The Women's Health Initiative Finds Risks with HRT

The Women's Heal Hormone Replacement Therapy (HRT) | Menopause | Imaginis - The Women's Health & Wellness Resource Network

The Women's Health Resource. On the web since 1997.

Hormone Replacement Therapy (HRT)

The Women's Health Initiative Finds Risks with HRT

The Women's Health Initiative was launched in 1991 to study combination HRT (estrogen plus progestin) and estrogen-only HRT. All together, its studies have involved 161,808 healthy post-menopausal women. The following summarizes the study's findings as of 2003.

Compared with women taking a placebo (an inactive pill), women who took estrogen plus progestin experienced:

  • Increased risk of heart attack
  • Increased risk of stroke
  • Increased risk of blood clots
  • Increased risk of breast cancer
  • Reduced risk of colorectal cancer
  • Fewer fractures
  • No protection against mild cognitive impairment and increased risk of dementia (study included only women 65 and older)

The study results also show that for every 10,000 women per year taking estrogen with progestin, there would be:

  • 6 fewer cases of colon cancer
  • 5 fewer cases of hip fracture

Compared with women taking a placebo (an inactive pill), women taking estrogen alone experienced:

  • No difference in risk for heart attack
  • Increased risk of stroke
  • Increased risk of blood clots
  • Uncertain effect for breast cancer
  • No difference in risk for colorectal cancer
  • Reduced risk of fracture

Source: Women's Health Initiative, 2005 (1)

Based on the results of the Women's Health Initiative, the U.S. Food and Drug Administration (FDA) issued a statement in February 2004 encouraging all manufacturers of estrogen and estrogen with progestin drug products indicated for use by postmenopausal women to update the labeling for their products to provide information about possible health risks (5). Furthermore, in May 2005, the U.S. Preventive Services Task Force, supported by the U.S. Agency for Healthcare Research and Quality, issued a new recommendation against the routine use of estrogen to prevent chronic conditions such as heart disease, stroke and osteoporosis in postmenopausal women who have undergone a hysterectomy (6). The Task Force did not examine the effects of estrogen only or combined estrogen and progestin for the treatment of menopausal symptoms, only for the prevention of chronic disease.

In 2008, the Women’s Health initiative published updated results that confirm that the health risks of long-term use of combination (estrogen plus progestin) hormone therapy in healthy, postmenopausal women persist even a few years after stopping the drugs and clearly outweigh the benefits. Researchers report that about three years after women stopped taking combination hormone therapy, many of the health effects of hormones such as increased risk of heart disease are diminished, but overall risks, including risks of stroke, blood clots, and cancer, remain high. Therefore, the WHI maintains that healthy women should not use HRT for the purpose of preventing disease.  

The National Institutes of Health, while acknowledging the health risks of HRT also recognize the benefits for some women with severe menopausal systems. According to the National Institute of Health, "Participants in the Women's Health study were randomly assigned to receive either hormones or placebo, and those women who had menopausal symptoms reported relief from symptoms with hormone use. Women who felt that they needed menopausal hormones to treat severe symptoms may not have been willing to take the chance of not receiving hormones and may, therefore, have been underrepresented in the study." (4)



The following chart summarizes the possible benefits and risks of ERT (estrogen without progestin). The benefits and risks may differ when estrogen is combined with progestin. For example, the increased risk of endometrial cancer is not associated with combination hormone therapy.

Possible Benefits of ERT Possible Risks of ERT
  • Relieves menopausal symptoms—hot flashes, vaginal dryness, etc.
  • Prevents and treats osteoporosis
  • May improve mood
  • May increase risk of heart attack and stroke (research is contradictory)
  • May increase risk of blood clots in legs and lungs
  • May increase risk of breast cancer
  • May increase risk of breast cancer when taken for more than 5 years
  • Increases risk of endometrial cancer�cancer of the uterine lining (risk counteracted if estrogen is combined with progestin)
  • Increases risk of ovarian cancer
  • May be associated with side effects, such as bloating, nausea, etc.

HRT is a tradeoff between the proven benefits of relieving menopausal symptoms and preventing diseases such as osteoporosis versus the possibility of increasing the risk of breast cancer. If a woman is at high risk of osteoporosis (due to age, family history, small build, etc.) and has a relatively low risk of breast cancer, then HRT may be an easy choice. If a woman is already at high risk of breast cancer due to genetic factors, family history, etc. then the decision to take HRT may be more complicated.

To further add to the confusion, the combined estrogen/progestin arm of the Women's Health Initiative (WHI)-a large clinical trial that was studying HRT, heart disease, osteoporosis, breast cancer, and colon cancer in 63,000 American women between the ages of 50 and 79-was halted in by the National Institutes of Health (NIH) in 2002. Researchers felt that the elevated risk of breast cancer, as well as higher than normal rates of heart attack, stroke, and blood clots, outweighed the benefits that HRT may provide against hip fractures and colon cancer. The arm of the WHI that studied estrogen alone (with progestin) did not find an increase in heath-related problems among women who took estrogen. That arm of the study will continue. At the moment, the best advice experts can give is for women to discuss the benefits and risks of HRT with their physicians and make informed choices.

Additional Resources and References

Updated: June 2010