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The following information is from the National Institute of Neurological Disorders and Stroke

Several large studies have shown that caffeine intake is associated with a reduced risk of developing Parkinson's disease (PD) in men, but studies in women have been inconclusive. A new study shows that hormone therapy is a possible explanation for the different effects of caffeine on PD risk in men and women.

"We hoped to find something that would explain the effect of caffeine on PD risk in men and the lack of an effect in women," says lead author Alberto Ascherio, M.D., Dr.P.H., of the Harvard School of Public Health. "Hormones seemed like a possible factor in this case."

Ascherio and his colleagues found combining coffee and hormones significantly increases women's risk of developing PD, even though each factor alone has previously been found to protect against PD. The study shows that postmenopausal women who took hormone replacement therapy (HRT) and drank more than five cups of coffee per day (heavy coffee drinkers) were one and a half times more likely to develop PD than heavy coffee drinkers who didn't take HRT.

Taking coffee out of the equation, HRT seemed to have a protective effect against PD; these results support those of earlier studies. Women who drank little or no coffee and took HRT had 65 percent less risk of developing PD than light coffee drinkers who didn't take HRT. The study was funded in part by the National Institute of Neurological Disorders and Stroke and appears in the March 11, 2003, issue of Neurology.

The researchers studied survey data from more than 77,000 nurses who participated in the Nurses' Health Study, a comprehensive 20-year study designed to take a closer look at women's health.2 One hundred fifty-four women in this group were diagnosed with PD during the study. Overall, there was no difference in disease incidence between women who were and weren't using HRT. However, when caffeine consumption was factored in, HRT made a big difference in PD risk.

Among women taking HRT, the increased risk of PD was confined to women who drank more than five cups of coffee per day. Drinking small amounts of coffee per day did not appear to affect the risk of PD in these women. Women who did not take hormones who drank less than half a cup of coffee per day had a PD risk similar to that of men, Dr. Ascherio says.

The type of hormones and the duration of use did not seem to affect outcomes. The researchers note that they controlled for possible effects of cigarette smoking, which has repeatedly been shown to be associated with a decreased risk of PD.

Dr. Ascherio says these results could explain the inconsistencies researchers have seen in the caffeine-PD association in women. He says it also lends further credibility to the argument that caffeine may have a protective effect against PD. "Now we know that when you take hormones out of the equation, caffeine has the same effect on women as it does in men," says Dr. Ascherio. "To me, this is very compelling."

While this study may help researchers build a more solid case for caffeine's relationship with PD, women should not read too much into it. "Women should not change their habits or stop taking hormones because of this study," Dr. Ascherio says. "We need more studies so we can take a closer look at the relationship and mechanisms involved.¬Ē Researchers say that while caffeine is clearly associated with PD in some way, they lack convincing evidence that caffeine actually prevents the disease. "Association does not equal causality," says co-author Michael Schwarzschild, M.D., Ph.D., of Harvard Medical School and Massachusetts General Hospital.

The mechanism by which caffeine affects PD remains a riddle. In animal models, researchers have shown that caffeine can prevent the loss of dopamine-producing nerve cells seen in PD, but researchers still don't know how this occurs. Dr. Schwarzschild says the protective effect could be related to caffeine's ability to block a particular receptor in the brain. How such a blockade might protect nerve cells remains unknown, he adds.

The effect of estrogen on the relationship between caffeine and PD is even harder to explain. "There are several possible explanations, all of which need to be tested," says Dr. Schwarzschild. Estrogen is known to have neuroprotective effects in PD, so there is a chance that estrogen and caffeine are competing and therefore canceling out each other's effect, he says. Another theory is that estrogen could in some way interfere with how caffeine is broken down in the body. To begin testing these theories, researchers are now studying whether the protective effects of caffeine differ in male and female animal models. Dr. Ascherio stresses the need to confirm the findings of this study in larger prospective studies of PD in women. Many other researchers continue to probe the complex differences in PD risk between men and women. In a recent study appearing in the March 2003 issue of the journal Movement Disorders,3 researchers at the Mayo Clinic in Rochester, Minnesota found that environmental factors may play a greater role in the development of PD in men than in women, and that genetic factors may have a greater influence on the disease in women than in men.

The researchers suggest that more men, especially of older generations, have been exposed in the workforce to environmental factors, such as pesticides, industrial chemicals and head injuries. On the other hand, they found that women require a stronger genetic susceptibility to develop PD. The researchers also affirmed previous findings that estrogen reduces the risk of developing PD. The Mayo Clinic study was also funded in part by NINDS.

The NINDS is a component of the National Institutes of Health in Bethesda, Maryland, part of the U.S. Department of Health and Human Services, and is the nation's primary supporter of biomedical research on the brain and nervous system.