Neuroendocrine Basis of the Hypothalamus–Pituitary–Ovary Axis Aging

Abstract

Female reproductive senescence is a lifelong process that begins before birth and culminates with ovarian follicular depletion and menopause. For many years, the menopausal transition was viewed to be simply the end product of accelerated oocyte depletion. Moreover, hypothalamic–pituitary–ovary (HPO) axis dysfunction was thought to reflect a compensatory response to the gradual decline in the number and quality of remaining oocytes. However, recent studies challenge the conventional belief that ovarian aging is the sole determinant of reproductive senescence and raise questions about the sequence of pathophysiological events that initiate reproductive aging. Moreover, aberrant responsiveness of the hypothalamic–pituitary–adrenal (HPA) axis to estrogen feedback and the subsequent generation of abnormal patterns of gonadotropin release may in itself accelerate ovarian follicular exhaustion. Understanding the mechanisms that propel women into menopause may offer opportunities for interventions that delay menopause-related increases in disease morbidity and thus improve overall quality of life for aging women.