Hypothalamic function in women with secondary hypogonadism and unresponsive to clomiphene therapy

Seven women with secondary hypogonadism who had been previously unresponsive to two 5-d courses of clomiphene citrate, were treated with clomiphene citrate 100 mg daily for 10 d. LH and FSH concentrations were measured in serum collected at 15-min intervals for 5 h before and on the 10th day of treatment and oestradiol was measured in the first two samples on each day. Four women responded with an increase in the amplitude of LH pulses and in mean LH values and in three there was a marked increase in serum oestradiol concentrations. Three women who showed no gonadotrophin response were subsequently unresponsive to pulsatile LHRH therapy. These preliminary data are consistent with the hypothesis that hypothalamic hypogonadotrophism may result from hypersensitivity of the hypothalamus to oestrogen negative feedback and that the hypothalamic potential for secretion of LHRH is unimpaired. Prolonged treatment with clomiphene may provide a simple test of hypothalamic function in women with normal pituitary function.