Ovary and ovulation: A model conforming the decline in follicle numbers to the age of menopause in women

Abstract

The store of primordial follicles in the ovary is fixed before birth and dwindles with age until it is unable to provide enough Graafian stages to sustain menstrual cyclicity. According to a simple bi-exponential model of ageing, the rate of follicle disappearance increases at age 37.5 years (or when 25 000 follicles remain) so that the numbers fall to approximately 1000 at 51 years, the median age of menopause in the population. This study attempts to produce a biologically more realistic model of follicle disappearance and harmonizes follicle dynamics with the distribution of menopausal ages from an American survey. The step-change in the rate of follicle attrition was replaced by a model which assumed that this rate changes more gradually with the size of the follicle store. This produced a distribution of predicted menopausal ages (based on an assumed threshold of 1000 follicles) which was closer to observed data. The fit further improved when the model was modified by having a threshold that varied across the population. Using such a stochastic threshold model for menopause, the number of fertile years remaining could be forecast with an acceptable margin of uncertainty if it ever becomes possible to estimate the size of the follicle store in vivo.