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Progestogens with Antiandrogenic Properties

Abstract

Chlormadinone acetate, cyproterone acetate and dienogest are potent, orally active progestogens, which have antiandrogenic instead of partial androgenic activity. They act mainly by blocking androgen receptors in target organs, but also reduce the activity of skin 5α-reductase, the enzyme responsible for converting testosterone to the more potent androgen, 5α-dihydrotestosterone, in sebaceous glands and hair follicles. Chlormadinone acetate and cyproterone acetate also suppress gonadotropin secretion, thereby reducing ovarian and adrenal androgen production.

Combined oral contraceptives (COCs) containing antiandrogenic progestogens provide highly effective contraception (gross and adjusted Pearl indices: 0–0.7 and 0–0.3, respectively) with excellent cycle control. Furthermore, COCs containing 2mg of chlormadinone acetate or cyproterone acetate plus 30 or 35μg of ethinylestradiol produced improvement or resolution of seborrhoea in 80% of users, acne in 59–70%, hirsutism in 36% and androgen-related alopecia in up to 86%.

These COCs are generally well tolerated, the main adverse effects being nonspecific or as expected for a COC (headache, breast tenderness and nausea). They have no clinically relevant effects on metabolic or liver functions or on body-weight. Effects on mood and libido are uncommon (<3.5% and <6% of women, respectively).

COCs containing antiandrogenic progestogens are likely to be particularly valuable in women with pre-existing androgen-related disorders who require contraception. They also increase the choice of products available for women with normal skin and hair who are concerned about the possibility of developing seborrhoea or acne with other COCs.

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Raudrant, D., Rabe, T. Progestogens with Antiandrogenic Properties. Drugs 63, 463–492 (2003). https://doi.org/10.2165/00003495-200363050-00003

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Keywords

  • Androgen Receptor
  • Acne
  • Ethinylestradiol
  • Cyproterone Acetate
  • Dienogest