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A Life Course Approach to Reproductive Aging Current Topics in Menopause 5 MENOPAUSE AS AN INDICATOR OF REPRODUCTIVE AGING Menopause marks the end of the reproductive phase and is an indicator of reproductive aging. Natural menopause occurs when the ovarian follicular reserve is depleted [17]. Menopause is determined after 12 months of amenorrhea resulting from depletion [18]. Women who begin to have changes to their menstrual cycle lengths or frequencies prior to menopause are considered perimenopausal [19]. A woman’s follicular reserve peaks in foetal life at approximately 5 million follicles and falls to around 2 million by birth [17, 20]. At natural menopause, the follicular reserve is around 1000 follicles [17, 20]. Early life production of, and decline of ovarian follicular reserve influence age at natural menopause. The earliest of these factors is the number of primordial germ cells that migrate to the gonadal ridge during foetal life. At gestational age of 16-20 weeks, the rate of mitosis of the primordial germ cells determines how many primordial follicles develop, which are the cells that will eventually participate in ovulation, if they survive to that stage. The rate of follicular atresia in foetal and post-natal environments through perimenopause also influences how many primordial follicles will be available for ovulation [17, 21]. Natural Menopause Age at menopause does not appear to vary greatly in different geographic spaces or at various points in time. Menopause generally occurs between ages 40 – 60 years [22-24], with reliable estimates of the median age at menopause in Western industrialized countries ranging from 48-52 years [25]. Most estimates from developing countries using similar methodology to estimate age at menopause as in Western industrialized countries [26, 27] have also been within this range [27- 33]. Though based on a limited number of studies, the existing evidence suggests a possible modest increase in the age at natural menopause over the 20th century in Western industrialized countries [34-38]. Surgical Menopause Prior to natural menopause, surgical menopause may also end reproductive life due to hysterectomy or oophorectomy [39]. Hysterectomy or oophorectomy may
20 Current Topics in Menopause, 2013, 20-53 Genetics of Menopause and Menopausal Age Volodymyr Dvornyk * CHAPTER 2 School of Biological Sciences, University of Hong Kong, Pokfulam Rd., Pokfulam, Hong Kong S.A.R., P.R. China Abstract: Menopause marks an upper limit of a female’s reproductive period. It is one of the key physiological events in female life and has a pronounced effect on postmenopausal health. Age at natural menopause (ANM) has been associated with many health problems and therefore attracted much attention in the last two decades. As a complex trait, ANM is determined by many genetic and environmental factors and their interactions. During last two decades, large efforts have been made to determine a genetic basis of natural menopause and its timing, which allowed for identifying a number of candidate genes and genomic regions. However, the problem is still far from its solution. The systems approach, which incorporates candidate gene association studies, genome-wide association studies, linkage analysis, gene expression microarrays and proteomics in a single pipeline, may open new venues and greatly advance progress in this area. Keywords: Age at natural menopause, genetic factors, genome-wide association, candidate genes, linkage, microarrays, systems approach. INTRODUCTION Send Orders of Reprints at bspsaif@emirates.net.ae Natural menopause is one of the key physiological events in a female life. It influences general health as well as functions of various organs and tissues. The most obvious result of menopause is cease of reproductive function. However, female fertility is not an only reason that prompts for an interest in menopause and its aetiology. Menopause is associated with profound biochemical and metabolic changes, e.g., decrease in estrogen, increase in low-density lipoprotein and decrease in high-density lipoprotein cholesterol. These changes contribute to the physiological mechanisms by which menopause can act as a risk factor for a number of postmenopausal health problems, such as decline in cardiovascular, skeletal, and genitourinary system functions [1-3]. Another well established fact is *Address correspondence to Volodymyr Dvornyk: School of Biological Sciences, University of Hong Kong, Pokfulam Rd., Pokfulam, Hong Kong S.A.R., P.R. China; E-mail: dvornyk@hku.hk Volodymyr Dvornyk (Ed) All rights reserved-© 2013 Bentham Science Publishers
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