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A Medical Puzzle

Until a few years ago, hormone replacement therapy was routinely prescribed for post-menopausal women. It was claimed that ongoing administration of female hormones (including estrogen and progesterone) had multiple beneficial effects, among which:

  • maintaining healthy bones (i.e., delaying the onset of osteoporosis)
  • alleviating unpleasant hot flashes
  • providing cardiovascular protection (i.e., reducing the risk for heart attacks, strokes, blood clots, etc)

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The presumption that hormonal therapy provides cardiovascular protection was in part based upon the fact that premenopausal women sustain on average less heart attacks than men of the same age. However, in post-menopausal women the rate of heart attacks appears to be equal to that in men of the same age. These findings seem to suggest that estrogens have a protective role against heart attacks and atherosclerosis.

But scientists were in for a surprise: Against all expectations, comparative double-blind studies revealed that post-menopausal women taking hormone replacement suffered a higher rate of cardiovascular events than post-menopausal women who were not taking hormones. The difference was so significant it eventually led physicians to reconsider the indication of hormonal replacement therapy in post-menopausal women. At present, this type of therapy is only indicated for severe, intractable hot flashes. As for the prevention of osteoporosis, a different class of medications is now being used for this purpose, namely the biphosphonates (e.g. Actonel, Fosamax, etc).

The above being said, one can't help but wonder: What causes this radical discrepancy between the expected result (i.e., the fact that hormone replacement would provide cardiovascular protection), and the reality of the situation, which happens to be the exact opposite?

It's a documented fact that prior to menopause, women experience on average fewer heart attacks than men. Multiple past studies, as well as anecdotal evidence, are attesting to this fact. So it appears that estrogens do have at least some protective role. But then, why the increase in heart attacks and strokes in post-menopausal women taking hormonal therapy?

Here's a possible explanation for this enigma: Over the past few decades, with obesity becoming a common-place condition which affects about 60% of Americans, a new factor was introduced in the equation. According to scientific research, fat cells produce estrone (a weak estrogen) as part of their normal metabolism. Estrone has an additive effect with other estrogen sources in the body, the net result being an overall increase in estrogen activity, which is sustained over time. It's possible this scenario is responsible for the increased incidence of cardiovascular events observed in women on hormonal treatment.

Simply put: Estrogen replacement treatment in overweight women may be associated with increased cardiovascular risk, whereas estrogen replacement in women of normal weight may in fact have a protective effect.

At this point, no clear medical conclusions have been reached regarding this issue, and routine hormonal therapy in post-menopausal women is currently not indicated in the US.

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