Cognitive Effects of Hormonal Therapy in Older Adults

There is ample preclinical evidence that gonadal steroids (estrogens and androgens) play an important role in central nervous system development and function. The abrupt decline of estrogen levels in women after menopause, and the slower, subtler decline in total and bioavailable testosterone serum levels that occurs in aging men (“andropause,” “male menopause,” partial androgen deficiency in ageing males [PADAM]), have been implicated in the pathogenesis of cognitive dysfunction prevalent in elderly adults. However, the current clinical evidence supporting hormonal replacement as a neuroprotective therapy is at best inconclusive. Anti-estrogen and anti-androgen hormonal therapies are used in the treatment of breast and prostate carcinomas, respectively. Although generally considered less toxic than conventional cytotoxic chemotherapy, these hormonal manipulations have side effects that are not trivial. This review will summarize the available evidence regarding the impact of these hormonal therapies on cognitive function in older adults. Additional clinical research in this field is needed to confirm the existence and severity of such a possible cognitive impact, which may then need to be considered prior to initiating hormonal therapies in the elderly, as many patients may be in the prodromal phase or early stages of a neurodegenerative disorder, such as Alzheimer's disease, and this information may influence treatment decision-making and subsequent management.