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MINIREVIEW

Ovarian Aging and Menopause: Current Theories, Hypotheses, and Research Models

Julie M. Wu^*,, Mary B. Zelinski, Donald K. Ingram and Mary Ann Ottinger^*,,1

^* Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742; Division of Reproductive Sciences, Oregon National Primate Research Center, Oregon Health & Sciences University, Beaverton, OR 97006; and Laboratory of Experimental Gerontology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224

To whom requests for reprints should be addressed at ¹ Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742. E-mail: maotting{at}umd.edu

Aging of the reproductive system has been studied in numerous vertebrate species. Although there are wide variations in reproductive strategies and hormone cycle components, many of the fundamental changes that occur during aging are similar. Evolutionary hypotheses attempt to explain why menopause occurs, whereas cellular hypotheses attempt to explain how it occurs. It is commonly believed that a disruption in the hypothalamic-pituitary-gonadal axis is responsible for the onset of menopause. Data exist to demonstrate that the first signs of menopause occur at the level of the brain or the ovary. Thus, finding an appropriate and representative animal model is especially important for the advancement of menopause research. In primates, there is a gradual decline in the function of the hypothalamic-pituitary-gonadal (HPG) axis ultimately resulting in irregularities in menstrual cycles and increasingly sporadic incidence of ovulation. Rodents also exhibit a progressive deterioration in HPG axis function; however, they also experience a period of constant estrus accompanied by intermittent ovulations, reduced progesterone levels, and elevated circulating estradiol levels. It is remarkable to observe that females of other classes also demonstrate deterioration in HPG axis function and ovarian failure. Comparisons of aging in various taxa provide insight into fundamental biological mechanisms of aging that could underlie reproductive decline.

Key Words: ovarian aging • perimenopause • ovarian steroid hormones • animal models • ovulatory cycles • inhibin

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