The menopausal transition

Reproductive aging in women is related to the depletion of a fixed number of germ cells within the ovary. Prenatally, almost 50% of the maximal follicle pool is lost. Thereafter, atresia slows until women reach their early 40s, when total remaining follicle numbers reach a critical threshold. Atresia then becomes rapid once again, and women progress through the menopausal transition until they are left with essentially zero oocytes by a median age of 51.4 years. Fewer follicles result in a loss of inhibin B production and less physiologic "restraint" of follicle-stimulating hormone (FSH) secretion. Based on the responsiveness of the follicles present in any given month, a wide spectrum of hormonal patterns may occur. Women may alternate between inadequate folliculogenesis and more normal cycling. In the Study of Women's Health Across the Nation (SWAN), daily urine sampling was performed to assess hormonal dynamics. Older age and larger body size predicted aluteal cycles, and hormone excretion was lower in larger women. When annual hormones are examined, most of the decrease in estradiol and increase in FSH associated with menopause is found to occur during the late menopausal transition. There also is evidence that the central nervous system does not respond normally to estrogen and fails to produce preovulatory luteinizing hormone surges in women in the early transition. Clinically, it is important to appreciate that the entire reproductive system, not just the ovary, is undergoing change across the transition. Reproductive hormonal fluctuations may underlie some of the common symptomatology of the perimenopause.