Cyproterone acetate

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Cyproterone acetate
Cyproterone acetate.svg
Acetato de ciproterona3D.png
Clinical data
Trade names Androcur, Androcur Depot, Cyprostat, many others
Synonyms SH-80714; SH-714; NSC-81430;[1] 6-Chloro-1β,2β-dihydro-17α-hydroxy-3'H-cyclopropa(1,2)pregna-1,4,6-triene-3,20-dione acetate; 6-Chloro-17α-hydroxy-1α,2α-methylenepregna-4,6-diene-3,20-dione acetate; 6-Chloro-1,2α-methylene-17α-hydroxy-δ6-progesterone acetate
AHFS/Drugs.com Micromedex Detailed Consumer Information
Pregnancy
category
  • X
Routes of
administration
Oral, intramuscular injection
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 100%[4]
Protein binding Albumin: 93%
Free: 7%[5][6][7][8]
Metabolism Hepatic (CYP3A4)[2][3]
Metabolites 15β-OH-CPA (major)[4][9]
Cyproterone (minor)[10]
Acetic acid (minor)[10]
Biological half-life Oral: 38 hours[10][11]
Intramusclar: 72 hours[10][11]
Excretion Feces: 70%[10]
Urine: 30%[10]
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard 100.006.409
Chemical and physical data
Formula C24H29ClO4
Molar mass 416.94 g/mol
3D model (JSmol)
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Cyproterone acetate (abbreviated as CPA), sold alone under the brand name Androcur or with ethinylestradiol (EE) as Diane or Diane-35 among others, is an antiandrogen and progestogen that is used in the treatment of androgen-related conditions like acne, hirsutism (excessive hair growth), early-onset puberty, and prostate cancer, as a component of hormone therapy for transgender women, and in oral contraceptives.[1][12][13] It is formulated and used both alone and in combination with an estrogen and is available for use both by mouth and by injection into muscle.

CPA blocks the effects of androgens like 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 and hence their concentrations in the body.[14] In addition, it has progesterone-like effects by activating the progesterone receptor (PR). CPA is well-absorbed, is extensively bound to plasma proteins, and has an elimination half-life of around 40 hours.[10][11]

Common side effects of non-contraceptive (i.e., high) dosages of CPA in men include gynecomastia (breast development) and feminization in general and in both men and women include hypogonadism (low sex hormone levels), reversible infertility, sexual dysfunction, mental symptoms like depression, fatigue, and irritability, vitamin B12 deficiency, and elevated liver enzymes. Rare but serious adverse reactions of CPA include blood clots, liver damage, and certain types of benign brain tumors (specifically prolactinomas and meningiomas). CPA can also cause adrenal insufficiency as a withdrawal effect if it is discontinued abruptly from a high dosage.

CPA was first marketed in 1973, and was the first antiandrogen to be introduced for medical use.[15] Other important antiandrogens besides CPA include spironolactone and bicalutamide.[16] The drug is available widely throughout the world,[17][18] but is notably not approved for use in the United States.[19]

Medical uses[edit]

Androgen-dependent conditions[edit]

CPA is used in the treatment of prostate cancer, precocious puberty, androgen-dependent skin and hair conditions such as acne, seborrhea, hirsutism (excessive hair growth), and androgenic alopecia (pattern hair loss), hyperandrogenism (e.g., in PCOS), and to reduce sex drive in sex offenders or men with paraphilias or hypersexuality.[20] CPA is also widely used as a component of hormone replacement therapy (HRT) for transgender women.[21] In the U.S., where CPA is not available, other drugs with antiandrogen properties like the diuretic spironolactone and the progestin medroxyprogesterone acetate are used instead to treat androgen-dependent conditions besides prostate cancer.[22]

In the treatment of acne in women, a formulation of low-dose CPA in combination with EE has been found to result in overall improvement in 75 to 90% of patients, with responses approaching 100% improvement.[23]

Hormonal contraception[edit]

The combination of CPA and EE, a formulation sometimes referred to as co-cyprindiol, has been available as a combined oral contraceptive since 1978.[24] This formulation is taken once daily for 21 days, followed by a 7-day free interval.[citation needed] CPA has also been available in combination with estradiol valerate (brand name Femilar) as a contraceptive in Finland since 1993.[25]

Contraindications[edit]

Use during pregnancy is contraindicated, and for women of childbearing age, CPA should be administered with a combined oral contraceptive.[citation needed]

Interactions[edit]

Inhibitors and inducers of the cytochrome P450 enzyme CYP3A4 may interact with CPA.[citation needed]

Side effects[edit]

Hypogonadism and feminization[edit]

Side effects in males resulting directly from the antiandrogen and antigonadotropic properties of CPA include physical demasculinization, gynecomastia (breast enlargement) and general physical feminization, breast pain/tenderness, galactorrhea (milk outflow), sexual dysfunction (including loss of libido and erectile dysfunction), impaired spermatogenesis, and reversible infertility.[15] In the treatment of men with prostate cancer, CPA has been described as causing "severe" suppression of libido and erectile potency, comparable to that seen with surgical castration.[26] Due to suppression of the production of estrogens, long-term use of high-dose CPA without concomitant estrogen therapy can result in the development of osteoporosis in both sexes.[27]

Depression[edit]

CPA has been associated with an increased rate of depression in both men and women.[28] It has been reported that as many as 20–30% of women treated with the drug for hirsutism (dosage range 25–100 mg) may show depressive symptoms.[29][30] Also, a study found that around 20% of women treated with Dianette (which contains only 2 mg CPA) for contraceptive purposes developed depression.[31] As the antiandrogen component of transgender HRT, treatment with CPA (as well as with spironolactone to a lesser extent) has also been associated with a significantly higher rate of depressive symptomatology in transgender women relative to treatment with GnRH analogues (which are more selective in their action and are considered not to have a significant risk of depression in this patient population (with concomitant supplementation of estrogen)).[32] The depressive effects of CPA may be related to its glucocorticoid, antiandrogen, or antigonadotropic effects, as glucocorticoids, antiandrogens (in men), and GnRH analogues have all been associated with depression.[33][34][35][36] Vitamin B12 deficiency induced by CPA might also or alternatively be a critical factor.[31] Because of the side effect of depression, CPA should be used with caution in individuals with a history of the condition, especially if severe.[37]

Vitamin B12 deficiency[edit]

High-dose CPA treatment has been found to produce vitamin B12 deficiency.[38][39] Low-dose (2 mg/day) CPA in combination with EE has also been associated with vitamin B12 deficiency.[40] It is notable that vitamin B12 deficiency is associated with depression, anxiety, irritability, and fatigue via depletion of central monoamine neurotransmitters,[41][42] and it has been suggested that this may be involved in the adverse neuropsychiatric consequences commonly observed with CPA therapy.[31] Serum vitamin B12 monitoring and supplementation as necessary is recommended during CPA treatment.[38][39][40]

Other side effects[edit]

CPA has been associated with the formation of stretch marks, due potentially to glucocorticoid activity or causing dry skin.[43]

Rare reactions[edit]

Blood clots[edit]

Used alone, CPA does not appear to have a significant effect on blood clotting factors, but in combination with EE, as in combined oral contraceptives, presents an increased risk of deep vein thrombosis.[44] Women who take contraceptive pills containing CPA have a 6- to 7-fold increased risk of developing thromboembolism compared to women not taking a contraceptive pill, and twice the risk of women who take a contraceptive pill containing levonorgestrel.[45] At least four cases of fatal venous thromboembolism have been attributed to low-dose CPA in combination with EE.[46]

Hepatotoxicity[edit]

The most serious potential side effect of CPA is hepatotoxicity.[47] A variety of manifestations of liver disease in association with CPA treatment have been documented, including immunoallergic cytotoxic reactions, cholestasis, autoimmune hepatitis, acute hepatitis, fulminant liver failure, and cirrhosis, as well as an increased risk of hepatocellular carcinoma.[48][49] Clinical features may include jaundice, fatigue, nausea, elevated liver enzymes, hepatic necrosis and inflammation, and features of hepatic decompensation.[49] Hepatotoxicity due to CPA therapy is most common in elderly patients who are treated with high dosages of the drug for prolonged periods of time, but has also occurred in younger patients.[48]

In a study of 1,685 patients treated with CPA, elevated liver enzymes were seen in 10% of patients at a dosage of 50 mg/day and in 20% of patients at a dosage of greater than 100 mg/day.[47] A study of 2,506 patients given 18–136 mg/day for less than 47.5 months per patient reported a rate of 9.6%.[48][49] In a trial of 89 prostate cancer patients who received high-dose CPA for 4 years, there were elevated liver enzymes in 28.2% of the patients.[49] Yet another study of 105 patients found a hepatotoxicity rate of 9.5%, with serious hepatic injury occurring in 3.8%.[49] In 2002, it was reported that there were 18 case reports of CPA-associated hepatitis in the medical literature, with 6 of the cases resulting in death.[47] In addition, a review article cited a report of 96 instances of hepatotoxicity that were attributed to CPA, and 33 of these instances resulted in death.[47] Moreover, a 2014 review found that 15 cases specifically of CPA-induced fulminant (sudden-onset and severe) liver failure had been reported to date, with only one of these cases not resulting in death.[49] As such, the prognosis of CPA-induced liver failure is fatal.[49]

The risk of hepatotoxicity and death associated with CPA treatment is the reason that CPA has not been approved by the FDA for use in the United States.[50] Patients being treated with high-dose CPA should be closely monitored with liver function tests.[51] The risk is dose-dependent, and the low doses of CPA used in birth control pills (2 mg) have been said to represent a non-significant risk.[52] However, a German woman who had been taking Diane-35 (containing 2 mg/day CPA) for contraception for 14 years died of liver cancer, and this led to a safety review by drug regulators and the eventual restriction of CPA throughout Europe for the indication of acne treatment in women.[46]

Hyperprolactinemia[edit]

High-dose CPA in combination with estrogen has been associated with a dramatically (400-fold) increased incidence of hyperprolactinemia in transgender women.[53] Estrogen alone has been associated only with single case reports of prolactinoma in this population.[53]

Meningiomas[edit]

Very rarely, high-dose (but not low-dose (i.e., contraceptive-dose)) CPA treatment has been associated with the incidence and aggravation of meningiomas (a type of usually-benign brain tumor).[54][55] For this reason, high-dose CPA is contraindicated in people with meningioma or a history of meningoma.[2][37]

Withdrawal[edit]

Adrenal insufficiency[edit]

Abrupt withdrawal of CPA can be harmful, and the package insert from Schering AG recommends the daily dose be reduced by no more than 50 mg at intervals of several weeks. The concern is the manner in which CPA affects the adrenal glands. Due to its glucocorticoid activity, high levels of CPA may reduce ACTH, resulting in adrenal insufficiency if discontinued abruptly. In addition, although CPA reduces androgen production in the gonads, it can increase the production of adrenal androgens, in some cases resulting in an overall rise in testosterone levels.[56] Thus, the sudden withdrawal of CPA could result in undesirable androgenic effects.[citation needed] This is a particular concern because androgens, especially DHT, suppress adrenal function, further reducing corticosteroid production.[57]

Suppression of adrenal function and reduced response to adrenocorticotropic hormone (ACTH) have been reported with CPA treatment. As a result, adrenal insufficiency and hence low cortisol and aldosterone levels and ACTH responsiveness can occur upon discontinuation of CPA. Low aldosterone levels may lead to hyponatremia (sodium loss) and hyperkalemia (excess potassium). Patients taking CPA should have their cortisol levels and electrolytes monitored, and if hyperkalemia develops, should reduce the consumption of foods with high potassium content or discontinue the medication.

Pharmacology[edit]

CPA is known to possess the following pharmacological activity:

CPA does not have significant affinity for the estrogen receptor (ER) or for the mineralocorticoid receptor (MR).[65]

CPA is said to be equipotent as a progestogen and antiandrogen.[66] CPA is said to be the most potent progestin of the 17α-hydroxyprogesterone group, reportedly being 1200-fold more potent than hydroxyprogesterone acetate, 12-fold more potent than medroxyprogesterone acetate, and 3-fold more potent than chlormadinone acetate.[66][67] CPA is also reportedly the most potent of the steroidal antiandrogens,[68] out of hundreds of other steroids.[24]

Antiandrogenic activity[edit]

CPA is a potent androgen receptor (AR) competitive antagonist.[58] It directly blocks endogenous androgens such as testosterone and dihydrotestosterone (DHT) from binding to and activating the AR, and thus prevents them from exerting their androgenic effects in the body. However, CPA, like spironolactone and other steroidal antiandrogens such as chlormadinone acetate and medroxyprogesterone acetate, is not actually a pure antagonist of the AR – that is, a silent antagonist – but rather is a very weak partial agonist.[58][69][70][71] Clinically, CPA generally behaves purely as an antiandrogen, as it displaces much more efficacious endogenous androgens such as T and DHT from interacting with the receptor and thus its net effect is usually to lower physiological androgenic activity. But unlike silent antagonists of the AR such as flutamide, CPA, by virtue of its slight intrinsic activity at the receptor, is inherently incapable of fully abolishing androgenic activity in the body and will always maintain at least some degree of it.

In accordance with its, albeit weak, capacity for activation of the AR, CPA has been found to stimulate androgen-sensitive carcinoma growth in the absence of other androgens, an effect which could be blocked by co-treatment with flutamide.[69][70] As a result, CPA may not be as effective in the treatment of certain androgen-sensitive conditions such as prostate cancer compared to non-steroidal antiandrogens with a silent antagonist profile at the AR such as flutamide, bicalutamide, and enzalutamide.[58][72] Indeed, CPA has never been found to extend life in prostate cancer patients when added to castration relative to castration alone, unlike non-steroidal antiandrogens.[16]

A paradoxical effect occurs with certain prostate cancer cells which have genetic mutations in their ARs. These altered ARs can be activated, rather than inhibited, by CPA. In such cases, withdrawal of CPA may result in a reduction in cancer growth, rather than the reverse.[73] This is known as antiandrogen withdrawal syndrome.

CPA may also have a slight direct inhibitory effect on 5α-reductase, though the evidence for this is sparse and conflicting.[74][75][76] In any case, the combination of CPA and finasteride, a well-established, selective 5α-reductase inhibitor, has been found to result in significantly improved effectiveness in the treatment of hirsutism relative to CPA alone, suggesting that if CPA does have any direct inhibitory effects on 5α-reductase, they must be far from maximal.[77][78]

Indirect estrogenic effects[edit]

Because CPA does not bind to the ER, and because it suppresses estrogen production via its action as an antigonadotropin, the drug produces no general estrogenic effects (direct or indirect) and is potently antiestrogenic at sufficient dosages. However, androgens strongly antagonize the action of estrogen in the breasts, so CPA can produce a sole indirect estrogenic effect of slight gynecomastia in males via its action as an antiandrogen. In any case, the incidence and severity of this side effect is less than that observed with non-steroidal antiandrogens such as flutamide and bicalutamide, which, in contrast, do not lower estrogen levels (and actually can increase them).[79][80]

Progestogenic activity[edit]

CPA is a highly potent progestogen.[81] The dosage needed to inhibit ovulation in women (i.e., to act as a contraceptive) is less than 1 mg per day,[82] and the drug is marketed as a contraceptive (combined with low-dose EE) at a dosage of 2 mg/day.[81][83]

Through its action as a progestogen, CPA has been found to significantly increase prolactin secretion and to induce extensive lobuloalveolar development of the mammary glands of female rhesus macaques.[84] In accordance, a study found that CPA, in all cases, induced full lobuloalveolar development of the breasts in transgender women treated with the drug in combination with estrogen for a prolonged period of time.[85][86][87] Pregnancy-like breast hyperplasia was observed in two of the subjects.[87] In contrast, the same study found that men with prostate cancer treated with a non-progestogenic antiandrogen like flutamide or bicalutamide and no estrogen produced only moderate and incomplete lobuloalveolar development of the breasts.[85] Based on the above research, it was concluded by the study authors that combined estrogenic and progestogenic action is required in transgender women for fully mature female-like histologic breast development (i.e., that includes complete lobuloalveolar maturation).[85][86] Also, it was observed that lobuloalveolar maturation reverses upon discontinuation of CPA after surgical castration, similarly to the case of mammary gland involution in postpartum women, indicating that continued progestogen treatment is necessary to maintain the histology.[85] It should be noted however that although these findings may have important implications in the context of lactation and breastfeeding, epithelial tissue accounts for approximately only 10% of breast volume (with the bulk of the breasts (80–90%) being represented by stromal or adipose tissue),[88][89][90][91] and it is uncertain to what extent, if any, that development of lobuloalveolar structures (a type of epithelial tissue) contributes to breast size or shape.[92]

The action of CPA as a progestogen is responsible for its antigonadotropic effects.[58][81]

Antigonadotropic effects[edit]

CPA has powerful antigonadotropic effects via activation of the PR.[26][58][58][81] In humans, it blunts the gonadotropin releasing hormone (GnRH)-induced secretion of gonadotropins,[93] and accordingly, markedly suppresses circulating levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) at high dosages.[citation needed] Consequently, progesterone (P4), androstenedione, T, DHT, and estradiol (E2) are also markedly lowered at high dosages, while an elevation in sex hormone-binding globulin (SHBG) and prolactin levels is observed.[94][95][96][97][98] CPA is able to lower circulating T concentrations by 70 to 80% in men at high dosages.[99] However, in spite of strong suppression of testosterone levels, CPA, at least by itself (e.g., without estrogen), is not able to reduce testosterone levels into the castrate range (<50 ng/dL), and testosterone levels may remain just above it at circulating levels of roughly 50 to 100 ng/dL.[100]

Although the reduction of sex steroid levels with CPA is predominantly mediated by its progestogenic and antigonadotropic activities, inhibition of steroidogenic enzymes by the drug may also contribute to this to some extent.[101]

Other actions[edit]

Glucocorticoid activity[edit]

Due to negative feedback on the hypothalamic–pituitary-adrenal (HPA) axis, administration of exogenous glucocorticoids such as prednisone and dexamethasone suppress the secretion of adrenocorticotropic hormone (ACTH) from the pituitary gland and the production of cortisol from the adrenal glands, resulting in adrenal suppression and atrophy and, upon discontinuation of the glucocorticoid, temporary adrenal insufficiency. Similarly, albeit relatively weakly, CPA has the ability to reduce ACTH and cortisol levels and produce adrenal gland shrinkage, as well as, upon discontinuation, adrenal insufficiency, in both animals and humans, indicating that it possesses weak glucocorticoid properties.[102][103][104][105][106][107][108] Paradoxically however, in vitro, CPA is an antagonist of the glucocorticoid receptor (GR)[60][109][110] and a suppressor of adrenal cortisol and corticosterone production by inhibiting the enzymes 3β-hydroxysteroid dehydrogenase and 21-hydroxylase,[104][111][112][113] which are antiglucocorticoid actions. This paradox may be explained by the fact that certain active metabolites of CPA, such as its major metabolite 15β-hydroxycyproterone acetate (which is present at serum levels approximately twice those of CPA in humans[9]),[114] are, contrarily, agonists of the GR,[115] and it can be assumed that their glucocorticoid actions overall significantly outweigh the simultaneous antiglucocorticoid actions of CPA. Both cyproterone and CPA, via their metabolites, have been found to possess glucocorticoid effects, and based on studies in mice, it has been suggested that CPA has approximately 1/5th the potency of prednisone as a glucocorticoid.[116]

While various studies have clearly shown reduced cortisol and ACTH levels and ACTH responsiveness in humans with CPA treatment, some studies contradict these findings and report no such effects even with high dosages.[115][117][118][119][120]

Megestrol acetate, medroxyprogesterone acetate, and chlormadinone acetate, steroidal progestins and close analogues of CPA, all similarly possess glucocorticoid properties and the potential for producing adrenal insufficiency upon their discontinuation.[121][122]

Binding to opioid receptors[edit]

CPA has been found to bind non-selectively to the opioid receptors, including the μ-, δ-, and κ-opioid receptor subtypes, albeit very weakly relative to its other actions (IC50 for inhibition of [3H]diprenorphine binding = 1.62 ± 0.33 µM).[123] It has been suggested that activation of opioid receptors could have the potential to explain the side effect of sedation sometimes seen at high doses with CPA treatment or its effectiveness in the treatment of cluster headaches.[123]

Pharmacokinetics[edit]

Absorption[edit]

The oral bioavailability of CPA is reported to be 100%.[4] However, it has also been said that CPA is poorly absorbed from the gastrointestinal tract and should be taken after the consumption of food, which it would be implied improves its absorption.[124]

Distribution[edit]

In terms of plasma protein binding, CPA does not bind to sex hormone-binding globulin or transcortin[125] and is instead bound exclusively to albumin (93%), with the remainder (7%) circulating free or unbound.[4][5][6][7][8]

Metabolism[edit]

CPA is metabolized primarily by hydroxylation via CYP3A4, forming the major active metabolite 15β-hydroxycyproterone acetate.[4][9] This metabolite circulates at concentrations approximately twice those of CPA, and has similar antiandrogen activity to that of CPA but only 10% of its activity as a progestogen.[4][9][126][127] As a result, the co-administration of CPA with drugs which inhibit CYP3A4 may increase its potency as a progestogen.[5]

A portion of ingested CPA is metabolized by hydrolysis into cyproterone and acetic acid.[128] However, unlike many other steroid esters, CPA is not extensively hydrolyzed, and much of the pharmacological activity of the drug is attributable to CPA itself in its unchanged form.[51] Cyproterone has approximately one-third the potency of CPA as an antiandrogen[129] and is devoid of progestogenic activity.[67]

The elimination half-life of oral CPA is relatively long at approximately 38 hours.[4][124] However, in spite of this, the drug is usually given in divided doses two to three times per day when it is used orally in the treatment of prostate cancer.[124] When given via depot intramuscular injection, circulating levels of CPA reach a peak at 82 hours and the drug has an elimination half-life of 72 hours.[10][11]

Excretion[edit]

CPA is excreted 70% in feces and 30% in urine.[10]

Chemistry[edit]

CPA is a pregnane steroid and an acetylated derivative of 17α-hydroxyprogesterone.[130] It is structurally related to other 17α-hydroxyprogesterone derivatives such as chlormadinone acetate, hydroxyprogesterone caproate, medroxyprogesterone acetate, and megestrol acetate.[130]

Chemical names[edit]

CPA is also known by the following equivalent chemical names:[131]

  • (1S,2S,3S,5R,11R,12S,15R,16S)-15-acetyl-9-chloro-2,16-dimethyl-6-oxopentacyclo[9.7.0.0²,⁸.0³,⁵.0¹²,¹⁶]octadeca-7,9-dien-15-yl acetate
  • 6-Chloro-1β,2β-dihydro-17α-hydroxy-3'H-cyclopropa(1,2)pregna-1,4,6-triene-3,20-dione acetate
  • 6-Chloro-17α-hydroxy-1α,2α-methylenepregna-4,6-diene-3,20-dione acetate[67]
  • 6-Chloro-1,2α-methylene-17α-hydroxy-δ6-progesterone acetate

History[edit]

CPA was discovered in the early 1960s, and Rudolf Wiechert, a Schering employee, together with F. Neumann in Berlin filed for a patent as "progestational agent" in 1962.[132] Only one year after patent approval in 1965, Neumann published evidence of CPA's antiandrogenic effect in rats; he reported an "organizational effect of CPA on the brain".[133] During the same year, in 1966, prenatal administration of CPA in male rats was shown to cause urogenital malformations by a group in Lund, Sweden.[134] CPA started being used in animal experiments around the world to investigate how antiandrogens affected fetal sexual differentiation.

In 1970, the first human experiments with CPA began by measuring serum levels after oral administration,[135] rates of spermatogenesis, and hair growth in women. Starting in 1972, psychiatrists trialed "sexually deviant" persons with CPA.[136] In 1973, CPA was first approved in Europe, under the brand name Androcur.[137][138] Until the development of leuprolide, CPA was one of the few drugs used to treat precocious puberty.[citation needed] CPA was first marketed in combination with EE as an oral contraceptive in 1978 under the brand name Diane.[24]

Along with the steroidal benorterone (17α-methyl-B-nortestosterone; SKF-7690), cyproterone, BOMT (Ro 7-2340), and trimethyltrienolone (R-2956) and the non-steroidal flutamide and DIMP (Ro 7-8117), CPA was one of the first antiandrogens to be discovered and studied.[40][139][140][141]

Society and culture[edit]

Generic name[edit]

The English and generic name of CPA is cyproterone acetate and this is its USAN, BANM, and JAN.[1][17][18][142] The English and generic name of unesterified cyproterone is cyproterone and this is its INN and BAN,[1][142][143] while cyprotérone is the DCF and French name and ciproterone is the DCIT and Italian name.[17][18] The name of unesterified cyproterone in Latin is cyproteronum, in German is cyproteron, and in Spanish is ciproterona.[17][18] These names of cyproterone correspond for CPA to acétate de cyprotérone in French, acetato de ciproterona in Spanish, ciproterone acetato in Italian, cyproteronacetat in German, cyproteronacetaat in Dutch, and ciproteron acetat in Slavic.

CPA is also known by the developmental code names SH-80714, SH-714, and NSC-81430, while unesterified cyproterone is known by the code names SH-80881, SH-881, and NSC-758636.[1][17][18][142]

Brand names[edit]

CPA is marketed under brand names including Androcur, Androcur Depot, Androcur-100, Androstat, Asoteron, Cyprone, Cyproplex, Cyprostat, Cysaxal, Imvel, and Siterone.[17][18] When CPA is formulated in combination with EE, 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.[17][18] CPA is also marketed in combination with estradiol valerate as Climen, Climene, Elamax, and Femilar.[17]

Availability[edit]

CPA is widely available throughout the world[17][18] and is marketed in almost every country,[144] with the notable major exception of the United States.[19] The drug is marketed both alone and in combination with EE or estradiol valerate.[17][18] Specific places in which CPA is marketed include the United Kingdom, other European countries, Canada, Australia, New Zealand, South Africa, Central and South America, and East and Southeast Asia.[17][18]

Research[edit]

Aggression and self-injury[edit]

CPA has been investigated for use in reducing aggression and self-injurious behavior via its antiandrogen effects in conditions like autism spectrum disorders and dementia (e.g., Alzheimer's disease).[145]

Obsessive-compulsive disorder[edit]

CPA may be effective in the treatment of obsessive-compulsive disorder (OCD).[146] In very limited clinical research, it has been reported to be "considerably" effective in the treatment of OCD in women.[147][148]

Cluster headaches[edit]

CPA has been studied in the treatment of cluster headaches in men.[149]

References[edit]

  1. ^ a b c d e J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 339–. ISBN 978-1-4757-2085-3. 
  2. ^ a b Dickman A (27 September 2012). Drugs in Palliative Care. OUP Oxford. pp. 137–138. ISBN 978-0-19-966039-1. 
  3. ^ 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. 
  4. ^ a b c d e f g Kuhl H (August 2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration" (PDF). Climacteric. 8 Suppl 1 (sup1): 3–63. PMID 16112947. doi:10.1080/13697130500148875. 
  5. ^ a b c Bińkowska M, Woroń J (June 2015). "Progestogens in menopausal hormone therapy". Przegla̜d Menopauzalny = Menopause Review. 14 (2): 134–43. PMC 4498031Freely accessible. PMID 26327902. doi:10.5114/pm.2015.52154. 
  6. ^ a b Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH (December 2003). "Classification and pharmacology of progestins" (PDF). Maturitas. 46 Suppl 1: S7–S16. PMID 14670641. doi:10.1016/j.maturitas.2003.09.014. Since there is no binding of CPA to SHBG and CBG in the serum, 93% of the compound is bound to serum albumin. 
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