Susan Sullivan doesn't know whether her health would be helped or harmed by hormone replacement therapy.
But the 55-year-old artist, who lives in Los Angeles' rustic Topanga Canyon area, is counting on one thing: By the time her 20-year-old daughter reaches menopause, there will finally be some solid, trustworthy medical information about who should be on hormones and why.
Like most U.S. women over age 45, Sullivan has watched with apprehension as studies made public during the past few months have presented disturbing and contradictory findings, leaving many women confused about the risks and benefits of using hormones.
Sullivan is doing her small part to bring some clarity to the confusion. She visits UCLA Medical Center several times a year to participate in the largest study to date of the medical impact of hormone therapy in women.
"When I arrived at meno-pause, I found there wasn't any good information out there," Sullivan says. "But I have a daughter, and I thought her generation deserves better."
Known as the Women's Health Initiative, the federally funded study involves 161,000 women between the ages of 50 and 79, as well as researchers at more than 40 sites. The 15-year, $700 million study (which also looks at other women's health issues) is considered a crown jewel in current women's health research.
"The Women's Health Initiative is the only [scientifically rigorous] trial that actually looks at the effect of estrogen on bones, brain, heart and other issues, including types of cancers," says Dr. Michele Blackwood, a breast surgeon in Stamford, Conn.
A major, long-term study of post-menopausal women with heart disease, called the Estrogen Replacement and Atherosclerosis (ERA) study, showed that hormone use did not slow the course of the disease.
If those results weren't disappointing enough, another study published last month found that soy, a popular alternative to estrogen for relieving hot flashes related to menopause, was ineffective.
Most doctors acknowledge that women will not be able to make well-informed decisions on hormone therapy until the completion of the Women's Health Initiative. Researchers have said they expect the trial's first major results to be released sometime in 2005.
"I feel we're at the tip of the iceberg in trying to figure out what will make a woman's [menopausal] symptoms go away in addition to making her life better," Blackwood says.
Adds Dr. Howard L. Judd, the principal investigator of the trial's study site at UCLA Medical Center, "We're feeling enormous pressure."
Many major questions remain about the effects of hormone replacement therapy. Estrogen is often recommended to women at menopause to alleviate some of its symptoms, such as hot flashes, vaginal dryness and mood swings.
It is also recommended for women at risk of osteoporosis because replacing the estrogen lost at menopause helps maintain strong bones.
"What I tell women is if you have symptoms [of menopause], there is no reason not to take hormones," Judd says. "And, if you are at risk for osteoporosis, take hormones."
Estrogen is also known to increase good cholesterol (high-density lipoprotein, or HDL) and reduce the bad kind (LDL) and maintain the elasticity of arterial walls. These findings have raised hopes that hormones can be used long-term to prevent heart disease.
And some small studies have hinted that estrogen may help prevent the dementia associated with Alzheimer's.
But, so far, there is no clear, convincing evidence that estrogen prevents heart disease or Alzheimer's disease, authorities say.
Two large, randomized, controlled clinical studies -- the recent ERA study and a 1998 study called the Heart and Estrogen-Progestin Replacement Study (HERS) -- produced disappointing results.
"The two best sources of data [on heart disease and estrogen] are the HERS and ERA studies, and both show the same thing: no benefit," says Dr. David Herrington, a cardiologist at Wake Forest University who presented the ERA study in March.
"It's possible," Herrington says, "that estrogen could be relatively helpful in preventing heart disease while being ineffective once disease has been established."
While it is strongly implied, there is no proof that estrogen helps prevent heart disease. Indeed, preliminary findings released earlier this month from a study by the National Heart, Lung and Blood Institute suggest that hormone replacement therapy might slightly increase the chance of heart attacks in the first two years that women take them.
Another major area of fierce controversy is how hormone use affects cancer risk.
Over the past two decades, epidemiological studies on hormone use and breast cancer have produced mixed results. Some studies have found no increased risk, while others have found a small increased risk.
What all of this means is hotly debated.
Until the completion of the Women's Health Initiative, women need to realize that any decision they make will be based on a platform of information that is only partially constructed.
There is general agreement among medical authorities that estrogen therapy has these effects:
* Usually alleviates some of the symptoms of menopause, such as hot flashes and vaginal dryness.
* Helps maintain bone health and reduce the risk of fractures.
* Increases the risk of uterine cancer if not combined with progesterone.
* Improves levels of good cholesterol.
Authorities generally agree that there is a significant -- although not conclusive -- body of scientific evidence supporting these effects:
* Helps to prevent or delay heart disease in at least some women.
* Is unsuccessful at slowing heart disease among women with established disease.
Many outstanding questions about the effects of replacement hormones remain unanswerable because of insufficient scientific evidence or disagreement among authorities over how to interpret available evidence:
* Whether hormone therapy increases the risk of breast cancer in some or all women.
* Whether adding progesterone changes the rate of protection against heart disease or changes breast cancer risk rates.
* Whether therapy has any effect on the development of colon and ovarian cancer.
* Whether hormone therapy improves cognitive function in women with Alzheimer's disease; also, whether it helps prevent or delay the onset of Alzheimer's.