The study of aging of the endocrine system in women has largely focused on ovarian failure, a certain event in every woman's life. Considerable morbidity and mortality have been attributed to this process. Ovarian hormone replacement appears to reduce heart disease and osteoporosis in older women. These findings have led to an increasingly routine consideration of hormonal therapy for postmenopausal women. The contributions of chronological aging and ovarian aging have seldom been separated in women. The current proposal plans to utilize a model of gonadal failure in an otherwise youthful endocrinologic milieu, i.e., women with premature ovarian failure (POF), to determine the relationship of general endocrine aging to ovarian failure. Growth hormone (GH), an endocrine facilitator or gonadotropin action in vitro and in vivo, declines with age and hypoestrogenemia. Since women with POF experience a menopause-like process at an inappropriately young age, the relationship of GH secretion to both age and estrogen administration will be compared in both age-appropriately menopausal (M) and POF women to detect age-related differences in the secretion or estrogen- responsiveness of GH. The findings may illustrate the need to consider further the impact of GH deficiency in aging women and may indicate endocrine markers useful for follow-up or treatment of ovarian failure. The contributions of aberrant neuroendocrine regulation of gonadotropin releasing hormone secretion in reproductive aging will be determined by studying the characteristics of pulsatile gonadotropin secretion in young prematurely menopausal women and older menopausal women. Long-term longitudinal series of urinary reproductive hormonal data will be investigated using statistical and mathematical methods to determine the relationships between excretion patterns of LH, FSH, E, (Estrone) conj and Pdg (pregnanediol) and to characterize the periodicity, if any, of the failing ovary in the perimenopause (PERI) and in POF. Previously collected long-term urinary hormonal data indicate that POF and PERI women demonstrate basal urinary Pdg excretion which is 2-3 fold greater than older M women. This increased Pdg may be ovarian or adrenal in origin, and may help to define age related differences in the ovaries or adrenal glands of M women. The source of urinary Pdg in this circumstance will be determined by selectively abolishing gonadotropin stimulation to the ovary. The studies outlined herein will allow for a determination of the components of endocrine aging which are associated with reproductive senescence. Such studies should further elucidate the pathophysiology of premature and age-appropriate menopause and the menopausal transition and may point up the need to tailor hormonal therapy of older women to approximate most closely the salutary features of a more youthful endocrine milieu.
