Hormone therapy that includes progestin plus estrogen may increase breast cancer risk, but estrogen alone may lower risk, according to long-term review.

A long-term review of two clinical trials has shed new light on menopausal hormone therapy and breast cancer risk over time.

In earlier clinical trials, combination hormone replacement therapy (HRT) consisting of progestin plus estrogen was linked to an increased risk of breast cancer and death from that disease.

Women who had a hysterectomy and took estrogen alone were found to have a reduced risk of breast cancer and breast cancer death.

Following those reports, use of both types of HRT declined.

Thirteen years later, researchers set out to determine both the short-term and long-term effects of HRT.

One analysis involved 16,608 women who had not had a hysterectomy. The women were assigned to receive estrogen plus progestin. Results showed this group was at increased risk of breast cancer while taking combination HRT. Within 2.75 years after stopping therapy, the risk was still present but not as high.

Another group of 10,739 women who previously had a hysterectomy were asked to take estrogen alone. This group had a reduced risk of breast cancer while receiving estrogen therapy. That lower risk continued for a few years after therapy ended. The benefit was lost after that.

The study authors concluded there is a “greater adverse influence for estrogen and progestin use and somewhat greater benefit for use of estrogen alone.”

The research team was led by Rowan T. Chlebowski, M.D., Ph.D., of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center. Details were published in JAMA Oncology.

This research focused on breast cancer risk and did not involve other potential risks of HRT.

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During menopause, a woman’s body begins to produce less estrogen and progesterone. Lack of estrogen can cause symptoms such as hot flashes, vaginal dryness, and painful intercourse. Replacing estrogen can help ease those symptoms.

Estrogen is prescribed for women who no longer have a uterus. Estrogen therapy may increase the risk of endometrial cancer, so women who still have a uterus usually take estrogen plus progestin. Progestin is a synthetic version of progesterone, a hormone that helps protect the uterus.

HRT may also increase risk of blood clots, heart attack, and stroke. According to the National Cancer Institute, evidence regarding risks and benefits come from the clinical trials conducted as part of the Women’s Health Initiative (WHI).

Benefits and risks of bioidentical hormones are the same as for other hormone products, according to the U.S. Food and Drug Administration.

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Menopause doesn’t always require treatment. If you have persistent symptoms that interfere with your quality of life, speak with your doctor. HRT may help alleviate some symptoms.

“This is a big subject,” Dr. Diana Bitner, of the Women’s Health Network of Spectrum Health Medical Group, told Healthline. “The information from the WHI has been helpful in terms of systemic exposure. The goal is the least possible amount of exposure to progesterone while still protecting the uterus.”

Bitner said treatment must be tailored to the individual. “What does the patient want? What is her quality of life? What options fit her and her risk factors?”

For patients who are at higher risk of breast cancer, Bitner explores alternative therapies for menopausal symptoms that will reduce exposure to progesterone.

If you have a personal history of breast cancer or are at higher risk, HRT may not be safe. Many factors aside from HRT influence breast cancer risk. Your doctor will also want to assess your risk factors for blood clots, heart attack, and stroke.

Bitner notes the WHI studies relate to systemic therapy, which includes oral pills, injections, or skin patches. These studies do not involve local therapies such as vaginal tablets, rings, and creams, which can help decrease symptoms without raising breast cancer risk.

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