Chapter 37 - Aging and Reproduction

Abstract

Reproductive aging involves all three levels of the hypothalamic-pituitary-gonadal (HPG) axis. In females, there may also be independent age-related effects at the level of the uterus. Age-related changes are observed in the release and actions of gonadotropin-releasing hormone (GnRH) from the hypothalamus, gonadotropins from the pituitary, sex steroids and protein hormones from the gonads, together with anatomical and additional functional changes to each of these HPG levels. In women, age-related changes in reproductive function begin in the mid-thirties with decreased fertility and compensatory hormonal changes in the HPG axis that maintain follicle development and estradiol secretion in the face of a waning pool of ovarian follicles. The menopause transition is characterized by marked variability in follicle development, ovulation, bleeding patterns, and symptoms of hyper- and hypoestrogenism. The menopause that is clinically defined by the last menstrual period is followed by the consistent absence of ovarian secretion of estradiol and can be associated with vasomotor symptoms, insomnia, vaginal dryness, mood changes, osteoporosis, and cardiovascular changes. In women, it is clear that ovarian follicular loss plays a primary causal role in the loss of reproductive function with aging, but animal studies reveal that the hypothalamus and pituitary may play an important role in this process, particularly in rodents. In contrast to females, aging in males is associated with a more gradual and variable decline in serum testosterone that is due primarily to testicular and, to a lesser degree, hypothalamic dysfunction. The clinical significance of this age-related decline in testosterone is still uncertain. Aging has more modest effects on spermatogenesis than steroidogenesis, and fertility in men may be preserved until very late in life. Thus, there are significant sex differences in reproductive capacity.