During the fertile period, there is continuing loss of follicles, of which only a maximum of about 500 will reach the stage of a Graafian follicle and then disappear by ovulation. All other follicles, including the non-growing primordial follicles as well as those in which growth has been initiated, disappear spontaneously, probably via a process of apoptosis and atresia, which is only partly understood. After the age of approximately 38 years, the disappearance of follicles becomes even more accelerated. Idiopathic premature menopause will be increasingly shown to be, at least in part, genetic in origin. Hysterectomy with uni- or bilateral conservation of the ovary can also advance menopause, possibly through disturbance of the ovarian circulation.
Cigarette smoking can accelerate follicular loss.
Heavy smokers reach menopause significantly earlier than non-smokers, on average 1 to 2 years earlier. Premature menopause, on the basis of premature permanent ovarian failure, with a fair amount of follicles still present has also been described. Ovarian failure, secondary to conditions such as diabetes mellitus, thyroid disease and anorexia nervosa is, in principle, transient and ovarian function will be restored by treatment directed to the underlying disease. Therefore, these conditions do not belong to the POF syndrome. Race, socioeconomic status, age of menarche and prior use of oral contraceptives are all factors not affecting age of menopause.