Suppression of the hypothalamic-pituitary-ovarian axis in normal women by glucocorticoids

To determine whether cortisol has an effect on hypothalamic-pituitary-gonadal function, we studied 11 eumenorrheic women in the early follicular phase of consecutive menstrual cycles by performing daytime 10-min blood sampling, one before and one during hydrocortisone administration. Daily blood sampling for gonadotropins and sex steroids was also performed. LH pulsations were determined by modification of a widely used threshold method and compared by paired t-testing. The LH interpulse interval was significantly prolonged (95 +/- 5 to 119 +/- 14 min; p = 0.001), and the mean LH pulse amplitude remained unchanged (1.3 +/- 0.1 and 1.5 +/- 0.2 mIU/ml) with glucocorticoid exposure. Mean estradiol was not altered (46 +/- 5 and 43 +/- 3 pg/ml), but mean LH and FSH from pooled serum aliquots were slightly but significantly reduced (2.6 +/- 0.2 to 2.2 +/- 0.2, 5.5 +/- 0.4 to 4.5 +/- 0.3 mIU/ml; p = 0.004, 0.012, respectively). Mean progesterone levels were also decreased (0.8 +/- 0.3 to 0.5 +/- 0.2 ng/ml; p = 0.011) in the presence of exogenous glucocorticoid. Twenty-four-hour urinary free cortisol levels confirmed a substantial increase in free cortisol excretion (74 +/- 10 to 305 +/- 50 micrograms/day; p = 0.001). These results demonstrate that cortisol can slow LH pulse frequency and, by inference, hypothalamic GnRH secretion, in a manner that appears independent of corticotropin releasing factor. Excess cortisol alone may therefore play a role in the development of stress-associated menstrual disturbances.