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Ethisterone molecule ball.png
Clinical data
Trade namesProluton C, Pranone, others
Other namesEthinyltestosterone; Ethynyltestosterone; Pregneninolone; Anhydrohydroxyprogesterone; Etisteron; Pregnin; Ethindrone
Routes of
By mouth, sublingual[1]
Drug classProgestogen; Progestin; Androgen; Anabolic steroid
ATC code
Pharmacokinetic data
CAS Number
PubChem CID
CompTox Dashboard (EPA)
ECHA InfoCard100.006.452 Edit this at Wikidata
Chemical and physical data
Molar mass312.446 g/mol g·mol−1
3D model (JSmol)

Ethisterone, also known as ethinyltestosterone, pregneninolone, and anhydrohydroxyprogesterone and formerly sold under the brand names Proluton C and Pranone among others, is a progestin medication which was used in the treatment of 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]

Side effects of ethisterone include masculinization among others.[4][7][8] Ethisterone is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone.[9] It has some androgenic and anabolic activity and no other important 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[edit]

Ethisterone was used in the treatment of gynecological disorders such as irregular menstruation, amenorrhea, and premenstrual syndrome.[3][21]

Available forms[edit]

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[edit]

Side effects of ethisterone include symptoms of masculinization such as acne and hirsutism among others.[4][7][8]



Ethisterone has weak progestogenic activity and weak androgenic activity, but does not seem to have estrogenic activity.[9][12][23]

Relative affinities of ethisterone and related steroids

Ethisterone 35 <1 <1 <1 <1 ? ?
5α-Dihydroethisterone 12 38–100a 4 120 ? 100 ?
Norethisterone 155 45 <1 3 <1 16 <1
Notes: Values are percentages (%). Reference ligands (100%) were progesterone for the PR, testosterone (a = DHT) for the AR, E2 for the ER, DEXA for the GR, aldosterone for the MR, DHT for SHBG, and cortisol for CBG. Sources: See template.

Affinities of 5α-dihydroethisterone for steroid hormone proteins

0.5–16 nM 38–100% 229 nM 3.5% >10,000 nM IA 130 nM 12% 7 nM 120% 0.18 nM 100%
Notes: IC50 values are for binding inhibition (affinity). Reference ligands for RBA (100%) were DHT for the AR, estradiol for the ERα and ERβ, progesterone for the PR, dexamethasone for the GR, and DHT for SHBG. Sources: See template.

Ethisterone is a major active metabolite of danazol (2,3-isoxazolethisterone), and is thought to contribute importantly to its effects.[23]

Progestogenic activity[edit]

Ethisterone is a progestogen, or an agonist of the progesterone receptors.[9] It has about 44% of the affinity of progesterone for the progesterone receptor.[24] The medication is described as a relatively weak progestogen, similarly to its analogue dimethisterone.[25] Ethisterone has about 20-fold lower potency as a progestogen relative to norethisterone.[26] It is said to have minimal antigonadotropic effect and to not suppress ovulation, which has precluded its use in hormonal contraception.[23]

Androgenic activity[edit]

Based on in vitro research, ethisterone and norethisterone are about equipotent in their EC50 values for activation of the androgen receptor (AR), whereas, conversely, norethisterone shows markedly increased potency relative to ethisterone in terms of its EC50 for the progesterone receptor.[9] As such, there is a considerable separation in the ratios of androgenic and progestogenic activity for ethisterone and norethisterone.[9] Moreover, at the larger dosages in which it is used to achieve equivalent progestogenic effect, ethisterone has more androgenic effect relative to norethisterone and other 19-nortestosterone progestins.[10][11] However, the androgenic activity of ethisterone has in any case been described as weak.[23] Due to its androgenic activity, ethisterone has been associated with the masculinization of female fetuses in women who have taken it during pregnancy.[8] The 5α-reduced metabolite of ethisterone, 5α-dihydroethisterone, has been found to show reduced androgenic activity relative to ethisterone.[2]

Estrogenic activity[edit]

Testosterone is aromatized into estradiol, and norethisterone, the 19-nortestosterone analogue of ethisterone, has similarly been shown to be aromatized into ethinylestradiol.[27] In accordance, high doses of norethisterone have been found to be associated with marked increases in urinary estrogen excretion (due to metabolism into ethinylestradiol), as well as with high rates of estrogenic side effects such as breast enlargement in women and gynecomastia in men and improvement of menopausal symptoms in postmenopausal women.[12][28] In contrast, ethisterone and other progestogens such as progesterone and hydroxyprogesterone caproate do not increase estrogen excretion and are not associated with estrogenic effects, indicating that they have little or no estrogenic activity.[12][13] Similarly, although ethisterone showed estrogenic effects in the uterus and vagina in rats, few or no such effects were observed in women treated with the medication, even at very high doses.[29][30] As such, ethisterone does not appear to share the estrogenic activity of norethisterone, at least in humans.[12][13][23]


Ethisterone is active both orally and sublingually in humans.[31] Good oral bioavailability of ethisterone has been observed in rats.[31] The medication was the first orally active progestin to be discovered and introduced for clinical use.[31] Ethisterone is not converted into pregnanediol in humans, indicating that it is not metabolized into progesterone.[31] No aromatization of ethisterone has been detected in vivo, and no estrogenic metabolites were observed in vitro upon incubation of ethisterone in placental homogenates.[31] 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.[32]


Ethisterone is a synthetic androstane steroid which was derived from testosterone and is also known by the following synonyms:[33][34]

  • 17α-Ethynyltestosterone (or simply ethinyltestosterone or ethynyltestosterone)
  • 17α-Ethynylandrost-4-en-17β-ol-3-one
  • 17α-Pregn-4-en-20-yn-17β-ol-3-one (or simply pregneninolone or pregnenynolone)[35][36]
  • 20,21-Anhydro-17β-hydroxyprogesterone (or simply anhydrohydroxyprogesterone)[37]

Closely related analogues of ethisterone include dimethisterone (6α,21-dimethylethisterone), norethisterone (19-norethisterone), and danazol (the 2,3-d-isoxazole ring-fused derivative of ethisterone), as well as vinyltestosterone, allyltestosterone, methyltestosterone, ethyltestosterone, and propyltestosterone.


Chemical syntheses of ethisterone have been published.[31]


Ethisterone was synthesized in 1938 by Hans Herloff Inhoffen, Willy Logemann, Walter Hohlweg, and Arthur Serini at Schering AG in Berlin.[14] It was derived from testosterone via ethynylation at the C17α position, and it was hoped, that, analogously to estradiol and ethinylestradiol, ethisterone would be an orally active form of testosterone.[38] However, the androgenic activity of ethisterone was attenuated and it showed considerable progestogenic activity.[38] 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.[34]

Society and culture[edit]

Generic names[edit]

Ethisterone is the generic name of the drug and its INN, USAN, and BAN, while ethistérone is its DCF.[33][34][4] It has also been referred to as ethinyltestosterone, pregneninolone, and anhydrohydroxyprogesterone.[33][34][4]

Brand names[edit]

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.[33][34][22][39]


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.[40]


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Further reading[edit]