Muscle Female Steroids Cyproterone Acetate 427-51-0 For Muscle Gaining

Muscle Female Steroids Cyproterone Acetate 427-51-0 For Muscle Gaining

Basic Information

Description

Cyproterone acetate (abbreviated as CPA), also sold under brand names such as Androcur among others, is a synthetic, steroidal antiandrogen, progestin, and antigonadotropin. It is primarily used in the treatment of androgen-related conditions by virtue of its ability to suppress androgenic activity in the body, an effect which it mediates by preventing endogenous androgens from interacting with the androgen receptor and by suppressing androgen biosynthesis. CPA is also used for its progestogenic effects, for instance, as a component of some combined oral contraceptive pills in combination with ethinyl estradiol (EE), such as in Diane-35 among others.

Medical uses

CPA has been in use as an antiandrogen since 1964, and was the first antiandrogen introduced for clinical use. It is used widely throughout Europe, and is also used in Canada, Mexico, and other countries. It is not FDA-approved for use in the United States, due to concerns about hepatotoxicity; medroxyprogesterone acetate has been used in the United States instead. CPA has been approved for the treatment of prostate cancer, precocious puberty, androgen-related dermatological conditions such as acne, seborrhea, hirsutism, and androgenic alopecia, and to reduce sex drive in sex offenders. Combination formulations of CPA with EE, a formulation sometimes referred to as co-cyprindiol, have been available as contraceptives since 1997.

Other uses of CPA include the treatment of benign prostatic hyperplasia, priapism, hypersexuality, paraphilias, hot flashes, and hyperandrogenism in women. In addition, with the exception of the United States, where it is not available and spironolactone, a diuretic with antiandrogen properties, is generally employed instead, CPA is widely used as a component of hormone replacement therapy (HRT) for trans women.

In the treatment of acne in women, a formulation of daily CPA in combination with EE has been found to result in overall improvement in 75–90% of people, with responses approaching 100% improvement.

Investigational

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

Side effects

Feminization

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. 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.

Depression

CPA has been associated with an increased rate of depression in both men and women. 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. Also, a study found that around 20% of women treated with Dianette (which contains only 2 mg CPA) for contraceptive purposes developed depression. 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 trans 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)). The depressive effects of CPA may be related to its glucocorticoid, antiandrogen, and/or antigonadotropic effects, as glucocorticoids, antiandrogens (in men), and GnRH analogues have all been associated with depression. Vitamin B12 deficiency induced by CPA might also or alternatively be a critical factor. Because of the side effect of depression, CPA 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 (2 mg/day) CPA in combination with EE has also been associated with vitamin B12 deficiency. It is notable that vitamin B12 deficiency is associated with depression, anxiety, irritability, and fatigue via depletion of central monoamine neurotransmitters, and it has been suggested that this may be involved in the adverse neuropsychiatric consequences commonly observed with CPA therapy. Serum vitamin B12 monitoring and supplementation as necessary is recommended during CPA treatment.

Blood clots
Used alone, CPA does not appear to have a significant effect on blood clotting factors, but in combination with EE, as in combined oral contraceptive pills, presents an increased risk of deep vein thrombosis. 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. At least four cases of fatal venous thromboembolism have been attributed to low-dose CPA in combination with EE.

Hepatotoxicity

The most serious potential side effect of CPA is hepatotoxicity. 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. Clinical features may include jaundice, fatigue, nausea, elevated liver enzymes, hepatic necrosis and inflammation, and features of hepatic decompensation. 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.

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. 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%. 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.Yet another study of 105 patients found a hepatotoxicity rate of 9.5%, with serious hepatic injury occurring in 3.8%.[33] 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. 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. 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. As such, the prognosis of CPA-induced liver failure is fatal.

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. Patients being treated with high-dose CPA should be closely monitored with liver function tests. 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. 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.

Meningiomas

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). For this reason, high-dose CPA is contraindicated in people with meningioma or a history of meningoma.

Miscellaneous

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

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.

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

Withdrawal

Abrupt withdrawal of CPA can be harmful, and the package insert from Schering AG recommends that the daily dose be reduced by no more than 50 mg at intervals of several weeks. The primary 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. 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.

Adrenal insufficiency

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.

Antiandrogen withdrawal syndrome

A paradoxical effect occurs with certain prostate cancer cells which have genetic mutations in their androgen receptors. These altered androgen receptors 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.

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