CPA was discovered in 1961.[18] It was originally developed as a progestin.[18] In 1965, the antiandrogenic effects of CPA were discovered.[19] CPA was first marketed, as an antiandrogen, in 1973, and was the first antiandrogen to be introduced for medical use.[20] A few years later, in 1978, CPA was introduced as a progestin in a birth control pill.[21] It has been described as a "first-generation" progestin[22] and as the prototypical antiandrogen.[23] CPA is available widely throughout the world.[24][25] An exception is theUnited States, where it is not approved for use.[26][27]
In 2020, theEuropean Medicine Agency issued a warning that high doses of cyproterone acetate may contribute to risk of meningioma, and recommended physicians use alternative treatment for most indications (or the minimum effective dose where no alternatives were available) with the exception ofprostate carcinoma.[29]
CPA is used withethinylestradiol as acombined birth control pill to preventpregnancy. This birth control combination has been available since 1978.[21] The formulation is taken once daily for 21 days, followed by a 7-day free interval.[31] CPA has also been available in combination withestradiol valerate (brand name Femilar) as a combined birth control pill inFinland since 1993.[32][33] High-dose CPA tablets have a contraceptive effect and can be used as a form of birth control, although they are not specifically licensed as such.[34]
CPA is used as an antiandrogen to treatandrogen-dependentskin and hair conditions such asacne,seborrhea,hirsutism (excessive hair growth),scalp hair loss, andhidradenitis suppurativa in women.[35][36][37][38][39][40][41] These conditions are worsened by the presence of androgens, and by suppressing androgen levels and blocking their actions, CPA improves the symptoms of these conditions. CPA is used to treat such conditions both at low doses as a birth control pill and on its own at higher doses.[35][36][37][38][42] A birth control pill containing low-dose CPA in combination withethinylestradiol to treat acne has been found to result in overall improvement in 75 to 90% of women, with responses approaching 100% improvement.[43] High-dose CPA alone likewise has been found to improve symptoms of acne by 75 to 90% in women.[44] Discontinuation of CPA has been found to result in marked recurrence of symptoms in up to 70% of women.[45] CPA is one of the most commonly used medications in the treatment of hirsutism, hyperandrogenism, and polycystic ovary syndrome in women throughout the world.[46][47]
Higher dosages of CPA are used in combination with an estrogen specifically at doses of 25 to 100 mg/day cyclically in the treatment of hirsutism in women.[47][48][49] The efficacy of such dosages of CPA in the treatment of hirsutism in women appear to be similar to that ofspironolactone,flutamide, andfinasteride.[48][49][46][47]Randomized controlled trials have found that higher dosages of CPA (e.g., 20 mg/day or 100 mg/day) added cyclically to abirth control pill containingethinylestradiol and 2 mg/day CPA were no more effective or only marginally more effective in the treatment of severe hirsutism in women than the birth control pill alone.[47][49][46][50][51][52] Maintenance therapy with lower doses of CPA, such as 25 mg/day, has been found to be effective in preventing relapse of symptoms of hirsutism.[45] CPA has typically been combined with ethinylestradiol, but it can alternatively be used in combination withhormone replacement therapy dosages ofestradiol instead.[47] CPA at a dosage of 50 mg/day in combination with 100 μg/day transdermal estradiol patches has been found to be effective in the treatment of hirsutism similarly to the combination of CPA with ethinylestradiol.[49][53]
The efficacy of the combination of an estrogen and CPA in the treatment of hirsutism in women appears to be due to marked suppression of total and freeandrogen levels as well as additional blockade of theandrogen receptor.[46][47][54]
CPA has been found to be effective in the treatment of acne in males, with marked improvement in symptoms observed at dosages of 25, 50, and 100 mg/day in different studies.[55][56][57][58] It can also halt further progression of scalp hair loss in men.[59][60][61] Increased head hair and decreased body hair has been observed with CPA in men with scalp hair loss.[62][13] However, its side effects in men, such asdemasculinization,gynecomastia,sexual dysfunction,bone density loss, and reversibleinfertility, make the use of CPA in males impractical in most cases.[59][60][56][57][63][64][65] In addition, lower dosages of CPA, such as 25 mg/day, have been found to be better-tolerated in men.[57] But such doses also show lower effectiveness in the treatment of acne in men.[55]
CPA is widely used as anantiandrogen andprogestogen infeminizing hormone therapy fortransgender individuals.[74][75][76][77][78][79][80] It has been historically used orally at a dosage of 10 to 100 mg/day and by intramuscular injection at a dosage of 300 mg once every 4 weeks.[81][82] Many transgender individuals seeking feminizing hormone therapy have breast growth as one of the goals for undergoing feminizing hormone therapy, making this particular side effect of CPA generally viewed as a beneficial outcome rather than an issue.[60]
CPA has an advantage overspironolactone as an antiandrogen in transgender people, as the combination of estrogen and CPA consistently suppressestestosterone levels into the normal female range whereas estrogen with spironolactone does not.[88][89][90][91][92][93][94] Spironolactone is the most widely used antiandrogen in transgender women in the United States, whereas CPA is widely used in Europe and throughout the rest of the world.[89][87]
CPA is used as an antiandrogen monotherapy and means ofandrogen deprivation therapy in thepalliative treatment ofprostate cancer in men.[9][99][100][101][102][103] It is used at very high doses by mouth or by intramuscular injection to treat this disease. Antiandrogens do not cure prostate cancer, but can significantly extend life in men with the disease.[104][105][99] CPA has similar effectiveness toGnRH modulators andsurgical castration,high-dose estrogen therapy (e.g., withdiethylstilbestrol), and high-dosenonsteroidal antiandrogen monotherapy (e.g., withbicalutamide), but has significantly inferior effectiveness tocombined androgen blockade with a GnRH modulator and a nonsteroidal antiandrogen (e.g., with bicalutamide orenzalutamide).[99][105][106][107][108] In addition, the combination of CPA with a GnRH modulator or surgical castration has not been found to improve outcomes relative to a GnRH modulator or surgical castration alone, in contrast to nonsteroidal antiandrogens.[109] Due to its inferior effectiveness,tolerability, andsafety, CPA is rarely used in the treatment of prostate cancer today, having largely been superseded by GnRH modulators and nonsteroidal antiandrogens.[110][111] CPA is the only steroidal antiandrogen that continues to be used in the treatment of prostate cancer.[105]
Dose-ranging studies of CPA for prostate cancer were not performed, and the optimal dosage of CPA for the treatment of the condition has not been established.[112][113] A dosage range of oral CPA of 100 to 300 mg/day is used in the treatment of prostate cancer, but generally 150 to 200 mg/day oral CPA is used.[114][115] Schröder (1993, 2002) reviewed the issue of CPA dosage and recommended a dosage of 200 to 300 mg/day for CPA as a monotherapy and a dosage of 100 to 200 mg/day for CPA incombined androgen blockade (that is, CPA in combination withsurgical ormedical castration).[116][101] However, the combination of CPA with castration for prostate cancer has been found to significantly decreaseoverall survival compared to castration alone.[117] Hence, the use of CPA as the antiandrogen component in combined androgen blockade would appear not to be advisable.[117] When used by intramuscular injection to treat prostate cancer, CPA is used at a dosage of 300 mg once a week.[65]
High-dose CPA significantly decreasessexual fantasies andsexual activity in 80 to 90% of men with paraphilias.[127] In addition, it has been found to decrease the rate of reoffending in sex offenders from 85% to 6%, with most of the reoffenses being committed by individuals who did not follow their CPA treatment prescription.[127] It has been reported that in 80% of cases, 100 mg/day CPA is adequate to achieve the desired reduction of sexuality, whereas in the remaining 20% of cases, 200 mg/day is sufficient.[131] When only a partial reduction in sexuality is desired, 50 mg/day CPA can be useful.[131] Reduced sexual desire and erectile function occurs with CPA by the end of the first week of treatment, and becomes maximal within three to four weeks.[131][65] The dosage range is 50 to 300 mg/day.[65][131]
CPA is used as an antiandrogen and antiestrogen to treatprecocious puberty in boys and girls.[13][67][132] However, it is not fully satisfactory for this indication because it is not able to completely suppress puberty. It does not suppress skeletal maturation enough to avoid a reduction in height at adulthood.[133] For this reason, CPA has mostly been superseded byGnRH agonists in the treatment of precocious puberty.[67] CPA is not satisfactory forgonadotropin-independent precocious puberty.[134] CPA has been used at dosages of 50 to 300 mg/m2 to treat precocious puberty.[65][13]
CPA is relatively safe in acuteoverdose.[152] It is used at very high doses of up to 300 mg/day by mouth and 700 mg per week by intramuscular injection.[152][159] For comparison, the dose of CPA used in birth control pills is 2 mg/day.[160] There have been no deaths associated with CPA overdose.[152] There are no specificantidotes for CPA overdose, and treatment should besymptom-based.[152]Gastric lavage can be used in the event of oral overdose within the last 2 to 3 hours.[152]
The dehydrogenation of17α-hydroxyprogesterone acetate [302-23-8] (1) withchloranil (tetrachloro-p-benzoquinone) gives a compound that has been called melengestrol acetate [425-51-4] (2). Dehydrogenation with selenium dioxide gives 17-acetoxy-1,4,6-pregnatriene-3,20-dione [2668-75-9] (3). Reacting this with diazomethane results in a 1,3-dipolar addition reaction at C1–C2 of the double bond of the steroid system, which forms a derivative of dihydropyrazole,CID:134990386 (4). This compound cleaves when reacted withperchloric acid,[173] releasing nitrogen molecules and forming a cyclopropane derivative, 6-deschloro cyproterone acetate [2701-50-0] (5). Selective oxidation of the C6=C7 olefin with benzoyl peroxide gives the epoxide, i.e. 6-deschloro-6,7-epoxy cyproterone [15423-97-9] (6). The penultimate step involves a reaction with hydrochloric acid in acetic acid, resulting in the formation of chlorine and its subsequent dehydration, and a simultaneous opening of the cyclopropane ring giving 1α-(chloromethyl) chlormadinone acetate [17183-98-1] (7). The heating of this in collidine reforms the cyclopropane ring, completing the synthesis of CPA (8).
CPA was initially developed as a progestogen for the prevention ofthreatened abortion.[65] As part of its development, it was assessed for androgenic activity to ensure that it would not produceteratogenic effects in femalefetuses.[65] The drug was administered topregnant rats and its effects on the rat fetuses were studied.[65] To the surprise of the researchers, all of the rat pups born appeared to be female.[65] After 20 female rat pups in a row had been counted, it was clear that this could not be a chance occurrence.[65] The rat pups were further evaluated and it was found that, in terms ofkaryotype, about 50% were actually males.[65] The male rat pups had been feminized, and this resultant finding constituted the discovery of the powerful antiandrogenic activity of CPA.[65] A year after patent approval in 1965, Neumann published additional evidence of CPA's antiandrogenic effect in rats; he reported an "organizational effect of CPA on the brain".[19] CPA started being used in animal experiments around the world to investigate how antiandrogens affected fetalsexual differentiation.[179]
The first clinical use of CPA in the treatment ofsexual deviance andprostate cancer occurred in 1966.[14][180][181] It was first studied in the treatment of androgen-dependent skin and hair symptoms, specifically acne, hirsutism, seborrhea, and scalp hair loss, in 1969.[182] CPA was first approved for medical use in 1973 inEurope under the brand name Androcur.[169][183] In 1977, a formulation of CPA was introduced for use by intramuscular injection.[184] CPA was first marketed as a birth control pill in 1978 in combination with ethinylestradiol under the brand name Diane.[21] Followingphase IIIclinical trials, CPA was approved for the treatment of prostate cancer in Germany in 1980.[184][185] CPA became available inCanada as Androcur in 1987, as Androcur Depot in 1990, and as Diane-35 in 1998.[186][187][188] Conversely, CPA was never introduced in any form in theUnited States.[26][30] This was reportedly due to concerns aboutbreast tumors observed with high-dosepregnane progestogens in beagle dogs as well as concerns about potentialteratogenicity in pregnant women.[189] Use of CPA intransgender women, anoff-label indication, was reported as early as 1977.[190][191] The use of CPA in transgender women was well-established by the early 1990s.[192]
The history of CPA, including its discovery, development, and marketing, has been reviewed.[193][13]
TheEnglish andgeneric name of CPA iscyproterone acetate and this is itsUSANTooltip United States Adopted Name,BANTooltip British Approved Name, andJANTooltip Japanese Accepted Name.[24][25][194][195] The English and generic name of unacetylatedcyproterone iscyproterone and this is itsINNTooltip International Nonproprietary Name andBANTooltip British Approved Name,[194][195][196] whilecyprotérone is theDCFTooltip Dénomination Commune Française andFrench name andciproterone is theDCITTooltip Denominazione Comune Italiana andItalian name.[24][25] The name of unesterified cyproterone inLatin iscyproteronum, inGerman iscyproteron, and inSpanish isciproterona.[24][25] These names of cyproterone correspond for CPA toacétate de cyprotérone in French,acetato de ciproterona in Spanish,ciproterone acetato in Italian,cyproteronacetat in German,siproteron asetat in Turkish, andcyproteronacetaat inDutch. CPA is also known by the developmental code namesSH-80714 andSH-714, while unacetylated cyproterone is known by the developmental code namesSH-80881 andSH-881.[24][25][194][195]
CPA is marketed under brand names including Androcur, Androcur Depot, Androcur-100, Androstat, Asoteron, Cyprone, Cyproplex, Cyprostat, Cysaxal, Imvel, and Siterone.[24][25] When CPA is formulated in combination with ethinylestradiol, it is also known asco-cyprindiol, and brand names for this formulation include Andro-Diane, Bella HEXAL 35, Chloe, Cypretil, Cypretyl, Cyproderm, Diane, Diane Mite, Diane-35, Dianette, Dixi 35, Drina, Elleacnelle, Estelle, Estelle-35, Ginette, Linface, Minerva, Vreya, and Zyrona.[24][25] CPA is also marketed in combination withestradiol valerate as Climen, Climene, Elamax, and Femilar.[24]
Availability of CPA in countries throughout the world (as of March 2018). Turquoise is combined with an estrogen at a low dose, dark blue is alone at a high dose, and light blue is both available.
It has been said that the lack of availability of CPA in the United States explains why there are relatively few studies of it in the treatment of androgen-dependent conditions such as hyperandrogenism and hirsutism in women.[153]
Progestins in birth control pills are sometimes grouped by generation.[201][202] While the19-nortestosterone progestins are consistently grouped into generations, thepregnane progestins that are or have been used in birth control pills are typically omitted from such classifications or are grouped simply as "miscellaneous" or "pregnanes".[201][202] In any case, CPA has been described as a "first-generation" progestin similarly to closely related progestins likechlormadinone acetate,medroxyprogesterone acetate, andmegestrol acetate.[22][203]
^abHuber J, Zeillinger R, Schmidt J, Täuber U, Kuhnz W, Spona J (November 1988). "Pharmacokinetics of cyproterone acetate and its main metabolite 15 beta-hydroxy-cyproterone acetate in young healthy women".International Journal of Clinical Pharmacology, Therapy, and Toxicology.26 (11):555–561.PMID2977383.
^abSchindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, et al. (December 2003). "Classification and pharmacology of progestins".Maturitas. 46 Suppl 1 (Suppl 1):S7 –S16.doi:10.1016/j.maturitas.2003.09.014.PMID14670641.Since there is no binding of CPA to SHBG and CBG in the serum, 93% of the compound is bound to serum albumin.
^Hammond GL, Lähteenmäki PL, Lähteenmäki P, Luukkainen T (October 1982). "Distribution and percentages of non-protein bound contraceptive steroids in human serum".Journal of Steroid Biochemistry.17 (4):375–380.doi:10.1016/0022-4731(82)90629-X.PMID6215538.
^Frith RG, Phillipou G (February 1985). "15-Hydroxycyproterone acetate and cyproterone acetate levels in plasma and urine".Journal of Chromatography.338 (1):179–186.doi:10.1016/0378-4347(85)80082-7.PMID3160716.
^abcdefWeber GF (22 July 2015).Molecular Therapies of Cancer. Springer. pp. 316–.ISBN978-3-319-13278-5.The terminal half-life is about 38 h. A portion of the drug is metabolized by hydrolysis to cyproterone and acetic acid. However, in contrast to many other steroid esters hydrolysis is not extensive, and much of the pharmacological activity is exerted by the acetate form. Excretion is about 70% in the feces, mainly in the form of glucuronidated metabolites, and about 30% in the urine, predominantly as non-conjugated metabolites.
^abcAAPL Newsletter(PDF). The Academy. 1998.Archived(PDF) from the original on 30 August 2017. Retrieved16 August 2016.CPA is 100% bioavailable when taken orally with a half life of 38 hours. The injectable form reaches maximum plasma levels in 82 hours and has a half life of about 72 hours.
^abcPucci E, Petraglia F (December 1997). "Treatment of androgen excess in females: yesterday, today and tomorrow".Gynecological Endocrinology.11 (6):411–433.doi:10.3109/09513599709152569.PMID9476091.
^abNeumann F, Elger W (December 1966). "Permanent changes in gonadal function and sexual behavior as a result of early feminization of male rats by treatment with an antiandrogenic steroid".Endokrinologie.50 (5):209–224.PMID5989926.
^abLouw-du Toit R, Storbeck KH, Cartwright M, Cabral A, Africander D (February 2017). "Progestins used in endocrine therapy and the implications for the biosynthesis and metabolism of endogenous steroid hormones".Molecular and Cellular Endocrinology.441:31–45.doi:10.1016/j.mce.2016.09.004.PMID27616670.S2CID38582443.
^Gourdy P, Bachelot A, Catteau-Jonard S, Chabbert-Buffet N, Christin-Maître S, Conard J, et al. (November 2012). "Hormonal contraception in women at risk of vascular and metabolic disorders: guidelines of the French Society of Endocrinology".Annales d'Endocrinologie.73 (5):469–487.doi:10.1016/j.ando.2012.09.001.PMID23078975.
^abBeylot C, Doutre MS, Beylot-Barry M (1998). "Oral contraceptives and cyproterone acetate in female acne treatment".Dermatology.196 (1):148–152.doi:10.1159/000017849.PMID9557250.S2CID46763689.
^abcMiller JA, Jacobs HS (May 1986). "Treatment of hirsutism and acne with cyproterone acetate".Clinics in Endocrinology and Metabolism.15 (2):373–389.doi:10.1016/S0300-595X(86)80031-7.PMID2941191.
^Bettoli V, Zauli S, Virgili A (July 2015). "Is hormonal treatment still an option in acne today?".The British Journal of Dermatology. 172 Suppl 1 (Suppl 1):37–46.doi:10.1111/bjd.13681.PMID25627824.S2CID35615492.
^abReed MJ, Franks S (September 1988). "Anti-androgens in gynaecological practice".Bailliere's Clinical Obstetrics and Gynaecology.2 (3):581–595.doi:10.1016/S0950-3552(88)80045-2.PMID2976627.
^Barth JH, Cherry CA, Wojnarowska F, Dawber RP (July 1991). "Cyproterone acetate for severe hirsutism: results of a double-blind dose-ranging study".Clinical Endocrinology.35 (1):5–10.doi:10.1111/j.1365-2265.1991.tb03489.x.PMID1832346.S2CID27293697.
^Jasonni VM, Bulletti C, Naldi S, Di Cosmo E, Cappuccini F, Flamigni C (April 1991). "Treatment of hirsutism by an association of oral cyproterone acetate and transdermal 17 beta-estradiol".Fertility and Sterility.55 (4):742–745.doi:10.1016/S0015-0282(16)54240-X.PMID1826278.
^abWard A, Brogden RN, Heel RC, Speight TM, Avery GS (July 1984). "Isotretinoin. A review of its pharmacological properties and therapeutic efficacy in acne and other skin disorders".Drugs.28 (1):6–37.doi:10.2165/00003495-198428010-00002.PMID6235105.
^abcCormane RH, van der Meeren HL (1981). "Cyproteronacetate in the management of severe acne in males".Archives of Dermatological Research.271 (2):183–187.doi:10.1007/BF00412545.ISSN0340-3696.S2CID12153042.
^Misch KJ, Dolman WF, Neild V, Rhodes EL (1986). "Response of male acne to antiandrogen therapy with cyproterone acetate".Dermatologica.173 (3):139–142.doi:10.1159/000249236.PMID2945742.
^Coskey RJ (July 1984). "Dermatologic therapy: December, 1982, through November, 1983".Journal of the American Academy of Dermatology.11 (1):25–52.doi:10.1016/S0190-9622(84)80163-2.PMID6376557.
^abNeumann F, Kalmus J (1991). "Cyproterone acetate in the treatment of sexual disorders: pharmacological base and clinical experience".Experimental and Clinical Endocrinology.98 (2):71–80.doi:10.1055/s-0029-1211103.PMID1838080.
^Giltay EJ, Gooren LJ (2009). "Potential side effects of androgen deprivation treatment in sex offenders".The Journal of the American Academy of Psychiatry and the Law.37 (1):53–58.PMID19297634.
^abcdLaron Z, Kauli R (July 2000). "Experience with cyproterone acetate in the treatment of precocious puberty".Journal of Pediatric Endocrinology & Metabolism. 13 Suppl 1 (Suppl 1):805–810.doi:10.1515/JPEM.2000.13.S1.805.PMID10969925.S2CID25398066.
^Reismann P, Likó I, Igaz P, Patócs A, Rácz K (August 2009). "Pharmacological options for treatment of hyperandrogenic disorders".Mini Reviews in Medicinal Chemistry.9 (9):1113–1126.doi:10.2174/138955709788922692.PMID19689407.
^abDiamanti-Kandarakis E (October 1998). "How actual is the treatment with antiandrogen alone in patients with polycystic ovary syndrome?".Journal of Endocrinological Investigation.21 (9):623–629.doi:10.1007/BF03350788.PMID9856417.S2CID46484837.
^abcHusmann F (1997). "Clinical Experiences with a Combination of Estradiol Valerate and Cyproterone Acetate for Hormone Replacement".Women's Health and Menopause. Medical Science Symposia Series. Vol. 11. Springer. pp. 257–261.doi:10.1007/978-94-011-5560-1_38.ISBN978-94-010-6343-2.ISSN0928-9550.
^abSchneider HP (December 2000). "The role of antiandrogens in hormone replacement therapy".Climacteric. 3 Suppl 2 (Suppl 2):21–27.PMID11379383.
^Gooren LJ, Giltay EJ, Bunck MC (January 2008). "Long-term treatment of transsexuals with cross-sex hormones: extensive personal experience".The Journal of Clinical Endocrinology and Metabolism.93 (1):19–25.doi:10.1210/jc.2007-1809.PMID17986639.
^Even Zohar N, Sofer Y, Yaish I, Serebro M, Tordjman K, Greenman Y (July 2021). "Low-Dose Cyproterone Acetate Treatment for Transgender Women".The Journal of Sexual Medicine.18 (7):1292–1298.doi:10.1016/j.jsxm.2021.04.008.PMID34176757.S2CID235660315.
^abFung R, Hellstern-Layefsky M, Lega I (2017). "Is a lower dose of cyproterone acetate as effective at testosterone suppression in transgender women as higher doses?".International Journal of Transgenderism.18 (2):123–128.doi:10.1080/15532739.2017.1290566.ISSN1553-2739.S2CID79095497.
^Burinkul S, Panyakhamlerd K, Suwan A, Tuntiviriyapun P, Wainipitapong S (July 2021). "Anti-Androgenic Effects Comparison Between Cyproterone Acetate and Spironolactone in Transgender Women: A Randomized Controlled Trial".The Journal of Sexual Medicine.18 (7):1299–1307.doi:10.1016/j.jsxm.2021.05.003.PMID34274044.S2CID236092532.
^Sofer Y, Yaish I, Yaron M, Bach MY, Stern N, Greenman Y (August 2020). "Differential Endocrine and Metabolic Effects of Testosterone Suppressive Agents in Transgender Women".Endocrine Practice.26 (8):883–890.doi:10.4158/EP-2020-0032.PMID33471679.S2CID225334013.
^Mahfouda S, Moore JK, Siafarikas A, Zepf FD, Lin A (October 2017). "Puberty suppression in transgender children and adolescents".The Lancet. Diabetes & Endocrinology.5 (10):816–826.doi:10.1016/S2213-8587(17)30099-2.PMID28546095.S2CID10690853.
^Tack LJ, Heyse R, Craen M, Dhondt K, Bossche HV, Laridaen J, et al. (May 2017). "Consecutive Cyproterone Acetate and Estradiol Treatment in Late-Pubertal Transgender Female Adolescents".The Journal of Sexual Medicine.14 (5):747–757.doi:10.1016/j.jsxm.2017.03.251.PMID28499525.S2CID31089247.
^abcTorri V, Floriani I (June 2005). "Cyproterone acetate in the therapy of prostate carcinoma".Archivio Italiano di Urologia, Andrologia.77 (3):157–163.CiteSeerX10.1.1.663.9458.PMID16372511.
^Schröder FH (1996). "Cyproterone Acetate — Results of Clinical Trials and Indications for Use in Human Prostate Cancer".Antiandrogens in Prostate Cancer. ESO Monographs. pp. 45–51.doi:10.1007/978-3-642-45745-6_4.ISBN978-3-642-45747-0.
^de Voogt HJ (1992). "The position of cyproterone acetate (CPA), a steroidal anti-androgen, in the treatment of prostate cancer".The Prostate. Supplement.4:91–95.doi:10.1002/pros.2990210514.PMID1533452.S2CID22747185.
^Goldenberg SL, Bruchovsky N (February 1991). "Use of cyproterone acetate in prostate cancer".The Urologic Clinics of North America.18 (1):111–122.doi:10.1016/S0094-0143(21)01398-7.PMID1825143.
^abcSeidenfeld J, Samson DJ, Hasselblad V, Aronson N, Albertsen PC, Bennett CL, et al. (April 2000). "Single-therapy androgen suppression in men with advanced prostate cancer: a systematic review and meta-analysis".Annals of Internal Medicine.132 (7):566–577.doi:10.7326/0003-4819-132-7-200004040-00009.PMID10744594.S2CID23128641.
^Wirth MP, Hakenberg OW, Froehner M (February 2007). "Antiandrogens in the treatment of prostate cancer".European Urology.51 (2):306–13, discussion 314.doi:10.1016/j.eururo.2006.08.043.PMID17007995.
^Singh SM, Gauthier S, Labrie F (February 2000). "Androgen receptor antagonists (antiandrogens): structure-activity relationships".Current Medicinal Chemistry.7 (2):211–247.doi:10.2174/0929867003375371.PMID10637363.When compared to flutamide, [cyproterone acetate] has significant intrinsic androgenic and estrogenic activities. [...] The effects of flutamide and the steroidal derivatives, cyproterone acetate, chlormadinone acetate, megestrol acetate and medroxyprogesterone acetate were compared in vivo in female nude mice bearing androgen-sensitive Shionogi tumors. All steroidal compounds stimulated tumor growth while flutamide had no stimulatory effect [51]. Thus, CPA due to its intrinsic properties stimulates androgen-sensitive parameters and cancer growth. Cyproterone acetate added to castration has never been shown in any controlled study to prolong disease-free survival or overall survival in prostate cancer when compared with castration alone [152-155].
^Chabner BA, Longo DL (8 November 2010).Cancer Chemotherapy and Biotherapy: Principles and Practice. Lippincott Williams & Wilkins. pp. 679–680.ISBN978-1-60547-431-1.Archived from the original on 10 January 2023. Retrieved12 September 2018.From a structural standpoint, antiandrogens are classified as steroidal, including cyproterone [acetate] (Androcur) and megestrol [acetate], or nonsteroidal, including flutamide (Eulexin, others), bicalutamide (Casodex), and nilutamide (Nilandron). The steroidal antiandrogens are rarely used.
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