Topics in Advanced Practice Nursing eJournal 2(3), 2002. © 2002 Medscape
The results from HERS II did not show that HRT provided cardiac protection in women who had previously diagnosed heart disease. The data actually indicated an increase in cardiac events during the first year of use for this group. However, a reanalysis of data from the HERS I study published in the June 25, 2002 issue of Circulation[2] reported that women enrolled in the study who were using HRT and an HMG-CoA reductase inhibitor (known as a "statin") were found to have the same risk of coronary events as those women in the placebo group. Additionally, women taking statins in this study were found to have fewer venous thrombotic events. In the first year of use, women in the HRT arm of the HERS I study had a higher rate of cardiovascular events, but this same effect was not shown for the women who also took statins in addition to HRT.
Another recently published study, the Women's Health Initiative (WHI), presented information in the July 17, 2002 issue of JAMA.[3] The estrogen and progestin arm of the WHI enrolled 16,608 postmenopausal women between the ages of 50 and 79 years who were randomly assigned to either HRT consisting of conjugated equine estrogen 0.625 mg per day combined with medroxyprogesterone acetate 2.5 mg per day (Prempro) or placebo. The planned duration of this trial was to be 8.5 years.
The purpose of this research was to assess the major benefits and risks of HRT with regard to specific outcomes: coronary heart disease, venous thrombotic events, breast cancer, colon cancer, and fractures. Limits for trends in adverse events were set prior to the start of the study that were used to determine whether the trial would continue. In addition, a global index was set to summarize the balance of risks vs benefits that were being studied. Quality-of-life issues, including reduction of hot flashes and vaginal dryness, were not part of the risk benefit analysis.
On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board of WHI recommended stopping the trial of the estrogen and progestin arm of the trial because the predetermined boundary for invasive breast cancer was exceeded. In addition, the global index supported the belief that the risks outweighed the benefits for the indicators that were being studied. Table 1 shows the hazard ratio for the study, representing the percentage of increase/decrease in the study outcomes, and the actual numbers of increase/decrease per 10,000 women. It should be noted that there was no difference in rates of mortality between the 2 groups.
1. Quality-of-life issues resulting from estrogen loss such as hot flashes, vaginal dryness, and cognitive issues were not part of the risk benefit equation studied.
2. The HRT arm of the trial was halted because the rate of breast cancer crossed a predetermined boundary set at the beginning of the trial. The rate of breast cancer of 1.26 (confidence interval 1.00-1.59) neared significance, but was not actually statistically significant when the trial was halted. This information is similar to what is in the package labeling. Data from the study suggest that the risk for an individual woman taking HRT is less than 1% (0.07%)
3. The fact that the slight increase in invasive breast cancer was noted at year 4, with a trend toward a later decline in the number of cases, supports the theory that HRT promotes the growth of existing breast cancer rather than causes breast cancer.[4] In general, breast cancer develops to the point where it can be diagnosed over an 8-10 year span. However, due to the premature termination of this arm of the study, this question cannot be answered.
4. Women in the HRT group were told that the study had been discontinued. Those women who wished to continue their HRT were told to talk to their personal healthcare professional. They were not told to stop therapy immediately.
5. The data safety monitoring board did not recommend discontinuing the estrogen-only arm of the trial for women who had hysterectomies.
6. The WHI data demonstrate that HRT reduces hip fractures and colon cancer.
7. Women who chose to discontinue HRT for any reason should consult their healthcare provider to consider other measures that will protect them from osteoporosis and other long-term illnesses.
1. Cardiac protection: Women who are taking or considering HRT only for the prevention of CVD should be counseled on other methods to lower their risks of CVD.
2. Osteoporosis: Women who are taking HRT only for the prevention of osteoporosis should talk to their healthcare professional about their personal risks and benefits for continuing. WHI concluded there were risks associated with long-term use, although the risk to an individual is very small. There are effective alternatives for the prevention of osteoporosis, such as bisphosphonates, raloxifene, and calcitonin. Those alternatives should be considered for those women whose only need for HRT is the prevention of osteoporosis.
3. Short-term (1-4 years) relief of menopausal symptoms: For women taking HRT for short-term relief of menopausal symptoms, the benefits of HRT are likely to outweigh the risks.
4. Longer-term (more than 4 years) relief of postmenopausal symptoms: While vasomotor symptoms (hot flashes and night sweats) tend to be of short duration for many women, symptoms such as vaginal dryness continue throughout the postmenopausal period. In addition, many women report that use of estrogen makes them feel, sleep, and think better. These women may also find that longer term-use, coupled with the proven benefits of prevention of fractures and reduction of colon cancer, may also outweigh the risks. Alternatives such as vaginal estrogen for vaginal dryness and other treatments for mood and sleep disorders may also be discussed. Long-term use of HRT should be discussed with each woman with consideration for her overall benefits and risks, including those benefits and risks that were not studied in the WHI.
5. Use of other combination HRT: The WHI studied one preparation of HRT. The data from the WHI cannot be applied to all HRT therapies containing estrogen and progestin (including transdermal therapies). However, because other preparations or delivery systems have not been studied in this same way, it cannot be concluded that the results would be different for other combined products. Therefore, women initiating or continuing all types of combined HRT should weigh the risks and benefits as suggested above. More studies are needed on other combination therapies, alternatives to oral therapy, doses, and regimens of combined products.
6. Individualized care: Care that views every woman as a unique person with different factors in terms of personal and family medical history, different emotional needs, and different values and belief systems has always been emphasized by NPWH. The results from the WHI put even greater emphasis on counseling and informed decision-making by women.
1. See their healthcare professional for recommended visits for breast, cervical, colon, and skin cancer screening, and undergo laboratory tests for evaluating bone density, lipids, glucose, thyroid, and other tests according to their personal and family history. Blood pressure, height, and weight are also important measurements to evaluate.
2. Decrease or stop smoking.
3. Maintain or achieve healthy weight through exercise and diet.
4. Stay active, including regular weight-bearing exercise.
5. Limit alcohol intake.
6. Try to eliminate stresses and conflicts that decrease overall well being.
7. Have something to look forward to, whether a vacation, a new interest, or family events like the birth of a grandchild.
8. Follow the recommendations of their healthcare professional with regard to ways to prevent diseases like heart disease and stroke or the complications of diseases such as diabetes and osteoporosis.
9. Recognize that happiness and long-term health cannot be manufactured or found in an herb or other product, but found through a variety of strategies that are different for every woman.
Outcomes Hazard Ratio Increased Risk in 10,000 Women Taking Prempro for 1 Year Coronary heart disease (CHD) +29% 7 more CHD events Stroke +41% 8 more strokes Venous thromboembolism (VTE) (blood clots) +111 18 more VTEs Breast cancer +26% 8 more invasive breast cancers Colorectal cancer -37% 6 fewer colorectal cancers Hip fracture -34% 5 fewer hip fractures
Adapted from Writing Group for the Women's Health Initiative Investigators. JAMA. 2002;288:321.
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NPWH recognizes and respects women as the decision-makers for their healthcare. NPWH's mission includes protecting and promoting a woman's right to make her own choices regarding her health within the context of her personal, religious, cultural, and family beliefs. Contact NPWH's President and CEO, Susan Wysocki, at swy1@aol.com.
*Published with the permission of the National Association of Nurse Practitioners in Women's Health (NPWH). Copyright held by NPWH.