The Puzzle of Aspirin and Sex

In the latest issue of the prestigious New England Journal of Medicine Dr Richard Levin takes a deeper look at the differential effect of aspirin in males and females brought to the fore by the publishing of the Women's Health Trial.

To summarise, the Physicians' Health Trial conducted in the 1980s looked at an exclusively male population to see whether low-dose aspirin had any effect on reducing cardiovascular problems (e.g. heart attacks, strokes) and found "that aspirin significantly reduced the risk of myocardial infarction: the reduction was 44 percent in men 50 years of age or older who did not have clinical evidence of coronary disease. There was no significant effect on the risk of stroke and no effect on mortality from cardiovascular causes."

The current Women’s Health Study shows, at least in women younger than 65 years of age who do not have a history of cardiovascular disease, that aspirin has no significant effect either on the risk of myocardial infarction or on the risk of death from cardiovascular causes but that it is associated with a 24 percent reduction in the risk of ischemic stroke and a 17 percent reduction in the risk of stroke overall...The findings in men and women are opposite. How can this be?

This is not the first biological phenomenon wherein a gender bias has been noted. An association between autoimmune diseases and females has been long recognised and the differing hormonal millieux have been implicated.

Some fascinating insights in the editorial:

• "Concentrations of salicylate are higher in women than in men after identical doses of aspirin, and platelets from women and men who have ingested aspirin show different responses when tested in vitro."


• "Women have smaller coronary arteries, and quite remarkably, when a man receives a woman’s heart through cardiac transplantation, the smaller female arteries grow larger in the male recipients, independently of body-surface area."


• "The cardiovascular systems of women and men are not the same, differing expression of disease follows, and the disquieting results of the current study should not be a complete surprise."

The article concludes:

On the basis of the Women’s Health Study, for now it would appear reasonable to avoid prescribing “low-dose” aspirin, defined as a daily dose of 75 to 100 mg or so, as a preventative measure for coronary disease in women under the age of 65 years unless the global risk score is very high.

But what about the prevention of stroke? Ridker and colleagues conclude, correctly, that the decision to prescribe aspirin for the primary prevention of stroke and other vascular events should be left to the patient and her physician, invoking an ancient truth. Hippocrates, dean of medicine on the island of Cos some 2400 years ago, popularized white-willow salicin, the precursor of aspirin, and wrote in the first of the Aphorisms, “Life is short, the art long, opportunity fleeting, experiment treacherous, judgment difficult.”

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