DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service

 

National Institute on Aging National Institutes of Health

 Bethesda, Maryland 20892

June 2004 

Understanding the Women’s Health Initiative Study of Using Estrogen Alone 

For many years women and their doctors have had questions about the benefits and risks of 

menopausal hormone therapy. Conflicting results from a variety of research studies did 

not give them the answers they needed. Therefore, the Women’s Health Initiative was 

designed to answer many of their questions. 

In July 2002 the estrogen plus progestin part of the WHI Hormone Trial was stopped, and 

follow up began. The estrogen-alone part of the WHI continued until late February 2004, 

when the National Institutes of Health (NIH) told women taking part in that study to stop 

taking their study pills. Follow-up of women in the estrogen plus progestin and estrogenalone trials is ongoing. 

Why stop the estrogen-alone trial? NIH experts carefully looked at the study information 

and found an increased risk of stroke. They decided that the results would probably not 

change if this trial, which had continued for an average of nearly 7 years, went on to its 

planned end in 2005. They also felt that the results provided information about the overall 

risks and benefits of using estrogen alone in this trial and that women should have this 

information for making their own health decisions. 

In April 2004, WHI scientists reported that women ages 50 to 79 using estrogen alone

were more likely to have a stroke and were not protected against heart disease.* Women 

using this hormone were also less likely to break a bone, and estrogen alone did not cause 

breast cancer in women in the study. In June, scientists with the substudy known as the 

Women’s Health Initiative Memory Study (WHIMS) reported that women age 65 and 

older using estrogen alone could have a small increase in the risk of dementia and had no 

reduction in their risk for cognitive loss.** See the box on the back to compare the results 

of the estrogen plus progestin and estrogen alone parts of the WHI and WHIMS trials. 

Experts still don’t have answers to some questions about menopausal hormone therapy 

such as: 

• Does using a different estrogen and/or progestin or another dose change the risks? 

• Does giving the hormones as a patch or cream, rather than a pill, change the risks? 

• Would taking the progestin for 10 to 14 days once a month or once every three 

months be better? 

• Would starting hormones closer to the age of menopause give different results? 

At present, the Food and Drug Administration suggests that women who want to use 

menopausal hormone therapy to control the troublesome symptoms of menopause such as 

hot flashes and vaginal dryness use the lowest effective dose for the shortest time 

necessary. 
In every 10,000 women each year, on average, using estrogen plus progestin (E+P) or estrogen 

alone (E) compared to placebo resulted in: 

Health Problem Cases per 10,000 women Difference in number of What the study 

 (hormone/placebo) cases per 10,000 women showed 

Heart disease – E+P 37 / 30 7 more increased risk; not likely 

 explained by chance 

 -- E alone 49 / 54 5 fewer decreased risk; might be 

 explained by chance 

Stroke -- E+P 29 / 21 8 more increased risk; not likely 

 explained by chance 

 -- E alone 44 / 32 12 more increased risk; not likely 

 explained by chance 

Blood Clots -- E+P 34 / 16 18 more increased risk; not likely 

 explained by chance 

 -- E alone 28 / 21 7 more increased risk; might be 

 explained by chance 

Breast cancer -- E+P 38 / 30 8 more increased risk; not likely 

 explained by chance 

 -- E alone 26 / 33 7 fewer decreased risk; might be 

 explained by chance 

Colorectal – E+P 10 / 16 6 fewer decreased risk; not likely 

cancer explained by chance 

 -- E alone 17 / 16 1 more no change 

Hip fractures -- E+P 10 / 15 5 fewer decreased risk; not likely 

 explained by chance 

 -- E alone 11 / 17 6 fewer decreased risk; not likely 

 explained by chance 

 

Dementia in -- E+P 45 / 22 23 more increased risk; not likely 

women over explained by chance 

age 65 -- E alone 37 / 25 12 more increased risk; might be 

 explained by chance 

For more information: Menopause, the health issues that are part of that time in a woman’s life, 

and the WHI studies are discussed in more detail in Menopause: One Woman’s Story, Every 

Woman’s Story and its Companion, 2003. Both are available online at 

www.niapublications.org/pubs/menopause/index.asp. Print copies may be ordered online at 

www.niapublications.org, or by calling 1-800-222-2225. 

*The Women’s Health Initiative Steering Committee. Effects of Conjugated Equine Estrogen in Postmenopausal 

Women with Hysterectomy: The Women’s Health Initiative Randomized Controlled Trial. JAMA. 2004; 291: 1701-

1712. 

**Shumaker SA, Legault C, Kuller L, Rapp SR, Thal L, Lane DS, Fillit H, Stefanick ML, Hendrix S, Lewis CE, Masaki 

K, Coker LH. Conjugated Equine Estrogens and Incidence of Probable Dementia and Mild Cognitive Impairment in 

Postmenopausal Women: Women’s Health Initiative Memory Study. JAMA. 2004; 291: 2947-2958. 

Espeland MA, Rapp SR, Shumaker SA, Brunner R, Manson JE, Sherwin BB, Hsia J, Margolis KL, Hogen PE, Wallace 

R, Dailey M, Freeman R, Hays J for the Women’s Health Initiative Memory Study. Conjugated Equine Estrogens and 

Global Cognitive Function in Postmenopausal Women: Women’s Health Initiative Memory Study. JAMA. 2004; 291: 

2959-2968.