Effects of Aging on Gonadotropin/Ovarian and Growth Hormone/Ovarian Relationships in Normal Women

With a dramatic improvement in life expectancy for women, attention has been increasingly focused on both age-associated reproductive and metabolic issues. With regard to the somatotropic axis, both hypothalamo-pituitary disease and aging are associated with variable degrees of hyposomatotropism, the depletion of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Postmenopausal women manifest combined reductions in systemic GH and estrogen availability. Hypoestrogenemia is relevant to progressive GH deprivation, because repletion of estradiol drives GH secretion in the ovariprival subject. With regard to the reproductive axis, it is clear that the ability to achieve and maintain a successful pregnancy declines as a function of age. It is possible that age-associated alterations in the reproductive components of the neuroendocrine axis may contribute to decrease in reproductive potential. However, it is unclear whether changes in the function of hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator activity and/or in the secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH) by anterior pituitary gonadotropes are a direct consequence of the aging process, or simply reflect changes in gonadal feedback. An improved understanding of how the process of aging adversely affects hypothalamic-pituitary-ovarian function may allow for significantly improved methods with which to enhance fertility in the aging female population.