Anagestone acetate, sold under the brand names Anatropin and Neo-Novum, is a

progestin A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural product, natural female sex hormone progesterone in the body. A progestin is a ''synthetic co ...

medication which was withdrawn from medical use due to carcinogenicity observed in animal studies.

Medical uses

Anagestone acetate was used in combination with the

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...

mestranol as a combined

birth control pill The combined oral contraceptive pill (COCP), often referred to as the birth control pill or colloquially as "the pill", is a type of birth control that is designed to be taken orally by women. The pill contains two important hormones: progest ...

Pharmacology

Based on its

chemical structure A chemical structure determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target molecule or other solid. Molecular geometry refers to the spatial arrangement of at ...

, namely the lack of a C3

ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bo ...

, it is probable that anagestone acetate is a

prodrug A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...

medroxyprogesterone acetate Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone acetate (DMPA) in injectable form and sold under the brand name Depo-Provera among others, is a hormonal medication of the progestin type. It is used as a method of bi ...

(the 3-keto analogue).

Chemistry

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 Pregnane, also known as 17β-ethylandrostane or as 10β,13β-dimethyl-17β-ethylgonane, is a C21 steroid and, indirectly, a parent of progesterone. It is a parent hydrocarbon for two series of steroids stemming from 5α-pregnane (originally allop ...

steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...

and a

derivative In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. F ...

progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...

and

17α-hydroxyprogesterone 17α-Hydroxyprogesterone (17α-OHP), also known as 17-OH progesterone (17-OHP), or hydroxyprogesterone (OHP), is an endogenous progestogen steroid hormone related to progesterone. It is also a chemical intermediate in the biosynthesis of many ot ...

. It is the C17α

acetate An acetate is a salt (chemistry), salt formed by the combination of acetic acid with a base (e.g. Alkali metal, alkaline, Alkaline earth metal, earthy, Transition metal, metallic, nonmetallic or radical Radical (chemistry), base). "Acetate" als ...

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...

anagestone Anagestone (), also known as 3-deketo-6α-methyl-17α-hydroxyprogesterone or as 6α-methyl-17α-hydroxypregn-4-en-20-one, is a progestin which was never marketed. An acylated derivative, anagestone acetate, was formerly used clinically as a pha ...

, which, in contrast to anagestone acetate, was never marketed. Anagestone acetate is closely related structurally to

(6α-methyl-17α-acetoxyprogesterone).

History

Anagestone acetate was introduced in combination with mestranol as a

in 1968 by

Ortho Pharmaceutical Ortho Pharmaceutical was initially formed in the United States in 1931 as a subsidiary of Johnson & Johnson to market the first prescription spermicidal contraceptive jelly, ''Ortho-Gynol''. History In the 1940s, Ortho introduced the coil-s ...

. It was withdrawn in 1969. In 1969, along with a variety of other progestogens including

chlormadinone acetate Chlormadinone acetate (CMA), sold under the brand names Belara, Gynorelle, Lutéran, and Prostal among others, is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy, as a component of menopausal hor ...

megestrol acetate Megestrol acetate (MGA), sold under the brand name Megace among others, is a progestin medication which is used mainly as an appetite stimulant to treat wasting syndromes such as cachexia.https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/ ...

ethynerone Ethynerone (International Nonproprietary Name, INN, United States Adopted Name, USAN), also known as 17α-(2-chloroethynyl)estra-4,9-dien-17β-ol-3-one, is a steroidal progestin of the 19-nortestosterone group that was first reported in 1961 but ...

, and

chloroethynyl norgestrel Chloroethynylnorgestrel (developmental code name WY-4355) is a steroidal progestin of the 19-nortestosterone group related to norgestrel that was investigated as an oral contraceptive in the 1970s but was never marketed. In combination with mest ...

, anagestone acetate was found to induce the development of

mammary gland A mammary gland is an exocrine gland in humans and other mammals that produces milk to feed young offspring. Mammals get their name from the Latin word ''mamma'', "breast". The mammary glands are arranged in organs such as the breasts in primat ...

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

s 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 Norgestrel, sold under the brand name Ovral among others, is a progestin medication which is used in birth control pills and in menopausal hormone therapy. It is available both in combination with an estrogen and alone. It is taken by mouth. S ...

norethisterone Norethisterone, also known as norethindrone and sold under many brand names, is a progestin medication used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. The medication is available in both ...

noretynodrel Noretynodrel, or norethynodrel, sold under the brand name Enovid among others, is a progestin medication which was previously used in birth control pills and in the treatment of gynecological disorders but is now no longer marketed. It was availa ...

, and

etynodiol diacetate Etynodiol diacetate, or ethynodiol diacetate, sold under the brand names Demulen and Femulen among others, is a progestin medication which is used in birth control pills. The medication is available only in combination with an estrogen. It is tak ...

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

derivatives as

hormonal contraceptive Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The origin ...

s from the market (though medroxyprogesterone acetate,

cyproterone acetate Cyproterone acetate (CPA), sold alone under the brand name Androcur or Ethinylestradiol/cyproterone acetate, with ethinylestradiol under the brand names Diane or Diane-35 among others, is an antiandrogen and progestin medication used in the treat ...

, 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." Subsequent research revealed species differences between dogs and humans and established that there is no similar risk in humans.

Society and culture

Generic names

''Anagestone acetate'' is the generic name of the drug and its . It is also known by its developmental code name ''ORF-1658''.

Brand names

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

mestranol.

Availability

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

References

{{Progesterone receptor modulators Acetate esters Ketones Pregnanes Prodrugs Progestogen esters Progestogens Withdrawn drugs