HPO Axis Feedback Integrity as a Modifiable Determinant of Perimenopause Onset and Severity

If chronic disruption to the hypothalamic-pituitary-ovarian (HPO) feedback loop (via cortisol competition with progesterone, estradiol receptor downregulation, and infradian rhythm suppression) accelerates the loss of HPO sensitivity that characterizes perimenopause, then women who maintain cycle regularity and minimize chronic HPA axis activation throughout their reproductive years will demonstrate delayed onset of perimenopausal symptoms and longer preservation of estradiol feedback function.