539. HPA axis response to metyrapone is stable across menstrual cycle

      Recent studies have indicated that in the mid-luteal phase of the menstrual cycle HPA axis reactivity is enhanced and sensitivity to glucocorticoid feedback is reduced. However, it is unclear whether enhanced HPA axis reactivity in the luteal phase is a reflection of increased hypothalamic responsivity to stress, or solely a consequence of reduced glucocorticoid feedback sensitivity at the pituitary. Metyrapone challenge was performed in eight healthy women in the evening in both the early follicular and mid-luteal phases of the menstrual cycle to determine whether central drive of the HPA axis changes across the cycle. There was a significant increase in ACTH secretion in response to the metyrapone challenge (F(16,112) = 5.6, p < .0001), but there was no difference in the magnitude of the response in the luteal compared to the follicular phase (F(16,112) = 0.6, p = .9). These data suggest that hyperactivity of the principal hypothalamic secretagogues which drive the HPA axis, CRH and AVP, does not contribute to the enhanced HPA axis reactivity seen in the mid-luteal phase. These data are consistent with animal studies showing reduced hypothalamic CRH mRNA and peptide content during estrogen treatment, despite enhanced HPA axis reactivity.
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