Anagestone acetate

Anagestone acetate (USAN) (brand name Anatropin; former developmental code name ORF-1658), also known as 3-deketo-6α-methyl-17α-acetoxyprogesterone or as 6α-methyl-17α-acetoxypregn-4-en-20-one, is a steroidal progestin that was formerly marketed by Ortho Pharmaceutical. Under the brand name Neo-Novum and in combination with the estrogen mestranol, it was introduced in 1968 as an oral contraceptive, but was withdrawn in 1969. Anagestone acetate is the acetate ester of anagestone, which, in contrast to anagestone acetate, was never marketed.

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. 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 Because of these findings, anagestone acetate was voluntarily withdrawn from the market by the manufacturer in 1969. The findings also led to the virtual disappearance of most 17α-hydroxyprogesterone derivatives as hormonal contraceptives from the market (though medroxyprogesterone acetate has 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." Subsequent research revealed species differences between dogs and humans and established that there is no similar risk in humans.