Abnormal Cortisol Secretion and Responses to Corticotropin-Releasing Hormone in Women with Hypothalamic Amenorrhea*

Hypothalamic amenorrhea (HA) is a common disorder associated with hypoestrogenemia and has adverse effects. The mechanism of GnRH deficiency in these women is not yet known. To investigate the role of the hypothalamic - pituitary-adrenal axis in HA, we studied 10 women [means age, 29 ± 7 (±sd) yr] with 0.5–13 yr of amenorrhea (mean, 4.3 ± 3.7 yr) related to simple weight loss or psychological stress. We investigated cortisol and ACTH responses to a bolus of ovine CRH, 24-h plasma cortisol levels obtained every 10 min, and urinary free cortisol levels in these patients. Results were compared with those obtained in normal women during all phases of the menstrual cycle. We found that mean basal concentrations of cortisol were significantly higher (P = 0.03) in the HA patients (mean, 210 ± 130 nmol/L) than in the normal women (100 ± 30 nmol/L). The Δ (peak - basal) cortisol was significantly lower (P = 0.004) in the HA patients than in the normal women (320 ± 100 vs. 440 ± 90 nmol/L, respectively). ACTH respo...