The neuroendocrine physiology of female reproductive aging: An update.

The transition into menopause is a complex process that affects fertility and increases the risk for a number of health problems in aging women that include, but are not limited to osteoporosis, heart disease, diabetes mellitus and cognitive dysfunction. Improved nutrition and enhanced access to medical care have increased the average lifespan for women in developed countries, and many will spend more than one-third of their life in a post-menopausal state. Epidemiological studies indicate that a delayed natural menopause confers longevity and decelerates the appearance of much age-related morbidity, suggesting that developing treatments to delay menopause would significantly improve quality of life for women. Although menopause is ultimately defined by ovarian follicular exhaustion, several lines of scientific evidence in humans and animals now suggest that dysregulation of estradiol feedback mechanisms and hypothalamic-pituitary dysfunction contributes to the onset and progression of reproductive senescence, independent of ovarian failure. This article provides a brief update on our current understanding of the role of the hypothalamic-pituitary axis in the onset of and transition into female reproductive senescence.