Endocrine Changes of the Perimenopause

Abstract

The human species is unique in that the female experiences a relatively early onset of failure of the reproductive system (menopause) compared to the other major organ systems. Among individual women, the length of the reproductive life span and age of menopause are variable and are ultimately dependent on follicular depletion.1 Mathematical models based on morphometric studies have been used to hypothesize that follicular depletion is bi-exponential with an accelerated loss occurring after age 38 years, approximately.1 This progressive loss of follicles with age is characteristic of all mammals studied to date, although the factors controlling this process are unknown. The hypothalamic-pituitary-ovarian axis is a highly integrated feedback loop resulting in the maintenance of regular, ovulatory menstrual cycles during the early stages of aging under the influence of a gradual increase in follicle-stimulating hormone (FSH) secretion. In the premenopausal woman, the FSH rise is initially sufficient to compensate for decreased ovarian responsiveness and secretory capacity, which result from declining follicle numbers. However, once the number of remaining follicles drops below a critical threshold, a further increase in FSH occurs along with the loss of regular menstrual cyclicity. The time period that begins with this loss of menstrual regularity has been termed the perimenopause, or the menopausal transition. Typically lasting for several months to a few years (4 years on average), the perimenopause is marked by waning ovarian function, inconsistent follicular development/ovulation, and ultimate loss of ovulatory function. The degree of unpredictability of the perimenopause is such that the diagnosis of menopause can only be made retrospectively, traditionally applied only after 1 year of amenorrhea. The following discussion will focus on the endocrine changes that are observed with reproductive aging in normal women before and during the perimenopause.