Hormone Replacement Therapy, Raloxifene and
Coronary Heart Disease


I was reading the medical journal The Lancet (May 9, 1998) last week and came across an article titled "Myth and Paradox of Coronary Risk and the Menopause."

The article spotlighted the myth that the risk of coronary heart disease in women is held low until menopause, when it rebounds, equalling and later surpassing that in men. The article shows (graphically) that mixed-age disease rates exaggerate rates in women against those in men, compared with age-specific rates. This is because of the older population mix of women and the relatively greater contribution, therefore, of older women to the combined rates.

The origin of the myth includes various circumstantial evidence, including observational studies on the apparent protective effect of hormone replacement therapy (HRT), which has been used successfully for 55 years to ease menopausal symptoms such as hot flashes. According to the article, these observational studies have created a professional (physicians) and commercial (drug companies) lobby to perpetuate the menopause myth, which feeds through into advertising, sponsored post graduate education and the lay press.

The myth is getting extra mileage now that HRT is being challenged by the new Eli Lilly drug, raloxifene. Eli Lilly is using the specter of increased breast cancer risk to scare women about HRT. HRT manufacturers are fighting back with HRT's alleged beneficial side effects, including reducing risk of osteoporosis and heart disease.

Then, today, I opened my copy of the Journal of the American Medical Association (May 13, 1998) and discovered a study titled "Effects of Raloxifene on Serum Lipids and Coagulation Factors in Healthy Menopausal Women." Researchers in this Eli Lilly-funded study report that raloxifene favorably alters certain biochemical markers of cardiovascular risk. But at least they acknowledged that "Further clinical trials are necessary to determine whether these favorable biochemical effects are associated with protection against cardiovascular disease."

So HRT and raloxifene are being marketed as reducing the risk of heart disease in older women -- a health outcome that has reached, according to the Lancet article, mythical proportions.

Perhaps the JAMA editorial accompanying the raloxifene study helps clear up some of the confusion.

Regarding HRT and coronary heart disease (CHD), the editorial says,

Notwithstanding the consistent, large, and statistically significant lower risk for CHD in HRT users, these observational studies do not, and cannot establish causality. Users differ from nonusers in important respects; e.g., they are thinner, better educated, and more health-conscious. Substantial differences in their CHD risk factor profiles before commencing estrogen use could easily explain most of the subsequent differences in CHD rates. Women who use estrogen replacement therapy for a number of years are good compliers, and as such may have other attributes that predict better health. In addition, these women are or will be under closer medical supervision and, thus, have earlier diagnosis and treatment of health conditions, leading to a lower mortality than that among nonusers. On the other hand, women who cease estrogen replacement therapy frequently do so because of illness, which makes remaining users appear even healthier. These various biases are quite strong, and may account for most or even all of the apparent benefit for CHD in observational studies.

Regarding raloxifene and coronary heart disease (CHD), the editorial states,

The uncertainties about the cardioprotective effect of estrogens apply doubly to raloxifene...

So if you're interested in reducing your risk of coronary heart disease, perhaps the best advice is to eat right, get plenty of exercise and have regular medical checkups.

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