1. Potera, Carol


New studies find associated health risks.


Article Content

The latest report from the Women's Health Initiative (WHI) clinical trial shows that at almost three years after the study ended, women who took hormone replacement therapy (HRT) during the five-year study have no higher incidence of cardiovascular disease than women who took placebos. But they may have a higher risk of cancer.


Experts had halted the trial in 2002 after finding a higher risk of invasive breast cancer and heart disease in those taking HRT. The new study followed 15,703 of the WHI's original 16,608 participants for an average of 2.4 years and found that former HRT users showed a 24% higher risk of all cancers, compared with nonusers. Rates for endometrial cancer continued to be lower in the HRT group than in the placebo group, and rates for invasive breast cancer were higher-but neither individual difference was statistically significant.


Other risks attributed to HRT. The observed higher risk of heart disease in the HRT group during the original study disappeared during follow-up; both groups showed similar rates of heart attacks, strokes, embolism, and venous thrombosis. Rates of colorectal cancer and of hip, vertebral, and other osteoporotic fractures were also similar during the follow-up period, despite earlier results hinting that HRT might prevent fractures and decrease the risk of colorectal cancer.


Study coauthor JoAnn Manson told AJN that for menopausal women considering HRT "the key question is whether symptoms of menopause [such as hot flashes or night sweats] are severe and frequent enough to disrupt sleep or quality of life." In such cases, she recommends HRT for only two to three years and not more than five.


More support for an estrogen-cancer association. The WHI and other studies support a link between estrogen and first-time breast cancer. Estrogen-blocking drugs such as tamoxifen (Nolvadex) have been effective in treating estrogen-responsive tumors. But does estrogen contribute to a recurrence of breast cancer in survivors?

Figure. Geraldine Bo... - Click to enlarge in new windowFigure. Geraldine Boggs, MS, RN, 64 (shown here on March 3 in Washington, DC), participated in a WHI study showing higher rates of cancer in postmenopausal women who'd taken HRT for five years than in women who hadn't. Boggs told

Yes, according to Rock and colleagues, who monitored disease-free breast cancer survivors during a seven-year dietary trial. About three-quarters had had estrogen-receptor positive tumors, and two-thirds took tamoxifen, shown to be effective in treating breast cancer; 93% were postmenopausal. The 153 survivors who developed new primary cancers were matched to 153 women who remained cancer free; there were no significant differences between the groups in baseline characteristics, such as treatment, prior use of HRT, tumor type, age, ethnicity, and physical condition. In women whose breast cancer recurred, blood levels of estradiol were twice as high as levels in those whose breast cancer didn't return.


Many general research papers report that moderate-to-vigorous exercise reduces circulating estrogens. "There is no reason to think that this effect would not also occur in breast cancer survivors," Rock told AJN.


Carol Potera


Heiss G, et al. JAMA 2008;299(9):1036-45; Rock CL, et al. Cancer Epidemiol Biomarkers Prev 2008;17(3):614-20.