal rats.","volume":"99","author":"Mennenga","year":"","journal-title":"Steroids"},{"key":"B73","doi-asserted-by":"publisher","first-page":"775796","DOI":"10.3389\/fnbeh.2022.775796","article-title":"Oral contraceptives modulate the relationship between resting brain activity, amygdala connectivity and emotion recognition \u2013 a resting state fMRI Study.","volume":"16","author":"Menting-Henry","year":"2022","journal-title":"Front. Behav. Neurosci."},{"key":"B74","doi-asserted-by":"publisher","first-page":"3316","DOI":"10.1523\/JNEUROSCI.19-09-03316.1999","article-title":"Granule cells in aging rats are sexually dimorphic in their response to estradiol.","volume":"19","author":"Miranda","year":"1999","journal-title":"J. Neurosci."},{"key":"B75","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/978-1-4939-2159-1_3","article-title":"The watermaze","author":"Morris","year":"2015","journal-title":"The Maze Book: Theories, Practice, and Protocols for Testing Rodent Cognition"},{"key":"B76","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1038\/297681a0","article-title":"Place navigation impaired in rats with hippocampal lesions.","volume":"297","author":"Morris","year":"1982","journal-title":"Nature"},{"key":"B77","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1515\/RNS.2011.022","article-title":"Estradiol acts through nuclear-and membrane-initiated mechanisms to maintain a balance between GABAergic and glutamatergic signaling in the brain: implications for hormone replacement therapy.","volume":"21","author":"Moura","year":"2010","journal-title":"Rev. Neurosci."},{"key":"B78","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/0010-7824(94)00015-o","article-title":"Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity. Pharmacological characterization in animal models.","volume":"51","author":"Muhn","year":"1995","journal-title":"Contraception"},{"key":"B79","doi-asserted-by":"publisher","first-page":"2550","DOI":"10.1523\/jneurosci.18-07-02550.1998","article-title":"Estradiol increases dendritic spine density by reducing GABA neurotransmission in hippocampal neurons.","volume":"18","author":"Murphy","year":"1998","journal-title":"J. Neurosci."},{"key":"B80","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1159\/000083657","article-title":"Estrogen and ovariectomy regulate mRNA and protein of glutamic acid decarboxylases and cation-chloride cotransporters in the adult rat hippocampus.","volume":"80","author":"Nakamura","year":"2004","journal-title":"Neuroendocrinology"},{"key":"B81","first-page":"71","article-title":"Psychosexual well-being in women using oral contraceptives containing drospirenone.","volume":"24","author":"Nappi","year":"2009","journal-title":"Funct. Neurol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1007\/s00213-013-3310-7","article-title":"Antagonism of brain insulin-like growth factor-1 receptors blocks estradiol effects on memory and levels of hippocampal synaptic proteins in ovariectomized rats.","volume":"231","author":"Nelson","year":"2014","journal-title":"Psychopharmacology"},{"key":"B83","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1037\/1082-989X.8.4.434","article-title":"Generalized eta and omega squared statistics: measures of effect size for some common research designs.","volume":"8","author":"Olejnik","year":"2003","journal-title":"Psychol. Methods"},{"key":"B84","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.fertnstert.2003.08.030","article-title":"Psychological effect of the oral contraceptive formulation containing 3 mg of drospirenone plus 30 \u03bcg of ethinyl estradiol.","volume":"81","author":"Paoletti","year":"2004","journal-title":"Fertil. Steril."},{"key":"B85","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.physbeh.2009.01.021","article-title":"Progesterone and medroxyprogesterone acetate differentially regulate alpha-4 subunit expression of GABA-A receptors in the CA1 hippocampus of female rats.","volume":"97","author":"Pazol","year":"2009","journal-title":"Physiol. Behav."},{"key":"B86","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1016\/j.contraception.2005.08.021","article-title":"Treatment of premenstrual dysphoric disorder with a new drospirenone-containing oral contraceptive formulation.","volume":"72","author":"Pearlstein","year":"2005","journal-title":"Contraception"},{"key":"B87","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1016\/j.neuroscience.2003.08.009","article-title":"The perirhinal-entorhinal cortex, but not the hippocampus, is critical for expression of individual recognition in the context of the Coolidge effect.","volume":"122","author":"Petrulis","year":"2003","journal-title":"Neuroscience"},{"key":"B88","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/GME.0000000000000921","article-title":"The 2017 hormone therapy position statement of The North American Menopause Society.","volume":"24","author":"Pinkerton","year":"2017","journal-title":"Menopause"},{"key":"B89","doi-asserted-by":"publisher","first-page":"100799","DOI":"10.1016\/j.yfrne.2019.100799","article-title":"The brain as a target of hormonal contraceptives: evidence from animal studies.","volume":"55","author":"Porcu","year":"2019","journal-title":"Front. Neuroendocrinol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neurobiolaging.2017.11.015","article-title":"Contrasting effects of individual versus combined estrogen and progestogen regimens as working memory load increases in middle-aged ovariectomized rats: one plus one does not equal two.","volume":"64","author":"Prakapenka","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"B91","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1016\/S0002-9378(99)70120-1","article-title":"The mechanism of action of hormonal contraceptives and intrauterine contraceptive devices.","volume":"181","author":"Rivera","year":"1999","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.brainres.2006.03.127","article-title":"Progestins inhibit the neuroprotective effects of estrogen in rat hippocampus.","volume":"1099","author":"Rosario","year":"2006","journal-title":"Brain Res."},{"key":"B93","doi-asserted-by":"publisher","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":"B94","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.bbr.2005.04.022","article-title":"Temporary inactivation of the rostral perirhinal cortex induces an anxiolytic-like effect on the elevated plus-maze and on the yohimbine-enhanced startle response.","volume":"163","author":"Schulz-Klaus","year":"2005","journal-title":"Behav. Brain Res."},{"key":"B95","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.psyneuen.2015.08.015","article-title":"Ethinyl estradiol and levonorgestrel alter cognition and anxiety in rats concurrent with a decrease in tyrosine hydroxylase expression in the locus coeruleus and brain-derived neurotrophic factor expression in the hippocampus.","volume":"62","author":"Simone","year":"2015","journal-title":"Psychoneuroendocrinology"},{"key":"B96","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.brainres.2013.01.027","article-title":"Progesterone-induced neuroprotection: factors that may predict therapeutic efficacy.","volume":"1514","author":"Singh","year":"2013","journal-title":"Brain Res."},{"key":"B97","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.maturitas.2004.01.001","article-title":"Pharmacological profile of progestins.","volume":"47","author":"Sitruk-Ware","year":"2004","journal-title":"Maturitas"},{"key":"B98","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1093\/humupd\/dmi046","article-title":"New progestagens for contraceptive use.","volume":"12","author":"Sitruk-Ware","year":"2006","journal-title":"Hum. Reprod. Update"},{"key":"B99","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/j.contraception.2010.04.004","article-title":"The use of newer progestins for contraception.","volume":"82","author":"Sitruk-Ware","year":"2010","journal-title":"Contraception"},{"key":"B100","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s11154-011-9182-4","article-title":"Metabolic effects of contraceptive steroids.","volume":"12","author":"Sitruk-Ware","year":"2011","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"B101","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1002\/hipo.22495","article-title":"17\u03b2 estradiol recruits GluN2B-containing NMDARs and ERK during induction of long-term potentiation at temporoammonic-CA1 synapses.","volume":"26","author":"Smith","year":"2016","journal-title":"Hippocampus"},{"key":"B102","doi-asserted-by":"publisher","first-page":"100874","DOI":"10.1016\/j.yfrne.2020.100874","article-title":"The scientific body of knowledge \u2013 whose body does it serve? A spotlight on oral contraceptives and the brain.","volume":"60","author":"Taylor","year":"2020","journal-title":"Front. Neuroendocrinol."},{"key":"B103","doi-asserted-by":"publisher","first-page":"1963","DOI":"10.1111\/aogs.13688","article-title":"Drospirenone (Slynd) - A New Progestin-Only Oral Contraceptive.","volume":"323","year":"2020","journal-title":"JAMA"},{"key":"B104","doi-asserted-by":"publisher","first-page":"2697","DOI":"10.1210\/endo.131.6.1446611","article-title":"Glutamic acid decarboxylase messenger ribonucleic acid is regulated by Estradiol and Progesterone in the Hippocampus.","volume":"131","author":"Weiland","year":"1992","journal-title":"Endocrinology"},{"key":"B105","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1210\/en.2012-1698","article-title":"Short-term estradiol administration in aging ovariectomized rats provides lasting benefits for memory and the hippocampus: a role for insulin-like growth factor-1.","volume":"154","author":"Witty","year":"2013","journal-title":"Endocrinology"},{"key":"B106","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/S0083-6729(10)82015-1","article-title":"Estradiol and GABAergic transmission in the hippocampus.","volume":"82","author":"W\u00f3jtowicz","year":"2010","journal-title":"Vitam. Horm."},{"key":"B107","article-title":"The cognitive effects of the highly selective progestin segesterone acetate in a rat model of surgical menopause. Program No. 586.16\/O19,","author":"Woner","year":"2019","journal-title":"Proceedings of the 2019 Neuroscience Meeting Planner"},{"key":"B108","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1002\/cne.903360210","article-title":"Roles of estradiol and progesterone in regulation of hippocampal dendritic spine density during the estrous cycle in the rat.","volume":"336","author":"Woolley","year":"1993","journal-title":"J. Comp. Neurol."},{"key":"B109","doi-asserted-by":"publisher","first-page":"7680","DOI":"10.1523\/JNEUROSCI.14-12-07680.1994","article-title":"Estradiol regulates hippocampal dendritic spine density via an N-methyl-D-aspartate receptor-dependent mechanism.","volume":"14","author":"Woolley","year":"1994","journal-title":"J. Neurosci."},{"key":"B110","doi-asserted-by":"publisher","first-page":"1848","DOI":"10.1523\/jneurosci.17-05-01848.1997","article-title":"Estradiol increases the sensitivity of hippocampal CA1 pyramidal cells to NMDA receptor-mediated synaptic input: correlation with dendritic spine density.","volume":"17","author":"Woolley","year":"1997","journal-title":"J. Neurosci."},{"key":"B111","doi-asserted-by":"publisher","first-page":"100248","DOI":"10.1016\/j.ynstr.2020.100248","article-title":"Brain activity during a post-stress working memory task differs between the hormone-present and hormone-absent phase of hormonal contraception.","volume":"13","author":"Ycaza Herrera","year":"2020","journal-title":"Neurobiol. Stress"},{"key":"B112","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1097\/01.AOG","article-title":"Efficacy of a new low-dose oral contraceptive with drospirenone in premenstrual dysphoric disorder.","volume":"106","author":"Yonkers","year":"2005","journal-title":"Obs. Gynecol."}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2022.885321\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T04:59:15Z","timestamp":1653454755000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2022.885321\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,25]]},"references-count":112,"alternative-id":["10.3389\/fnins.2022.885321"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2022.885321","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,25]]},"article-number":"885321"}}