Allylestrenol

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Allylestrenol
Clinical data
Trade namesGestanin, Gestanon, Perselin, Turinal, others
Other namesAllyloestrenol; 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
Pregnancy
category
  • Used in threatened miscarriage and recurrent pregnancy loss
Progestin
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
conjugation; CYP3A4)[1][2][5]
Metabolites• 17α-Allyl-19-NTTooltip 17α-Allyl-19-nortestosterone[3][1][2]
Elimination half-life"Several hours" or 10 hours[4][1][2]
ExcretionUrine (as conjugates)[1][2]
Identifiers
  • (8R,9S,10R,13S,14S,17R)-13-methyl-17-prop-2-enyl-2,3,6,7,8,9,10,11,12,14,15,16-dodecahydro-1H-cyclopenta[a]phenanthren-17-ol
JSmol)
  • C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@]2(CC=C)O)CCC4=CCCC[C@H]34
  • InChI=1S/C21H32O/c1-3-12-21(22)14-11-19-18-9-8-15-6-4-5-7-16(15)17(18)10-13-20(19,21)2/h3,6,16-19,22H,1,4-5,7-14H2,2H3/t16-,17+,18+,19-,20-,21-/m0/s1 checkY
  • Key:ATXHVCQZZJYMCF-XUDSTZEESA-N checkY
  (verify)

Allylestrenol, sold under the brand names Gestanin and Turinal among others, is a

progesterone deficiency, its use for such purposes is no longer recommended.[6] It is also used in Japan to treat benign prostatic hyperplasia (BPH) in men.[9][10][11] The medication is used alone and is not formulated in combination with an estrogen.[12] It is taken by mouth.[13]

17α-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 few European countries and in a number of Asian countries.[23][6][24][25]

Medical uses

Allylestrenol is used in the treatment of

endometrial transformation in women in combination with estradiol valerate.[26] On the other hand, allylestrenol was found to be effective in the treatment of hot flashes in postmenopausal women.[27]

Allylestrenol has been commonly used in Japan 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, include chlormadinone acetate, gestonorone caproate, and oxendolone.[33][38] Allylestrenol has also been studied in the treatment of prostate cancer in Japan.[44][28] The medication has been studied as a puberty blocker in the treatment of precocious puberty as well.[45]

Available forms

Allylestrenol is available in the form of 5 mg oral tablets.[12][46][47] It is typically used at a dosage of 5 to 40 mg/day.[46][47] In Japan, a 25 mg allylestrenol oral tablet, under the brand name Perselin, is marketed for the treatment of BPH.[37]

Side effects

See also:
Progestin § Side effects

Allylestrenol should not be taken by people who are allergic to

peptic ulcers, mild diabetes, or gastritis seek medical advice before using allylestrenol.[48]

symptoms of hypogonadism and sexual dysfunction.[31][34][35] The medication indeloxazine may be able to counteract allylestrenol-associated sexual dysfunction.[39] Allylestrenol has no androgenic or other off-target hormonal side effects.[31][3][16]

Pharmacology

Pharmacodynamics

17α-Allyl-19-nortestosterone, also known as 3-ketoallylestrenol, the active form of allylestrenol.

Progestogenic and off-target activities

Allylestrenol is a

endometrial 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 of androgenic, estrogenic, and glucocorticoid activity.[3][16] As such, it appears to have properties more similar to those of natural progesterone.[3][16]

The binding and activity profiles of allylestrenol and its major

external genitalia of female and male rat fetuses.[3]

Relative affinities (%) of allylestrenol and metabolites
Compound PRTooltip Progesterone receptor ARTooltip Androgen receptor ERTooltip Estrogen receptor GRTooltip Glucocorticoid receptor MRTooltip Mineralocorticoid receptor SHBGTooltip Sex hormone-binding globulin
CBG
Tooltip 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 (%). Reference
CBGTooltip Corticosteroid-binding globulin. Sources: [3]

Antigonadotropic effects

Testosterone levels with 50 mg/day allylestrenol or 50 mg/day chlormadinone acetate orally over 12 weeks in men with benign prostatic hyperplasia.[34]

Similarly to other progestogens, allylestrenol has potent

prostate gland growth, similarly to other progestins.[54] Some studies have found that allylestrenol is less effective for BPH than chlormadinone acetate but also produces fewer side effects and sexual dysfunction.[31][34][35] Allylestrenol therapy for BPH is associated with a significant decrease in prostate-specific antigen levels, which may mask the detection of prostate cancer.[54][43]

Other activities

Allylestrenol is not a significant

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]

Pharmacokinetics

Following

radioactivity, an unconjugated metabolite accounted for 4 to 10% of radioactivity, and the rest of the radioactivity corresponded to conjugated metabolites.[1][2] Allylestrenol is eliminated mainly in urine, 44% by 24 hours and 67% within 4 days.[1][2] It is excreted almost completely as conjugates, with 75% of these being sulfate conjugates and 24% being glucuronide conjugates.[1][2]

Chemistry

See also: List of progestogens

Allylestrenol, also known as 3-deketo-17α-allyl-19-nortestosterone or as 17α-allylestr-4-en-17β-ol, is a

17α-ethynyltestosterone.[60][3][18]

Allylestrenol is also unique among most 19-nortestosterone progestins in that it lacks the

anabolic–androgenic steroid (AAS) ethylestrenol (17α-ethylestr-4-en-17β-ol).[58] Allylestrenol is the C17α allyl and C3 deketo derivative of the AAS nandrolone (19-nortestosterone), as well as the C17α allyl and C3 deketo analogue of the AAS normethandrone (17α-methyl-19-nortestosterone) and norethandrolone (17α-methyl-19-nortestosterone).[58]

Synthesis

Chemical syntheses of allylestrenol have been published.[58][19][61][62][63]

History

Allylestrenol was patented in 1958

Organon Laboratories.[22][21]

Society and culture

Generic names

Allylestrenol is the

INNTooltip International Nonproprietary Name, BANTooltip British Approved Name, and JANTooltip Japanese Accepted Name, while allylestrénol is its DCFTooltip Dénomination Commune Française and allilestrenolo is its DCITTooltip Denominazione Comune Italiana.[58][25][64][24] The BANTooltip British Approved Name was originally allyloestrenol, but it was eventually changed.[58][25][24] The medication is also known by its developmental code name SC-6393.[58][25][24]

Brand names

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, Gestanyn, Gestin, Geston, Gestormone, Gestrenol, Gravida, Gravidin, Gravinol, Gravion, Gravynon, Gynerol, Gynonys, Iugr, Lestron, Loestrol, Maintane, Meieston, Moresafe, Nidagest, Orageston, Pelias, Preabor, Pregnolin, Pregtenol, Pregular, Prelab, Premaston, Prenolin, Prestrenol, Profar, Progeston, Protanon, and Shegest.[23][6][24][25][19]

Availability

Availability of allylestrenol in countries throughout the world as of December 2017. Blue is currently marketed, green is formerly marketed.

Allylestrenol has been marketed widely throughout the world, including in

Southeastern Asia, Africa, Oceania, and Latin 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 in Bangladesh, the Czech Republic, Egypt, Hong Kong, India, Indonesia, Japan, Lithuania, Malaysia, the Philippines, Russia, Singapore, and Taiwan.[23][6][24][25] Previously, allylestrenol has also been available in Australia, Austria, Belgium, Brazil, Germany, Greece, Hungary, Italy, Luxembourg, Mexico, Poland, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the United Kingdom, and Yugoslavia (now Serbia and Montenegro).[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 the United States or Canada.[23][6][24][25]

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