Gmail - [ProCOR] Hormone Replacement Therapy in Postmenopausal Women
Title: Main Morbidities Recorded in the Women's International Study of Long Duration Oestrogen After Menopause (WISDOM): A Randomised Controlled Trial of Hormone Replacement Therapy in Postmenopausal Women
Authors: MR Vickers, AH MacLennan, B Lawton, D Ford, J Martin, SK Meredith, BL DeStavola, S Rose, A Dowell, HC Wilkes, JH Darbyshire, TW Meade
Reference: BMJ 2007; 335: 239,http://www.bmj.com/cgi/content/abstract/335/7613/239
Reviewer: Robert Goldberg, PhD, ProCor contributing editor
Results of the study below suggest that postmenopausal women starting or restarting hormone replacement therapy are at increased risk for developing coronary heart disease than women not treated with this drug regimen.
Problem addressed: Long-term risks and benefits associated with use of hormone replacement therapy (HRT) in postmenopausal women.
Purpose of study: To assess the long-term benefits as well as risks associated with HRT in a large sample of postmenopausal women recruited from nearly 500 general practices in the UK, Australia and New Zealand.
Location of study: London, England, UK
Study design: RCT
Results: The WISDOM Trial recruited a large number of postmenopausal womenbetween the ages of 50-69 years from a total of 499 general practices in the UK (# of practices = 384), Australia (n=91) and New Zealand (n=24) to the receipt of estrogen only therapy, combined hormone therapy, or to placebo medication. A total of more than 56,000 women were screened for trial entry, 8,980 entered a trial run-in phase, and 5,692 were randomly assigned to the different treatment modalities. Recruitment to the trial began in 1999 and 2000; of the women enrolled in the trial, the vast majority was from the UK.
The trial randomization schema was stratified based on hysterectomy status and intended use of HRT. Women with an intact uterus were randomly assigned to the receipt of either combined estrogen plus progestogen therapy or to placebo. In parallel, women without a uterus or who were unwilling to take placebo therapy were randomly assigned to estrogen therapy, combined estrogen plus progestogen therapy or to placebo treatment.
A number of predefined primary as well as secondary study outcomes were examined in this trial. The primary trial outcomes were the occurrence of a major CHD event (e.g., unstable angina, fatal or nonfatal MI, or SCD), osteoporotic fractures, and breast cancer. The secondary trial outcomes included mortality from breast and other cancers, deaths from all causes, venous thromboembolic disease, cerebrovascular disease and dementia. The mean age of participating women at the time of study enrollment was 63 years, the majority were white, the average BMI was 28 and the primary comparison groups were relatively well balanced on the trial entry characteristics.
Over an average follow-up of approximately one year, women taking combined HRT had markedly increased rates of CVD and venous thromboembolic disease, and a nonsignificant reduction in the risk of developing osteoporatic fractures (31% reduction), as compared to those taking placebo. The incidence rates of cerebrovascular disease, breast cancer and other cancers were not significantly different between the respective comparison groups. The incidence rates of serious adverse events did not significantly differ in either of the randomized comparisons performed.
While there were no significant differences in the incidence rates of CVD events or venous thrombosis between women prescribed estrogen therapy, as compared to those taking estrogen plus progestogen treatment, there were suggestions of an increase in these primary endpoints in women prescribed combination therapy. Twice as many women in the combined therapy versus placebo groups withdrew from the trial while the rates of study withdrawal were similar in the combined versus estrogen therapy groups. This trial was prematurely stopped because of the results of the Women's Health Initiative Study which were published in 2002.
Comments: The results of the WISDOM Trial suggest that postmenopausal women starting or restarting combined estrogen and progestogen therapy are at increased risk for developing CHD than women not treated with this drug regimen. On the other hand, treatment with HRT was associated with a decreased risk of osteoporotic practices and decreased risk of osteoporotic fractures and no apparent impact on the risk of stroke or malignancy. Despite the large number of women included in this study, and rigorous trial design, appropriate caveats need to be placed in interpreting the results of this investigation given the premature discontinuation of this trial, relatively short duration of follow-up, and small number of events accrued at the time of study completion.
Similar to the Women's Health Initiative, the WISDOM trial tested the hypothesis that the use of HRT in elderly asymptomatic postmenopausal women might reduce the risk of developing several major comorbidities including CHD, stroke and cancer and have possible beneficial effects on reducing the risk of osteoporotic fractures.
A considerable amount of adverse publicity and patient concern and confusion has resulted from the results of the Women's Health Initiative trial. The results of the WISDOM trial and the Women's Health Initiative call into question any health benefits that might be accrued from the initiation of HRT in postmenopausal women in their 60s, especially on the occurrence of CVD. Decisions about the use of HRT in peri and postmenopausal women need to be carefully considered by patients and their physicians, together with considerations about quality of life, with benefits and risks carefully weighed in both absolute and relative terms.
Showing posts with label HRT. Show all posts
Showing posts with label HRT. Show all posts
Monday, August 27, 2007
Wednesday, July 11, 2007
HRT and Cardiac Risk - Debate
Medical News Today News Article
Wall Street Journal Examines Women's Health Initiative Findings On HRT's Effect On Heart Attack Risk
11 Jul 2007
The Wall Street Journal on Monday examined findings from the 15-year, $725 million NIH-sponsored Women's Health Initiative on hormone replacement therapy's effects on heart attack risk. According to the Journal, in the five years since the study was released, many in the medical community have said "some aspects" of the initial findings "were either misleading" or "overgeneralized in large part because they excluded many of the study's own investigators and physicians from the first review" (Parker-Pope, Wall Street Journal, 7/9).
NIH researchers in July 2002 ended the WHI study on combination HRT three years early because they determined that the treatment might increase the risk for heart disease, invasive breast cancer and other health problems. A later WHI analysis, published in the April 4 issue of the Journal of the American Medical Association, found that HRT use among women in their 50s does not increase their risk for heart attack (Kaiser Daily Women's Health Policy Report, 4/4).
In addition, a study published last month in the New England Journal of Medicine found that women in their 50s who took estrogen on a regular basis were 60% less likely than those who took a placebo to have large amounts of plaque in their arteries, an indicator of heart attack risk. Participants who took estrogen were 30% to 40% less likely than those who took a placebo to have large amounts of plaque in their arteries. However, participants who took estrogen had a higher risk for stroke than those who took a placebo, according to the study (Kaiser Daily Women's Health Policy Report, 6/22).
According to the Journal, the WHI's 40 researchers in 2002 were told 11 days before the initial WHI study report in JAMA was released that it had been halted early. Although some of them were concerned that the results were "too broadly interpreted," it was "too late to make meaningful changes" to the JAMA article, the Journal reports. Two ongoing studies are examining the role of estrogen in the development of heart disease, the Journal reports. Both studies also will examine whether using natural progesterone, instead of synthetic progestin used in WHI, reduces or eliminates breast cancer risk.
Comments
Jacques Rossouw, a physician with the National Heart Lung and Blood Institute who had overseen the WHI since its inception, said it was an "NIH decision supported by the WHI executive committee to keep it to a small group because we realized it was a sensitive paper." He said that the handling of the study's results was "based on what we knew at the time," adding, "Our main job ... was to turn around the prevailing notion that hormones would be useful for a long-term prevention of heart disease." It was a "worthy objective, which we achieved," Rossouw said.
Robert Langer -- former principal investigator for WHI's clinical center at the University of California-San Diego, who has since spoken as a witness for HRT maker Wyeth -- said, "I think that had the initial report been written by a broader group, as almost all of our later papers have been, it would have been framed differently."
According to the Journal, key questions about long-term use of HRT are "far from resolved." Most experts agree that HRT is a reasonable option for women to treat menopausal symptoms, but the "bigger question" is whether the drugs should be used to prevent heart-related conditions, the Journal reports. NHLBI says that HRT should not be used to prevent heart disease because of its potential to increase risk for breast cancer, blood clots and strokes. According to the health care information company IMS Health, HRT sales have declined 30% since the WHI results were published in 2002 (Wall Street Journal, 7/9).
Wall Street Journal Examines Women's Health Initiative Findings On HRT's Effect On Heart Attack Risk
11 Jul 2007
The Wall Street Journal on Monday examined findings from the 15-year, $725 million NIH-sponsored Women's Health Initiative on hormone replacement therapy's effects on heart attack risk. According to the Journal, in the five years since the study was released, many in the medical community have said "some aspects" of the initial findings "were either misleading" or "overgeneralized in large part because they excluded many of the study's own investigators and physicians from the first review" (Parker-Pope, Wall Street Journal, 7/9).
NIH researchers in July 2002 ended the WHI study on combination HRT three years early because they determined that the treatment might increase the risk for heart disease, invasive breast cancer and other health problems. A later WHI analysis, published in the April 4 issue of the Journal of the American Medical Association, found that HRT use among women in their 50s does not increase their risk for heart attack (Kaiser Daily Women's Health Policy Report, 4/4).
In addition, a study published last month in the New England Journal of Medicine found that women in their 50s who took estrogen on a regular basis were 60% less likely than those who took a placebo to have large amounts of plaque in their arteries, an indicator of heart attack risk. Participants who took estrogen were 30% to 40% less likely than those who took a placebo to have large amounts of plaque in their arteries. However, participants who took estrogen had a higher risk for stroke than those who took a placebo, according to the study (Kaiser Daily Women's Health Policy Report, 6/22).
According to the Journal, the WHI's 40 researchers in 2002 were told 11 days before the initial WHI study report in JAMA was released that it had been halted early. Although some of them were concerned that the results were "too broadly interpreted," it was "too late to make meaningful changes" to the JAMA article, the Journal reports. Two ongoing studies are examining the role of estrogen in the development of heart disease, the Journal reports. Both studies also will examine whether using natural progesterone, instead of synthetic progestin used in WHI, reduces or eliminates breast cancer risk.
Comments
Jacques Rossouw, a physician with the National Heart Lung and Blood Institute who had overseen the WHI since its inception, said it was an "NIH decision supported by the WHI executive committee to keep it to a small group because we realized it was a sensitive paper." He said that the handling of the study's results was "based on what we knew at the time," adding, "Our main job ... was to turn around the prevailing notion that hormones would be useful for a long-term prevention of heart disease." It was a "worthy objective, which we achieved," Rossouw said.
Robert Langer -- former principal investigator for WHI's clinical center at the University of California-San Diego, who has since spoken as a witness for HRT maker Wyeth -- said, "I think that had the initial report been written by a broader group, as almost all of our later papers have been, it would have been framed differently."
According to the Journal, key questions about long-term use of HRT are "far from resolved." Most experts agree that HRT is a reasonable option for women to treat menopausal symptoms, but the "bigger question" is whether the drugs should be used to prevent heart-related conditions, the Journal reports. NHLBI says that HRT should not be used to prevent heart disease because of its potential to increase risk for breast cancer, blood clots and strokes. According to the health care information company IMS Health, HRT sales have declined 30% since the WHI results were published in 2002 (Wall Street Journal, 7/9).
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