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| Trade names | Gestanin, Gestanon, Perselin, Turinal, others |
| Other names | Allyloestrenol; SC-6393; Org AL-25; 3-Deketo-17α-allyl-19-nortestosterone; 17α-Allylestr-4-en-17β-ol; 17α-(Prop-2-en-1-yl)estr-4-en-17β-ol |
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| Routes of administration | By mouth |
| Drug class | Progestogen;Progestin |
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| Protein binding | "Considerable"[1][2] (and low affinity forSHBGTooltip sex hormone-binding globulin)[3] |
| Metabolism | Liver (reduction,hydroxylation,conjugation;CYP3A4)[1][2][5] |
| Metabolites | •17α-Allyl-19-NTTooltip 17α-Allyl-19-nortestosterone[3][1][2] |
| Eliminationhalf-life | "Several hours" or 10 hours[4][1][2] |
| Excretion | Urine (as conjugates)[1][2] |
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| ECHA InfoCard | 100.006.440 |
| Chemical and physical data | |
| Formula | C21H32O |
| Molar mass | 300.486 g·mol−1 |
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Allylestrenol, sold under the brand namesGestanin andTurinal among others, is aprogestin medication which is used to treatrecurrent andthreatened miscarriage and to preventpremature labor inpregnant women.[6][7] However, except in the case of provenprogesterone deficiency, its use for such purposes is no longer recommended.[6] A Cochrane review in 2025 found that it had little to no effect in subsequent pregnancy outcomes for women with unexplained, recurrent miscarriage.[8] It is also used inJapan to treatbenign prostatic hyperplasia (BPH) in men.[9][10][11] The medication is used alone and is not formulated in combination with anestrogen.[12] It is takenby mouth.[13]
Side effects of allylestrenol are few and have not been well-defined, but are assumed to be similar to those of related medications.[14] Allylestrenol is a progestin, or asyntheticprogestogen, and hence is anagonist of theprogesterone receptor, thebiological target of progestogens likeprogesterone.[15] It has no other importanthormonal activity.[3][16] The medication is aprodrug of17α-allyl-19-nortestosterone (3-ketoallylestrenol) in the body.[17][18][3]
Allylestrenol was first described in 1958 and was introduced for medical use by 1961.[19][20][21][22] It has been marketed widely throughout the world in the past, but today its availability and usage are relatively limited.[23][6][24][25] It remains available in a fewEuropean countries and in a number ofAsian countries.[23][6][24][25]
Allylestrenol is used in the treatment ofrecurrent andthreatened miscarriage and to preventpremature labor.[6][7] However, except in the case of provenprogesterone deficiency, its use for such indications is no longer recommended.[6] Allylestrenol is one of only a handful of progestogens that has commonly been used for such purposes, the others includingprogesterone,hydroxyprogesterone caproate, anddydrogesterone.[8] The medication has also been studied in the treatment ofgynecological disorders such asamenorrhea,irregular menstruation, andpremenstrual syndrome.[14] Unlike other progestins, allylestrenol has not been used inhormonal contraception or inmenopausal hormone therapy. In one study, it was found to be inadequate forendometrial transformation in women in combination withestradiol valerate.[26] On the other hand, allylestrenol was found to be effective in the treatment ofhot flashes in postmenopausal women.[27]
Allylestrenol has been commonly used inJapan at high dosages, typically 50 mg/day but as much as 100 mg/day, to treat BPH in men.[11][28][29][30][31][32][33][34][35][9][10][36][37][38][39][40][41][42][43] Related medications that have similarly been used to treat BPH, particularly in Japan, includechlormadinone acetate,gestonorone caproate, andoxendolone.[33][38] Allylestrenol has also been studied in the treatment ofprostate cancer in Japan.[44][28] The medication has been studied as apuberty blocker in the treatment ofprecocious puberty as well.[45]
Allylestrenol is available in the form of 5 mgoraltablets.[12][46][47] It is typically used at a dosage of 5 to 40 mg/day.[46][47] InJapan, a 25 mg allylestrenol oral tablet, under the brand name Perselin, is marketed for the treatment of BPH.[37]
Allylestrenol should not be taken by people who are allergic toibuprofen ornaproxen,[48] or who havesalicylate intolerance[49] or a more generalizeddrug intolerance to NSAIDs, and caution should be exercised in those withasthma or NSAID-precipitatedbronchospasm. Owing to its effect on the stomach lining, manufacturers recommend people withpeptic ulcers, milddiabetes, orgastritis seek medical advice before using allylestrenol.[48]
Side effects of allylestrenol are few and have not been well-defined, but are assumed to be similar to those of related medications (i.e., other progestins).[14] When used at high dosages in the treatment of BPH in men, allylestrenol can causesymptoms ofhypogonadism andsexual dysfunction.[31][34][35] The medicationindeloxazine may be able to counteract allylestrenol-associated sexual dysfunction.[39] Allylestrenol has noandrogenic or otheroff-targethormonal side effects.[31][3][16]
Allylestrenol is aprogestogen, or anagonist of theprogesterone receptor (PR).[15] It is lacking theketo group at the C3 position (part of the important3-keto-4-ene structure) that is common in progestogens and is considered to be necessary for activity, and in relation to this, is thought to be aprodrug of17α-allyl-19-nortestosterone (3-ketoallylestrenol).[17][18][50] Allylestrenol is a far less potent progestogen than many other 19-nortestosterone derivatives.[15] The effectiveovulation-inhibiting orcontraceptive dosage of allylestrenol in women has been studied, albeit limitedly.[51] At 20 mg/day allylestrenol, ovulation occurred in 50% of 6 cycles, and at 25 mg/day, ovulation occurred in 0% of 3 cycles.[51][52] The totalendometrial transformation dosage of allylestrenol in women across the cycle is 150 to 250 mg.[53] Unlike virtually all other 19-nortestosterone derivatives, allylestrenol is reported to be a pure progestogen and hence to be devoid ofandrogenic,estrogenic, andglucocorticoid activity.[3][16] As such, it appears to have properties more similar to those of naturalprogesterone.[3][16]
The binding and activity profiles of allylestrenol and its majoractive metabolite atsteroid hormone receptors and relatedproteins have been studied.[3][17] Allylestrenol has less than 0.2% of theaffinity ofORG-2058 and less than 2% of the affinity of progesterone for the PR.[3] Similarly, it has less than 0.2% of the affinity oftestosterone for theandrogen receptor (AR), less than 0.2% of the affinity ofestradiol for theestrogen receptor (ER), less than 0.2% of the affinity ofdexamethasone for theglucocorticoid receptor (GR), and 0.9% of the affinity of testosterone forsex hormone-binding globulin (SHBG).[3] Conversely, itsmetabolite 17α-allyl-19-nortestosterone has 24% of the affinity of ORG-2058 and 186% of the affinity of progesterone for the PR, 4.5% of the affinity of testosterone for the AR, 9.8% of the affinity of dexamethasone for the GR, and 2.8% of the affinity of testosterone for SHBG, while it similarly has less than 0.2% of the affinity of estradiol for the ER.[3] The affinity of 17α-allyl-19-nortestosterone for the AR was less than that ofnorethisterone andmedroxyprogesterone acetate and its affinity for SHBG was much lower than that of norethisterone.[3] These findings may help to explain the absence ofteratogenic effects of allylestrenol on theexternal genitalia of female and male ratfetuses.[3]
| Compound | PRTooltip Progesterone receptor | ARTooltip Androgen receptor | ERTooltip Estrogen receptor | GRTooltip Glucocorticoid receptor | MRTooltip Mineralocorticoid receptor | SHBGTooltip Sex hormone-binding globulin | CBGTooltip Corticosteroid binding globulin |
|---|---|---|---|---|---|---|---|
| Allylestrenol | 0 | 0 | 0 | 0 | ? | 1 | ? |
| 17α-Allyl-19-NTTooltip 17α-Allyl-19-nortestosterone | 186 | 5 | 0 | 10 | ? | 3 | ? |
| Notes: Values are percentages (%). Referenceligands (100%) wereP4Tooltip progesterone (medication) for thePRTooltip progesterone receptor,TTooltip testosterone (medication) for theARTooltip androgen receptor,E2 for theERTooltip estrogen receptor,DEXATooltip dexamethasone for theGRTooltip glucocorticoid receptor,aldosterone for theMRTooltip mineralocorticoid receptor,TTooltip testosterone (medication) forSHBGTooltip sex hormone-binding globulin, andcortisol forCBGTooltip Corticosteroid-binding globulin.Sources:[3] | |||||||
Similarly to other progestogens, allylestrenol has potentantigonadotropic effects.[54] It is able to considerably decrease circulating concentrations ofluteinizing hormone,testosterone, anddihydrotestosterone in men.[32][34][39][40] At a dosage of 50 mg/day, allylestrenol has been found to suppress circulating testosterone levels by 78% in men with BPH.[54] This is about the maximum that progestogens are known to be able to suppress testosterone levels in men.[55][56][57] In accordance, the reduction of testosterone and luteinizing hormone levels with allylestrenol in men has been found in a study to be equivalent to that ofchlormadinone acetate andoxendolone.[33] However, another study found a significantly lower decrease in testosterone levels with 50 mg/day allylestrenol relative to 50 mg/day chlormadinone acetate of about 49–52% versus 76–85%, respectively.[34]Animal research suggests that allylestrenol produces its beneficial effects in BPH via its antigonadotropic effects and consequent suppression ofandrogen levels and inhibition ofprostate glandgrowth, similarly to other progestins.[54] Some studies have found that allylestrenol is less effective for BPH than chlormadinone acetate but also produces fewerside effects andsexual dysfunction.[31][34][35] Allylestrenol therapy for BPH is associated with a significant decrease inprostate-specific antigen levels, which may mask the detection of prostate cancer.[54][43]
Allylestrenol is not a significant5α-reductase inhibitor.[54] In one study, it showed about 80,000-fold lowerpotency forinhibition of5α-reductasein vitro than the established 5α-reductase inhibitorepristeride (IC50Tooltip half-maximal inhibitory concentration = 11.3 nM for epristeride and 890 μM for allylestrenol).[54] In another study, there was 70% inhibition of 5α-reductase by allylestrenol at a concentration of 60 μM.[54] This difference may have been due to different experimental conditions, but is still much lower than epristeride.[54]
Followingoral administration,peak levels of allylestrenol occur after 2 to 4 hours.[1][2] The medication shows considerableplasma protein binding.[1][2] It has relatively low affinity for SHBG, much lower than that of norethisterone.[3] Allylestrenol ismetabolized in theliver, viareduction,hydroxylation, andconjugation.[1][2] It is known to be asubstrate ofCYP3A4.[5] It is thought to be aprodrug of17α-allyl-19-nortestosterone (3-ketoallylestrenol), which, in accordance, is a knownactive metabolite of allylestrenol.[17][18] Thebiological half-life of allylestrenol has been reported to be "several hours" or, presumably in its active form, reportedly about 10 hours.[1][2][4] In the blood, unchanged allylestrenol accounted for 15 to 40% ofradioactivity, an unconjugated metabolite accounted for 4 to 10% of radioactivity, and the rest of the radioactivity corresponded to conjugated metabolites.[1][2] Allylestrenol iseliminated mainly inurine, 44% by 24 hours and 67% within 4 days.[1][2] It isexcreted almost completely as conjugates, with 75% of these beingsulfate conjugates and 24% beingglucuronide conjugates.[1][2]
Allylestrenol, also known as 3-deketo-17α-allyl-19-nortestosterone or as 17α-allylestr-4-en-17β-ol, is asyntheticestranesteroid and aderivative oftestosterone.[58] It is a member of the estrane subgroup of the19-nortestosterone family of progestins,[59] but unlike most other 19-nortestosterone progestins, is not a derivative ofnorethisterone (17α-ethynyl-19-nortestosterone).[60][3][18] This is because it possesses anallyl group at the C17α position rather than the usualethynyl group.[60][3][18] As such, along withaltrenogest (17α-allyl-19-nor-δ9,11-testosterone), allylestrenol is a derivative of17α-allyltestosterone rather than of17α-ethynyltestosterone.[60][3][18]
Allylestrenol is also unique among most 19-nortestosterone progestins in that it lacks theketone at the C3 position.[58] It shares this property withlynestrenol (17α-ethynylestr-4-en-17β-ol),desogestrel (11-methylene-17α-ethynyl-18-methylestr-4-en-17β-ol), and theanabolic–androgenic steroid (AAS)ethylestrenol (17α-ethylestr-4-en-17β-ol).[58] Allylestrenol is the C17α allyl and C3 deketo derivative of the AASnandrolone (19-nortestosterone), as well as the C17α allyl and C3 deketoanalogue of the AASnormethandrone (17α-methyl-19-nortestosterone) andnorethandrolone (17α-methyl-19-nortestosterone).[58]
Chemical syntheses of allylestrenol have been published.[58][19][61][62][63]
Allylestrenol was patented in 1958[19] and has been marketed for medical use since 1961.[20][21][22] It was developed byOrganon Laboratories.[22][21]
Allylestrenol is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name,BANTooltip British Approved Name, andJANTooltip Japanese Accepted Name, whileallylestrénol is itsDCFTooltip Dénomination Commune Française andallilestrenolo is itsDCITTooltip Denominazione Comune Italiana.[58][25][64][24] TheBANTooltip British Approved Name was originallyallyloestrenol, but it was eventually changed.[58][25][24] The medication is also known by its developmental code nameSC-6393.[58][25][24]
The major brand names of allylestrenol include Gestanin, Gestanon, Perselin, and Turinal.[23][6][24][25][19] It has also been marketed under a variety of other brand names, including Alese, Alilestrenol, Allynol, Allytry, Alynol, Anin, Arandal, Astanol, Cobarenol, Crestanon, Elmolan, Fetugard, Foegard, Fulterm, Gestanin, Gestanin, Gestanol, Gestanon, Gestanyn, Gestin, Geston, Gestormone, Gestrenol, Gravida, Gravidin, Gravinol, Gravion, Gravynon, Gynerol, Gynonys, Iugr, Lestron, Loestrol, Maintane, Meieston, Moresafe, Nidagest, Nobor, Orageston, Pelias, Preabor, Pregnolin, Pregtenol, Pregular, Prelab, Premaston, Prenolin, Prestrenol, Profar, Progeston, Protanon, and Shegest.[23][6][24][25][19]
Allylestrenol has been marketed widely throughout the world, including inEurope,Southern,Eastern, andSoutheastern Asia,Africa,Oceania, andLatin America.[23][6][24][25] However, although it has been widely marketed in the past, the availability of allylestrenol is relatively limited today.[23][6][24][25] It appears to still be available inBangladesh, theCzech Republic,Egypt,Hong Kong,India,Indonesia,Japan,Lithuania,Malaysia, thePhilippines,Russia,Singapore, andTaiwan.[23][6][24][25] Previously, allylestrenol has also been available inAustralia,Austria,Belgium,Brazil,Germany,Greece,Hungary,Italy,Luxembourg,Mexico,Poland,South Africa,Spain,Sweden,Switzerland,Turkey,Ukraine, theUnited Kingdom, andYugoslavia (nowSerbia andMontenegro).[23][6][24][25] However, it seems to have been discontinued in these countries.[23][6][24][25] It does not seem to have been marketed in theUnited States orCanada.[23][6][24][25]
Other examples are allylestrenol (42), a pro-drug converted to the 3-keto analogue (43), which is used in the treatment of threatened abortion [78,79] and altrenogest (44), used in sows and mares to suppress ovulation and estrus behaviour [80]. [...] Progestins with a 17a-allyl side chain: (42) allylestrenol, (43), (44) altrenogest.
1961 Lancet 21 Jan. 135/1 Allylestrenol ('Gestanin', Organon)..seems to be completely free from androgenic activity. 1962 Med. Jrnl. Austral. 8 Sept. 375/2 Each tablet of the combined hormone preparation, 'Premenquil', contains 5 mg. of allyloestrenol. [...]
Just released in South Africa is Gestanin, Organon Laboratories' new safe oral progestogen. Gestanin is allylestrenol, one of a new group of steroids synthesized by Organon.
