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New data emerge from the WHI: How will they impact your practice?
Hormone therapy initiated closest to menopause onset is safest
Has your treatment of menopausal women changed since the initial findings released from the Women's Health Initiative (WHI) randomized, controlled trials of hormone therapy (HT)? Findings from a just-published secondary analysis of data from the WHI indicate that women who initiated HT closer to menopause tended to have reduced risk of coronary heart disease (CHD), while women further from menopause tended to have a slightly higher risk for the disease.1
While the news may be seen as reassuring for younger women with moderate to severe menopause symptoms who are considering hormone therapy use, they do not change the current recommendation that hormone therapy should not be used at any age for prevention of CHD, caution scientists involved with the analysis.
Hormone therapy appears to be a reasonable option for the short-term treatment of moderate to severe menopausal symptoms in women who are less than 10 years past the onset of menopause, says Jacques Rossouw, MD, lead author of the study and chief of the WHI branch at the National Heart, Lung, and Blood Institute of the National Institutes of Health. The therapy does not appear to increase the risk of heart disease in such women, though they should take care of risk factors such as high blood pressure and also have regular mammograms, he observes.
"The average duration of treatment in the trials was four to five years, which is longer than the two to three years most women would need to see them through the initial menopausal symptoms," states Rossouw. "The findings for short-term treatment do not imply that any benefit, or lack of harm, will persist over longer periods of time; therefore, women should use the hormones for the shortest time needed to alleviate their symptoms."
Review the history
The WHI, a long-term national health study, is focused on strategies for preventing heart disease, breast and colorectal cancer, and osteoporotic fractures in postmenopausal women. One component of the study was designed to examine the effects of combined hormones or estrogen alone on the prevention of coronary heart disease and osteoporotic fractures and on associated risk for breast cancer.
The estrogen plus progestin trial was halted early in July 2002 after 5.2 years after researchers found that the therapy's (Prempro, Wyeth; Philadelphia) risks outweighed its benefits.2 The cessation of the estrogen/progestin therapy set off a flurry of concerned calls from patients and a subsequent drop in use of hormone therapy. Findings from a just-published study indicate that a sharp decline in the rate of new breast cancer cases in 2003 may be related to the decline in the use of hormone therapy.3 Age-adjusted breast cancer incidence rates in women in the United States fell 6.7% in 2003, according to the study results.
The WHI estrogen-alone study was stopped at the end of February 2004 because results indicated that the drug therapy [combined equine estrogen (CEE), Premarin, Wyeth; Philadelphia] increased the risk of stroke and did not reduce the risk of coronary heart disease, a key question of the trial.4 The drug did not increase the risk of breast cancer, researchers noted.
What do new data show?
In the latest WHI analysis, the authors combined data from the estrogen/progestin and estrogen-only trials to explore previously observed trends in hormone effects by distance from the onset of menopause. Differences in hormone therapy effects were examined in three age categories (50 to 59, 60 to 69, and 70 to 79) or in years since the onset of menopause (less than 10, 10 to 19, and 20 or more).
What did the analysis discover? The increased risk in heart disease due to hormone therapy in older women is primarily in those who also have hot flashes and night sweats. Women in the study who had these symptoms were more likely to have risk factors for CHD such as high blood pressure or high blood cholesterol. Researchers could not determine whether this finding explained their higher risk on hormone therapy.1
Other findings from the analysis include:
What is your approach?
Most women requesting treatment of vasomotor and related symptoms are patients in their late perimenopausal years and young postmenopausal women — those whose last period was less than one decade prior, observes Andrew Kaunitz, MD, professor and assistant chairman of the Department of Obstetrics and Gynecology at the University of Florida Health Science Center in Jacksonville. Unfortunately, the use of complementary approaches, such as soy supplements and black cohosh, and nonhormonal prescription therapies, such as antidepressants, have not consistently proved more effective than placebo in treatment of such symptoms,5 says Kaunitz.
"In looking both at relative and absolute benefits and risks from WHI and other evidence, hormone therapy represents a reasonable approach to treatment of bothersome symptoms in late perimenopausal and young postmenopausal women," says Kaunitz. "After initiation of treatment, clinicians and their patients can consider reducing the dose of hormone therapy gradually, over a number of years."
Some women ultimately may choose to discontinue therapy when symptoms are no longer bothersome, while others — particularly those in whom skeletal health concerns are present — may choose to continue a low dose of hormone therapy indefinitely, says Kaunitz. When vasomotor symptoms are not a concern and symptoms of genital atrophy are bothersome, vaginal rather than systemic therapy is appropriate, he states.
The North American Menopause Society (NAMS) recently released an updated position paper on use of hormone therapy.6 Current evidence supports the use of estrogen/progestin or estrogen-alone therapy for menopause-related symptoms and disease prevention in appropriate populations of peri- and postmenopausal women, the position paper states.6 (Access the statement at the NAMS web site, www.menopause.org. Click on "Other Healthcare Professionals," then "NAMS Estrogen and Progestogen Position Statement," to download the statement.)
Clinicians should use the new WHI data to talk to women in both relative and absolute terms, help them understand what risks are involved, and discuss the "considerable" benefits offered by hormone therapy, says Lee Shulman, MD, distinguished physician and professor in the Department of Obstetrics and Gynecology at Northwestern University's Feinberg School of Medicine in Chicago. Shulman presented information on hormone therapy at the recent Contraceptive Technology conference in Washington, DC.
In randomized trials and observational studies, estrogen/progestin and estrogen-alone therapies have been shown to be effective in treating and preventing vasomotor symptoms, vulvovaginal atrophy, urinary symptoms of dysuria, frequency and nocturia, as well as preventing osteoporotic fractures of the hip and spine,7 says Shulman. "While hormone therapy is not for everyone, it is clearly an important component of menopausal management for the majority of women who are seeking relief from menopausal symptoms," Shulman states.