Low-dose cyproterone acetate plus mini-dose diethylstilbestrol--a protocol for reversible medical castration

To determine whether a low dose of cyproterone acetate (CPA) (50 mg twice a day) with minidose diethylstilbesterol (DES) is efficacious in rapidly reducing and maintaining serum testosterone at less than 10% of pretreatment level and whether the effect is reversible upon cessation of therapy.

Data were collected prospectively on 62 subjects, aged 50 to 90 years (mean 69) with histologically confirmed prostate cancer and normal serum testosterone levels. Treatment was initiated with CPA 50 mg twice a day plus DES 0.11 mg once a day, both administered orally, and continued or 6 months unless discontinued for reasons unrelated to the study. Subsequent management was at the discretion of the investigator/managing physician. Treatment was discontinued with determination of at least one follow-up testosterone level in 28 patients.

Mean pretreatment testosterone level was 13.8 nmol/L (range 4.5 to 46.6, median 14.0, 95% confidence interval [CI] 12.0 to 15.0). Testosterone dropped to a mean of 0.6 nmol/L (range 0.1 to 2.2, median 0.5, 95% CI 0.4 to 0.6) by first follow-up (usually 1 month) in all patients (P <0.001) and remained at this level as long as treatment continued. Testosterone normalized in all subjects whose treatment was discontinued. Side effects were minimal.

An oral dosage of CPA of 50 mg twice a day in combination with a mini-dose of DES results in rapid and reversible reduction in serum testosterone to castrate levels. This regimen minimizes morbidity and monetary costs of therapy and allows the implementation of novel treatment approaches such as intermittent or neoadjuvant withdrawal therapy.