Hormone Replacement Therapy and Cognitive Function

Hormone replacement therapy describes the use of exogenous hormones, specifically estrogen and progestins, to replace the endogenous sources that are depleted, usually due to age or surgical intervention. The term hormone replacement therapy (HRT) typically refers to the general replacement of estrogen and/or progesterone. It is now well understood that among women with an intact uterus the estrogen regimen must be supplemented with progesterone to avoid hyperplasia. The term estrogen replacement therapy (ERT) reflects the use of estrogen alone as the primary hormone that requires replacement, and it is the therapy used in surgical menopause with hysterectomy, wherein the addition of progesterone is not necessary. Despite the sometimes interchangeable use of these terms, these two hormone regimens, as well as the many agents used to replace estrogen and progesterone, may have different effects on cognition. The primary indication for this therapy is the treatment of menopausal symptoms including hot flushes, night sweats, vaginal dryness, and osteoporosis, and the effectiveness on these symptoms is well established in repeated studies. The transition through the menopause starts years before menstruation cessation. Symptoms during this time include mood swings, hot flushes, and loss of sexual drive. Other symptoms and medical conditions that increase with aging, such as cardiovascular disease and cognitive decline, are less clearly associated with the menopause. This chapter examines the data describing cognitive function during the adult life with a focus on cognitive changes in adulthood and aging through the menopause. The effect of hormone replacement on these functions are examined. While animal and laboratory studies have been used to understand hormonal activity, the focus is on clinical conditions and results from human clinical trials.