http://www.cnn.com/2002/HEALTH/cond...rapy/index.html

WASHINGTON (CNN) -- U.S. government scientists Tuesday stopped a major study of hormone replacement therapy exploring the risks and benefits of combined estrogen and progestin in healthy menopausal women, citing an increased risk of invasive breast cancer.

The National Heart, Lung and Blood Institute of the National Institutes of Health also found increases in coronary heart disease, stroke and pulmonary embolism.

"Women with a uterus who are currently taking estrogen plus progestin should have a serious talk with their doctor to see if they should continue it," said Jacques Rossouw in a statement. Rossouw is acting director of the Women's Health Initiative, which sponsored the study.

"If they are taking this hormone combination for short-term relief of symptoms, it may be reasonable to continue since the benefits are likely to outweigh the risks," Rossouw continued. "Longer term use or use for disease prevention must be re-evaluated."

A statement from the institute noted the benefits of estrogen combined with progestin, "including fewer cases of hip fractures and colon cancer, but on balance the harm was greater than the benefit."

EXTRA INFORMATION
• Q&A: Hormone replacement



• Hormone replacement: Pros and cons






About 6 million women in the United States are taking estrogen and progestin for various reasons, including relief of menopausal symptoms and long-term use for the prevention of heart disease and brittle bones.

The estrogen and progestin trial study involved 16,608 women ages 50 to 79 with an intact uterus.

A major objective of the trial study was to explore the effect of estrogen and progestin on the prevention of heart disease and hip fractures and any associated change in risk for breast and colon cancer.

"We have long sought the answer to the question: Does postmenopausal hormone therapy prevent heart disease and, if it does, what are the risks? The bottom-line answer from [the Women's Health Initiative] is that this combined form of hormone therapy is unlikely to benefit the heart," said Dr. Claude Lenfant, director of the heart, lung and blood institute, in a statement.


"The cardiovascular and cancer risks of estrogen plus progestin outweigh any benefits -- and a 26 percent increase in breast cancer risk is too high a price to pay, even if there were a heart benefit. Similarly, the risks outweigh the benefits of fewer hip fractures.

"Menopausal women who might have been candidates for estrogen plus progestin should now focus on well-proven treatments to reduce the risk of cardiovascular disease, including measures to prevent and control high blood pressure, high blood cholesterol and obesity," Lenfant added.

In a statement, Garnet Anderson, a biostatistician who led the analysis at the Fred Hutchinson Cancer Research Center in Seattle, Washington, said, "The trial was stopped at the first clear indication of increased risk."

Anderson also said that, at that point, there was no indication of increased risk for breast cancer in the estrogen-only group.

Hormone Replacement

Linda Ward, CBC News Online | July 9, 2002

What is Hormone Replacement Therapy (HRT)?

Hormone replacement therapy is estrogen or combination estrogen/progestin medication, available only by prescription. It is generally prescribed to relieve menopausal symptoms. Estrogen and progestin are usually given together because estrogens given alone increase the risk for endometrial cancer in women with a uterus. Prescribing progestin along with the estrogen, creating a balance, alleviates this effect. Estrogen is a female hormone that brings about changes in other organs in the body. It generally comes from animal sources. Progestin is a female hormone that prepares the uterus for a pregnancy each month.

These are available in oral formulations, injections, vaginal creams and transdermal (patch) forms. There are also formulations (pills and a patch) that combine estrogen/progestin into one dosage form.

What are the risks of HRT?

The National Institutes of Health stopped its 16,600-woman study of Hormone Replacement Therapy three years early and advised other women who use the estrogen-progestin combination to ask their doctors if they, too, should quit. The NIH found out early on that long-term use of estrogen and progestin significantly increased the women's risk of breast cancer, strokes and heart attacks.

Six million American women use this hormone combination, either for short-term relief of menopausal symptoms or to prevent heart disease and osteoporosis. The National Institutes of Health has discovered that, in fact, long-term use of estrogen and progestin increased women's risk of a stroke by 41 per cent, of a heart attack by 29 per cent and of breast cancer by 24 per cent.

It did, however, cut by a third the risk of colon cancer and hip fractures but, in this case, the risks outweigh the benefits.

The results mean that in one year, for every 10,000 women who take the estrogen-progestin combination there will be eight more breast cancers, eight more strokes and seven more heart attacks, as well as six fewer colon cancers and five fewer hip fractures – compared with 10,000 women who didn't take the hormones.

HRT also increases the breast density of many women, making breast abnormalities harder to detect in mammograms.

The study shows visible short-term risks of heart disease, with the cardiovascular risk actually jumping within the first year of HRT use. The cancer risk didn't appear until around the fourth year, suggesting a long-term risk posed by HRT.

Some women report side effects from taking HRT, including unusual vaginal discharge and bleeding, headaches, nausea, fluid retention and swollen breasts.

The NIH is letting a second smaller study of those women who have had hysterectomies and take only estrogen continue for now. So far the balance of risks and benefits remains uncertain.

The 16,600 women who participated in the study published in July in the Journal of the American Medical Association were taking Prempro (called Premplus in Canada) for at least five years.

According to the Kaiser Family Foundation, a nonprofit research group, 46 million prescriptions worth $1 billion were written for Premarin, a hormone replacement drug, in 2000, making it the second most prescribed drug in the U.S. after cholesterol-lowering Lipitor, made by Pfizer Inc.

What are the alternatives to HRT?

Regular exercise, coupled with 1,500 mg of calcium and 400 IU of vitamin D per day is one proposed treatment to decrease the bone loss associated with osteoporosis. Regular exercise, good diet and non-smoking will help prevent heart disease and is recommended for all patients, regardless of the use of HRT. Non-hormonal therapies are available to reduce the symptoms of menopause, varying from the use of soy products, lubricants and vitamin supplements, to prescription medications that stabilize the nervous system.

Thanks Doreen, I was hoping someone had something to add about this. As we all know from the current LC "debate", you can't always totally believe what you read!

Ain't it the truth! And unhappily, some aspects of this story appear to be the same. The first article states that women who are taking HRT that is "just estrogen alone" are not at any kind of risk, and shouldn't worry. Yet, I've been hearing news reports all afternoon about this .. and many health experts are cautioning women that ALL HRT should be questioned, and women should contact their doctors about this situation.

I find it ironic that HRT has often been plugged in the past for its BENEFITS to cardiovascular health and prevention of heart disease.

As for the need for estrogen HRT in preventing osteoporosis, studies show that weight-bearing exercise such as walking, and an adequate protein intake combined with calcium and vitamin D supplements is just as effective in increasing bone density in post-menopausal women.

Just as an aside, about osteoporosis ... Contrary to the myth that a high protein diet will leach the calcium out of your bones .. a number of studies published this spring proved that this is simply not true. In fact, the one study showed that bone density increased proportionally with the level of protein in the diet, and specifically ANIMAL protein, not vegetable. I posted those studies here in the Research forum, check out High-Protein Diet Won't Weaken Your Bones.

Doreen

Cancer Epidemiol Biomarkers Prev 2002 Jul;11(7):593-600

Postmenopausal estrogen and progestin use in relation to breast cancer risk.

Newcomb PA, Titus-Ernstoff L, Egan KM, Trentham-Dietz A, Baron JA, Storer BE, Willett WC, Stampfer MJ.

University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin 53706 [P. A. N., A. T-D.].

Epidemiological evidence now consistently supports a modestincrease in breast cancer risk among women using postmenopausal hormones, usually estrogens.Less is known regarding how the addition of progestin affects breast cancer risk. The objective of this study was to investigate the type and duration of postmenopausal therapy and breast cancer risk. We performed a multicenter population-based case-control study set in Massachusetts, New Hampshire, and Wisconsin. The subjects were 5298 postmenopausal women (age range, 50-79 years) with a new diagnosis of invasive breast cancer from statewide tumor registries. For comparison, 5571 controls were randomly selected from population lists. Participants completed a structured telephone interview covering hormone use and breast cancer risk factors. Multivariable regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). The RR for breast cancer increased with longer durations of hormone use, about 2%/year for estrogen alone (RR, 1.02; 95% CI, 1.01-1.03) and 4%/year for estrogen-progestin use (RR, 1.04; 95% CI, 1.01-1.08). Estrogen-progestin use that was both recent and long term (>5 years in duration) was more strongly associated with breast cancer risk (RR, 1.57; 95% CI, 1.15-2.14) than similar use of estrogen alone (RR, 1.39; 95% CI, 1.17-1.65). In estrogen-progestin users, risks were similar for sequential and continuous use regimens but perhaps stronger for lobular than ductal breast cancer. Use of progestin alone was associated with a doubling of risk (RR, 2.09; 95% CI, 1.07-4.07 for ever use versus nonuse). Estrogen-progestin use, both sequential and continuous, appears to be more strongly associated with risk of breast cancer than use of estrogen alone.

On a personal note, my grandmother never took estrogen and her bones were as brittle as glass sculpture. She was always having very painful breaks. This is inspite of the fact that she ate plenty of dairy and calcium and danced every day until she died at 83 of stroke.

Again, you have to look at the lesser of two evils. Perhaps spend some of your later years on estrogen and some not on HRT. There are fortunately also if the need arises, new drugs that increase bone density. (However, no one knows the long term side-effects of these either, do they?) It's a tough decision.

Did your grandmother eat much meat? It seems to me we have been reading (and much in posts from you, Voyager ) that dairy is not necessarily a good source of calcium and that we should be making sure we get enough protein and magnesium.

Just wondering...

;-Deb

Good point Deb,

She seemed to eat meat pretty often, but maybe that was only when family was around. I don't know.

I just always thought that estrogen would have helped her somewhat. I know it's not for everyone, but I think predisposition to osteoporosis is hereditary.

Doreen said walking was a weight-bearing exercise, so dancing should have been too. I mean she didn't actually lift any weights. Maybe she needed to, but I think she was afraid she might break an arm if she tried.

Personally I think there is some benefit to estrogen therapy like any other hormone that depletes with age: DHEA, Human Growth Hormone, Melatonin, etc. I think they all must help make your body think younger. There seems to be a cut-off point that a person gets to where they have higher risk for cancer like greater than 5 years use of HRT.

But I am having a hard time deciding what is the best course for me personally when I get there. I suppose I will have to get into weight-training or something so I don't have to worry about it.

I think one of the things to do, if you are concerned, is to get a bone density test. Another is to do what you can to make sure that, by the time you go into menopause, you have as good a set of bones as you can.

I think I'm in good shape because we ate a lot of meat when I was growing up (and we were taught young by an English friend to gnaw on chicken bones, a great source of calcium). I have had a number of opportunities to break bones and they held up (knock wood ). But I went for a lot of years eating very little meat and not taking any supplements.

So now, I eat meat and I take supplements and I exercise. I have a few more years to prepare according to my GYN. And I read all I can of the research that is so kindly provided on this site to learn all I can do to make sure my bones are as strong as possible.

And the last thing to keep in mind is that some people have weak bones no matter what they do. My maternal grandmother was like that. She also appeared to eat a good diet to get calcium and protein, but she started breaking bones when she was still in her twenties, which kept her from being as active as she should have been. She broke her hip twice, once before menopause. Luckily, my mom and I don't seem to take after her.

;-Deb