MENOPAUSE

One Woman’s Story, Every Woman’s Story

C O M P A N I O N, 2003
In the 21/2 years since printing Menopause: One Woman’s Story,

Every Woman’s Story—A Resource for Making Healthy Choices,

there have been several significant research findings involving

the treatment used for the symptoms of menopause. This companion explains the most important new studies. It is designed

to be read in conjunction with the full Menopause booklet.

We’ve tagged some of the updated material with page numbers

from the full Menopause booklet where more detailed information is available. So, by combining this information with the

earlier booklet, you will have the most up-to-date information

to help make a decision about whether menopausal hormone

therapy is right for you. Information about ordering the full

booklet or more copies of this companion is at the end.

Terminology

The terms that describe the use of estrogen with or without a

progestin to treat the symptoms of menopause are changing.

Risks and Benefits of Hormones

This is a confusing time for any woman dealing with the

symptoms of menopause. In the past, women were told that

using menopausal hormone therapy would control their hot

flashes and vaginal dryness while protecting them from heart

disease and osteoporosis. Results from the Women’s Health

Initiative (WHI) in 2002 did confirm some of these uses, but

questioned others. While all the answers are still not in, the

latest results do give women more information to use when

considering their choices.

Booklet?

1

Why a Companion

THERAPY WAS NOW

Using estrogen with 

or without progestin

Using estrogen alone

Using estrogen with 

a progestin

hormone replacement 

therapy (HRT)

estrogen replacement 

therapy (ERT)

hormone replacement 

therapy (HRT)

menopausal hormone 

therapy (MHT)

estrogen therapy (ET)

estrogen-progestin 

therapy (EPT)
Page 23 discusses the

WHI trial which included

women between the ages 

of 50 and 79 when they

entered the study. The WHI

was designed to help women

and their doctors know the

benefits and risks of using

menopausal hormone therapy

(MHT) to prevent chronic 

illnesses such as heart disease.

It was planned to run for 

81/2 years. In July 2002, part

of the study was stopped—

more than 3 years early.

Why did this happen? In

the part of the study that was

stopped, each day women received PremproTM (see sidebar)

or a placebo (see sidebar). Scientists stopped this arm of the

WHI research when they found that the possible risks of

this estrogen-progestin therapy (EPT) exceeded the safety

limits established at the outset of the study. A second part

of the research where women were given PremarinTM (see

sidebar) or a placebo is continuing, and the risks and benefits are being monitored carefully.

What were the risks?

WHI scientists found that women using this combined estrogen plus progestin (EPT) had more heart attacks, breast cancers, blood clots, and strokes than women not receiving any

hormones. Some of these results were not a surprise. Experts

had already suspected that using estrogen plus progestin

could add to a woman’s chance of developing breast cancer

or a blood clot. The increase in heart disease was unexpected

because scientists had hoped to lower the risk of heart disease

by giving women in the study this combination.

Another surprise finding was reported in May 2003.

Investigators in a WHI substudy, called the Women’s Health

2

PremproTM is a pill containing:

■ 0.625 mg of conjugated equine 

estrogens (CEEs) and 

■ 2.5 mg of a progestin called medroxyprogesterone acetate (MPA).

PremarinTM is a pill containing only 

0.625 mg of CEEs, without the MPA.

A placebo looks like the hormone pills, 

but has no hormones in it.
Initiative Memory Study (WHIMS), reported that women over

age 65 using PremproTM were at twice the risk for developing

dementia as women not using any hormones and were also

not protected from cognitive decline. This was unexpected

because earlier studies had suggested that estrogen plus progestin might prevent or delay some of the serious cognitive

problems that occur in some older women.

Were there benefits? 

The WHI had some positive findings, too. Women taking

combined estrogen plus progestin had fewer cases of colon

cancer and a decrease in the number of bone fractures.

These results were expected. Earlier studies had suggested

that estrogen plus progestin might prevent colon cancer

and protect against bone fractures. At the time the WHI

study began, there were few treatments for osteoporosis.

Now several drugs are available.

Often women believe that relief from menopausal symptoms improves their daily functioning and quality-of-life. But,

the WHI study of women ages 50 to 79 reported in May 2003

that PremproTM did not change how women described their

mood, energy level, sexual satisfaction, or general health.

Women did, however, after 1 year have a small, but meaningful improvement in sleep, physical functioning, and bodily

pain. After 3 years, there were no benefits. Younger women in

the WHI (those ages 50 to 54) with moderate to severe hot

flashes and/or night sweats, found PremproTM improved their

hot flashes/night sweats and sleep, but nothing else.

3
How big are the risks or benefits?

There are two ways to describe the WHI results. One is relative

risk. In the WHI relative risk compares the chance of one

woman who takes combined estrogen plus progestin getting a

health problem with that risk in another woman who does not

take any menopausal hormone therapy. Relative risk is usually

expressed as a number in decimal form, but may be easier to

understand as a percentage. In the WHI and the WHIMS substudy the relative risks of using this combined estrogen plus

progestin are shown in the top part of the chart below.

The second way to describe these results is absolute risk.

This tells us the number of health problems that result from,

or are prevented by, using estrogen plus progestin. It is usually

expressed as the number of cases per people treated. For the

WHI and the WHIMS substudy, changes in the absolute risk 

in 10,000 women receiving this combined estrogen plus progestin yearly are shown in the bottom part of the chart below.

Heart attack 7 more cases in 10,000 women

Breast cancer 8 more cases in 10,000 women

Stroke 8 more cases in 10,000 women

Blood clot 18 more cases in 10,000 women

Dementia 23 more cases in 10,000 women over age 65

Hip fracture 5 fewer cases in 10,000 women

Colon cancer 6 fewer cases in 10,000 women

Heart attack 1.29 29% increase

Breast cancer 1.26 26% increase

Stroke 1.41 41% increase

Blood clot 2.11 111% increase

Dementia 2.05 105% increase in women over age 65

Hip fracture 0.66 33% decrease

Colon cancer 0.63 37% decrease

RISK/BENEFIT CHANGE PER YEAR

RISK/BENEFIT CHANGE

4

RELATIVE RISK ABSOLUTE RISK
Questions remain

Experts still have questions. These include:

◗ How long is it safe to use menopausal hormone 

therapy to manage symptoms? In the WHI study of

women age 50 to 79, the increase in breast cancer did

not develop until after 4 years of use, but the extra

cases of heart disease, stroke, blood clots, and, in

WHIMS, cognitive decline in women age 65 and older

began within 2 years after starting this combined 

estrogen plus progestin.

◗ Will these results prove true for other types of estrogen

and progestin? Scientists don’t know. The WHI looked

only at PremarinTM and PremproTM, which were the two

most commonly prescribed types of menopausal hormone

therapy when the study began.

◗ What about forms other than pills, like patches or

creams? These have not been studied as thoroughly as

the hormones used in the WHI project, and no information is available to compare them.

◗ Will smaller doses of these hormones have lower risks?

Lower benefits? Experts don’t know. New information

may become available as other studies are concluded.

◗ If a woman decides to stop using estrogen alone or

estrogen plus progestin, what is the best way? Some

doctors suggest tapering off—reducing the dose gradually.

Others say it’s fine to just stop.

◗ Does progestin cause the increased risk of health 

problems from using this combined estrogen plus

progestin? Experts don’t know. More study is needed.

But we do know that taking estrogen without a progestin does cause a thickening of the lining of the uterus

and slightly increases a woman’s risk of cancer of the

lining of the uterus (endometrial cancer). That is why

estrogen alone is only recommended for use in women

who have had a hysterectomy.

5
◗ Does estrogen protect your mind from the effects of

growing older or even Alzheimer’s disease? The part of

WHIMS using estrogen only is continuing and may 

provide a better understanding.

◗ Does estrogen alone cause ovarian cancer? In 2002 

an observational study of women using estrogen alone

found that the cases of ovarian cancer almost doubled

after 10 to 19 years of estrogen use, and more than

doubled after 20 years. The absolute risks in 10,000

women each year are shown in the chart below. This is

being studied in the estrogen alone part of the WHI.

In Summary

Since 2002, studies from the WHI have reported that

women using a particular combination estrogen-progestin

therapy were at increased risk for heart disease, stroke,

blood clots, breast cancer, and dementia, but were at

decreased risk for colorectal cancer and bone fracture. 

The therapy also only slightly improved hot flashes, 

sleep, and physical functioning in the women studied.

The surprising findings from this study were that 

the estrogen-progestin therapy used did not prevent 

heart disease or cognitive decline. Lifestyle changes and

other medications are more effective for protecting the

heart than using this combined estrogen plus progestin

(page 24).

Menopausal hormone therapy—whether estrogen

alone or estrogen plus progestin—is a single treatment

with several uses. It is still approved by the Food and 

Drug Administration for controlling the symptoms of

6

Using no hormones, after 10 –19 years 4.4 cases in 10,000 women

Using estrogen alone for 10 –19 years 7 cases in 10,000 women

Using estrogen alone for 20 years or more 14 cases in 10,000 women

ABSOLUTE RISK
menopause, especially hot flashes,

night sweats, and vaginal dryness, but also for protecting

women from osteoporosis. 

At present, experts suggest 

that women use menopausal

hormone therapy, if they need

to, for the shortest time necessary at the lowest dose that

works. The booklet Menopause

discusses the other uses for

menopausal hormone therapy

on pages 6–7, 13, 14, and 24.

What Do I Do Now?

Talk to your doctor. It doesn’t

matter if you are currently using

menopausal hormone therapy or

if you are just starting to think

about taking it to help with hot

flashes or vaginal dryness. In

any case, you can use the WHI

study results to help make health care decisions that 

will match your own health risks and medical needs.

Remember, the final story on estrogen and progestin

has not been written yet. Even the WHI study is not 

complete because scientists are still studying all the 

information collected. The women who took estrogen

plus progestin as part of the WHI and the WHIMS substudy will continue to be checked on for several years. 

So, whatever you decide, at no point is your decision

about using menopausal hormone therapy final. You 

can start or stop this treatment at any time. You and

your doctor should review it carefully at your regular

checkup. Take into consideration things like: Have there

been any changes in your medical history or that of 

close family members? Have there been new research

findings? Regardless of your decision, follow the general

7
8

recommendations about staying healthy found on pages

26–28 of the larger Menopause book as the first step in a

healthy life for years to come.

If you have received this companion without the

Menopause book or would like more copies of either one,

contact 1-800-222-2225 for your free publications.

RESOURCES

Menopause: One Woman’s Story, Every Woman’s Story— 

A Resource for Making Healthy Choices

http://www.nia.nih.gov/health/pubs/menopause/menopause.pdf

Report of the WHI results, July 2002

Writing Group for the Women’s Health Initiative Investigators.

“Risks and Benefits of Estrogen Plus Progestin in Healthy

Postmenopausal Women: Principal Results From the Women’s

Health Initiative Randomized Controlled Trial.” JAMA. 2002;

288:321–333.

Report of the WHI quality-of-life results, May 2003

Hays J, Ockene JK, Brunner RL, Kotchen JM, Manson JE,

Patterson RE, Aragaki AK, Shumaker SA, Brzyski RG, LaCroix

AZ, Granek IA, and Valanis BG. “Effects of Estrogen/Progestin

on Health-Related Quality of Life.” New England Journal of

Medicine. 2003; 348:19:1839–1854.

Two Reports of the WHIMS results, May 2003

Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK,

Hendrix SL, Jones III BN, Assaf AR, Jackson RD, Kotchen JM,

Wassertheil-Smoller S, and Wactawski-Wende J, for the WHIMS

Investigators. “Estrogen Plus Progestin and the Incidence of

Dementia and Mild Cognitive Impairment in Postmenopausal
Women: The Women’s Health Initiative Memory Study: A

Randomized Controlled Trial.” JAMA. 2003; 289:2651–2662.

Rapp SR, Espeland MA, Shumaker SA, Henderson VW, Brunner

RL, Manson JE, Gass MLS, Stefanick ML, Lane DS, Hays J,

Johnson KC, Coker LH, Dailey M, Bowen D, for the WHIMS

Investigators. “Effect of Estrogen Plus Progestin on Global

Cognitive Function in Postmenopausal Women: The Women’s

Health Initiative Memory Study: A Randomized Controlled

Trial.” JAMA. 2003; 2898:2663–2672.

Understanding Risk: What Do Those Headlines Really Mean?

http://www.niapublications.org/engagepages/risk.asp

National Institutes of Health (NIH) Menopausal Hormone

Therapy Web Site

http://www.nih.gov/PHTindex.htm

Women’s Health Initiative 

(WHI) Web Site

http://www.nhlbi.nih.gov/whi/

NIA Information Center

PO Box 8057

Gaithersburg, MD 20898-8057

1-800-222-2225

TTY: 1-800-222-4225

http://www.nia.nih.gov
U.S. Department of Health and Human Services

Public Health Service

National Institutes of Health

NIH Publication No. 03-5383

August 2003