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| THE "MENOPAUSE": CAUSES AND REPERCUSSIONS OF HYPOESTROGENICITY Phyllis M.Wise, Ph.D., Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky Interests in gender-determined, gender-predominant and gender-biased events in life and disease have increased tremendously as we begin to appreciate more fully the complex pleiotropic effects of estradiol as an organizational factor, activational factor and trophic/survival factor. At the same time, interests in the causes and repercussions of the menopause have increased recently because more women are living longer and spending a larger proportion of their lives in a postmenopausal state. The menopause signals the permanent end of fertility. A hallmark of the postmenopausal state is the permanent and dramatic decrease in estradiol levels. This chronic hypoestrogenicity appears to influence multiple reproductive organs. More importantly, it is becoming clear that it affects several functions that were not thought traditionally to be reproductive in nature, such as memory and cognition and the progression of age-related diseases. For many years, it was accepted that the menopause resulted simply from exhaustion of ovarian follicles: changes in other components of the reproductive axis that accompany the menopause were considered consequences of declining ovarian function. More recently, increasing attention has been paid to the possibility that age-related changes in the hypothalamus and central nervous system are important players in the ensemble of events that lead to the menopause: the final exhaustion of ovarian follicles may be accelerated as a consequence of desynchronization of neural signals. I will present data that demonstrate that, in middle-aged animals, steroid-dependent rhythms in neurochemical and neuroendocrine signals deteriorate and impact on the pattern of pituitary hormone secretion, which, in turn, may precipitate the increased rate of loss of the follicular pool. In addition, I will discuss our recent findings that the hypoestrogenic state makes the brain more vulnerable to injury. We have found that ovariectomized rats suffer greater brain damage after ischemic injury than animals that have been treated with physiological levels of estrogen. Together our findings demonstrate that the central nervous system is involved in regulating the timing of the menopause and, conversely, that menopause has broad repercussions on central nervous system function.
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