Menopause Archives

ERT and Ovarian Cancer

Office of Communications/ Mass Media Branch/ Building 31,
Room 10A19, Bethesda, MD 20892
National Institutes of Health : NCI Press Office (301) 496-6641

July 16, 2002

Increased Risk of Ovarian Cancer is Linked to Estrogen
Replacement Therapy

Researchers from the National Cancer Institute (NCI) have
found that women in a large study who used estrogen
replacement therapy after menopause were at increased risk
for ovarian cancer. The report was published in the July 17,
2002, issue of JAMA.*

The scientists followed 44,241 women for approximately 20
years. Compared to postmenopausal women not using hormone
replacement therapy, users of estrogen-only therapy had a 60
percent greater risk of developing ovarian cancer. The risk
increased with length of estrogen use. The women, who were
followed from 1979 to 1998, were former participants in the
Breast Cancer Detection Demonstration Project, a mammography
screening program conducted between 1973 and 1980.

"The main finding of our study was that postmenopausal women
who used estrogen replacement therapy for 10 or more years
were at significantly higher risk of developing ovarian
cancer than women who never used hormone replacement
therapy," said James V. Lacey, Jr., Ph.D., lead author of
the study from NCI's Division of Cancer Epidemiology and
Genetics. The relative risk for 10 to 19 years of use was
1.8, which translates to an 80 percent higher risk than
non-users, and increased to 3.2 (a 220 percent higher risk
than non-users) for women who took estrogen for 20 or more
years.

Estrogen is a natural hormone produced primarily by the
ovaries. After menopause, the ovaries produce lower levels
of the hormones estrogen and progesterone. By the time
natural menopause is complete - usually between ages 45 and
55 - hormone output decreases significantly. As early as the
1940s, women began using estrogens in high doses to
counteract some of the short-term discomforts of menopause
(hot flashes, vaginal drying and thinning, and urinary tract
incontinence and infections).

However, after it became clear in the 1970s that women who
took estrogen alone had a six to eight times higher risk of
developing endometrial cancer (cancer of the lining of the
uterus), doctors began prescribing progestin along with much
lower doses of estrogen. Progestin is a synthetic form of
the natural hormone progesterone. The addition of progestin
to estrogen therapy reduces the increased risk of
endometrial cancer associated with using estrogen alone. As
a result, it has become increasingly common to prescribe
estrogen-progestin therapy for women who have not had a
hysterectomy.

In addition to studying the effect of estrogen use alone,
Lacey and his colleagues looked at whether women using
estrogen-progestin therapy were more likely to develop
ovarian cancer. No increased risk was found.

Lacey commented, "Even though our data showed that women who
took estrogen combined with progestin were not at increased
risk for ovarian cancer, only a few women in our study who
developed ovarian cancer had used estrogen-progestin therapy
for more than four years. So, at this point, there simply
aren't enough data to say whether taking the combined
therapy has any effect on ovarian cancer."

Past studies suggested that postmenopausal hormone
treatments might be effective in preventing or reducing some
of the negative long-term effects of aging, such as heart
disease and osteoporosis. However, the results from a large
multi-center clinical trial, also published in the July 17
issue of JAMA (JAMA 2002;288:321-333), showed increases in
breast cancer, coronary heart disease, stroke, and blood
clots in the lungs and legs for women on estrogen-progestin
therapy for an average of 5.2 years. The trial, part of the
Women's Health Initiative (WHI), also found fewer cases of
hip fractures and colon cancer among women taking the
combined therapy. However, because overall the harm was
greater than the benefit, the trial was stopped last week,
three years ahead of schedule. The WHI randomized trial for
estrogen alone in women who have had their uterus removed is
continuing.

Lacey emphasized the complexity of weighing the various
risks and benefits of hormone use. "Because hormone therapy
may influence so many conditions that affect women after
menopause - cardiovascular disease, osteoporosis, breast
cancer, uterine cancer, gallbladder disease, blood clots,
and now potentially ovarian cancer - we should no longer
think of a woman basing her decision to use hormones on the
potential risk of just one condition. Women should continue
to talk to their health care providers about whether
hormones might be right for them."

Previous studies looking at the effect of postmenopausal
hormones on ovarian cancer risk have been inconsistent. Some
reported increased risk with estrogen use while others
reported either no effect or a protective one. Most of these
earlier studies were relatively small and limited by
incomplete information about ovarian cancer risk factors.

Two recent large studies found a link between hormone use
and ovarian cancer. A large prospective study published last
year (JAMA 2001;285:1460-1465) showed that postmenopausal
estrogen use for 10 or more years was associated with
increased risk of ovarian cancer mortality, and a recent
Swedish study (J. Natl. Cancer Inst. 2002;94:497-504)
reported that estrogen use alone and estrogen-progestin used
sequentially (progestin used on average 10 days/month) may
be associated with an increased risk for ovarian cancer. In
contrast, estrogen-progestin used continuously (progestin
used on average 28 days/month) seemed to confer no increased
ovarian cancer risk.

Lacey said that some of the unknowns concerning hormone use
and ovarian cancer include the following:

? Duration vs. dose of estrogen therapy
It is not clear from this study whether the increased risk
with estrogen use is due to higher doses of estrogen, longer
duration of estrogen use, or both dose and duration. It is
also not clear whether long-term use of lower-dose estrogen
is associated with ovarian cancer.

? Duration of estrogen-progestin therapy
Most women in this study were on the combined therapy for
less than four years, so more data will be needed to
determine whether estrogen-progestin use increases risk. The
effect of long-term use of estrogen-progestin therapy is not
known.

? The type of estrogen-progestin regimen
The continuous regimen involves taking both hormones
simultaneously throughout the month. The sequential regimen,
on the other hand, involves taking estrogen every day, and
progestin for 10 to 14 days each month.

? Use of more than one type of hormone replacement therapy
For instance, after taking estrogen alone, some women
changed to a combined regimen after reports of increased
endometrial cancer risk with estrogen alone. More data are
needed to analyze the effect of switching from one regimen
to another.

? The form of estrogen administration
Most studies have analyzed the use of estrogens in pill
form, but it can also be administered by patches, shots, and
creams.

Every year, about 23,000 U.S. women are diagnosed with
ovarian cancer and 14,000 women die from the disease. A
woman's lifetime risk of developing ovarian cancer is 1.7
percent. This means that in a group of 100 women followed
from birth to age 85, fewer than two would get ovarian
cancer. In comparison, about 13 women would get breast
cancer (lifetime risk is 13.3 percent), fewer than three
women would develop uterine cancer (lifetime risk is 2.7
percent), and between 16 and 32 women would develop
osteoporosis.

An estimated 40 million U.S. women will experience menopause
during the next 20 years, and women today are living
approximately one-third of their life after menopause.

Anywhere from 20 percent to 45 percent of U.S. women take
some form of hormone therapy between the ages of 50 and 75.
According to industry estimates, about 8 million U.S. women
use estrogen alone and about 6 million U.S. women use
estrogen-progestin therapy. About 20 percent of hormone
users continue for more than five years.

* The study is titled "Menopausal hormone replacement
therapy and risk of ovarian cancer." The authors are James
V. Lacey, Jr., Pamela J. Mink, Jay H. Lubin, Mark E.
Sherman, Rebecca Troisi, Patricia Hartge, Arthur Schatzkin,
and Catherine Schairer. JAMA 2002;288:334-341.

Follow Ups:

• Re: ERT and Ovarian Cancer (Archive in HRT.) Walt Stoll 08:32:14 7/18/02 (0)

In Reply to: ERT and Ovarian Cancer posted by gdpawel on July 17, 2002 at 00:13:43:

Thanks, gdpawel.

I believe that this study was done with conjugated estrogens (the most commonly used for HRT).

Please see my note about this within the past week.

It would be a shame to throw out the baby with the bathwater.

Also see the aging archives.

Walt