Value of long-term hormone replacement therapy questioned

Short-term benefits are clear, but physicians and patients are faced with an ever-increasing collection of conflicting reports about advantages over the long run.

By Victoria Stagg Elliott, amednews staff. March 4, 2002.

Last month, a study in the Journal of the American Medical Association found that the incidence of breast cancer increased by as much as 85% among women who used hormone replacement therapy over the long term. Another study in JAMA just the week before found that quality of life, long a deciding factor in whether to initiate therapy, did not improve.

These studies are the latest in a barrage of papers looking into the risks and benefits of HRT.

Weighing in on HRT
Links

"It's impossible to keep up," said Ann Zerr, MD, medical director of the Indiana University National Center of Excellence for Women's Health in Indianapolis. "This is a very frustrating area for physicians right now."

HRT has been implicated in increasing the risk of ovarian cancer, blood clots, gallbladder disease and dry eye syndrome. It may worsen asthma and may increase insulin resistance.

Or maybe not. Or maybe other benefits outweigh the risks.

It may improve heart health, although the American Heart Assn. issued a scientific statement last year saying there was not enough evidence to recommend it for primary prevention. For those who already have some heart disease, it may make the situation worse. It may prevent Alzheimer's disease and macular degeneration, and it definitely staves off osteoporosis.

"There must be some good things about hormone replacement therapy," Dr. Zerr said. "But I'm not sure what they are right now."

For doctors, short-term use of the decades-old therapy is considered a no-brainer with clear-cut benefits, but the advantages of its use for more than the hot flashes and night sweats associated with the onset of menopause are a question mark.

"Estrogen is clearly justified for the management of acute menopausal symptoms and for the prevention of osteoporosis," said JoAnn V. Pinkerton, MD, director of the Women's Place Midlife Health Center at the University of Virginia in Charlottesville. "Beyond those two indications, the use of estrogen is less clear and may even be contraindicated."

Sifting through the pros and cons

Doctors are asking whether it is appropriate to use HRT to prevent osteoporosis when there are effective drugs that also do that but without the same side-effect profile. It appears to increase the risk of breast cancer, but physicians are wondering whether this risk is manageable with regular mammograms and breast exams, particularly in women who are otherwise at low risk.

The possible breast cancer risk has long been known, but most physicians felt comfortable prescribing HRT as long as the woman was informed and had regular mammograms.

"Now that we're uncertain about HRT and primary cardiac prevention, we feel we really don't know enough," Dr. Zerr said. "As for osteoporosis, until five years ago we didn't have alternatives. Now we do."

Blood clots and gallbladder disease are definitely a concern. The links to ovarian cancer, dry eye syndrome, asthma and insulin resistance, however, are far less clear, with numerous studies contradicting each other. Therefore, those three are not really part of the decision-making process.

And what about the ever-fuzzy quality-of-life question?

The recent JAMA study found that the answer to this question was "yes" among women who had hot flashes, but "no" for women without them.

Like many studies in this area, however, this one had significant limitations. Experts say that because the study looked at a population with an average age of 67 and with coronary artery disease -- not much like the average woman taking HRT -- the results are interesting but cannot be generalized. Physicians who treat a lot of menopausal women in their practices say the quality-of-life improvements are clear.

"It seems that women who are using some kind of hormone replacement therapy are much more confident with the transition," said Arie Birkenfeld, MD, co-director of the Diamond Institute for Infertility and Menopause in Milburn, N.J. "It's different with every woman, but especially for some, it's like a magic touch."

The breast cancer question

As for the breast cancer studies, the percentage increases are often high, but the actual incidence still remains low.

"In general, the risk for women using estrogen is still small," Dr. Pinkerton said.

Where many studies fail for many physicians is that they group together information about all forms of HRT, rather than comparing the formulations. Many doctors are waiting for the results of the Women's Health Initiative, a National Institutes of Health-funded randomized, clinically controlled trial that is one of the largest of its kind and due to end around 2007.

"What we hope is that we actually will have some answers," said Dr. Pinkerton. "The problem is that everyone has to make decisions now about what they're going to do."

But most physicians expect the situation to become easier with the development of new therapy formulations. HRT has shifted to smaller doses over the decades, but many expect that treatment to become even more targeted. Already, there are a couple of selective estrogen receptor modulators -- SERMs -- either on the market or very close to approval that attempt to improve the benefits while decreasing the risks. Many more are in development.

Meanwhile, physicians and patients are wading through large amounts of information, much of it conflicting.

But it's ultimately the woman's choice to accept the risks in exchange for the perceived benefits.

ADDITIONAL INFORMATION:

Weighing in on HRT

Pros

Alleviates hot flashes, night sweats and other acute menopausal symptoms.
Prevents osteoporosis.
Improves lipid profile.
May improve heart health.
May prevent Alzheimer's disease and macular degeneration.
May improve quality of life.

Cons

Increases the risk of breast cancer, blood clots and gallbladder disease.
Worsens heart health in women who already have heart disease.
May increase the risk of ovarian cancer and dry eye syndrome.
May worsen asthma or increase insulin resistance.

Weblink

Abstract, "Hormone Replacement Therapy in Relation to Breast Cancer," JAMA, Feb. 13 (http://jama.ama-assn.org/issues/v287n6/abs/joc10761.html)

Abstract, (http://jama.ama-assn.org/issues/v287n5/abs/joc10108.html) , "Quality-of-Life and Depressive Symptoms in Postmenopausal Women After Receiving Hormone Therapy," JAMA, Feb. 6

AHA statement, "Hormone Replacement Therapy and Cardiovascular Disease," Circulation, July 24, 2001 (http://circ.ahajournals.org/cgi/content/full/104/4/499)

North American Menopause Society (http://www.menopause.org/)

NIH Women's Health Initiative (http://www.nhlbi.nih.gov/whi/)