Ethisterone

Source: Wikipedia, the free encyclopedia.
"Pregneninolone" redirects here. For the similarly named steroid, see Pregnenolone.
Ethisterone
Progestin; Androgen; Anabolic steroid
ATC code
Pharmacokinetic data
Metabolites• 5α-Dihydroethisterone[2]
Identifiers
  • (8R,9S,10R,13R,14S,17R)-17-Ethynyl-17-hydroxy-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one
JSmol)
  • C[C@]12CCC(=O)C=C1CC[C@@H]3[C@@H]2CC[C@]4([C@H]3CC[C@]4(C#C)O)C
  • InChI=1S/C21H28O2/c1-4-21(23)12-9-18-16-6-5-14-13-15(22)7-10-19(14,2)17(16)8-11-20(18,21)3/h1,13,16-18,23H,5-12H2,2-3H3/t16-,17+,18+,19+,20+,21+/m1/s1 checkY
  • Key:CHNXZKVNWQUJIB-CEGNMAFCSA-N checkY
  (verify)

Ethisterone, also known as ethinyltestosterone, pregneninolone, and anhydrohydroxyprogesterone and formerly sold under the brand names Proluton C and Pranone among others, is a

gynecological disorders but is now no longer available.[3][4][5] It was used alone and was not formulated in combination with an estrogen.[1][6] The medication is taken by mouth.[4]

hormonal activity.[9][10][11][12][13]

Ethisterone was discovered in 1938 and was introduced for medical use in Germany in 1939 and in the United States in 1945.[14][15][16] It was the second progestogen to be marketed, following injected progesterone in 1934, and was both the first orally active progestogen and the first progestin to be introduced.[17][18][15] Ethisterone was followed by the improved and much more widely used and known progestin norethisterone in 1957.[19][20]

Medical uses

Ethisterone was used in the treatment of

gynecological disorders such as irregular menstruation, amenorrhea, and premenstrual syndrome.[3][21]

Available forms

Ethisterone was available in the form of 5, 10, and 25 mg oral and sublingual tablets, as well as 50 , 100 , and 250 mg oral capsules.[1][6][22] The usual dosage was 25 mg, up to four times per day.[6]

Side effects

See also:
Progestin § Side effects, and Anabolic steroid § Adverse effects

anabolic effects of high doses of ethisterone.[23]

Pharmacology

Pharmacodynamics

Ethisterone has weak progestogenic activity and weak androgenic activity, but does not seem to have estrogenic activity.[9][12][24]

Ethisterone is a major active metabolite of danazol (2,3-isoxazolethisterone), and is thought to contribute importantly to its effects.[24]

Progestogenic activity

Ethisterone is a

antigonadotropic effect and to not suppress ovulation, which has precluded its use in hormonal contraception.[24]

Androgenic activity

Based on

5α-dihydroethisterone, has been found to show reduced androgenic activity relative to ethisterone.[2] Interestingly, ethisterone showed antiandrogenic activity when co-administered with dihydrotestosterone (DHT) in animals, whereas 5α-dihydroethisterone did not.[2]

Estrogenic activity

17α-ethynyl-3β-androstanediol may be estrogenic metabolites of ethisterone.[33]

Pharmacokinetics

Absorption

Ethisterone is active both orally and sublingually in humans.[34] Good oral bioavailability of ethisterone has been observed in rats.[34] The medication was the first orally active progestin to be discovered and introduced for clinical use.[34]

Distribution

Ethisterone has relatively high

affinity for sex hormone-binding globulin, about 14% of that of dihydrotestosterone and 49% of that of testosterone in one study.[35]

Metabolism

In terms of

17α-ethynyl-3β-androstanediol, also formed via 5α-reductase, as well as other enzymes, are also potential metabolites of ethisterone.[33]

Chemistry

See also:
List of androgens/anabolic steroids

Ethisterone is a

synthetic androstane steroid which was derived from testosterone and is also known by the following synonyms:[36][37]

Closely related

17α-ethynyl-3β-androstanediol
.

Synthesis

Chemical syntheses of ethisterone have been published.[34]

History

Ethisterone was

ethynylation at the C17α position, and it was hoped, that, analogously to estradiol and ethinylestradiol, ethisterone would be an orally active form of testosterone.[41] However, the androgenic activity of ethisterone was attenuated and it showed considerable progestogenic activity.[41] As such, it was developed as a progestogen instead and was introduced for medical use in Germany in 1939 as Proluton C and by Schering in the United States in 1945 as Pranone.[15][16] Ethisterone remained in use as late as 2000.[37]

Society and culture

Generic names

Ethisterone is the

INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, and BANTooltip British Approved Name, while ethistérone is its DCFTooltip Dénomination Commune Française.[36][37][4] It has also been referred to as ethinyltestosterone, pregneninolone, and anhydrohydroxyprogesterone.[36][37][4]

Brand names

Ethisterone has been marketed under a variety of brand names including Amenoren, Cycloestrol-AH Progestérone, Duosterone, Estormon, Etherone, Ethisteron, Luteosterone, Lutocyclin, Lutocylol, Lutogynestryl, Menstrogen, Nugestoral, Oophormin Luteum, Ora-Lutin, Orasecron, Pranone, Pre Ciclo, Prodroxan, Produxan, Progestab, Progesteron lingvalete, Progestoral, Proluton C, Syngestrotabs, and Trosinone among others.[36][37][22][42]

Availability

Ethisterone was previously available in France, Germany, Italy, Japan, the United Kingdom, and the United States, among other countries.[22] It is no longer marketed and hence is no longer available in any country.[43]

References

  1. ^ a b c Hospital Formulary and Compendium of Useful Information. University of California Press. 1952. pp. 49–. GGKEY:2UAAZRZ5LN0.
  2. ^
    S2CID 33771349
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  3. ^
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  4. ^
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    .
  5. ^ "Ethisterone". Drugs.com. Archived from the original on 2019-06-24. Retrieved 2018-02-04.
  6. ^ a b c Krug EE (1963). Pharmacology in nursing. Mosby.
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  12. ^
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  13. ^
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  14. ^
    ISBN 978-1-4511-4847-3
    . The discovery of ethinyl substitution and oral potency led (at the end of the 1930s) to the preparation of ethisterone, an orally active derivative of testosterone. In 1951, it was demonstrated that removal of the 19-carbon from ethisterone to form norethindrone did not destroy the oral activity, and most importantly, it changed the major hormonal effect from that of an androgen to that of a progestational agent. Accordingly, the progestational derivatives of testosterone were designated as 19-nortestosterones (denoting the missing 19-carbon).
  15. ^
    ISBN 978-0-203-48612-2
    . Ethisterone, the first orally effective progestagen, was synthesized by Inhoffen and Hohlweg in 1938. Norethisterone, a progestogen still used worldwide, was synthesized by Djerassi in 1951. But this progestogen was not used immediately and in 1953 Colton discovered norethynodrel, used by Pincus in the first oral contraceptive. Numerous other progestogens were subsequently synthesized, e.g., lynestrenol and ethynodiol diacetate, which were, in fact, prhormones converted in vivo to norethisterone. All these progestogens were also able to induce androgenic effects when high doses were used. More potent progestogens were synthesized in the 1960s, e.g. norgestrel, norgestrienone. These progestogens were also more androgenic.
  16. ^
    ISBN 978-3-527-33739-2
    . Im Prinzip hatten Hohlweg und Inhoffen die Lösung schon 1938 in der Hand, denn ihr Ethinyltestosteron (11) war eine oral wirksame gestagene Verbindung und Schering hatte daraus bereits 1939 ein Medikament (Proluton C®) entwickelt.
  17. ^ Twombly GH (1947). Endocrinology of Neoplastic Diseases: A Symposium by Eighteen Authors. Oxford University Press. p. 7.
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  19. ISBN 978-1-4832-8903-8
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  20. ISBN 978-0-300-16791-7
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  21. PMC 1890213
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  22. ^
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  23. PMID 14442516
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  24. ^
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  29. S2CID 20759583
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  30. PMID 14261416
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  31. S2CID 83694494
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  32. S2CID 102020650
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  33. ^
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  34. ^
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  35. PMID 7195405
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  36. ^
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  37. ^
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    .
  38. ^ Roche Review ... Hoffman-La Roche, and Roche-organon. 1940. Hohlweg, Naturwiss., 1938, 26:96, added the ethinyl radical to testosterone and obtained pregneninolone. This substance has been referred to in the literature as Δ4 pregnen-in-20-on-3-ol-17; Δ4 pregnene-in, 17-ol, 3-one; ethinyl testosterone; anhydro-oxy-progesterone; anhydro-hydroxy-progesterone; and pregneninolone.
  39. S2CID 46648877
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  40. PMID 13475464
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  41. ^ a b Kuhl H (2011). "Pharmacology of Progestogens" (PDF). J Reproduktionsmed Endokrinol. 8 (1): 157–177.
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  43. ^ "IBM Watson Health Products: System Status". Micromedexsolutions.com. Retrieved 2022-09-17.

Further reading
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