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Key Words

Breast cancer, menopause, hot flashes. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ⁴.)

Summary

A single injection of a progesterone-like drug controlled hot flashes better than daily treatment with the antidepressant venlafaxine (Effexor®), a new study reports.

Source

Journal of Clinical Oncology, published online February 27, 2006; in print March 20, 2006 (see the journal abstract)
(J Clin Oncol. 2006 Feb 27; [Epub ahead of print])

Background

Hot flashes - increases in body temperature that occur as a result of fluctuating hormone levels - are a common problem for women approaching menopause. Hot flashes also afflict premenopausal women treated with chemotherapy (which can shut down their ovaries) and are one of the main side effects of breast cancer therapies such as tamoxifen (Nolvadex®) and anastrozole (Arimidex®). Many men undergoing hormone treatments for prostate cancer also get hot flashes.

Hormone replacement therapy (HRT, a combination of the hormones estrogen and progesterone) used to be widely prescribed for women suffering from menopause-related hot flashes. However, a large clinical trial published in 2002 showed that HRT increased women’s risk of developing breast cancer and heart disease. (For more information, see Menopausal Hormone Use ⁵.) Some women who have no history of breast cancer still use HRT for short periods to relieve menopausal symptoms, but HRT is not recommended for breast cancer patients, whose tumors may grow in response to estrogen.

In 2000, researchers at the Mayo Clinic in Rochester, Minnesota, reported that four weeks of treatment with the antidepressant drug venlafaxine substantially reduced both the number and severity of hot flashes in 62 percent of women who took the drug in a clinical trial (see A New Treatment for Hot Flashes: Antidepressants ⁶). Venlafaxine has since become a popular nonhormonal alternative treatment for hot flashes, particularly in women who have, or are at risk of, breast cancer.

Drugs that are chemically related to the hormone progesterone have also shown some effectiveness at controlling hot flashes. The current study evaluated a drug called medroxyprogesterone acetate (MPA), a long-acting, synthetic form of progesterone.

The Study

In this study, 227 women with bothersome hot flashes were randomly assigned to one of three treatments: a venlafaxine pill daily for six weeks, a single dose of MPA injected into the muscle, or three doses of MPA injected into the muscle (one every two weeks).

About 60 percent of the women had a history of breast cancer, the rest did not. Women who were already taking drugs such as tamoxifen, raloxifene, or anastrozole continued to take them while enrolled in this study. However, women could not participate in this study if they were currently receiving chemotherapy for breast cancer.

The women kept daily diaries in which they recorded the number and severity of their hot flashes. They also completed questionnaires that asked about other symptoms (such as changes in appetite, nausea, dizziness, changes in mood, and loss of sexual libido) as well as about their general well being and quality of life.

After six weeks, all the women were contacted and asked how satisfied they were with their hot-flash control. Those who were satisfied were called monthly for the next five months, and then every other month for another six months, to find out if they were still having hot flashes and if so, how frequent and severe they were.

The study’s lead author is Charles L. Loprinzi, M.D., of the Mayo Clinic in Rochester, Minn. Loprinzi also led the study published in 2000 that found venlafaxine to be effective against hot flashes.

Results

Following a slow start to recruitment, the researchers decided to discontinue the arm of the trial in which women were to receive three MPA injections. The final study report compares outcomes for women who received venlafaxine with outcomes for those who received a single MPA injection. Only nine women were assigned to receive three MPA injections; their results are not reported because of the small patient numbers.

After six weeks, 74 percent of the women assigned to a single injection of MPA reported that the frequency and severity of their hot flashes dropped by more than half. By contrast, 46 percent of the women assigned to venlafaxine reported the same level of reduction in their hot flashes.

The effectiveness of the two treatments was similar whether women had a history of breast cancer or not, whether they were taking tamoxifen or not, and regardless of the severity of their hot flashes when they entered the study.

Compared with women who received venlafaxine, women treated with MPA reported lower levels of hot-flash distress, abnormal sweating, sleep problems, and several other symptoms at six weeks.

The levels of other symptoms were similar in both groups, including nausea, increase in appetite, mood changes, and loss of libido. Overall well-being and quality of life also appeared to be much the same in both groups.

After six months, 27 percent of the women assigned to MPA reported that their hot flashes had declined in number and severity by more than 90 percent from when they entered the study. Among women assigned to venlafaxine, 10 percent reported a reduction of this magnitude after six months.

Many women said they found getting a single injection of MPA to be more convenient than taking a pill every day to control their hot flashes.

Limitations

Some laboratory studies suggest that even brief exposure to progesterone (the hormone from which MPA is derived) may stimulate breast cancer growth, although other data suggest that the hormone can inhibit breast cancer growth.

Comments

This study’s findings “demonstrate that MPA reduces hot flashes to a more substantial degree than does venlafaxine,” the study authors write. They concede, however, “that there is no definitive answer regarding the safety of a single 400-mg dose of MPA” with regard to breast cancer.

Jennifer Eng-Wong, M.D., a medical oncologist with the National Cancer Institute’s Center for Cancer Research, thinks it is unlikely that doctors treating patients with breast cancer will embrace MPA as a treatment for hot flashes on the basis of this study’s findings.

“We have a nonhormonal agent - venlafaxine - that does a reasonable job of controlling hot flashes in women with a history of breast cancer,” she says. “Given the data that progesterone may fuel breast cancer growth, I don’t think this study alone will change clinical practice in this group of patients.”

Glossary Terms

An anticancer drug that is used to decrease estrogen production and suppress the growth of tumors that need estrogen to grow. It is a type of nonsteroidal aromatase inhibitor.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.

A type of hormone made by the body that helps develop and maintain female sex characteristics and the growth of long bones. Estrogens can also be made in the laboratory. They may be used as a type of birth control and to treat symptoms of menopause, menstrual disorders, osteoporosis, and other conditions.

Having to do with the time before menopause. Menopause ("change of life") is the time of life when a woman's menstrual periods stop permanently.

A type of hormone made by the body that plays a role in the menstrual cycle and pregnancy. Progesterone can also be made in the laboratory. It may be used as a type of birth control and to treat menstrual disorders, infertility, symptoms of menopause, and other conditions.

The active ingredient in a drug used to reduce the risk of invasive breast cancer in postmenopausal women who are at high risk of the disease or who have osteoporosis. It is also used to prevent and treat osteoporosis in postmenopausal women. It is also being studied in the prevention of breast cancer in certain premenopausal women and in the prevention and treatment of other conditions. Raloxifene blocks the effects of the hormone estrogen in the breast and increases the amount of calcium in bone. It is a type of selective estrogen receptor modulator (SERM).

A drug used to treat certain types of breast cancer in women and men. It is also used to prevent breast cancer in women who have had ductal carcinoma in situ (abnormal cells in the ducts of the breast) and in women who are at a high risk of developing breast cancer. Tamoxifen is also being studied in the treatment of other types of cancer. It blocks the effects of the hormone estrogen in the breast. Tamoxifen is a type of antiestrogen. Also called tamoxifen citrate.