ORLANDO — When counseling postmenopausal women about hormone therapy, frame the discussion in terms of absolute rather than relative risks, a principal investigator of the Women's Health Initiative said.
“Hormone therapy still has a clinical role in treatment of moderate to severe hot flashes and other menopausal symptoms,” Dr. JoAnn E. Manson said. “Recently menopausal women tend to be the best candidates due to low absolute risks and a greater frequency of symptoms. Very often the results of the WHI are discussed in terms of relative risk,” she said. For example, the widely publicized findings were that women taking estrogen plus progestin therapy had a 29% increase in coronary heart disease risk, 41% for stroke, 113% for pulmonary embolism, and 26% for breast cancer (JAMA 2002;288:321–33).
From the perspective of absolute risk, stroke occurs in about 1 in 1,000 women aged 50–59 years in the general population. “For a woman struggling with severe vasomotor symptoms and sleep trouble … telling her the risk will increase from 1 in 1,000 to 1.4 in 1,000 sounds better than telling her the stroke risk will increase 40%,” Dr. Manson said at the annual meeting of the North American Menopause Society.
That is not to say that the risk should be dismissed, she qualified. “It is still an important risk and should not be discounted.”
WHI researchers also found that adverse effects increased with age. “The number of excess cases of stroke or pulmonary embolism that would be caused by hormone therapy would be much less in younger women,” said Dr. Manson, chair of the division of preventive medicine, Brigham and Women's Hospital, and professor of medicine and women's health at Harvard Medical School, both in Boston.
In 2006, in an estrogen-only trial, “we did see a difference between younger and older women for outcomes of coronary heart disease death or MI,” Dr. Manson said (Arch. Intern. Med. 2006;166:357–65). Compared with women not taking estrogen, the relative risk of cardiac death or MI was 0.63 among women aged 50–59 years, 0.94 for women aged 60–69, and 1.11 in women aged 70–79.
In a more recent study, they found the hazard ratio for coronary heart disease among women on hormone therapy was 0.93 for the younger age group, 0.98 for women aged 60–69, and 1.26 for women aged 70–79 (JAMA 2007;297:1465–77). The differences were not significant.
However, Dr. Manson and her associates also found a statistically significant 30% reduction in total mortality in 50- to 59-year-olds. Specifically, younger women taking hormone therapy had a 0.70 hazard ratio for mortality, compared with 1.05 for women aged 60–69 years and 1.14 for women aged 70–79.
Hormone therapy may have a neutral or beneficial effect on the heart if started during early menopause, when the arteries and endothelium are likely to be relatively healthy, Dr. Manson suggested. In contrast, therapy may be associated with a deleterious effect if started in late menopause, when advanced atherosclerosis and unstable plaques may be present.
The implication is not that recently menopausal patients should take hormone therapy to prevent coronary artery disease, Dr. Manson said. Rather, the results could reassure younger women about cardiac risks when they are pondering short-term therapy to ameliorate vasomotor symptoms.
The cardiovascular risks associated with estrogen and progestin may diminish after therapy is stopped, according to another secondary analysis (JAMA 2008;299:1036–45).
Saying 'the risk will increase from 1 in 1,000 to 1.4 in 1,000 sounds better than [saying it] will increase 40%.' DR. MANSON