Follicular Depletion During the Menopausal Transition: Evidence for Accelerated Loss and Ultimate Exhaustion*

TLDR

Menopause is thought to result from follicular exhaustion, but the link between follicle count and the menopausal transition has not been explicitly examined. The authors studied 17 women aged 45–55 undergoing hysterectomy, grouping them by menstrual history (regular, perimenopausal, postmenopausal), confirming histories with hormone levels and histology, and serially sectioning one ovary per woman to count follicles. They found that regularly menstruating women had about ten times more primordial follicles than perimenopausal women, postmenopausal ovaries had virtually none, and follicular depletion accelerates in the last decade of reproductive life, supporting the idea that declining reserve drives the perimenopausal and menopausal transitions and that depletion rate changes in the final phase.

Abstract

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 (>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.