anagestone acetate

Anagestone acetate was used in combination with the estrogen mestranol as a combined birth control pill.

Based on its chemical structure, namely the lack of a C3 ketone, it is probable that anagestone acetate is a prodrug of medroxyprogesterone acetate (the 3-keto analogue).{{cite book| vauthors = Fraser IS |title=Estrogens and Progestogens in Clinical Practice|url=https://books.google.com/books?id=eO5qAAAAMAAJ|year=1998|publisher=Churchill Livingstone|isbn=978-0-443-04706-0|page=281|quote=Progestational activity depends on the presence of a 3-keto group in ring A of the steroid skeleton. Most of the progestogens used today do indeed carry such a group in their original molecules. However, the 3-keto group is initially missing in the case of desogestrel and norgestimate. They are prodrugs which undergo metabolic conversion to active 3-keto derivatives in the body.}}{{cite journal | vauthors = McRobb L, Handelsman DJ, Kazlauskas R, Wilkinson S, McLeod MD, Heather AK | title = Structure-activity relationships of synthetic progestins in a yeast-based in vitro androgen bioassay | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 110 | issue = 1–2 | pages = 39–47 | date = May 2008 | pmid = 18395441 | doi = 10.1016/j.jsbmb.2007.10.008 | quote = Prodrugs (lack 3-keto): Ethylestrenol, Lynestrenol, Ethynodiol, Allylestrenol, Norgestimate | s2cid = 5612000 }}

{{See also|List of progestogens|Progestogen ester|List of progestogen esters}}

Anagestone acetate, also known as 3-deketo-6α-methyl-17α-acetoxyprogesterone or as 6α-methyl-17α-acetoxypregn-4-en-20-one, is a synthetic pregnane steroid and a derivative of progesterone and 17α-hydroxyprogesterone. It is the C17α acetate ester of anagestone, which, in contrast to anagestone acetate, was never marketed. Anagestone acetate is closely related structurally to medroxyprogesterone acetate (6α-methyl-17α-acetoxyprogesterone).

Anagestone acetate was introduced in combination with mestranol as a birth control pill in 1968 by Ortho Pharmaceutical.{{cite book| vauthors = Schreiner WE | chapter = The Ovary | veditors = Labhart A |title=Clinical Endocrinology: Theory and Practice|chapter-url=https://books.google.com/books?id=DAgJCAAAQBAJ&pg=PA571|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-96158-8|pages=571–}}{{cite book| vauthors = Streffer C, Bolt H, Follesdal D, Hall P, Hengstler JG, Jacob P, Oughton D, Prieß K, Rehbinder E, Swaton E | display-authors = 6 | chapter = Interspecies Extrapolation |title=Low Dose Exposures in the Environment: Dose-Effect Relations and Risk Evaluation|chapter-url=https://books.google.com/books?id=eiL4CAAAQBAJ&pg=PA135|date=11 November 2013|publisher=Springer Science & Business Media|isbn=978-3-662-08422-9|pages=135–}} It was withdrawn in 1969.

In 1969, along with a variety of other progestogens including progesterone, chlormadinone acetate, megestrol acetate, medroxyprogesterone acetate, ethynerone, and chloroethynyl norgestrel, anagestone acetate was found to induce the development of mammary gland tumors in Beagle dogs after extensive treatment (2–7 years) with very high doses (10–25 times the recommended human dose), though notably not with 1–2 times the human dosage.{{cite journal | vauthors = Diczfalusy E | title = Gregory Pincus and steroidal contraception: a new departure in the history of mankind | journal = Journal of Steroid Biochemistry | volume = 11 | issue = 1A | pages = 3–11 | date = July 1979 | pmid = 385985 | doi = 10.1016/0022-4731(79)90271-1 | url = }}{{cite book | vauthors = Casey HW, Giles RC, Kwapien RP | chapter = Mammary Neoplasia in Animals: Pathologic Aspects and the Effects of Contraceptive Steroids | title = Carcinogenic Hormones | journal = Recent Results in Cancer Research. Fortschritte der Krebsforschung. Progres dans les Recherches Sur le Cancer | volume = 66 | issue = | pages = 129–160 (149) | date = 1979 | pmid = 107546 | doi = 10.1007/978-3-642-81267-5_4 | isbn = 978-3-540-08995-7 | chapter-url = }} In contrast, the non-halogenated 19-nortestosterone derivatives norgestrel, norethisterone, noretynodrel, and etynodiol diacetate were not found to produce such nodules. Because of these findings, anagestone acetate was voluntarily withdrawn from the market by the manufacturer in 1969.{{cite book|title=Consolidated List of Products Whose Consumption And/or Sale Have Been Banned, Withdrawn, Severely Restricted Or Not Approved by Governments|url=https://books.google.com/books?id=leVCukUgNlsC&pg=PA25|year=1983|publisher=United Nations Publications|isbn=978-92-1-130230-1|pages=25–}} The findings also led to the virtual disappearance of most 17α-hydroxyprogesterone derivatives as hormonal contraceptives from the market (though medroxyprogesterone acetate, cyproterone acetate, and chlormadinone acetate have continued to be used). According to Hughes et al., "It is still doubtful how much relevance these findings have for humans as the dog mammary gland seems to be the only one which can be directly maintained by progestogens."{{cite book | vauthors = Gräf KJ, Brotherton J, Neumann F | chapter = The Clinical Uses of Antiandrogens | veditors = Hughes A, Hasan SH, Oertel GW, Voss HE, Bahner F, Neumann F, Steinbeck H, Gräf KJ, Brotherton J, Horn HJ, Wagner RK | display-editors = 6 |title=Androgens II and Antiandrogens / Androgene II und Antiandrogene|chapter-url=https://books.google.com/books?id=7JPsCAAAQBAJ&pg=PA531|date=27 November 2013|publisher=Springer Science & Business Media|isbn=978-3-642-80859-3|pages=531–}} Subsequent research revealed species differences between dogs and humans and established that there is no similar risk in humans.{{cite book| vauthors = Runnebaum BC, Rabe T, Kiesel L | chapter = Development of Progestogens |title=Female Contraception: Update and Trends| chapter-url=https://books.google.com/books?id=LtT6CAAAQBAJ&pg=PA134|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-73790-9|pages=134–135}}

{{Clear}}

Anagestone acetate is the generic name of the drug and its {{abbrlink|USAN|United States Adopted Name}}. It is also known by its developmental code name ORF-1658.

Anagestone acetate was marketed under the brand names Anatropin and Neo-Novum, the latter in combination with the estrogen mestranol.

Anagestone acetate was withdrawn from the market and is no longer available.

• Acetomepregenol

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{{Progesterone receptor modulators}}

Category:Acetate esters

Category:Ketones

Category:Pregnanes

Category:Prodrugs

Category:Progestogen esters

Category:Progestogens

Category:Withdrawn drugs