Cyproterone acetate explained

Cyproterone acetate (CPA), sold alone under the brand name Androcur or with ethinylestradiol under the brand names Diane or Diane-35 among others, is an antiandrogen and progestin medication used in the treatment of androgen-dependent conditions such as acne, excessive body hair growth, early puberty, and prostate cancer, as a component of feminizing hormone therapy for transgender individuals, and in birth control pills.[1] [2] [3] [4] [5] It is formulated and used both alone and in combination with an estrogen. CPA is taken by mouth one to three times per day.

Common side effects of high-dose CPA in men include gynecomastia (breast development) and feminization. In both men and women, possible side effects of CPA include low sex hormone levels, reversible infertility, sexual dysfunction, fatigue, depression, weight gain, and elevated liver enzymes. At very high doses in older individuals, significant cardiovascular complications can occur. Rare but serious adverse reactions of CPA include blood clots, liver damage and brain tumors. CPA can also cause adrenal insufficiency as a withdrawal effect if it is discontinued abruptly from a high dosage. CPA blocks the effects of androgens such as testosterone in the body, which it does by preventing them from interacting with their biological target, the androgen receptor (AR), and by reducing their production by the gonads, hence their concentrations in the body.[6] In addition, it has progesterone-like effects by activating the progesterone receptor (PR). It can also produce weak cortisol-like effects at very high doses.

CPA was discovered in 1961.[7] 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.[8] 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.[9] CPA is available widely throughout the world. An exception is the United States, where it is not approved for use.[10]

Medical uses

CPA is used as a progestin and antiandrogen in hormonal birth control and in the treatment of androgen-dependent conditions. Specifically, CPA is used in combined birth control pills, in the treatment of androgen-dependent skin and hair conditions such as acne, seborrhea, excessive hair growth, and scalp hair loss, high androgen levels, in transgender hormone therapy, to treat prostate cancer, to reduce sex drive in sex offenders or men with paraphilias or hypersexuality, to treat early puberty, and for other uses.[11] It is used both at low doses and at higher doses.

In the United States, where CPA is not available, other medications with antiandrogenic effects are used to treat androgen-dependent conditions instead.[12] Examples of such medications include gonadotropin-releasing hormone modulators (GnRH modulators) like leuprorelin and degarelix, nonsteroidal antiandrogens like flutamide and bicalutamide, the diuretic and steroidal antiandrogen spironolactone, the progestin medroxyprogesterone acetate, and the 5α-reductase inhibitors finasteride and dutasteride. The steroidal antiandrogen and progestin chlormadinone acetate is used as an alternative to CPA in Japan, South Korea, and a few other countries.

Birth control

CPA is used with ethinylestradiol as a combined birth control pill to prevent pregnancy. This birth control combination has been available since 1978.[13] The formulation is taken once daily for 21 days, followed by a 7-day free interval.[14] CPA has also been available in combination with estradiol valerate (brand name Femilar) as a combined birth control pill in Finland since 1993.[15] [16] 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.[17]

Skin and hair conditions

Females

CPA is used as an antiandrogen to treat androgen-dependent skin and hair conditions such as acne, seborrhea, hirsutism (excessive hair growth), scalp hair loss, and hidradenitis suppurativa in women.[18] [19] [20] [21] [22] [23] 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.[24] 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.[25] High-dose CPA alone likewise has been found to improve symptoms of acne by 75 to 90% in women.[26] Discontinuation of CPA has been found to result in marked recurrence of symptoms in up to 70% of women.[27] 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.[28] [29] 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.[29] [30] [31] [32] [33] 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.[34] 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.[29] [35]

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.

Males

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.[36] [37] [38] [39] It can also halt further progression of scalp hair loss in men.[40] [41] [42] 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.[43] [44] 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.

High androgen levels

CPA is used as an antiandrogen to treat high androgen levels and associated symptoms such as masculinization due to conditions like polycystic ovary syndrome (PCOS) and congenital adrenal hyperplasia (CAH) in women.[45] [46] [47] [48] It is almost always combined with an estrogen, such as ethinylestradiol, when it is used in the treatment of PCOS in women.[49]

Menopausal hormone therapy

CPA is used at low doses in menopausal hormone therapy in combination with an estrogen to provide endometrial protection and treat menopausal symptoms.[50] [51] [52] It is used in menopausal hormone therapy under the brand name Climen, which is a sequential preparation that contains 2 mg estradiol valerate and 1 mg CPA. Climen was the first product for use in menopausal hormone therapy containing CPA to be marketed. It is available in more than 40 countries.

Transgender hormone therapy

CPA is widely used as an antiandrogen and progestogen in feminizing hormone therapy for transgender individuals.[53] [54] [55] [56] [57] [58] 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.[59] [60] 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.

Studies have found that 10, 25, 50, and 100 mg/day CPA in combination with estrogen all result in equivalent and full testosterone suppression in transgender women.[61] [62] [63] [64] In light of risks of CPA such as fatigue, blood clots, benign brain tumors, and liver damage, the use of lower dosages of CPA may help to minimize such risks. As a result, a CPA dosage of 10mg/day and no greater is now recommended by the World Professional Association for Transgender Health (WPATH) Standards of Care for the Health of Transgender and Gender Diverse People, Version 8 (SOC8).[65]

CPA has an advantage over spironolactone as an antiandrogen in transgender people, as the combination of estrogen and CPA consistently suppresses testosterone levels into the normal female range whereas estrogen with spironolactone does not.[66] [67] [68] [69] [70] [71] [72] 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.

Aside from adult transgender people, CPA has also been used as a puberty blocker and hence as an antiandrogen and antiestrogen to suppress puberty in transgender adolescents, although GnRH modulators are primarily used and more effective for this purpose.[73] [74] [75] [76]

Prostate cancer

CPA is used as an antiandrogen monotherapy and means of androgen deprivation therapy in the palliative treatment of prostate cancer in men.[77] [78] [79] [80] [81] 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.[82] [83] CPA has similar effectiveness to GnRH modulators and surgical castration, high-dose estrogen therapy (e.g., with diethylstilbestrol), and high-dose nonsteroidal antiandrogen monotherapy (e.g., with bicalutamide), but has significantly inferior effectiveness to combined androgen blockade with a GnRH modulator and a nonsteroidal antiandrogen (e.g., with bicalutamide or enzalutamide).[84] [85] [86] 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.[87] Due to its inferior effectiveness, tolerability, and safety, CPA is rarely used in the treatment of prostate cancer today, having largely been superseded by GnRH modulators and nonsteroidal antiandrogens.[88] [89] CPA is the only steroidal antiandrogen that continues to be used in the treatment of prostate cancer.

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.[90] [91] 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.[92] [93] 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 in combined androgen blockade (that is, CPA in combination with surgical or medical castration).[94] However, the combination of CPA with castration for prostate cancer has been found to significantly decrease overall survival compared to castration alone.[95] Hence, the use of 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.[96]

The combination of CPA with an estrogen such as ethinylestradiol sulfonate or low-dose diethylstilbestrol has been used as a form of combined androgen blockade and as an alternative to the combination of CPA with surgical or medical castration.[97]

Sexual deviance

CPA is used as an antiandrogen and form of chemical castration in the treatment of paraphilias and hypersexuality in men.[98] [99] [100] [101] [102] [103] It is used to treat sex offenders. The medication is approved in more than 20 countries for this indication and is predominantly employed in Canada, Europe, and the Middle East. CPA works by decreasing sex drive and sexual arousal and producing sexual dysfunction. CPA can also be used to reduce sex drive in individuals with inappropriate sexual behaviors, such as people with intellectual disability and dementia.[104] [105] The medication is also used to reduce sexual behavior diagnosed as self-harmful, such as masochism.[106] CPA has comparable effectiveness to medroxyprogesterone acetate in suppressing sexual urges and function but appears to be less effective than GnRH modulators like leuprorelin and has more side effects.

High-dose CPA significantly decreases sexual fantasies and sexual activity in 80 to 90% of men with paraphilias.[107] 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.[108] 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.

Early puberty

CPA is used as an antiandrogen and antiestrogen to treat precocious puberty in boys and girls.[109] [110] However, it is not fully satisfactory for this indication because it is not able to completely suppress puberty.[111] For this reason, CPA has mostly been superseded by GnRH agonists in the treatment of precocious puberty. CPA is not satisfactory for gonadotropin-independent precocious puberty.[112] CPA has been used at dosages of 50 to 300 mg/m2 to treat precocious puberty.

Other uses

CPA is useful in the treatment of hot flashes, for instance due to androgen deprivation therapy for prostate cancer.[113] [114] [115]

CPA is useful for suppressing the testosterone flare at the initiation of GnRH agonist therapy.[116] [117] [118] [119] [120] [121] It has been used successfully both alone and in combination with estrogens such as diethylstilbestrol for this purpose.[122]

Available forms

See also: Estradiol valerate/cyproterone acetate and Ethinylestradiol/cyproterone acetate.

CPA is available in the form of oral tablets alone (higher-dose; 10 mg, 50 mg, 100 mg) or in combination with ethinylestradiol or estradiol valerate (low-dose; 1 or 2 mg CPA) and in the form of ampoules for intramuscular injection (higher-dose; 100 mg/mL, 300 mg/3 mL; brand name Androcur Depot).[123] [124] [125] [126]

The higher-dose formulations are used to treat prostate cancer and certain other androgen-related indications while the low-dose formulations which also have an estrogen are used as combined birth control pills and are used in menopausal hormone therapy for the treatment of menopausal symptoms.[127]

Contraindications

Contraindications of CPA include:[128] [129] [130]

When CPA is used in combination with an estrogen, contraindications for birth control pills should also be considered.

Side effects

CPA is generally well-tolerated and has a mild side-effect profile regardless of dosage when it is used in combination with an estrogen in women.[131] [132] Side effects of CPA in general include hypogonadism (low sex-hormone levels) and associated symptoms such as demasculinization, sexual dysfunction, infertility, and osteoporosis (fragile bones); breast changes such as breast tenderness, breast enlargement, and gynecomastia (breasts in men); emotional changes such as fatigue and depression; and other side effects such as vitamin B12 deficiency, weak glucocorticoid effects, and elevated liver enzymes. Weight gain can occur with CPA when it is used at high doses.[133] [32] Some of the side effects of CPA can be improved or fully prevented if it is combined with an estrogen to prevent estrogen deficiency.[25] Few quantitative data are available on many of the potential side effects of CPA.[134] Pooled tolerability data for CPA is not available in the literature.[135] Cyproterone is also known to suppress adrenocortical function.[136]

At very high doses in aged men with prostate cancer, CPA can cause cardiovascular side effects. Rarely, CPA can produce blood clots, liver toxicity (including hepatitis, liver failure, and liver cancer), excessively high prolactin levels, and certain benign brain tumors including meningiomas (tumors of the meninges) and prolactinomas (prolactin-secreting tumors of the pituitary gland). Upon discontinuation from high doses, CPA can produce adrenal insufficiency as a withdrawal effect.

Overdose

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.[137] For comparison, the dose of CPA used in birth control pills is 2 mg/day.[138] 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.

Interactions

Inhibitors and inducers of the cytochrome P450 enzyme CYP3A4 may interact with CPA. Examples of strong CYP3A4 inhibitors include ketoconazole, itraconazole, clotrimazole, and ritonavir, while examples of strong CYP3A4 inducers include rifampicin, rifampin, phenytoin, carbamazepine, phenobarbital, and St. John's wort. Certain anticonvulsant medications can substantially reduce levels of CPA, by as much as 8-fold.

Pharmacology

Pharmacodynamics

CPA has antiandrogenic activity,[139] progestogenic activity, weak partial glucocorticoid activity,[140] weak steroidogenesis inhibitor activity,[141] and agonist activity at the pregnane X receptor.[142] [143] [144] It has no estrogenic or antimineralocorticoid activity. In terms of potency, CPA is described as a highly potent progestogen, a moderately potent antiandrogen, and a weak glucocorticoid. Due to its progestogenic activity, CPA has antigonadotropic effects, and is able to suppress fertility and sex-hormone levels in both males and females.

Pharmacokinetics

CPA can be taken by mouth or by injection into muscle. It has near-complete oral bioavailability, is highly and exclusively bound to albumin in terms of plasma protein binding, is metabolized in the liver by hydroxylation and conjugation, has 15β-hydroxycyproterone acetate (15β-OH-CPA) as a single major active metabolite, has a long elimination half-life of about 2 to 4 days regardless of route of administration, and is excreted in feces primarily and to a lesser extent in urine.

Chemistry

See also: List of progestogens, Progestogen ester, List of progestogen esters, Steroidal antiandrogen and List of steroidal antiandrogens.

CPA, also known as 1α,2α-methylene-6-chloro-17α-acetoxy-δ6-progesterone or as 1α,2α-methylene-6-chloro-17α-hydroxypregna-4,6-diene-3,20-dione acetate, is a synthetic pregnane steroid and an acetylated derivative of 17α-hydroxyprogesterone.[145] [146] It is structurally related to other 17α-hydroxyprogesterone derivatives such as chlormadinone acetate, hydroxyprogesterone caproate, medroxyprogesterone acetate, and megestrol acetate.

Synthesis

Chemical syntheses of CPA have been published.[147] [148] [149] The following is one such synthesis:[150] [151]

The dehydrogenation of 17α-hydroxyprogesterone acetate [302-23-8] (1) with chloranil (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 with perchloric acid,[152] 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).

History

CPA was first synthesized in 1961 by Rudolf Wiechert, a Schering employee, and together with Friedmund Neumann in Berlin, they filed for a patent for CPA as "progestational agent" in 1962. The antiandrogenic activity of CPA was discovered serendipitously by Hamada, Neumann, and Karl Junkmann in 1963.[153] Along with the steroidal antiandrogens benorterone (17α-methyl-B-nortestosterone; SKF-7690), cyproterone, BOMT (Ro 7–2340), and trimethyltrienolone (R-2956) and the nonsteroidal antiandrogens flutamide and DIMP (Ro 7–8117), CPA was one of the first antiandrogens to be discovered and researched.[154] [155] [156]

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".[157] CPA started being used in animal experiments around the world to investigate how antiandrogens affected fetal sexual differentiation.[158]

The first clinical use of CPA in the treatment of sexual deviance and prostate cancer occurred in 1966.[159] [160] It was first studied in the treatment of androgen-dependent skin and hair symptoms, specifically acne, hirsutism, seborrhea, and scalp hair loss, in 1969.[161] CPA was first approved for medical use in 1973 in Europe under the brand name Androcur.[162] In 1977, a formulation of CPA was introduced for use by intramuscular injection.[163] CPA was first marketed as a birth control pill in 1978 in combination with ethinylestradiol under the brand name Diane. Following phase III clinical trials, CPA was approved for the treatment of prostate cancer in Germany in 1980.[164] CPA became available in Canada as Androcur in 1987, as Androcur Depot in 1990, and as Diane-35 in 1998.[165] [166] [167] 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.[168] Use of CPA in transgender women, an off-label indication, was reported as early as 1977.[169] [170] The use of CPA in transgender women was well-established by the early 1990s.[171]

The history of CPA, including its discovery, development, and marketing, has been reviewed.[172]

Society and culture

Generic names

The English and generic name of CPA is cyproterone acetate and this is its,, and .[173] [174] The English and generic name of unacetylated cyproterone is cyproterone and this is its and,[175] while cyprotérone is the and French name and ciproterone is the 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, siproteron asetat in Turkish, and cyproteronacetaat in Dutch. 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.

Brand names

CPA is marketed under brand names including Androcur, Androcur Depot, Androcur-100, Androstat, Asoteron, Cyprone, Cyproplex, Cyprostat, Cysaxal, Imvel, and Siterone.[176] [177] 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

CPA is widely available throughout the world, and is marketed in almost every developed country,[178] with the notable major exceptions of the United States and Japan.[179] [180] [181] In almost all countries in which CPA is marketed, it is available both alone and in combination with an estrogen in birth control pills. CPA is marketed widely in combination with both ethinylestradiol and estradiol valerate. CPA-containing birth control pills are available in South Korea, but CPA as a standalone medication is not marketed in this country. In Japan and South Korea, the closely related antiandrogen and progestin chlormadinone acetate, as well as other medications, are used instead of CPA.[182] Specific places in which CPA is marketed include the United Kingdom, elsewhere throughout Europe, Canada, Australia, New Zealand, South Africa, Latin America, and Asia. CPA is not marketed in most of Africa and the Middle East.

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.[131]

Generation

Progestins in birth control pills are sometimes grouped by generation.[183] [184] While the 19-nortestosterone progestins are consistently grouped into generations, the pregnane 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". In any case, CPA has been described as a "first-generation" progestin similarly to closely related progestins like chlormadinone acetate, medroxyprogesterone acetate, and megestrol acetate.[185] [186]

Research

CPA has been studied and used in combination with low-dose diethylstilbestrol in the treatment of prostate cancer.[187] [188] [189] The combination results in suppression of testosterone levels into the castrate range, which normally cannot be achieved with CPA alone. CPA has been studied as a form of androgen deprivation therapy for the treatment of benign prostatic hyperplasia (enlarged prostate).[190] [191] [192] The medication has been studied in the treatment of breast cancer as well.[193] [194]

CPA has been studied for use as a potential male hormonal contraceptive both alone and in combination with testosterone in men.[195] [196] CPA was under development by Barr Pharmaceuticals in the 2000s for the treatment of hot flashes in prostate cancer patients in the United States.[197] It reached phase III clinical trials for this indication and had the tentative brand name CyPat but development was ultimately discontinued in 2008. CPA is not satisfactorily effective as topical antiandrogen, for instance in the treatment of acne. CPA has been used to treat estrogen hypersensitivity vulvovaginitis in women.[198]

CPA has been investigated for use in reducing aggression and self-injurious behavior via its antiandrogenic effects in conditions like autism spectrum disorders, dementias like Alzheimer's disease, and psychosis.[199] [200] [201] [202] CPA may be effective in the treatment of obsessive–compulsive disorder (OCD).[203] [204] [205] [206] CPA has been studied in the treatment of cluster headaches in men.[207]

See also

Further reading

External links

Notes and References

  1. Kuhl H . Pharmacology of estrogens and progestogens: influence of different routes of administration . Climacteric . 8 . Suppl 1 . 3–63 . 2005 . 16112947 . 10.1080/13697130500148875. 24616324 .
  2. Barradell LB, Faulds D . Cyproterone. A review of its pharmacology and therapeutic efficacy in prostate cancer . Drugs Aging . 5 . 1 . 59–80 . July 1994 . 7919640 . 10.2165/00002512-199405010-00006 . 260845477 .
  3. Neumann F . The antiandrogen cyproterone acetate: discovery, chemistry, basic pharmacology, clinical use and tool in basic research . Exp. Clin. Endocrinol. . 102 . 1 . 1–32 . 1994 . 8005205 . 10.1055/s-0029-1211261 . free .
  4. Neumann F . Pharmacology and potential use of cyproterone acetate . Horm. Metab. Res. . 9 . 1 . 1–13 . January 1977 . 66176 . 10.1055/s-0028-1093574 . 7224893 .
  5. Neumann F, Töpert M . Pharmacology of antiandrogens . Journal of Steroid Biochemistry . 25 . 5B . 885–95 . November 1986 . 2949114 . 10.1016/0022-4731(86)90320-1.
  6. Book: Berek JS . Berek & Novak's Gynecology . 2007 . Lippincott Williams & Wilkins . 978-0-7817-6805-4 . 1085.
  7. Pucci E, Petraglia F . Treatment of androgen excess in females: yesterday, today and tomorrow . Gynecol. Endocrinol. . 11 . 6 . 411–33 . December 1997 . 9476091 . 10.3109/09513599709152569 .
  8. Book: Wakelin SH . Systemic Drug Treatment in Dermatology: A Handbook . 1 June 2002 . CRC Press . 978-1-84076-013-2 . 32 . 27 September 2016 . 14 January 2023 . https://web.archive.org/web/20230114143141/https://books.google.com/books?id=F1ZiAgAAQBAJ&pg=PA32 . live .
  9. Book: Jameson JL, De Groot LJ. Endocrinology: Adult and Pediatric E-Book. 25 February 2015. Elsevier Health Sciences. 978-0-323-32195-2. 2293, 2464, 2479, 6225. 2 August 2018. 6 July 2024. https://web.archive.org/web/20240706162108/https://books.google.com/books?id=xmLeBgAAQBAJ&pg=PA2293#v=onepage&q&f=false. live.
  10. Book: 10.1016/B978-0-12-387817-5.00030-3 . Cancer Chemotherapy . Drug-Induced Liver Disease . 2013 . Deleve LD . 541–567 . Academic Press . 9780123878175 .
  11. Book: Maggi M . Hormonal Therapy for Male Sexual Dysfunction . 17 November 2011 . John Wiley & Sons . 978-1-119-96380-6 . 104.
  12. Book: Duker M, Malsch M . Incapacitation: Trends and New Perspectives . 28 January 2013 . Ashgate Publishing, Ltd. . 978-1-4094-7151-6 . 77.
  13. Book: Plewig G, Kligman AM . ACNE and ROSACEA. 6 December 2012. Springer Science & Business Media. 978-3-642-59715-2. 662, 685.
  14. Web site: PrDIANE® -35 . https://web.archive.org/web/20160508183945/https://omr.bayer.ca/omr/online/diane-35-pm-en.pdf . May 8, 2016 . September 2, 2015 . dead.
  15. Fruzzetti F, Trémollieres F, Bitzer J . An overview of the development of combined oral contraceptives containing estradiol: focus on estradiol valerate/dienogest . Gynecol. Endocrinol. . 28 . 5 . 400–8 . May 2012 . 22468839 . 3399636 . 10.3109/09513590.2012.662547 .
  16. Fruzzetti F, Bitzer J . Review of clinical experience with estradiol in combined oral contraceptives . Contraception . 81 . 1 . 8–15 . 2010 . 20004267 . 10.1016/j.contraception.2009.08.010 .
  17. 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 . 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 . November 2012 . 23078975 . 10.1016/j.ando.2012.09.001 .
  18. Van der Spuy ZM, le Roux PA . Cyproterone acetate for hirsutism . Cochrane Database Syst Rev . 4 . CD001125 . 2003 . 2010 . 14583927 . 10.1002/14651858.CD001125 . 8955083 .
  19. Bitzer J, Römer T, Lopes da Silva Filho A . The use of cyproterone acetate/ethinyl estradiol in hyperandrogenic skin symptoms - a review . Eur J Contracept Reprod Health Care . 22 . 3 . 172–182 . June 2017 . 28447864 . 10.1080/13625187.2017.1317339 . free .
  20. Beylot C, Doutre MS, Beylot-Barry M . Oral contraceptives and cyproterone acetate in female acne treatment . Dermatology (Basel) . 196 . 1 . 148–52 . 1998 . 9557250 . 10.1159/000017849 . 46763689 .
  21. Miller JA, Jacobs HS . Treatment of hirsutism and acne with cyproterone acetate . Clin Endocrinol Metab . 15 . 2 . 373–89 . May 1986 . 2941191 . 10.1016/S0300-595X(86)80031-7 .
  22. Ingram JR, Woo PN, Chua SL, Ormerod AD, Desai N, Kai AC, Hood K, Burton T, Kerdel F, Garner SE, Piguet V . Interventions for hidradenitis suppurativa . Cochrane Database Syst Rev . 10 . CD010081 . October 2015 . 2017 . 26443004 . 10.1002/14651858.CD010081.pub2 . 6464653 .
  23. Book: Ioannides D, Lazaridou E . Alopecias - Practical Evaluation and Management . Female pattern hair loss . Curr. Probl. Dermatol. . 47 . 45–54 . 2015 . 26370643 . 10.1159/000369404 . Current Problems in Dermatology . 978-3-318-02774-7 .
  24. Arowojolu AO, Gallo MF, Lopez LM, Grimes DA . Arowojolu AO . Combined oral contraceptive pills for treatment of acne . Cochrane Database Syst Rev . 7 . CD004425 . July 2012 . 22786490 . 10.1002/14651858.CD004425.pub6 .
  25. Diamanti-Kandarakis E . Current aspects of antiandrogen therapy in women . Curr. Pharm. Des. . 5 . 9 . 707–23 . September 1999 . 10.2174/1381612805666230111201150 . 10495361 . 18 December 2018 . 11 January 2023 . https://web.archive.org/web/20230111121904/https://books.google.com/books?id=9rfNZL6oEO0C&pg=PA707 . live .
  26. Bettoli V, Zauli S, Virgili A . Is hormonal treatment still an option in acne today? . Br. J. Dermatol. . 172 . Suppl 1 . 37–46 . 2015 . 25627824 . 10.1111/bjd.13681 . 35615492 .
  27. Reed MJ, Franks S . Anti-androgens in gynaecological practice . Baillière's Clin Obstet Gynaecol . 2 . 3 . 581–95 . September 1988 . 2976627 . 10.1016/S0950-3552(88)80045-2 .
  28. Rittmaster RS . Hirsutism . Lancet . 349 . 9046 . 191–5 . January 1997 . 9111556 . 10.1016/S0140-6736(96)07252-2 . 208789457 .
  29. Azziz R, Carmina E, Sawaya ME . Idiopathic hirsutism . Endocrine Reviews . 21 . 4 . 347–62 . August 2000 . 10950156 . 10.1210/edrv.21.4.0401 . free .
  30. Sahin Y, Kelestimur F . Medical treatment regimens of hirsutism . Reproductive Biomedicine Online . 8 . 5 . 538–46 . May 2004 . 15151716 . 10.1016/S1472-6483(10)61100-5 . free .
  31. Liew SH . Unwanted body hair and its removal: a review . Dermatologic Surgery . 25 . 6 . 431–9 . June 1999 . 10469088 . 10.1046/j.1524-4725.1999.08130.x .
  32. Belisle S, Love EJ . Clinical efficacy and safety of cyproterone acetate in severe hirsutism: results of a multicentered Canadian study . Fertility and Sterility . 46 . 6 . 1015–20 . December 1986 . 2946604 . 10.1016/S0015-0282(16)49873-0 . free .
  33. Barth JH, Cherry CA, Wojnarowska F, Dawber RP . Cyproterone acetate for severe hirsutism: results of a double-blind dose-ranging study . Clinical Endocrinology . 35 . 1 . 5–10 . July 1991 . 1832346 . 10.1111/j.1365-2265.1991.tb03489.x . 27293697 .
  34. Nikolaou D, Gilling-Smith C . Hirsutism. Current Obstetrics & Gynaecology. 15. 3. 2005. 174–182. 0957-5847. 10.1016/j.curobgyn.2005.03.006.
  35. Jasonni VM, Bulletti C, Naldi S, Di Cosmo E, Cappuccini F, Flamigni C . Treatment of hirsutism by an association of oral cyproterone acetate and transdermal 17 beta-estradiol . Fertility and Sterility . 55 . 4 . 742–5 . April 1991 . 1826278 . 10.1016/S0015-0282(16)54240-X .
  36. Ward A, Brogden RN, Heel RC, Speight TM, Avery GS . Isotretinoin. A review of its pharmacological properties and therapeutic efficacy in acne and other skin disorders . Drugs . 28 . 1 . 6–37 . July 1984 . 6235105 . 10.2165/00003495-198428010-00002 .
  37. Book: Rasmusson GH . Chapter 18. Chemical Control of Androgen Action. 21. 1986. 179–188. 0065-7743. 10.1016/S0065-7743(08)61128-8. Annual Reports in Medicinal Chemistry. Academic Press . 9780120405213.
  38. Cormane RH, van der Meeren HL . Cyproteronacetate in the management of severe acne in males. Archives of Dermatological Research . 271 . 2 . 1981 . 183–187. 0340-3696. 10.1007/BF00412545. 12153042.
  39. Misch KJ, Dolman WF, Neild V, Rhodes EL . Response of male acne to antiandrogen therapy with cyproterone acetate . Dermatologica . 173 . 3 . 139–42 . 1986 . 2945742 . 10.1159/000249236 .
  40. Book: Simpson NB . Pharmacology of the Skin II. 87 / 2. 1989. 495–508. 0171-2004. 10.1007/978-3-642-74054-1_37. Handbook of Experimental Pharmacology. 978-3-642-74056-5. The Effect of Drugs on Hair. Springer .
  41. Book: Unger WP . Androgenetic alopecia and its treatment. A historical overview. 1–33. Hair Transplantation, Third Edition. 1 February 1995. Taylor & Francis. 978-0-8247-9363-0.
  42. Coskey RJ . Dermatologic therapy: December, 1982, through November, 1983 . Journal of the American Academy of Dermatology . 11 . 1 . 25–52 . July 1984 . 6376557 . 10.1016/S0190-9622(84)80163-2 .
  43. Giltay EJ, Gooren LJ . 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 . 2009 . 19297634 .
  44. Book: Lam SM, Hempstead BR, Williams EF . Aesthetic Medicine. Medical Management Options for Hair Loss. 2012. 529–535. Springer . 10.1007/978-3-642-20113-4_41. 978-3-642-20112-7.
  45. Wiegratz I, Kuhl H . Managing cutaneous manifestations of hyperandrogenic disorders: the role of oral contraceptives . Treat Endocrinol . 1 . 6 . 372–86 . 2002 . 15832490 . 10.2165/00024677-200201060-00003 . 71806394 .
  46. Ruan X, Kubba A, Aguilar A, Mueck AO . Use of cyproterone acetate/ethinylestradiol in polycystic ovary syndrome: rationale and practical aspects . Eur J Contracept Reprod Health Care . 22 . 3 . 183–190 . June 2017 . 28463030 . 10.1080/13625187.2017.1317735 . free .
  47. Book: Catteau-Jonard S, Cortet-Rudelli C, Richard-Proust C, Dewailly D . Pediatric and Adolescent Gynecology . Hyperandrogenism in adolescent girls . Endocr Dev . 22 . 181–93 . 2012 . 22846529 . 10.1159/000326688 . Endocrine Development . 978-3-8055-9336-6 .
  48. Reismann P, Likó I, Igaz P, Patócs A, Rácz K . Pharmacological options for treatment of hyperandrogenic disorders . Mini Rev Med Chem . 9 . 9 . 1113–26 . August 2009 . 19689407 . 10.2174/138955709788922692 .
  49. Diamanti-Kandarakis E . How actual is the treatment with antiandrogen alone in patients with polycystic ovary syndrome? . J. Endocrinol. Invest. . 21 . 9 . 623–9 . October 1998 . 9856417 . 10.1007/BF03350788 . 46484837 .
  50. Book: Husmann F . Women's Health and Menopause. 11. 1997. 257–261. 0928-9550. 10.1007/978-94-011-5560-1_38. Medical Science Symposia Series. 978-94-010-6343-2. Clinical Experiences with a Combination of Estradiol Valerate and Cyproterone Acetate for Hormone Replacement. Springer .
  51. Schneider HP . Androgens and antiandrogens . Ann. N. Y. Acad. Sci. . 997 . 1. 292–306 . November 2003 . 14644837 . 10.1196/annals.1290.033 . 2003NYASA.997..292S . 8400556 .
  52. Schneider HP . The role of antiandrogens in hormone replacement therapy . Climacteric . 3 . Suppl 2 . 21–7 . December 2000 . 11379383 .
  53. Gooren LJ, Giltay EJ, Bunck MC . Long-term treatment of transsexuals with cross-sex hormones: extensive personal experience . The Journal of Clinical Endocrinology and Metabolism . 93 . 1 . 19–25 . January 2008 . 17986639 . 10.1210/jc.2007-1809 .
  54. Hembree WC, Cohen-Kettenis PT, Gooren L, Hannema SE, Meyer WJ, Murad MH, Rosenthal SM, Safer JD, Tangpricha V, T'Sjoen GG . 6 . Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline . The Journal of Clinical Endocrinology and Metabolism . 102 . 11 . 3869–3903 . November 2017 . 28945902 . 10.1210/jc.2017-01658 . free .
  55. Chew D, Anderson J, Williams K, May T, Pang K . Hormonal Treatment in Young People With Gender Dysphoria: A Systematic Review . Pediatrics . 141 . 4 . e20173742 . April 2018 . 29514975 . 10.1542/peds.2017-3742 . free .
  56. Book: Barrett J. Transsexual and Other Disorders of Gender Identity: A Practical Guide to Management. 29 September 2017. CRC Press. 978-1-315-34513-0. 216–217, 221. 2 August 2018. 6 July 2024. https://web.archive.org/web/20240706162108/https://books.google.com/books?id=P803DwAAQBAJ&pg=PT216#v=onepage&q&f=false. live.
  57. Book: Ettner R, Monstrey S, Coleman E. Principles of Transgender Medicine and Surgery. 20 May 2016. Routledge. 978-1-317-51460-2. 169, 171, 216. 2 August 2018. 6 July 2024. https://web.archive.org/web/20240706162109/https://books.google.com/books?id=LwszDAAAQBAJ&pg=PA169#v=onepage&q&f=false. live.
  58. Book: Israel GE. Transgender Care: Recommended Guidelines, Practical Information, and Personal Accounts. March 2001. Temple University Press. 978-1-56639-852-7. 66–. 2 August 2018. 6 July 2024. https://web.archive.org/web/20240706162110/https://books.google.com/books?id=IlPX6E5glDEC&pg=PA66#v=onepage&q&f=false. live.
  59. Winkler-Crepaz K, Mueller A, Boettcher B, Wildt L . Hormonbehandlung bei Transgenderpatienten. Hormone treatment of transgender patients. Gynäkologische Endokrinologie. 15. 1. 2017. 39–42. 1610-2894. 10.1007/s10304-016-0116-9. 12270365.
  60. Urdl W . Behandlungsgrundsätze bei Transsexualität. Therapeutic principles in transsexualism. Gynäkologische Endokrinologie. 7. 3. 2009. 153–160. 1610-2894. 10.1007/s10304-009-0314-9. 8001811.
  61. Kuijpers SM, Wiepjes CM, Conemans EB, Fisher AD, T'Sjoen G, den Heijer M . Toward a Lowest Effective Dose of Cyproterone Acetate in Trans Women: Results From the ENIGI Study . J Clin Endocrinol Metab . 106 . 10 . e3936–e3945 . September 2021 . 34125226 . 8571811 . 10.1210/clinem/dgab427 .
  62. Even Zohar N, Sofer Y, Yaish I, Serebro M, Tordjman K, Greenman Y . Low-Dose Cyproterone Acetate Treatment for Transgender Women . J Sex Med . 18 . 7 . 1292–1298 . July 2021 . 34176757 . 10.1016/j.jsxm.2021.04.008 . 235660315 .
  63. Meyer G, Mayer M, Mondorf A, Fluegel AK, Herrmann E, Bojunga J . Safety and rapid efficacy of guideline-based gender affirming hormone therapy: an analysis of 388 individuals diagnosed with gender dysphoria . European Journal of Endocrinology . 182. 2. November 2019 . 149–156 . 31751300 . 10.1530/EJE-19-0463 . free .
  64. Fung R, Hellstern-Layefsky M, Lega I . Is a lower dose of cyproterone acetate as effective at testosterone suppression in transgender women as higher doses?. International Journal of Transgenderism. 18. 2. 2017. 123–128. 1553-2739. 10.1080/15532739.2017.1290566. 79095497.
  65. Coleman E, Radix AE, Bouman WP, Brown GR, de Vries AL, Deutsch MB, Ettner R, Fraser L, Goodman M, Green J, Hancock AB, Johnson TW, Karasic DH, Knudson GA, Leibowitz SF, Meyer-Bahlburg HF, Monstrey SJ, Motmans J, Nahata L, Nieder TO, Reisner SL, Richards C, Schechter LS, Tangpricha V, Tishelman AC, Van Trotsenburg MA, Winter S, Ducheny K, Adams NJ, Adrián TM, Allen LR, Azul D, Bagga H, Başar K, Bathory DS, Belinky JJ, Berg DR, Berli JU, Bluebond-Langner RO, Bouman MB, Bowers ML, Brassard PJ, Byrne J, Capitán L, Cargill CJ, Carswell JM, Chang SC, Chelvakumar G, Corneil T, Dalke KB, De Cuypere G, de Vries E, Den Heijer M, Devor AH, Dhejne C, D'Marco A, Edmiston EK, Edwards-Leeper L, Ehrbar R, Ehrensaft D, Eisfeld J, Elaut E, Erickson-Schroth L, Feldman JL, Fisher AD, Garcia MM, Gijs L, Green SE, Hall BP, Hardy TL, Irwig MS, Jacobs LA, Janssen AC, Johnson K, Klink DT, Kreukels BP, Kuper LE, Kvach EJ, Malouf MA, Massey R, Mazur T, McLachlan C, Morrison SD, Mosser SW, Neira PM, Nygren U, Oates JM, Obedin-Maliver J, Pagkalos G, Patton J, Phanuphak N, Rachlin K, Reed T, Rider GN, Ristori J, Robbins-Cherry S, Roberts SA, Rodriguez-Wallberg KA, Rosenthal SM, Sabir K, Safer JD, Scheim AI, Seal LJ, Sehoole TJ, Spencer K, St Amand C, Steensma TD, Strang JF, Taylor GB, Tilleman K, T'Sjoen GG, Vala LN, Van Mello NM, Veale JF, Vencill JA, Vincent B, Wesp LM, West MA, Arcelus J . 6 . Standards of Care for the Health of Transgender and Gender Diverse People, Version 8 . International Journal of Transgender Health . 23 . Suppl 1 . S1–S259 . 19 August 2022 . 36238954 . 9553112 . 10.1080/26895269.2022.2100644 . free .
  66. Defreyne J, Vander Stichele C, Iwamoto SJ, T'Sjoen G . Gender-affirming hormonal therapy for transgender and gender-diverse people-A narrative review . Best Pract Res Clin Obstet Gynaecol . 86 . 102296 . February 2023 . 36596713 . 10.1016/j.bpobgyn.2022.102296 . 254818114 . 11197232 .
  67. Glintborg D, T'Sjoen G, Ravn P, Andersen MS . MANAGEMENT OF ENDOCRINE DISEASE: Optimal feminizing hormone treatment in transgender people . Eur J Endocrinol . 185 . 2 . R49–R63 . June 2021 . 34081614 . 10.1530/EJE-21-0059 . 235335361 . free .
  68. Angus LM, Nolan BJ, Zajac JD, Cheung AS . A systematic review of antiandrogens and feminization in transgender women . Clin Endocrinol (Oxf) . 94 . 5 . 743–752 . May 2021 . 32926454 . 10.1111/cen.14329 . 11343/276405 . 221724686 . free .
  69. Sudhakar D, Huang Z, Zietkowski M, Powell N, Fisher AR . Feminizing gender-affirming hormone therapy for the transgender and gender diverse population: An overview of treatment modality, monitoring, and risks . Neurourol Urodyn . 42. 5. 903–920. November 2022 . 36403287 . 10.1002/nau.25097 . 253707685 .
  70. Burinkul S, Panyakhamlerd K, Suwan A, Tuntiviriyapun P, Wainipitapong S . Anti-Androgenic Effects Comparison Between Cyproterone Acetate and Spironolactone in Transgender Women: A Randomized Controlled Trial . J Sex Med . 18 . 7 . 1299–1307 . July 2021 . 34274044 . 10.1016/j.jsxm.2021.05.003 . 236092532 .
  71. Sofer Y, Yaish I, Yaron M, Bach MY, Stern N, Greenman Y . Differential Endocrine and Metabolic Effects of Testosterone Suppressive Agents in Transgender Women . Endocr Pract . 26 . 8 . 883–890 . August 2020 . 33471679 . 10.4158/EP-2020-0032 . 225334013 .
  72. Angus L, Leemaqz S, Ooi O, Cundill P, Silberstein N, Locke P, Zajac JD, Cheung AS . Cyproterone acetate or spironolactone in lowering testosterone concentrations for transgender individuals receiving oestradiol therapy . Endocr Connect . 8 . 7 . 935–940 . July 2019 . 31234145 . 6612061 . 10.1530/EC-19-0272 .
  73. Panagiotakopoulos L . Transgender medicine - puberty suppression . Reviews in Endocrine & Metabolic Disorders . 19 . 3 . 221–225 . September 2018 . 30112593 . 10.1007/s11154-018-9457-0 . 52009542 .
  74. Rosenthal SM . Approach to the patient: transgender youth: endocrine considerations . The Journal of Clinical Endocrinology and Metabolism . 99 . 12 . 4379–89 . December 2014 . 25140398 . 10.1210/jc.2014-1919 . free .
  75. Mahfouda S, Moore JK, Siafarikas A, Zepf FD, Lin A . Puberty suppression in transgender children and adolescents . The Lancet. Diabetes & Endocrinology . 5 . 10 . 816–826 . October 2017 . 28546095 . 10.1016/S2213-8587(17)30099-2 . 10690853 .
  76. Tack LJ, Heyse R, Craen M, Dhondt K, Bossche HV, Laridaen J, Cools M . Consecutive Cyproterone Acetate and Estradiol Treatment in Late-Pubertal Transgender Female Adolescents . The Journal of Sexual Medicine . 14 . 5 . 747–757 . May 2017 . 28499525 . 10.1016/j.jsxm.2017.03.251 . 31089247 .
  77. Torri V, Floriani I . Cyproterone acetate in the therapy of prostate carcinoma . Archivio Italiano di Urologia, Andrologia . 77 . 3 . 157–63 . June 2005 . 16372511 . 10.1.1.663.9458 .
  78. Book: Schröder FH . Antiandrogens in Prostate Cancer. 1996. 45–51. 10.1007/978-3-642-45745-6_4. 978-3-642-45747-0. Cyproterone Acetate — Results of Clinical Trials and Indications for Use in Human Prostate Cancer. ESO Monographs .
  79. Schröder FH . Cyproterone acetate--mechanism of action and clinical effectiveness in prostate cancer treatment . Cancer . 72 . 12 Suppl . 3810–5 . December 1993 . 8252496 . 10.1002/1097-0142(19931215)72:12+<3810::AID-CNCR2820721710>3.0.CO;2-O . 221762 . free .
  80. de Voogt HJ . The position of cyproterone acetate (CPA), a steroidal anti-androgen, in the treatment of prostate cancer . The Prostate. Supplement . 4 . 91–5 . 1992 . 1533452 . 10.1002/pros.2990210514 . 22747185 .
  81. Goldenberg SL, Bruchovsky N . Use of cyproterone acetate in prostate cancer . The Urologic Clinics of North America . 18 . 1 . 111–22 . February 1991 . 10.1016/S0094-0143(21)01398-7 . 1825143 .
  82. Book: Lemke TL, Williams DA . Foye's Principles of Medicinal Chemistry. 2008. Lippincott Williams & Wilkins. 978-0-7817-6879-5. 1288–.
  83. Seidenfeld J, Samson DJ, Hasselblad V, Aronson N, Albertsen PC, Bennett CL, Wilt TJ . Single-therapy androgen suppression in men with advanced prostate cancer: a systematic review and meta-analysis . Annals of Internal Medicine . 132 . 7 . 566–77 . April 2000 . 10744594 . 10.7326/0003-4819-132-7-200004040-00009 . 23128641 .
  84. Book: Mydlo JH, Godec CJ . Prostate Cancer: Science and Clinical Practice . 29 September 2015 . Elsevier Science . 978-0-12-800592-7 . 516–521, 534–540 . live . https://web.archive.org/web/20170908222331/https://books.google.com/books?id=292cBAAAQBAJ&pg=PA530 . 8 September 2017 .
  85. Miyamoto H, Messing EM, Chang C . Androgen deprivation therapy for prostate cancer: current status and future prospects . The Prostate . 61 . 4 . 332–53 . December 2004 . 15389811 . 10.1002/pros.20115 . 22300358 . free .
  86. Wirth MP, Hakenberg OW, Froehner M . Antiandrogens in the treatment of prostate cancer . European Urology . 51 . 2 . 306–13; discussion 314 . February 2007 . 17007995 . 10.1016/j.eururo.2006.08.043 .
  87. Singh SM, Gauthier S, Labrie F . Androgen receptor antagonists (antiandrogens): structure-activity relationships . Current Medicinal Chemistry . 7 . 2 . 211–47 . February 2000 . 10637363 . 10.2174/0929867003375371 . 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]. .
  88. Kaliks RA, Del Giglio A . Management of advanced prostate cancer . Revista da Associação Médica Brasileira . 54 . 2 . 178–82 . 2008 . 18506331 . 10.1590/S0104-42302008000200025 . live . https://web.archive.org/web/20170510112152/http://www.scielo.br/pdf/ramb/v54n2/a25v54n2.pdf . dmy-all . 10 May 2017 . free .
  89. Book: Chabner BA, Longo DL . Cancer Chemotherapy and Biotherapy: Principles and Practice . 8 November 2010 . Lippincott Williams & Wilkins . 978-1-60547-431-1 . 679–680 . 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. . 12 September 2018 . 10 January 2023 . https://web.archive.org/web/20230110224032/https://books.google.com/books?id=WL4arNFsQa8C&pg=PA680 . live .
  90. Book: Horwich A . Systemic Treatment of Prostate Cancer. 11 February 2010. OUP Oxford. 978-0-19-956142-1. 44–.
  91. Anderson J . The role of antiandrogen monotherapy in the treatment of prostate cancer . BJU International . 91 . 5 . 455–61 . March 2003 . 12603397 . 10.1046/j.1464-410X.2003.04026.x . 8639102 . free .
  92. Dalesio O, van Tinteren H, Clarke M, Peto R, Schroder F, Dechering I, Evans V, Godwin J, Blumenstein B, Crawford E, Denis L, Hall R, Hill C, Iversen P, Shipley W, Soloway M, Sylvester R . 6 . Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials. The Lancet. 355. 9214. 2000. 1491–1498. 0140-6736. 10.1016/S0140-6736(00)02163-2. 25366526.
  93. Book: Denis L. Antiandrogens in Prostate Cancer: A Key to Tailored Endocrine Treatment. 6 December 2012. Springer Science & Business Media. 978-3-642-45745-6. 70–. 25 September 2018. 6 July 2024. https://web.archive.org/web/20240706074500/https://books.google.com/books?id=jqZDBQAAQBAJ&pg=PT70#v=onepage&q&f=false. live.
  94. Book: Schröder FH, Radlmaier A . 2009 . Steroidal Antiandrogens . 325–346 . 10.1007/978-1-59259-152-7_15 . Hormone Therapy in Breast and Prostate Cancer . Cancer Drug Discovery and Development . limited . V. Craig Jordan . Barrington J. A. Furr . Humana Press . 978-1-60761-471-5.
  95. Chodak G, Gomella L, Phung DH . Combined androgen blockade in advanced prostate cancer: looking back to move forward . Clinical Genitourinary Cancer . 5 . 6 . 371–8 . September 2007 . 17956709 . 10.3816/CGC.2007.n.019 .
  96. Book: Neumann F . Antiandrogens in Prostate Cancer. 1996. 31–44. 10.1007/978-3-642-45745-6_3. 978-3-642-45747-0. Pharmacology of Cyproterone Acetate — A Short Review. ESO Monographs .
  97. Book: Hinkelbein W, Miller K, Wiegel T. Prostatakarzinom — urologische und strahlentherapeutische Aspekte: urologische und strahlentherapeutische Aspekte. Prostate carcinoma — urological and radiotherapeutic aspects: urological and radiotherapeutic aspects. 7 March 2013. Springer-Verlag. 978-3-642-60064-7. 99–. 27 December 2018. 12 January 2023. https://web.archive.org/web/20230112173056/https://books.google.com/books?id=wdTLBgAAQBAJ&pg=PA99. live.
  98. Khan O, Ferriter M, Huband N, Powney MJ, Dennis JA, Duggan C . Pharmacological interventions for those who have sexually offended or are at risk of offending . Cochrane Database Syst Rev . 2 . CD007989 . February 2015 . 2015 . 25692326 . 10.1002/14651858.CD007989.pub2 . 6544815 .
  99. Silvani M, Mondaini N, Zucchi A . Androgen deprivation therapy (castration therapy) and pedophilia: What's new . Arch Ital Urol Androl . 87 . 3 . 222–6 . September 2015 . 26428645 . 10.4081/aiua.2015.3.222 . free . 11568/1073189 . free .
  100. Reilly DR, Delva NJ, Hudson RW . Protocols for the use of cyproterone, medroxyprogesterone, and leuprolide in the treatment of paraphilia . Can J Psychiatry . 45 . 6 . 559–63 . August 2000 . 10986575 . 10.1177/070674370004500608 . free .
  101. Neumann F, Kalmus J . Cyproterone acetate in the treatment of sexual disorders: pharmacological base and clinical experience . Exp. Clin. Endocrinol. . 98 . 2 . 71–80 . 1991 . 1838080 . 10.1055/s-0029-1211103 .
  102. Freund K . Therapeutic sex drive reduction . . 287 . 5–38 . 1980 . 7006321 . 10.1111/j.1600-0447.1980.tb10433.x . 21981060 .
  103. Codispoti VL . Pharmacology of sexually compulsive behavior . Psychiatr. Clin. North Am. . 31 . 4 . 671–9 . December 2008 . 18996306 . 10.1016/j.psc.2008.06.002 .
  104. Guay DR . Inappropriate sexual behaviors in cognitively impaired older individuals . Am J Geriatr Pharmacother . 6 . 5 . 269–88 . December 2008 . 19161930 . 10.1016/j.amjopharm.2008.12.004 .
  105. Clarke DJ . Antilibidinal drugs and mental retardation: a review . Med Sci Law . 29 . 2 . 136–46 . April 1989 . 2526280 . 10.1177/002580248902900209 . 37808515 .
  106. Hucker SJ . Self-harmful sexual behavior . Psychiatr. Clin. North Am. . 8 . 2 . 323–37 . June 1985 . 3895195 . 10.1016/s0193-953x(18)30698-1.
  107. Assumpção AA, Garcia FD, Garcia HD, Bradford JM, Thibaut F . Pharmacologic treatment of paraphilias . Psychiatr. Clin. North Am. . 37 . 2 . 173–81 . June 2014 . 24877704 . 10.1016/j.psc.2014.03.002 .
  108. Laschet U, Laschet L . Antiandrogens in the treatment of sexual deviations of men . J. Steroid Biochem. . 6 . 6 . 821–6 . June 1975 . 1177426 . 10.1016/0022-4731(75)90310-6 .
  109. Laron Z, Kauli R . Experience with cyproterone acetate in the treatment of precocious puberty . J. Pediatr. Endocrinol. Metab. . 13 . Suppl 1 . 805–10 . July 2000 . 10969925 . 10.1515/JPEM.2000.13.S1.805 . 25398066 .
  110. Brito VN, Latronico AC, Arnhold IJ, Mendonça BB . Update on the etiology, diagnosis and therapeutic management of sexual precocity . Arq Bras Endocrinol Metabol . 52 . 1 . 18–31 . February 2008 . 18345393 . 10.1590/S0004-27302008000100005 . free .
  111. Book: Sachdeva A, Dutta AK. Advances in Pediatrics. 31 August 2012. JP Medical Ltd. 978-93-5025-777-7. 1202–. 27 August 2018. 13 January 2023. https://web.archive.org/web/20230113004839/https://books.google.com/books?id=I2FHFyCaDeIC&pg=PA1202. live.
  112. Holland FJ . Gonadotropin-independent precocious puberty . Endocrinol. Metab. Clin. North Am. . 20 . 1 . 191–210 . March 1991 . 1903104 . 10.1016/s0889-8529(18)30288-3.
  113. Frisk J . Managing hot flushes in men after prostate cancer--a systematic review . Maturitas . 65 . 1 . 15–22 . January 2010 . 19962840 . 10.1016/j.maturitas.2009.10.017 . free .
  114. Spetz AC, Zetterlund EL, Varenhorst E, Hammar M . 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 . 2003 . 15334868 .
  115. Radlmaier A, Bormacher K, Neumann F . Hot flushes: mechanism and prevention . Prog. Clin. Biol. Res. . 359 . 131–40; discussion 141–53 . 1990 . 2149457 .
  116. Thompson IM . Flare Associated with LHRH-Agonist Therapy . Rev Urol . 3 . Suppl 3 . S10–4 . 2001 . 16986003 . 1476081 .
  117. Book: Denis LJ, Griffiths K, Kaisary AV, Murphy GP. Textbook of Prostate Cancer: Pathology, Diagnosis and Treatment: Pathology, Diagnosis and Treatment. 1 March 1999. CRC Press. 978-1-85317-422-3. 308–. 12 September 2018. 6 July 2024. https://web.archive.org/web/20240706074500/https://books.google.com/books?id=GreZlojD-tYC&pg=PA308#v=onepage&q&f=false. live.
  118. Sugiono M, Winkler MH, Okeke AA, Benney M, Gillatt DA . Bicalutamide vs cyproterone acetate in preventing flare with LHRH analogue therapy for prostate cancer—a pilot study . Prostate Cancer and Prostatic Diseases . 8 . 1 . 91–4 . 2005 . 15711607 . 10.1038/sj.pcan.4500784. 9151853 .
  119. Schulze H, Senge T . 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 . October 1990 . 2144596 . 10.1016/S0022-5347(17)39625-8 .
  120. Boccon-Gibod L, Laudat MH, Dugue MA, Steg A . 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 . 1986 . 2949980 . 10.1159/000472667 .
  121. Book: Klosterhalfen H, Jacobi GH . Klosterhalfen H . 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 . Endocrine Management of Prostatic Cancer . De Gruyter . 1988 . 127–137 . 10.1515/9783110853674-014. 9783110853674 .
  122. Bruchovsky N, Goldenberg SL, Akakura K, Rennie PS . Luteinizing hormone-releasing hormone agonists in prostate cancer. Elimination of flare reaction by pretreatment with cyproterone acetate and low-dose diethylstilbestrol . Cancer . 72 . 5 . 1685–91 . September 1993 . 7688656 . 10.1002/1097-0142(19930901)72:5<1685::AID-CNCR2820720532>3.0.CO;2-3 . 21824595 . free .
  123. Rabe T, Albring C, Blume-Peytavi U, Egarter C, Geisthövel F, König K, Kuhl H, Merkle E, Mueck AO, Reisch N, Schüring A, Stute P, Toth B, Wildt L, Zouboulis CC . Hirsutismus – Medikamentöse Therapie Gemeinsame Stellungnahme der Deutschen Gesellschaft für Gynäkologische Endokrinologie und Fortpflanzungsmedizin e.V. und des Berufsverbands der Frauenärzte e.V. . Hirsutism – Medicinal treatment. Joint statement of the German Society of Gynaecological Endocrinology and Reproductive Medicine and the Professional Association of Gynaecologists . Journal für Reproduktionsmedizin und Endokrinologie . 2015 . 12 . 3 . 102–149 . de . 1810-2107 . 22 December 2018 . 5 December 2020 . https://web.archive.org/web/20201205085747/https://www.kup.at/journals/summary/12989.html . live .
  124. Book: Muller NF, Dessing RP. European Drug Index: European Drug Registrations, Fourth Edition. 19 June 1998. CRC Press. 978-3-7692-2114-5. 79–. 29 November 2017. 6 July 2024. https://web.archive.org/web/20240706074500/https://books.google.com/books?id=2HBPHmclMWIC&pg=PA79#v=onepage&q&f=false. live.
  125. Book: Bolognia JL, Jorizzo JL, Schaffer JV. Dermatology E-Book. 8 June 2012. Elsevier Health Sciences. 978-0-7020-5182-1. 557–. 29 November 2017. 6 July 2024. https://web.archive.org/web/20240706074500/https://books.google.com/books?id=A78BaiEKnzIC&pg=PA557#v=onepage&q&f=false. live.
  126. Book: Altmeyer P. Therapielexikon Dermatologie und Allergologie. 2 July 2013. Springer-Verlag. 978-3-662-10498-9. 27–. 20 September 2018. 6 July 2024. https://web.archive.org/web/20240706074529/https://books.google.com/books?id=f-WzBgAAQBAJ&pg=PA27#v=onepage&q&f=false. live.
  127. Book: Kassirer JP, Greene HL. Current Therapy in Adult Medicine. 1997. Mosby. 978-0-8151-5480-8. 174. 29 November 2017. 6 July 2024. https://web.archive.org/web/20240706074501/https://books.google.com/books?id=XqBLAQAAIAAJ. live.
  128. Web site: Androcur Label . 23 December 2018 . 8 March 2017 . https://web.archive.org/web/20170308062025/http://www.bayerresources.com.au/resources/uploads/PI/file9701.pdf . live .
  129. Web site: Mylan-Cyproterone Label . 2 August 2018 . 26 January 2021 . https://web.archive.org/web/20210126094105/https://pdf.hres.ca/dpd_pm/00011374.PDF . live .
  130. Book: Hammerstein J . Hair and Hair Diseases. 1990. 827–886. 10.1007/978-3-642-74612-3_35. 978-3-642-74614-7. Antiandrogens: Clinical Aspects. Springer .
  131. Bachelot A, Chabbert-Buffet N, Salenave S, Kerlan V, Galand-Portier MB . Anti-androgen treatments . Ann. Endocrinol. (Paris) . 71 . 1 . 19–24 . February 2010 . 20096826 . 10.1016/j.ando.2009.12.001 .
  132. Burton JL . Anti-androgen therapy in dermatology: a review . Clin. Exp. Dermatol. . 4 . 4 . 501–7 . December 1979 . 394887 . 10.1111/j.1365-2230.1979.tb01648.x . 29236094 .
  133. Rittmaster RS . Antiandrogen treatment of polycystic ovary syndrome . Endocrinol. Metab. Clin. North Am. . 28 . 2 . 409–21 . June 1999 . 10352926 . 10.1016/S0889-8529(05)70077-3 .
  134. Guay DR . Drug treatment of paraphilic and nonparaphilic sexual disorders . Clin Ther . 31 . 1 . 1–31 . January 2009 . 19243704 . 10.1016/j.clinthera.2009.01.009 . No quantitative data on these adverse events are available, even in the product prescribing information and data sheets..
  135. Migliari R, Muscas G, Murru M, Verdacchi T, De Benedetto G, De Angelis M . Antiandrogens: a summary review of pharmacodynamic properties and tolerability in prostate cancer therapy . Arch Ital Urol Androl . 71 . 5 . 293–302 . December 1999 . 10673793 .
  136. Mylan-Cypersterone Monograph at 4. https://pdf.hres.ca/dpd_pm/00011374.PDF
  137. Book: Saleh FM, Grudzinskas AJ, Bradford JM . Sex Offenders: Identification, Risk Assessment, Treatment, and Legal Issues. 11 February 2009. Oxford University Press, USA. 978-0-19-517704-6. 197–.
  138. Book: Fritz MA, Speroff L. Clinical Gynecologic Endocrinology and Infertility. 2011. Lippincott Williams & Wilkins. 978-0-7817-7968-5. 1091–. 23 November 2018. 6 July 2024. https://web.archive.org/web/20240706074501/https://books.google.com/books?id=Ll73ZsBKLkwC&pg=PA1091#v=onepage&q&f=false. live.
  139. Book: Figg W, Chau CH, Small EJ . Drug Management of Prostate Cancer . 14 September 2010 . Springer . 978-1-60327-829-4 . 71 . 27 September 2016 . 10 January 2023 . https://web.archive.org/web/20230110224030/https://books.google.com/books?id=4KDrjeWA5-UC&pg=PA71 . live .
  140. Honer C, Nam K, Fink C, Marshall P, Ksander G, Chatelain RE, Cornell W, Steele R, Schweitzer R, Schumacher C . 6 . Glucocorticoid receptor antagonism by cyproterone acetate and RU486 . Molecular Pharmacology . 63 . 5 . 1012–20 . May 2003 . 12695529 . 10.1124/mol.63.5.1012 . 23872584 .
  141. Ayub M, Levell MJ . 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 . July 1987 . 2956461 . 10.1016/0022-4731(87)90122-1 .
  142. Book: Han C, Davis CB, Wang B . Evaluation of Drug Candidates for Preclinical Development: Pharmacokinetics, Metabolism, Pharmaceutics, and Toxicology. 6 January 2010. John Wiley & Sons. 978-0-470-57488-1. 92–.
  143. Lehmann JM, McKee DD, Watson MA, Willson TM, Moore JT, Kliewer SA . The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions . The Journal of Clinical Investigation . 102 . 5 . 1016–23 . September 1998 . 9727070 . 508967 . 10.1172/JCI3703 .
  144. Christians U, Schmitz V, Haschke M . Functional interactions between P-glycoprotein and CYP3A in drug metabolism . Expert Opinion on Drug Metabolism & Toxicology . 1 . 4 . 641–54 . December 2005 . 16863430 . 10.1517/17425255.1.4.641 . 17742146 .
  145. Book: Gräf KJ, Brotherton J, Neumann F . Clinical Uses of Antiandrogens . Androgens II and Antiandrogens / Androgene II und Antiandrogene. Handbuch der experimentellen Pharmakologie/Handbook of Experimental Pharmacology . 1974. 485–542. Springer . 10.1007/978-3-642-80859-3_7. 978-3-642-80861-6.
  146. Book: Knaus JV, Isaacs JH . Office Gynecology: Advanced Management Concepts. 6 December 2012. Springer Science & Business Media. 978-1-4612-4340-3. 150–.
  147. Book: Engel J, Kleemann A, Kutscher B, Reichert D. Pharmaceutical Substances: Syntheses, Patents and Applications of the most relevant APIs. 5th. 14 May 2014. Thieme. 978-3-13-179275-4. 351–352. 7 September 2018. 6 July 2024. https://web.archive.org/web/20240706162111/https://books.google.com/books?id=4lCGAwAAQBAJ&pg=PA351. live.
  148. Book: William Andrew Publishing. Pharmaceutical Manufacturing Encyclopedia. 22 October 2013. Elsevier. 978-0-8155-1856-3. 1182–1183.
  149. Buddhasukh D, Maier R, Manosroi A, Manosroi J, Sripalakit P, Werner R . EP . 1359154A1 . Further syntheses of cyproterone acetate . 5 November 2003 .
  150. Web site: Verfahren zur Herstellung von 1, 2alpha-Methylen-delta-17alpha-hydroxy-progesteronen . 20 September 2018 . 8 February 2021 . https://web.archive.org/web/20210208015752/https://patents.google.com/patent/DE1189991B . live .
  151. Web site: 6-chloro-1, 2alpha-methylene-delta6-17alpha-hydroxyprogesterone compounds and compositions . 20 September 2018 . 8 February 2021 . https://web.archive.org/web/20210208032819/https://patents.google.com/patent/US3234093A . live .
  152. Rudolf Wiechert, (1964).
  153. Hamada H, Neumann F, Junkmann K . Intrauterine Antimaskuline Beeinflussung von Rattenfeten Durch ein Stark Gestagen Wirksames Steroid . de . Acta Endocrinologica . 44 . 3 . 380–8 . November 1963 . 14071315 . 10.1530/acta.0.0440380 . Intrauterine antimasculine influence of Rat Fetuses by Birtue of a Powerful Steroid Acting as a Progestogen .
  154. Book: Mann T, Lutwak-Mann C . Male Reproductive Function and Semen: Themes and Trends in Physiology, Biochemistry and Investigative Andrology. 6 December 2012. Springer Science & Business Media. 978-1-4471-1300-3. 352–.
  155. Book: Norman AW, Litwack G . Hormones. 28 June 2014. Elsevier Science. 978-1-4832-5810-2. 508–.
  156. Book: Mainwaring WI . The Mechanism of Action of Androgens. 6 December 2012. Springer Science & Business Media. 978-3-642-88429-0. 53–.
  157. Neumann 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. 5989926 .
  158. Jost A . Use of androgen antagonists and antiandrogens in studies on sex differentiation . Gynecol Invest . 2 . 1 . 180–201 . 1971 . 4949979 . 10.1159/000301861 .
  159. Thibaut F, De La Barra F, Gordon H, Cosyns P, Bradford JM . 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 . June 2010 . 20459370 . 10.3109/15622971003671628 . 14949511 .
  160. Namer M . Clinical applications of antiandrogens . Journal of Steroid Biochemistry . 31 . 4B . 719–29 . October 1988 . 2462132 . 10.1016/0022-4731(88)90023-4 .
  161. Hammerstein J, Cupceancu B . [Management of hirsutism using cyproterone acetate] . de . Deutsche Medizinische Wochenschrift . 94 . 16 . 829–34 . April 1969 . 4304873 . 10.1055/s-0028-1111126 . 71214286 . Management of hirsutism using cyproterone acetate .
  162. Book: Tobias JS, Hochhauser D . Cancer and its Management . 3 October 2014 . Wiley . 978-1-118-46871-5 . 379–.
  163. Book: Jacobi GR, Tunn UW, Senge TH . Clinical experience with cyproterone acetate for palliation of inoperable prostate cancer . Jacobi GH, Hohenfellner R . Prostate Cancer . https://books.google.com/books?id=4HNrAAAAMAAJ . 1 December 1982 . Williams & Wilkins . 978-0-683-04354-9 . 305–319 . 10 July 2019 . 6 July 2024 . https://web.archive.org/web/20240706075014/https://books.google.com/books?id=4HNrAAAAMAAJ . live .
  164. Jacobi GH, Altwein JE, Kurth KH, Basting R, Hohenfellner R . Treatment of advanced prostatic cancer with parenteral cyproterone acetate: a phase III randomised trial . British Journal of Urology . 52 . 3 . 208–15 . June 1980 . 7000222 . 10.1111/j.1464-410X.1980.tb02961.x .
  165. Web site: Androcur . Drug Product Database Online Query . Health Canada . 25 April 2012 . 2 January 2019 . 3 December 2020 . https://web.archive.org/web/20201203170453/https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=7394#fn1 . live .
  166. Web site: Androcur Depot . Drug Product Database Online Query . Health Canada . 25 April 2012 . 2 January 2019 . 3 December 2020 . https://web.archive.org/web/20201203160911/https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=11880#fn1-rf . live .
  167. Web site: DIANE-35 . Drug Product Database Online Query . Health Canada . 25 April 2012 . 2 January 2019 . 3 December 2020 . https://web.archive.org/web/20201203155956/https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=53444 . live .
  168. Book: Becker KL . Principles and Practice of Endocrinology and Metabolism. 2001. Lippincott Williams & Wilkins. 978-0-7817-1750-2. 1004–.
  169. Steinbeck AW . Of Homosexuality: The Current State of Knowledge. Journal of Christian Education. os-20. 2. 1977. 58–82. 0021-9657. 10.1177/002196577702000204 . 149168765.
  170. Zingg E, König MP, Cornu F, Wildholz A, Blaser A . Transsexualismus: Erfahrungen mit der operativen Korrektur bei männlichen Transsexuellen. Transsexualism: Experience with surgical correction in male transsexuals. Aktuelle Urologie. 11. 2. 1980. 67–77. 0001-7868. 10.1055/s-2008-1062961. 56512058 .
  171. Asscheman H, Gooren LJ . Hormone Treatment in Transsexuals. Journal of Psychology & Human Sexuality. 5. 4. 1993. 39–54. 0890-7064. 10.1300/J056v05n04_03. 144580633 .
  172. Neumann F, Wiechert R . Das Antiandrogen Cyproteronacetat Seine Geschichte von der Entdeckung bis zur Marktreife . The antiandrogen cyproterone acetate. Its history from discovery to marketing . de . Pharmazie in unserer Zeit . 17 . 2 . 33–50 . March 1988 . 0048-3664 . 2967500 . 10.1002/pauz.19880170202 .
  173. Book: Elks J . The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. 14 November 2014. Springer. 978-1-4757-2085-3. 339–.
  174. Book: Morton IK, Hall JM . Concise Dictionary of Pharmacological Agents: Properties and Synonyms. 6 December 2012. Springer Science & Business Media. 978-94-011-4439-1. 89–.
  175. Book: Zink C . Dictionary of Obstetrics and Gynecology. 1 January 1988. Walter de Gruyter. 978-3-11-085727-6. 61–.
  176. Web site: Cyproterone . 1 December 2016 . 9 September 2018 . https://web.archive.org/web/20180909222231/https://www.drugs.com/international/cyproterone.html . live .
  177. Book: Index Nominum 2000: International Drug Directory. January 2000. Taylor & Francis. 978-3-88763-075-1. 289–.
  178. Book: Danby FW . Acne: Causes and Practical Management. 27 January 2015. John Wiley & Sons. 978-1-118-23277-4. 142–.
  179. Book: Schechter LS. Surgical Management of the Transgender Patient. 22 September 2016. Elsevier Health Sciences. 978-0-323-48408-4. 26–. 30 October 2016. 6 July 2024. https://web.archive.org/web/20240706075014/https://books.google.com/books?id=eGkgDQAAQBAJ&pg=PP26#v=onepage&q&f=false. live.
  180. http://www.micromedexsolutions.com/micromedex2/{{dead link|date=July 2018 |bot=MutchyMan112 |fix-attempted=yes }}
  181. Book: Sweetman, Sean C. . Sex hormones and their modulators . Martindale: The Complete Drug Reference . 36th . 2009 . 2082 . Pharmaceutical Press . London . 978-0-85369-840-1 . https://www.medicinescomplete.com/mc/martindale/2009/9034-b.htm . 11 March 2018 . 6 July 2024 . https://web.archive.org/web/20240706075023/https://www.medicinescomplete.com/log-in/#/ . live .
  182. Book: Mydlo JH, Godec CJ. Prostate Cancer: Science and Clinical Practice. 11 July 2003. Academic Press. 978-0-08-049789-1. 437–. 11 March 2018. 6 July 2024. https://web.archive.org/web/20240706075017/https://books.google.com/books?id=EIXDBJj6H4wC&pg=PA437#v=onepage&q&f=false. live.
  183. Book: Unzeitig V, van Lunsen RH . Contraceptive Choices and Realities: Proceedings of the 5th Congress of the European Society of Contraception. 15 February 2000. CRC Press. 978-1-85070-067-8. 73–.
  184. Book: IARC Working Group on the Evaluation of Carcinogenic Risks to Humans . World Health Organization . International Agency for Research on Cancer . Combined Estrogen-progestogen Contraceptives and Combined Estrogen-progestogen Menopausal Therapy . 2007 . World Health Organization . 978-92-832-1291-1 . 44,437.
  185. Louw-du Toit R, Storbeck KH, Cartwright M, Cabral A, Africander D . Progestins used in endocrine therapy and the implications for the biosynthesis and metabolism of endogenous steroid hormones . Mol. Cell. Endocrinol. . 441 . 31–45 . February 2017 . 27616670 . 10.1016/j.mce.2016.09.004 . 38582443 .
  186. Book: Gordon JD . Obstetrics, Gynecology & Infertility: Handbook for Clinicians. 2007. Scrub Hill Press, Inc.. 978-0-9645467-7-6. 228–.
  187. Cox RL, Crawford ED . Estrogens in the treatment of prostate cancer . The Journal of Urology . 154 . 6 . 1991–1998 . December 1995 . 7500443 . 10.1016/S0022-5347(01)66670-9 .
  188. Goldenberg SL, Bruchovsky N, Rennie PS, Coppin CM . The combination of cyproterone acetate and low dose diethylstilbestrol in the treatment of advanced prostatic carcinoma . The Journal of Urology . 140 . 6 . 1460–1465 . December 1988 . 2973529 . 10.1016/S0022-5347(17)42073-8 .
  189. Goldenberg SL, Bruchovsky N, Gleave ME, Sullivan LD . Low-dose cyproterone acetate plus mini-dose diethylstilbestrol--a protocol for reversible medical castration . Urology . 47 . 6 . 882–884 . June 1996 . 8677581 . 10.1016/S0090-4295(96)00048-9 .
  190. Matzkin H, Braf Z . Endocrine treatment of benign prostatic hypertrophy: current concepts . Urology . 37 . 1 . 1–16 . January 1991 . 1702565 . 10.1016/0090-4295(91)80069-j .
  191. Tenaglia R, Nicolai M, Di Federico G, Iantorno R, Zezza A, Lombardi G . [Androgen deprivation in benign prostatic hypertrophy] . fr . Journal d'Urologie . 99 . 6 . 296–298 . 1993 . 7516371 .
  192. Di Silverio F, D'Eramo G, Flammia GP, Buscarini M, Frascaro E, Mariani M, Sciarra A . [Pharmacological combinations in the treatment of benign prostatic hypertrophy] . fr . Journal d'Urologie . 99 . 6 . 316–320 . 1993 . 7516378 .
  193. Locker GY . Hormonal therapy of breast cancer . Cancer Treatment Reviews . 24 . 3 . 221–240 . June 1998 . 9767736 . 10.1016/S0305-7372(98)90051-2 .
  194. Willemse PH, Dikkeschei LD, Mulder NH, van der Ploeg E, Sleijfer DT, de Vries EG . Clinical and endocrine effects of cyproterone acetate in postmenopausal patients with advanced breast cancer . European Journal of Cancer & Clinical Oncology . 24 . 3 . 417–421 . March 1988 . 2968261 . 10.1016/S0277-5379(98)90011-6 .
  195. Nieschlag E . Clinical trials in male hormonal contraception . Contraception . 82 . 5 . 457–70 . November 2010 . 20933120 . 10.1016/j.contraception.2010.03.020 . 29 January 2019 . 5 December 2020 . https://web.archive.org/web/20201205082822/https://www.kup.at/kup/pdf/10172.pdf . live .
  196. Book: Nieschlag E, Behre HM, Nieschlag E, Behre HM, Nieschlag S . Nieschlag E, Behre HM, Nieschlag S . Testosterone. The essential role of testosterone in hormonal male contraception . 2012 . 470–493. Cambridge University Press . 10.1017/CBO9781139003353.023 . 9781139003353.
  197. Web site: Cyproterone acetate - Barr Laboratories - AdisInsight . 11 December 2017 . 2 August 2018 . https://web.archive.org/web/20180802193342/https://adisinsight.springer.com/drugs/800015250 . live .
  198. Nguyen Y, Bradford J, Fischer G . Cyproterone acetate in the treatment of oestrogen hypersensitivity vulvovaginitis . The Australasian Journal of Dermatology . 59 . 1 . 52–54 . February 2018 . 28718897 . 10.1111/ajd.12657 . 22365089 .
  199. Geier DA, Kern JK, King PG, Sykes LK, Geier MR . An evaluation of the role and treatment of elevated male hormones in autism spectrum disorders . Acta Neurobiol Exp (Wars) . 72 . 1 . 1–17 . 2012 . 10.55782/ane-2012-1876 . 22508080 . 11909534 . free .
  200. Bolea-Alamanac BM, Davies SJ, Christmas DM, Baxter H, Cullum S, Nutt DJ . Cyproterone to treat aggressivity in dementia: a clinical case and systematic review . J. Psychopharmacol. (Oxford) . 25 . 1 . 141–5 . 2011 . 19942637 . 10.1177/0269881109353460 . 11479701 .
  201. Albert DJ, Walsh ML, Jonik RH . Aggression in humans: what is its biological foundation? . Neurosci Biobehav Rev . 17 . 4 . 405–25 . 1993 . 8309650 . 10.1016/S0149-7634(05)80117-4 . 28557481 .
  202. Thibaut F, Kuhn JM, Colonna L . A possible antiaggressive effect of cyproterone acetate . Br J Psychiatry . 159 . 2. 298–9 . August 1991 . 1837749 . 10.1192/bjp.159.2.298b . free .
  203. Nomani H, Mohammadpour AH, Moallem SM, YazdanAbad MJ, Barreto GE, Sahebkar A . Anti-androgen drugs in the treatment of obsessive-compulsive disorder: a systematic review . Curr Med Chem . December 2019 . 27 . 40 . 6825–6836 . 31814547 . 10.2174/0929867326666191209142209 . 208956450 .
  204. Book: Rapoport JL . Obsessive-compulsive Disorder in Children and Adolescents . registration . 1 January 1989 . American Psychiatric Pub . 978-0-88048-282-0 . 229–231.
  205. Kellner M . Drug treatment of obsessive-compulsive disorder . Dialogues in Clinical Neuroscience . 12 . 2 . 187–97 . 2010 . 10.31887/DCNS.2010.12.2/mkellner . 20623923 . 3181958 .
  206. Book: López Ibor JJ, Cercós CL, Masiá CC . Images of Spanish Psychiatry . 2004 . Editorial Glosa, S.L. . 978-84-7429-200-8 . 376–.
  207. Sicuteri F . Antiandrogenic medication of cluster headache . Int J Clin Pharmacol Res . 8 . 1 . 21–4 . 1988 . 3366500 .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Cyproterone acetate".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.