Hormone replacement therapy: Review choices in light of new data
Help women assess risk/benefit ratio, reasons for HRT use
If your practice includes a large number of women who are using hormone replacement therapy (HRT), chances are your office telephone lines haven’t stopped ringing since July, when news of the cessation of the estrogen/progestin trial of the Women’s Health Initiative (WHI) touched off a wave of calls from worried patients and caused providers to take a second look at the risks and benefits of the drug therapy.
In the large-scale clinical trial, almost 17,000 menopausal women who were ages 50-79 and who had an intact uterus at the time of enrollment were randomized to use combined HRT vs. a placebo. The use of combined estrogen and progestin was halted after 5.2 years because researchers found that the therapy’s risks outweighed its benefits.1 (See p. 99 for a review of the study design, and p. 100 to gain a perspective of the determined risks. To read the full-text results of the study free of charge, go to the Journal of the American Medical Association (JAMA) web site, www.jama.com.)
What effect has the halted HRT trial had?
For providers and patients affiliated with Kaiser Permanente Northern California (KPNC) in Oakland, the impact has been "enormous," says Ruth Shaber, MD, women’s health leader.
"In Northern California, we have at least 100,000 members on these medications," explains Shaber. "We thought it was very important that women learn that HRT was no longer recommended for prevention of heart disease."
Jeffrey Maurus, MD, is a Rock Island, IL, OB/GYN who is active in private practice at Medical Arts Associates and serves as medical director of the Rock Island County Health Department family planning clinic. He says his office has never received so many telephone calls in response to a media report.
Maurus says he is stopping all combined progestin/estrogen HRT for women using the drug regimen for long-term prevention. Many of his patients will continue to need to use HRT on a short-term basis for moderate-severe vasomotor symptoms. "Patients who are surgically menopausal will need estrogen and/or androgen until age 50," he notes. "Postmenopausal women on estrogen only may continue until results from that part of the WHI study are completed."
Weigh the results
Compared with the placebo users, those assigned to the HRT group in the WHI trial experienced more strokes, heart attacks, and blood clots, as well as an increased risk of invasive breast cancer. Although the HRT users also experienced a reduced risk of colorectal cancer and fractures (including hip fractures), overall, observed risks outweighed benefits.
News of the WHI trial cessation came on the heels of the published results from a follow-up from the Heart and Estrogen/Progestin Replacement Follow-Up Study (HERS II), which was designed to assess the efficacy of HRT for secondary prevention of coronary heart disease (CHD). The findings from that randomized trial indicate that HRT should not be used to reduce risk for CHD events in women with pre-existing heart disease.2,3
"While the publication of the studies is new, much of what has been reported regarding breast cancer and blood clots has been in package labeling for HRT many years," says Susan Wysocki, RNC, NP, president and chief executive officer of the Washington, DC-based National Association of Nurse Practitioners in Women’s Health (NPWH). "What is new is there is more information to guide safe clinical practice as well as informed decision-making by women on the issue of whether or not to use HRT."
Give women guidance
How should you counsel women in light of the WHI news? Review the following suggestions from the NPWH:
• Cardiac protection: Women who are taking or considering HRT only for the prevention of cardiovascular disease should be counseled on other methods to lower their risks of cardiovascular disease.
• Osteoporosis: Women who are taking HRT only for the prevention of osteoporosis should talk to their health care professional about their personal risks and benefits for continuing the drug regimen. WHI concluded there were risks associated with long-term use, although the risk to an individual is very small. Because there are alternatives for the long-term prevention of osteoporosis, such as raloxifene, bisphosphonates, and calcitonin, those alternatives should be considered for those women whose only need for HRT is the prevention of osteoporosis.
• Short-term 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.
• Longer-term 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 also may find that longer-term use, coupled with the proven benefits of prevention of fractures and reduction of colon cancer, also may outweigh the risks. Alternatives such as vaginal estrogen for vaginal dryness and other treatments for mood and sleep disorders also may 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. (Contraceptive Technology Update reviewed suggestions for managing perimenopausal symptoms in the July 1998 article, "Multiple approaches ease perimenopausal symptoms;" see p. 93.)
• Use of other combination HRT: The WHI studied one preparation of HRT. The data from 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.
• Individualized care: The NPWH always has emphasized care that views every woman as an individual with different personal and family medical histories, emotional needs, and values and belief systems. The results from WHI put even greater emphasis on counseling and informed decision making by women.
Within 36 hours of the public announcement of the study’s cessation, KPNC medical experts developed a WHI fact sheet for the managed care organization’s members, says Shaber.
Within the next two weeks, the fact sheets, along with a letter explaining the organization’s consensus of opinion on HRT use, were mailed to all members using HRT regimens. KPNC also instituted special phone lines at its call centers for women to hear a recorded message on the subject. Despite these efforts, KPNC physicians and nurse practitioners continue to be inundated with messages and calls from panicked women, says Shaber.
"Although KPNC had softened its recommendations for cardiac prevention over the past several years following the HERS trial, we still have many patients who have been on HRT for over 10 years, just for preventive health," says Shaber says of her organization’s decisions following the WHI news. "We also wanted to reassure women who were taking the hormones for symptomatic relief of hot flashes that there was no reason to panic, and it was safe to stay on their medications until they had a chance to talk with their physicians and re-evaluate whether they wanted to stay on HRT." (Register your response to the question "What does the halted WHI estrogen/progestin study mean for your practice?" on the CTU web site, www.contraceptiveupdate.com.)
1. Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002; 288:321-333.
2. Grady D, Herrington D, Bittner V, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/Progestin Replacement Study Follow-up (HERS II). JAMA 2002; 288:49-57.
3. Hulley S, Furberg C, Barrett-Connor E, et al. Noncardio-vascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/Progestin Replacement Study Follow-up (HERS II). JAMA 2002; 288:58-66.
A guide for the post-HRT world
What do you tell patients looking for advice in a world where hormone replacement therapy is no longer universally recommended? "Post HRT: An Evidence-based Guide to Alternative Therapies" is available from American Health Consultants to help you find your way. The cost is $99, which includes a $50 discount for Contraceptive Technology Update subscribers. Call (800) 688-2421 and ask for book number S02114.