New evidence today adds to the belief that hormone replacement therapy may do more harm than good for many women after menopause, and it has many experts trying to figure out for which women the therapy is safe.
New results released Tuesday from the ongoing Women's Health Initiative trial found that not only do postmenopausal women who take a combination of estrogen and progestin therapy have a higher chance of getting aggressive forms of breast cancer, but that they may be at higher risk of dying from the disease.
The results, from an 11-year follow up with more than 12,000 women who were randomly assigned to receive either the combination hormone therapy or a placebo, found 385 women taking the therapy developed an aggressive form of breast cancer, compared to 293 in the placebo group. Twenty-five women who took hormone therapy died from breast cancer during the study, compared to 12 women in the placebo group.
"It is early in the follow-up and the number of breast cancer deaths will certainly substantially increase as we move forward," said Dr. Rowan Chlebowski, professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles, and lead author of the study.
Women in the study who used estrogen and progestin for five-and-a-half years -- which is considered long-term use of the therapy -- were at higher risk of getting breast cancer, said Chlebowksi.
Earlier results of this trial indicated a connection between synthetic hormone therapy -- commonly marketed as as the drug Prempro -- and less aggressive forms of breast cancer. But results now suggest that women who took hormones may be at risk of any, including more aggressive and late-stage, forms of breast cancer.
"For women currently on HRT, I think it warrants a significant talk with their physician as to whether they warrant the therapy," said Dr. Jennifer Litton, assistant professor of breast oncology at MD Anderson Cancer Center in Houston.
Hormone replacement therapy includes medications containing female hormones to replace the ones the body no longer makes after menopause. Although the FDA has only approved hormone replacement therapy to reduce the risk of osteoporosis in postmenopausal women and prevent hot flashes, the medication is also likely to be prescribed off-label to control groups of symptoms such as mood swings, and dryness.
While experts said diet and exercise often curb these symptoms, hormone therapy is prescribed for women with severe symptoms.
"For some women, these symptoms are so severe that it's life-altering," said Litton.
A decade ago, hormone replacement therapy was prescribed routinely to women going through menopause.
At age 51, Linda Spinale of Halifax, Mass., said she doesn't remember her doctor telling her why she needed combination hormone replacement therapy.
"I was having slight hot flashes, and it seemed like they were giving out hormone replacement therapy like candy and many women were doing it," said Spinale. "I loved taking them. Your boobs look better, your skin looks better. And I felt good with them."
In 1999, at age 58, with no family history of the disease, Spinale was diagnosed with Stage 1 breast cancer. After a lumpectomy and radiation, Spinale thought she was in the clear. But in December 2008, Spinale was diagnosed with Stage 4 breast cancer that her doctors said metastasized to her lungs, liver, and brain.
It is unclear whether Spinale's cancer is associated with her having taken hormone therapy.
"When I blamed the HRT for the reason why I got breast cancer, it was inconclusive as far as they [my doctors] were concerned," said Spinale. "I don't remember being told of any side effects of HRT, except being told that it would help the hot flashes."
Chlebowski's study initially warned of a link between combination hormone replacement therapy and breast cancer in 2002. Since then, many doctors have prescribed a variety of combinations, including lower-dose combinations of estrogen and progestin, or estrogen alone, without knowing what type of therapy might offer the greatest benefit to women. Many doctors say they now prescribe lower doses of the hormones at shorter intervals.
"We significantly reduced use of HRT when the link to HRT first came out [in 2002]," said Dr. Randy Wexler, assistant professor of family medicine at Ohio State University.
"There is still a role for hormone therapy," said Dr. Hugh Taylor, director of reproductive endocrinology at Yale School of Medicine.
The concern lies mainly with the combination of estrogen and progestin and not on estrogen alone, according to Taylor.
"With low doses of of estrogen we can get away with small and infrequent progestin use," said Taylor. "Let's not throw the baby out with the bath water. Estrogen therapy is the only thing that works well and estrogen is not the cause of breast cancer."
But there's no scientific evidence that any variation of hormone therapy at any length of time provides a safer alternative. Litton said non-hormone therapies, such as antidepressants or acupuncture, may provide some women some benefit.
"I don't think that we can counsel patients saying that it's safe to take for a shorter time at a lower dose," said Litton. "I think that for the general practitioner or gynecologist, it should be a drug of very last resort."
According to Dr. Dian Ginsberg, obstetrician and gynecologist at Children's Memorial Hermann Hospital and in and in private practice in Houston, TX, lifestyle changes during a women's premenopausal years may help women ease through their symptoms and divert hormone therapy altogether.
"I hope that as we learn more about the hormone replacement pill not being the answer, we can maybe approach the woman differently in her 30s and 40s," said Ginsberg.
Still, she said the type of therapy depends on a woman's personal history and understanding the risk. And before abandoning hormone therapy, women should talk to their doctor.
"Don't throw your hormones out," said Ginsberg. "Call your physician, go in, learn a little bit more about this study, go over your own medical background, and see a good way, potentially, to wean off your hormone."