Follicular depletion during the menopausal transition: evidence for accelerated loss and ultimate exhaustion

Although the menopause is generally considered to be the consequence of follicular exhaustion, the relationship between follicle number and the menopausal transition has not been explicity studied. We addressed this question in 17 women, aged 45-55 yr, who were undergoing elective total abdominal hysterectomy and salpingo-oophorectomy. The women were divided into 3 groups according to their menstrual history: 1) menstruating regularly (n = 6), 2) perimenopausal (irregular menses; n = 7), and 3) postmenopausal (greater than 1 yr since last menses; n = 4). The mean ages of the 3 groups were similar. Menstrual histories were confirmed by plasma hormone levels and endometrial histology. One ovary from each woman was serially sectioned for determination of follicle numbers. The mean number of primordial follicles in the ovaries of women who were still menstruating regularly was 10-fold higher than that in perimenopausal women [1392 +/- 355 (+/- SEM) vs. 142 +/- 72]. Follicles were virtually absent in the postmenopausal ovaries. Comparison of these data with those obtained by others in younger women suggests that follicular depletion accelerates dramatically in the last decade of menstrual life. These results support the view that declining follicular reserve is the immediate cause of both the perimenopausal and menopausal transitions, and indicate that the rate and, therefore, the regulation of follicular depletion change during the final phase of reproductive life.