文献_2009-Ovarian Aging Mechanisms and Clinical.pdf

R E V I E W Ovarian Aging: Mechanisms and Clinical Consequences F. J. Broekmans, M. R. Soules, and B. C. Fauser Department of Reproductive Medicine and Gynecology (F.J.B., B.C.F.), University Medical Center, 3584 CX Utrecht, The Netherlands; and Seattle Reproductive Medicine (M.R.S.), Seattle, Washington 98109 Menopause is the final step in the process referred to as ovarian ageing. The age related decrease in follicle numbers dictates the onset of cycle irregularity and the final cessation of menses. The parallel decay in oocyte quality contributes to the gradual decline in fertility and the final occurrence of natural sterility. Endocrine changes mainly relate to the decline in the negative feedback from ovarian factors at the hypothalamo-pituitary unit. The declining cohort of antral follicles with age first results in gradually elevated FSH levels, followed by subsequent stages of overt cycle irregularity. The gradual decline in the size of the antral follicle cohort is best represented by decreasing levels of anti-Mullerian hormone. The variability of ovarian ageing among women is evident from the large variation in age at menopause. The identification of