British Journal of Obstetrics and Gynaecology February 1977. Vol84. pp 119-123
THE TREATMENT OF HIRSUTISM WITH CYPROTERONE ACETATE (AN ANTI-ANDROGEN) BY
C. J. DEWHURST
R. UNDERHILL S . GOLDMAN AND
M. MANSFIELD Institute of Obstetrics and Gynaecology, Chelsea Hospital for Women Dovehouse Street, London S W3 Summary The rationale of anti-androgen treatment for hirsutism is explained. The results are presented of treatment with cyproterone acetate of idiopathic hirsutism or hirsutism associated with polycystic ovarian disease. Ten out of 14 patients showed a good response after six months treatment. The response was dramatic in two patients.
Hammerstein and Cupceancu (1969) recommend a sequential regime of cyproterone acetate with 100 to 200 mg daily from the 5th to 14th days of the menstrual cycle and 50 pg of ethinyl oestradiol from the 5th to 25th days of the cycle. This regime was evolved for two reasons; first, the drug has a cumulative effect and reaches equilibrium in the plasma in about 14 days and in the fat in about 28 days (Gerhards et al, 1970); second, it is necessary to inhibit ovulation with certainty to obviate the possibility of the patient becoming pregnant when on the drug. Intrauterine feminization of male fetuses after administration of cyproterone acetate to pregnant rats (Hamada et al, 1963) has been reported. In males, cyproterone acetate has given rise to loss of libido, lethargy and a negative nitrogen balance; the latter effect is not seen in females on a diet adequate in calories and protein (Van Wayjen and van den Ende, 1971). Cyproterone acetate is contraindicated in liver disease. It influences the enzymatic activity of the liver, especially the glucuronyl transferase
CYPROTERONE is an anti-androgen, the chemical structure of which is similar to that of chlormadinone. The acetylated compound has strong progestogenic activity in addition to its anti-androgen activity and can be shown to convert an oestrogen-primed endometrium to a secretory pattern (Fixson, 1963; Vokaer and Kridelka, 1963). It reduces the luteinizing hormone (LH) peak (Barnes et al, 1975) but is not a reliable suppressor of ovulation (Jurgensen and Taubert, 1970; Bettendorf, 1968). The anti-androgen properties arise from the drug’s competition with testosterone at end-organ receptors (Voigt et al, 1968;Neumann, 1971). The drug has been tested extensively in animals and has been used since the 1960s in male sexual offenders (Laschet et al, 1967; Davies, 1970; Cooper et al, 1972). Because of its ability to suppress the hypothalamus its use in precocious puberty in children of both sexes is now being investigated. There are a limited number of studies of its effect on hirsute women (Barnes et al, 1975; Hammerstein and Cupceancu, 1969). 119
120 DEWHURST, UNDERHILL, GOLDMAN AND MANSFIELD TABLE Details about patients in Maximum hormone levels No, Age in 24 hour urine ( P d a hours)
Maximum hormone levels in plasma
17KS 170HCS
A
5a
LH
-
Hirsuties DuraDistribution FSH tion (MIU/ml) (years) Face Trunk Limbs
26 23 20 39
18.4 8.2 11.5 13.7
16.6 10.4 8.2 9.0
65 188 220 110
140 280 825 45
18 29 73 41
19.1 33 5.6
12.1 13.5 5.6
5 23 Hirsuties and oligomenorrhoea* 6 16 (Tpolycysticovarian 7 16 disease)
18.3 3.5 6.6
20.6 3.2 7.2
85
77 55
105
52
5.3
2.3
Hirsuties without oligomenorrhoea*
7.6 13.0 10.6 9.2 8.1 11.0 8.7
17.8 9.8 12.3 7.9 7.8 13.0 2.5
20 75 155 55
THE TREATMENT OF HIRSUTISM WITH CYPROTERONE ACETATE (AN ANTI-ANDROGEN) BY
C. J. DEWHURST
R. UNDERHILL S . GOLDMAN AND
M. MANSFIELD Institute of Obstetrics and Gynaecology, Chelsea Hospital for Women Dovehouse Street, London S W3 Summary The rationale of anti-androgen treatment for hirsutism is explained. The results are presented of treatment with cyproterone acetate of idiopathic hirsutism or hirsutism associated with polycystic ovarian disease. Ten out of 14 patients showed a good response after six months treatment. The response was dramatic in two patients.
Hammerstein and Cupceancu (1969) recommend a sequential regime of cyproterone acetate with 100 to 200 mg daily from the 5th to 14th days of the menstrual cycle and 50 pg of ethinyl oestradiol from the 5th to 25th days of the cycle. This regime was evolved for two reasons; first, the drug has a cumulative effect and reaches equilibrium in the plasma in about 14 days and in the fat in about 28 days (Gerhards et al, 1970); second, it is necessary to inhibit ovulation with certainty to obviate the possibility of the patient becoming pregnant when on the drug. Intrauterine feminization of male fetuses after administration of cyproterone acetate to pregnant rats (Hamada et al, 1963) has been reported. In males, cyproterone acetate has given rise to loss of libido, lethargy and a negative nitrogen balance; the latter effect is not seen in females on a diet adequate in calories and protein (Van Wayjen and van den Ende, 1971). Cyproterone acetate is contraindicated in liver disease. It influences the enzymatic activity of the liver, especially the glucuronyl transferase
CYPROTERONE is an anti-androgen, the chemical structure of which is similar to that of chlormadinone. The acetylated compound has strong progestogenic activity in addition to its anti-androgen activity and can be shown to convert an oestrogen-primed endometrium to a secretory pattern (Fixson, 1963; Vokaer and Kridelka, 1963). It reduces the luteinizing hormone (LH) peak (Barnes et al, 1975) but is not a reliable suppressor of ovulation (Jurgensen and Taubert, 1970; Bettendorf, 1968). The anti-androgen properties arise from the drug’s competition with testosterone at end-organ receptors (Voigt et al, 1968;Neumann, 1971). The drug has been tested extensively in animals and has been used since the 1960s in male sexual offenders (Laschet et al, 1967; Davies, 1970; Cooper et al, 1972). Because of its ability to suppress the hypothalamus its use in precocious puberty in children of both sexes is now being investigated. There are a limited number of studies of its effect on hirsute women (Barnes et al, 1975; Hammerstein and Cupceancu, 1969). 119
120 DEWHURST, UNDERHILL, GOLDMAN AND MANSFIELD TABLE Details about patients in Maximum hormone levels No, Age in 24 hour urine ( P d a hours)
Maximum hormone levels in plasma
17KS 170HCS
A
5a
LH
-
Hirsuties DuraDistribution FSH tion (MIU/ml) (years) Face Trunk Limbs
26 23 20 39
18.4 8.2 11.5 13.7
16.6 10.4 8.2 9.0
65 188 220 110
140 280 825 45
18 29 73 41
19.1 33 5.6
12.1 13.5 5.6
5 23 Hirsuties and oligomenorrhoea* 6 16 (Tpolycysticovarian 7 16 disease)
18.3 3.5 6.6
20.6 3.2 7.2
85
77 55
105
52
5.3
2.3
Hirsuties without oligomenorrhoea*
7.6 13.0 10.6 9.2 8.1 11.0 8.7
17.8 9.8 12.3 7.9 7.8 13.0 2.5
20 75 155 55
