A mathematical model of follicle dynamics in the human ovary.

A mathematical model has been developed to describe the rates of growth and death of follicles in human ovaries between 19 and 50 years of age. It was based on the numbers of follicles at three successive stages of development, which were obtained by counting follicles in histological sections of ovaries from 52 normal women. The model indicated that follicle dynamics were age dependent, with a transition at 38 years of age when the rate of follicle disappearance increased. The rates of follicle growth increased at successive stages but did not change with age. The annual egress from stage III (consisting of follicles with two or more granulosa cell layers) was affected by the declining numbers of small follicles, and corresponded to 31, nine and one follicles per day at 29-30, 39-40 and 49-50 years of age respectively. The rate of death at stage I (representing small, resting follicles) was the only parameter which varied significantly with age: no evidence of significant atresia was found for this stage in ovaries < or = 38 years old, but there was significant death above this age. As a consequence, only 40% of follicles leaving stage I reached stage III in older ovaries and just 1500 follicles in toto remained at 50 years of age from the 300,000 present at 19 years. This high death rate of small follicles appears to be responsible for advancing the timing of ovarian failure, and therefore of menopause, to midlife in our species.