ACOG Statement of WHI Report
July 10, 2002
Preliminary Statement to ACOG Membership on the Women’s Health Initiative Study
On July 9, 2002, it was announced that the Women’s Health Initiative (WHI) study evaluating combined estrogen and progestin use in postmenopausal women was halted. This component of the WHI series of randomized trials, sponsored by the National Heart, Lung, and Blood Institute of the National Institutes of Health, assessed the effects of combined hormone replacement therapy use in healthy postmenopausal women with an intact uterus. After review of reported data, the study safety monitoring board concluded that the risk of combined HRT use in this study population outweighed the benefits.
In response to these developments, the American College of Obstetricians and Gynecologists has reviewed the published study results and offers the following preliminary observations:
The evidence presented indicates a true increased risk for breast cancer and for cardiovascular disease for women taking combined estrogen and progestin as follows:.
o Breast cancer risk 1.26 [95% confidence interval (CI) 1.00-1.59]
o Coronary heart disease risk 1.29 [CI 1.02-1.63]
o Stroke risk 1.41 [CI 1.07-1.85]
o Pulmonary embolism risk 2.13 [CI 1.39-3.25]
Although the risk of breast cancer and cardiovascular disease is increased, the magnitude of the actual risk is small for individual women (8 additional cases of breast cancer per 10,000 women; 7 more coronary heart disease events, 8 more strokes, and 8 additional pulmonary embolism cases per 10,000 women)
It is also important to note that the study results indicate that women taking combined estrogen and progestin had a decreased risk of hip fracture (0.66 [95% CI 0.45-0.98]) and of colorectal cancer (0.63 [95% CI 0.43-0.92]).
The WHI study of estrogen-only use in women who had previously undergone hysterectomy is continuing with no reported increased risk of breast cancer.
Although the study tested only one drug regimen (conjugated equine estrogen 0.625mg/d plus medroxyprogesterone acetate 2.5 mg/d), all patients on hormone replacement therapy should be made aware of this small but significant increased risk, in particular those taking estrogen and progestin combinations.
The risk for an individual woman should be identified based on years of hormone replacement therapy use and her individual health history. The WHI trial was halted when significant risk was observed after an average of 5.2 years of use. The increased breast cancer risk did not appear in the first four years of use. Risks for blood clots were greatest during the first 2 years of hormone use. The reduced risk of colorectal cancer emerged after 3 years of hormone use.
Hormone replacement therapy for the treatment of acute menopausal symptoms, when indicated, continues to be appropriate for short-term use without an apparent increase in risk of breast cancer for up to 4 years.
Women at risk for cardiovascular disease who choose to discontinue use of combined estrogen and progestin therapy should explore alternative therapies to hormone replacement, including the use of statin drugs and lifestyle modifications such as regular exercise and smoking cessation.
Women at risk for osteoporosis who choose to discontinue use of combined estrogen and progestin therapy should explore alternative therapies such as alendronate.
Women who choose to switch from combined estrogen and progestin therapy to estrogen alone, and who have not undergone hysterectomy, should be advised of the increased risk of endometrial cancer with estrogen alone and should be monitored with endometrial biopsy or ultrasound or both.
ACOG has formed an expert working group to review and evaluate immediately the WHI study results and expeditiously to provide recommendations. The College has also formed a Task Force to review in depth the overall risks and benefits of hormone replacement therapy and to provide detailed clinical practice guidance. ACOG members will be apprised of these new recommendations as soon as they are available.
A full report of the Women’s Health Initiative study is currently available on the JAMA web site at http://jama.ama-assn.org/issues/v288n3/ffull/joc21036.html or in the July 17, 2002, issue (JAMA 2002;288:321-3). Additional information on WHI, including statements of the study authors and fact sheets, can be found at www.nhlbi.nih.gov and www.whi.org.