Clomiphene citrate was administered to 17 patients with either secondary
amenorrhea or
oligomenorrhea to study its effect on hypothalamic-pituitary response. Measurement of pulsatile
gonadotropin output was accomplished utilizing samples collected every 20 minutes for 6 to 8 hours before and after
clomiphene administration. Response to 100 mug synthetic
luteinizing hormone releasing hormone (LRH) was measured at the end of the sampling period. Patients with polycystic
ovarian disease who ovulated showed increased baseline FSH and LH, decreased peak LH, and a decrease in the percentage increase over baseline for both LH and FSH. On patient wil clinical
anorexia nervosa responded to
clomiphene as an
estrogen, with lowered baseline LH and FSH values. Patients with resolving
anorexia responded to
clomiphene as an
antiestrogen, with increased baseline
gonadotropins, and decreased
gonadotropin peak values. A patient with a surgically treated
chromophobe adenoma showed no change in parameters measured before and after
clomiphene administration. Baseline and pulsatile LH output appear to reflect the tonic output of
gonadotropin as affected by
estrogen acting in a negative feedback system, and the peak response to LRH administration, the response to the positive feedback of
estrogen. Thus, LRH stimulation in clomipheneresistent patients may be of value in diagnosing the site and degree of the defect and aid in improving
therapy.