Janet Hungerford, 74, never really saw herself as a medical subject. "I've lived long enough, really," she says, "but if I can help someone else — my daughter, my granddaughter, even a great-granddaughter now — that's worth it."

A UC Davis patient, Hungerford has participated in the nationwide Women's Health Initiative since 1997. Although she "resisted" hormone replacement therapy when she went through menopause 24 years ago, she was assigned by the WHI to the clinical trial of Prempro™ — a trial that was halted last year when researchers concluded the risks of this estrogen- progestin combination outweighed the benefits.

"I was surprised — very much so," says Hungerford, who had expected to keep taking the drug until the end of the study in 2005. With a history of cardiac problems, she also fit the profile of older women once believed to benefit the most from an uninterrupted regimen of HRT.

But this, of course, is the most stunning discovery to come out of the WHI thus far: Instead of offering cardiac benefits, as was long believed based on observational studies, HRT seems to increase the risk of a cardiac event.

"There was a 29 percent increase in the risk of heart disease," says John Robbins, professor of medicine and principal investigator for the WHI. "But in terms of each participant's increased risk, the dangers are very small. For every 10,000 women years, there will be seven more cardiac events."

Small individual risks or not, the WHI halted the trial and the media grabbed the story, eventually causing millions of women to eschew HRT of any kind, and others to flounder in an overload of information and indecision.

"For 20 years, my wife has been beating on me to let patients make their own decisions," says Richard L. Sweet, professor of OB-GYN and director of UC Davis Women's Center for Health. "And when this came up, she said, 'No, no, just tell me what to do."

In Sweet's opinion, however, there is not yet a clear answer. The American College of Obstetricians and Gynecologists no longer recommends HRT for post- menopausal women with cardiac concerns — like Hungerford — but the issues get murkier for women in the throes of menopause.

"The question is still open," says Sweet. "Only one combination was shown to be bad — and that may not have even been statisti- cally significant." He suggests, for example, other forms of hormones may prove to be safer, such as pure estrogen patches, Estradiol™ (as opposed to Premarin™) or Norethindrone™.

Robbins agrees all the answers are not yet in, particularly with regard to estrogen by itself. "We now have a very sensitive data and safety monitoring board — and the clinical trials of estrogen alone have not been stopped," he says. "Reading the tea leaves, it seems there is not a significant increase in risks. It may also mean that progestin will prove to be the worst player."

In fact, Robbins believes the combination of estrogen and progestin "is no longer the treat- ment of choice for anything but hot flashes" and other primary menopausal symptoms, and that the controversy for women outside this narrow range of health issues is pretty much over.

Earlier beliefs that HRT offered protection against colon cancer and osteoporosis have been borne out, but there are better choices than hormones for patients and their doctors, according to Robbins. For example, "there are a number of other treatments for osteoporo- sis," he says, such as the bisphos- phonates and SERMs (selective estrogen receptor modulators), as well as appropriate calcium intake. "So if you have a patient with a risk of hip fracture, estrogens are not a good choice."

He recommends that these alternative treatments should be aggressively prescribed. "Don't be afraid to treat osteoporosis just because hormones can't be used," says Robbins. He fears a public health disaster if the many women taking HRT for osteoporosis stop taking hormones and don't take anything else.

Finally, what about those women — popping up now in national radio interviews — who claim their quality of life is extremely poor without HRT? "It's 100 percent appropriate for women who know the risks to choose to stay on these drugs," says Robbins. "We take all sorts of risks in life."

Sweet agrees, saying the "pendulum is going to swing back" and more women may choose HRT, even with this new information. "We've heard that of all the people who quit HRT after the findings were publicized," he says, "maybe as many as 40 or 50 percent are coming back." Mostly, he recom- mends "women have long discus- sions with their doctors."

Even Hungerford, who won't — and can't — go back on HRT as a continuing WHI participant, regrets her decision to give up the drug "cold turkey" without first consulting her primary care physician. "Here I am 74 years old," she says with a rueful smile, "and I'm having hot flashes."