CHICAGO—Taking estrogen provides no overall benefit for chronic disease prevention in postmenopausal women with previous hysterectomy, but does appear to increase the risk of stroke and decrease the risk of hip fracture, according to a study in the April 14 issue of the Journal of the American Medical Association (JAMA).

Estrogen therapy has been available to postmenopausal women for more than 60 years, according to background information in the article. Despite decades of use and considerable research, the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain.

The Women's Health Initiative (WHI) clinical trials of hormone therapy were undertaken to determine whether conjugated equine estrogen (CEE) alone (for women with prior hysterectomy) or in combination with progestin (medroxyprogesterone acetate) would reduce coronary heart disease (CHD) events in mostly healthy postmenopausal women. The WHI estrogen plus progestin trial was halted in July 2002 because health risks exceeded benefits, including increased risks for CHD, stroke and breast cancer.

In this new report on the estrogen alone intervention, the WHI investigators assessed the effects of CEE, the most commonly used postmenopausal hormone therapy in the U.S., on major disease incidence rates. In this randomized, double-blind, placebo-controlled disease prevention trial conducted in 40 U.S. clinical centers beginning in 1993, 10,739 postmenopausal women, aged 50-79 years, with prior hysterectomy were enrolled, including 23 percent of minority race/ethnicity. The women were randomly assigned to receive either 0.625 mg/day of CEE or placebo.

The WHI authors write that in February 2004, the National Institutes of Health (NIH) decided to end the intervention phase of the trial early. Based on data for the major clinical outcomes available through February 29, 2004, the researchers found that with an average of 6.8 years of follow-up, CEE had no significant effect on reducing the risk of CHD (376 cases), but did cause a significant increase (39 percent increase) in risk of stroke (276 cases). CEE significantly reduced the risk of hip fracture (39 percent reduction, 102 cases), was associated with a non-significant reduction in risk of breast cancer, (218 cases), and had no significant effect on risk of pulmonary embolism (85 cases) or colorectal cancer (119 cases). Corresponding results for composite outcomes were a significant increase (12 percent) in the risk of total cardiovascular disease, and a significantly decreased risk (30 percent) of total fractures, but no significant effect on total cancer, total mortality, and a global index . For the outcomes significantly affected by CEE, there was an absolute excess risk of 12 additional strokes per 10,000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10,000 person-years. The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10,000 person-years.

CHICAGO—The accuracy of computed tomographic colonography ("virtual colonoscopy") for the detection of colorectal cancer is lower than that for conventional colonoscopy, suggesting that use of "virtual" colonoscopy should be limited until techniques and training can be improved, according to a study in the April 14 issue of the Journal of the American Medical Association (JAMA).

According to background information in the article, conventional colonoscopy is the best available method for detection of colorectal cancer and its precursors. However, it is invasive and not without risk, so a simpler alternative would be welcome. Computed tomographic colonography (CTC) has been reported to be reasonably accurate in the diagnosis of colorectal tumors in studies performed at expert centers. CTC involves the examination of computer-generated images of the colon constructed from data obtained from an abdominal computed tomographic examination.

Peter B. Cotton, M.D., of the Digestive Disease Center at the Medical University of South Carolina, Charleston, S.C., and colleagues assessed the accuracy of CTC in a large number of participants from multiple centers. The study included 615 patients aged 50 years or older who were referred for routine, clinically indicated colonoscopy at nine major hospital centers between April 17, 2000 and October 3, 2001. The CTC was performed before the standard colonoscopy and results were compared.

The researchers found that the sensitivity of CTC for detecting participants with one or more lesions sized at least 6 mm was only 39 percent and for lesions sized at least 10 mm, it was only 55 percent. These results were significantly lower than those for conventional colonoscopy, with sensitivities of 99 percent and 100 percent, respectively. The accuracy of CTC varied considerably between centers and did not improve as the study progressed.

CHICAGO—An article in the April 14 issue of the Journal of the American Medical Association (JAMA) reviews current information on the "epidemic" of lung cancer in U.S. women, and explores contributing factors and possible reasons for increased lung cancer deaths in women..

Jyoti D. Patel, M.D., of the Feinberg School of Medicine, Northwestern University, Chicago, and colleagues write that the death rate from lung cancer in U.S. women rose 600 percent from 1930 to 1997, surpassing breast cancer as the leading cause of cancer death by nearly 20,000 patients a year. The authors cite data that indicate "an estimated 80,100 U.S. women were diagnosed as having lung cancer in 2003 and 68,800 died from their disease."

However, the authors point out that women are targeted in tobacco advertising, and teenage girls are often drawn to cigarette smoking under a variety of social pressures, and also that "smoking remains the primary cause of lung cancer, and nearly one-quarter of women in the United States continue to smoke. Whether women are more susceptible to the carcinogenic effects of tobacco smoke than men is debatable. What is not debatable, however, is that important differences exist among men and women with lung cancer. Women smokers are more likely than men to develop adenocarcinoma of the lung. Women who have never smoked are more likely to develop lung cancer than men who have never smoked. Mounting evidence suggests that this could be due, in part, to estrogen signaling."

The authors add that in the past, major studies for lung cancer prevention and early diagnosis have excluded women. "... it is critical that future lung cancer research specifically include a proportion of women that reflects the true incidence of lung cancer in women."

According to the authors, one of the most important challenges lies in avoiding the U.S. scenario in other parts of the world.

ESTROGEN LINKED TO STROKES