Washington, March 5 : Latest findings by the Women's Health Initiative (WHI) have confirmed that the health risks of long-term use of combination hormone therapy - wherein both estrogen and progestin are involved - in healthy, postmenopausal women persist even a few years after stopping the medication, and clearly outweigh the benefits.
The results of the WHI three-year follow-up study of the estrogen-plus-progestin clinical trial suggest that three years after the combination hormone therapy was stopped, many of the health effects of hormones such as increased risk of heart disease were diminished. However, overall risks, including the likelihood of stroke, blood clots, and cancer, remained high.
"The good news is that after women stop taking combination hormone therapy, their risk of heart disease appears to decrease. However, these findings also indicate that women who take estrogen plus progestin continue to be at increased risk of breast cancer, even years after stopping therapy. Today's report confirms the study's primary conclusion that combination hormone therapy should not be used to prevent disease in healthy, postmenopausal women," noted Dr. Elizabeth G. Nabel, Director, the National Heart, Lung, and Blood Institute (NHLBI).
The follow-up study focussed on 15,730 postmenopausal women with an intact uterus, aged 50 to 79 years at enrolment, who participated in the WHI estrogen-plus-progestin clinical trial. Participants were randomly assigned to receive a combination of estrogen (0.625 milligrams of conjugated equine estrogens per day) plus progestin (2.5 mg of medroxyprogesterone acetate) or placebo (inactive pill).
It began in July 2002 after women in the study were instructed to stop taking combination hormone therapy, and continued through March 2005, with participants followed for an average of 2.4 years.
The subjects were examined at least once a year, and received an annual breast examination and mammogram, with biopsies performed as needed.
According to the study report, the numbers of heart attacks, strokes, and blood clots were not significantly different between the two groups during the study - overall, 343 cardiovascular events among those who initially received hormone therapy versus 323 among those who did not.
Besides, the number of deaths was not significantly different - 233 women in the hormone therapy group died, compared to 196 in the placebo group.
"After being on combination hormone therapy for several years, the women's risk of cardiovascular disease was significantly higher - from a 29 percent increase in heart attacks to a 41 percent increase in strokes and nearly twice the risk of serious blood clots - compared to the women who did not take hormones," said Dr. Michael S. Lauer, director of the NHLBI Division of Prevention and Population Sciences.
"While it is reassuring that heart attack risk decreased and that the risks for stroke and blood clots did not grow after the women stopped taking hormones, this study provides further evidence that five years of combination hormone therapy is harmful. All the accumulated risks do not simply disappear," he added.
The researchers also report that other effects of combination hormones, such as decreased risk of colorectal cancer and hip fractures, also stopped when therapy ended.
"We continue to encourage women to use hormones only if needed for menopausal symptoms, and for the shortest time possible, and to adopt and maintain a healthy lifestyle, that is, engage in regular physical activity, maintain a healthy body weight, consume a diet low in saturated fat, and to not smoke, to reduce their risks of cardiovascular and other chronic diseases," said Dr. Marcia Stefanick, professor of medicine at Stanford University, Stanford, California, and a co-author of the paper, as well as chair of the WHI Steering Committee.
She feels that women should receive tests for cholesterol levels, blood pressure and other health risks, and take preventative measures as needed.
The research team has also reported that the risk of breast cancer among women continued at a rate similar to that seen during treatment,
Participants who had stopped taking estrogen plus progestin were about 27 percent more likely to develop breast cancer than the women who didn't take hormones during the study, with 79 women in the post-treatment group developing breast cancer during the three-year follow-up study, compared to 60 women in the non-treatment group.
"The hormones' effects on breast cancer appear to linger. These findings reinforce the importance of women getting regular breast exams and mammograms, even after they stop hormone therapy," noted Dr. Leslie Ford, associate director for clinical research in the Division of Cancer Prevention of the NIH's National Cancer Institute.
The study report, published in the Journal of the American Medical Association, further reveals a 24 percent increased risk of developing any form of cancer among women who had been in the treatment group. A more detailed analysis on the cancer findings is underway.
"The continued increased risk of breast cancer clearly plays a role in the increased overall risk of cancer years after stopping long-term estrogen plus progestin therapy, and it is important that we continue to follow these women," added Stefanick, noting that the new results provide further evidence that the health risks of long-term combination hormone therapy outweigh the benefits.