Sex steroids and the brain:
Significance for mental health in postmenopause

By Sarah L. Berga, MD

Clinical studies suggest that estrogen therapy may have benefit in protecting against dementia, and this may help preserve the mental health of older women.

Beyond their role in reproduction, estrogen and progesterone exert powerful beneficial effects on the urogenital, skeletal, and cardiovascular systems, among others. Decades of endocrinologic research indicate that therapeutic replacement of sex hormones in postmenopausal women can help maintain or even restore the healthy functioning of these systems, significantly improving women’s overall health, quality of life, and possibly even extending their life span. Hormone replacement therapy (HRT) has thus evolved from short-term palliative treatment for the hot flushes of menopause to long-term replenishment of hormones that are essential for the optimum functioning of many organ systems.

Now, neurophysiologic research is shedding light on another key target of sex steroids: the brain. Estrogen’s effects on the hypothalamus relative to ovulation and reproduction have been well studied. We are just beginning to appreciate the impact of sex steroid actions on other brain centers, however, especially those areas vital for cognition, memory, emotionality, and mood.

The decline in estrogen levels at menopause has been linked with cognitive and emotional difficulties experienced by many women, such as trouble remembering names and feelings of depression. Estrogen replacement therapy improves cognitive function and mood in postmenopausal women. Indeed, whether HRT can prevent or delay the onset of Alzheimer’s disease or be an effective treatment in the management of depressive disorders is the subject of ongoing investigation.

This article outlines estrogen’s effects on various tissues, especially central nervous system functions. Recent clinical studies are discussed from the perspective of how sex steroids play a role in maintaining mental health in older women. For clinicians who treat women, the emerging evidence on the estrogen-brain connection is directly pertinent to their practice, since approximately 31.2 million women are currently older than 55 years. By the year 2020, an estimated 45.9 million women will be in this age group.