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Estrogen-Plus-Testosterone Therapy Increases Breast Cancer Risk

And alternatives to HRT rely on a placebo effect, researchers say

MONDAY, July 24, 2006 (HealthDay News) -- Women who take the hormones estrogen and testosterone in tandem to treat symptoms of menopause appear to have an increased risk of breast cancer, researchers report.

The finding are published in the July 24 issue of the Archives of Internal Medicine.

Another report in the same journal issue finds that alternative therapies to hormone replacement therapy (HRT) don't seem to work.

In the first report, Rulla M. Tamimi, of Brigham and Women's Hospital in Boston and Harvard Medical School, and her colleagues collected data on 121,700 women, who were part of the Nurses' Health Study. The researchers looked at the long-term effects of estrogen-plus-testosterone therapy.

"Estrogen plus testosterone increases the risk of breast cancer," Tamimi said. "There needs to be other studies to support these findings, but there does seem to be an increased risk, and women and their physicians should weigh the risks and benefits of estrogen-plus-testosterone therapy before starting," she said.

There is some evidence that many of the symptoms of menopause --including decreased sex drive, mood swings and poorer quality of life, such as hot flashes, night sweats, vaginal dryness and sleep problems -- are related to this decline in testosterone, the authors noted. Previous clinical trials had shown that testosterone in combination with estrogen may reduce these symptoms and promote bone health.

The increased breast cancer risk associated with testosterone may be because enzymes in breast tissue convert testosterone to estradiol, an estrogen-like hormone that could contribute to the development of breast cancer, the authors said. Higher levels of testosterone alone have also been linked to increased breast-cancer risk in postmenopausal women.

Currently in the United States, there is only one estrogen-plus-testosterone therapy available, but such treatments are expected to increase in coming years, according to the report.

During 24 years of follow-up for the study, there were 4,610 cases of breast cancer. The 29 women who were taking estrogen plus testosterone had a 77 percent higher risk of developing breast cancer than those who never used hormone therapy, the researchers reported.

The risk associated with this combination therapy was higher than the risk associated with estrogen therapy (15 percent) and of estrogen-plus-progestin therapy (58 percent), Tamimi said.

Looking only at women who had gone through menopause naturally rather than those who had had a hysterectomy, Tamimi's group found that the 17 women who took estrogen plus testosterone had 2.5 times the risk of breast cancer compared with those who had never used hormones.

One expert doesn't think that, in most cases, testosterone should be prescribed for women.

"We have always been careful about prescribing testosterone to women, based on unknown risks," said Dr. Hugh Taylor, an associate professor of obstetrics and gynecology at Yale University School of Medicine. Testosterone doesn't appear to offer a benefit much beyond a placebo effect, he added.

"We have always been hesitant about using it, and this re-enforces it," Taylor said. "The usual reason women request testosterone is for decreased libido. But for most women, decreased libido is not due to decreased testosterone. It's due to a myriad of other problems."

Concerns about hormone-replacement therapy were first raised in 2002 by the Women's Health Initiative, the landmark study involving 27,000 participants that caused many women to discontinue their use of hormone therapy.

In the second study in the journal, researchers who reviewed 70 previous studies of alternative and complementary therapies for menopause-related symptoms found there was insufficient evidence that these therapies relieve menopause-related symptoms.

"There is a significant placebo effect in almost anything that is used for the management of menopause," said study lead researcher Dr. Anne Nedrow, of the Oregon Evidence-based Practice Center and Oregon Health and Science University. "There is a lack of any evidence that of the millions and millions of dollars spent on alternative therapies that anything really works.

Nedrow's group looked at 48 studies that examined vitamins, proteins, complete diets or other biologically based treatments; nine studies that focused on mind-body therapies, including meditation and guided imagery; one study of osteopathic manipulation, a body-based therapy; two that looked at the energy-based treatments reflexology and magnet therapy; and 10 that assessed whole medical systems, such as traditional Chinese medicine or ayurvedic medicine, a traditional therapy from India.

Nedrow said the study found there really aren't any good alternative or complementary choices for women going through menopause. "The truly symptomatic women may need to reconsider estrogen," she said. "Or we may want to take advantage of the placebo effect, which has shown a 50 percent reduction in symptoms in 12 weeks," she added.

Nedrow said she doesn't think there's any harm in using alternative therapies. She recommended black cohosh or soy supplements, with the understanding that most of the effect would be a placebo effect.

One expert agreed that the benefit of alternative therapy to relieve menopausal symptoms is largely a placebo effect.

"Currently, the best medication we have to remove menopausal symptoms is estrogen," said Dr. Jennifer Wu, an obstetrician/gynecologist at Lenox Hill Hospital, in New York City. But, she added, "The associated risks make it less than desirable."

More information

For more on menopause, visit the National Library of Medicine.

SOURCES: Rulla M. Tamimi, Sc.D., Brigham and Women's Hospital and Harvard Medical School, Boston; Anne Nedrow, M.D., Oregon Evidence-based Practice Center and Oregon Health and Science University, Portland; Jennifer Wu, M.D., obstetrician/gynecologist, Lenox Hill Hospital, New York City; Hugh Taylor, M.D., associate professor of obstetrics and gynecology, Yale University School of Medicine, New Haven, Conn.; July 24, 2006, Archives of Internal Medicne
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