Three new articles that help explain why the public is so confused about what they should or should not be doing to promote their health
(June 2007)

In the first few months of 2007, three articles and the attending publicity did the following:

1. Suggested vitamin intake is dangerous.

2. Indicated hormone replacement therapy may not be so dangerous after all for women who start estrogens and progestin at the time of or shortly after the menopause.

3. Said women ages 40 to 49 may not need to follow the recommendation for annual mammograms.

Let’s look at the three articles.

1. Vitamin use may be dangerous for your health.  The study that created all the anxiety about multi-vitamin supplements was published in the Journal of the   American Medical Association, February 28, 2007.  It is a summary review of 68 antioxidant vitamin trials.  There was no evidence of harm when all the studies were considered together.  Then, the authors analyzed the 47 studies they considered the best.  According to that analysis, vitamin A increased deaths by 16 percent, beta carotene increased deaths by 7 percent, and vitamin E by 4 percent.  Neither vitamin C nor selenium either increased or reduced deaths.  A   careful look at the individual studies included suggests:

- The modest increase in deaths with vitamin A probably related to high doses, well above the 3,000 International Units per day that is recommended.

- The small increase in deaths with beta carotene may or may not be real, may not be  significant and probably related to doses above the recommended 3 to 15 milligrams a day.  But, nobody should be taking a specific beta carotene supplement anyway.

- The even smaller alleged increase in deaths with vitamin E is probably invalid.  The real finding is that there was no evidence of decreased death rates with administration of vitamin E; that is hardly surprising and there are multiple studies that suggest vitamin E supplements to prevent coronary heart disease and heart attacks are not useful.

In sum, there is really no good evidence that standard doses of antioxidants in one-a-day multivitamins are harmful and the scare is unwarranted.  At the same time, the best evidence in regard to health benefits of vitamin supplements is for vitamin D, folic acid, and vitamin B12.  There is not much good evidence for most of the other constituents of one-a-day multivitamins other than to prevent deficiency in those who are undernourished or malnourished or follow certain diets (such as strict vegetarian diets).

2. Hormone replacement treatments.  Four years ago, investigators from the Womens’ Health Initiative told the world how dangerous hormone replacement treatment (estrogens plus progestins) are for postmenopausal women, complications including increased risk of heart attack, breast cancer, and stroke. Based on these results and ominous warning from experts, women in large numbers stopped using the hormones and physicians stopped prescribing them, even though hormone replacement therapy (HRT) is clearly the best treatment for hot flashes and other menopausal symptoms.  Now, four years later, a new     report by basically the same investigators in the Journal of the American Medical Association, April 4, 2007 concludes HRT may be okay for younger women who   start the drugs within the first ten years after the start of the menopause.  But, they could have figured that out from their earlier reports and they could have    provided the public with balanced conclusions.  At the same time, some experts        did point out that other studies suggested that the dangers were much less for     younger women who started treatment around the time of or shortly after the menopause.  Healthful Life was very clear about this (see Archives under “Estrogens”, ‘More negative reports on postmenopausal hormone treatment - but maybe the treatment is okay for some women’; ‘Estrogen alone for postmenopausal women - the other shoe drops part way’; ‘The postmenopausal hormone use debate - it won't stop').

The new report is a re-analysis of the original data.  The critical data, none of which is statistically significant, among women starting HRT within ten years of menopause show:

- A 12 percent drop in heart attacks during the five to seven year followup period.

- A 38 percent increased risk of stroke.

- A 19 percent drop in deaths.

The authors note “there were no significant increases in risk due to hormone therapy for any outcome (heart attack, stroke) at ages 50 to 59".

Most women who start HRT do so within five years of the menopause.  The benefit:risk ratio would probably look even better for such younger women.

So, the experts and many investigators scared the public with dire warnings that now appear, at least for younger women, to have been clear exaggeration.  Since HRT is the most effective treatment for menopausal symptoms, the conclusion is that use is okay with the caveat that risk of stroke and breast cancer occurrence (but not breast cancer deaths) will still be increased a bit; the benefits include likely resolution of menopausal symptoms, less bone strength loss, perhaps a reduced risk of heart attack and perhaps reduced deaths.  The investigators urge that postmenopausal estrogen use be limited to several years, but they actually do not know whether prolonged use starting at the time of menopause is really dangerous or whether it could result in additional benefit by:   preventing or postponing osteoporosis; lowering occurrence of heart attack, lowering overall deaths (mortality); and possibly reducing the risk of memory impairment during aging and even reducing the risk of developing Alzheimer Disease.

One thing is clear.  The investigators have succeeded in confusing the public.  What can we conclude?

- HRT is reasonable and good treatment for moderate to severe menopausal symptoms.  If used, it is obligatory to get yearly mammograms.  There may be a modest increased risk of stroke (not yet proved).

- Among women who start HRT at the time of or shortly after the menopause, whether continuing use beyond several years increases its benefits or becomes more dangerous is not known.

- Women ten years or more post menopause or older than age 60 should not start HRT at that time to prevent coronary heart disease, osteoporosis, or any other disease.

3. The new mammography recommendation for women ages 40 to 49 from the American College of Physicians.

Breast cancer is one of the leading causes of death in women ages 40 to 49.  It causes almost as many deaths as heart disease in this age group.  About 36,000 women ages 40 to 49 are diagnosed with breast cancer annually and about 5,000 in this age group die each year from the disease.  There has been consensus that women should be screened with mammography starting at age 40 in order to diagnose the disease early so it can be treated effectively before it spreads and kills.  Why would the American College of Physicians want to weaken that consensus?  Why would they want to let a large number of these cancers become more advanced or spread before they are diagnosed?  To support a new recommendation that will discourage women ages 40 to 49 from obtaining mammograms the American College of Physicians commissioned a review of mammogram studies in this age group.  Eight previous such analyses had been done; this review adds no new information, insights, or different results.  It concludes that mammography results in a modest reduction in deaths from breast cancer in the 40 to 49 year age group, but the reduction was not as great as found with mammography done regularly after age 50.  That is not exactly news.

But, they probably underestimated the benefit for three reasons:

- They reviewed older studies in which the mammogram technology was much less sophisticated than it is now.

- In many of the studies, mammography was recommended less frequently  than yearly (that is, every 18 months to 2 years).

- The studies they reviewed were intention to treat meaning that if a woman was assigned to have mammograms, did not follow the assignment, developed breast cancer and died she was listed as a mammogram failure even though she never had a mammogram.  That is a program failure, not a mammogram failure.

Then they listed the disadvantages:

- Possible induction of breast cancer from the low doses of radiation during mammogram testing.  They point out there is no current evidence for this.

- The problem of false positives.  That is an issue, but they point out women know about this, accept it, and false positives do not cause women to stop regular mammogram screening.

- Overdiagnosis, that is finding tumors that will never become invasive and spread.  That, too, is an issue, but there is no direct evidence of this and the percentage of detected tumors that will, if not stopped, become invasive is so great that this is no real issue.

- Pain or discomfort during the mammography.  Suggesting this might be a rationale for discouraging use of mammograms is ridiculous.

The American College of Physicians recommendations said: (a) that physicians should do risk analysis (high versus low risk) even though, for the overwhelming majority of women, it is not clear exactly how to do that; (b) the decision to do or not do mammography should be based on a discussion of the benefits and risks and on women’s preferences.  Unfortunately, the overwhelming majority of women and their physicians will not be familiar with the details of the individual mammogram studies or the alleged risks.

This is an unwarranted and unnecessary action by the American College of Physicians.  They add nothing new, provide no new insights; they seem to put themselves in the position of saying it is not necessary to detect breast cancer early in the majority of women ages 40 to 49, and it is okay to wait until after age 50 even though the cancers will be more advanced and some women will die because their cancers were not detected early enough.  It is not okay.

Bjelakovic, G., et al.  Mortality in randomized trials of antioxidant supplements for primary and secondary prevention.  Journal of the American Medical Association.  Vol 297 (February 28) Pgs 842-857.  2007.

Rossouw, J.E., et al.  Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause.  Journal of the American Medical Association.  Vol 297 (April 4) Pgs 1465-1477.  2007.

Qaseen, A., et al.  Screening mammography for women 40 to 49 years of age. Annals of Internal Medicine.  Vol 146 (April 3) Pgs 511-515.  2007.

Armstrong, K., et al.  Screening mammography in women 40 to 49 years of age: systematic review.  Annals of Internal Medicine.  Vol 146 (April 3) Pgs 516-526.  2007.