Endocrine Changes of the Perimenopause

Reproductive aging in women is closely tied to the loss of ovarian follicles through atresia. The sentinel endocrinologic finding is the monotropic FSH rise, associated with a decline in ovarian inhibin B secretion. Fertility becomes significantly compromised long before overt clinical signs occur, such as cycle irregularity. Compromised fertility is primarily related to oocyte dysfunction. As women with regular cycles near the end of the reproductive years, the following changes are usually manifested: 1) the selection and development of a dominant follicle occurs earlier; 2) there is earlier ovulation; 3) there is a short follicular phase and total cycle length; and 4) ovarian steroid secretion is normal. The relationships, if any, between the monotropic FSH rise, accelerated follicular atresia, shortened follicular phase, and oocyte quality remain to be determined. The next phase of reproductive aging is the perimenopause. Lack of predictability is the rule with regard to the nature and duration of the perimenopause. Long cycles are interspersed with short ones, and intermittent ovulatory cycles are intermingled with periods that are hormonally indistinct from the postmenopausal state. Even after the last menstrual period, evidence of intermittent ovarian estradiol production may still be detected. Although fertility is severely compromised during the perimenopause, ovulation may occur without warning and contraception must be practiced if pregnancy is not desired. Further studies are needed to elucidate the factors contributing to oocyte abnormalities in women of advanced reproductive age, as well as the factors that determine the rate of follicle atresia and the length of the reproductive life span.