Study: Estrogen Protects Some from Breast Cancer

A woman holding a hormone therapy pill.

hide captionWomen taking estrogen-only therapy who have had a hysterectomy face no increased risk of breast cancer, says a new study.

T & L/Image Point FR/Corbis

A new analysis of the large-scale Women's Health Initiative Estrogen-Alone trial offers some reassurance to women who take estrogen following a hysterectomy. The study found that postmenopausal women treated with estrogen therapy for seven years did not experience an increased risk of breast cancer. The findings are published in the Journal of the American Medical Association.

Estrogen Therapy Guidelines

Scroll down to find excerpts from the National Institutes of Health's recommendations on estrogen as a hormone therapy in postmenopausal women.

The findings do not overturn prior thinking about hormones. Rather they suggest that it's the combination of estrogen and a second hormone, progestin, needed to protect the uterus that have been shown to increase the risk of breast cancer. This risk seems to disappear when women take estrogen alone.

"There's been a lot of confusion about hormones" says Marcia Stefanick, professor of obstetrics and gynecology at Stanford University. "Many women heard all the news back in July 2002 about estrogen and progestin therapies increasing breast cancer," says Stefanick. "The message that women got was that hormones increase breast cancer. People didn't distinguish between estrogen-alone therapy and a combination therapy of estrogen and progestin. Now we see that estrogen-alone therapy from the Women’s Health Initiative trial does not increase breast cancer."

The Women's Health Initiative Estrogen-Alone trial enrolled 10,739 women, ages 50-79. The women were divided into two groups. One group took a daily dose of estrogen therapy known as CEE, which is made of conjugated horse estrogens. The other group took a placebo pill. The trial was halted earlier than planned because of an increased rate of strokes and no reduction in the risk of coronary heart disease among the women.

Some of the Women's Health Initiative (WHI) researchers expected to find an elevated risk of breast cancer as well, since previous studies had found some evidence that estrogen increases the risk of breast cancer. Also, a separate arm of the WHI had found that women taking a combination estrogen/progestin therapy did increase their risk of breast cancer. But researchers’ predictions were wrong.

"The finding that estrogen alone taken for seven years doesn't increase the risk of breast cancer is surprising" says JoAnn Manson, professor of medicine at Harvard Medical School.

The study suggests that estrogen-alone therapy seemed to offer some additional protection against breast cancer for women who had no family history of the disease. In groups of about 5,000 each, there were 129 cancers in the estrogen group and 161 cancers in the placebo group. Manson says what remains unclear is the mechanism.

Researchers also question whether the effect will hold up over a lifetime. "Would a longer duration of treatment with estrogen alone eventually lead to an increased risk of breast cancer? We need to look further into this issue because some women are taking hormone therapy for longer than seven years" says Manson.

The results of the new estrogen-alone study may be reassuring to some women. It's particularly applicable to women taking estrogen for a few years following a hysterectomy.

But Manson cautions the estrogen-only study results can't be generalized to the population at large. "The findings apply only to women who've had a hysterectomy," says Manson.

The reason is that women who still have a uterus need to take progestin when they're on hormones in order to protect against uterine cancer.

Some experts say a fresh approach is needed for all menopausal women. "I think we must rethink how we administer hormone therapy in this country", says Hugh Taylor, professor of obstetrics and gynecology at Yale University and a paid speaker for a hormone manufacturer. Taylor suggests one solution might be to find a better balance of estrogen and progestin.

"Perhaps we ought to think about going back to some of the cyclic regimens where progestin is used during just part of a woman's cycle or maybe we can use lower doses of progestin," Taylor says.

These options are being evaluated.

"The latest findings reinforce the importance of the message we have always given about hormone therapy," says Joseph Sanfilippo, president of the American Society of Reproductive Medicine. "Women must make decisions about the use of hormone therapy in conjunction with their physician. Each woman is different and her symptoms and risk factors will be different.

The guidelines for using hormone therapies remain the same, says Janet Pregler, director of the Iris Cantor Women's Health Center at University of California, Los Angeles. "Hormone therapy should be used in the smallest possible dose," she says, "for the shortest period of time needed to control symptoms."

With this approach women can limit their risks of strokes and blood clots, which are elevated by the use of hormone therapy. including estrogen alone.

NIH Recommendations on Estrogen Therapy

A new study finds that estrogen-only therapy does not increase the risk of breast cancer in women who have had hysterectomies. The research adds to a growing body of evidence that hormone therapies offer benefits for some women, but risks for others.

Here, excerpts from the National Institutes of Health's (NIH) recommendations on estrogen as a hormone therapy in postmenopausal women:* Find the complete list at NIH's 2005 consensus statement on the management of menopause-related symptoms.

Evidence for the Benefits and Harms of Treatments for Relief of Menopause-Related Symptoms

A variety of treatments have been studied in randomized clinical trials (RCTs) for management of menopausal symptoms. By far, the most intensively studied treatment is estrogen, often in combination with progestin. Additional treatments that have been studied include other hormones, antidepressants, isoflavones and other phytoestrogens, botanicals, acupuncture, and behavioral interventions. However, many studies, including some RCTs, have not been designed, conducted, or analyzed in ways that can support reliable conclusions.

Benefits and Risks of Estrogen as a Hormone Therapy

Estrogen, either by itself or with progestins, is the most consistently effective therapy for hot flashes and night sweats. Low-dose estrogen ... has been shown to be effective for many women, although some women require a higher dose for relief of hot flashes.

Estrogen therapy at doses equivalent to 0.625 mg of conjugated equine estrogen increases the risk for serious disease events, specifically, stroke deep venous thrombosis, pulmonary embolism, or both; and, when combined with progestin medroxyprogesterone acetate, coronary events and breast cancer. In studies in which women were treated for 5 to 7 years, increased risks for coronary and thromboembolic events started to emerge in the first year of use. Risks for stroke started to increase after 2 years of use. Risks for breast cancer started to increase after 3 to 4 years of use. Although experts theorize that long-term adverse effects associated with low-dose estrogen are lower, the precise risks and benefits are not known.

Risk–benefit analyses are important for women whose symptoms of hot flashes and night sweats are severe and create a burden on daily life. These women may be willing to assume greater risk for the sake of reducing these symptoms.

Oral estrogen, either by itself or with progestins, and a variety of vaginal estrogen preparations are beneficial for some urogenital symptoms, such as vaginal dryness and painful intercourse.

Results of studies regarding the effectiveness of transdermal estradiol for the management of these urogenital symptoms are mixed. Results from two large studies of oral estrogen, either alone or with progestins, showed increased risk for the development of urinary incontinence and for its worsening in women who were already experiencing it.

Estrogen has also been found to be helpful for sleep disturbances and for improved quality of life. The results from studies investigating the use of estrogen for the treatment of mood symptoms are mixed. There may be a small subset of women who experience improvement in mood symptoms with estrogen therapy.

What to Consider When Choosing a Treatment

Decision making for women regarding treatment of menopausal symptoms requires balancing of potential benefits against potential risks. Women at high risk for serious medical outcomes with the use of estrogen include those with:

— a history of breast cancer

— an elevated risk for breast, ovarian, or both types of cancer on the basis of genetic factors, family history, or both

— a high risk for cardiovascular disease

Women with these risk factors may be particularly motivated to seek nonhormonal therapies to treat menopausal symptoms. A few small studies in breast cancer survivors suggest that some antidepressants (such as venlafaxine) can effectively treat hot flashes and night sweats symptoms in women with breast cancer.

Other treatments, including clonidine and megestrol acetate, have also shown positive effects in a few studies. These treatments have their own adverse effects (such as decreased libido, nausea, dry mouth, or constipation) that need to be weighed against the potential benefits.

The long-term safety of these agents in women with breast cancer has not been studied but is of concern because of their potential estrogenic actions. Vaginal estrogen preparations to treat vaginal dryness and pain with intercourse may also be an attractive option for these women.

Such topical therapies are known to increase circulating estrogen levels, but by much smaller amounts than oral estrogen therapy. Because these topical therapies have not been studied in large numbers of women for long periods of time, actual levels of risk for long-term complications, such as breast cancer occurrence or recurrence, while probably much lower than those of oral therapy, are not fully known.

Women who have had their ovaries surgically removed (causing surgically induced menopause) often experience more severe symptomatology, including hot flashes and vaginal dryness. Benefits and risks of estrogen therapy in these women are generally similar to those found in studies of other women who have had hysterectomies and are taking estrogen. Risks may be elevated, however, in women whose oophorectomies were performed specifically to treat or prevent cancer.

*Excerpts do not include the latest findings on estrogen therapy and the risk of breast cancer in women with hysterectomies.

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