CPA was discovered in 1961. It was originally developed as a progestin. In 1965, the antiandrogenic effects of CPA were discovered. CPA was first marketed, as an antiandrogen, in 1973, and was the first antiandrogen to be introduced for medical use. A few years later, in 1978, CPA was introduced as a progestin in a birth control pill. It has been described as a "first-generation" progestin and as the prototypical antiandrogen. CPA is available widely throughout the world. An exception is the United States, where it is not approved for use.
CPA is used with ethinylestradiol as a combined birth control pill to prevent pregnancy. This birth control combination has been available since 1978. The formulation is taken once daily for 21 days, followed by a 7-day free interval. CPA has also been available in combination with estradiol valerate (brand name Femilar) as a combined birth control pill in Finland since 1993. 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.
Skin and hair conditions
CPA is used as an antiandrogen to treat androgen-dependentskin and hair conditions such as acne, seborrhea, hirsutism (excessive hair growth), scalp hair loss, and hidradenitis suppurativa in women. 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. A birth control pill containing low-dose CPA in combination with ethinylestradiol to treat acne has been found to result in overall improvement in 75 to 90% of women, with responses approaching 100% improvement. High-dose CPA alone likewise has been found to improve symptoms of acne by 75 to 90% in women. Discontinuation of CPA has been found to result in marked recurrence of symptoms in up to 70% of women. CPA is one of the most commonly used medications in the treatment of hirsutism, hyperandrogenism, and polycystic ovary syndrome in women throughout the world.
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. The efficacy of such dosages of CPA in the treatment of hirsutism in women appear to be similar to that of spironolactone, flutamide, and finasteride.Randomized controlled trials have found that higher dosages of CPA (e.g., 20 mg/day or 100 mg/day) added cyclically to a birth control pill containing ethinylestradiol 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. 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. CPA has typically been combined with ethinylestradiol, but it can alternatively be used in combination with hormone replacement therapy dosages of estradiol instead. 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.
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 free androgen levels as well as additional blockade of the androgen receptor.
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. It can also halt further progression of scalp hair loss in men. Increased head hair and decreased body hair has been observed with CPA in men with scalp hair loss. However, its side effects in men, such as demasculinization, gynecomastia, sexual dysfunction, bone density loss, and reversible infertility, make the use of CPA in males impractical in most cases. In addition, lower dosages of CPA, such as 25 mg/day, have been found to be better-tolerated in men. But such doses also show lower effectiveness in the treatment of acne in men.
CPA is widely used as an antiandrogen and progestogen in feminizing hormone therapy for transgender women. It is 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. Studies have found that 10, 25, and 50 mg/day CPA in combination with estrogen all result in equivalent and full testosterone suppression in transgender women. In light of risks of CPA such as fatigue, blood clots, benign brain tumors, and liver damage, the use of lower dosages of the medication may help to minimize such risks. The side effects of CPA are more acceptable for transgender women than for cisgender men.
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. 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. Schröder (1993, 2009) 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 in combined androgen blockade (that is, CPA in combination with surgical or medical castration). However, the combination of CPA with castration for prostate cancer has been found to significantly decrease overall survival compared to castration alone. Hence, the use CPA as the antiandrogen component in combined androgen blockade would appear not to be advisable. When used by intramuscular injection to treat prostate cancer, CPA is used at a dosage of 300 mg once a week.
High-dose CPA significantly decreases sexual fantasies and sexual activity in 80 to 90% of men with paraphilias. 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. 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. When only a partial reduction in sexuality is desired, 50 mg/day CPA can be useful. 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. The dosage range is 50 to 300 mg/day.
Notes: Side effects are for dosages of cyproterone acetate (Androcur) of 10 to 300 mg/day. Sources: See template.
CPA is relatively safe in acute overdose. It is used at very high doses of up to 300 mg/day by mouth and 700 mg per week by intramuscular injection. For comparison, the dose of CPA used in birth control pills is 2 mg/day. There have been no deaths associated with CPA overdose. There are no specific antidotes for CPA overdose, and treatment should be symptom-based.Gastric lavage can be used in the event of oral overdose within the last 2 to 3 hours.
The dehydrogenation of 17α-hydroxyprogesterone acetate [302-23-8] (1) with chloranil (tetrachloro-p-benzoquinone) gives a compound that has been called melengestro 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 with perchloric acid, 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 of threatened abortion. As part of its development, it was assessed for androgenic activity to ensure that it would not produce teratogenic effects in female fetuses. The drug was administered to pregnant rats and its effects on the rat fetuses were studied. To the surprise of the researchers, all of the rat pups born appeared to be female. After 20 female rat pups in a row had been counted, it was clear that this could not be a chance occurrence. The rat pups were further evaluated and it was found that, in terms of karyotype, about 50% were actually males. The male rat pups had been feminized, and this resultant finding constituted the discovery of the powerful antiandrogenic activity of CPA. 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". CPA started being used in animal experiments around the world to investigate how antiandrogens affected fetal sexual differentiation.
The first clinical use of CPA in the treatment of sexual deviance and prostate cancer occurred in 1966. It was first studied in the treatment of androgen-dependent skin and hair symptoms, specifically acne, hirsutism, seborrhea, and scalp hair loss, in 1969. CPA was first approved for medical use in 1973 in Europe under the brand name Androcur. In 1977, a formulation of CPA was introduced for use by intramuscular injection. CPA was first marketed as a birth control pill in 1978 in combination with ethinylestradiol under the brand name Diane. Following phase IIIclinical trials, CPA was approved for the treatment of prostate cancer in Germany in 1980. CPA became available in Canada as Androcur in 1987, as Androcur Depot in 1990, and as Diane-35 in 1998. Conversely, CPA was never introduced in any form in the United States. This was reportedly due to concerns about breast tumors observed with high-dose pregnane progestogens in beagle dogs as well as concerns about potential teratogenicity in pregnant women. Use of CPA in transgender women, an off-label indication, was reported as early as 1977. The use of CPA in transgender women was well-established by the early 1990s.
The history of CPA, including its discovery, development, and marketing, has been reviewed.
Society and culture
The English and generic name of CPA is cyproterone acetate and this is its USAN, BAN, and JAN. The English and generic name of unacetylated cyproterone is cyproterone and this is its INN and BAN, while cyprotérone is the DCF and French name and ciproterone is the DCIT and Italian name. The name of unesterified cyproterone in Latin is cyproteronum, in German is cyproteron, and in Spanish is ciproterona. These names of cyproterone correspond for CPA to acétate de cyprotérone in French, acetato de ciproterona in Spanish, ciproterone acetato in Italian, cyproteronacetat in German, cyproteronacetaat in Dutch, and ciproteron acetat in Slavic. CPA is also known by the developmental code names SH-80714 and SH-714, while unacetylated cyproterone is known by the developmental code names SH-80881 and SH-881.
CPA is marketed under brand names including Androcur, Androcur Depot, Androcur-100, Androstat, Asoteron, Cyprone, Cyproplex, Cyprostat, Cysaxal, Imvel, and Siterone. When CPA is formulated in combination with ethinylestradiol, it is also known as co-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. CPA is also marketed in combination with estradiol valerate as Climen, Climene, Elamax, and Femilar.
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.
^ 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". Int J Clin Pharmacol Ther Toxicol. 26 (11): 555–61. PMID2977383.
^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): 375–80. doi:10.1016/0022-4731(82)90629-X. PMID6215538.
^ 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. 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.
^ abNeumann F, Elger W (1966). "Permanent changes in gonadal function and sexual behaviour as a result of early feminization of male rats by treatment with an antiandrogenic steroid". Endokrinologie. 50 (5): 209–225. 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". Mol. Cell. Endocrinol. 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, Fredenrich A, Gompel A, Lamiche-Lorenzini F, Moreau C, Plu-Bureau G, Vambergue A, Vergès B, Kerlan V (November 2012). "Hormonal contraception in women at risk of vascular and metabolic disorders: guidelines of the French Society of Endocrinology". Ann. Endocrinol. (Paris). 73 (5): 469–87. doi:10.1016/j.ando.2012.09.001. PMID23078975.
^ abBelisle S, Love EJ (December 1986). "Clinical efficacy and safety of cyproterone acetate in severe hirsutism: results of a multicentered Canadian study". Fertility and Sterility. 46 (6): 1015–20. doi:10.1016/S0015-0282(16)49873-0. PMID2946604.
^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): 742–5. 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.
^ abNeumann F, Kalmus J (1991). "Cyproterone acetate in the treatment of sexual disorders: pharmacological base and clinical experience". Exp. Clin. Endocrinol. 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): 53–8. PMID19297634.
^Reismann P, Likó I, Igaz P, Patócs A, Rácz K (August 2009). "Pharmacological options for treatment of hyperandrogenic disorders". Mini Rev Med Chem. 9 (9): 1113–26. doi:10.2174/138955709788922692. PMID19689407.
^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.
^Tack LJ, Heyse R, Craen M, Dhondt K, Bossche HV, Laridaen J, Cools M (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): 157–63. CiteSeerX10.1.1.663.9458. PMID16372511.
^Singh SM, Gauthier S, Labrie F (February 2000). "Androgen receptor antagonists (antiandrogens): structure-activity relationships". Current Medicinal Chemistry. 7 (2): 211–47. 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 . 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. 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.
^ abGoldenberg SL, Bruchovsky N, Gleave ME, Sullivan LD (June 1996). "Low-dose cyproterone acetate plus mini-dose diethylstilbestrol--a protocol for reversible medical castration". Urology. 47 (6): 882–884. doi:10.1016/S0090-4295(96)00048-9. PMID8677581.
^ abcGoldenberg SL, Bruchovsky N, Rennie PS, Coppin CM (December 1988). "The combination of cyproterone acetate and low dose diethylstilbestrol in the treatment of advanced prostatic carcinoma". The Journal of Urology. 140 (6): 1460–1465. doi:10.1016/S0022-5347(17)42073-8. PMID2973529.
^Spetz AC, Zetterlund EL, Varenhorst E, Hammar M (2003). "Incidence and management of hot flashes in prostate cancer". J Support Oncol. 1 (4): 263–6, 269–70, 272–3, discussion 267–8, 271–2. PMID15334868.
^Radlmaier A, Bormacher K, Neumann F (1990). "Hot flushes: mechanism and prevention". Prog. Clin. Biol. Res. 359: 131–40, discussion 141–53. PMID2149457.
^Schulze H, Senge T (October 1990). "Influence of different types of antiandrogens on luteinizing hormone-releasing hormone analogue-induced testosterone surge in patients with metastatic carcinoma of the prostate". J. Urol. 144 (4): 934–41. doi:10.1016/S0022-5347(17)39625-8. PMID2144596.
^Boccon-Gibod L, Laudat MH, Dugue MA, Steg A (1986). "Cyproterone acetate lead-in prevents initial rise of serum testosterone induced by luteinizing hormone-releasing hormone analogs in the treatment of metastatic carcinoma of the prostate". Eur. Urol. 12 (6): 400–2. doi:10.1159/000472667. PMID2949980.
^Klosterhalfen H, Jacobi GH (1988). "Long-term results of an LH-RH agonist monotherapy in patients with carcinoma of the prostate and reflections on the so-called total androgen blockade with pre-medicated cyproterone acetate". In Klosterhalfen H (ed.). Endocrine Management of Prostatic Cancer. De Gruyter. pp. 127–137. doi:10.1515/9783110853674-014. ISBN9783110853674.
^Guay DR (January 2009). "Drug treatment of paraphilic and nonparaphilic sexual disorders". Clin Ther. 31 (1): 1–31. doi:10.1016/j.clinthera.2009.01.009. PMID19243704. No quantitative data on these adverse events are available, even in the product prescribing information and data sheets.
^Migliari R, Muscas G, Murru M, Verdacchi T, De Benedetto G, De Angelis M (December 1999). "Antiandrogens: a summary review of pharmacodynamic properties and tolerability in prostate cancer therapy". Arch Ital Urol Androl. 71 (5): 293–302. PMID10673793.
^Ayub M, Levell MJ (July 1987). "Inhibition of rat testicular 17 alpha-hydroxylase and 17,20-lyase activities by anti-androgens (flutamide, hydroxyflutamide, RU23908, cyproterone acetate) in vitro". Journal of Steroid Biochemistry. 28 (1): 43–7. doi:10.1016/0022-4731(87)90122-1. PMID2956461.
^Hamada H, Neumann F, Junkmann K (November 1963). "Intrauterine Antimaskuline Beeinflussung von Rattenfeten Durch ein Stark Gestagen Wirksames Steroid" [Intrauterine antimasculine influence of Rat Fetuses by Birtue of a Powerful Steroid Acting as a Progestogen]. Acta Endocrinologica (in German). 44 (3): 380–8. doi:10.1530/acta.0.0440380. PMID14071315.
^Jost A (1971). "Use of androgen antagonists and antiandrogens in studies on sex differentiation". Gynecol Invest. 2 (1): 180–201. doi:10.1159/000301861. PMID4949979.
^Thibaut F, De La Barra F, Gordon H, Cosyns P, Bradford JM (June 2010). "The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of paraphilias". The World Journal of Biological Psychiatry. 11 (4): 604–55. doi:10.3109/15622971003671628. PMID20459370. S2CID14949511.
^Hammerstein J, Cupceancu B (April 1969). "[Management of hirsutism using cyproterone acetate]" [Management of hirsutism using cyproterone acetate]. Deutsche Medizinische Wochenschrift (in German). 94 (16): 829–34. doi:10.1055/s-0028-1111126. PMID4304873.
^Jacobi GH, Altwein JE, Kurth KH, Basting R, Hohenfellner R (June 1980). "Treatment of advanced prostatic cancer with parenteral cyproterone acetate: a phase III randomised trial". British Journal of Urology. 52 (3): 208–15. doi:10.1111/j.1464-410X.1980.tb02961.x. PMID7000222.
^"Androcur". Drug Product Database Online Query. Health Canada. 2012-04-25.
^Zingg E, König MP, Cornu F, Wildholz A, Blaser A (1980). "Transsexualismus: Erfahrungen mit der operativen Korrektur bei männlichen Transsexuellen" [Transsexualism: Experience with surgical correction in male transsexuals]. Aktuelle Urologie. 11 (2): 67–77. doi:10.1055/s-2008-1062961. ISSN0001-7868.
^Neumann F, Wiechert R (March 1988). "Das Antiandrogen Cyproteronacetat Seine Geschichte von der Entdeckung bis zur Marktreife" [The antiandrogen cyproterone acetate. Its history from discovery to marketing]. Pharmazie in unserer Zeit (in German). 17 (2): 33–50. doi:10.1002/pauz.19880170202. ISSN0048-3664. PMID2967500.
^Tenaglia R, Nicolai M, Di Federico G, Iantorno R, Zezza A, Lombardi G (1993). "[Androgen deprivation in benign prostatic hypertrophy]". Journal d'Urologie (in French). 99 (6): 296–298. PMID7516371.
^Di Silverio F, D'Eramo G, Flammia GP, Buscarini M, Frascaro E, Mariani M, Sciarra A (1993). "[Pharmacological combinations in the treatment of benign prostatic hypertrophy]". Journal d'Urologie (in French). 99 (6): 316–320. PMID7516378.
^Willemse PH, Dikkeschei LD, Mulder NH, van der Ploeg E, Sleijfer DT, de Vries EG (March 1988). "Clinical and endocrine effects of cyproterone acetate in postmenopausal patients with advanced breast cancer". European Journal of Cancer & Clinical Oncology. 24 (3): 417–421. doi:10.1016/S0277-5379(98)90011-6. PMID2968261.
^Nieschlag E, Behre HM, Nieschlag E, Behre HM, Nieschlag S (2012). "The essential role of testosterone in hormonal male contraception". In Nieschlag E, Behre HM, Nieschlag S (eds.). Testosterone. pp. 470–493. doi:10.1017/CBO9781139003353.023. ISBN9781139003353.
^Nguyen Y, Bradford J, Fischer G (February 2018). "Cyproterone acetate in the treatment of oestrogen hypersensitivity vulvovaginitis". The Australasian Journal of Dermatology. 59 (1): 52–54. doi:10.1111/ajd.12657. PMID28718897. S2CID22365089.
^Geier DA, Kern JK, King PG, Sykes LK, Geier MR (2012). "An evaluation of the role and treatment of elevated male hormones in autism spectrum disorders". Acta Neurobiol Exp (Wars). 72 (1): 1–17. PMID22508080.
^Bolea-Alamanac BM, Davies SJ, Christmas DM, Baxter H, Cullum S, Nutt DJ (2011). "Cyproterone to treat aggressivity in dementia: a clinical case and systematic review". J. Psychopharmacol. (Oxford). 25 (1): 141–5. doi:10.1177/0269881109353460. PMID19942637. S2CID11479701.
Hammerstein J, Meckies J, Leo-Rossberg I, Moltz L, Zielske F (June 1975). "Use of cyproterone acetate (CPA) in the treatment of acne, hirsutism and virilism". J. Steroid Biochem. 6 (6): 827–36. doi:10.1016/0022-4731(75)90311-8. PMID126335.
Neumann F, Wiechert R (March 1988). "Das Antiandrogen Cyproteronacetat: Seine Geschichte von der Entdeckung bis zur Marktreife" [The Antiandrogen Cyproterone Acetate: Its History from Discovery to Marketing]. Pharm unserer Zeit (in German). 17 (2): 33–50. doi:10.1002/pauz.19880170202. PMID2967500.
Tunn UW (1989). "Cyproterone acetate in the management of prostatic cancer". Prog. Clin. Biol. Res. 303: 105–10. PMID2528734.
Neumann F, Kalmus J (1991). "Cyproterone acetate in the treatment of sexual disorders: pharmacological base and clinical experience". Exp. Clin. Endocrinol. 98 (2): 71–80. doi:10.1055/s-0029-1211103. PMID1838080.
Diamanti-Kandarakis E (October 1998). "How actual is the treatment with antiandrogen alone in patients with polycystic ovary syndrome?". J. Endocrinol. Invest. 21 (9): 623–9. doi:10.1007/BF03350788. PMID9856417. S2CID46484837.
Migliari R, Muscas G, Murru M, Verdacchi T, De Benedetto G, De Angelis M (December 1999). "Antiandrogens: a summary review of pharmacodynamic properties and tolerability in prostate cancer therapy". Arch Ital Urol Androl. 71 (5): 293–302. PMID10673793.
Bolea-Alamanac BM, Davies SJ, Christmas DM, Baxter H, Cullum S, Nutt DJ (January 2011). "Cyproterone to treat aggressivity in dementia: a clinical case and systematic review". J. Psychopharmacol. (Oxford). 25 (1): 141–5. doi:10.1177/0269881109353460. PMID19942637. S2CID11479701.