Researchers halted the study in 2002 after they found the regimen entailed more health risks -- most notably an increased risk for breast cancer and stroke -- than benefits.
But an expert who has conducted a new critique of the study contends it had major methodological flaws.
"I looked at the way they designed the study, and they did make some major mistakes," said Dr. Edward L. Klaiber, a consultant endocrinologist at the University of Massachusetts Medical Center. He is the lead author of the article, published in the December issue of Fertility and Sterility.
The estrogen/progestin arm of the Women's Health Initiative (WHI) was halted when researchers found the regimen increased the risk of invasive breast cancer and blood clots in the legs and lungs, in addition to not protecting women from heart disease and strokes.
Then, in 2004, the estrogen-only phase of the study was stopped because it was linked to an increased risk of stroke, with no reduction in women's risk for heart disease.
In the wake of the WHI study, the American Heart Association recommended that long-term hormone therapy not be used for cardiovascular disease prevention and that its use for other reasons "should be cautiously considered with the advice of a physician."
According to Klaiber, in the estrogen/progestin arm, 73 percent of the women -- who averaged 63 years of age -- had never taken HRT before. In the estrogen-only group, 52 percent of those women (also averaging 63 years of age) had not taken hormone therapy before.
Klaiber's major criticism of the WHI: "They were putting women in their 60s and 70s who hadn't been on hormones on hormones for the first time," he said. Because these women were older, they were already at greater risk of cardiovascular problems, he reasoned.
Another flaw? One of the two regimens in the study "used daily progesterone," said Klaiber, who prefers non-continuous administration of progesterone.
"That hormone pattern had never been tested at that time for its effect on breast cancer and heart disease," Klaiber said. The other regimen, administered to women who had had a hysterectomy, used only estrogen.
Klaiber argues that hormone replacement therapy in other doses or delivery forms is not only safe, but still has a positive health effect. He pointed to previous findings from the large-scale Nurses' Health Study, in which women were placed on hormone therapy earlier -- in their 40s and 50s -- and did not take the combination continuously. That study found a heart-protective effect, he said.
"The women in the Nurses' Study were not taking progestin daily," Klaiber said. "They took it cyclically, usually 10 to 12 days a month instead of daily."
The new review is basically a rehash of previous criticisms, said Dr. Nieca Goldberg, chief of women's cardiac care at Lenox Hill Hospital in New York City.
"It's a critique," she said. "It has no new information."
"Many of these issues were brought up a couple years ago," she added. "In order for them to prove any of these other things -- such as other forms [of HRT] would be better -- they need to do a study." Goldberg said Klaiber's article won't change the way she practices.
Klaiber agreed that more study is needed. He said one study, currently underway, is evaluating the worth of earlier intervention with hormones as a way to protect the heart.
The Massachusetts expert said he's convinced that transdermal estrogen, given in patch form, is superior to oral estrogen. "Oral estrogen passes through the liver and stimulates the blood-clotting factors too much, leading to heart attacks," he said. Not every woman who uses oral hormones will get a heart attack, he emphasized, but women who already have cardiovascular problems might be at raised risk.
Until more studies are done on other forms of therapy, Klaiber said, "the best evidence we have comes from the earlier studies." And those include regimens of estrogen and non-continuous progestin, he said.
More information
To learn more about hormone therapy, visit the Mayo Clinic.
The joy of the holiday season may be tinged with blue for some older adults, who can miss loved ones or start thinking about how quickly time has passed. Many may also have health or money worries.
But the American Geriatrics Society Foundation for Health in Aging offers the following advice on how older people can cope with holiday melancholy:
- Get out and about. Invite family and friends over and ask them for help traveling to parties and events. Volunteering is another good way to improve mood.
- Go easy on the alcohol, which can lower mood.
- Accept sadness. There's nothing wrong with not feeling jolly during the holidays.
- Talk with someone. Discussing those blue feelings can help increase understanding.
- Recognize depression's warning signs. These include sadness that won't lift, loss of interest or pleasure, changes in appetite or weight, sleeping much more or less than normal, crying often, feeling restless or tired all the time, feeling worthless or helpless or guilty, slowed thinking, thoughts of death or suicide.
- If you think you have depression, see your doctor.
There's also advice for people with older relatives or friends who seem down:
- Invite them out to do things and to get-togethers. Take into account their needs for transportation or special diets.
- Lend support by offering to help them with shopping or preparing for gatherings in their homes.
- Be a good listener and encourage them to talk about their feelings. Acknowledge difficult feelings, such as the sense of loss if family or friends have died or moved away.
- Watch for signs of depression and, if necessary, encourage them to talk with their doctor.
More information
The National Mental Health Association has more about holiday depression and stress.
