Women's Health Initiative (WHI): Risks and benefits of hormone replacement therapy (HRT) and estrogen replacement therapy (ERT)
Hormone replacement therapy (HRT) was part of a large set of clinical trials called the Women's Health Initiative (WHI). The HRT portion of the study was ended 3 years early because of a small but unacceptable increase in the rate of breast cancer among the women taking a combination of 0.625 mg of estrogen plus 2.5 mg of progestin daily. As WHI data has been analyzed, blood clots, heart disease, stroke, ovarian cancer, and dementia risks have also been identified. Experts do not yet know whether lower-dose, shorter-term HRT reduces or eliminates these risks.
- HRT-related breast cancers first become apparent after 4 years of HRT use. The number of HRT-related breast cancers increased with each additional year of HRT use. Women taking HRT generally had larger, more advanced tumours than women who developed breast cancer while taking placebo treatment.1
- HRT slightly increases stroke risk in all healthy post-menopausal women, regardless of risk factors.1, 2 The increase in strokes first becomes apparent during the second year of HRT use.3
- In women who are 10 or more years past menopause, HRT slightly raises the risk of heart disease. Early signs of heart disease can first become apparent during the first year of hormone use.4, 5, 6
- HRT slightly raises the risk of blood clots in the lungs (pulmonary embolism) and legs (deep vein thrombosis) in all healthy post-menopausal women regardless of risk factors.3
- HRT raises the risk for Alzheimer’s disease and other dementias in women ages 65 and older. The increased risk first becomes apparent in women taking HRT for more than 4 years. The WHI researchers have concluded that HRT does not provide protection from dementia or cognitive impairment, as was previously believed.7
- HRT slightly raises ovarian cancer risk. This means that for a small number of women, taking HRT causes ovarian cancer.8
- Among HRT users, the number of abnormal mammograms increases by approximately 4% per year, first apparent after 1 year of HRT use. (Daily estrogen plus progestin increased breast density compared with estrogen alone or placebo.) Although the abnormal mammograms required additional medical evaluation, they were not linked to the increase in breast cancer. Studies are ongoing to determine the significance of this finding.9
Estrogen replacement therapy (ERT) use causes stroke and ovarian cancer in a small number of women. For this reason, the Women's Health Initiative ERT trial was stopped sooner than originally planned. Other ERT results show that women using ERT had no change in heart disease risk, had fewer hip fractures (a sign of estrogen's bone-protecting effect).10
Serious health events caused or prevented by HRT, per 1,000 women (estrogen 0.625 mg plus progestin 2.5 mg)1, 11 Health event After 2 years of HRT use After 5.2 years of HRT use Blood clots (venous thromboembolism) 6 more* 9 more Coronary artery disease 3 more** 4 more Breast cancer No change*** 4 more Stroke 1 more**** 4 more Colorectal cancer No change 3 fewer#
Hip fractures 1 fewer 2 fewer Death No change No change
* Risk is greatest during the first 2 years of use.
** First signs appear during the first year of use.
*** Risk first appears after 4 years of use.
**** Risk first appears after 1 year of use.
# Benefit appears after 3 years of use.
Estrogen, progestin, and breast, ovarian, and endometrial cancer risks
Taking estrogen with progestin (HRT) or estrogen without progestin (ERT) raises the risk of breast cancer and ovarian cancer. Taking estrogen raises the risk of endometrial (uterine) cancer.12, 8 These increased cancer risks are relatively low for the general population of post-menopausal women. But your personal risk that hormone therapy may stimulate cancerous cell growth may be significantly lower or higher, depending on your risk factors. For more information about cancer risk factors, see the topics Breast Cancer, Ovarian Cancer, and Endometrial Cancer.
| Author: | Kathe Gallagher, MSW Carrie Henley | Last Updated: August 4, 2006 |
| Medical Review: | Joy Melnikow, MD, MPH - Family Medicine Tom Bailey, MD - Family Medicine Carla J. Herman, MD, MPH - Internal Medicine | |
 | ||
| |