Cyproterone acetate ( CPA ), sold itself under the brand name Androcur or with ethinylestradiol (EE) under the brand name Diane or Diane-35 among others, are antiandrogens and progestogens used in the treatment of androgen-dependent conditions such as acne, excessive hair growth, early puberty, and prostate cancer, as a component of feminine hormone therapy for transgender women, and in birth control pills. It is formulated and used separately and combined with estrogen and is available for use both by mouth and by injection into the muscle.
Common side effects of non-contraceptive (ie, high) doses of CPA in men include gynecomastia (breast development) and feminization in general and in men and women including low sex hormone levels, reversible infertility, sexual dysfunction, mental symptoms such as depression, fatigue, and irritability, vitamin B12 deficiency, and elevated liver enzymes. At very high doses, cardiovascular side effects may occur. The rare but serious side effects of CPA include blood clotting, liver damage, and certain types of benign brain tumors. The CPA may also cause adrenal insufficiency as a withdrawal effect if it is stopped suddenly from high doses.
CPAs block the effects of androgens such as testosterone in the body, which is done by preventing them interacting with their biological targets, androgen receptors (AR), and by reducing their production by the gonads and hence their concentration in the body. In addition, it has effects such as progesterone by activating the progesterone (PR) receptor. CPA is well absorbed, extensively bound to plasma proteins, and has a elimination half-life of about 40 hours.
The CPA was first marketed in 1973, and was the first antiandrogen introduced for medical use. Other important antiandrogens other than CPA include spironolactone and bicalutamide. The drug is widely available worldwide, but is not approved for use in the United States.
Video Cyproterone acetate
Medical use
Androgen-dependent conditions
CPA is used in the treatment of prostate cancer, premature puberty, androgen-dependent skin and hair conditions such as acne, seborrhea, hirsutism (excessive hair growth), and androgenic alopecia (hair loss pattern), hyperandrogenism (eg, in PCOS ), and to reduce the sex drive of sex offenders or men with paraphilias or hypersexuality. CPA is also widely used as a component of feminization hormone therapy for transgender women. In the US, where BPA is not available, other drugs with antiandrogen properties such as diuretic spironolactone and progestin medroxyprogesterone acetate are used instead to treat androgen-dependent conditions other than prostate cancer.
In the treatment of acne in women, low-dose CPA formulations in combination with EE have been found to result in overall improvement in 75 to 90% of patients, with responses approaching 100% improvement.
Birth control
The combination of CPA and EE, formulations sometimes referred to as co-cyprindiol , has been available as a combined oral contraceptive since 1978. This formulation is taken once daily for 21 days, followed by 7- day free intervals. The CPA has also been available in combination with estradiol valerate (brand name Femilar) as a contraceptive in Finland since 1993.
Available form
CPA is available in the form of oral tablet alone (high dose, 10 mg, 50 mg, 100 mg) or in combination with ethinylestradiol or estradiol valerate (low dose, 2 mg CPA) and in ampoule form for intramuscular injection (high dose 100 mg/mL, 300 mg/3 mL, brand name Androcur Depot). High-dose formulations are used to treat prostate cancer and certain other androgen-related indications while low-dose formulations that also have estrogen are used as a combination pill and are used in menopausal hormone therapy for the treatment of menopausal symptoms.
Maps Cyproterone acetate
Contraindications
Use during pregnancy is contraindicated.
Interactions
CYP3A4 enzyme inhibitors and cytochrome P450 enzymes may interact with CPA.
Side effects
Common side effects of CPA include hypogonadism and related symptoms such as demasculinization, sexual dysfunction, infertility, and osteoporosis, breast changes such as gynecomastia, mental changes such as depression, anxiety, fatigue, and suicidal ideation, vitamin B12 deficiency, glucocorticoid side effects such as stretch marks, and elevated liver enzymes. At very high doses, CPA can cause cardiovascular side effects. Rarely, CPA can cause blood clotting, liver damage, too high prolactin levels, prolactinomas, and meningiomas. After termination at high doses, the CPA may have a withdrawal effect, namely adrenal insufficiency.
Hypogonadism
Side effects in men resulting from antiandrogenic and antigonadotropic properties of CPA include physical demasculinization, sexual dysfunction (including loss of libido and erectile dysfunction), spermatogenesis disorders, absence of ejaculation, and reversible infertility. In the treatment of men with prostate cancer, the CPA has been described as a cause of the "heavy" emphasis of libido and erectile potential, comparable to that seen by surgical castration. Because of the suppression of estrogen production, long-term use of high-dose BPA without concurrent estrogen therapy may result in the development of osteoporosis in both sexes. CPAs can also sometimes cause breast changes in men including gynecomastia, breast pain, and galactorrhoea. Gynecomastia rates of 7 to 13% have been reported.
Depression
CPA has been associated with potential side effects of depression in both men and women. It has been reported that as many as 20 to 30% of women treated with drugs for hirsutism (dose range 25-100 mg) may show symptoms of depression. Also, one study found that about 20% of women treated with Dianette (who only contain 2 mg CPA) for contraceptive purposes developed depression. As an HRT transgender antiandrogen component, treatment with CPA (as well as with spironolactone to lower levels) has also been associated with significantly higher levels of symptomatology of depression in transgender women relative to treatment with GnRH analogues (which are more selective in action and considered risk-free a significant depression in this patient population (with concurrent estrogen supplementation)). The effects of CPA depression may be related to the effects of glucocorticoids, antiandrogens, or antigonadotropic, such as glucocorticoids, antiandrogens (in men), and GnRH analogues are all associated with depression. Vitamin B12 deficiency induced by CPA may also be or as a critical factor. Because of the side effects of depression, CPAs should be used with caution in individuals with a history of the condition, especially if severe.
Vitamin B12 deficiency
High-dose CPA treatment has been found to produce vitamin B12 deficiency. Low dose BPA (2 mg/day) combined with EE is also associated with vitamin B12 deficiency. It should be noted that vitamin B12 deficiency is associated with depression, anxiety, irritability, and fatigue through the depletion of central monoamine neurotransmitters, and it has been suggested that this may be involved in the neuropsychiatric consequences that are usually observed with CPA therapy. Serum vitamin B12 supplementation and supplementation is recommended during CPA treatment.
Cardiovascular
At very high doses used to treat men with prostate cancer, CPA is associated with cardiovascular side effects including coagulation and blood clotting (5%), fluid retention (4%), ischemic cardiomyopathy (4-40%), and the effects undesirable. on serum lipid profile. Severe cardiovascular complications occur in about 10% and are sometimes fatal.
Other side effects
CPA has been associated with the formation of stretch marks, because of the potential for glucocorticoid activity or causing dry skin.
Rare reaction
Liver Toxicity
The most serious potential side effect of CPA is hepatotoxicity. Various 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. Clinical features may include jaundice, fatigue, nausea, elevated liver enzymes, liver necrosis and inflammation, and liver decompensation features. Hepatotoxicity due to CPA therapy is most common in elderly patients who are treated with high doses of drugs for long periods of time, but also occurs in younger patients.
In a study of 1,685 patients treated with CPA, elevated liver enzymes were seen in 10% of patients with doses of 50 mg/day and in 20% of patients with doses greater than 100 mg/day. A study of 2,506 patients given 18-136 mg/day for less than 48 months per patient reported a rate of 9.6%. In an experiment of 89 prostate cancer patients who received high dose BPA for 4 years, there was elevated liver enzymes in 28.2% of patients. Yet another study of 105 patients found a 9.5% hepatotoxicity rate, with serious liver injury occurring at 3.8%. In 2002, it was reported that there were 18 reports of CPA-related cases of hepatitis in medical literature, with 6 cases resulting in death. In addition, a review article cited a report of 96 cases of hepatotoxicity attributed to the CPA, and 33 of these examples resulted in death. Additionally, a 2014 review found that 15 cases of particularly CPA-induced fulminant liver failure (sudden and severe) have been reported to date, with only one of these cases not resulting in death. Thus, the prognosis of CPA-induced liver failure is death.
The risk of hepatotoxicity and death associated with CPA treatment reported the reason that the CPA has not been approved by the FDA for use in the United States. Patients treated with high-dose BPA should be closely monitored with liver function tests. The risk depends on the dose, and the low dose CPA used in birth control pills (2 mg) has been said to represent an insignificant risk. However, a German woman who has used Diane-35 (containing 2 mg/day BPA) for contraception for 14 years died of liver cancer, and this led to safety reviews by drug regulators and CPA restrictions across Europe for indications of acne treatment in women.
Blood clotting
Used alone, CPA does not seem 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. Women taking CPC containing CPA have a 6 to 7 fold increase in thromboembolism compared with women who do not take the contraceptive pill, and twice the risk of women taking the contraceptive pill containing levonorgestrel. At least four cases of fatal venous thromboembolism have been associated with low-dose CPAs in combination with EE. The glucocorticoid and progestogenic activity of CPA is considered to be involved in an increased risk of thrombosis with CPA in combination with estrogen.
High prolactin levels
High-dose BPA in combination with estrogen has been associated with an increased incidence of 400-fold hyperprolactinemia (high prolactin levels) in transgender women. Estrogens alone are associated only with single cases of prolactinoma in this population.
Meningiomas
Very rarely, high doses (but not low doses (ie, dose contraceptives)) CPA treatment has been linked to the incidence and aggravation of meningiomas (a type of usually benign brain tumor). For this reason, high-dose BPA is contraindicated in people with meningiomas or a history of meningomas.
Withdrawal
Adrenal insufficiency
The sudden withdrawal of CPAs can be dangerous, and packets submitted from Schering AG recommend a daily dose less than 50 mg in intervals of several weeks. Attention is the way in which the CPA affects the adrenal gland. Because of its glucocorticoid activity, high levels of CPA may reduce ACTH, resulting in adrenal insufficiency if stopped suddenly. In addition, although the CPA reduces the production of androgens in the gonads, CPAs can increase adrenal androgen production, in some cases resulting in an overall increase in testosterone levels. Thus, sudden CPA withdrawal may cause unwanted androgenic effects. This is a particular problem because androgens, especially DHT, suppresses adrenal function, further reducing corticosteroid production.
Emphasis of adrenal function and reduced response to adrenocorticotropic hormone (ACTH) has been reported with CPA treatment. As a result, adrenal insufficiency and therefore cortisol and aldosterone levels and low ACTH response may occur after CPA termination. Low levels of aldosterone can cause hyponatremia (loss of sodium) and hyperkalemia (excess potassium). Patients taking CPA should have their cortisol and electrolyte levels monitored, and if hyperkalemia develops, it should reduce the consumption of foods with high potassium content or discontinue treatment.
Pharmacology
Pharmacodynamics
CPA is known to have the following pharmacological activity:
- Very weak paragon antagonist/agonist (IC 50 = 57 nM)
- Reconstitute progesterone agonist (PR) (K d = 15 nM; IC 50 = 79 nM)
- Glucocorticoid receptor antagonist (GR) (K d = 45 nM; IC 50 = 360 nM)
- The pregnant X receptor (PXR) agonist (EC 50 = 1,6? M) (and thus CYP3A4 and P-glycoprotein inducer)
- Weak inhibitor 3-hydroxisteroid dehydrogenase, 17? -hydroxylase/17,20-lyase, and 21-hydroxylase
CPAs have no significant affinity for estrogen receptor (ER) or for mineralocorticoid receptor (MR).
Antiandrogenic Activities
CPA is a strong androgen receptor-competitive antagonist (AR). It is reportedly the most powerful of steroidal antiandrogens, from hundreds of other steroids. It directly blocks endogenous androgens such as testosterone and dihydrotestosterone (DHT) from binding to and activation of AR, and thereby preventing them from using androgenic effects in the body. However, CPAs, such as spironolactone and other steroidal antiandrogens such as chlormadinone acetate and medroxyprogesterone acetate, are not really pure antagonists of AR - that is, a silent antagonist - but rather a very weak partial agonist. Clinically, CPA generally behaves purely as an antiandrogen, because it replaces many endogenous androgens such as T and DHT interacting with receptors and thus the net effect is usually to decrease the androgenic physiological activity. But unlike the silent antagonist of AR such as flutamide, CPA, based on its slight intrinsic activity on the receptor, it is inherently incapable of completely eliminating androgenic activity in the body and will always maintain at least some degree of it.
In keeping with capacity, although weak, for AR activation, CPA has been found to stimulate the growth of androgen-sensitive carcinoma in the absence of other androgens, an effect that can be blocked by co-treatment with flutamide. Consequently, CPAs may not be effective in the treatment of certain androgen conditions such as prostate cancer compared to nonsteroidal antiandrogens with a silent antagonist profile in AR such as flutamide, bicalutamide, and enzalutamide. Indeed, CPAs have never been found to prolong life in patients with prostate cancer when added to castration relative to castration alone, unlike nonsteroidal antiandrogens.
Paradoxical effects occur in certain prostate cancer cells that have a genetic mutation in AR. This modified ARS can be enabled, rather than inhibited, by the CPA. In such cases, CPA withdrawal may lead to a decrease in cancer growth, not vice versa. This is known as the antiandrogen withdrawal syndrome.
CPA may also have a slight direct inhibitory effect on 5? -reductase, although the evidence for this is uncommon and contradictory. In any case, a combination of CPA and finasteride, selective 5-reductase inhibitor, has been shown to result in a significant increase in efficacy in the treatment of hirsutism relative to CPA alone, suggesting that if the CPA has a direct inhibitory effect on 5? - reductase, they should be far from the maximum.
The estrogenic effect
Since the CPA does not bind ER, and because it suppresses estrogen production through its action as antigonadotropin, it does not produce general (direct or indirect) estrogenic effects and is potentially antiestrogenic at sufficient doses. However, androgens strongly contradict the action of estrogen in the breast, so the CPA can produce a single indirect estrogenic effect of mild gynecomastia in men through its action as an antiandrogen. However, the incidence and severity of these side effects are less than those observed with nonsteroidal antiandrogens such as flutamide and bicalutamide, which, on the other hand, do not decrease estrogen levels (and can actually increase it).
Progestogenic activity
CPA is a very strong progestogen. It is described as the most powerful progestin of the 17-hydroxyprogesterone group, being about 1,200 times stronger than hydroxyprogesterone acetate, 12 times stronger than medroxyprogesterone acetate, and 3 times stronger than chlormadinone acetate in animal bioassay. Based on the results of the Clauberg test, it is also said to be the most powerful progestin known, with 1,000 times the potential for progesterone. However, with oral administration in humans, CPAs are clearly less potent as progestogen than other progestin-like 19-nortestosterone derivatives. The effective dose required to inhibit ovulation in women (ie, to act as a contraceptive) is 1 mg/day, and the drug is marketed as a contraceptive (combined with low dose EE) at a dose of 2 mg/day. For comparison, the ovulation dose-inhibiting levonorgestrel is 50 Ã,Âμg/day. CPA is said to be equipotent as progestogen and antiandrogen.
Through its action as a progestogen, CPA has been found to significantly increase prolactin secretion and to induce the extensive lobuloalveolar development of the female rhesus gland. Accordingly, a study found that the CPA, in all cases, induced full lobuloalveolar development of the breast in transgendered women treated with the drug in combination with estrogen for long periods of time. Breast hyperplasia as pregnancy is observed in two subjects. In contrast, the same study found that men with prostate cancer were treated with non-progestogenic antiandrogens such as flutamide or bicalutamide and no estrogen produced a moderate but incomplete lobuloalveolar development. Based on the above research, it was concluded by the study authors that a combination of estrogenic and progestogenic action is required in transgender women for histologic breast development such as fully mature women (ie, including complete lobuloalveolar maturation). Also, it was observed that lobuloalveolar maturation reverses after CPA cessation after surgical castration, similar to cases of mammary gland involution in postpartum women, suggesting that continued progestogen treatment is needed to maintain histology. However, it should be noted that although these findings may have important implications in the context of lactation and breastfeeding, epithelial tissue is only about 10% of breast volume (with most breasts (80-90%) represented by stroma or adipose tissue), and uncertain , if any, that the development of the lobuloalveolar structure (a type of epithelial tissue) contributes to the size or shape of the breast.
Antigonadotropic Effects
CPAs have strong antigonadotropic effects through PR activation. It clogs the hormone releasing gonadotropin (GnRH) -the excess of gonadotropin secretion, and therefore, significantly suppresses the circulating luteinizing hormone (LH) and follicle stimulating hormone (FSH) at a sufficiently high dose. As a result, levels of progesterone, androstenedione, testosterone, DHT, and estradiol are also significantly lowered at fairly high doses, while elevated levels of sex hormone binding globulin (SHBG) and prolactin levels are observed. CPA can reduce circulating testosterone concentrations by 70 to 80% in men with a high enough dose. However, regardless of the strong emphasis of testosterone, CPA, at least by itself (eg, without estrogen), it usually can not reduce testosterone levels into the castrate/lady distance (<50 ng/dL) at any dose, and testosterone levels generally remain above it at a circulating rate of about 50 to 100 ng/dL.
Doses as low as oral CPA of 10 mg/day have been found to suppress testosterone levels circulating in men by 50 to 70%. In comparison, a high dose of 100 mg/day oral CPA was found to suppress testosterone levels circulating in men around 77% and a very high dose of 300 mg/week intramuscular BPA was found to suppress testosterone levels circulating in men around 76% found differences in suppression of testosterone levels circulating in transgender women with a combination of estrogen and oral CPA 25 Âμg/day (95% emphasis) and estrogen combination and 50 μg/day oral CPA (94% emphasis). Estrogens used were oral or transdermal oral estradiol (mean 3.3 mg/day orally, 3.4 g/day gel, 95.6 ppm/day patch).
Glucocorticoid activity
Because of the negative feedback on the hypothalamic-pituitary-adrenal (HPA), administration of glucocorticoids exogenous 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, which produce adrenal suppression and atrophy and, after the cessation of glucocorticoid , temporary adrenal insufficiency. Similarly, although relatively weak, CPA has the ability to reduce the levels of ACTH and cortisol and the adrenal glands produce shrinkage, as well, after the suspension, adrenal insufficiency, in animals and humans, suggesting that he had a weak glucocorticoid properties. But paradoxically, in vitro , CPA is a glucocorticoid receptor antagonists (GR) and suppressing the production of cortisol and adrenal corticosteroids by inhibiting the enzyme 3 -hidroksieroid dehydrogenase and 21-hydroxylase, which is antiglukokortikoid. action. This paradox can be explained by the fact that some of the active metabolite of CPA, as its main metabolite 15 -hydroxycyproterone acetate (which is present in the serum levels of approximately two times that of the CPA in humans), by contrast, GR agonist, and it can be assumed that their overall glucocorticoid action greater than simultaneous anticonecep- ticoid actions of the CPA. Both cyproterone and CPA, through their metabolites, have been found to have a glucocorticoid effect, and based on studies in mice, it has been suggested that CPAs have about one-fifth of prednisone potential as glucocorticoids.
While studies have clearly shown decreased levels of cortisol and ACTH and ACTH response in humans with CPA treatment, several studies contradict this finding and report no such effects even with high doses.
Megestrol acetate, medroxyprogesterone acetate, and chlormadinone acetate, steroid progestin and near analogue of CPA, all have glucocorticoid properties and the potential to produce adrenal insufficiency at the time of discontinuation.
Other activities
CPA has been found to bind non-selectively to opioid receptors, including receptor subtypes? -? -, and? -soioid, although very weak relative to other actions (IC 50 for inhibition of [ 3 H] diprenorphine binding = 1.62 Ã, Â ± 0.33 ÂμM). It has been suggested that activation of opioid receptors may have the potential to account for the sometimes occurring side effects of sedation at high doses with CPA treatment or its effectiveness in the treatment of cluster headaches.
Pharmacokinetics
Absorption
Oral bioavailability of CPAs is reported to be 100%. However, it has also been said that CPA is poorly absorbed from the gastrointestinal tract and must be taken after food consumption, which will implicitly increase its absorption.
Distribution
In the case of plasma binding proteins, CPAs do not bind to SHBG or corticosteroid-binding globulin and are not exclusively bound for albumin (93%), with the remainder (7%) free or unbound.
Metabolism
CPA is metabolized mainly by hydroxylation through CYP3A4, forming a major active metabolite 15? -hydroxycyproterone acetate. This metabolite circulates at a concentration approximately twice that of CPA, and has antiandrogen activity similar to CPA but only 10% of its activity as a progestogen. Consequently, co-administration of CPAs with drugs inhibiting CYP3A4 may increase its potency as a progestogen.
Some of the digested CPAs are metabolized by hydrolysis to cyproterone and acetic acid. However, unlike many other steroid esters, CPAs are not extensively hydrolyzed, and many pharmacological activities of these drugs are caused by CPA itself in unchanged form. Cyproterone has about one-third of CPA potential as an antiandrogen and has no progestogenic activity.
The oral half-life of the oral CPA is relatively long at about 38 hours. However, regardless of this, the drug is usually given in divided doses two to three times per day when used orally in the treatment of prostate cancer. When administered via intramuscular depot injection, the CPA circulation level peaked at 82 hours and the drug had a 72-hour elimination half-life.
Excression
CPA is excreted 70% in stool and 30% in urine.
Chemistry
CPA, also known as 6-chloro-1,2? -methylene-17? -acetoxy -? 6 -progesterone or as 6-chloro-17? -hydroxy-1 ?, 2? -methylenepregna -4,6-diene-3,20-dione acetate, is a synthetic pregnancy steroid and an acetylation derivative of 17? -hydroxyprogesterone. It is structurally related to other 17-hydroxyprogesterone derivatives such as chlormadinone acetate, hydroxyprogesterone caproate, medroxyprogesterone acetate, and megestrol acetate.
History
The CPA was discovered in the early 1960s, and Rudolf Wiechert, a Schering employee, together with F. Neumann in Berlin filed a patent as a "progestational agent" in 1962. Only one year after the patent agreement in 1965, Neumann published evidence of an antiandrogenic CPA effects on mice; he reported "the effect of CPA organizations in the brain". During the same year, in 1966, prenatal prenatal CPA in male rats was shown to cause urogenital malformation by a group in Lund, Sweden. CPAs are being used in animal experiments around the world to investigate how antiandrogens affect fetal sexual differentiation.
In 1970, the first human experiment with CPA began with measuring serum levels after oral administration, spermatogenesis levels, and hair growth in women. Beginning in 1972, psychiatrists tested "sexually distorted people" with the CPA. In 1973, the CPA was first approved in Europe, under the brand name Androcur. Until the development of leuprolide, CPA is one of several drugs used to treat puberty prematurely. The CPA was first marketed in combination with EE as an oral contraceptive in 1978 under the brand name Diane.
Together with steroid benorterone (17? -methyl-B-nortestosterone, SKF-7690), cyproterone, BOMT (Ro 7-2340), and trimethyltrienolone (R-2956) and nonsteroidal flutamide and DIMP (Ro 7-8117), CPA one of the first antiandrogens to be discovered and studied.
Society and culture
Common names
English and CPA generic names are cyproterone acetate and this is USAN , BAN , and JAN . The generic and generic English name of cyproterone is cyproterone and this is INN and BAN , while cyprotÃÆ' Â © rone is DCF and the French name and ciproterone is DCIT and the Italian name. The un-esterified cyproterone name in Latin is cyproteronum , in German is cyproteron , and in Spanish is ciproterona . These cyproterone names correspond to CPAs for acÃÆ' Â © tate de cyprotÃÆ' Â © rone in French, acetato de ciproterona in Spanish, ciproterone acetato in Italian, cyproteronacetat in German, cyproteronacetaat in Dutch, and ciproteron acetate in Slavic.
CPAs are also known under the development code SH-80714 and SH-714 , while cyproterone unacetylated is known as development code SH-80881 and SH-881 .
Brand name
CPAs are marketed under trademarks including Androcur, Androcur Depot, Androcur-100, Androstat, Asoteron, Cyprone, Cyproplex, Cyprostat, Cysaxal, Imvel, and Siterone. When the CPA is formulated in combination with EE, it is also known as co-cyprindiol , and the brand names for this formulation include Andro-Diane, Bella HEXAL 35, Chloe, Cypretil, Cypretyl, Cyproderm, Diane, Diane Mite, Diane-35, Dianette, Dixi 35, Drina, Elleacnelle, Estelle, Estelle-35, Ginette, Linface, Minerva, Vreya, and Zyrona. CPA is also marketed in combination with estradiol valerate as Climen, Climene, Elamax, and Femilar.
Availability
CPAs are widely available worldwide, and marketed in almost every developed country, with the exception of the United States and Japan. In Japan, chlormadinone acetate-related drugs are used instead. CPAs are marketed on their own and combined with EE or estradiol valerate. Special places where CPAs are marketed include the UK, elsewhere across Europe, Canada, Australia, New Zealand, South Africa, Latin America, Asia.
Research
CPAs have been studied for use as potential male hormonal contraceptives in combination with testosterone in men.
CPA is being developed by Barr Pharmaceuticals in the 2000s for the treatment of hot flashes in patients with prostate cancer in the United States. It achieved phase III clinical trials for this indication and had a temporary CyPat brand name but the development was eventually discontinued in 2008.
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