{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:36:41Z","timestamp":1792154201905,"version":"4.4.0"},"reference-count":60,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Estetrol (E4) is a natural estrogenic steroid that is normally produced by human fetal liver. Recent research has demonstrated that it is a potent, orally bioavailable, natural selective estrogen receptor modulator; it has a moderate affinity for both human estrogen receptor alpha (ER\u03b1) and ER\u03b2, with a preference for ER\u03b1. Clinical studies have demonstrated possible use as an estrogen in combined oral contraceptives (COC). COCs containing E4 and drospirenone (DRSP) showed a high acceptability, tolerability, and user satisfaction also when compared to COCs containing ethinylestradiol (EE). E4\/DRSP effectively inhibits ovulation, with a similar effect on endometrium thickness than that of EE-containing COCs. Low doses (15 mg) of E4 with DRSP (3 mg) showed promising results in term of bleeding pattern and cycle control, also when compared to other COCs containing synthetic estrogens. Moreover, the association has limited effects on serum lipids, liver, SHBG levels, and carbohydrate metabolism. This combination also could drive a lower risk of venous thromboembolism than EE-containing COCs. In this review, we will summarize the actual knowledge about the new E4-containing contraceptive. Further large-scale studies in the full target population are needed to provide more insights into the cardiovascular safety profile and user satisfaction of E4\/DRSP.<\/jats:p>","DOI":"10.3390\/jcm10235625","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T22:01:11Z","timestamp":1638309671000},"page":"5625","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Estetrol: A New Choice for Contraception"],"prefix":"10.3390","volume":"10","author":[{"given":"Franca","family":"Fruzzetti","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Pisa University Hospital, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9191-6385","authenticated-orcid":false,"given":"Tiziana","family":"Fidecicchi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Pisa University Hospital, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8648-3845","authenticated-orcid":false,"given":"Maria Magdalena","family":"Montt Guevara","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Pisa University Hospital, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Simoncini","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Pisa University Hospital, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,29]]},"reference":[{"key":"ref_1","first-page":"207","article-title":"Metabolism of 17\u03b2-oestradiol-4-14C in early infancy","volume":"49","author":"Hagen","year":"1965","journal-title":"Endocrinology"},{"key":"ref_2","first-page":"413","article-title":"Isolation of 15-alpha-hydroxy-oestriol from pregnancy urine and from the urine of newborn infants","volume":"56","author":"Zucconi","year":"1967","journal-title":"Acta Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/0304-4165(65)90464-2","article-title":"15\u03b1-hydroxylation: A new pathway of estrogen metabolism in the human fetus and newborn","volume":"100","author":"Schwers","year":"1965","journal-title":"BBA\u2014Gen. 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