The results were presented July 3 at the 18th UICC International Cancer Congress in Oslo, Norway.
First randomised trial
Funded by the United States' National Cancer Institute, the study is the first randomized clinical trial to assess the effect of exercise on blood estrogens in postmenopausal women.
The study included 173 women between the ages of 50 and 75 years who were previously sedentary, overweight or obese, and not taking hormone- replacement therapy. The women were recruited from the Seattle, area. The women were carefully screened for eligibility and were assigned at random to either a moderate-intensity aerobic exercise group or a stretching control group. The exercise group exercised 45 to 60 minutes, five days a week, for a year. The control group met weekly for a 45-60 minute stretching class for a year.
The exercise program consisted of facility-based and home exercise. The participants met three times a week with an exercise physiologist at an exercise facility, where they performed treadmill walking and stationary biking. They also exercised two days a week at home, doing exercises of their own choosing, mostly walking. The exercisers were highly adherent to the exercise intervention: 81 percent of the exercisers completed 80 percent or more of their prescribed 225 minutes per week of exercise. Adherence was lower at 12 months than at three months. After one year, cardiorespiratory fitness increased by 13 percent in exercisers, and by less than 1 percent in controls.
Decrease in level of estradiol and estrone
At the beginning of the study, there was a strong, statistically significant correlation between body size and levels of estrogens: heavier women had higher levels of all three estrogens studied (estradiol, estrone and free estradiol). After three months, women in the exercise group had a 7 percent decrease in the level of estradiol, the most potent blood estrogen, while women in the stretching group had no change in estradiol levels. Among exercisers, there was a 4 percent decrease in estrone levels compared with a 3 percent increase in controls, and the difference was statistically significant. After 12 months, there was still a difference in blood estrogens between exercisers and controls, although the effect was lower than at three months.
Among the exercisers who lost body fat, the effect of exercise was strongest: exercisers who lost more than 2 percent of their initial body fat had a 14 percent decrease in estradiol levels. Controls who lost body fat, however, did not experience a decrease in estradiol levels.
The changes in estrogen levels were not due to dietary changes; on average, exercisers did not change the amount of calories they took in, and controls had only a slight, decrease in calorie intake.
High estrogen levels – high risk
The results of this study are very significant, says principal investigator Anne McTiernan, M.D., Ph.D., director of Fred Hutchinson's Prevention Studies Clinic and Exercise Testing and Training Center, and a member of the center's Cancer Prevention Research Program in the Public Health Sciences Division.
"We know that women still make estrogen after menopause, although they make it in their fat cells instead of in their ovaries. Women who have high blood-estrogen levels after menopause have a high risk of developing breast cancer. Therefore, it is important to find ways to lower estrogen levels for women who want to lower their risk of breast cancer," says McTiernan, also a research associate professor at the University of Washington schools of Public Health and Medicine.
"Previous studies have found associations between high levels of body fat, a sedentary lifestyle and high blood-estrogen levels. However, these were observational studies and therefore we did not know if the observed associations were real or if they were due to another variable. For example, women who choose to exercise may have different diets or drink less alcohol, and these behaviors also may affect estrogen levels. This is the first study to directly test the effect of an exercise program on blood-estrogen levels in women who were previously sedentary. This tells us that the effect of exercise on estrogen is likely real, and that exercise can affect estrogen levels even if started later in life."
The average age of the study participants was 60 years. Most (86 percent) were Caucasian and highly educated (99 percent were high-school graduates). Their average Body Mass Index (weight corrected for height) was 30.7, which means that on average they were very overweight to obese. In addition to being sedentary, they had low cardiorespiratory fitness as measured by a treadmill test. Exercisers and controls were virtually identical on these demographic and health characteristics.
Direct evidence
"This study gives us direct evidence that exercise can affect biology related to breast cancer in older women. More than two dozen epidemiologic studies have found that women who exercise have a 30 to 40 percent reduced risk of developing breast cancer. Researchers have hypothesized that some of the protective effect of exercise may occur through its effect on estrogen levels. However, no study before has been able to directly test this in postmenopausal women," McTiernan says.
The particular strength of this study was its randomized, controlled clinical-trial design. This is considered the gold standard of study designs in medicine, according to McTiernan. "In this type of study, we are able to directly control for extraneous factors, and we are also able to directly observe what the women are doing rather than just relying on what they report on questionnaires. Therefore, we have more confidence in the results."
Weight loss did not have same effect
Another important finding was that weight loss by itself did not seem to have the same effect of exercise. Some of the controls lost weight during the year, but their estrogen levels did not decrease. Exercisers who did not lose weight, however, did not experience lowered estrogen levels. Therefore, it appears that exercise that results in weight loss is important. Two thirds of the exercisers lost some amount of body fat, and 31 percent lost more than 2 percent body fat. Among controls, in contrast, only 13 percent lost more than 2 percent body fat.
"The beauty of exercise as a method to prevent breast cancer is that it can be done by most women at low cost and with low risk of side effects. In addition, exercise has many other health benefits. The good news is that it is never to late to enjoy the health benefits of exercise," McTiernan says.
The Fred Hutchinson Cancer Research Center, home of two Nobel Prize laureates, is an independent, nonprofit research institution dedicated to the development and advancement of biomedical technology to eliminate cancer and other potentially fatal diseases. Fred Hutchinson receives more funding from the National Institutes of Health than any other independent U.S. research center. Recognized internationally for its pioneering work in bone-marrow transplantation, the center's four scientific divisions collaborate to form a unique environment for conducting basic and applied science. Fred Hutchinson is the only National Cancer Institute-designated comprehensive cancer center in the Pacific Northwest and is one of 41 nationwide. For more information, visit the center's Web site at www.fhcrc.org.