Risk of Ovarian Cancer is Linked to
Estrogen Replacement Therapy
article syndicated from NIH
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
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
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 administratio
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
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.
For background information on hormone replacement therapy: http://newscenter.cancer.gov/pressreleases/estrogenplus.html.
For more information on recent studies on hormone therapy: http://cancer.gov/clinicaltrials/digest-page-menopausal-hormone-use.
Call the NCI's Cancer Information Service for information about hormone replacement
therapy and cancer risk. The number is 1-800-422-6237 (1-800-4-CANCER). For hearing
impaired callers, TTY: 1-800-332-8615.
*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.
article syndicated from National
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