Follicular depletion during the menopausal transition.

From mid-fetal life, the human ovary steadily loses follicles. While age-related alterations at the level of the hypothalamus-pituitary appear to determine the timing of menarche, the number of follicles remaining in the mature ovary is the major determinant of the timing of both the perimenopause and the menopause. As the residual follicle reserve nears exhaustion, some of the remaining follicles appear to be defective, as evidenced by the higher incidence of chromosomal abnormalities in the ova of older women. It is presently not possible, however, to distinguish the specific contribution of the ovum to the age-related decrease in fecundity and higher abortion rate because of such confounding variables as aging sperm or changes in the endometrium. When follicle counts from peri- and postmenopausal ovaries are placed with those from previous studies of younger women and children there appears to be an acceleration in the rate of follicle loss in the decade preceding menopause. We hypothesize that the elevated FSH levels observed in normal women in the decade preceding the menopause may be responsible for this apparent acceleration in the rate of follicle loss.