Ovarian aging, follicular depletion, and steroidogenesis

The follicular population. Menopause occurs as a consequence of the continuous utilization of a fixed store of primordial follicles leading to almost total depletion at mid-life or sometimes earlier. The great majority of follicles that disappear are lost by atresia rather than by ovulation, and the rate of loss accelerates in the last decade of menstrual life. The numbers of growing follicles at a given age are correlated with those of the primordial stages, but there are always more being recruited than required for a single ovulation each month. The extent to which a dwindling number is responsible for the character of cycles of the menopausal transition remains unclear. Ovarian secretion. While menstrual cycles remain regular, circulating concentrations of estradiol and progesterone are relatively independent of age. On the other hand, serum levels of inhibin are substantially lower in women approaching menopausal age, probably reflecting smaller numbers of growing follicles at the beginning of the cycle. Alleviation of negative feedback on the pituitary gland results in a greater output of follicle-stimulating hormone (FSH), but the effects of chronic superstimulation on the aging ovary are not known. Follicular aging. Aging of long-lived oocytes could affect the developmental potential of the follicle unit as well as compromising the chances of late pregnancy. Another important field of investigation is therefore to determine the balance of responsibility between cumulated damage to molecules by toxins, on the one hand, and the effects of physiological aging and such epiphenomena as the changing hormonal or paracrine environments, on the other.