The effect of flutamide on pulsatile gonadotrophin secretion in hyperandrogenaemic women

The pulsatile gonadotrophin secretion in hyperandrogenaemic women was examined, following short-term androgen antagonism induced by flutamide, a specific androgen receptor blocker. Flutamide was administered to seven hyperandrogenaemic women and five normal cycling women, at a dose of 250 mg on the evening of day 1, followed by daily doses of 750 mg for 6 days. Blood samples were collected at 10 min intervals for 8 h before (day 1) and during treatment (days 2 and 6). Gonadotrophin and prolactin concentrations were measured in all samples while sex hormone concentrations were analysed in selected samples. Flutamide administration to hyperandrogenaemic women was followed by a decrease in luteinizing hormone (LH) pulse amplitude (P < 0.05), associated with an apparent decline in mean LH concentrations. Follicle stimulating hormone (FSH) showed a significant fall after 6 days of treatment (P < 0.05). Total testosterone, free testosterone, androstenedione and dihydroepiandrosterone sulphate were significantly decreased during flutamide administration, while sex-hormone-binding globulin and oestradiol were not affected. Normal women showed no significant changes in the above mentioned parameters. These results demonstrate that short-term androgen receptor blockade with flutamide reduces gonadotrophin secretion and androgen concentration in hyperandrogenaemic women. Since flutamide is devoid of intrinsic hormonal activity, it is suggested that the observed hormonal changes are secondary to the androgen blockade.