More Hormone Therapy Risks Emerging

Main Category: Menopause
Article Date: 10 Aug 2003 - 0:00 PDT


Reports this week in medical journals on both sides of the Atlantic are taking aim at hormone replacement therapy and the results are fairly clear: though the overall risks remain low, the dangers of heart attack and breast cancer begin to increase with the very first pill a woman takes.

An article in the New England Journal of Medicine suggests taking the estrogen-progestin combination called Prempro increases heart attack risk -- compared to overall risk -- by 81 percent within the first year of treatment.

In England, researchers conducting the Million Women Study disclose that all hormone therapy -- whether estrogen alone or estrogen combined with some form of progestin -- increases the risk for breast cancer and, just like the heart attack story, the risk begins on day one of treatment.

Moreover, the British researchers, who report their findings in The Lancet, said hormone replacement not only increases the risk for breast cancer, but also increases the risk of dying from breast cancer.

Dr. Wulf Utian, executive director of the North American Menopause Society in Cleveland, said the findings are not unexpected because they 'are really not terribly different from what came out last July', but in an interview with United Press International he predicted the studies will trigger yet another flurry of concern among both women and physicians.

In July 2002 the National Institutes of Health halted a hormone study called the Women's Health Initiative when it discovered women taking the study drug, Prempro, suffered a significant increase in risk for heart attack, stroke, breast cancer, and dangerous blood clots called deep vein thrombosis or DVT.

The report in the New England Journal of Medicine is a new analysis of Women's Health Initiative data.

Dr. JoAnn Manson, lead investigator of the study and chief of preventive medicine at Brigham and Women's Hospital in Boston, said the new analysis clearly demonstrates increased risk for heart attacks among women taking the estrogen-progestin combination begins very early.

'The risk increases by 81 percent during the first year,' she told UPI. By the time the study was stopped women had been taking hormones for about five-and-a-half years and the average increase in risk over that period was 24 percent.

'No group of women received any cardiovascular protection from hormone therapy,' Manson said, noting women who entered the study with certain risk factors, such as higher cholesterol levels, suffered an even higher risk.

Manson urged calm, however, when evaluating the latest hormone research. There is, she said, no reason to panic. Estrogen is an effective treatment for women who are faced with menopause symptoms, such as hot flashes, night sweats, sleep disturbances and vaginal dryness.

She pointed out the increased risk reported in her study and others actually is 'a low risk overall. We are still talking about well below 1 percent of women having a heart attack per year of hormone therapy.'

Although the heart attack numbers are not encouraging, the risk of breast cancer might be more of a consideration for many women, said Dr. Emily Banks, deputy director of the Cancer Research UK Epidemiology Unit at Oxford University and one of the authors of the Million Woman Study.

Banks said use of hormone therapy increased the risk of breast cancer by 45 percent compared to women who did not take hormones.

'To put that into prospective consider it this way,' she explained. 'Among 1,000 women aged 50 to 60 who never used hormone replacement, there would 20 cases of breast cancer diagnosed over a 10-year period. Among 1,000 women who took just estrogen, we could expect to diagnose 25 cases over that 10-year period. But if the 1,000 women took both estrogen and progestin, 39 cases of breast cancer would be diagnosed.'

Banks also told UPI the risk of dying from breast cancer was 22 percent greater among women taking hormones compared to women who never took hormones.

Utian said although this is the first study to report an increased risk for breast cancer mortality, the results are unexpected.

'Estrogen is a powerful growth hormone and it also promotes the growth of tumors,' he said, but added he doubts estrogen is the cause of the cancer. 'It is more likely that estrogen is promoting growth of a cancer that was already there.'

Another study, however -- again, in The Lancet -- provided what might be considered 'good' news about hormone replacement: A group of French researchers found when estrogen is delivered by a skin patch or gel it is safer than when taken orally, at least in terms of risk for DVT. The Women's Health Initiative found DVT risk doubled among women taking hormone replacement therapy.

Dr. Pierre Yves Scarabin from the French Institute of Health and Medical Research and colleagues compared 155 women who were diagnosed with either pulmonary embolism or DVT from 1999 to 2002 and compared their estrogen use to 381 age-matched, estrogen-using women who were never treated for blood clots.

He said women who used oral estrogen were 'three times more likely to develop (blood clots) than women who used estrogen patches.'

Manson said these findings suggest estrogen patches probably deserve more study. She noted when estrogen is delivered through the skin it bypasses the liver, which is where clotting factors triggered by estrogen are produced.

But she noted at least one other small study of estrogen patches reported delivering the hormone through the skin does not reduce the risk of heart attack.

Taken together, the research reported this week suggests women should consider carefully the option of hormone replacement, said Utian. When the first results from the Women's Health Initiative were published last year, he noted, the 'estrogen evangelists' refused to accept the negative findings, while the 'estrogen nay-sayers said the results were the last nail in the estrogen coffin. As it turns out, neither was right and the estrogen story is continuing.'

Utian predicted the days of estrogen being promoted for disease prevention are over. Manson agreed, adding there now is an accumulation of data from carefully conducted studies demonstrating estrogen does not protect the heart, nor does it prevent the onset of dementia.

Although estrogen does prevent the bone-wasting disease osteoporosis, other options, such as the drugs Evista and Fosamax, work just as well without the risks associated with estrogen.

However, estrogen remains the best treatment for symptoms of menopause, which is why both Manson and Banks said physicians should continue to prescribe estrogen for women who have severe symptoms. The key, said both, is short-term rather than long-term treatment.

The difficulty is no one can agree on what constitutes 'short-term' treatment. Utian said the North American Menopause Society plans to issue new guidelines for the use of hormone replacement therapy next month and timing of treatment is proving to be a stumbling block. 'So far we have not reached agreement' about optimal length of treatment, he said.

Utian said he leans toward treating for two years and 'then discontinuing hormones to see if symptoms recur. If they recur, it is time for careful discussions about the risks and benefits of continued treatment,' he commented.

Manson said a year ago she was recommending under five years, but now she suggests treatment usually should not extend beyond four years. Banks and Scarabin urged an individualized treatment plan for each woman, rather than establishing a time limit for treatment.

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