{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:17:57Z","timestamp":1788254277649,"version":"build-2803163510"},"reference-count":95,"publisher":"Canadian Science Publishing","issue":"6","license":[{"start":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T00:00:00Z","timestamp":1527811200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":["cdnsciencepub.com"],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:p> Estrogen deficiency has been associated with increased incidence of cardiovascular diseases , and recent clinical trials of standard formulations of hormonal therapies have not demonstrated consistent beneficial effects. Estrogen\u2013progestin therapy has been used as exogenous estrogen to normalize depressed estrogen level during menopause. Ovariectomized rodents mimic an estrogen-deficient state in that they develop cardiometabolic dysfunction, including insulin resistance (IR). We therefore hypothesized that hormonal therapy with combined oral contraceptive steroids, ethinylestradiol\u2013levonorgestrel (EEL), improves IR, obesity, and glycogen synthase kinase-3 (GSK-3) through reduction of circulating mineralocorticoid in ovariectomized rats. Twelve-week-old female Wistar rats were divided into 4 groups: sham-operated (SHM) and ovariectomized (OVX) rats were treated with or without EEL (1.0 \u03bcg ethinylestradiol and 5.0 \u03bcg levonorgestrel) daily for 8 weeks. Results showed that OVX or SHM + EEL treated rats had increased HOMA-IR (homeostatic model assessment of IR), 1 h postload glucose, HOMA-\u03b2, triglycerides (TG), total cholesterol (TC), TC\/HDL cholesterol, TG\/HDL cholesterol, plasma insulin, GSK-3, corticosterone, and aldosterone. On the other hand, OVX + EEL treatment ameliorated all these effects except that of aldosterone. Taken together, the results demonstrate that oral hormonal replacement with EEL improves IR and pancreatic \u03b2-cell function and suppresses GSK-3 and glucocorticoid independent of circulating aldosterone, suggesting a positive cardiometabolic effect of oral EEL therapy in estrogen-deficient rats. <\/jats:p>","DOI":"10.1139\/cjpp-2017-0630","type":"journal-article","created":{"date-parts":[[2018,2,3]],"date-time":"2018-02-03T22:37:14Z","timestamp":1517697434000},"page":"577-586","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Oral hormonal therapy with ethinylestradiol\u2013levonorgestrel improves insulin resistance, obesity, and glycogen synthase kinase-3 independent of circulating mineralocorticoid in estrogen-deficient rats"],"prefix":"10.1139","volume":"96","author":[{"given":"Oluwaseun A.","family":"Adeyanju","sequence":"first","affiliation":[{"name":"Cardiovascular Research Laboratory, Department of Physiology, University of Ilorin, Ilorin, Nigeria."},{"name":"Cardiometabolic Research Unit, Department of Physiology, Afe Babalola University, Ado-Ekiti, Ekiti State, Nigeria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaniyi A.","family":"Soetan","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Laboratory, Department of Physiology, University of Ilorin, Ilorin, Nigeria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayodele O.","family":"Soladoye","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Laboratory, Department of Physiology, University of Ilorin, Ilorin, Nigeria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence A.","family":"Olatunji","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Laboratory, Department of Physiology, University of Ilorin, Ilorin, Nigeria."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"155","reference":[{"key":"refg1\/ref1","doi-asserted-by":"publisher","DOI":"10.1139\/y11-053"},{"key":"refg2\/ref2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803157"},{"key":"refg3\/ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2004.05.009"},{"issue":"5","key":"refg4\/ref4","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/BF00281829","volume":"19","author":"Bailey C.J.","year":"1980","journal-title":"Diabetologia"},{"key":"refg5\/ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.08.005"},{"key":"refg6\/ref6","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-3971"},{"key":"refg94\/ref94","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-1791"},{"key":"refg95\/ref95","doi-asserted-by":"publisher","DOI":"10.3275\/8971"},{"key":"refg96\/ref96","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-011-0182-2"},{"key":"refg7\/ref7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.90248.2008"},{"key":"refg8\/ref8","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.8.2087"},{"key":"refg9\/ref9","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-030242"},{"key":"refg10\/ref10","doi-asserted-by":"publisher","DOI":"10.1016\/j.nutres.2012.10.002"},{"key":"refg98\/ref98","doi-asserted-by":"publisher","DOI":"10.1038\/378785a0"},{"key":"refg72\/ref72","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-010-1684-1"},{"issue":"19","key":"refg73\/ref73","doi-asserted-by":"crossref","first-page":"10228","DOI":"10.1073\/pnas.93.19.10228","volume":"93","author":"Eldar-Finkelman H.","year":"1996","journal-title":"Proc. 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