Cyproterone acetate

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Cyproterone acetate
Cyproterone acetate.svg
Cyproterone-acetate-from-xtal-view-1-Mercury-3D-balls-thin.png
Clinical data
Trade names Androcur, Androcur Depot, Cyprostat, Siterone, others
Other namesSH-80714; SH-714; NSC-81430; 1α,2α-Methylene-6-chloro-17α-hydroxy-δ6-progesterone acetate; 1α,2α-Methylene-6-chloro-17α-hydroxypregna-4,6-diene-3,20-dione acetate
AHFS/Drugs.com Micromedex Detailed Consumer Information
Pregnancy
category
  • X
Routes of
administration 		By mouth, intramuscular injection
Drug class Steroidal antiandrogen; Progestogen; Progestin; Progestogen ester; Antigonadotropin
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability Oral: 68–100% [1] [2]
Protein binding Albumin: 93%
Free: 7% [3] [4] [5] [6]
Metabolism Hepatic (CYP3A4) [7] [8]
Metabolites • 15β-OH-CPA Tooltip 15β-Hydroxycyproterone acetate (major) [1] [9]
• Cyproterone (minor) [10]
• Acetic acid (minor) [10]
Elimination half-life Oral: 1.6–4.3 days [10] [11] [12]
IM: 3–4.3 days [2] [10] [12]
Excretion Feces: 70% [10]
Urine: 30% [10]
Identifiers
  • (2aR,3aS,3bS,3cS,5aS,6R,8aS,8bR)-6-acetyl-10-chloro-3b,5a-dimethyl-2-oxo-2,2a,3,3a,3b,3c,4,5,5a,6,7,8,8a,8b-tetradecahydrocyclopenta[a]cyclopropa[g]phenanthren-6-yl acetat
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.006.409 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C24H29ClO4
Molar mass 416.94 g·mol−1
3D model (JSmol)
Melting point 200 to 201 °C (392 to 394 °F)
  • CC(=O)[C@]1(CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2C=C(C4=CC(=O)[C@@H]5C[C@@H]5[C@]34C)Cl)C)OC(=O)C
  • InChI=1S/C24H29ClO4/c1-12(26)24(29-13(2)27)8-6-16-14-10-20(25)19-11-21(28)18(15)23(19,4)17(14)5-7-22(16,24)3/h10-11,14-18H,5-9H2,1-4H3/t14-,15+,16-,17-,18-,22-,23-,24-/m0/s1
  • Key:UWFYSQMTEOIJJG-FDTZYFLXSA-N
   (verify)

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] [11] [13] [14] [15] It is formulated and used both alone and in combination with an estrogen. CPA is taken by mouth one to three times per day.

Contents

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. With prolonged use, brain tumors prompting surgery are common, from 5% at high doses [16] to 2% at low doses. At very high doses in older individuals, significant cardiovascular complications can occur[ vague ]. Rare but serious adverse reactions of CPA include blood clots, and liver damage. 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. [1] [13] [17] In addition, it has progesterone-like effects by activating the progesterone receptor (PR). [1] [13] It can also produce weak cortisol-like effects at very high doses. [1]

CPA was discovered in 1961. [18] It was originally developed as a progestin. [18] In 1965, the antiandrogenic effects of CPA were discovered. [19] CPA was first marketed, as an antiandrogen, in 1973, and was the first antiandrogen to be introduced for medical use. [20] A few years later, in 1978, CPA was introduced as a progestin in a birth control pill. [21] It has been described as a "first-generation" progestin [22] and as the prototypical antiandrogen. [23] CPA is available widely throughout the world. [24] [25] An exception is the United States, where it is not approved for use. [26] [27]

Medical uses

CPA is used as a progestin and antiandrogen in hormonal birth control and in the treatment of androgen-dependent conditions. [13] 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. [28] Treatment dosages range from 2mg or less, to 100mg or more daily. [29]

In the United States, where CPA is not available, other medications with antiandrogenic effects are used to treat androgen-dependent conditions instead. [30] 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. [30] The steroidal antiandrogen and progestin chlormadinone acetate is used as an alternative to CPA in Japan, South Korea, and a few other countries.[ citation needed ]

In 2020, the European Medicine Agency issued a warning that high doses of cyproterone acetate may contribute to risk of meningioma, and recommended physicians use alternative treatment for most indications (or the minimum effective dose where no alternatives were available) with the exception of prostate carcinoma. [29]

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. [21] The formulation is taken once daily for 21 days, followed by a 7-day free interval. [31] CPA has also been available in combination with estradiol valerate (brand name Femilar) as a combined birth control pill in Finland since 1993. [32] [33] High-dose CPA tablets have a contraceptive effect and can be used as a form of birth control, although they are not specifically licensed as such. [34]

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. [35] [36] [37] [38] [39] [40] [41] These conditions are worsened by the presence of androgens, and by suppressing androgen levels and blocking their actions, CPA improves the symptoms of these conditions. CPA is used to treat such conditions both at low doses as a birth control pill and on its own at higher doses. [35] [36] [37] [38] [42] A birth control pill containing low-dose CPA in combination with ethinylestradiol to treat acne has been found to result in overall improvement in 75 to 90% of women, with responses approaching 100% improvement. [43] High-dose CPA alone likewise has been found to improve symptoms of acne by 75 to 90% in women. [44] Discontinuation of CPA has been found to result in marked recurrence of symptoms in up to 70% of women. [45] CPA is one of the most commonly used medications in the treatment of hirsutism, hyperandrogenism, and polycystic ovary syndrome in women throughout the world. [46] [47]

Higher dosages of CPA are used in combination with an estrogen specifically at doses of 25 to 100 mg/day cyclically in the treatment of hirsutism in women. [47] [48] [49] The efficacy of such dosages of CPA in the treatment of hirsutism in women appear to be similar to that of spironolactone, flutamide, and finasteride. [48] [49] [46] [47] Randomized controlled trials have found that higher dosages of CPA (e.g., 20 mg/day or 100 mg/day) added cyclically to 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. [47] [49] [46] [50] [51] [52] Maintenance therapy with lower doses of CPA, such as 25 mg/day, has been found to be effective in preventing relapse of symptoms of hirsutism. [45] CPA has typically been combined with ethinylestradiol, but it can alternatively be used in combination with hormone replacement therapy dosages of estradiol instead. [47] CPA at a dosage of 50 mg/day in combination with 100 μg/day transdermal estradiol patches has been found to be effective in the treatment of hirsutism similarly to the combination of CPA with ethinylestradiol. [49] [53]

The efficacy of the combination of an estrogen and CPA in the treatment of hirsutism in women appears to be due to marked suppression of total and free androgen levels as well as additional blockade of the androgen receptor. [46] [47] [54]

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. [55] [56] [57] [58] It can also halt further progression of scalp hair loss in men. [59] [60] [61] Increased head hair and decreased body hair has been observed with CPA in men with scalp hair loss. [62] [13] However, its side effects in men, such as demasculinization, gynecomastia, sexual dysfunction, bone density loss, and reversible infertility, make the use of CPA in males impractical in most cases. [59] [60] [56] [57] [63] [64] [65] In addition, lower dosages of CPA, such as 25 mg/day, have been found to be better-tolerated in men. [57] But such doses also show lower effectiveness in the treatment of acne in men. [55]

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. [36] [41] [66] [67] [68] [69] It is almost always combined with an estrogen, such as ethinylestradiol, when it is used in the treatment of PCOS in women. [70]

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. [71] [1] [72] [73] 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. [71] [72] [73] Climen was the first product for use in menopausal hormone therapy containing CPA to be marketed. [72] It is available in more than 40 countries. [71]

Transgender hormone therapy

CPA is widely used as an antiandrogen and progestogen in feminizing hormone therapy for transgender individuals. [74] [75] [76] [77] [78] [79] [80] It has been historically used orally at a dosage of 10 to 100 mg/day and by intramuscular injection at a dosage of 300 mg once every 4 weeks. [81] [82] Many transgender individuals seeking feminizing hormone therapy have breast growth as one of the goals for undergoing feminizing hormone therapy, making this particular side effect of CPA generally viewed as a beneficial outcome rather than an issue. [60]

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. [83] [84] [85] [86] 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. [86] As a result, a CPA dosage of 10 mg/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). [87]

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. [88] [89] [90] [91] [92] [93] [94] Spironolactone is the most widely used antiandrogen in transgender women in the United States, whereas CPA is widely used in Europe and throughout the rest of the world. [89] [87]

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. [95] [96] [76] [97] [98]

Prostate cancer

CPA is used as an antiandrogen monotherapy and means of androgen deprivation therapy in the palliative treatment of prostate cancer in men. [11] [99] [100] [101] [102] [103] It is used at very high doses by mouth or by intramuscular injection to treat this disease. Antiandrogens do not cure prostate cancer, but can significantly extend life in men with the disease. [104] [105] [99] CPA has similar effectiveness 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). [99] [105] [106] [107] [108] In addition, the combination of CPA with a GnRH modulator or surgical castration has not been found to improve outcomes relative to a GnRH modulator or surgical castration alone, in contrast to nonsteroidal antiandrogens. [109] Due to its inferior effectiveness, tolerability, and safety, CPA is rarely used in the treatment of prostate cancer today, having largely been superseded by GnRH modulators and nonsteroidal antiandrogens. [110] [111] CPA is the only steroidal antiandrogen that continues to be used in the treatment of prostate cancer. [105]

Dose-ranging studies of CPA for prostate cancer were not performed, and the optimal dosage of CPA for the treatment of the condition has not been established. [112] [113] A dosage range of oral CPA of 100 to 300 mg/day is used in the treatment of prostate cancer, but generally 150 to 200 mg/day oral CPA is used. [114] [115] Schröder (1993, 2002) reviewed the issue of CPA dosage and recommended a dosage of 200 to 300 mg/day for CPA as a monotherapy and a dosage of 100 to 200 mg/day for CPA in combined androgen blockade (that is, CPA in combination with surgical or medical castration). [116] [101] However, the combination of CPA with castration for prostate cancer has been found to significantly decrease overall survival compared to castration alone. [117] Hence, the use of CPA as the antiandrogen component in combined androgen blockade would appear not to be advisable. [117] When used by intramuscular injection to treat prostate cancer, CPA is used at a dosage of 300 mg once a week. [65]

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. [116] [118] [119] [120] [121]

Sexual deviance

CPA is used as an antiandrogen and form of chemical castration in the treatment of paraphilias and hypersexuality in men. [122] [123] [124] [62] [125] [126] It is used to treat sex offenders.[ citation needed ] The medication is approved in more than 20 countries for this indication and is predominantly employed in Canada, Europe, and the Middle East. [127] 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. [128] [129] The medication is also used to reduce sexual behavior diagnosed as self-harmful, such as masochism. [130] 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. [123]

High-dose CPA significantly decreases sexual fantasies and sexual activity in 80 to 90% of men with paraphilias. [127] In addition, it has been found to decrease the rate of reoffending in sex offenders from 85% to 6%, with most of the reoffenses being committed by individuals who did not follow their CPA treatment prescription. [127] It has been reported that in 80% of cases, 100 mg/day CPA is adequate to achieve the desired reduction of sexuality, whereas in the remaining 20% of cases, 200 mg/day is sufficient. [131] When only a partial reduction in sexuality is desired, 50 mg/day CPA can be useful. [131] Reduced sexual desire and erectile function occurs with CPA by the end of the first week of treatment, and becomes maximal within three to four weeks. [131] [65] The dosage range is 50 to 300 mg/day. [65] [131]

Early puberty

CPA is used as an antiandrogen and antiestrogen to treat precocious puberty in boys and girls. [13] [67] [132] However, it is not fully satisfactory for this indication because it is not able to completely suppress puberty. [133] For this reason, CPA has mostly been superseded by GnRH agonists in the treatment of precocious puberty. [67] CPA is not satisfactory for gonadotropin-independent precocious puberty. [134] CPA has been used at dosages of 50 to 300 mg/m2 to treat precocious puberty. [65] [13]

Other uses

CPA is useful in the treatment of hot flashes, for instance due to androgen deprivation therapy for prostate cancer. [106] [135] [136] [137]

CPA is useful for suppressing the testosterone flare at the initiation of GnRH agonist therapy. [138] [106] [139] [11] [67] [140] [141] [142] [143] It has been used successfully both alone and in combination with estrogens such as diethylstilbestrol for this purpose. [138] [144]

Available forms

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). [145] [146] [147] [148] [149]

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. [148] [150]

Contraindications

Contraindications of CPA include: [151] [152] [54]

When CPA is used in combination with an estrogen, contraindications for birth control pills should also be considered. [54]

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. [153] [154] 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. [54] Weight gain can occur with CPA when it is used at high doses. [155] [51] Some of the side effects of CPA can be improved or fully prevented if it is combined with an estrogen to prevent estrogen deficiency. [70] [43] Few quantitative data are available on many of the potential side effects of CPA. [156] Pooled tolerability data for CPA is not available in the literature. [157] Cyproterone is also known to suppress adrenocortical function. [158]

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.

Side effects of high-dose cyproterone acetate
Frequency System Organ Class Side effect
Very common (≥10%) General disorders and administration site conditions
Psychiatric disorders
Reproductive system and breast disorders
Hepatobiliary disorders Elevated liver enzymes
Common (≥1% and <10%) Metabolism and nutrition disorders Weight gain or loss (can be associated with fluid retention)
Psychiatric disorders
Reproductive system and breast disorders
General disorders and administration site conditions
Respiratory, thoracic, and mediastinal disorders Shortness of breath
Gastrointestinal disorders
Uncommon (≥0.1% and <1%) Psychiatric disorders Decreased libido (women)
Skin and subcutaneous tissue disorders Rash
Rare (≥0.01% and <0.1%) Immune system disorders Hypersensitivity reactions (rash, itching, shortness of breath)
Psychiatric disorders Increased libido (women)
Very rare (<0.01%) Neoplasms benign and malignant Benign and malignant liver tumors
Musculoskeletal and connective tissue disorders Osteoporosis
Cardiovascular disorders
Reproductive system and breast disorders Galactorrhea
General disorders and administration site conditions Sleep disturbances
UnspecifiedUnsorted
Low
Dysmenorrhea
Vaginal discharge
Skin discoloration
Stretch marks
Rare
Liver toxicity (including jaundice, hepatitis, liver failure)
Notes: Side effects are for dosages of cyproterone acetate (Androcur) of 10 to 300 mg/day. Sources: See template.

Overdose

CPA is relatively safe in acute overdose. [152] It is used at very high doses of up to 300 mg/day by mouth and 700 mg per week by intramuscular injection. [152] [159] For comparison, the dose of CPA used in birth control pills is 2 mg/day. [160] There have been no deaths associated with CPA overdose. [152] There are no specific antidotes for CPA overdose, and treatment should be symptom-based. [152] Gastric lavage can be used in the event of oral overdose within the last 2 to 3 hours. [152]

Interactions

Inhibitors and inducers of the cytochrome P450 enzyme CYP3A4 may interact with CPA. [152] 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. [152] Certain anticonvulsant medications can substantially reduce levels of CPA, by as much as 8-fold. [38]

Pharmacology

Pharmacodynamics

CPA has antiandrogenic activity, [1] [161] progestogenic activity, [1] [161] weak partial glucocorticoid activity, [162] weak steroidogenesis inhibitor activity, [163] and agonist activity at the pregnane X receptor. [164] [165] [166] It has no estrogenic or antimineralocorticoid activity. [1] In terms of potency, CPA is described as a highly potent progestogen, a moderately potent antiandrogen, and a weak glucocorticoid. [54] [155] [43] Due to its progestogenic activity, CPA has antigonadotropic effects, and is able to suppress fertility and sex-hormone levels in both males and females. [1] [13] [54]

Pharmacokinetics

CPA can be taken by mouth or by injection into muscle. [13] 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. [1] [4] [12]

Chemistry

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. [167] [168] It is structurally related to other 17α-hydroxyprogesterone derivatives such as chlormadinone acetate, hydroxyprogesterone caproate, medroxyprogesterone acetate, and megestrol acetate. [168]

Synthesis

Chemical syntheses of CPA have been published. [146] [169] [170] The following is one such synthesis: [171] [172]

Thieme Partial synthesis of CPA, using hydroxyprogesterone acetate as a starting material, by Wiechert & Neumann (1965) and Wiechert (1966). Cyproterone acetate synthesis.png
Thieme Partial synthesis of CPA, using hydroxyprogesterone acetate as a starting material, by Wiechert & Neumann (1965) and Wiechert (1966).

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, [173] releasing nitrogen molecules and forming a cyclopropane derivative, 6-deschloro cyproterone acetate [2701-50-0] (5). Selective oxidation of the C6=C7 olefin with benzoyl peroxide gives the epoxide, i.e. 6-deschloro-6,7-epoxy cyproterone [15423-97-9] (6). The penultimate step involves a reaction with hydrochloric acid in acetic acid, resulting in the formation of chlorine and its subsequent dehydration, and a simultaneous opening of the cyclopropane ring giving 1α-(chloromethyl) chlormadinone acetate [17183-98-1] (7). The heating of this in collidine reforms the cyclopropane ring, completing the synthesis of CPA (8).

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. [18] [174] The antiandrogenic activity of CPA was discovered serendipitously by Hamada, Neumann, and Karl Junkmann in 1963. [175] [65] 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. [43] [176] [177] [178]

CPA was initially developed as a progestogen for the prevention of threatened abortion. [65] As part of its development, it was assessed for androgenic activity to ensure that it would not produce teratogenic effects in female fetuses. [65] The drug was administered to pregnant rats and its effects on the rat fetuses were studied. [65] To the surprise of the researchers, all of the rat pups born appeared to be female. [65] After 20 female rat pups in a row had been counted, it was clear that this could not be a chance occurrence. [65] The rat pups were further evaluated and it was found that, in terms of karyotype, about 50% were actually males. [65] The male rat pups had been feminized, and this resultant finding constituted the discovery of the powerful antiandrogenic activity of CPA. [65] A year after patent approval in 1965, Neumann published additional evidence of CPA's antiandrogenic effect in rats; he reported an "organizational effect of CPA on the brain". [19] CPA started being used in animal experiments around the world to investigate how antiandrogens affected fetal sexual differentiation. [179]

The first clinical use of CPA in the treatment of sexual deviance and prostate cancer occurred in 1966. [14] [180] [181] It was first studied in the treatment of androgen-dependent skin and hair symptoms, specifically acne, hirsutism, seborrhea, and scalp hair loss, in 1969. [182] CPA was first approved for medical use in 1973 in Europe under the brand name Androcur. [169] [183] In 1977, a formulation of CPA was introduced for use by intramuscular injection. [184] CPA was first marketed as a birth control pill in 1978 in combination with ethinylestradiol under the brand name Diane. [21] Following phase III clinical trials, CPA was approved for the treatment of prostate cancer in Germany in 1980. [184] [185] CPA became available in Canada as Androcur in 1987, as Androcur Depot in 1990, and as Diane-35 in 1998. [186] [187] [188] Conversely, CPA was never introduced in any form in the United States. [26] [30] 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. [189] Use of CPA in transgender women, an off-label indication, was reported as early as 1977. [190] [191] The use of CPA in transgender women was well-established by the early 1990s. [192]

The history of CPA, including its discovery, development, and marketing, has been reviewed. [193] [13]

Society and culture

Generic names

The English and generic name of CPA is cyproterone acetate and this is its USAN Tooltip United States Adopted Name, BAN Tooltip British Approved Name, and JAN Tooltip Japanese Accepted Name. [24] [25] [194] [195] The English and generic name of unacetylated cyproterone is cyproterone and this is its INN Tooltip International Nonproprietary Name and BAN Tooltip British Approved Name, [194] [195] [196] while cyprotérone is the DCF Tooltip Dénomination Commune Française and French name and ciproterone is the DCIT Tooltip Denominazione Comune Italiana and Italian name. [24] [25] The name of unesterified cyproterone in Latin is cyproteronum, in German is cyproteron, and in Spanish is ciproterona. [24] [25] 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. [24] [25] [194] [195]

Brand names

CPA is marketed under brand names including Androcur, Androcur Depot, Androcur-100, Androstat, Asoteron, Cyprone, Cyproplex, Cyprostat, Cysaxal, Imvel, and Siterone. [24] [25] When CPA is formulated in combination with ethinylestradiol, it is also known 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. [24] [25] CPA is also marketed in combination with estradiol valerate as Climen, Climene, Elamax, and Femilar. [24]

Availability

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. Cyproterone acetate availability.png
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.

CPA is widely available throughout the world, and is marketed in almost every developed country, [197] with the notable major exceptions of the United States and Japan. [24] [25] [26] [198] [199] In almost all countries in which CPA is marketed, it is available both alone and in combination with an estrogen in birth control pills. [24] [198] [199] CPA is marketed widely in combination with both ethinylestradiol and estradiol valerate. [24] [25] [198] [199] CPA-containing birth control pills are available in South Korea, but CPA as a standalone medication is not marketed in this country. [24] [25] [198] [199] In Japan and South Korea, the closely related antiandrogen and progestin chlormadinone acetate, as well as other medications, are used instead of CPA. [200] Specific places in which CPA is marketed include the United Kingdom, elsewhere throughout Europe, Canada, Australia, New Zealand, South Africa, Latin America, and Asia. [24] [25] [198] [199] CPA is not marketed in most of Africa and the Middle East. [24] [25] [198] [199]

It has been said that the lack of availability of CPA in the United States explains why there are relatively few studies of it in the treatment of androgen-dependent conditions such as hyperandrogenism and hirsutism in women. [153]

Generation

Progestins in birth control pills are sometimes grouped by generation. [201] [202] 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". [201] [202] 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. [22] [203]

Research

CPA has been studied and used in combination with low-dose diethylstilbestrol in the treatment of prostate cancer. [118] [120] [119] The combination results in suppression of testosterone levels into the castrate range, which normally cannot be achieved with CPA alone. [120] CPA has been studied as a form of androgen deprivation therapy for the treatment of benign prostatic hyperplasia (enlarged prostate). [204] [205] [206] The medication has been studied in the treatment of breast cancer as well. [207] [208]

CPA has been studied for use as a potential male hormonal contraceptive both alone and in combination with testosterone in men. [209] [210] CPA was under development by Barr Pharmaceuticals in the 2000s for the treatment of hot flashes in prostate cancer patients in the United States. [211] It reached phase III clinical trials for this indication and had the tentative brand name CyPat but development was ultimately discontinued in 2008. [211] CPA is not satisfactorily effective as topical antiandrogen, for instance in the treatment of acne. [167] CPA has been used to treat estrogen hypersensitivity vulvovaginitis in women. [212]

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. [213] [214] [215] [216] CPA may be effective in the treatment of obsessive–compulsive disorder (OCD). [217] [218] [219] [220] CPA has been studied in the treatment of cluster headaches in men. [221]

See also

Related Research Articles

<span class="mw-page-title-main">Antiandrogen</span> Class of pharmaceutical drugs

Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the androgen receptor (AR) and/or inhibiting or suppressing androgen production. They can be thought of as the functional opposites of AR agonists, for instance androgens and anabolic steroids (AAS) like testosterone, DHT, and nandrolone and selective androgen receptor modulators (SARMs) like enobosarm. Antiandrogens are one of three types of sex hormone antagonists, the others being antiestrogens and antiprogestogens.

<span class="mw-page-title-main">Spironolactone</span> Steroidal antiandrogen and antimineralocorticoid

Spironolactone, sold under the brand name Aldactone among others, is a diuretic medication primarily used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It is also used in the treatment of high blood pressure, and low blood potassium that does not improve with supplementation, early puberty in boys, acne and excessive hair growth in women. Spironolactone is taken by mouth.

<span class="mw-page-title-main">Bicalutamide</span> Antiandrogen medication

Bicalutamide, sold under the brand name Casodex among others, is an antiandrogen medication that is primarily used to treat prostate cancer. It is typically used together with a gonadotropin-releasing hormone (GnRH) analogue or surgical removal of the testicles to treat metastatic prostate cancer (mPC). To a lesser extent, it is used at high doses for locally advanced prostate cancer (LAPC) as a monotherapy without castration. Bicalutamide was also previously used as monotherapy to treat localized prostate cancer (LPC), but authorization for this use was withdrawn following unfavorable trial findings. Besides prostate cancer, bicalutamide is limitedly used in the treatment of excessive hair growth and scalp hair loss in women, as a puberty blocker and component of feminizing hormone therapy for transgender girls and women, to treat gonadotropin-independent early puberty in boys, and to prevent overly long-lasting erections in men. It is taken by mouth.

<span class="mw-page-title-main">Flutamide</span> Chemical compound

Flutamide, sold under the brand name Eulexin among others, is a nonsteroidal antiandrogen (NSAA) which is used primarily to treat prostate cancer. It is also used in the treatment of androgen-dependent conditions like acne, excessive hair growth, and high androgen levels in women. It is taken by mouth, usually three times per day.

<span class="mw-page-title-main">Nilutamide</span> Chemical compound

Nilutamide, sold under the brand names Nilandron and Anandron, is a nonsteroidal antiandrogen (NSAA) which is used in the treatment of prostate cancer. It has also been studied as a component of feminizing hormone therapy for transgender women and to treat acne and seborrhea in women. It is taken by mouth.

Feminizing hormone therapy, also known as transfeminine hormone therapy, is hormone therapy and sex reassignment therapy to change the secondary sex characteristics of transgender people from masculine or androgynous to feminine. It is a common type of transgender hormone therapy and is used to treat transgender women and non-binary transfeminine individuals. Some, in particular intersex people, but also some non-transgender people, take this form of therapy according to their personal needs and preferences.

<span class="mw-page-title-main">Chlormadinone acetate</span> Chemical compound

Chlormadinone acetate (CMA), sold under the brand names Belara, Gynorelle, Lutéran, and Prostal among others, is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy, as a component of menopausal hormone therapy, in the treatment of gynecological disorders, and in the treatment of androgen-dependent conditions like enlarged prostate and prostate cancer in men and acne and hirsutism in women. It is available both at a low dose in combination with an estrogen in birth control pills and, in a few countries like France and Japan, at low, moderate, and high doses alone for various indications. It is taken by mouth.

The first antiandrogen was discovered in the 1960s. Antiandrogens antagonise the androgen receptor (AR) and thereby block the biological effects of testosterone and dihydrotestosterone (DHT). Antiandrogens are important for men with hormonally responsive diseases like prostate cancer, benign prostatic hyperplasia (BHP), acne, seborrhea, hirsutism and androgen alopecia. Antiandrogens are mainly used for the treatment of prostate diseases. Research from 2010 suggests that ARs could be linked to the disease progression of triple-negative breast cancer and salivary duct carcinoma and that antiandrogens can potentially be used to treat it.

<span class="mw-page-title-main">Estradiol undecylate</span> Chemical compound

Estradiol undecylate, also known as estradiol undecanoate and formerly sold under the brand names Delestrec and Progynon Depot 100 among others, is an estrogen medication which has been used in the treatment of prostate cancer in men. It has also been used as a part of hormone therapy for transgender women. Although estradiol undecylate has been used in the past, it was discontinued. The medication has been given by injection into muscle usually once a month.

<span class="mw-page-title-main">Cyproterone</span> Chemical compound

Cyproterone, also known by its developmental code name SH-80881, is a steroidal antiandrogen which was studied in the 1960s and 1970s but was never introduced for medical use. It is a precursor of cyproterone acetate (CPA), an antiandrogen, progestin, and antigonadotropin which was introduced instead of cyproterone and is widely used as a medication. Cyproterone and CPA were among the first antiandrogens to be developed.

<span class="mw-page-title-main">Benorterone</span> Chemical compound

Benorterone, also known by its developmental code name SKF-7690 and as 17α-methyl-B-nortestosterone, is a steroidal antiandrogen which was studied for potential medical use but was never marketed. It was the first known antiandrogen to be studied in humans. It is taken by mouth or by application to skin.

<span class="mw-page-title-main">Nonsteroidal antiandrogen</span> Antiandrogen with a nonsteroidal chemical structure

A nonsteroidal antiandrogen (NSAA) is an antiandrogen with a nonsteroidal chemical structure. They are typically selective and full or silent antagonists of the androgen receptor (AR) and act by directly blocking the effects of androgens like testosterone and dihydrotestosterone (DHT). NSAAs are used in the treatment of androgen-dependent conditions in men and women. They are the converse of steroidal antiandrogens (SAAs), which are antiandrogens that are steroids and are structurally related to testosterone.

<span class="mw-page-title-main">BOMT</span> Chemical compound

BOMT, also known by its developmental code name Ro 7-2340 and as 6α-bromo-4-oxa-17α-methyl-5α-dihydrotestosterone, is a synthetic steroidal antiandrogen which was first produced in 1970 and was never marketed for medical use. It is the 6α-brominated, 4-oxygenated, and 17α-methylated derivative of the androgen dihydrotestosterone (DHT). Along with benorterone, cyproterone, and flutamide, BOMT was among the earliest antiandrogens to be developed and extensively studied, although it is less well-documented in comparison to the others. BOMT has been investigated clinically in the treatment of benign prostatic hyperplasia, though development for this use did not continue. There was also interest in BOMT for the potential applications of acne, pattern hair loss, and possibly prostate cancer, but it was not developed for these indications either.

<span class="mw-page-title-main">Steroidal antiandrogen</span> Class of compounds

A steroidal antiandrogen (SAA) is an antiandrogen with a steroidal chemical structure. They are typically antagonists of the androgen receptor (AR) and act both by blocking the effects of androgens like testosterone and dihydrotestosterone (DHT) and by suppressing gonadal androgen production. SAAs lower concentrations of testosterone through simulation of the negative feedback inhibition of the hypothalamus. SAAs are used in the treatment of androgen-dependent conditions in men and women, and are also used in veterinary medicine for the same purpose. They are the converse of nonsteroidal antiandrogens (NSAAs), which are antiandrogens that are not steroids and are structurally unrelated to testosterone.

The medical uses of bicalutamide, a nonsteroidal antiandrogen (NSAA), include the treatment of androgen-dependent conditions and hormone therapy to block the effects of androgens. Indications for bicalutamide include the treatment of prostate cancer in men, skin and hair conditions such as acne, seborrhea, hirsutism, and pattern hair loss in women, high testosterone levels in women, hormone therapy in transgender women, as a puberty blocker to prevent puberty in transgender girls and to treat early puberty in boys, and the treatment of long-lasting erections in men. It may also have some value in the treatment of paraphilias and hypersexuality in men.

Comparison of the nonsteroidal antiandrogen (NSAA) bicalutamide with other antiandrogens reveals differences between the medications in terms of efficacy, tolerability, safety, and other parameters. Relative to the other first-generation NSAAs, flutamide and nilutamide, bicalutamide shows improved potency, efficacy, tolerability, and safety, and has largely replaced these medications in clinical practice. Compared to the second-generation NSAAs, enzalutamide and apalutamide, bicalutamide has inferior potency and efficacy but similar tolerability and safety and a lower propensity for drug interactions.

<span class="mw-page-title-main">Pharmacology of cyproterone acetate</span> Pharmaceutical compound

The pharmacology of cyproterone acetate (CPA) concerns the pharmacology of the steroidal antiandrogen and progestin medication cyproterone acetate.

The side effects of cyproterone acetate (CPA), a steroidal antiandrogen and progestin, including its frequent and rare side effects, have been studied and characterized. It is generally well-tolerated and has a mild side-effect profile, regardless of dosage, when it used as a progestin or antiandrogen in combination with an estrogen such as ethinylestradiol or estradiol valerate in women. Side effects of CPA include hypogonadism and associated symptoms such as demasculinization, sexual dysfunction, infertility, and osteoporosis; breast changes such as breast tenderness, enlargement, and gynecomastia; 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. Some of the side effects of CPA can be improved or fully prevented if it is combined with an estrogen to prevent estrogen deficiency. Few quantitative data are available on many of the potential side effects of CPA. Pooled tolerability data for CPA is not available in the literature.

<span class="mw-page-title-main">Estradiol valerate/cyproterone acetate</span> Combination drug

Estradiol valerate/cyproterone acetate (EV/CPA), sold under the brand names Climen and Femilar among others, is a combination product of estradiol valerate (EV), an estrogen, and cyproterone acetate (CPA), a progestogen, which is used in menopausal hormone therapy and as a birth control pill to prevent pregnancy. It is taken by mouth. Climen, which is used in menopausal hormone therapy, is a sequential preparation that contains 2 mg estradiol valerate and 1 mg CPA. It was the first product for use in menopausal hormone therapy containing CPA to be marketed and is available in more than 40 countries. Femilar, which is an estradiol-containing birth control pill, contains 1 to 2 mg estradiol valerate and 1 to 2 mg CPA, and has been approved for use in Finland since 1993.

<span class="mw-page-title-main">Ethinylestradiol/cyproterone acetate</span> Combination drug

Ethinylestradiol/cyproterone acetate (EE/CPA), also known as co-cyprindiol and sold under the brand names Diane and Diane-35 among others, is a combination of ethinylestradiol (EE), an estrogen, and cyproterone acetate (CPA), a progestin and antiandrogen, which is used as a birth control pill to prevent pregnancy in women. It is also used to treat androgen-dependent conditions in women such as acne, seborrhea, excessive facial/body hair growth, scalp hair loss, and high androgen levels associated with ovaries with cysts. The medication is taken by mouth once daily for 21 days, followed by a 7-day free interval.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 Kuhl H (August 2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration". Climacteric. 8 Suppl 1 (Suppl 1): 3–63. doi:10.1080/13697130500148875. PMID   16112947. S2CID   24616324.
  2. 1 2 Huber J, Zeillinger R, Schmidt J, Täuber U, Kuhnz W, Spona J (November 1988). "Pharmacokinetics of cyproterone acetate and its main metabolite 15 beta-hydroxy-cyproterone acetate in young healthy women". International Journal of Clinical Pharmacology, Therapy, and Toxicology. 26 (11): 555–561. PMID   2977383.
  3. ↑ Bińkowska M, Woroń J (June 2015). "Progestogens in menopausal hormone therapy". Przeglad Menopauzalny = Menopause Review. 14 (2): 134–143. doi:10.5114/pm.2015.52154. PMC   4498031 . PMID   26327902.
  4. 1 2 Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, et al. (December 2003). "Classification and pharmacology of progestins". Maturitas. 46 Suppl 1 (Suppl 1): S7–S16. doi:10.1016/j.maturitas.2003.09.014. PMID   14670641. Since there is no binding of CPA to SHBG and CBG in the serum, 93% of the compound is bound to serum albumin.
  5. ↑ Wakelin SH, Maibach HI, Archer CB (1 June 2002). Systemic Drug Treatment in Dermatology: A Handbook. CRC Press. pp. 32–. ISBN   978-1-84076-013-2. Archived from the original on 14 January 2023. Retrieved 27 September 2016. It is almost exclusively bound to plasma albumin.
  6. ↑ Hammond GL, Lähteenmäki PL, Lähteenmäki P, Luukkainen T (October 1982). "Distribution and percentages of non-protein bound contraceptive steroids in human serum". Journal of Steroid Biochemistry. 17 (4): 375–380. doi:10.1016/0022-4731(82)90629-X. PMID   6215538.
  7. ↑ Dickman A (27 September 2012). Drugs in Palliative Care. OUP Oxford. pp. 137–138. ISBN   978-0-19-966039-1.
  8. ↑ Boarder M, Newby D, Navti P (25 March 2010). Pharmacology for Pharmacy and the Health Sciences: A Patient-centred Approach. OUP Oxford. pp. 632–. ISBN   978-0-19-955982-4. Archived from the original on 6 July 2024. Retrieved 27 September 2016.
  9. ↑ Frith RG, Phillipou G (February 1985). "15-Hydroxycyproterone acetate and cyproterone acetate levels in plasma and urine". Journal of Chromatography. 338 (1): 179–186. doi:10.1016/0378-4347(85)80082-7. PMID   3160716.
  10. 1 2 3 4 5 6 Weber GF (22 July 2015). Molecular Therapies of Cancer. Springer. pp. 316–. ISBN   978-3-319-13278-5. 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.
  11. 1 2 3 4 Barradell LB, Faulds D (July 1994). "Cyproterone. A review of its pharmacology and therapeutic efficacy in prostate cancer". Drugs & Aging. 5 (1): 59–80. doi:10.2165/00002512-199405010-00006. PMID   7919640. S2CID   260845477.
  12. 1 2 3 AAPL Newsletter (PDF). The Academy. 1998. Archived (PDF) from the original on 30 August 2017. Retrieved 16 August 2016. CPA is 100% bioavailable when taken orally with a half life of 38 hours. The injectable form reaches maximum plasma levels in 82 hours and has a half life of about 72 hours.
  13. 1 2 3 4 5 6 7 8 9 10 Neumann F (1994). "The antiandrogen cyproterone acetate: discovery, chemistry, basic pharmacology, clinical use and tool in basic research". Experimental and Clinical Endocrinology. 102 (1): 1–32. doi: 10.1055/s-0029-1211261 . PMID   8005205.
  14. 1 2 Neumann F (January 1977). "Pharmacology and potential use of cyproterone acetate". Hormone and Metabolic Research = Hormon- und Stoffwechselforschung = Hormones et Metabolisme. 9 (1): 1–13. doi:10.1055/s-0028-1093574. PMID   66176. S2CID   7224893.
  15. ↑ Neumann F, Töpert M (November 1986). "Pharmacology of antiandrogens". Journal of Steroid Biochemistry. 25 (5B): 885–895. doi:10.1016/0022-4731(86)90320-1. PMID   2949114.
  16. ↑ Roland N, Neumann A, Hoisnard L, Duranteau L, Froelich S, Zureik M, et al. (March 2024). "Use of progestogens and the risk of intracranial meningioma: national case-control study". BMJ. 384: e078078. doi:10.1136/bmj-2023-078078. PMC   10966896 . PMID   38537944.
  17. ↑ Berek JS (2007). Berek & Novak's Gynecology. Lippincott Williams & Wilkins. p. 1085. ISBN   978-0-7817-6805-4.
  18. 1 2 3 Pucci E, Petraglia F (December 1997). "Treatment of androgen excess in females: yesterday, today and tomorrow". Gynecological Endocrinology. 11 (6): 411–433. doi:10.3109/09513599709152569. PMID   9476091.
  19. 1 2 Neumann F, Elger W (December 1966). "Permanent changes in gonadal function and sexual behavior as a result of early feminization of male rats by treatment with an antiandrogenic steroid". Endokrinologie. 50 (5): 209–224. PMID   5989926.
  20. ↑ Wakelin SH (1 June 2002). Systemic Drug Treatment in Dermatology: A Handbook. CRC Press. p. 32. ISBN   978-1-84076-013-2. Archived from the original on 14 January 2023. Retrieved 27 September 2016.
  21. 1 2 3 Plewig G, Kligman AM (6 December 2012). ACNE and ROSACEA. Springer Science & Business Media. pp. 662, 685. ISBN   978-3-642-59715-2.
  22. 1 2 Louw-du Toit R, Storbeck KH, Cartwright M, Cabral A, Africander D (February 2017). "Progestins used in endocrine therapy and the implications for the biosynthesis and metabolism of endogenous steroid hormones". Molecular and Cellular Endocrinology. 441: 31–45. doi:10.1016/j.mce.2016.09.004. PMID   27616670. S2CID   38582443.
  23. ↑ Jameson JL, De Groot LJ (25 February 2015). Endocrinology: Adult and Pediatric E-Book. Elsevier Health Sciences. pp. 2293, 2464, 2479, 6225. ISBN   978-0-323-32195-2. Archived from the original on 6 July 2024. Retrieved 2 August 2018.
  24. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 "Cyproterone". Archived from the original on 9 September 2018. Retrieved 1 December 2016.
  25. 1 2 3 4 5 6 7 8 9 10 11 12 Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 289–. ISBN   978-3-88763-075-1.
  26. 1 2 3 Schechter LS (22 September 2016). Surgical Management of the Transgender Patient. Elsevier Health Sciences. pp. 26–. ISBN   978-0-323-48408-4. Archived from the original on 6 July 2024. Retrieved 30 October 2016.
  27. ↑ Deleve LD (2013). "Cancer Chemotherapy". Drug-Induced Liver Disease. Academic Press. pp. 541–567. doi:10.1016/B978-0-12-387817-5.00030-3. ISBN   9780123878175.
  28. ↑ Maggi M (17 November 2011). Hormonal Therapy for Male Sexual Dysfunction. John Wiley & Sons. p. 104. ISBN   978-1-119-96380-6.
  29. 1 2 EMA. European Medicines Agency. Assessment report cyproterone. 13 February 2020. https://www.ema.europa.eu/en/documents/referral/cyproterone-article-31-referral-prac-assessment-report_en.pdf. Accessed 9 Apr 2020.
  30. 1 2 3 Duker M, Malsch M (28 January 2013). Incapacitation: Trends and New Perspectives. Ashgate Publishing, Ltd. p. 77. ISBN   978-1-4094-7151-6.
  31. ↑ "PrDIANE® -35" (PDF). 2 September 2015. Archived from the original (PDF) on 8 May 2016.
  32. ↑ Fruzzetti F, Trémollieres F, Bitzer J (May 2012). "An overview of the development of combined oral contraceptives containing estradiol: focus on estradiol valerate/dienogest". Gynecological Endocrinology. 28 (5): 400–408. doi:10.3109/09513590.2012.662547. PMC   3399636 . PMID   22468839.
  33. ↑ Fruzzetti F, Bitzer J (January 2010). "Review of clinical experience with estradiol in combined oral contraceptives". Contraception. 81 (1): 8–15. doi:10.1016/j.contraception.2009.08.010. PMID   20004267.
  34. ↑ Gourdy P, Bachelot A, Catteau-Jonard S, Chabbert-Buffet N, Christin-Maître S, Conard J, et al. (November 2012). "Hormonal contraception in women at risk of vascular and metabolic disorders: guidelines of the French Society of Endocrinology". Annales d'Endocrinologie. 73 (5): 469–487. doi:10.1016/j.ando.2012.09.001. PMID   23078975.
  35. 1 2 Van der Spuy ZM, le Roux PA (2003). "Cyproterone acetate for hirsutism". The Cochrane Database of Systematic Reviews. 2003 (4): CD001125. doi:10.1002/14651858.CD001125. PMC   8955083 . PMID   14583927.
  36. 1 2 3 Bitzer J, Römer T, Lopes da Silva Filho A (June 2017). "The use of cyproterone acetate/ethinyl estradiol in hyperandrogenic skin symptoms - a review". The European Journal of Contraception & Reproductive Health Care. 22 (3): 172–182. doi: 10.1080/13625187.2017.1317339 . PMID   28447864.
  37. 1 2 Beylot C, Doutre MS, Beylot-Barry M (1998). "Oral contraceptives and cyproterone acetate in female acne treatment". Dermatology. 196 (1): 148–152. doi:10.1159/000017849. PMID   9557250. S2CID   46763689.
  38. 1 2 3 Miller JA, Jacobs HS (May 1986). "Treatment of hirsutism and acne with cyproterone acetate". Clinics in Endocrinology and Metabolism. 15 (2): 373–389. doi:10.1016/S0300-595X(86)80031-7. PMID   2941191.
  39. ↑ Ingram JR, Woo PN, Chua SL, Ormerod AD, Desai N, Kai AC, et al. (October 2015). "Interventions for hidradenitis suppurativa". The Cochrane Database of Systematic Reviews. 2015 (10): CD010081. doi:10.1002/14651858.CD010081.pub2. PMC   6464653 . PMID   26443004.
  40. ↑ Ioannides D, Lazaridou E (2015). "Female pattern hair loss". Current Problems in Dermatology. 47: 45–54. doi:10.1159/000369404. ISBN   978-3-318-02774-7. PMID   26370643.
  41. 1 2 Wiegratz I, Kuhl H (2002). "Managing cutaneous manifestations of hyperandrogenic disorders: the role of oral contraceptives". Treatments in Endocrinology. 1 (6): 372–386. doi:10.2165/00024677-200201060-00003. PMID   15832490. S2CID   71806394.
  42. ↑ Arowojolu AO, Gallo MF, Lopez LM, Grimes DA (July 2012). Arowojolu AO (ed.). "Combined oral contraceptive pills for treatment of acne". The Cochrane Database of Systematic Reviews. 2012 (7): CD004425. doi:10.1002/14651858.CD004425.pub6. PMC   11437354 . PMID   22786490.
  43. 1 2 3 4 Diamanti-Kandarakis E (September 1999). "Current aspects of antiandrogen therapy in women". Current Pharmaceutical Design. 5 (9): 707–723. doi:10.2174/1381612805666230111201150. PMID   10495361. Archived from the original on 11 January 2023. Retrieved 18 December 2018.
  44. ↑ Bettoli V, Zauli S, Virgili A (July 2015). "Is hormonal treatment still an option in acne today?". The British Journal of Dermatology. 172 Suppl 1 (Suppl 1): 37–46. doi:10.1111/bjd.13681. PMID   25627824. S2CID   35615492.
  45. 1 2 Reed MJ, Franks S (September 1988). "Anti-androgens in gynaecological practice". Bailliere's Clinical Obstetrics and Gynaecology. 2 (3): 581–595. doi:10.1016/S0950-3552(88)80045-2. PMID   2976627.
  46. 1 2 3 4 Sahin Y, Kelestimur F (May 2004). "Medical treatment regimens of hirsutism". Reproductive Biomedicine Online. 8 (5): 538–546. doi: 10.1016/S1472-6483(10)61100-5 . PMID   15151716.
  47. 1 2 3 4 5 6 Nikolaou D, Gilling-Smith C (2005). "Hirsutism". Current Obstetrics & Gynaecology. 15 (3): 174–182. doi:10.1016/j.curobgyn.2005.03.006. ISSN   0957-5847.
  48. 1 2 Rittmaster RS (January 1997). "Hirsutism". Lancet. 349 (9046): 191–195. doi:10.1016/S0140-6736(96)07252-2. PMID   9111556. S2CID   208789457.
  49. 1 2 3 4 Azziz R, Carmina E, Sawaya ME (August 2000). "Idiopathic hirsutism". Endocrine Reviews. 21 (4): 347–362. doi: 10.1210/edrv.21.4.0401 . PMID   10950156.
  50. ↑ Liew SH (June 1999). "Unwanted body hair and its removal: a review". Dermatologic Surgery. 25 (6): 431–439. doi:10.1046/j.1524-4725.1999.08130.x. PMID   10469088.
  51. 1 2 Belisle 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): 1015–1020. doi: 10.1016/S0015-0282(16)49873-0 . PMID   2946604.
  52. ↑ Barth JH, Cherry CA, Wojnarowska F, Dawber RP (July 1991). "Cyproterone acetate for severe hirsutism: results of a double-blind dose-ranging study". Clinical Endocrinology. 35 (1): 5–10. doi:10.1111/j.1365-2265.1991.tb03489.x. PMID   1832346. S2CID   27293697.
  53. ↑ Jasonni VM, Bulletti C, Naldi S, Di Cosmo E, Cappuccini F, Flamigni C (April 1991). "Treatment of hirsutism by an association of oral cyproterone acetate and transdermal 17 beta-estradiol". Fertility and Sterility. 55 (4): 742–745. doi:10.1016/S0015-0282(16)54240-X. PMID   1826278.
  54. 1 2 3 4 5 6 Hammerstein J (1990). "Antiandrogens: Clinical Aspects". Hair and Hair Diseases. Springer. pp. 827–886. doi:10.1007/978-3-642-74612-3_35. ISBN   978-3-642-74614-7.
  55. 1 2 Ward 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. PMID   6235105.
  56. 1 2 Rasmusson GH (1986). Chapter 18. Chemical Control of Androgen Action. Annual Reports in Medicinal Chemistry. Vol. 21. Academic Press. pp. 179–188. doi:10.1016/S0065-7743(08)61128-8. ISBN   9780120405213. ISSN   0065-7743.
  57. 1 2 3 Cormane RH, van der Meeren HL (1981). "Cyproteronacetate in the management of severe acne in males". Archives of Dermatological Research. 271 (2): 183–187. doi:10.1007/BF00412545. ISSN   0340-3696. S2CID   12153042.
  58. ↑ Misch KJ, Dolman WF, Neild V, Rhodes EL (1986). "Response of male acne to antiandrogen therapy with cyproterone acetate". Dermatologica. 173 (3): 139–142. doi:10.1159/000249236. PMID   2945742.
  59. 1 2 Simpson NB (1989). "The Effect of Drugs on Hair". Pharmacology of the Skin II. Handbook of Experimental Pharmacology. Vol. 87 / 2. Springer. pp. 495–508. doi:10.1007/978-3-642-74054-1_37. ISBN   978-3-642-74056-5. ISSN   0171-2004.
  60. 1 2 3 Unger WP (1 February 1995). "Androgenetic alopecia and its treatment. A historical overview". Hair Transplantation, Third Edition. Taylor & Francis. pp. 1–33. ISBN   978-0-8247-9363-0.
  61. ↑ Coskey RJ (July 1984). "Dermatologic therapy: December, 1982, through November, 1983". Journal of the American Academy of Dermatology. 11 (1): 25–52. doi:10.1016/S0190-9622(84)80163-2. PMID   6376557.
  62. 1 2 Neumann F, Kalmus J (1991). "Cyproterone acetate in the treatment of sexual disorders: pharmacological base and clinical experience". Experimental and Clinical Endocrinology. 98 (2): 71–80. doi:10.1055/s-0029-1211103. PMID   1838080.
  63. ↑ Giltay EJ, Gooren LJ (2009). "Potential side effects of androgen deprivation treatment in sex offenders". The Journal of the American Academy of Psychiatry and the Law. 37 (1): 53–58. PMID   19297634.
  64. ↑ Lam SM, Hempstead BR, Williams EF (2012). "Medical Management Options for Hair Loss". Aesthetic Medicine. Springer. pp. 529–535. doi:10.1007/978-3-642-20113-4_41. ISBN   978-3-642-20112-7.
  65. 1 2 3 4 5 6 7 8 9 10 11 12 13 Neumann F (1996). "Pharmacology of Cyproterone Acetate — A Short Review". Antiandrogens in Prostate Cancer. ESO Monographs. pp. 31–44. doi:10.1007/978-3-642-45745-6_3. ISBN   978-3-642-45747-0.
  66. ↑ Ruan X, Kubba A, Aguilar A, Mueck AO (June 2017). "Use of cyproterone acetate/ethinylestradiol in polycystic ovary syndrome: rationale and practical aspects". The European Journal of Contraception & Reproductive Health Care. 22 (3): 183–190. doi: 10.1080/13625187.2017.1317735 . PMID   28463030.
  67. 1 2 3 4 Laron Z, Kauli R (July 2000). "Experience with cyproterone acetate in the treatment of precocious puberty". Journal of Pediatric Endocrinology & Metabolism. 13 Suppl 1 (Suppl 1): 805–810. doi:10.1515/JPEM.2000.13.S1.805. PMID   10969925. S2CID   25398066.
  68. ↑ Catteau-Jonard S, Cortet-Rudelli C, Richard-Proust C, Dewailly D (2012). "Hyperandrogenism in adolescent girls". Endocrine Development. 22: 181–193. doi:10.1159/000326688. ISBN   978-3-8055-9336-6. PMID   22846529.
  69. ↑ Reismann P, Likó I, Igaz P, Patócs A, Rácz K (August 2009). "Pharmacological options for treatment of hyperandrogenic disorders". Mini Reviews in Medicinal Chemistry. 9 (9): 1113–1126. doi:10.2174/138955709788922692. PMID   19689407.
  70. 1 2 Diamanti-Kandarakis E (October 1998). "How actual is the treatment with antiandrogen alone in patients with polycystic ovary syndrome?". Journal of Endocrinological Investigation. 21 (9): 623–629. doi:10.1007/BF03350788. PMID   9856417. S2CID   46484837.
  71. 1 2 3 Husmann F (1997). "Clinical Experiences with a Combination of Estradiol Valerate and Cyproterone Acetate for Hormone Replacement". Women's Health and Menopause. Medical Science Symposia Series. Vol. 11. Springer. pp. 257–261. doi:10.1007/978-94-011-5560-1_38. ISBN   978-94-010-6343-2. ISSN   0928-9550.
  72. 1 2 3 Schneider HP (November 2003). "Androgens and antiandrogens". Annals of the New York Academy of Sciences. 997 (1): 292–306. Bibcode:2003NYASA.997..292S. doi:10.1196/annals.1290.033. PMID   14644837. S2CID   8400556.
  73. 1 2 Schneider HP (December 2000). "The role of antiandrogens in hormone replacement therapy". Climacteric. 3 Suppl 2 (Suppl 2): 21–27. PMID   11379383.
  74. ↑ Gooren LJ, Giltay EJ, Bunck MC (January 2008). "Long-term treatment of transsexuals with cross-sex hormones: extensive personal experience". The Journal of Clinical Endocrinology and Metabolism. 93 (1): 19–25. doi:10.1210/jc.2007-1809. PMID   17986639.
  75. ↑ Hembree WC, Cohen-Kettenis PT, Gooren L, Hannema SE, Meyer WJ, Murad MH, et al. (November 2017). "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. doi: 10.1210/jc.2017-01658 . PMID   28945902.
  76. 1 2 Chew D, Anderson J, Williams K, May T, Pang K (April 2018). "Hormonal Treatment in Young People With Gender Dysphoria: A Systematic Review". Pediatrics. 141 (4): e20173742. doi: 10.1542/peds.2017-3742 . PMID   29514975.
  77. ↑ Deutsch M (17 June 2016), Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People (PDF) (2nd ed.), University of California, San Francisco: Center of Excellence for Transgender Health, p. 28, archived (PDF) from the original on 22 May 2019, retrieved 2 August 2018
  78. ↑ Barrett J (29 September 2017). Transsexual and Other Disorders of Gender Identity: A Practical Guide to Management. CRC Press. pp. 216–217, 221. ISBN   978-1-315-34513-0. Archived from the original on 6 July 2024. Retrieved 2 August 2018.
  79. ↑ Ettner R, Monstrey S, Coleman E (20 May 2016). Principles of Transgender Medicine and Surgery. Routledge. pp. 169, 171, 216. ISBN   978-1-317-51460-2. Archived from the original on 6 July 2024. Retrieved 2 August 2018.
  80. ↑ Israel GE (March 2001). Transgender Care: Recommended Guidelines, Practical Information, and Personal Accounts. Temple University Press. pp. 66–. ISBN   978-1-56639-852-7. Archived from the original on 6 July 2024. Retrieved 2 August 2018.
  81. ↑ Winkler-Crepaz K, Mueller A, Boettcher B, Wildt L (2017). "Hormonbehandlung bei Transgenderpatienten" [Hormone treatment of transgender patients]. Gynäkologische Endokrinologie. 15 (1): 39–42. doi:10.1007/s10304-016-0116-9. ISSN   1610-2894. S2CID   12270365.
  82. ↑ Urdl W (2009). "Behandlungsgrundsätze bei Transsexualität" [Therapeutic principles in transsexualism]. Gynäkologische Endokrinologie. 7 (3): 153–160. doi:10.1007/s10304-009-0314-9. ISSN   1610-2894. S2CID   8001811.
  83. ↑ Kuijpers SM, Wiepjes CM, Conemans EB, Fisher AD, T'Sjoen G, den Heijer M (September 2021). "Toward a Lowest Effective Dose of Cyproterone Acetate in Trans Women: Results From the ENIGI Study". The Journal of Clinical Endocrinology and Metabolism. 106 (10): e3936–e3945. doi:10.1210/clinem/dgab427. PMC   8571811 . PMID   34125226.
  84. ↑ Even Zohar N, Sofer Y, Yaish I, Serebro M, Tordjman K, Greenman Y (July 2021). "Low-Dose Cyproterone Acetate Treatment for Transgender Women". The Journal of Sexual Medicine. 18 (7): 1292–1298. doi:10.1016/j.jsxm.2021.04.008. PMID   34176757. S2CID   235660315.
  85. ↑ Meyer G, Mayer M, Mondorf A, Flügel AK, Herrmann E, Bojunga J (February 2020). "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): 149–156. doi: 10.1530/EJE-19-0463 . PMID   31751300.
  86. 1 2 Fung R, Hellstern-Layefsky M, Lega I (2017). "Is a lower dose of cyproterone acetate as effective at testosterone suppression in transgender women as higher doses?". International Journal of Transgenderism. 18 (2): 123–128. doi:10.1080/15532739.2017.1290566. ISSN   1553-2739. S2CID   79095497.
  87. 1 2 Coleman E, Radix AE, Bouman WP, Brown GR, de Vries AL, Deutsch MB, et al. (19 August 2022). "Standards of Care for the Health of Transgender and Gender Diverse People, Version 8". International Journal of Transgender Health. 23 (Suppl 1): S1–S259. doi: 10.1080/26895269.2022.2100644 . PMC   9553112 . PMID   36238954.
  88. ↑ Defreyne J, Vander Stichele C, Iwamoto SJ, T'Sjoen G (February 2023). "Gender-affirming hormonal therapy for transgender and gender-diverse people-A narrative review". Best Practice & Research. Clinical Obstetrics & Gynaecology. 86: 102296. doi:10.1016/j.bpobgyn.2022.102296. PMC   11197232 . PMID   36596713. S2CID   254818114.
  89. 1 2 Glintborg D, T'Sjoen G, Ravn P, Andersen MS (June 2021). "MANAGEMENT OF ENDOCRINE DISEASE: Optimal feminizing hormone treatment in transgender people". European Journal of Endocrinology. 185 (2): R49–R63. doi: 10.1530/EJE-21-0059 . PMID   34081614. S2CID   235335361.
  90. ↑ Angus LM, Nolan BJ, Zajac JD, Cheung AS (May 2021). "A systematic review of antiandrogens and feminization in transgender women". Clinical Endocrinology. 94 (5): 743–752. doi:10.1111/cen.14329. hdl: 11343/276405 . PMID   32926454. S2CID   221724686.
  91. ↑ Sudhakar D, Huang Z, Zietkowski M, Powell N, Fisher AR (June 2023). "Feminizing gender-affirming hormone therapy for the transgender and gender diverse population: An overview of treatment modality, monitoring, and risks" (PDF). Neurourology and Urodynamics. 42 (5): 903–920. doi:10.1002/nau.25097. PMID   36403287. S2CID   253707685.
  92. ↑ Burinkul S, Panyakhamlerd K, Suwan A, Tuntiviriyapun P, Wainipitapong S (July 2021). "Anti-Androgenic Effects Comparison Between Cyproterone Acetate and Spironolactone in Transgender Women: A Randomized Controlled Trial". The Journal of Sexual Medicine. 18 (7): 1299–1307. doi:10.1016/j.jsxm.2021.05.003. PMID   34274044. S2CID   236092532.
  93. ↑ Sofer Y, Yaish I, Yaron M, Bach MY, Stern N, Greenman Y (August 2020). "Differential Endocrine and Metabolic Effects of Testosterone Suppressive Agents in Transgender Women". Endocrine Practice. 26 (8): 883–890. doi:10.4158/EP-2020-0032. PMID   33471679. S2CID   225334013.
  94. ↑ Angus L, Leemaqz S, Ooi O, Cundill P, Silberstein N, Locke P, et al. (July 2019). "Cyproterone acetate or spironolactone in lowering testosterone concentrations for transgender individuals receiving oestradiol therapy". Endocrine Connections. 8 (7): 935–940. doi:10.1530/EC-19-0272. PMC   6612061 . PMID   31234145.
  95. ↑ Panagiotakopoulos L (September 2018). "Transgender medicine - puberty suppression". Reviews in Endocrine & Metabolic Disorders. 19 (3): 221–225. doi:10.1007/s11154-018-9457-0. PMID   30112593. S2CID   52009542.
  96. ↑ Rosenthal SM (December 2014). "Approach to the patient: transgender youth: endocrine considerations". The Journal of Clinical Endocrinology and Metabolism. 99 (12): 4379–4389. doi: 10.1210/jc.2014-1919 . PMID   25140398.
  97. ↑ 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. PMID   28546095. S2CID   10690853.
  98. ↑ Tack LJ, Heyse R, Craen M, Dhondt K, Bossche HV, Laridaen J, et al. (May 2017). "Consecutive Cyproterone Acetate and Estradiol Treatment in Late-Pubertal Transgender Female Adolescents". The Journal of Sexual Medicine. 14 (5): 747–757. doi:10.1016/j.jsxm.2017.03.251. PMID   28499525. S2CID   31089247.
  99. 1 2 3 Torri V, Floriani I (June 2005). "Cyproterone acetate in the therapy of prostate carcinoma". Archivio Italiano di Urologia, Andrologia. 77 (3): 157–163. CiteSeerX   10.1.1.663.9458 . PMID   16372511.
  100. ↑ Schröder FH (1996). "Cyproterone Acetate — Results of Clinical Trials and Indications for Use in Human Prostate Cancer". Antiandrogens in Prostate Cancer. ESO Monographs. pp. 45–51. doi:10.1007/978-3-642-45745-6_4. ISBN   978-3-642-45747-0.
  101. 1 2 Schröder FH (December 1993). "Cyproterone acetate--mechanism of action and clinical effectiveness in prostate cancer treatment". Cancer. 72 (12 Suppl): 3810–3815. doi: 10.1002/1097-0142(19931215)72:12+<3810::AID-CNCR2820721710>3.0.CO;2-O . PMID   8252496. S2CID   221762.
  102. ↑ de Voogt HJ (1992). "The position of cyproterone acetate (CPA), a steroidal anti-androgen, in the treatment of prostate cancer". The Prostate. Supplement. 4: 91–95. doi:10.1002/pros.2990210514. PMID   1533452. S2CID   22747185.
  103. ↑ Goldenberg SL, Bruchovsky N (February 1991). "Use of cyproterone acetate in prostate cancer". The Urologic Clinics of North America. 18 (1): 111–122. doi:10.1016/S0094-0143(21)01398-7. PMID   1825143.
  104. ↑ Lemke TL, Williams DA (2008). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 1288–. ISBN   978-0-7817-6879-5.
  105. 1 2 3 Seidenfeld J, Samson DJ, Hasselblad V, Aronson N, Albertsen PC, Bennett CL, et al. (April 2000). "Single-therapy androgen suppression in men with advanced prostate cancer: a systematic review and meta-analysis". Annals of Internal Medicine. 132 (7): 566–577. doi:10.7326/0003-4819-132-7-200004040-00009. PMID   10744594. S2CID   23128641.
  106. 1 2 3 Mydlo JH, Godec CJ (29 September 2015). Prostate Cancer: Science and Clinical Practice. Elsevier Science. pp. 516–521, 534–540. ISBN   978-0-12-800592-7. Archived from the original on 8 September 2017.
  107. ↑ Miyamoto H, Messing EM, Chang C (December 2004). "Androgen deprivation therapy for prostate cancer: current status and future prospects". The Prostate. 61 (4): 332–353. doi: 10.1002/pros.20115 . PMID   15389811. S2CID   22300358.
  108. ↑ Wirth MP, Hakenberg OW, Froehner M (February 2007). "Antiandrogens in the treatment of prostate cancer". European Urology. 51 (2): 306–13, discussion 314. doi:10.1016/j.eururo.2006.08.043. PMID   17007995.
  109. ↑ Singh SM, Gauthier S, Labrie F (February 2000). "Androgen receptor antagonists (antiandrogens): structure-activity relationships". Current Medicinal Chemistry. 7 (2): 211–247. doi:10.2174/0929867003375371. PMID   10637363. 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].
  110. ↑ Kaliks RA, Del Giglio A (2008). "Management of advanced prostate cancer" (PDF). Revista da Associacao Medica Brasileira. 54 (2): 178–182. doi: 10.1590/S0104-42302008000200025 . PMID   18506331. Archived (PDF) from the original on 10 May 2017.
  111. ↑ Chabner BA, Longo DL (8 November 2010). Cancer Chemotherapy and Biotherapy: Principles and Practice. Lippincott Williams & Wilkins. pp. 679–680. ISBN   978-1-60547-431-1. Archived from the original on 10 January 2023. Retrieved 12 September 2018. From a structural standpoint, antiandrogens are classified as steroidal, including cyproterone [acetate] (Androcur) and megestrol [acetate], or nonsteroidal, including flutamide (Eulexin, others), bicalutamide (Casodex), and nilutamide (Nilandron). The steroidal antiandrogens are rarely used.
  112. ↑ Horwich A (11 February 2010). Systemic Treatment of Prostate Cancer. OUP Oxford. pp. 44–. ISBN   978-0-19-956142-1.
  113. ↑ Anderson J (March 2003). "The role of antiandrogen monotherapy in the treatment of prostate cancer". BJU International. 91 (5): 455–461. doi: 10.1046/j.1464-410X.2003.04026.x . PMID   12603397. S2CID   8639102.
  114. ↑ Dalesio O, van Tinteren H, Clarke M, Peto R, Schroder F, Dechering I, et al. (2000). "Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials". The Lancet. 355 (9214): 1491–1498. doi:10.1016/S0140-6736(00)02163-2. ISSN   0140-6736. S2CID   25366526.
  115. ↑ Denis L (6 December 2012). Antiandrogens in Prostate Cancer: A Key to Tailored Endocrine Treatment. Springer Science & Business Media. pp. 70–. ISBN   978-3-642-45745-6. Archived from the original on 6 July 2024. Retrieved 25 September 2018.
  116. 1 2 Schröder FH, Radlmaier A (2009). "Steroidal Antiandrogens". In Jordan VC, Furr BJ (eds.). Hormone Therapy in Breast and Prostate Cancer . Cancer Drug Discovery and Development. Humana Press. pp.  325–346. doi:10.1007/978-1-59259-152-7_15. ISBN   978-1-60761-471-5.
  117. 1 2 Chodak G, Gomella L, Phung DH (September 2007). "Combined androgen blockade in advanced prostate cancer: looking back to move forward". Clinical Genitourinary Cancer. 5 (6): 371–378. doi:10.3816/CGC.2007.n.019. PMID   17956709.
  118. 1 2 Cox RL, Crawford ED (December 1995). "Estrogens in the treatment of prostate cancer". The Journal of Urology. 154 (6): 1991–1998. doi:10.1016/S0022-5347(01)66670-9. PMID   7500443.
  119. 1 2 Goldenberg 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. PMID   8677581.
  120. 1 2 3 Goldenberg 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. PMID   2973529.
  121. ↑ Hinkelbein W, Miller K, Wiegel T (7 March 2013). Prostatakarzinom — urologische und strahlentherapeutische Aspekte: urologische und strahlentherapeutische Aspekte [Prostate carcinoma — urological and radiotherapeutic aspects: urological and radiotherapeutic aspects]. Springer-Verlag. pp. 99–. ISBN   978-3-642-60064-7. Archived from the original on 12 January 2023. Retrieved 27 December 2018.
  122. ↑ Khan O, Ferriter M, Huband N, Powney MJ, Dennis JA, Duggan C (February 2015). "Pharmacological interventions for those who have sexually offended or are at risk of offending". The Cochrane Database of Systematic Reviews. 2015 (2): CD007989. doi:10.1002/14651858.CD007989.pub2. PMC   6544815 . PMID   25692326.
  123. 1 2 Silvani M, Mondaini N, Zucchi A (September 2015). "Androgen deprivation therapy (castration therapy) and pedophilia: What's new". Archivio Italiano di Urologia, Andrologia. 87 (3): 222–226. doi: 10.4081/aiua.2015.3.222 . hdl: 11568/1073189 . PMID   26428645.
  124. ↑ Reilly DR, Delva NJ, Hudson RW (August 2000). "Protocols for the use of cyproterone, medroxyprogesterone, and leuprolide in the treatment of paraphilia". Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie. 45 (6): 559–563. doi: 10.1177/070674370004500608 . PMID   10986575.
  125. ↑ Freund K (1980). "Therapeutic sex drive reduction". Acta Psychiatrica Scandinavica. Supplementum. 287: 5–38. doi:10.1111/j.1600-0447.1980.tb10433.x. PMID   7006321. S2CID   21981060.
  126. ↑ Codispoti VL (December 2008). "Pharmacology of sexually compulsive behavior". The Psychiatric Clinics of North America. 31 (4): 671–679. doi:10.1016/j.psc.2008.06.002. PMID   18996306.
  127. 1 2 3 Assumpção AA, Garcia FD, Garcia HD, Bradford JM, Thibaut F (June 2014). "Pharmacologic treatment of paraphilias". The Psychiatric Clinics of North America. 37 (2): 173–181. doi:10.1016/j.psc.2014.03.002. PMID   24877704.
  128. ↑ Guay DR (December 2008). "Inappropriate sexual behaviors in cognitively impaired older individuals". The American Journal of Geriatric Pharmacotherapy. 6 (5): 269–288. doi:10.1016/j.amjopharm.2008.12.004. PMID   19161930.
  129. ↑ Clarke DJ (April 1989). "Antilibidinal drugs and mental retardation: a review". Medicine, Science, and the Law. 29 (2): 136–146. doi:10.1177/002580248902900209. PMID   2526280. S2CID   37808515.
  130. ↑ Hucker SJ (June 1985). "Self-harmful sexual behavior". The Psychiatric Clinics of North America. 8 (2): 323–337. doi:10.1016/s0193-953x(18)30698-1. PMID   3895195.
  131. 1 2 3 4 Laschet U, Laschet L (June 1975). "Antiandrogens in the treatment of sexual deviations of men". Journal of Steroid Biochemistry. 6 (6): 821–826. doi:10.1016/0022-4731(75)90310-6. PMID   1177426.
  132. ↑ Brito VN, Latronico AC, Arnhold IJ, Mendonça BB (February 2008). "Update on the etiology, diagnosis and therapeutic management of sexual precocity". Arquivos Brasileiros de Endocrinologia e Metabologia. 52 (1): 18–31. doi: 10.1590/S0004-27302008000100005 . PMID   18345393.
  133. ↑ Sachdeva A, Dutta AK (31 August 2012). Advances in Pediatrics. JP Medical Ltd. pp. 1202–. ISBN   978-93-5025-777-7. Archived from the original on 13 January 2023. Retrieved 27 August 2018.
  134. ↑ Holland FJ (March 1991). "Gonadotropin-independent precocious puberty". Endocrinology and Metabolism Clinics of North America. 20 (1): 191–210. doi:10.1016/s0889-8529(18)30288-3. PMID   1903104.
  135. ↑ Frisk J (January 2010). "Managing hot flushes in men after prostate cancer--a systematic review". Maturitas. 65 (1): 15–22. doi: 10.1016/j.maturitas.2009.10.017 . PMID   19962840.
  136. ↑ Spetz AC, Zetterlund EL, Varenhorst E, Hammar M (2003). "Incidence and management of hot flashes in prostate cancer". The Journal of Supportive Oncology. 1 (4): 263–6, 269–70, 272–3, discussion 267–8, 271–2. PMID   15334868.
  137. ↑ Radlmaier A, Bormacher K, Neumann F (1990). "Hot flushes: mechanism and prevention". Progress in Clinical and Biological Research. 359: 131–40, discussion 141–53. PMID   2149457.
  138. 1 2 Thompson IM (2001). "Flare Associated with LHRH-Agonist Therapy". Reviews in Urology. 3 Suppl 3 (Suppl 3): S10–S14. PMC   1476081 . PMID   16986003.
  139. ↑ Denis LJ, Griffiths K, Kaisary AV, Murphy GP (1 March 1999). Textbook of Prostate Cancer: Pathology, Diagnosis and Treatment: Pathology, Diagnosis and Treatment. CRC Press. pp. 308–. ISBN   978-1-85317-422-3. Archived from the original on 6 July 2024. Retrieved 12 September 2018.
  140. ↑ Sugiono M, Winkler MH, Okeke AA, Benney M, Gillatt DA (2005). "Bicalutamide vs cyproterone acetate in preventing flare with LHRH analogue therapy for prostate cancer--a pilot study". Prostate Cancer and Prostatic Diseases. 8 (1): 91–94. doi:10.1038/sj.pcan.4500784. PMID   15711607. S2CID   9151853.
  141. ↑ 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". The Journal of Urology. 144 (4): 934–941. doi:10.1016/S0022-5347(17)39625-8. PMID   2144596.
  142. ↑ 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". European Urology. 12 (6): 400–402. doi:10.1159/000472667. PMID   2949980.
  143. ↑ 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. ISBN   9783110853674.
  144. ↑ Bruchovsky N, Goldenberg SL, Akakura K, Rennie PS (September 1993). "Luteinizing hormone-releasing hormone agonists in prostate cancer. Elimination of flare reaction by pretreatment with cyproterone acetate and low-dose diethylstilbestrol". Cancer. 72 (5): 1685–1691. doi: 10.1002/1097-0142(19930901)72:5<1685::AID-CNCR2820720532>3.0.CO;2-3 . PMID   7688656. S2CID   21824595.
  145. ↑ Rabe T, Albring C, Blume-Peytavi U, Egarter C, Geisthövel F, König K, et al. (2015). "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 (in German). 12 (3): 102–149. ISSN   1810-2107. Archived from the original on 5 December 2020. Retrieved 22 December 2018.
  146. 1 2 Engel J, Kleemann A, Kutscher B, Reichert D (14 May 2014). Pharmaceutical Substances: Syntheses, Patents and Applications of the most relevant APIs (5th ed.). Thieme. pp. 351–352. ISBN   978-3-13-179275-4. Archived from the original on 6 July 2024. Retrieved 7 September 2018.
  147. ↑ Muller NF, Dessing RP (19 June 1998). European Drug Index: European Drug Registrations, Fourth Edition. CRC Press. pp. 79–. ISBN   978-3-7692-2114-5. Archived from the original on 6 July 2024. Retrieved 29 November 2017.
  148. 1 2 Bolognia JL, Jorizzo JL, Schaffer JV (8 June 2012). Dermatology E-Book. Elsevier Health Sciences. pp. 557–. ISBN   978-0-7020-5182-1. Archived from the original on 6 July 2024. Retrieved 29 November 2017.
  149. ↑ Altmeyer P (2 July 2013). Therapielexikon Dermatologie und Allergologie. Springer-Verlag. pp. 27–. ISBN   978-3-662-10498-9. Archived from the original on 6 July 2024. Retrieved 20 September 2018.
  150. ↑ Kassirer JP, Greene HL (1997). Current Therapy in Adult Medicine. Mosby. p. 174. ISBN   978-0-8151-5480-8. Archived from the original on 6 July 2024. Retrieved 29 November 2017.
  151. ↑ "Androcur Label" (PDF). Archived (PDF) from the original on 8 March 2017. Retrieved 23 December 2018.
  152. 1 2 3 4 5 6 7 8 "Mylan-Cyproterone Label" (PDF). Archived (PDF) from the original on 26 January 2021. Retrieved 2 August 2018.
  153. 1 2 Bachelot A, Chabbert-Buffet N, Salenave S, Kerlan V, Galand-Portier MB (February 2010). "Anti-androgen treatments". Annales d'Endocrinologie. 71 (1): 19–24. doi:10.1016/j.ando.2009.12.001. PMID   20096826.
  154. ↑ Burton JL (December 1979). "Anti-androgen therapy in dermatology: a review". Clinical and Experimental Dermatology. 4 (4): 501–507. doi:10.1111/j.1365-2230.1979.tb01648.x. PMID   394887. S2CID   29236094.
  155. 1 2 Rittmaster RS (June 1999). "Antiandrogen treatment of polycystic ovary syndrome". Endocrinology and Metabolism Clinics of North America. 28 (2): 409–421. doi:10.1016/S0889-8529(05)70077-3. PMID   10352926.
  156. ↑ Guay DR (January 2009). "Drug treatment of paraphilic and nonparaphilic sexual disorders". Clinical Therapeutics. 31 (1): 1–31. doi:10.1016/j.clinthera.2009.01.009. PMID   19243704. No quantitative data on these adverse events are available, even in the product prescribing information and data sheets.
  157. ↑ 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". Archivio Italiano di Urologia, Andrologia. 71 (5): 293–302. PMID   10673793.
  158. ↑ "Mylan-Cypersterone Monograph" (PDF). p. 4. Archived from the original (PDF) on 26 January 2021.
  159. ↑ Saleh FM, Grudzinskas AJ, Bradford JM (11 February 2009). Sex Offenders: Identification, Risk Assessment, Treatment, and Legal Issues. Oxford University Press, USA. pp. 197–. ISBN   978-0-19-517704-6.
  160. ↑ Fritz MA, Speroff L (2011). Clinical Gynecologic Endocrinology and Infertility. Lippincott Williams & Wilkins. pp. 1091–. ISBN   978-0-7817-7968-5. Archived from the original on 6 July 2024. Retrieved 23 November 2018.
  161. 1 2 Figg W, Chau CH, Small EJ (14 September 2010). Drug Management of Prostate Cancer. Springer. p. 71. ISBN   978-1-60327-829-4. Archived from the original on 10 January 2023. Retrieved 27 September 2016.
  162. ↑ Honer C, Nam K, Fink C, Marshall P, Ksander G, Chatelain RE, et al. (May 2003). "Glucocorticoid receptor antagonism by cyproterone acetate and RU486". Molecular Pharmacology. 63 (5): 1012–1020. doi:10.1124/mol.63.5.1012. PMID   12695529. S2CID   23872584.
  163. ↑ 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): 43–47. doi:10.1016/0022-4731(87)90122-1. PMID   2956461.
  164. ↑ Han C, Davis CB, Wang B (6 January 2010). Evaluation of Drug Candidates for Preclinical Development: Pharmacokinetics, Metabolism, Pharmaceutics, and Toxicology. John Wiley & Sons. pp. 92–. ISBN   978-0-470-57488-1.
  165. ↑ Lehmann JM, McKee DD, Watson MA, Willson TM, Moore JT, Kliewer SA (September 1998). "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): 1016–1023. doi:10.1172/JCI3703. PMC   508967 . PMID   9727070.
  166. ↑ Christians U, Schmitz V, Haschke M (December 2005). "Functional interactions between P-glycoprotein and CYP3A in drug metabolism". Expert Opinion on Drug Metabolism & Toxicology. 1 (4): 641–654. doi:10.1517/17425255.1.4.641. PMID   16863430. S2CID   17742146.
  167. 1 2 Gräf KJ, Brotherton J, Neumann F (1974). "Clinical Uses of Antiandrogens". Androgens II and Antiandrogens / Androgene II und Antiandrogene. Handbuch der experimentellen Pharmakologie/Handbook of Experimental Pharmacology. Springer. pp. 485–542. doi:10.1007/978-3-642-80859-3_7. ISBN   978-3-642-80861-6.
  168. 1 2 Knaus JV, Isaacs JH (6 December 2012). Office Gynecology: Advanced Management Concepts. Springer Science & Business Media. pp. 150–. ISBN   978-1-4612-4340-3.
  169. 1 2 William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia. Elsevier. pp. 1182–1183. ISBN   978-0-8155-1856-3.
  170. ↑ EP 1359154A1,Buddhasukh D, Maier R, Manosroi A, Manosroi J, Sripalakit P, Werner R,"Further syntheses of cyproterone acetate",published 5 November 2003
  171. 1 2 "Verfahren zur Herstellung von 1, 2alpha-Methylen-delta-17alpha-hydroxy-progesteronen". Archived from the original on 8 February 2021. Retrieved 20 September 2018.
  172. 1 2 "6-chloro-1, 2alpha-methylene-delta6-17alpha-hydroxyprogesterone compounds and compositions". Archived from the original on 8 February 2021. Retrieved 20 September 2018.
  173. ↑ US 3127396,Wiechert R, Kaspar E, Schenck M,"Production of 1,2-methylene and 16,17-methylene Ketosteroids ",issued 31 March 1964, assigned to Schering A.G.
  174. ↑ US 3234093,Wiechert R,"6-chloro-1, 2alpha-methylene-delta6-17alpha-hydroxyprogesterone compounds and compositions",issued 8 February 1966, assigned to Bayer Pharma A.G.
  175. ↑ 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): 380–388. doi:10.1530/acta.0.0440380. PMID   14071315.
  176. ↑ Mann T, Lutwak-Mann C (6 December 2012). Male Reproductive Function and Semen: Themes and Trends in Physiology, Biochemistry and Investigative Andrology. Springer Science & Business Media. pp. 352–. ISBN   978-1-4471-1300-3.
  177. ↑ Norman AW, Litwack G (28 June 2014). Hormones. Elsevier Science. pp. 508–. ISBN   978-1-4832-5810-2.
  178. ↑ Mainwaring WI (6 December 2012). The Mechanism of Action of Androgens. Springer Science & Business Media. pp. 53–. ISBN   978-3-642-88429-0.
  179. ↑ Jost A (1971). "Use of androgen antagonists and antiandrogens in studies on sex differentiation". Gynecologic Investigation. 2 (1): 180–201. doi:10.1159/000301861. PMID   4949979.
  180. ↑ 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): 604–655. doi:10.3109/15622971003671628. PMID   20459370. S2CID   14949511.
  181. ↑ Namer M (October 1988). "Clinical applications of antiandrogens". Journal of Steroid Biochemistry. 31 (4B): 719–729. doi:10.1016/0022-4731(88)90023-4. PMID   2462132.
  182. ↑ 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): 829–834. doi:10.1055/s-0028-1111126. PMID   4304873. S2CID   71214286.
  183. ↑ Tobias JS, Hochhauser D (3 October 2014). Cancer and its Management. Wiley. pp. 379–. ISBN   978-1-118-46871-5.
  184. 1 2 Jacobi GR, Tunn UW, Senge TH (1 December 1982). "Clinical experience with cyproterone acetate for palliation of inoperable prostate cancer". In Jacobi GH, Hohenfellner R (eds.). Prostate Cancer. Williams & Wilkins. pp. 305–319. ISBN   978-0-683-04354-9. Archived from the original on 6 July 2024. Retrieved 10 July 2019.
  185. ↑ 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): 208–215. doi:10.1111/j.1464-410X.1980.tb02961.x. PMID   7000222.
  186. ↑ "Androcur". Drug Product Database Online Query. Health Canada. 25 April 2012. Archived from the original on 3 December 2020. Retrieved 2 January 2019.
  187. ↑ "Androcur Depot". Drug Product Database Online Query. Health Canada. 25 April 2012. Archived from the original on 3 December 2020. Retrieved 2 January 2019.
  188. ↑ "DIANE-35". Drug Product Database Online Query. Health Canada. 25 April 2012. Archived from the original on 3 December 2020. Retrieved 2 January 2019.
  189. ↑ Becker KL (2001). Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins. pp. 1004–. ISBN   978-0-7817-1750-2.
  190. ↑ Steinbeck AW (1977). "Of Homosexuality: The Current State of Knowledge". Journal of Christian Education. os-20 (2): 58–82. doi:10.1177/002196577702000204. ISSN   0021-9657. S2CID   149168765.
  191. ↑ 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. ISSN   0001-7868. S2CID   56512058.
  192. ↑ Asscheman H, Gooren LJ (1993). "Hormone Treatment in Transsexuals". Journal of Psychology & Human Sexuality. 5 (4): 39–54. doi:10.1300/J056v05n04_03. ISSN   0890-7064. S2CID   144580633.
  193. ↑ Neumann F, Wiechert R (March 1988). "[The antiandrogen cyproterone acetate. Its history from discovery to marketing]" [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. PMID   2967500.
  194. 1 2 3 Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 339–. ISBN   978-1-4757-2085-3.
  195. 1 2 3 Morton IK, Hall JM (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 89–. ISBN   978-94-011-4439-1.
  196. ↑ Zink C (1 January 1988). Dictionary of Obstetrics and Gynecology. Walter de Gruyter. pp. 61–. ISBN   978-3-11-085727-6.
  197. ↑ Danby FW (27 January 2015). Acne: Causes and Practical Management. John Wiley & Sons. pp. 142–. ISBN   978-1-118-23277-4.
  198. 1 2 3 4 5 6 http://www.micromedexsolutions.com/micromedex2/%5B‍%5D
  199. 1 2 3 4 5 6 Sweetman SC, ed. (2009). "Sex hormones and their modulators". Martindale: The Complete Drug Reference (36th ed.). London: Pharmaceutical Press. p. 2082. ISBN   978-0-85369-840-1. Archived from the original on 6 July 2024. Retrieved 11 March 2018.
  200. ↑ Mydlo JH, Godec CJ (11 July 2003). Prostate Cancer: Science and Clinical Practice. Academic Press. pp. 437–. ISBN   978-0-08-049789-1. Archived from the original on 6 July 2024. Retrieved 11 March 2018.
  201. 1 2 Unzeitig V, van Lunsen RH (15 February 2000). Contraceptive Choices and Realities: Proceedings of the 5th Congress of the European Society of Contraception. CRC Press. pp. 73–. ISBN   978-1-85070-067-8.
  202. 1 2 IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, World Health Organization, International Agency for Research on Cancer (2007). Combined Estrogen-progestogen Contraceptives and Combined Estrogen-progestogen Menopausal Therapy. World Health Organization. pp. 44, 437. ISBN   978-92-832-1291-1.
  203. ↑ Gordon JD (2007). Obstetrics, Gynecology & Infertility: Handbook for Clinicians. Scrub Hill Press, Inc. pp. 228–. ISBN   978-0-9645467-7-6.
  204. ↑ Matzkin H, Braf Z (January 1991). "Endocrine treatment of benign prostatic hypertrophy: current concepts". Urology. 37 (1): 1–16. doi:10.1016/0090-4295(91)80069-j. PMID   1702565.
  205. ↑ 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. PMID   7516371.
  206. ↑ Di Silverio F, D'Eramo G, Flammia GP, Buscarini M, Frascaro E, Mariani M, et al. (1993). "[Pharmacological combinations in the treatment of benign prostatic hypertrophy]". Journal d'Urologie (in French). 99 (6): 316–320. PMID   7516378.
  207. ↑ Locker GY (June 1998). "Hormonal therapy of breast cancer". Cancer Treatment Reviews. 24 (3): 221–240. doi:10.1016/S0305-7372(98)90051-2. PMID   9767736.
  208. ↑ 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. PMID   2968261.
  209. ↑ Nieschlag E (November 2010). "Clinical trials in male hormonal contraception" (PDF). Contraception. 82 (5): 457–470. doi:10.1016/j.contraception.2010.03.020. PMID   20933120. Archived (PDF) from the original on 5 December 2020. Retrieved 29 January 2019.
  210. ↑ 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. Cambridge University Press. pp. 470–493. doi:10.1017/CBO9781139003353.023. ISBN   9781139003353.
  211. 1 2 "Cyproterone acetate - Barr Laboratories - AdisInsight". Archived from the original on 2 August 2018. Retrieved 11 December 2017.
  212. ↑ 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. PMID   28718897. S2CID   22365089.
  213. ↑ 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 Neurobiologiae Experimentalis. 72 (1): 1–17. doi: 10.55782/ane-2012-1876 . PMID   22508080. S2CID   11909534.
  214. ↑ 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". Journal of Psychopharmacology. 25 (1): 141–145. doi:10.1177/0269881109353460. PMID   19942637. S2CID   11479701.
  215. ↑ Albert DJ, Walsh ML, Jonik RH (1993). "Aggression in humans: what is its biological foundation?". Neuroscience and Biobehavioral Reviews. 17 (4): 405–425. doi:10.1016/S0149-7634(05)80117-4. PMID   8309650. S2CID   28557481.
  216. ↑ Thibaut F, Kuhn JM, Colonna L (August 1991). "A possible antiaggressive effect of cyproterone acetate". The British Journal of Psychiatry. 159 (2): 298–299. doi: 10.1192/bjp.159.2.298b . PMID   1837749.
  217. ↑ Nomani H, Mohammadpour AH, Moallem SM, YazdanAbad MJ, Barreto GE, Sahebkar A (December 2019). "Anti-Androgen Drugs in the Treatment of Obsessive-Compulsive Disorder: A Systematic Review". Current Medicinal Chemistry. 27 (40): 6825–6836. doi:10.2174/0929867326666191209142209. PMID   31814547. S2CID   208956450.
  218. ↑ Rapoport JL (1 January 1989). Obsessive-compulsive Disorder in Children and Adolescents . American Psychiatric Pub. pp.  229–231. ISBN   978-0-88048-282-0.
  219. ↑ Kellner M (2010). "Drug treatment of obsessive-compulsive disorder". Dialogues in Clinical Neuroscience. 12 (2): 187–197. doi:10.31887/DCNS.2010.12.2/mkellner. PMC   3181958 . PMID   20623923.
  220. ↑ López Ibor JJ, Cercós CL, Masiá CC (2004). Glosa SL (ed.). Images of Spanish Psychiatry. Editorial Glosa, S.L. pp. 376–. ISBN   978-84-7429-200-8.
  221. ↑ Sicuteri F (1988). "Antiandrogenic medication of cluster headache". International Journal of Clinical Pharmacology Research. 8 (1): 21–24. PMID   3366500.

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