Etynodiol diacetate, or ethynodiol diacetate, sold under the brand name Ovulen among others, is a progestin medication which is used in birth control pills.[4][5][6] The medication is available only in combination with an estrogen.[7] It is taken by mouth.[8]
Etynodiol, a related compound, was discovered in 1954, and etynodiol diacetate was introduced for medical use in 1965.[15][16] The combination ethynodiol with mestranol (Ovulen) was approved for medical use in the United States in 1966.[17] The combination ethinylestradiol with ethynodiol (Demulen) was approved for medical use in the United States in 1970.[18]
In 2021, the combination with ethinylestradiol was the 276th most commonly prescribed medication in the United States, with more than 800,000 prescriptions.[19][20]
Notes: Values are percentages (%). Reference ligands (100%) were promegestone for the PRTooltip progesterone receptor, metribolone for the ARTooltip androgen receptor, estradiol for the ERTooltip estrogen receptor, dexamethasone for the GRTooltip glucocorticoid receptor, aldosterone for the MRTooltip mineralocorticoid receptor, dihydrotestosterone for SHBGTooltip sex hormone-binding globulin, and cortisol for CBGTooltip Corticosteroid-binding globulin. Footnotes:a = Active or inactive metabolite, prodrug, or neither of norethisterone. Sources: See template.
Reduction of norethisterone (1) affords the 3,17-diol. The 3β-hydroxy compound is the desired product; since reactions at C3 do not show nearly the stereoselectivity as those at C17 by virtue of the relative lack of stereo-directing proximate substituents, the formation of the desired isomer is engendered by use of a bulky reducing agent, lithium tri-tert-butoxyaluminum hydride. Acetylation of the 3β,17β-diol affords etynodiol diacetate (3).[23]
Etynodiol diacetate is the generic name of the drug (the INNTooltip International Nonproprietary Name of its free alcohol form is etynodiol), while ethynodiol diacetate is its USANTooltip United States Adopted Name, BANTooltip British Approved Name, and JANTooltip Japanese Accepted Name.[5][6][7] It is also known by its former developmental code names CB-8080 and SC-11800.[5][6][7]
Brand namesedit
Etynodiol diacetate is or has been marketed under brand names including Conova, Continuin, Demulen,[18][25] Femulen, Kelnor,[3][25] Lo-Malmorede,[26] Luteonorm, Luto-Metrodiol, Malmorede,[27] Metrodiol, Ovulen,[17][25] Soluna, Zovia,[2] and others.[5][6][7]
Availabilityedit
Etynodiol diacetate is marketed in only a few countries, including the United States, Canada, Argentina, and Oman.[7]
Referencesedit
^ abSchindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, et al. (December 2003). "Classification and pharmacology of progestins". Maturitas. 46 (Suppl 1): S7–S16. doi:10.1016/j.maturitas.2003.09.014. PMID 14670641.
^ ab"Zovia 1/35- ethynodiol diacetate and ethinyl estradiol tablets kit". Archived from the original on 28 September 2022. Retrieved 20 January 2024.
^ ab"Kelnor 1/35- ethynodiol diacetate and ethinyl estradiol kit". Archived from the original on 29 March 2023. Retrieved 20 January 2024.
^Shoupe D, Haseltine FP (6 December 2012). Contraception. Springer Science & Business Media. pp. 21–. ISBN 978-1-4612-2730-4.
^ abcdefgElks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 522–. ISBN 978-1-4757-2085-3.
^ abcdefgIndex Nominum 2000: International Drug Directory. Taylor & Francis US. 2000. p. 422. ISBN 978-3-88763-075-1. Retrieved 30 May 2012.
^ abcde"Etynodiol". Drugs.com. Archived from the original on 5 February 2018. Retrieved 4 February 2018.
^ abBlum RW (22 October 2013). Adolescent Health Care: Clinical Issues. Elsevier Science. pp. 216–. ISBN 978-1-4832-7738-7.
^ abcHammerstein J (December 1990). "Prodrugs: advantage or disadvantage?". American Journal of Obstetrics and Gynecology. 163 (6 Pt 2): 2198–2203. doi:10.1016/0002-9378(90)90561-K. PMID 2256526.
^ abcdIARC Working Group on the Evaluation of Carcinogenic Risks to Humans, World Health Organization, International Agency for Research on Cancer (2007). Combined Estrogen-progestogen Contraceptives and Combined Estrogen-progestogen Menopausal Therapy. World Health Organization. pp. 146–. ISBN 978-92-832-1291-1.
^ abTashjian AH, Armstrong EJ (21 July 2011). Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. Lippincott Williams & Wilkins. pp. 523–. ISBN 978-1-4511-1805-6. Archived from the original on 11 January 2023. Retrieved 11 October 2016.
^ abcBecker KL (24 April 2001). Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins. p. 1004. ISBN 978-0-7817-1750-2. Retrieved 30 May 2012.
^ abGoroll AH, Mulley AG (27 January 2009). Primary Care Medicine: Office Evaluation and Management of the Adult Patient. Lippincott Williams & Wilkins. p. 876. ISBN 978-0-7817-7513-7. Retrieved 30 May 2012.
^ abcStanczyk FZ (September 2002). "Pharmacokinetics and potency of progestins used for hormone replacement therapy and contraception". Reviews in Endocrine & Metabolic Disorders. 3 (3): 211–224. doi:10.1023/A:1020072325818. PMID 12215716. S2CID 27018468.
^ abPetrow V (1971). "Antifertility agents". Progress in Medicinal Chemistry. 8 (2): 171–229. doi:10.1016/s0079-6468(08)70130-9. ISBN 9780408703147. PMID 4947236.
^ abWilliam Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 1516–. ISBN 978-0-8155-1856-3. Archived from the original on 20 January 2024. Retrieved 4 February 2018.
^ ab"Ovulen: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Archived from the original on 8 December 2022. Retrieved 20 January 2024.
^ ab"Demulen: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Archived from the original on 10 May 2021. Retrieved 20 January 2024.
^"The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
^"Ethinyl Estradiol; Ethynodiol - Drug Usage Statistics". ClinCalc. Archived from the original on 18 January 2024. Retrieved 14 January 2024.
^Runnebaum BC, Rabe T, Kiesel L (6 December 2012). Female Contraception: Update and Trends. Springer Science & Business Media. pp. 36–. ISBN 978-3-642-73790-9.
^ abKonstitution J (27 November 2013). "Eigenschaften der Gestagene". Handbuch der Experimentellen Pharmakologie. Cham: Springer-Verlag. pp. 14–15, 286. ISBN 978-3-642-99941-3.
^ abKlimstra PD, Colton FB (October 1967). "The synthesis of 3beta-hydroxyestr-4-en-17-one and 3beta-hydroxyandrost-4-en-17-one". Steroids. 10 (4): 411–424. doi:10.1016/0039-128X(67)90119-5. PMID 6064262.
^Sondheimer F, Klibansky Y (1959). "Synthesis of 3β-hydroxy analogues of steroidal hormones, a biologically active class of compounds". Tetrahedron. 5: 15–26. doi:10.1016/0040-4020(59)80066-1.
^ abc"Estrogen and Progestin (Oral Contraceptives)". Archived from the original on 18 January 2024. Retrieved 20 January 2024.
^"Lo-Malmorede". Archived from the original on 24 March 2021. Retrieved 20 January 2024.
^"Malmorede". Archived from the original on 1 October 2023. Retrieved 20 January 2024.