HRT May Protect Against Alzheimer Disease and Cognitive Decline

Alzheimer Disease (AD) currently is the most common cause of dementia, accounting for more than 64% of dementia cases in Canada. More than 161,000 people are afflicted with this disease and that number is expected to rise to 800,000 by the year 2030. Alzheimer Disease is a progressive neurodegenerative disorder that gradually destroys vital brain cells. It begins with short-term memory loss and eventually affects all aspects of your life. More women than men are affected by this disease. To date, there is no known cure.

Research strongly suggests that estrogen may delay the onset of AD in postmenopausal women. Laboratory studies indicate that estrogen may protect the brain by increasing blood flow, strengthening brain cells and even stimulating cell regrowth. In addition, studies have shown that women taking long-term hormone replacement therapy (HRT) had a lower incidence of AD compared to non-HRT users. This raises the possibility that women taking postmenopausal HRT may be at a significantly lower risk for this disease. Given these findings, there is an urgent need for randomized, placebo controlled clinical trials to determine whether estrogen replacement can prevent or delay the course of AD in women at risk for this disease.

A study is currently underway at Sunnybrook & Women’s evaluating the effectiveness of estrogen in improving memory in postmenopausal women. The focus is on older women, ranging from 60-90 years of age, who may be at higher risk for AD due to memory problems. This is a 2-year, double blind, placebo controlled, clinical trial. The study is headed by Dr. Mary C. Tierney, Senior Scientist at Sunnybrook & Women’s, along with a team of specialists including Drs. Paul Oh, Ellen Greenblatt, Neil MacLusky, John Paul Szalai and John Iazzetta. Funding has been provided by the Canadian Institutes of Health Research.

Unfortunately, a sense of caution has been aligned with HRT use given recent concerns raised by the Women’s Health Initiative (WHI). Their study was a prevention trial of 5.2 years duration, assessing the preventative affects of Prempro, a combination of equine estrogens (CEE) plus medroxyprogestrone acetate (MPA), in postmenopausal women (age range from 50-69 yrs with an average age of 63). Overall, their findings suggest this form of HRT, while reducing the risk of colorectal cancer and hip fractures, was associated with a slight increase risk for breast cancer, heart disease, and stroke. However, we cannot conclude from the findings of this trial that other hormone preparations will have similar effects.

It is clear that further randomized studies are needed before definitive conclusions can be drawn about the overall relationship between HRT use and cardiovascular disease. According to a report from the North American Menopause Society (NAMS) Advisory Panel, future research is needed to determine whether “different estrogens and progestins, different doses, and different routes of administration have the same benefit-risk profiles as the hormones used in the HERS and WHI studies.” They also recognize the need to examine other potentialities including whether “continuous progestin, as opposed to sequential progestin, was responsible for adverse cardiovascular and breast effects”, whether different progestins have an effect on breast cancer risk, whether genetic or environmental factors play a role, and how the issue of quality of life factors in to benefit-risk profiles of HRT use.

Given a profusion of hype and media attention, thousands of postmenopausal women on HRT are filled with uncertainty. The Society of Obstetricians and Gynaecologists of Canada (SOGC), in an effort to alleviate confusion and concerns, recently revised its guidelines. These guidelines confirmed that HRT is effective for the relief of moderate to severe menopausal systems, and protection against hip and osteoporatic fractures, and they recommend women considering HRT use for more than 4 years seek annual reviews in consultation with a physician (1 year earlier than previously recommended). Overall they offer many reassurances stating that “…women who have menopausal symptoms that interfere with their quality of life can feel confident choosing continuous, combined HRT to ease their physical distress, and, at the same time, benefit from the protective features of hormone therapy.”

Regrettably, the overgeneralizations made about the WHI study may still deter women from using HRT for these proven health benefits. As well, it may gravely affect further research investigations of other kinds of estrogen-progestin combinations on cardiovascular disease and other health benefits, including promising studies investigating its potential for the prevention of AD and memory impairment in women.

If we were to dismiss years of positive research and prevent further HRT investigation on other health benefits on the basis of the WHI trial alone, with one particular combination of estrogen-progestin, it would be seriously injurious to women’s health and scientific enquiry.

To learn more about the Estrogen Memory Study, please call (416) 480-6100 ext. 2378.