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Cyproterone acetate (CPA) has been discovered more than 25 years ago and it was the first antiandrogen suitable for clinical use. CPA inhibits the action of endogenous and exogenous androgens at all androgen target organs; these include the prostate, seminal vesicles, testes, and the vas deferens. However, this antiandrogen also antagonizes less sex-specific effects of androgens, for example ossification of the epiphyseal cartilage, sebaceous gland function and skin thickness. Indications for CPA: Prostate cancer, androgen induced disorders of the skin (acne, seborrhoea, hirsutism, alopecia), precocious puberty and sexual disorders in men. Concerning sexual deviations clinical trials started in 1966. CPA leads to loss of libido and the ability to achieve erection, followed by the inability to achieve orgasm, after about 14 days of treatment (100-200 mg daily orally or 300 mg weekly i.m.). These effects are reversed in the same order as the onset. About 75 to 80% of patients respond to this therapy. CPA is generally well tolerated. Tiredness, lack of drive, listlessness and depressive moods have been reported as non-specific side-effects. Slight gynecomastia occurs in about 20% of patients. There are no good alternatives in this indication. Pure antiandrogens are unsuitable, because these are unable to inhibit libido sufficiently. Tranquilizers are not very effective, high doses of estrogens are associated with severe (cardiovascular) side effects. Orchidectomy is an irreversible intervention, LHRH analogues are associated with hot flushes and the initial increase in testosterone (flare phenomenon).

It is reported the accumulated experience over the last ten years on a synthetic gestegen with a powerful antiandrogenic action: the cyproterone acetate. The effects on androgen dependent processes like: structure and function of genital accesory glands, on skin and sebaceous glands, bone maturation and growth, libido and testicular function are reported, together with the clinical results obtained in the treatment of acne, hirsutism, sexual perversions and as male anticonceptive. The influence of cyproterone acetate on the androgen dependent embrionary processew of differentiation are also discussed as wll as the female anticonceptive action and its effects on other endocrine systems.

Principally, antiandrogens affect all androgen-dependent organs and functions as for instance accessory sexual glands, spermatogenesis, skin and skin appendages, libido and potency, male sexual differentiation, longitudinal bone growth and bone maturation. Pharmacologically, it is important to distinguish between the steroidal antiandrogens of the cyproterone acetate type and the nonsteroidal pure antiandrogens (flutamide, anandrone). For the clinical use of cyproterone acetate and similar antiandrogens in both men and women the three main properties are important: Cyproterone acetate is antiandrogenic, it is a quite potent progestogen and it is antigonadotrophic. Based on pharmacological and biochemical backgrounds cyproterone acetate is used in the following indications: Androgen mediated disorders of the skin such as acne, seborrhoea, hirsutism, alopecia, advanced prostatic carcinoma, precocious puberty and male hypersexuality. In order to avoid undesired systemic side effects local application of antiandrogens, e.g. of cyproterone acetate, has been tried several times. All these attempts have failed probably because insufficient concentration of the antiandrogen at the pilo sebaceous unit. 17 alpha-propylmesterolone is active when given topically (hamster ear model) and has no systemic antiandrogenic effects. This antiandrogen is highly lipophilic and does penetrate preferentially through the hair follicle as has been shown by autoradiography.

Unlabelled: The first antiandrogen which was also of clinical interest--cyproterone acetate (CPA)--was discovered at the beginning of the 60th. CPA acts in all target organs for androgens and in principle affects all functions which are governed or influenced by androgens under physiological or pathophysiological conditions., Examples: Accessory sexual gland function and spermatogenesis are inhibited, there is a loss of libido in most species, the onset of puberty and bone maturation is delayed, sebaceous gland function and lipogenesis is inhibited, androgen mediated steps in male sexual differentiation do not occur. CPA is also a highly effective progestrogen and it inhibits gonadotrophine secretion. The progestational partial effect is especially important for the use of this drug in women in the treatment of certain dermatological disorders. CPA has certain glucocorticoid-like properties in animals. In humans these effects were only seen under high-dose therapy of children with precocious puberty (greater than 80 to 100 mg/m3 body area) but never in adults. Proven indications for CPA: Prostatic carcinoma, precocious puberty, hypersexuality and sexual deviations, androgenization in women (hirsutism, acne, seborrhoea oleosa, alopecia androgentica).

The effect of a new antiandrogenic steroid, 6-chloro-17-hydroxy-la,2a-methylenepregna-4,6-diene-3,20-dione acetate (cyproterone acetate) on sebaceous glands of mature male mice as well as mature castrated mice treated with testosterone propionate has been studied qualitatively and quantitatively. A dosage of 1 mg cyproterone acetate every second day for a period of 4 weeks induces a reduction of the relative total sebaceous gland volume of about 80% in intact mice. The stimulant effect of 0.5 mg testosterone propionate every second day and over a period of 4 weeks on sebaceous glands is inhibited by the simultaneous treatment with 1 mg cyproterone acetate every second day. The effect of cyproterone acetate produces a decrease of the number of sebaceous gland alveoli, elicits a reduction of the number of cells per alveolus as well as a decline in cell size. The thickness of the epidermis was decreased in the animals treated with cyproterone acetate. The mechanism of action of this antiandrogen has been explained by a competitive testosterone antagonism since, in contrast to estrogens, the stimulant effect of exogenous testosterone on sebaceous glands is also inhibited.