A longitudinal study of disturbances of the hypothalamic-pituitary-adrenal axis in women with progestin-negative functional hypothalamic amenorrhea

Objective: To longitudinally evaluate disturbances of the hypothalamic-pituitary-adrenal (HPA) axis in women with secondary progestin-negative hypothalamic amenorrhea. Design: Retrospective cohort study. Setting: Yokohama City University, Yokohama, Japan. Patient(s): Twenty-four women with progestin-negative hypothalamic amenorrhea. Intervention(s): Administration of human corticotropin-releasing hormone (hCRH) and treatment with a combination of estrogen and progesterone. Main Outcome Measure(s): Plasma cortisol and ACTH concentrations and period required for recovery from amenorrhea. Result(s): Plasma ACTH concentrations 30 and 60 minutes after injection of hCRH and the percent maximum increment (%Cmax) of ACTH were significantly lower in the amenorrheic patients compared with the control group patients. The basal cortisol was significantly higher, and the %Cmax of cortisol was significantly lower. In the 16 patients who recovered from amenorrhea, there was a significant positive correlation (Y = 1.93X- 10.8, r = 0.629) between the basal cortisol concentrations (X) and the period for recovery (Y). The serum E-2 gradually increased before recovery, and this E-2 increase was preceded by changes in the plasma cortisol concentration and the %C-max values of cortisol and ACTH. Conclusion(s): The CRH test might be useful for evaluating the roles of stress and for estimating the period required for recovery in hypothalamic amenorrhea. (Fertil Steril(R) 2001;76:748-52. (C) 2001 by American Society for Reproductive Medicine.).