The early hormonal changes that lead to follicular maturation and/or hyperstimulation in women requiring ovulation induction with either human menopausal gonadotropin or gonadotropin-releasing hormone have not been elucidated. This study was undertaken to assess the relative contribution of follicle-stimulating hormone and luteinizing hormone to estradiol secretion and follicular maturation in patients receiving human menopausal gonadotropin or gonadotropin-releasing hormone. The study group consisted of 10 women (26 to 38 years of age) with secondary amenorrhea as a result of hypothalamic dysfunction who had failed to ovulate when given clomiphene citrate. The patients were randomly assigned to either human menopausal gonadotropin (n = 5) or gonadotropin-releasing hormone (n = 5) treatment. On day 5 after the onset of induced menses, all women had baseline blood samples obtained at 10-minute intervals for 4 hours. At this time either 150 U of human menopausal gonadotropin or 75 ng/kg of gonadotropin-releasing hormone administered hourly was given, and blood sampling every 10 minutes was continued for an additional 6 hours. Thereafter, patients were evaluated daily until ovulation. A significant and sustained increase in the mean plasma follicle-stimulating hormone level was first measured during the third hour after human menopausal gonadotropin administration (p less than 0.05. The area under the curve of the mean plasma follicle-stimulating hormone value after this initial increase was significantly greater than its baseline (2119 +/- 240 versus 1425 +/- 188 mlU/ml; p less than 0.01). This rise in mean follicle-stimulating hormone level was followed in less than 2 hours by a significant and uniform rise in mean plasma estradiol concentration (p less than 0.05). In contrast, no immediate change in the mean levels of luteinizing hormone, follicle-stimulating hormone, or estradiol occurred after gonadotropin-releasing hormone administration. The mean daily levels of luteinizing hormone were similar in both groups; however, mean daily follicle-stimulating hormone (20.0 +/- 1.1 versus 9.2 +/- 1.4 mlU/ml) and estradiol (1004 +/- 174 versus 495 +/- 83 pg/ml) levels were significantly higher in patients treated with human menopausal gonadotropin than in those treated with gonadotropin-releasing hormone (p less than 0.001 and p less than 0.05, respectively). In addition, only in patients receiving human menopausal gonadotropin was a positive correlation found between mean daily plasma estradiol and follicle-stimulating hormone (r = 0.685, p less than 0.05) levels and between mean daily plasma estradiol and prolactin (r = 0.94, p less than 0.001) levels.(ABSTRACT TRUNCATED AT 400 WORDS)