The endocrinology of the menopause

Menopause is defined as the permanent cessation of menstruation resulting from the loss of ovarian follicular activity. Ovarian primordial follicle numbers decrease with increasing age up to about age 38 following which there is a much steeper decline in the last 12 or so years of reproductive life. At the time of the menopause itself, few follicles remain within the ovary. The recent availability of assays specific for the dimeric inhibins A and B has permitted clarification of the endocrine events leading up to and occurring around the time of final menses. Those women who show clear elevations in serum FSH above age 40, while continuing to cycle regularly have significantly lower inhibin B levels than those whose FSH levels remain in the range seen earlier in reproductive life. Early in the menopause transition, when cycle irregularity is first observed, the initial event is a decline in circulating inhibin B levels in the early follicular phase. In the late perimenopause, levels of estradiol and inhibin A also fall, inhibin B levels remain low and FSH is markedly elevated. The variability of hormone levels in women in their 40s, even in those who are continuing to cycle regularly makes FSH and estradiol unreliable markers of menopausal status. Serum androgen levels appear to fall with age rather than having any clear cut relationship to the menopause transition or menopause. The endocrine changes which occur during the menopausal transition and early postmenopausal period have clinical consequences in terms of symptoms and changes in bone mass.