{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:53:39Z","timestamp":1789052019061,"version":"build-2803163510"},"reference-count":36,"publisher":"Georg Thieme Verlag KG","issue":"01","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Thromb Hemost"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The development of oral contraceptives (OCs) began in 1921 and continued in the following years until the first regulatory approval from the Food and Drug Administration was granted in 1960. However, it took several years to realize that OCs presented an important but not frequent risk of venous thrombosis. Several reports ignored this dangerous effect and only in 1967 the Medical Research Council clearly stated this as an important risk. Later, research led to the formulation of second-generation OCs containing progestins, which nevertheless presented an increased thrombotic risk. In early 1980s, OCs containing third-generation progestins were introduced into the market. Only in 1995, it became clear that these new compounds induced a higher thrombotic risk than that related to the second-generation progestins. It appeared clear that the modulating action of progestins was against the procoagulant activity of estrogens. Lastly, at the end of the 2000s, OCs containing natural estrogens and a fourth-generation progestin (dienogest) became available. The prothrombotic effect of those natural products was not different from that of preparations containing second-generation progestins. Moreover, research over the years has produced much data on risk factors associated with OCs use such as age, obesity, cigarette smoking, and thrombophilia. These findings allowed us to better assess the individual thrombotic risk (both arterial and thrombotic) of each woman before offering an OC. Furthermore, research has shown that in high-risk people the use of single progestin is not dangerous as far as thrombosis is concerned. In conclusion, the OCs road has been long and difficult but has led to a great and unthinkable scientific and social enrichment since the 1960s.<\/jats:p>","DOI":"10.1055\/s-0043-1764382","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T19:59:31Z","timestamp":1678737571000},"page":"091-095","source":"Crossref","is-referenced-by-count":11,"title":["Contraceptives and Thrombosis: An Intertwined Revolutionary Road"],"prefix":"10.1055","volume":"50","author":[{"given":"Doris","family":"Barcellona","sequence":"additional","affiliation":[{"name":"Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy"},{"name":"Departmental Unit of Thrombosis and Haemostasis, Azienda Ospedaliero-Universitaria di Cagliari, Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Marongiu","sequence":"additional","affiliation":[{"name":"Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy"},{"name":"Departmental Unit of Thrombosis and Haemostasis, Azienda Ospedaliero-Universitaria di Cagliari, Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvira","family":"Grandone","sequence":"additional","affiliation":[{"name":"Thrombosis and Haemostasis Unit, I.R.C.C.S. \u2018Casa Sollievo della Sofferenza\u2019, San Giovanni Rotondo, Foggia, Italy"},{"name":"Department of Medical and Surgical Sciences, University of Foggia, Foggia, FG, Italy"},{"name":"Department of Obstetrics, Gynaecology and Perinatal Medicine, First I.M. Sechenov Moscow State Medical University, Moscow, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2023,3,13]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s00508-009-1271-y","article-title":"Ludwig Haberlandt\u2013\u201cGrandfather of the Pill\u201d","volume":"121","author":"C Djerassi","year":"2009","journal-title":"Wien Klin Wochenschr"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1007\/s00508-009-1280-x","article-title":"Ludwig Haberlandt\u2014a pioneer in hormonal contraception","volume":"121","author":"E Haberlandt","year":"2009","journal-title":"Wien Klin Wochenschr"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"269","DOI":"10.3181\/00379727-35-8934P","article-title":"The effect of progestin and progesterone on ovulation in the rabbit","volume":"35","author":"A W Makepeace","year":"1937","journal-title":"Exp Biol Med"},{"key":"ref4","volume-title":"Woman and the New Race","author":"S Margaret","year":"1920"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3109\/00016348209155312","article-title":"Gregory Pincus and steroidal contraception revisited","volume":"105","author":"E Diczfalusy","year":"1982","journal-title":"Acta Obstet Gynecol Scand Suppl"},{"issue":"06","key":"ref6","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1210\/endo-59-6-695","article-title":"Studies of the biological activity of certain 19-nor steroids in female animals","volume":"59","author":"M C Chang","year":"1956","journal-title":"Endocrinology"},{"key":"ref7","first-page":"45","article-title":"Min Chueh Chang\u2014October 10, 1908-June 5, 1991","volume":"68","author":"R O Greep","year":"1995","journal-title":"Biogr Mem Natl Acad Sci"},{"issue":"S 02","key":"ref8","doi-asserted-by":"crossref","first-page":"S12","DOI":"10.3109\/13625187.2010.513071","article-title":"History of oral contraception","volume":"15","author":"M Dhont","year":"2010","journal-title":"Eur J Contracept Reprod Health Care"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1016\/S0140-6736(61)91061-3","article-title":"Pulmonary embolism","volume":"2","author":"W M Jordan","year":"1961","journal-title":"Lancet"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1001\/jama.1963.03060100056018","article-title":"FDA report on Enovid. Ad hoc Advisory Committee for the evaluation of a possible etiologic relation with thromboembolic conditions","volume":"185","author":"E Amador","year":"1963","journal-title":"JAMA"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1126\/science.141.3584.892","article-title":"Enovid: contraceptive pill and recent FDA report clearing it stir continued medical dispute","volume":"141","author":"E Langer","year":"1963","journal-title":"Science"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1136\/bmj.2.5413.843","article-title":"Eight years' experience with oral contraception and an analysis of use of low-dosage norethisterone","volume":"2","author":"E T Tyler","year":"1964","journal-title":"BMJ"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1136\/bmj.2.5456.270","article-title":"Oral contraceptive hormones and blood coagulability","volume":"2","author":"J M Thomson","year":"1965","journal-title":"BMJ"},{"issue":"04","key":"ref14","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1136\/jcp.10.4.348","article-title":"Thrombosis and factor VII activity","volume":"10","author":"L Poller","year":"1957","journal-title":"J Clin Pathol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1136\/bmj.2.5417.1132-b","article-title":"Cerebrovascular accidents and oral contraception","volume":"2","author":"K J Zilkha","year":"1964","journal-title":"BMJ"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1136\/bmj.1.5325.220","article-title":"Oral contraception and blood coagulability","volume":"1","author":"O Egeberg","year":"1963","journal-title":"BMJ"},{"issue":"01","key":"ref17","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.thromres.2010.01.045","article-title":"Mechanisms of estrogen-induced venous thromboembolism","volume":"126","author":"S N Tchaikovski","year":"2010","journal-title":"Thromb Res"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1136\/bmj.2.5548.355","article-title":"Risk of thromboembolic disease in women taking oral contraceptives. A preliminary communication to the Medical Research Council by a Subcommittee","volume":"2","year":"1967","journal-title":"BMJ"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"131","DOI":"10.2147\/PPA.S3692","article-title":"Safety, efficacy and patient satisfaction with continuous daily administration of levonorgestrel\/ethinylestradiol oral contraceptives","volume":"3","author":"G Benagiano","year":"2009","journal-title":"Patient Prefer Adherence"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"d6423","DOI":"10.1136\/bmj.d6423","article-title":"Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9","volume":"343","author":"\u00d8 Lidegaard","year":"2011","journal-title":"BMJ"},{"issue":"S 01","key":"ref21","first-page":"32","article-title":"Clinical experience with the recently developed progestogens","volume":"36","author":"S O Skouby","year":"1991","journal-title":"Int J Fertil"},{"issue":"S 02","key":"ref22","first-page":"98","article-title":"Metabolic profile of six oral contraceptives containing norgestimate, gestodene, and desogestrel","volume":"40","author":"A Teichmann","year":"1995","journal-title":"Int J Fertil Menopausal Stud"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1016\/S0140-6736(95)91928-7","article-title":"Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptives with differing progestagen components","volume":"346","author":"H Jick","year":"1995","journal-title":"Lancet"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1016\/S0140-6736(95)91927-9","article-title":"Effect of different progestagens in low oestrogen oral contraceptives on venous thromboembolic disease","volume":"346","author":"World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception","year":"1995","journal-title":"Lancet"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.thromres.2018.03.005","article-title":"Systematic review and meta-analysis of the association of combined oral contraceptives on the risk of venous thromboembolism: The role of the progestogen type and estrogen dose","volume":"165","author":"C Oedingen","year":"2018","journal-title":"Thromb Res"},{"issue":"02","key":"ref26","doi-asserted-by":"crossref","first-page":"188","DOI":"10.2165\/00003495-199651020-00002","article-title":"Comparative pharmacology of newer progestogens","volume":"51","author":"H Kuhl","year":"1996","journal-title":"Drugs"},{"issue":"06","key":"ref27","first-page":"482","article-title":"Can changes in sex hormone binding globulin predict the risk of venous thromboembolism with combined oral contraceptive pills?","volume":"81","author":"V Odlind","year":"2002","journal-title":"Acta Obstet Gynecol Scand"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"75","DOI":"10.2147\/OAJC.S179673","article-title":"Venous thrombosis and hormonal contraception: what's new with estradiol-based hormonal contraceptives?","volume":"9","author":"F Fruzzetti","year":"2018","journal-title":"Open Access J Contracept"},{"issue":"08","key":"ref29","doi-asserted-by":"crossref","first-page":"573","DOI":"10.2165\/11590220-000000000-00000","article-title":"Metabolic and haemostatic effects of estradiol valerate\/dienogest, a novel oral contraceptive: a randomized, open-label, single-centre study","volume":"31","author":"W Junge","year":"2011","journal-title":"Clin Drug Investig"},{"issue":"02","key":"ref30","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2165\/11591200-000000000-00000","article-title":"Hemostatic effects of a novel estradiol-based oral contraceptive: an open-label, randomized, crossover study of estradiol valerate\/dienogest versus ethinylestradiol\/levonorgestrel","volume":"11","author":"C Klipping","year":"2011","journal-title":"Drugs R D"},{"issue":"04","key":"ref31","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.contraception.2016.06.010","article-title":"Impact of estrogen type on cardiovascular safety of combined oral contraceptives","volume":"94","author":"J Dinger","year":"2016","journal-title":"Contraception"},{"issue":"10","key":"ref32","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1517\/14740338.2014.950654","article-title":"Hormonal contraception, thrombosis and age","volume":"13","author":"\u00d8 Lidegaard","year":"2014","journal-title":"Expert Opin Drug Saf"},{"issue":"01","key":"ref33","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.fertnstert.2016.09.027","article-title":"Combined hormonal contraception and the risk of venous thromboembolism: a guideline","volume":"107","author":"Practice Committee of the American Society for Reproductive Medicine. Electronic address: ASRM@asrm.org","year":"2017","journal-title":"Fertil Steril"},{"issue":"25","key":"ref34","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1056\/NEJMoa003216","article-title":"Oral contraceptives and the risk of myocardial infarction","volume":"345","author":"B C Tanis","year":"2001","journal-title":"N Engl J Med"},{"issue":"07","key":"ref35","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1111\/jth.13349","article-title":"Combined oral contraceptives, thrombophilia and the risk of venous thromboembolism: a systematic review and meta-analysis","volume":"14","author":"E F van Vlijmen","year":"2016","journal-title":"J Thromb Haemost"},{"issue":"10","key":"ref36","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1177\/2047487318774847","article-title":"Association between progestin-only contraceptive use and cardiometabolic outcomes: a systematic review and meta-analysis","volume":"25","author":"M Glisic","year":"2018","journal-title":"Eur J Prev Cardiol"}],"container-title":["Seminars in Thrombosis and Hemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0043-1764382.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T05:53:46Z","timestamp":1730786026000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0043-1764382"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,13]]},"references-count":36,"journal-issue":{"issue":"01","published-online":{"date-parts":[[2024,1,2]]},"published-print":{"date-parts":[[2024,2]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0043-1764382","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0094-6176","1098-9064"],"issn-type":[{"value":"0094-6176","type":"print"},{"value":"1098-9064","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,13]]}}}