And Antiandrogen Therapies

Antiandrogens are molecules that bind the androgen receptor (AR) and act as androgen antagonists at the target cell level. Cyproterone acetate (CPA) and spironolactone are the most commonly used androgenic antagonists [3, 12].

Additional hormonal treatment of hyperan-drogenism includes: (1) inhibition of the conversion of testosterone (T) into its active metabolite dihydrotestosterone (DHT) through 5a-reductase inhibition; (2) suppression of ovarian androgen production with oral contraceptives (OC); (3) elevation of sex-hormone-binding globulin (SHBG) levels through oestrogens, either natural oestradiol, (E2, as oestrogen therapy) or ethinyloestradiol (EE, with OC), with a further decrease in plasma free androgen levels (Table 16.1).

Table 16.1. Treatments for androgenic disorders

Antiandrogens = androgenic antagonists

Cyproterone acetate

Spironolactone

Others

5a-Reductase inhibition Finasteride

Ovarian suppression Combination OC Progestogens (non-androgenic) Oestrogens

Increase of SHBG Oestrogens

Combination OC (non-androgenic) Weight loss

Non-hormonal Depilation, epilation Anti-acne (retinoids, antibiotics)

CPA is a progestin with several antiandrogenic activities: binding to AR, inhibition of androgen metabolism and antigonadotropic activity. CPA has been used extensively in Europe for 30 years in the treatment of hirsutism. It can be given according to various regimens (usually 50 mg daily on days 1-20 of each menstrual cycle, but other regimens are possible with CPA of 50 or 100 mg) together with natural E2 or with an OC pill. Good results may be obtained in hirsutism and also in women with severe and/or persistent acne or with androgenic alopecia. Side-effects are uncommon and the anti-androgen is well tolerated [6, 11, 17, 18].

Spironolactone is the most generally used anti-androgen in countries where CPA has not been approved. Spironolactone binds to AR but is devoid of antigonadotropic activity. Doses needed for antiandrogenic efficacy are 75-200 mg daily depending upon the indication (acne, alopecia or hirsutism). Concomitant use of OC or a non-androgenic progestin can prevent menstruation disorders. Tolerance is good even on long-term therapy [3, 10].

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