Neuroendocrine Changes with Reproductive Aging in Women

Aging has dramatic effects on the reproductive system in women. Undoubtedly, the most notable changes in the neuroendocrine axis arise from the loss of ovarian function, and thus, the loss of negative feedback on the hypothalamus and pituitary. Progressive decreases in inhibin B and inhibin A result in an early increase in follicle-stimulating hormone (FSH), which initially maintains folliculogenesis and estradiol secretion. Over time, regular ovulatory cycles give way to inconsistent folliculogenesis and ovulation, dramatic swings in estradiol and gonadotropin levels, and markedly irregular cycles. Changes in estrogen positive feedback may contribute to cycle disruption. Studies in younger and older postmenopausal women indicate that changes in the neuroendocrine axis occur with aging that are independent of the changing ovarian hormonal milieu of the menopausal transition. Luteinizing hormone and FSH decrease progressively after the menopause, as does gonadotropin-releasing hormone (GnRH) pulse frequency. However, the overall amount of GnRH increases with aging, consistent with a significant degree of adaptability in the aging brain in women, and suggesting that aging alters pituitary responsiveness to GnRH. Estrogen negative feedback is not altered by aging; studies of the effects of aging on estrogen positive feedback are ongoing.