Menstrual cycle variability and the perimenopause

Menopause, the final cessation of menstrual cycling, occurs when the pool o f ovarian follicles is depleted. The one to five years just prior to the me nopause are usually marked by increasing variability in menstrual cycle len gth, frequency of ovulation, and levels of reproductive hormones. Little is known about the mechanisms that account for these characteristics of ovari an cycles as the menopause approaches. Some evidence suggests that the dwin dling pool of follicles itself is responsible for cycle characteristics dur ing the perimenopausal transition. Another hypothesis is that the increased variability reflects "slippage" of the hypothalamus, which loses the abili ty to regulate menstrual cycles at older reproductive ages. This paper exam ines the underlying cause of the increasing variability in menstrual cycle length prior to the menopause. A model of ovarian cycles is developed, base d on the process of follicular growth and depletion. Under this model, the follicular phase of each menstrual cycle is preceded by an inactive phase, a period of time when no ovarian follicles have left; the resting state and begun secreting steroids in response to gonadotropin stimulation. The mode l makes predictions about the variability in menstrual cycles across the re productive life span based on the size of the surviving pool of ovarian fol licles. We show that the model can explain several characteristics of the p erimenopause in humans and macaques and illustrate how the model can be app lied to research on the biological and cultural correlates of the timing of menopause. (C) 2001 Wiley-Liss, Inc.