Neuroendocrinology of female aging

Abstract

Because the average human life span has increased, a greater part of more women's lives will be lived in a hypoestrogenic state. This article provides an overview of our current knowledge of the neuroendocrine processes in the aging female brain. Using the search terms cardiovascular disease, cognition, dementia, depression, estrogens, female aging, gonadotropins, immune function, mood, neuroendocrinology, neurotransmitters, osteoporosis, and ovarian steroids, a review of English-language literature on the MEDLINE database was conducted from 1970 through June 2004. It is thought that the temporal patterns of neural signals are altered during middle age, leading to cessation of reproductive cycles, and that the complex interplay of ovarian and hypothalamic/pituitary pacemakers becomes increasingly dysfunctional with aging, ultimately resulting in menopause. Estrogen deficiency is associated with low mood, whereas estrogen therapy tends to be linked with improvements in measures of well-being and a decline in depression scores. It is likely that these effects of estrogens are mediated through changes in the metabolism of serotonin and nor epinephrine. Evidence exists to support the role of estrogens in specific effects on cognitive functioning in women, enhancing aspects of verbal memory, abstract reasoning, and information processing. Significant gender dimorphism is evident in both humoral and cell-mediated immune responses. The effects of estrogens on the cardiovascular system are complex; recent evidence suggests a negative role for oral estrogen in primary and secondary prevention of cardiovascular events. Additionally, estrogens increase the risk of stroke, and estrogen deficiency influences the pathogenesis of osteoporosis in both men and women. Changes in the neuroendocrine system due to the loss of ovarian function at menopause have an important biological role in the control of reproductive and nonreproductive functions, and regulate mood, memory, cognition, behavior, immune function, the locomotor system, and cardiovascular functions. More detailed insights are needed into the complex mechanisms of neuroendocrine alterations with aging.