Women with functional hypothalamic amenorrhea but not other forms of anovulation display amplified cortisol concentrations

Objective: To test the hypothesis that increased cortisol secretion is specific to women with decreased GnRH drive and not found in eumenorrheic women or those with other causes of anovulation. Design: Cortisol concentrations in blood were determined at 30-minute intervals for 24 hours in three well-characterized groups: women with functional hypothalamic amenorrhea, those with other causes of anovulation, and eumenorrheic women. Setting: Academic medical center. Patient(s): Women aged 20 through 35 years, with well-defined reproductive states. Intervention(s): Venous blood samples were obtained from, and psychometric inventories were completed by, the participants. Main Outcome Measure(s): Twenty-four-hour cortisol levels, 24- hour LH pulse patterns, and serial P levels were measured in women with functional hypothalamic amenorrhea, eumenorrheic women, and those with other causes of anovulation. Result(s): Cortisol secretion was higher in women with functional hypothalamic amenorrhea (n = 19) than in those with other causes of anovulation (n = 19) or eumenorrheic women (n = 19). Six women who recovered from functional hypothalamic amenorrhea had cortisol levels comparable to those of eumenorrheic women and those with other causes of anovulation. Conclusion(s): These data underscore the association between increased hypothalamic-pituitary-adrenal activity and reduced GnRH drive and support the concept that functional hypothalamic amenorrhea develops in response to stress-induced alterations in central neural function that modify hypothalamic function.