Anagestone acetate, sold under the brand names Anatropin and Neo-Novum, is a
progestin medication which was
withdrawn from medical use due to carcinogenicity observed in animal studies.[1][2][3]
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 glandtumors 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.[5][9][8] In contrast, the non-halogenated
19-nortestosterone derivatives
norgestrel,
norethisterone,
noretynodrel, and
etynodiol diacetate were not found to produce such nodules.[8] Because of these findings, anagestone acetate was voluntarily withdrawn from the market by the manufacturer in 1969.[5][8][10] The findings also led to the virtual disappearance of most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).[5][9] 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."[8][11] Subsequent research revealed species differences between dogs and humans and established that there is no similar risk in humans.[12]
Society and culture
Generic names
Anagestone acetate is the
generic name of the drug and its
USANTooltip United States Adopted Name.[1] It is also known by its developmental code name ORF-1658.[1]
Brand names
Anagestone acetate was marketed under the brand names Anatropin and Neo-Novum, the latter in combination with the
estrogenmestranol.[1]
Availability
Anagestone acetate was withdrawn from the market and is no longer available.[5][8][10]
^IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (1987).
IV. OESTROGEN-PROGESTIN COMBINATIONS. International Agency for Research on Cancer. Retrieved 24 June 2022.
^
abSchreiner WE (6 December 2012).
"The Ovary". In Labhart A (ed.). Clinical Endocrinology: Theory and Practice. Springer Science & Business Media. pp. 571–.
ISBN978-3-642-96158-8.
^
abcdefgStreffer C, Bolt H, Follesdal D, Hall P, Hengstler JG, Jacob P, et al. (11 November 2013).
"Interspecies Extrapolation". Low Dose Exposures in the Environment: Dose-Effect Relations and Risk Evaluation. Springer Science & Business Media. pp. 135–.
ISBN978-3-662-08422-9.
^Fraser IS (1998).
Estrogens and Progestogens in Clinical Practice. Churchill Livingstone. p. 281.
ISBN978-0-443-04706-0. 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.
^McRobb L, Handelsman DJ, Kazlauskas R, Wilkinson S, McLeod MD, Heather AK (May 2008). "Structure-activity relationships of synthetic progestins in a yeast-based in vitro androgen bioassay". The Journal of Steroid Biochemistry and Molecular Biology. 110 (1–2): 39–47.
doi:
10.1016/j.jsbmb.2007.10.008.
PMID18395441.
S2CID5612000. Prodrugs (lack 3-keto): Ethylestrenol, Lynestrenol, Ethynodiol, Allylestrenol, Norgestimate
^
abDiczfalusy E (July 1979). "Gregory Pincus and steroidal contraception: a new departure in the history of mankind". Journal of Steroid Biochemistry. 11 (1A): 3–11.
doi:
10.1016/0022-4731(79)90271-1.
PMID385985.
^Gräf KJ, Brotherton J, Neumann F (27 November 2013).
"The Clinical Uses of Antiandrogens". In Hughes A, Hasan SH, Oertel GW, Voss HE, Bahner F, Neumann F, et al. (eds.). Androgens II and Antiandrogens / Androgene II und Antiandrogene. Springer Science & Business Media. pp. 531–.
ISBN978-3-642-80859-3.