U.S. halts hormone-therapy study

Tuesday, July 9, 2002 | 11:17 a.m.

SUN STAFF AND WIRE REPORTS

A large federal study of hormone replacement therapy in postmenopausal women was abruptly halted, researchers say, because the drugs caused a slight but significant increase in the risk of invasive breast cancer.

The directors of the study, known as the Women's Health Initiative, sent letters to the study's 16,000 participants, which they were to receive today, telling them to stop taking their medications.

An estimated 6 million women nationally take the drugs -- estrogen and progestin -- to replace the hormones lost at menopause. The hope was that the drugs would not just relieve the hot flashes, night sweats and vaginal dryness that can plague women at menopause but that they would also improve women's health. That, the study investigators report, did not happen. The results of this study have been long anticipated because it is the first and only large study to compare the effects of hormone replacement therapy with placebos in healthy women.

Dr. Rachel McConnell, a reproductive endocrinologist with a practice in Summerlin, called the long-awaited study findings "extremely significant" and said, "If they're seeing these kinds of results, I would certainly feel obligated to tell my patients to stop taking these medications immediately."

McConnell added that hormone-replacement therapy has become "almost automatic" as the prescribed course of treatment for "all post-menopausal women." Women who have undergone a hysterectomy, she said, are typically given estrogen alone, a treatment option that is still being studied, while women who still have their uteruses are "nearly always prescribed progestin and estrogen now."

"We've all been waiting for the results of The Women's Health Initiative Study," McConnell said. "This will have a significant impact on my practice."

Larry Matheis, executive director of the Nevada State Medical Association, said the study would change practices.

"Large-scale studies on women's health have really picked up in the last few years, and these results show us why that is so important," Matheis said. "Unfortunately, this is bad news for what had looked like a promising new treatment."

The data indicate that if 10,000 women take the drugs for a year, eight more will develop invasive breast cancer compared with 10,000 who were not taking hormone replacement drugs. An additional seven will have a heart attack, eight will have a stroke and 18 will have blood clots. But there will be six fewer colorectal cancers and five fewer hip fractures.

The study was intended to continue until 2005, said Jacques E. Rossouw, who is its acting director. For the first few years that the women took the drugs, they were at no increased risk of cancer, heart disease or blood clots and the study did not address the benefits of using the drugs for a short period to relieve the symptoms of menopause.

The decision to end the study came on May 31, in a periodic look at accumulating data by an expert panel, the data safety and monitoring board. Suddenly, Rossouw said, after women had taken the drugs for an average of 5.2 years, the data had crossed a line. "The breast cancer risk exceeded the predefined boundary for safety," he said.

While cautioning that the danger to an individual woman is tiny, the study investigators say that over all the drugs' risks exceed their benefits.

The study did not address the question of estrogen alone. Women who have had hysterectomies take estrogen by itself -- progestin is added only to prevent estrogen from causing cancer of the uterine lining, and doctors do not prescribe estrogen alone for women with uteruses. The risks and benefits of estrogen alone are under study in a second clinical trial, of 11,000 women, being conducted by the Women's Health Initiative. That study is continuing because there is no evidence so far that the drug's risks exceed its benefits. For now, Rossouw said, with just estrogen, "the risks and benefits remain unclear" but, "we can say there is no indication of an increased risk of breast cancer."

The findings on the hormone combination are to be published in the July 17 issue of the Journal of the American Medical Association. The journal planned to release them this morning so that the data would be available to doctors and women at the same time as the women in the study received their letters telling them to stop taking the drugs. But Cox News Service published the story Monday.

Now, with the cessation of this large study, many observers said, the tide may be turning. Hormone replacement therapy, once thought to be a way for women to remain forever young, protect them from heart disease and from osteoporosis, and generally leave them healthier than they would otherwise be, may be fast losing its allure. Some worry that the news will be seem so frightening that women will overreact.

"This is a bombshell," said Wulf Utian, executive director of the North American Menopause Society, a nonprofit group that has long advocated hormone replacement therapy for women with a clear reason for taking it, like those who have hot flashes or bone loss. "I think there is a real danger of panicking literally hundreds of thousands, if not millions, of women."

Now the question is, what should women do?

Victoria Kusiak, who is vice president of clinical affairs and North American director at Wyeth, the largest maker of the hormones, emphasized that there were no other effective treatments for the symptoms of menopause.

Sun reporter Lanette Fisher-Hertz contributed to this report.