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Estrogen and Heart Disease - Women's Health Initiative - Hormone Replacement Therapy Potential Risks and Benefits - HRT

April 13th 2006

Estrogen and Heart Disease - Women's Health Initiative - Hormone Replacement Therapy Potential Risks and Benefits - HRT


This new analysis of the Women's Health Initiative Estrogen-Alone trial is being touted much too strongly by the media, Wyeth, and certain physicians. They have looked at the data, run with it, and made conclusions, which is VERY irresponsible at this point in time.

The analysis showed an insignificant "trend" toward heart disease prevention among women in their 50s, the group of women at lowest risk for heart disease. There were no trends seen for older women. The problem with interpreting these results as "beneficial" is that the number of younger women was too few to draw any conclusions.

What's more, the only significant "trend" regarding estrogen alone and heart disease was in the first 2 years of the study, which showed a small INCREASED risk. After that, almost half of the women dropped out of the study, thus potentially obscuring the results. Like estrogen-progestin, estrogen alone significantly upped the risk of stroke and there was also a small risk of blood clots.


The composite outcome for dementia or mild cognitive impairment was also slightly increased among those taking estrogen. While it is interesting that women on estrogen required fewer revascularization procedures, this finding does not inherently equate with "fewer heart attacks." It's like saying fractures are the same as low bone density. The analysis of this study is unstable, not only because it lacks significance, but also because it disregards the earliest time trends, the high dropout rates, and the looming question of whether or not estrogen's effects (if they are truly beneficial) would be SUSTAINED into old age when women are most likely to suffer a heart attack and in whom no beneficial trends were observed in this trial.

Also muddying this analysis is whether the scientists' assumptions about heart disease in general are even true - that older women who have not had a heart attack MUST have undiagnosed heart disease and that younger women have pre-subclinical disease with a hypothetical "window of opportunity" for prevention. Again, a coronary EVENT is not the same as aging arteries.


There is a myriad of cardiovascular effects seen with estrogens, some positive, some negative. Though estrogen most certainly has a good effect on cholesterol levels and MIGHT slow atherosclerosis, there are proven drawbacks, including blood clots, elevated CRP, and increased triglycerides. What proponents of estrogen therapy need to be very careful about not doing is putting something into practice based on an analysis that focuses on surrogates or clinically unproven parameters, such as a procedure or splicing of subjects by age. The latter most importantly is a continuum, not an absolute with cutoffs.

Lastly, what should not have been ignored in this analysis was unfortunately. The absolute CHD outcomes of the WHI estrogen alone trial practically mirrored those of HERS I and II (the very first secondary prevention trials utilizing estrogen/progestin), showing an early significant increase in coronary events that tapered off to yield an overall neutral effect. WHI I (Prempro) yielded similar increased risks initially, but the increase in coronary heart disease never did taper off, yielding overall risk.


High doses of Premarin increased the risk of heart disease in men treated for prostate cancer. Combining this data with the results of secondary outcome trials and the knowledge about the blood clotting, stroke and coronary risks associated with contraceptives (used by YOUNG women by the way) and even with pregnancy (when endogenous estrogen is highest), you can see how this incessant attempt by 'experts' to find a benefit to the heart winds up seeming foolhardy. And, hypothetically, if estrogen alone were to ultimately yield benefit after consideration of all of the lingering questions, scientists would THEN have to prove whether this effect would apply to a non-hysterectomized woman, who may implicity have a lower heart disease risk to begin with simply because her ovaries are intact.

All in all, the results of WHI should be taken at face value, which indicate either net harm or overall lack of benefit. Sub-analyses of data within data have to be considered very carefully if the effects either lack true significance or are in stark contrast to the overall effects observed.

Therefore, trying to reinstate estrogen as a preventative would be cavalier at this point and any woman or physician trying to digest this new spin needs to be leery about thinly disguised sales pitches for pharmaceuticals trying to make a rebound. What's more, they should investigate very carefully who's spewing out this "good news" (namely Lila Nachtigall, Wolf Utian, Mitchell Harman, Frederick Naftolin, Howard Hodis, Mary Jane Minkin etc.) and what the driving force behind their motivations might be.

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Jonathan Raymond

Books on Heart Disease

Keywords and misspellings:  coranary micro-vascular disfunction iscemic iskemic ishcemic ishcemia angiograf blood presure stroke embolism imbolism embilism embelism bloode clot

Important:  The material on Best Syndication is for informational purposes only and is not a substitute for medical advice or treatment for any medical conditions. You should promptly seek professional medical care if you have any concern about your health, and you should always consult your physician before starting a fitness program.

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