EFFECTS OF SYNTHETIC ORAL OESTROGENS IN NORMAL MEN AND PATIENTS WITH PROSTATIC CARCINOMA: LACK OF GONADOTROPHIN SUPPRESSION BY CHLOROTRIANISENE

Abstract

SUMMARY: The effects of the oral synthetic oestrogens, diethylstiboestrol and chlorotrianisene, have been studied in healthy male volunteers and in patients with prostatic carcinoma. The plasma levels of follicle stimulating hormone, luteinizing hormone and testosterone decreased significantly during treatment with diethylstilboestrol. Although plasma levels of testosterone decreased during treatment with chlorotrianisene, levels of follicle stimulating and luteinizing hormones were not significantly suppressed. This pattern of response was observed both in healthy males and in patients with prostatic carcinoma, regardless of whether chlorotrianisene was used as the primary therapy in the latter group or following therapy with diethylstilboestrol or orchidectomy. The capacity of the sex steroid binding globulin for testosterone was increased following prolonged administration of both agents. It is concluded that suppression of plasma testosterone levels observed during chlorotrianisene therapy is the result of a direct effect on the testis and that this agent may be of value in studies of gonadotrophin physiology.Although the palliative effect of treating prostatic carcinoma with synthetic oestrogens such as diethylstilboestrol (DES) and chlorotrianisene (CTA) has been known for many years, the mechanism of this action is obscure. It is generally believed that reduction of circulating androgens secondary to suppression of pituitary gonadotrophin secretion is the main effect, but it is possible such drugs have direct effects both on the testis and the carcinoma. During investigations designed to evaluate the mode of action of these two drugs, an interesting difference emerged between their effects on serum levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH). An earlier study had demonstrated that when a patient who had been previously treated with DES was given CTA, plasma levels of testosterone remained low despite rising levels of FSH and LH (Burger et al., 1972). This paper reports the results of more detailed investigations of the effects of DES and CTA in healthy volunteers and in patients with carcinoma of the prostate.