Health Briefs: Estrogen and Dementia

June 18, 2004

UPDATE ON ESTROGEN & DEMENTIA

After claiming, for years, that hormone replacement therapy (HRT) reduces the risk of dementia in postmenopausal women, manufacturers of HRT pills had to eat their words when the huge Women’s Health Initiative (WHI) study conclusively showed that the long-term use of estrogen combined with the other female sex hormone, progesterone, actually increased the risk of dementia (as reported in 2002).  This was only one of several serious side effects associated with the chronic use of the so-called combined HRTs.  (Women who have not previously undergone a hysterectomy are generally advised to use combination HRTs, if they choose to take hormones after menopause, due to the well-known increase in the risk of uterine cancer associated with “unopposed” estrogen use.)  Significant increases in the risks of breast cancer, heart disease, stroke and other life-threatening ailments were also associated with prolonged combination HRT use in the WHI study (and contrary to the opinions and recommendations of most HRT proponents over the past four decades).  The interim results of the WHI study’s combination HRT study were so damning, from a public health perspective, that this arm of the study was prematurely terminated in the summer of 2002, while the estrogen-only arm of the study was allowed to continue until it too was shutdown two months ago, also prematurely.  In the case of the estrogen-only HRT arm of the WHI study, no cardiovascular or other health-related benefits were identified among women who had previously undergone hysterectomy, and who were randomized to receive estrogen pills.  Moreover, a preliminary analysis of the data from this arm of the WHI study revealed a worrisome increase in the risk of stroke and blood clots among the women who were randomized to receive estrogen pills instead of placebo pills.  At this time, a more exhaustive analysis of the WHI estrogen-only HRT study data is underway.

Now, two new updates from the WHI study group, published in this week’s Journal of the American Medical Association (JAMA), further assess the impact of combination and estrogen-only HRT on the incidence of dementia.  In the first update, 4,532 women who participated in the combination HRT arm, and 2,947 women who participated in the estrogen-only HRT arm, were evaluated for changes in cognitive function between July 2002 and February 2004.  All women were 65 to 79 years of age, and all lived independently at home.  In this analysis, the use of estrogen-only HRT was associated with a 49% increase in the relative risk of developing probable dementia during the very short duration of this study.  When compared to the increase in dementia rates seen among women participating in the WHI combination HRT arm, the women taking estrogen-only HRT experienced essentially equivalent increases in the risk of developing dementia, as well as mild cognitive impairment, (i.e., when compared to women, in both arms of the WHI study, who were randomized to receive placebo pills).  Thus, it appears that women who take estrogen-only HRT are at a similarly increased risk of developing both mild cognitive dysfunction and dementia as are women who take combination HRT.

In the second WHI study group update, a broader analysis of the impact of HRT on global cognitive function was performed.  Despite largely anecdotal previous studies suggesting that HRT use was associated with a reduced risk of age-related cognitive decline, the WHI study, as reported in 2002, showed no such protective effect among women taking combination HRT.  In this new update, the impact of estrogen-only HRT on cognition among 3,200 women aged 65 and older is described.  During an average follow-up of more than 5 years, the estrogen-only HRT arm of the WHI study found that estrogen-only HRT was associated with a measurable and significant decline in overall cognitive function over the duration of the study.  Moreover, the adverse effects of estrogen-only HRT on cognitive function were especially pronounced in those women who already exhibited measurable decreases in cognitive functioning when they first entered the study.

These two updates from the WHI study group once again demonstrate that HRT, whether estrogen-only HRT or combination HRT, fails to protect older women from age-related declines in cognitive function, including dementia.  Worse still, both forms of HRT are associated with an actual increase in the risk of cognitive function decline and dementia, when compared to age-matched women who do not take HRT pills.

In my forthcoming book, The Great Hormone Debate: What Every Woman (and Man) Should Know About Hormone Replacement Therapy, it becomes clear that the mythology of HRT, which began taking form in the early 1960s (and which was then quickly adopted by most women’s physicians in the US and Western Europe), essentially replaced both common sense and established and reputable research that had gradually accumulated over the preceding three decades.  As this HRT mythology begins to unravel after four decades of unquestioning loyalty to its miraculous claims by the pharmaceutical industry, women’s healthcare providers, and many women’s health advocates, a paradigm shift in attitudes towards menopause and HRT is occurring now.  In my book, the HRT onion is peeled back, one layer at a time, leaving the reader with a clear, concise and objective understanding of the health-related issues associated with HRT, as well as science-based recommendations for safer non-HRT approaches to menopause symptom alleviation.  Stay tuned….

BRIEFLY…

JAMA:  Obesity, which has reached epidemic proportions in the US, has previously been linked to an increase in the risk of male erectile dysfunction.  A new randomized study looked at the impact of weight loss among 110 obese men, aged 35 to 55 years, with previously diagnosed erectile dysfunction.  All study participants were free of diabetes, high blood pressure or high cholesterol levels (all diseases that are also associated with erectile dysfunction) upon entry into this study.  The 55 men randomly assigned to the weight loss intervention group were actively assisted in attaining a weight loss of at least 10 percent of their total body weight, while the remaining 55 men were given pamphlets suggesting exercise and healthy diet strategies.   After two years, 17 of the 55 men in the intervention group were objectively found to have an improvement in erectile function, while only 3 of the 55 men in the non-intervention group showed an improvement in erectile function.  Following a statistical analysis of the data, decreased body mass index (BMI), increased levels of physical activity, and reduced blood levels of the C-reactive inflammatory protein (CRP) were all associated with improved erectile function.  In summary, healthy lifestyle changes were associated with a significant improvement in erectile function in one-third of obese men with previously diagnosed erectile dysfunction.

Journal of the National Cancer Institute:  Previous studies have suggested that a calcium-rich diet may be associated with a reduced risk of developing polyps within the colon and rectum.  (Most colon and rectal cancers are thought to arise from these initially benign “adenomatous” polyps.)  A new randomized, double-blinded, placebo-controlled study of 930 volunteers looked at the impact of supplemental calcium (1200 mg per day) on the incidence of colorectal polyps, as assessed by serial colonoscopies.  In this study, calcium supplementation was associated with an 11 percent reduction in the relative risk of developing the most benign form of adenomatous colorectal polyps (tubular adenomas) during the average 4-year duration of this study.  More strikingly, the relative risk of developing more advanced adenomatous colorectal polyps (which are associated with a higher risk of progressing to colorectal cancers) was reduced by a very significant 35 percent in the group of volunteers who were randomized to receive calcium supplementation.  Additionally, the protective effects of calcium in the colon and rectum appeared to be most prominent among study volunteers with high dietary intakes of calcium and fiber, and low intake of fat, although these correlations did not reach statistical significance.

Circulation:  A recent study suggested that ibuprofen, a common non-steroidal antiinflammatory drug (NSAID), when taken together with aspirin (another NSAID), might counteract aspirin’s well-known heart-protective effects.  A new study from the United Kingdom looked at almost 5,000 heart attack and coronary artery disease victims, and assessed the interactions, if any, from combined ibuprofen and aspirin use.  These patients were, in turn, compared with another 20,000 patients without a history of cardiac disease.  Contrary to previous reports, this new British study did not find any reduction in the heart-protective effects of aspirin when aspirin was combined with ibuprofen, or with another NSAID, Naproxen.