Every woman is unique in their health status when approaching the menopausal transition. Many women (80%) present with hot flushes, night sweats, insomnia and mood symptoms. Other women will have low sexual libido, vaginal dryness and cognitive impairment. These symptoms can disturb women’s relationships, work responsibilities and self-confidence.
Cognitive impairment, such as spatial and verbal memory, word finding, anxiety, depression, and executive function (planning, organizing, attention to details and time management) are among the most distressing to women. These women come to me to rule out dementia and are especially concerned if there is a family history of dementia.
Recent research shows that women have reason to be concerned. The main hormone lost in menopause is estrogen. Progesterone is lost earlier during peri-menopause. Converging evidence over the past 2 decades have strongly revealed that estradiol (17 beta-estradiol) protects the postmenopausal female brain.
Strong observational and clinical studies suggest significant benefits to cognitive function and decreased risk of Alzheimer’s disease (AD) for women on estradiol, especially with transdermal application (creams, patches). Conjugated equine estrogens (CEE), such as Premarin on the other hand, negatively effects cognitive function or shows no benefit, and may actually increase the risk of dementia for women over the age of 65.
Our countries demographic shift to a much more elderly population predicts an increase of Alzheimer’s disease from 4.5 million in 2000 to 13.2 million in 2050 as Baby Boomers age. More evidence shows that the pathology of AD starts decades before symptoms even start. Once symptoms appear, significant nerve loss has already occurred and the progression of the disease is inevitable. Even though the time in which brain deterioration begins is unknown, there is compelling evidence that the steep drop in estrogen levels during menopause is closely linked to an increase risk of dementia in women.
The basic science shows that estrogen receptors are found in selective areas of the brain which are associated with mood and memory and also areas affected by neurodegeneration in AD. Estrogen supports the major neurotransmitter systems of the brain, specifically acetylcholine (attention, learning, memory), serotonin, dopamine, and norepinephrine. All of these are involved in the cognitive functions affected by AD.
Lastly, amyloid beta (AB) plaque deposition is one of the main contributing factors of AD. Estrogen reduces AB levels and estrogen deficiency accelerates AB plaque formation. Estrogen also reduces inflammation and increases blood flow to the brain.
More and more women are living longer and undoubtedly, women want the last 1/3 of their lives after menopause to be meaningful and productive. It’s not how long they live, but the quality of their lives that matter. Unfortunately the number of women with Alzheimer’s disease increases with each year of age. The KEEPS cognitive and affective study is due to come out this year which is a longitudinal study using transdermal estradiol as one of the major hormone variables that will answer many questions on the risks and benefits of hormone replacement therapy (HRT).
HRT of course comes with its side effects and risks. The complex decision whether to begin HRT is a personal choice that a women needs to discuss with a trusted practitioner. The risk of osteoporosis, cardiovascular disease, breast, uterine and ovarian cancers, along with dementia must be weighed with its risks and benefits. We await the KEEPS and other studies to understand how to optimize cognitive and other health factors for women beginning during the peri-menopausal transition and the many years to follow.
Reference: Hathaway, A. Women, Estrogen, Cognition, and Alzheiner’s Disease. Townsend Letter- June 2012, pp. 64-69.
Hoppel, A. A Bioidentical Balancing Act. Clinician Reviews. April 2013, Volume 23, Number 4, pp 41-43.