Hormone Replacement Therapy’s Risks Are Complex

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After about 13 years of follow-up, the two parts of the Women’s Health Initiative (WHI) trial have found that the link between combination hormone replacement therapy (HRT) and higher breast cancer risk is long-term, but estrogen-only HRT may lower breast cancer risk.

The research was published in the Oct. 2, 2013 issue of the Journal of the American Medical Association. Read the abstract of “Menopausal Hormone Therapy and Health Outcomes During the Intervention and Extended Poststopping Phases of the Women’s Health Initiative Randomized Trials.”

The WHI started in 1993 and included nearly 27,350 postmenopausal women ages 50 to 79. Women who had a uterus were randomly assigned to get either:

  • combination HRT (combination HRT contains both estrogen and progesterone)
  • a placebo (a sugar pill that looked just like combination HRT)

Women who didn’t have a uterus (hysterectomy is surgery to remove the uterus) were randomly assigned to get either:

  • estrogen-only HRT
  • a placebo (a sugar pill that looked just like estrogen-only HRT)

In 2002, the combination HRT part of the WHI was stopped after about 6 years of follow-up because an early analysis showed that the women taking combination HRT were much more likely to be diagnosed with breast cancer compared to women taking the placebo. In 2004, the estrogen-only HRT part of the study also was stopped because of concerns about the women’s risk of breast cancer.

When the two parts of the WHI study ended, more than 12,700 women who had been taking combination HRT and more than 7,640 women who had been taking estrogen-only HRT agreed to be followed for more time. The researchers followed these women through Sept. 30, 2010. Fewer than 4% of the women continued to take HRT (either combination or estrogen-only) after the WHI trial officially ended.

Combination HRT long-term results

Compared to women who didn’t take combination HRT, women who did take combination HRT were 28% more likely to be diagnosed with breast cancer.

Women who took combination HRT and had gone through menopause more than 20 years earlier also were more likely to have coronary heart disease.

Combination HRT did seem to reduce the risk of breaking a hip as well as reduce the risk of endometrial cancer.

Other risks linked to combination HRT, such as blood clots and stroke, seemed to ease over the long-term follow-up.

Estrogen-only HRT long-term results

Compared to women who didn’t take estrogen-only HRT, women who did take estrogen-only HRT didn’t have a higher risk of coronary heart disease or breast cancer. The long-term results suggest that women who took estrogen-only HRT were about 20% less likely to be diagnosed with breast cancer. While this result is encouraging, more research is needed since earlier studies found a link between estrogen-only HRT and breast cancer risk.

An earlier analysis showed that estrogen-only HRT seemed to increase the risk of blood clots and stroke, but these problems seemed to ease over the long-term follow-up.

Many studies have shown a link between higher breast cancer risk and using hormone replacement therapy (HRT) to treat menopausal symptoms. The results of all the studies aren't exactly the same, but there is good evidence that:

  • HRT increases invasive breast cancer risk
  • breast cancer risk goes up during the first several years of using HRT; risk seems to keep increasing the longer a woman uses HRT
  • high-dose HRT increases risk more than low-dose HRT

Menopausal side effects can dramatically reduce quality of life for some women. These women have to weigh the benefits of HRT against the risks. If you're having severe hot flashes or other menopausal side effects and are considering HRT, talk to your doctor about all of your options. Ask how you can minimize your breast cancer risk AND relieve your symptoms. Be sure to discuss the pros and cons of different types and doses of HRT.

If you’ve been diagnosed with breast cancer, you should NOT take any type of HRT.

Almost all other research suggests that estrogen-only HRT increases breast cancer risk less than combination HRT. The long-term results from the WHI suggest that breast cancer risk actually may go down with estrogen-only HRT. Still, other health risks went up a lot when women took estrogen-only HRT. It's reassuring that those risks went down after HRT was stopped.

If you do decide to take HRT, try to take it for the shortest time possible. You also may want to ask your doctor about vaginal or transdermal HRT.

Learn more about menopause and ways to manage side effects on the Breastcancer.org Managing Menopausal Symptoms pages.

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