Allylestrenol

{{short description|Chemical compound}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Drugbox | Verifiedfields = verified | Watchedfields = verified | verifiedrevid = 477248526 | IUPAC_name = (8''R'',9''S'',10''R'',13''S'',14''S'',17''R'')-13-methyl-17-prop-2-enyl-2,3,6,7,8,9,10,11,12,14,15,16-dodecahydro-1''H''-cyclopenta[''a'']phenanthren-17-ol | image = Allylestrenol.svg | image_class = skin-invert-image | width = 200px | image2 = Allylestrenol molecule ball.png | image_class2 = bg-transparent | width2 = 250px

| tradename = Gestanin, Gestanon, Perselin, Turinal, others | pregnancy_AU =  | pregnancy_US =  | pregnancy_category = Used in threatened miscarriage and recurrent pregnancy loss | legal_AU =  | legal_CA =  | legal_UK =  | legal_US =  | legal_status = RX-only | routes_of_administration = By mouth | class = Progestogen; Progestin

| bioavailability = | protein_bound = "Considerable"<ref name="Bengtsson_1972" /><ref name="Thijssen_1967" /> (and low affinity for {{abbrlink|SHBG|sex hormone-binding globulin}})<ref name="Bergink_1985" /> | metabolism = Liver (reduction, hydroxylation, conjugation; CYP3A4)<ref name="Bengtsson_1972" /><ref name="Thijssen_1967" /><ref name="SuperCYP">{{cite web | title = SuperCYP | url = https://bioinformatics.charite.de/supercyp/ }}</ref> | metabolites = • {{abbrlink|17α-Allyl-19-NT|17α-Allyl-19-nortestosterone}}<ref name="Bergink_1985" /><ref name="Bengtsson_1972" /><ref name="Thijssen_1967" /> | elimination_half-life = "Several hours" or 10 hours<ref name="Saha_2000" /><ref name="Bengtsson_1972" /><ref name="Thijssen_1967" /> | excretion = Urine (as conjugates)<ref name="Bengtsson_1972" /><ref name="Thijssen_1967" />

| CAS_number_Ref = {{cascite|correct|CAS}} | CAS_number = 432-60-0 | ATC_prefix = G03 | ATC_suffix = DC01 | PubChem = 235905 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB01431 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 205855 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = I47VB5DZ8O | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D01374 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 31189 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 2105618 | synonyms = 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

| C=21 | H=32 | O=1 | SMILES = C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@]2(CC=C)O)CCC4=CCCC[C@H]34 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 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 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = ATXHVCQZZJYMCF-XUDSTZEESA-N }}

'''Allylestrenol''', sold under the brand names '''Gestanin''' and '''Turinal''' among others, is a progestin medication which is used to treat recurrent and threatened miscarriage and to prevent premature labor in pregnant women.<ref name="Martindale">{{cite book | veditors = Sweetman SC | chapter = Sex hormones and their modulators | title = Martindale: The Complete Drug Reference | location = London | pages = 2082 | year = 2009 | edition = 36th | publisher = Pharmaceutical Press | isbn = 978-0-85369-840-1 | chapter-url = https://www.medicinescomplete.com/mc/martindale/2009/9023-n.htm }}</ref><ref name="CortesPrieto_1980">{{cite journal | vauthors = Cortés-Prieto J, Bosch AO, Rocha JA | title = Allylestrenol: three years of experience with Gestanon in threatened abortion and premature labor | journal = Clinical Therapeutics | volume = 3 | issue = 3 | pages = 200–208 | year = 1980 | pmid = 7459930 }}</ref> However, except in the case of proven progesterone deficiency, its use for such purposes is no longer recommended.<ref name="Martindale" /> A Cochrane review in 2025 found that it had little to no effect in subsequent pregnancy outcomes for women with unexplained, recurrent miscarriage.<ref name="Haas_2025">{{cite journal | vauthors = Haas DM, Bofill Rodriguez M, Hathaway TJ, Ramsey PS | title = Progestogen for preventing miscarriage in women with recurrent miscarriage of unclear etiology | journal = The Cochrane Database of Systematic Reviews | volume = 6 | issue = 6 | date = June 2025 | pmid = 40497447 | pmc = 12153038 | doi = 10.1002/14651858.CD003511.pub6 | article-number = CD003511 }}</ref> It is also used in Japan to treat benign prostatic hyperplasia (BPH) in men.<ref name="Kanimoto_1991" /><ref name="Umeda_1991" /><ref name="Ishizuka_2002">{{cite journal | vauthors = Ishizuka O, Nishizawa O, Hirao Y, Ohshima S | title = Evidence-based meta-analysis of pharmacotherapy for benign prostatic hypertrophy | journal = International Journal of Urology | volume = 9 | issue = 11 | pages = 607–612 | date = November 2002 | pmid = 12534901 | doi = 10.1046/j.1442-2042.2002.00539.x | doi-access = free }}</ref> The medication is used alone and is not formulated in combination with an estrogen.<ref name="Muller_1998" /> It is taken by mouth.<ref name="Ganguly_2009">{{cite book | vauthors = Ganguly NK, Bano R, Seth SD | veditors = Seth SD, Seth V | chapter = Drug Discovery and Development | title = Textbook Of Pharmacology | pages = 1– | date = 18 November 2009 | chapter-url = https://books.google.com/books?id=51ozlZRBvQwC&pg=RA1-PA71 | publisher = Elsevier India | isbn = 978-81-312-1158-8 }}</ref>

Side effects of allylestrenol are few and have not been well-defined, but are assumed to be similar to those of related medications.<ref name="Borglin_1960" /> Allylestrenol is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone.<ref name="FieldRichards_1961" /> It has no other important hormonal activity.<ref name="Bergink_1985" /><ref name="Madjerekde Visser1960" /> The medication is a prodrug of 17α-allyl-19-nortestosterone (3-ketoallylestrenol) in the body.<ref name="McRobb_2008" /><ref name="Zeelen_1990" /><ref name="Bergink_1985" />

Allylestrenol was first described in 1958 and was introduced for medical use by 1961.<ref name="Publishing_2013" /><ref name="FieldRichards_1961a" /><ref name="Simpson_1997" /><ref name="Juta1962" /> It has been marketed widely throughout the world in the past, but today its availability and usage are relatively limited.<ref name="Micromedex" /><ref name="Martindale" /><ref name="cite7458195b" /><ref name="IndexNominum2000" /> It remains available in a few European countries and in a number of Asian countries.<ref name="Micromedex" /><ref name="Martindale" /><ref name="cite7458195b" /><ref name="IndexNominum2000" />

==Medical uses== Allylestrenol is used in the treatment of recurrent and threatened miscarriage and to prevent premature labor.<ref name="Martindale" /><ref name="CortesPrieto_1980" /> However, except in the case of proven progesterone deficiency, its use for such indications is no longer recommended.<ref name="Martindale" /> Allylestrenol is one of only a handful of progestogens that has commonly been used for such purposes, the others including progesterone, hydroxyprogesterone caproate, and dydrogesterone.<ref name="Haas_2025" /> The medication has also been studied in the treatment of gynecological disorders such as amenorrhea, irregular menstruation, and premenstrual syndrome.<ref name="Borglin_1960">{{cite journal | vauthors = Borglin NE | title = Clinical Evaluation of the Progestational Effect of Allylestrenol | journal = European Journal of Endocrinology | volume = 35 | issue = 4 | pages = NP–S15 | year = 1960 | doi = 10.1530/acta.0.XXXVS0NP | issn = 0804-4643 }}</ref> Unlike other progestins, allylestrenol has not been used in hormonal contraception or in menopausal hormone therapy. In one study, it was found to be inadequate for endometrial transformation in women in combination with estradiol valerate.<ref name="Birkenfeld_1987">{{cite journal | vauthors = Birkenfeld A, Navot D, Ezra Y, Ron A, Schenker JG | title = The effect of estradiol valerate and allylestrenol on endometrial transformation in hypergonadotropic hypogonadic women | journal = European Journal of Obstetrics, Gynecology, and Reproductive Biology | volume = 25 | issue = 3 | pages = 221–229 | date = July 1987 | pmid = 3609436 | doi = 10.1016/0028-2243(87)90102-X }}</ref> On the other hand, allylestrenol was found to be effective in the treatment of hot flashes in postmenopausal women.<ref name="Bartak_1992">{{cite journal | vauthors = Barták A, Rozprávka M, Blovský J | title = [Lynestrenol and allylestrenol in the therapy of postmenopausal hot flushes] | journal = Ceskoslovenska Gynekologie | volume = 57 | issue = 8 | pages = 408–413 | date = October 1992 | pmid = 1473164 | language = cs }}</ref>

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.<ref name="Ishizuka_2002" /><ref name="Yamanaka_1983">{{cite journal | vauthors = Yamanaka H, Kosaku N, Makino T, Shida K | title = [Fundamental and clinical study of the anti-prostatic effect of allylestrenol] | journal = Hinyokika Kiyo. Acta Urologica Japonica | volume = 29 | issue = 9 | pages = 1133–1145 | date = September 1983 | pmid = 6203385 | language = ja }}</ref><ref name="Tajima_1986">{{cite journal | vauthors = Tajima A, Aso Y, Ushiyama T, Hata M, Kambayashi T, Ohmi Y, Masuda H, Nakahara M, Kitagawa M, Suzuki A | title = [Clinical effect of allylestrenol on benign prostatic hypertrophy] | journal = Hinyokika Kiyo. Acta Urologica Japonica | volume = 32 | issue = 3 | pages = 477–485 | date = March 1986 | pmid = 2425610 | language = ja }}</ref><ref name="Kohri_1986">{{cite journal | vauthors = Kohri K, Kurita T, Iguchi M, Kataoka K | title = [Clinical effects of allylestrenol on prostatic hypertrophy] | journal = Hinyokika Kiyo. Acta Urologica Japonica | volume = 32 | issue = 3 | pages = 486–492 | date = March 1986 | pmid = 2425611 | language = ja }}</ref><ref name="Shida_1986">{{cite journal | vauthors = Shida K, Koyanagi T, Kawakura K, Nishida T, Kumamoto Y, Orikasa S, Sato S, Takeda M, Yamanaka H, Shimazaki J | title = [Clinical effects of allylestrenol on benign prostatic hypertrophy by double-blind method] | journal = Hinyokika Kiyo. Acta Urologica Japonica | volume = 32 | issue = 4 | pages = 625–648 | date = April 1986 | pmid = 2426932 | language = ja }}</ref><ref name="Ohyama_1986">{{cite journal | vauthors = Ohyama M, Tanifuji T, Haraguchi C, Fujii N, Higaki Y, Yoshida H, Imamura K | title = [Clinical study of allylestrenol (Org AL-25) on patients with prostatic hypertrophy--transrectal ultrasonography and urodynamic examination] | journal = Hinyokika Kiyo. Acta Urologica Japonica | volume = 32 | issue = 4 | pages = 649–659 | date = April 1986 | pmid = 2426933 | language = ja }}</ref><ref name="Katayama_1986">{{cite journal | vauthors = Katayama T, Umeda K, Kazama T | title = [Hormonal environment and antiandrogenic treatment in benign prostatic hypertrophy] | journal = Hinyokika Kiyo. Acta Urologica Japonica | volume = 32 | issue = 11 | pages = 1584–1589 | date = November 1986 | pmid = 2435122 | language = ja }}</ref><ref name="Kumamoto_1990">{{cite journal | vauthors = Kumamoto Y, Yamaguchi Y, Sato Y, Suzuki R, Tanda H, Kato S, Mori K, Matsumoto H, Maki A, Kadono M | title = [Effects of anti-androgens on sexual function. Double-blind comparative studies on allylestrenol and chlormadinone acetate Part I: Nocturnal penile tumescence monitoring] | journal = Hinyokika Kiyo. Acta Urologica Japonica | volume = 36 | issue = 2 | pages = 213–226 | date = February 1990 | pmid = 1693037 | language = ja }}</ref><ref name="Kumamoto_1990a">{{cite journal | vauthors = Kumamoto Y, Yamaguchi Y, Sato Y, Suzuki R, Tanda H, Kato S, Mori K, Matsumoto H, Maki A, Kadono M | title = [Effects of anti-androgens on sexual function. Double-blind comparative studies on allylestrenol and chlormadinone acetate. Part II: Self-assessment questionnaire method] | journal = Hinyokika Kiyo. Acta Urologica Japonica | volume = 36 | issue = 2 | pages = 227–244 | date = February 1990 | pmid = 1693038 | language = ja | url = https://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/116823/1/36_213.pdf }}</ref><ref name="Kanimoto_1991">{{cite journal | vauthors = Kanimoto Y, Okada K | title = [Antiandrogen therapy of benign prostatic hyperplasia--review of the agents evaluation of the clinical results] | journal = Hinyokika Kiyo. Acta Urologica Japonica | volume = 37 | issue = 11 | pages = 1423–1428 | date = November 1991 | pmid = 1722627 | language = ja }}</ref><ref name="Umeda_1991">{{cite journal | vauthors = Umeda K | title = [Clinical results and problems of anti-androgen therapy of benign prostatic hypertrophy] | journal = Hinyokika Kiyo. Acta Urologica Japonica | volume = 37 | issue = 11 | pages = 1429–1433 | date = November 1991 | pmid = 1722628 | language = ja }}</ref><ref name="Tsuji_1992">{{cite journal | vauthors = Tsuji Y, Ariyoshi A, Nakamura H, Michinaga S, Tomita Y, Ohmori A, Tahara H, Yamashita Y, Fujisawa Y, Kajiwara I | title = [Antiandrogen therapy of benign prostatic hypertrophy: clinical effects of allylestrenol evaluated by transrectal ultrasonographic measurement] | journal = Hinyokika Kiyo. Acta Urologica Japonica | volume = 38 | issue = 8 | pages = 961–966 | date = August 1992 | pmid = 1384295 | language = ja }}</ref><ref name="Fukuoka_1993">{{cite journal | vauthors = Fukuoka H, Ishibashi Y, Shiba T, Tuchiya F, Sakanishi S | title = [Clinical study of allylestrenol (Perselin) on patients with prostatic hypertrophy] | journal = Hinyokika Kiyo. Acta Urologica Japonica | volume = 39 | issue = 7 | pages = 679–683 | date = July 1993 | pmid = 7689782 | language = ja }}</ref><ref name="Iguchi_1994">{{cite journal | vauthors = Iguchi H, Ikeuchi T, Kai Y, Yoshida H | title = [Influence of anti-androgen therapy for prostatic hypertrophy on lipid metabolism] | journal = Hinyokika Kiyo. Acta Urologica Japonica | volume = 40 | issue = 3 | pages = 215–219 | date = March 1994 | pmid = 7513937 | language = ja }}</ref><ref name="Horita_1995">{{cite journal | vauthors = Horita H, Kumamoto Y, Satoh Y, Suzuki N, Wada H, Shibuya A, Adachi H, Kurohata T, Tsukamoto T | title = [The preventive effect of indeloxazine hydrochloride to the sexual dysfunction caused by anti-androgenergic agent (allylestrenol)] | journal = Nihon Hinyokika Gakkai Zasshi |trans-journal=The Japanese Journal of Urology] | volume = 86 | issue = 5 | pages = 1044–1050 | date = May 1995 | pmid = 7541089 | doi = 10.5980/jpnjurol1989.86.1044 | language = ja | doi-access = free }}</ref><ref name="Noguchi_1998">{{cite journal | vauthors = Noguchi K, Harada M, Masuda M, Takeda M, Kinoshita Y, Fukushima S, Miyai K, Fukuoka H, Hosaka M | title = Clinical significance of interruption of therapy with allylestrenol in patients with benign prostatic hypertrophy | journal = International Journal of Urology | volume = 5 | issue = 5 | pages = 466–470 | date = September 1998 | pmid = 9781436 | doi = 10.1111/j.1442-2042.1998.tb00389.x | doi-access = free }}</ref><ref name="Noguchi_2000">{{cite journal | vauthors = Noguchi K, Uemura H, Takeda M, Sekiguchi Y, Ogawa K, Hosaka M | title = [Rebound of prostate specific antigen after discontinuation of antiandrogen therapy for benign prostatic hyperplasia] | journal = Hinyokika Kiyo. Acta Urologica Japonica | volume = 46 | issue = 9 | pages = 605–607 | date = September 2000 | pmid = 11107528 | language = ja }}</ref><ref name="Noguchi_2002">{{cite journal | vauthors = Noguchi K, Takeda M, Hosaka M, Kubota Y | title = [Clinical effects of allylestrenol on patients with benign prostatic hyperplasia (BPH) evaluated with criteria for treatment efficacy in BPH] | journal = Hinyokika Kiyo. Acta Urologica Japonica | volume = 48 | issue = 5 | pages = 269–273 | date = May 2002 | pmid = 12094708 | language = ja }}</ref><ref name="Noguchi_2006">{{cite journal | vauthors = Noguchi K, Suzuki K, Teranishi J, Kondo K, Kishida T, Saito K, Uemura H, Kubota Y | title = Recovery of serum prostate specific antigen value after interruption of antiandrogen therapy with allylestrenol for benign prostatic hyperplasia | journal = Hinyokika Kiyo. Acta Urologica Japonica | volume = 52 | issue = 7 | pages = 527–530 | date = July 2006 | pmid = 16910584 }}</ref> Related medications that have similarly been used to treat BPH, particularly in Japan, include chlormadinone acetate, gestonorone caproate, and oxendolone.<ref name="Katayama_1986" /><ref name="Iguchi_1994" /> Allylestrenol has also been studied in the treatment of prostate cancer in Japan.<ref name="Takeuchi_1981">{{cite journal | vauthors = Takeuchi H | title = The therapeutic effect of concurrent administration of 5-fluorouracil and allylestrenol or hexestrol in small doses on prostatic carcinoma | journal = The Prostate. Supplement | volume = 1 | pages = 111–117 | date = 1981 | pmid = 6281750 | doi = 10.1002/pros.2990020518 | s2cid = 33940589 }}</ref><ref name="Yamanaka_1983" /> The medication has been studied as a puberty blocker in the treatment of precocious puberty as well.<ref name="Riquelme_Moreno_1972">{{cite journal | vauthors = Riquelme Moreno E, Montiel López P, Bravo Guerra R, Escobar Cauz G | title = [Control of 5 cases of idiopathic precocious puberty with allylestrenol] | journal = Ginecologia Y Obstetricia De Mexico | volume = 32 | issue = 189 | pages = 99–108 | date = July 1972 | pmid = 5057420 | language = es }}</ref>

===Available forms=== Allylestrenol is available in the form of 5 mg oral tablets.<ref name="Muller_1998">{{cite book | vauthors = Muller | title = European Drug Index: European Drug Registrations | pages = 545– | date = 19 June 1998 | edition = Fourth | url = https://books.google.com/books?id=2HBPHmclMWIC&pg=PA545 | publisher = CRC Press | isbn = 978-3-7692-2114-5 }}</ref><ref name="Tripathi_2013">{{cite book | vauthors = Tripathi KD | title = Essentials of Medical Pharmacology | pages = 318– | date = 30 September 2013 | url = https://books.google.com/books?id=FfG8AQAAQBAJ&pg=PA318 | publisher = JP Medical Ltd | isbn = 978-93-5025-937-5 }}</ref><ref name="Satoskar_1973">{{cite book | vauthors = Satoskar RS, Bhandarkar SD, Rege NN | chapter = Gonadotropins, Estrogens, and Progesins | title = Pharmacology and Pharmacotherapeutics | pages = 941– | year = 1973 | chapter-url = https://books.google.com/books?id=7d493VOD4P8C&pg=PA941 | publisher = Popular Prakashan | isbn = 978-81-7991-527-1 }}</ref> It is typically used at a dosage of 5 to 40 mg/day.<ref name="Tripathi_2013" /><ref name="Satoskar_1973" /> In Japan, a 25 mg allylestrenol oral tablet, under the brand name Perselin, is marketed for the treatment of BPH.<ref name="Fukuoka_1993" />

==Side effects== {{See also|Progestin#Side effects}}

Allylestrenol should not be taken by people who are allergic to ibuprofen or naproxen,<ref name="cite8e8db79a">{{cite web | title = Aspirin information from Drugs.com | url = https://www.drugs.com/aspirin.html | url-status = live | archive-url = https://web.archive.org/web/20080509163105/http://www.drugs.com/aspirin.html | archive-date = 9 May 2008 | access-date = 8 May 2008 }}</ref> or who have salicylate intolerance<ref>{{cite journal | vauthors = Raithel M, Baenkler HW, Naegel A, Buchwald F, Schultis HW, Backhaus B, Kimpel S, Koch H, Mach K, Hahn EG, Konturek PC | title = Significance of salicylate intolerance in diseases of the lower gastrointestinal tract | journal = Journal of Physiology and Pharmacology | volume = 56 | issue = Suppl 5 | pages = 89–102 | date = September 2005 | pmid = 16247191 }}</ref> or a more generalized drug intolerance to NSAIDs, and caution should be exercised in those with asthma or NSAID-precipitated bronchospasm. Owing to its effect on the stomach lining, manufacturers recommend people with peptic ulcers, mild diabetes, or gastritis seek medical advice before using allylestrenol.<ref name="cite8e8db79a" />

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).<ref name="Borglin_1960" /> When used at high dosages in the treatment of BPH in men, allylestrenol can cause symptoms of hypogonadism and sexual dysfunction.<ref name="Shida_1986" /><ref name="Kumamoto_1990" /><ref name="Kumamoto_1990a" /> The medication indeloxazine may be able to counteract allylestrenol-associated sexual dysfunction.<ref name="Horita_1995" /> Allylestrenol has no androgenic or other off-target hormonal side effects.<ref name="Shida_1986" /><ref name="Bergink_1985" /><ref name="Madjerekde Visser1960" />

====Progestogenic and off-target activities==== Allylestrenol is a progestogen, or an agonist of the progesterone receptor (PR).<ref name="FieldRichards_1961">{{cite journal | vauthors = Field-Richards S, Snaith L | title = Allylestrenol: a new oral progestogen | journal = Lancet | volume = 1 | issue = 7169 | pages = 134–136 | date = January 1961 | pmid = 13699366 | doi = 10.1016/s0140-6736(61)91310-1 }}</ref> It is lacking the keto group at the C3 position (part of the important ''3-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 a prodrug of 17α-allyl-19-nortestosterone (3-ketoallylestrenol).<ref name="McRobb_2008">{{cite journal | vauthors = McRobb L, Handelsman DJ, Kazlauskas R, Wilkinson S, McLeod MD, Heather AK | title = Structure-activity relationships of synthetic progestins in a yeast-based in vitro androgen bioassay | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 110 | issue = 1–2 | pages = 39–47 | date = May 2008 | pmid = 18395441 | doi = 10.1016/j.jsbmb.2007.10.008 | s2cid = 5612000 }}</ref><ref name="Zeelen_1990">{{cite book | vauthors = Zeelen FJ | title = Medicinal chemistry of steroids | pages = 108–109 | year = 1990 | url = https://books.google.com/books?id=px9tAAAAMAAJ | publisher = Elsevier Science Limited | isbn = 978-0-444-88727-6 | quote = 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. }}</ref><ref name="Rozenbaum_1982">{{cite journal | vauthors = Rozenbaum H | title = Relationships between chemical structure and biological properties of progestogens | journal = American Journal of Obstetrics and Gynecology | volume = 142 | issue = 6 Pt 2 | pages = 719–724 | date = March 1982 | pmid = 7065053 | doi = 10.1016/S0002-9378(16)32477-2 }}</ref> Allylestrenol is a far less potent progestogen than many other 19-nortestosterone derivatives.<ref name="FieldRichards_1961" /> The effective ovulation-inhibiting or contraceptive dosage of allylestrenol in women has been studied, albeit limitedly.<ref name="Endrikat_2011">{{cite journal | vauthors = Endrikat J, Gerlinger C, Richard S, Rosenbaum P, Düsterberg B | title = Ovulation inhibition doses of progestins: a systematic review of the available literature and of marketed preparations worldwide | journal = Contraception | volume = 84 | issue = 6 | pages = 549–557 | date = December 2011 | pmid = 22078182 | doi = 10.1016/j.contraception.2011.04.009 }}</ref> At 20 mg/day allylestrenol, ovulation occurred in 50% of 6 cycles, and at 25 mg/day, ovulation occurred in 0% of 3 cycles.<ref name="Endrikat_2011" /><ref name="Pincus_2013">{{cite book | vauthors = Pincus G | title = The Control of Fertility | pages = 222– | date = 3 September 2013 | url = https://books.google.com/books?id=ehQlBQAAQBAJ&pg=PA222 | publisher = Elsevier | isbn = 978-1-4832-7088-3 }}</ref> The total endometrial transformation dosage of allylestrenol in women across the cycle is 150 to 250 mg.<ref name="Leidenberger_2009">{{cite book | vauthors = Leidenberger FA, Strowitzki T, Ortmann O | title = Klinische Endokrinologie für Frauenärzte | pages = 225– | date = 29 August 2009 | url = https://books.google.com/books?id=bqokBAAAQBAJ&pg=PA225 | publisher = Springer-Verlag | isbn = 978-3-540-89760-6 }}</ref> 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.<ref name="Bergink_1985">{{cite journal | vauthors = Bergink EW, Loonen PB, Kloosterboer HJ | title = Receptor binding of allylestrenol, a progestagen of the 19-nortestosterone series without androgenic properties | journal = Journal of Steroid Biochemistry | volume = 23 | issue = 2 | pages = 165–168 | date = August 1985 | pmid = 3928974 | doi = 10.1016/0022-4731(85)90232-8 }}</ref><ref name="Madjerekde Visser1960">{{cite journal | vauthors = Madjerek Z, De Visser J, Van Der Vies J, Overbeek GA | title = Allylestrenol, a pregnancy maintaining oral gestagen | journal = Acta Endocrinologica | volume = 35 | issue = I | pages = 8–19 | date = September 1960 | pmid = 13765069 | doi = 10.1530/acta.0.XXXV0008 }}</ref> As such, it appears to have properties more similar to those of natural progesterone.<ref name="Bergink_1985" /><ref name="Madjerekde Visser1960" />

The binding and activity profiles of allylestrenol and its major active metabolite at steroid hormone receptors and related proteins have been studied.<ref name="Bergink_1985" /><ref name="McRobb_2008" /> Allylestrenol has less than 0.2% of the affinity of ORG-2058 and less than 2% of the affinity of progesterone for the PR.<ref name="Bergink_1985" /> Similarly, it has less than 0.2% of the affinity of testosterone for the androgen receptor (AR), less than 0.2% of the affinity of estradiol for the estrogen receptor (ER), less than 0.2% of the affinity of dexamethasone for the glucocorticoid receptor (GR), and 0.9% of the affinity of testosterone for sex hormone-binding globulin (SHBG).<ref name="Bergink_1985" /> Conversely, its metabolite 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.<ref name="Bergink_1985" /> The affinity of 17α-allyl-19-nortestosterone for the AR was less than that of norethisterone and medroxyprogesterone acetate and its affinity for SHBG was much lower than that of norethisterone.<ref name="Bergink_1985" /> These findings may help to explain the absence of teratogenic effects of allylestrenol on the external genitalia of female and male rat fetuses.<ref name="Bergink_1985" />

{| class="wikitable mw-collapsible mw-collapsed" style="text-align:left; margin-left:auto; margin-right:auto; border:none;" |+ class="nowrap" | Relative affinities (%) of allylestrenol and metabolites |- ! Compound || {{abbrlink|PR|Progesterone receptor}} || {{abbrlink|AR|Androgen receptor}} || {{abbrlink|ER|Estrogen receptor}} || {{abbrlink|GR|Glucocorticoid receptor}} || {{abbrlink|MR|Mineralocorticoid receptor}} || {{abbrlink|SHBG|Sex hormone-binding globulin}} || {{abbrlink|CBG|Corticosteroid binding globulin}} |- | Allylestrenol || 0 || 0 || 0 || 0 || ? || 1 || ? |- | {{abbrlink|17α-Allyl-19-NT|17α-Allyl-19-nortestosterone}} || 186 || 5 || 0 || 10 || ? || 3 || ? |- class="sortbottom" | colspan="8" style="width: 1px; background-color:var(--background-color-notice-subtle,#eaecf0); color:inherit; text-align: center;" | '''Notes:''' Values are percentages (%). Reference ligands (100%) were {{abbrlink|P4|progesterone (medication)}} for the {{abbrlink|PR|progesterone receptor}}, {{abbrlink|T|testosterone (medication)}} for the {{abbrlink|AR|androgen receptor}}, {{abbr|E2|estradiol}} for the {{abbrlink|ER|estrogen receptor}}, {{abbrlink|DEXA|dexamethasone}} for the {{abbrlink|GR|glucocorticoid receptor}}, aldosterone for the {{abbrlink|MR|mineralocorticoid receptor}}, {{abbrlink|T|testosterone (medication)}} for {{abbrlink|SHBG|sex hormone-binding globulin}}, and cortisol for {{abbrlink|CBG|Corticosteroid-binding globulin}}. '''Sources:''' <ref name="Bergink_1985" /> |}

====Antigonadotropic effects==== [[File:Testosterone levels with 50 mg per day allylestrenol or 50 mg per day chlormadinone acetate over 12 weeks in men with benign prostatic hyperplasia.png|thumb|right|300px|class=skin-invert-image|Testosterone levels with 50 mg/day allylestrenol or 50 mg/day chlormadinone acetate orally over 12 weeks in men with benign prostatic hyperplasia.<ref name="Kumamoto_1990" />]]

Similarly to other progestogens, allylestrenol has potent antigonadotropic effects.<ref name="Yasuda_1997" /> It is able to considerably decrease circulating concentrations of luteinizing hormone, testosterone, and dihydrotestosterone in men.<ref name="Ohyama_1986" /><ref name="Kumamoto_1990" /><ref name="Horita_1995" /><ref name="Noguchi_1998" /> At a dosage of 50 mg/day, allylestrenol has been found to suppress circulating testosterone levels by 78% in men with BPH.<ref name="Yasuda_1997" /> This is about the maximum that progestogens are known to be able to suppress testosterone levels in men.<ref name="Jacobi_1980">{{cite journal | vauthors = Jacobi GH, Altwein JE, Kurth KH, Basting R, Hohenfellner R | title = Treatment of advanced prostatic cancer with parenteral cyproterone acetate: a phase III randomised trial | journal = British Journal of Urology | volume = 52 | issue = 3 | pages = 208–215 | date = June 1980 | pmid = 7000222 | doi = 10.1111/j.1464-410X.1980.tb02961.x }}</ref><ref name="Knuth_1984">{{cite journal | vauthors = Knuth UA, Hano R, Nieschlag E | title = Effect of flutamide or cyproterone acetate on pituitary and testicular hormones in normal men | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 59 | issue = 5 | pages = 963–969 | date = November 1984 | pmid = 6237116 | doi = 10.1210/jcem-59-5-963 }}</ref><ref name="Sander_1978">{{cite journal | vauthors = Sander S, Nissen-Meyer R, Aakvaag A | title = On gestagen treatment of advanced prostatic carcinoma | journal = Scandinavian Journal of Urology and Nephrology | volume = 12 | issue = 2 | pages = 119–121 | date = 1978 | pmid = 694436 | doi = 10.3109/00365597809179977 }}</ref> 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 of chlormadinone acetate and oxendolone.<ref name="Katayama_1986" /> 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.<ref name="Kumamoto_1990" /> Animal research suggests that allylestrenol produces its beneficial effects in BPH via its antigonadotropic effects and consequent suppression of androgen levels and inhibition of prostate gland growth, similarly to other progestins.<ref name="Yasuda_1997">{{cite journal | vauthors = Yasuda N, Fujino K, Shiraji T, Nambu F, Kondo K | title = Effects of steroid 5alpha-reductase inhibitor ONO-9302 and anti-androgen allylestrenol on the prostatic growth, and plasma and prostatic hormone levels in rats | journal = Japanese Journal of Pharmacology | volume = 74 | issue = 3 | pages = 243–252 | date = July 1997 | pmid = 9268084 | doi = 10.1254/jjp.74.243 | doi-access = free }}</ref> Some studies have found that allylestrenol is less effective for BPH than chlormadinone acetate but also produces fewer side effects and sexual dysfunction.<ref name="Shida_1986" /><ref name="Kumamoto_1990" /><ref name="Kumamoto_1990a" /> Allylestrenol therapy for BPH is associated with a significant decrease in prostate-specific antigen levels, which may mask the detection of prostate cancer.<ref name="Yasuda_1997" /><ref name="Noguchi_2006" />

====Other activities==== Allylestrenol is not a significant 5α-reductase inhibitor.<ref name="Yasuda_1997" /> In one study, it showed about 80,000-fold lower potency for inhibition of 5α-reductase ''in vitro'' than the established 5α-reductase inhibitor epristeride ({{abbrlink|IC<sub>50</sub>|half-maximal inhibitory concentration}} = 11.3 nM for epristeride and 890 μM for allylestrenol).<ref name="Yasuda_1997" /> In another study, there was 70% inhibition of 5α-reductase by allylestrenol at a concentration of 60 μM.<ref name="Yasuda_1997" /> This difference may have been due to different experimental conditions, but is still much lower than epristeride.<ref name="Yasuda_1997" />

===Pharmacokinetics=== Following oral administration, peak levels of allylestrenol occur after 2 to 4 hours.<ref name="Bengtsson_1972">{{cite book | vauthors = Bengtsson LP, Tausk M | title = Pharmacology of the endocrine system and related drugs: progesterone, progestational drugs and antifertility agents | pages = 235–237 | date = September 1972 | url = https://books.google.com/books?id=Nv5sAAAAMAAJ | publisher = Pergamon Press | isbn = 978-0-08-015745-0 }}</ref><ref name="Thijssen_1967">{{cite thesis | vauthors = Thijssen JH | title = Het metabolisme van progestatieve stoffen | date = 1967 | publisher = Rijksuniversiteit te Utrecht }}</ref> The medication shows considerable plasma protein binding.<ref name="Bengtsson_1972" /><ref name="Thijssen_1967" /> It has relatively low affinity for SHBG, much lower than that of norethisterone.<ref name="Bergink_1985" /> Allylestrenol is metabolized in the liver, via reduction, hydroxylation, and conjugation.<ref name="Bengtsson_1972" /><ref name="Thijssen_1967" /> It is known to be a substrate of CYP3A4.<ref name="SuperCYP" /> It is thought to be a prodrug of 17α-allyl-19-nortestosterone (3-ketoallylestrenol), which, in accordance, is a known active metabolite of allylestrenol.<ref name="McRobb_2008" /><ref name="Zeelen_1990" /> The biological half-life of allylestrenol has been reported to be "several hours" or, presumably in its active form, reportedly about 10 hours.<ref name="Bengtsson_1972" /><ref name="Thijssen_1967" /><ref name="Saha_2000">{{cite journal | vauthors = Saha A, Roy K, Kakali DE | title = Effects of Allylestrenol on Blood Lipids in Relation to its Biological Activity | journal = Indian Journal of Pharmaceutical Sciences | volume = 62 | issue = 2 | pages = 115 | year = 2000 }}</ref> In the blood, unchanged allylestrenol accounted for 15 to 40% of radioactivity, an unconjugated metabolite accounted for 4 to 10% of radioactivity, and the rest of the radioactivity corresponded to conjugated metabolites.<ref name="Bengtsson_1972" /><ref name="Thijssen_1967" /> Allylestrenol is eliminated mainly in urine, 44% by 24 hours and 67% within 4 days.<ref name="Bengtsson_1972" /><ref name="Thijssen_1967" /> It is excreted almost completely as conjugates, with 75% of these being sulfate conjugates and 24% being glucuronide conjugates.<ref name="Bengtsson_1972" /><ref name="Thijssen_1967" />

==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 synthetic estrane steroid and a derivative of testosterone.<ref name="Elks_2014" /> It is a member of the estrane subgroup of the 19-nortestosterone family of progestins,<ref name="Anita_2017">{{cite book | vauthors = Anita MV, Sandhya J, Jain, Goel N | title = Use of Progestogens in Clinical Practice of Obstetrics and Gynecology | pages = 10– | date = 31 December 2017 | url = https://books.google.com/books?id=VrpEDwAAQBAJ&pg=PA10 | publisher = JP Medical Ltd | isbn = 978-93-5270-218-3 }}</ref> but unlike most other 19-nortestosterone progestins, is not a derivative of norethisterone (17α-ethynyl-19-nortestosterone).<ref name="Aronson_2009">{{cite book | vauthors = Aronson JK | title = Meyler's Side Effects of Endocrine and Metabolic Drugs | pages = 289– | date = 21 February 2009 | url = https://books.google.com/books?id=BWMeSwVwfTkC&pg=PA289 | publisher = Elsevier | isbn = 978-0-08-093292-7 }}</ref><ref name="Bergink_1985" /><ref name="Zeelen_1990" /> This is because it possesses an allyl group at the C17α position rather than the usual ethynyl group.<ref name="Aronson_2009" /><ref name="Bergink_1985" /><ref name="Zeelen_1990" /> As such, along with altrenogest (17α-allyl-19-nor-δ<sup>9,11</sup>-testosterone), allylestrenol is a derivative of 17α-allyltestosterone rather than of 17α-ethynyltestosterone.<ref name="Aronson_2009" /><ref name="Bergink_1985" /><ref name="Zeelen_1990" />

Allylestrenol is also unique among most 19-nortestosterone progestins in that it lacks the ketone at the C3 position.<ref name="Elks_2014" /> It shares this property with lynestrenol (17α-ethynylestr-4-en-17β-ol), desogestrel (11-methylene-17α-ethynyl-18-methylestr-4-en-17β-ol), and the anabolic–androgenic steroid (AAS) ethylestrenol (17α-ethylestr-4-en-17β-ol).<ref name="Elks_2014" /> 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).<ref name="Elks_2014" />

===Synthesis=== Chemical syntheses of allylestrenol have been published.<ref name="Elks_2014" /><ref name="Publishing_2013" /><ref name="Gunnet_2000">{{cite book | vauthors = Gunnet JW, Dixon LA | chapter = Hormones, Sex Hormones | title = Kirk-Othmer Encyclopedia of Chemical Technology | year = 2000 | doi = 10.1002/0471238961.19052407211414.a01 | isbn = 978-0-471-23896-6 }}</ref><ref name="Springer2013">{{cite book | title = Die Gestagene | pages = 16 | date = 27 November 2013 | url = https://books.google.com/books?id=t8GpBgAAQBAJ&pg=PA16 | publisher = Springer-Verlag | isbn = 978-3-642-99941-3 }}</ref><ref name="De_Winter_1959">{{cite journal | vauthors = De Winter MS, Siegman CM, Szpilfogel SA | title = 17-alkylated-3-deoxo-19-nor-testosterone | journal = Chem. Ind. | pages = 905 | date = 1959 }}</ref>

A Chinese chemical synthesis of allylestrenol was recently reported:<ref>郑正春, et al. CN102225960 (2012 to Beijing Keyifeng Biotech Development Co ltd).</ref> Prior art:<ref>, GB841411 (1960 to Organon).</ref>

center|500px|class=skin-invert-image

Bolandione [734-32-7] ('''1''') is reacted with 1 equivalent of ethane-1,2-dithiol to give PC13831215 ('''2'''). Protection of the remaining ketone with ethyleneglycol gives PC71579263 ('''3'''). Reduction with lithium metal in liquid ammonia gives PC71579264 ('''4'''). Deprotection of the ketal protecting group by heating in aqueous acid gives Estr-4-en-17-one [3646-28-4] ('''5'''). Grignard reaction with allyl chloride completed the synthesis of allylestrenol ('''6''').

==History== Allylestrenol was patented in 1958<ref name="Publishing_2013">{{cite book | vauthors = Publishing WA | title = Pharmaceutical Manufacturing Encyclopedia, 3rd Edition | pages = 170– | date = 22 October 2013 | url = https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA170 | publisher = Elsevier | isbn = 978-0-8155-1856-3 }}</ref> and has been marketed for medical use since 1961.<ref name="FieldRichards_1961a">{{cite journal | vauthors = Field-Richards S, Snaith L | title = Allylestrenol: a new oral progestogen | journal = Lancet | volume = 1 | issue = 7169 | pages = 134–136 | date = January 1961 | pmid = 13699366 | doi = 10.1016/S0140-6736(61)91310-1 }}</ref><ref name="Simpson_1997">{{cite book | vauthors = Simpson JA, Weiner ES | title = Oxford English Dictionary Additions Series | pages = 36– | year = 1997 | url = https://books.google.com/books?id=gUGcAQAAQBAJ&pg=PA36 | publisher = Clarendon Press | isbn = 978-0-19-860027-5 | quote = 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. [...] }}</ref><ref name="Juta1962">{{cite book | title = Medical Proceedings: A South African Journal for the Advancement of Medical Science | year = 1962 | url = https://books.google.com/books?id=QORDAQAAIAAJ | publisher = Juta and Company | quote = 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. }}</ref> It was developed by Organon Laboratories.<ref name="Juta1962" /><ref name="Simpson_1997" />

==Society and culture==

===Generic names=== ''Allylestrenol'' is the generic name of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|BAN|British Approved Name}}, and {{abbrlink|JAN|Japanese Accepted Name}}, while ''allylestrénol'' is its {{abbrlink|DCF|Dénomination Commune Française}} and ''allilestrenolo'' is its {{abbrlink|DCIT|Denominazione Comune Italiana}}.<ref name="Elks_2014">{{cite book | vauthors = Elks J | title = The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies | pages = 31– | date = 14 November 2014 | url = https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA31 | publisher = Springer | isbn = 978-1-4757-2085-3 }}</ref><ref name="IndexNominum2000">{{cite book | title = Index Nominum 2000: International Drug Directory | pages = 29– | date = January 2000 | url = https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA29 | publisher = Taylor & Francis | isbn = 978-3-88763-075-1 }}</ref><ref name="Morton_2012">{{cite book | vauthors = Morton IK, Hall JM | title = Concise Dictionary of Pharmacological Agents: Properties and Synonyms | pages = 11– | date = 6 December 2012 | url = https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA11 | publisher = Springer Science & Business Media | isbn = 978-94-011-4439-1 }}</ref><ref name="cite7458195b">{{cite web | title = Allylestrenol | url = https://www.drugs.com/international/allylestrenol.html }}</ref> The {{abbrlink|BAN|British Approved Name}} was originally ''allyloestrenol'', but it was eventually changed.<ref name="Elks_2014" /><ref name="IndexNominum2000" /><ref name="cite7458195b" /> The medication is also known by its developmental code name ''SC-6393''.<ref name="Elks_2014" /><ref name="IndexNominum2000" /><ref name="cite7458195b" />

===Brand names=== The major brand names of allylestrenol include Gestanin, Gestanon, Perselin, and Turinal.<ref name="Micromedex" /><ref name="Martindale" /><ref name="cite7458195b" /><ref name="IndexNominum2000" /><ref name="Publishing_2013" /> 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.<ref name="Micromedex" /><ref name="Martindale" /><ref name="cite7458195b" /><ref name="IndexNominum2000" /><ref name="Publishing_2013" />

===Availability=== thumb|right|300px|class=skin-invert-image|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 Europe, Southern, Eastern, and Southeastern Asia, Africa, Oceania, and Latin America.<ref name="Micromedex">{{cite web | title = Micromedex Products: Please Login | url = https://www.micromedexsolutions.com/micromedex2/librarian/ }}</ref><ref name="Martindale" /><ref name="cite7458195b" /><ref name="IndexNominum2000" /> However, although it has been widely marketed in the past, the availability of allylestrenol is relatively limited today.<ref name="Micromedex" /><ref name="Martindale" /><ref name="cite7458195b" /><ref name="IndexNominum2000" /> 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.<ref name="Micromedex" /><ref name="Martindale" /><ref name="cite7458195b" /><ref name="IndexNominum2000" /> 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).<ref name="Micromedex" /><ref name="Martindale" /><ref name="cite7458195b" /><ref name="IndexNominum2000" /> However, it seems to have been discontinued in these countries.<ref name="Micromedex" /><ref name="Martindale" /><ref name="cite7458195b" /><ref name="IndexNominum2000" /> It does not seem to have been marketed in the United States or Canada.<ref name="Micromedex" /><ref name="Martindale" /><ref name="cite7458195b" /><ref name="IndexNominum2000" />{{clear}}

== References == {{Reflist}}

{{Progestogens and antiprogestogens}} {{Drugs used in benign prostatic hypertrophy}} {{Progesterone receptor modulators}}

Category:Tertiary alcohols Category:Allyl compounds Category:Antigonadotropins Category:Estranes Category:Hormonal antineoplastic drugs Category:Obstetric drugs Category:Prodrugs Category:Progestogens