Latest on HRT: Good news on life expectancy, Alzheimer’s disease
HRT may offer longer, healthier life but risks must be balanced
As the baby-boom generation moves toward menopause, more clinicians are faced with questions on the use of hormone replacement therapy (HRT). New information is available in three recently published articles, which indicate that HRT can increase life expectancy and possibly decrease the risk of Alzheimer’s disease for many women.
The most recent study, published in the New England Journal of Medicine (NEJM), looks at HRT’s effects on mortality. The second study, published in the June issue of Neurology, examines the effects of HRT on the risks of developing Alzheimer’s disease. The third study, published in the April 9 issue of The Journal of the American Medical Association (JAMA), reviews the use of an analytical model that shows that for most women, HRT use boosts life expectancy. (See story, p. 108, for a review of those studies.)
"I believe the NEJM article can be a very positive report," says David Archer, MD, professor of obstetrics and gynecology at The Jones Institute for Reproductive Medicine at The Eastern Virginia Medical School in Norfolk. He serves as chairman of the scientific program for this month’s annual meeting of the North American Menopause Society in Boston.
"No. 1, overall mortality is reduced in HRT users; No. 2, cardiovascular mortality is reduced 37% in current HRT users and 57% in women with risk factors for cardiovascular disease; and No. 3, long-term use increases the risk of dying from breast cancer, but the preventive health risk benefit ratio is strongly in favor of HRT" he says.
In the NEJM study, the beneficial effect is strongest for those women at high risk of heart disease, explains Michael Rosenberg, MD, MPH, clinical associate professor of obstetrics/gynecology and epidemiology at the University of North Carolina at Chapel Hill and president of Health Decisions, a private research firm in Chapel Hill. On the negative side, for women with a history or risk of breast cancer, individualized decisions must be made, he points out.
"The NEJM piece is important because it helps define exactly what benefits are strongest, and thus who the best candidates are," Rosenberg says. "Although these findings are qualified in some regard and represent a single study, they suggest that HRT is broadly beneficial and is currently underutilized."
While all major issues about HRT are not resolved in the NEJM , the data are more encouraging than alarming, says Andrew Kaunitz, MD, professor and assistant chair in the department of obstetrics/gynecology at the University of Florida Health Sciences Center in Jacksonville.
"It provides more mostly reassuring data about HRT improving women’s life expectancies," he observes. "It’s not the final answer about whether it really reduces the risk of heart attack or really increases the risk of breast cancer."
Nonetheless, Kaunitz points out that some have taken the same information published in the NEJM article simply to say that long-term use of HRT increases breast cancer mortality.
"It’s interesting that depending on what people’s focus is, they have take-home points from the same article that are completely different," he notes. "The discrepancy is striking."
Indeed, not all clinicians are accepting the NEJM article as proof positive of HRT’s benefits.
If the NEJM study shows a decrease in HRT benefits after 10 years due to the counteracting effects of breast cancer, what will be the case in 20 or 30 years? asks Susan Love, MD, adjunct associate professor of surgery at the University of California in Los Angeles.
"This gives one pause on the benefits of using HRT for the rest of a woman’s life," says Love, author of Dr. Susan Love’s Hormone Book (Random House, 1997), which argues for the inclusion of alternative therapies in menopause. "To my way of thinking, if HRT is for prevention, there are alternatives. We have to set the bar higher when we’re talking about prevention."
Even if one of every three women receives protection against coronary heart disease through HRT use, as shown in the NEJM study, that leaves two women who were never at risk for the disease in the first place on the medication. Should they remain on HRT?
"There are alternatives to preventing heart disease," Love says. "When considering long-term use of HRT, I would think very carefully about its use. It would be only for some patients, not the general population."
Clinicians are looking toward the results of the Women’s Health Initiative (WHI) to give definitive answers on the benefits of HRT. The largest prevention study ever funded by the National Institutes of Health, the WHI represents the gold standard of research: a large, prospective randomized controlled trial. The 15-year study of 164,500 women, which will include 100,000 in an observational study and the remainder in a randomized clinical trial, is estimated to cost $628 million.
The WHI clinical trial will examine whether HRT prevents heart disease or osteoporosis, as well as how it affects the risk of breast cancer. Other areas of study include how a low-fat diet affects the risks of breast and colorectal cancers and heart disease, as well as how calcium and vitamin D supplementation prevent osteoporosis and colorectal cancer.
An ancillary study of Alzheimer’s disease, called the Memory Study, has been added to the WHI. It will examine two questions: whether HRT will decrease the incidence of Alzheimer’s disease and dementia of any cause in postmenopausal women, and what its effects will be in slowing disease progression in women who do develop dementia.
Researchers hope that by adding the Memory Study, the number of women ages 65 to 79 enrolled in the study will increase. Women in this age bracket have been slower to enroll than women in their 50s, study organizers say.
Solving the menopause puzzle
With the wealth of information now available on HRT, how should a clinician approach the subject? Just know each patient represents a unique individual, says Nananda Col, MD, MPP, assistant professor of medicine at Tufts University School of Medicine, lead author of the study published in JAMA.
"We are trying to make a simple rule, so you can at least discern patients who might benefit from [HRT from] those who won’t, but also realize that this is a highly individual decision," she says of the analytical decision-making model reviewed in the study.
"Many have equated a gain in life expectancy with [the idea that HRT] should be recommended for everybody. And we explicitly discuss that in our paper and say, No, that’s not all what we’re saying.’"
Francine Grodstein, PhD, of Harvard University’s department of epidemiology and lead author of the NEJM article, concurs with Col’s assessment. "There still are many things that should lead to the [HRT] decision," she says. "Quality of life and individual preferences are important to women. What we did is just add one piece of information that might help them make that decision."
Many options, both traditional and alternative, are now available to women. For some patients, HRT may be appropriate, while for others, it may not, Kaunitz says.
"Most people would consider me and a lot of other gynecologists pro-hormone, but that’s not actually where I’m coming from at all," he says. "I’m really into assessing individual issues with each patient and helping them to make decisions as an individual, and part of that is offering as broad an array of appropriate therapeutic options as possible."
New options include the Estring Vaginal Ring, an estradiol vaginal ring introduced earlier this year by Pharmacia and Upjohn of Kalamazoo, MI. A soft flexible ring inserted in the vagina, the product releases a low continuous dose of estradiol directly to the vaginal mucosa for a 90-day period. Little of the estradiol is absorbed, so systemic effects are minimal, the company reports. Kaunitz has used the device after making collaborative decisions with breast cancer patients and their oncologists to treat atrophic genital symptoms to avoid systemic estrogen replacement.
Other bone-building medications, such as Fosomax (alendronate sodium) from Merck Laboratories of Rahway, NJ, may be used to treat osteoporosis, Kaunitz says. He has prescribed the medication for breast cancer patients with premature menopause due to chemotherapy who are not considered optimal candidates for conventional hormonal replacement therapy and who have low bone density on a dual-energy X-ray absorptiometry scan.
"The more I do this, and a big proportion of my practice is menopause and HRT, the more I recognize that every candidate brings different issues and priorities to her HRT decision making," Kaunitz says.
"We need to stay well clear of thinking that we should make decisions for patients, but rather help guide them to make what seems to be a good decision for them, based on their issues and priorities."
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content