{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T01:48:35Z","timestamp":1791856115504,"version":"4.3.4"},"reference-count":66,"publisher":"The Endocrine Society","issue":"7","license":[{"start":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T00:00:00Z","timestamp":1647129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100007247","name":"Swedish Cultural Foundation in Finland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007247","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Helsinki University Hospital"},{"name":"The Sigrid Jus\u00e9lius Foundation"},{"DOI":"10.13039\/100010135","name":"Finnish Medical Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010135","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006432","name":"University of Oulu Graduate School","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006432","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004756","name":"Emil Aaltonen Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004756","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Limited studies have compared the effects of combined oral contraceptives (COCs) containing natural estrogens and synthetic ethinylestradiol (EE) on reproductive hormones.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To compare estradiol valerate (EV)\u2005+\u2005dienogest (DNG), EE\u2005+\u2005DNG, and DNG alone (active control) on levels of follicle stimulating hormone (FSH), luteinizing hormone, anti-M\u00fcllerian hormone (AMH), ovarian steroids, sex hormone binding globulin (SHBG), and the free androgen index (FAI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This spin-off study from a randomized trial enrolled 59 healthy, 18 to 35-year-old ovulatory women, outpatients at Helsinki and Oulu University Hospitals, Finland, who were randomized to EV 2 mg\u2005+\u2005DNG 2-3 mg (n\u2005=\u200520); EE 0.03 mg\u2005+\u2005DNG 2 mg (n\u2005=\u200520); and DNG 2 mg (n\u2005=\u200519) for 9 weeks. Blood samples were drawn at baseline, and at 5 and 9 weeks. Age and BMI were comparable between groups; 3 women discontinued.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>EV\u2005+\u2005DNG suppressed FSH by \u221227% (\u221251% to \u22123%) (median [95% CI]) vs EE\u2005+\u2005DNG, \u221264% (\u221278 to \u221251), P\u2005=\u20050.04, but AMH levels decreased similarly by \u22129% (\u221218 to \u22120.1) vs \u221213% (\u221228 to 0.2), P\u2005=\u20050.38, respectively. EV\u2005+\u2005DNG increased SHBG levels by 56% (30% to 82%) and EE\u2005+\u2005DNG by 385% (313% to 423%), P\u2005&amp;lt;\u20050.001. Total testosterone decreased by 16% (\u221227% to \u22125%) in the EV\u2005+\u2005DNG group but it did not decrease in the EE\u2005+\u2005DNG group, whereas the FAI decreased by \u221239% (\u221254% to \u221225%) vs \u221272% (\u221278% to \u221267%), P\u2005&amp;lt;\u20050.001. DNG alone did not induce changes in any of these parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Compared with EE\u2005+\u2005DNG, treatment with EV\u2005+\u2005DNG resulted in milder pituitary downregulation and reduced induction of hepatic SHBG synthesis\u2014potentially carrying more beneficial health effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgac150","type":"journal-article","created":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T01:20:35Z","timestamp":1647134435000},"page":"e3008-e3017","source":"Crossref","is-referenced-by-count":23,"title":["Estradiol Valerate vs Ethinylestradiol in Combined Oral Contraceptives: Effects on the Pituitary-Ovarian 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University Hospital and Medical Research Centre PEDEGO Research Unit , PO Box 5000, 90014 Oulu , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9921-7300","authenticated-orcid":false,"given":"Terhi T","family":"Piltonen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Oulu, Oulu University Hospital and Medical Research Centre PEDEGO Research Unit , PO Box 5000, 90014 Oulu , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steinar","family":"Hustad","sequence":"additional","affiliation":[{"name":"Department of Clinical Science and Core Facility for Metabolomics, University of Bergen , NO-5020 Bergen , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8671-130X","authenticated-orcid":false,"given":"Oskari","family":"Heikinheimo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics 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