Cyproterone

Cyproterone is a steroidal antiandrogen that was researched in the 1960s and 1970s but was never introduced for medical use. It is an analog of cyproterone acetate (CPA), an antiandrogen, progestin, and antigonadotropin that was introduced in place of cyproterone and is widely used as a medication. Cyproterone and CPA were among the first antiandrogens to be developed. It is important to clarify that the term cyproterone is often used as a synonym and abbreviation for cyproterone acetate, and when the term occurs, confusingly, it almost always means CPA and not really cyproterone. Cyproterone itself, unlike CPA, has never been introduced for medical use and is therefore not available as a drug. Therefore, only cyproterone acetate, which is in use, will be discussed below. CPA is used as a progestin and antiandrogen in hormonal birth control and in the treatment of androgen-dependent conditions. Specifically, CPA is used in combined birth control pills, in the treatment of androgen-dependent skin and hair conditions such as acne, seborrhea, excessive hair growth and scalp hair loss, high androgen levels, in transgender hormone therapy, to treat prostate cancer, to reduce sex drive in sex offenders or men with paraphilias or hypersexuality, to treat early puberty, and for other purposes. It is used in both low doses and higher doses.

Pharmacodynamics

CPA has antiandrogenic activity, progestogenic activity, weak partial glucocorticoid activity, weak steroidogenesis inhibitor activity, and agonist activity at the pregnane X receptor. It has no estrogenic or antimineralocorticoid activity. In terms of potency, CPA is described as a highly potent progestogen, moderately potent antiandrogen, and weak glucocorticoid. Due to its progestogenic activity, CPA has antigonadotropic effects and is capable of suppressing fertility and sex hormone levels in both men and women.

Pharmacokinetics

CPA can be applied by mouth or by injection into muscle. It has almost complete oral bioavailability, exhibits high plasma protein binding while being bound exclusively to albumin, and is metabolized in the liver by hydroxylation and conjugation. It has a long elimination half-life of approximately 2 to 4 days, regardless of route of administration, and is excreted primarily in the feces and to a lesser extent in the urine.

Side effects

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 (temporary) infertility, sexual dysfunction, fatigue, depression, weight gain, and elevated liver enzymes. Significant cardiovascular complications may occur at very high doses in the elderly.

Rare but serious side effects of CPA include blood clots, liver damage, and certain types of benign brain tumors. CPA may also cause adrenal insufficiency as a withdrawal effect if abruptly discontinued from a high dosage.