16 AWHONN Lifelines Volume 7 Issue 1

cContinuous combined estrogen-plus-a-

progestin therapy for menopause management

is associated with an increased breast cancer

risk among women who are currently taking

such hormone therapy (HT) and who have

been doing so for five years or more. This find-

ing is consistent with the data released in mid-

July from the Women’s Health Initiative (WHI)

and was confirmed by two studies reported in

the December issue of Obstetrics & Gynecology.

Particularly, researchers report, breast cancer

risk may vary by hormone regimen and how

recently it was used.

The confirmation of the WHI results comes

from the Women’s Contraceptive and

Reproductive Study, which studied 3,823 post-

menopausal women on continuous combined

HT (defined here as estrogen combined with

25-31 days per month of progestin use), from

the National Institute of Child Health and

Human Development (NICHD) and data

New Studies YieldResults ConsistentWith WHI; CautionAgainst AntioxidantVitamins in WomenWith Existing Heart Disease

Risk FromBreast Cancer

HRT Confirmed

Carolyn Davis Cockey, MS

analysis from the Heart and Estrogen/Progestin

Replacement Study (HERS).

The NICHD findings, however, found no

association between past use of continuous

combined HT and breast cancer risk. This sug-

gests that “the increased risk associated with

continuous combined HT use dissipates quick-

ly once use is discontinued,” researchers

observed.

Unlike the WHI, the NICHD study looked

at pill and patch hormone users as well as sev-

eral types of hormone regimens. Researchers

found no association between breast cancer

risk and the regimens of either estrogen-alone

therapy or sequential HT (estrogen combined

with 5-14 days per month of progestin use).

This was a multicenter, population-based case-

control study conducted in five U.S. metropoli-

tan areas from 1994 to 1998. Analyzed were

1,870 women diagnosed with invasive or in situ

breast cancer and 1,953 women as controls,

ages 35 to 64 years.

In what may be the first report to document

the effect of HT on hot flashes in older women,

researchers analyzing data from the HERS trial

found that symptoms typically attributed to

menopause are common in elderly women. For

these women, continuous combined hormone

therapy can provide relief of vasomotor symp-

toms—though perhaps lower doses may be

preferable to the dosages studied, note

researchers.

Most studies of menopausal symptoms

focus on midlife women between 45 and 60

years of age. Researchers here examined the

data from 2,763 participants in HERS, which

was a large, randomized placebo-controlled

trial of women with documented heart disease,

funded by Wyeth-Ayerst Research. The mean

age of participants studied was 67, and the

women averaged 18 years since menopause. Of

the HERS participants:

• 16 percent at baseline reported frequent hot

flashes

• 26 percent vaginal dryness

• 10 percent genital irritation

• 55 percent trouble sleeping

• 53 percent early awakening

Although the prevalence of symptoms declined

with age, hot flashes were still a complaint

among women one or more decades after

menopause.

Researchers found that women treated with

combined continuous HT (at the dosage of

conjugated estrogens 0.625 mg plus medroxy-

progesterone acetate 2.5 mg) were less likely

than women on placebo to report hot flashes,

vaginal dryness and trouble sleeping. By year 1

of treatment, improvement was especially

marked for hot flashes. There was no improve-

ment in early awakening with hormone treat-

ment, suggesting this symptom may not be

related to estrogen status.

Side effects of HT were also evident.

Women assigned to this dosage of HT were

more likely to develop somewhat or very fre-

quent vaginal discharge, genital irritation, uter-

ine bleeding and breast symptoms than women

assigned to placebo. The authors note that

lower doses of HT may be advisable for such

women, depending on the reasons for starting

therapy.

In separate but related news, a study of

menopausal women with heart disease found

no benefit but potential harm from HT and

antioxidant vitamins. The study, sponsored by

the National Heart, Lung, and Blood Institute

(NHLBI) of the National Institutes of Health,

found that postmenopausal women with heart

disease who took hormone therapy and high-

dose antioxidant vitamins—either alone or in

combination with hormones—did not have

fewer heart attacks, deaths, or progression of

coronary disease. In fact, both treatments

showed a potential for harm. Although the

actual numbers of deaths in the study were

small, participants taking both active hor-

mones and vitamins had the highest death rate

while participants on placebo versions of both

treatments had the lowest death rate.

Furthermore, participants taking hormones

and vitamins had either more or equal progres-

sion of their coronary disease compared with

participants taking placebo versions of these

treatments.

The results of the Women’s Angiographic

Vitamin and Estrogen (WAVE) trial were pub-

lished in the November 20, 2002, issue of the

Journal of the American Medical Association.

WAVE, which studied 423 postmenopausal

women at seven clinical centers in the U.S. and

A study of

menopausal women

with heart disease

found no benefit but

potential harm from

HT and antioxidant

vitamins

February | March 2003 AWHONN Lifelines 17

In the wake of the

results of the

Women’s Health

Initiative regarding

hormone replacement

therapy (HRT), health

care providers

dramatically changed

their prescribing

habits regarding

menopause

management

Canada, is the largest trial to use angiography

(a special x-ray technique that shows blockages

in the blood vessels of the heart) to assess the

effects of hormone replacement therapy

(HRT). It is also the first angiographic trial to

look at antioxidants—high-dose vitamins E

and C—in conjunction with hormone therapy.

The vitamin doses in the WAVE study were

much higher than what is used in standard

multivitamin preparations.

“Although some other studies with lower

doses of vitamins have suggested that antioxi-

dant vitamin supplements might not be help-

ful, the trend toward more deaths found in

WAVE was unexpected,” investigators said. “The

good news is that there are proven therapies to

treat and prevent coronary heart disease,

including weight control and controlling high

blood cholesterol and high blood pressure.”

Participants in the WAVE study were ran-

domly assigned to one of four treatment

groups:

• Hormone therapy and placebo vitamin

• Placebo hormone and vitamins C and E

• Hormone therapy and vitamins C and E

• Placebo hormone and placebo vitamin

Participants taking active hor-

mone took either one daily tablet

of conjugated equine estrogen

(Premarin, 0.625 mg) if they did

not have a uterus or one daily tablet

of conjugated equine estrogen

(Premarin, 0.625 mg) plus medroxy-

progesterone (2.5 mg, Prempro).

Participants taking active vitamin were

prescribed 400 IU of vitamin E and 500

mg of vitamin C, each to be taken two times

a day.

The hormone preparation taken by women

with a uterus was the same as that used in the

much larger WHI study, which was stopped in

July 2002 due to an increased risk of breast

cancer and because, overall, risks from use of

the hormones outweighed and outnumbered

the benefits. Unlike WAVE participants, most

women in the WHI study did not have prior

evidence of heart disease. In the WAVE trial,

angiograms were performed when women

entered the study and at study exit—approxi-

mately three years later. Specific findings

include,

• In the active hormone group, 26 patients

died, had a nonfatal heart attack, or suffered

a stroke, compared with 15 in the hormone

placebo group

• In the active vitamin group, 16 patients died

from all causes, compared with 6 in the vita-

min placebo group

• In the active vitamin group, 20 patients expe-

rienced either death or a nonfatal heart attack,

compared with 10 in the placebo group

There were few cases of breast cancer or other

cancers—and no differences in the occurrence

of cancer between the groups.

HRT Findings Spark Change in Prescribing Habits

In the wake of the results of the Women’s

Health Initiative regarding HRT, health care

providers dramatically changed their prescrib-

ing habits regarding menopause management,

a new survey released from the medical research

and communications firm MedPanel reveals.

The survey shows that health care providers

and patients alike were highly concerned about

the findings that were released,

and that concern translated

into both an increase in

patient visits and a

decrease in the num-

ber of HRT pre-

scriptions, as

well as,

• health care

providers among the

panel and survey reduced

the number of HRT prescrip-

tions for postmenopausal women from

52 percent in 2001 to 12 percent in 2002

• 96 percent of health care providers said the

results of the WHI was the major influenc-

ing factor in reducing HRT prescription

recommendations

• 80 percent said the treatment change came

about from a combination of both provider

and patient concerns

When health care providers were asked

about whether they would prescribe HRT in

the future,

18 AWHONN Lifelines Volume 7 Issue 1

Carolyn Davis Cockey,

MS, is executive editor

of AWHONN

Lifelines.