Estrogen-alone hormone therapy could increase risk of dementia in older women

June 22, 2004

Older women using estrogen-alone hormone therapy could be at a slightly greater risk of developing dementia, including Alzheimer's disease (AD), than women who do not use any menopausal hormone therapy, according to a new report by scientists with the Women's Health Initiative Memory Study (WHIMS). The scientists also found that estrogen alone did not prevent cognitive decline in these older women. These findings from WHIMS appear in the June 23/30, 2004, Journal of the American Medical Association*.

"These studies further support last year's recommendations that menopausal hormone therapy should not be used to prevent cognitive decline or dementia in older postmenopausal women," stated Judith A. Salerno, MD, MS, Deputy Director of the National Institute on Aging (NIA). "Women should follow the Food and Drug Administration's recommendation that those who want to use menopausal hormone therapy to control their menopausal symptoms should use it at the lowest effective dose for the shortest time necessary."

The latest findings were reported by WHIMS Principal Investigator Sally A. Shumaker, PhD, Wake Forest University School of Medicine, and her colleagues at the 39 study sites. This research was funded by Wyeth Pharmaceuticals, which manufactures PremarinTM, the conjugated equine estrogens used in this trial, and Wake Forest University Baptist Medical Center. WHIMS is a substudy of the Women's Health Initiative (WHI) Hormone Trial, which is funded by the National Institutes of Health (NIH) at the Department of Health and Human Services (DHHS). The National Institute on Aging (NIA), a component of NIH, has been involved in reviewing the current findings as the lead NIH institute on age-related cognitive change and dementia.

The WHI Hormone Trial using estrogen plus progestin was stopped early in July 2002 when researchers found an increased risk of breast cancer, along with greater risks of heart disease, stroke, and blood clots, and determined that these risks outweighed the benefits of reduced risks of hip fracture and colorectal cancer. In May 2003, WHIMS investigators reported the results of the estrogen plus progestin part of their memory substudy**. They found that estrogen plus progestin increased the risk of probable dementia in women 65 and older and did not preserve cognitive function. This part of WHIMS was also stopped in July 2002.

At the end of February 2004, the remaining parts of the WHI Hormone Trial and WHIMS, the estrogen-alone components, were halted because results were showing an increased risk of stroke and no reduction in the risk of heart disease in the women using estrogen alone. Scientists further believed that continuing the study until its planned conclusion next year would probably not add new information. In April 2004, the WHI investigators reported that they found an increased risk of blood clots, but no significant effect on breast or colorectal cancer and also a reduced risk of fractures in those women using estrogen alone.

Now, the WHIMS scientists have evaluated the cognition and dementia data from the estrogen-alone part of the trial. Some 2,947 women age 65 to 79 at the beginning of the trial received estrogen alone (a daily dose of 0.625 mg of PremarinTM) or a placebo. (The women received estrogen alone because they had all had hysterectomies at some time before beginning the study. A progestin is used with estrogen in menopausal hormone therapy in any woman with a uterus to prevent thickening and, sometimes, cancer of the lining of the uterus, the endometrium. Because the uterus is removed in a hysterectomy, there is no need for progestin when women who have had hysterectomies use menopausal hormone therapy.)

Participants were determined to be dementia free before they were enrolled in WHIMS. At the beginning and then annually for the more than 5-year average duration of the trial, WHIMS participants were evaluated to determine if they might have developed dementia or mild cognitive impairment (MCI). All women received the Modified Mini Mental State Exam (3MSE), and those suspected of having dementia also received an extensive clinical evaluation by a specialist physician.

At the end of the study, the risk of dementia in the estrogen-alone group was 49% higher than the risk in women using the placebo. That is, among 10,000 women using conjugated equine estrogens, 37 could be expected to develop dementia, compared to 25 in 10,000 women using the placebo--12 extra cases of dementia in every 10,000 women using estrogen alone each year. This increased risk was not statistically significant.

Last year WHIMS scientists reported a 105% increase in the risk of dementia in older women using estrogen plus progestin compared to those using a placebo. That means, on average, each year in 10,000 women over age 65 using estrogen plus progestin there might be 45 cases of dementia compared to 22 cases in 10,000 older women on placebo.

Almost half of the dementia cases in the estrogen-alone study--46% in older women using estrogen alone and 47% of those in older women using the placebo--were Alzheimer's disease (AD). Similarly, in the estrogen plus progestin study, 50% of the cases in older women using estrogen plus progestin and 57% of those in older women using placebo were classified as AD.

A second article on general cognitive function*** from Mark A. Espeland, PhD, and other WHIMS investigators appears in the same issue of JAMA. It reports that beginning estrogen-alone hormone therapy after age 65 can have a small negative effect on overall cognitive abilities and that this negative effect may be greater in women with existing cognitive problems. The differences in scores on cognitive testing for the estrogen-alone and placebo groups were statistically significant, but the differences were so small that they are not considered clinically relevant by the investigators.

As with the earlier WHI and WHIMS result reports, these increases in risk must be viewed in perspective. Significant increases in risk are important for public health officials who are concerned with large groups in the population, where a small increase could have health implications for millions of people. For an individual woman, however, the increased risk is still quite small. (A detailed discussion of risk is presented in the NIA Fact Sheet, Understanding Risk: What Do Those Headlines Really Mean?, available online at http://www.niapublications.org/engagepages/risk.asp).

Further, these findings relate to women age 65 and older taking this particular estrogen-alone hormone therapy. The cognitive risks and benefits for younger women using PremarinTM or other estrogen formulations are unknown. Any younger woman who is considering menopausal hormone therapy because of her menopausal symptoms should talk to her doctor about how the various Women's Health Initiative study findings relate to her own medical history and treatment. General information on menopause, menopausal hormone therapy, and the Women's Health Initiative can be found on the NIH home page, http://www.nih.gov, by clicking on the link "Menopausal Hormone Therapy," or by going directly to http://www.nih.gov/PHTindex.htm.
-end-
The NIA leads the Federal research effort on aging in general and on aging and memory, including Alzheimer's disease. For more information on these topics, the public and media are invited to visit the NIA's websites. Information on memory and Alzheimer's disease may be viewed at http://www.alzheimers.org, the NIA's Alzheimer's Disease Education and Referral (ADEAR) Center website. The general public also may call the ADEAR Center toll free at 1-800-438-4380. General information on health and aging may be viewed at http://www.nia.nih.gov. Publications may be ordered online at http://www.niapublications.org or by calling the NIA Information Center toll free at 1-800-222-2225.

Shumaker SA, Legault C, Kuller L, Rapp SR, Thal L, Lane DS, Fillit H, Stefanick ML, Hendrix S, Lewis CE, Masaki K, Coker LH, Conjugated Equine Estrogens and Incidence of Probable Dementia and Mild Cognitive Impairment in Postmenopausal Women: Women's Health Initiative Memory Study. JAMA. 2004; 291: 2947-2958.

Shumaker SA, Legault C, Rapp SR. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women. The Women's Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003; 289:2651-2662.

Rapp S, Espeland MA, Shumaker SA, et al. Effect of estrogen plus progestin on global cognitive function in postmenopausal women: Women's Health Initiative Memory Study; A Randomized Controlled Trial. JAMA. 2003; 289: 2663-2672.

Espeland MA, Rapp SR, Shumaker SA, Brunner R, Manson JE, Sherwin BB, Hsia J, Margolis KL, Hogen PE, Wallace R, Dailey M, Freeman R, Hays J for the Women's Health Initiative Memory Study. Conjugated Equine Estrogens and Global Cognitive Function in Postmenopausal Women: Women's Health Initiative Memory Study. JAMA. 2004; 291: 2959-2968.

NIH/National Institute on Aging

Related Heart Disease Articles from Brightsurf:

Cellular pathway of genetic heart disease similar to neurodegenerative disease
Research on a genetic heart disease has uncovered a new and unexpected mechanism for heart failure.

Mechanism linking gum disease to heart disease, other inflammatory conditions discovered
The link between periodontal (gum) disease and other inflammatory conditions such as heart disease and diabetes has long been established, but the mechanism behind that association has, until now, remained a mystery.

New 'atlas' of human heart cells first step toward precision treatments for heart disease
Scientists have for the first time documented all of the different cell types and genes expressed in the healthy human heart, in research published in the journal Nature.

With a heavy heart: How men and women develop heart disease differently
A new study by researchers from McGill University has uncovered that minerals causing aortic heart valve blockage in men and women are different, a discovery that could change how heart disease is diagnosed and treated.

Heart-healthy diets are naturally low in dietary cholesterol and can help to reduce the risk of heart disease and stroke
Eating a heart-healthy dietary pattern rich in vegetables, fruits, whole grains, low-fat dairy products, poultry, fish, legumes, vegetable oils and nuts, which is also limits salt, red and processed meats, refined-carbohydrates and added sugars, is relatively low in dietary cholesterol and supports healthy levels of artery-clogging LDL cholesterol.

Pacemakers can improve heart function in patients with chemotherapy-induced heart disease
Research has shown that treating chemotherapy-induced cardiomyopathy with commercially available cardiac resynchronization therapy (CRT) delivered through a surgically implanted defibrillator or pacemaker can significantly improve patient outcomes.

Arsenic in drinking water may change heart structure raising risk of heart disease
Drinking water that is contaminated with arsenic may lead to thickening of the heart's main pumping chamber in young adults, according to a new study by researchers at Columbia University Mailman School of Public Health.

New health calculator can help predict heart disease risk, estimate heart age
A new online health calculator can help people determine their risk of heart disease, as well as their heart age, accounting for sociodemographic factors such as ethnicity, sense of belonging and education, as well as health status and lifestyle behaviors.

Wide variation in rate of death between VA hospitals for patients with heart disease, heart failure
Death rates for veterans with ischemic heart disease and chronic heart failure varied widely across the Veterans Affairs (VA) health care system from 2010 to 2014, which could suggest differences in the quality of cardiovascular health care provided by VA medical centers.

Heart failure: The Alzheimer's disease of the heart?
Similar to how protein clumps build up in the brain in people with some neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, protein clumps appear to accumulate in the diseased hearts of mice and people with heart failure, according to a team led by Johns Hopkins University researchers.

Read More: Heart Disease News and Heart Disease Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.