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http://www.nytimes.com/2002/07/15/national/15HORM.html

Many Taking Hormone Pills Now Face a Difficult Choice

By GINA KOLATA

ast week, when a large federal study on hormone replacement therapy came to an abrupt halt, Cheryl Kipfer's husband handed her a news report on the stunning findings. The drugs, the report said, had risks, including invasive breast cancer, which, although slight, were not counterbalanced by benefits.

Ms. Kipfer said her husband, Gary, told her she was crazy. "Why," she said he asked her, "are you taking those pills?"

Then her daughter sent her an e-mail message, attaching another report with the same bad news. She wrote, "I want you to read this and I want you to know that I love you."

But Ms. Kipfer, 56, a retired school administrator who lives in Omaha, does not know what to do. Her bones were markedly thinned from osteoporosis, and her doctor told her the only thing keeping them from eroding further was the hormone replacement therapy she takes each day.

"I am afraid," Ms. Kipfer said — afraid of fractured bones if she stops taking the hormones, afraid of breast cancer if she continues. "If I was taking it for hot flashes, I would come right off," she said. But what about osteoporosis?

For the 16,000 healthy women in the Women's Health Initiative study on combination hormone therapy, the decision was clear.

Investigators informed them on Tuesday that they were to stop taking the pills, estrogen and progestin, immediately. The study had been stopped because the drugs' risks had been found to outweigh their benefits.

According to the data, if 10,000 women took the drugs for a year and 10,000 did not, women in the first group would have 8 more cases of invasive breast cancer, 7 more heart attacks, 8 more strokes and 18 more instances of blood clots. But there would be 6 fewer colorectal cancers and 5 fewer hip fractures.

In doctors' offices and in women's homes, however, it is more than a question of numbers. Many women have no problems stopping the hormones and see no reason to continue taking them: they feel fine or, at worst, have mild symptoms of menopause, like warm flushes that are not disabling, for a few months.

While it is unclear how many women fall into that category, Dr. Deborah Grady, who directs the University of California San Francisco/ Mount Zion Women's Health Clinical Research Center, says studies of prescription use indicate that half of the women who start taking the hormones are no longer renewing their prescriptions a year later.

For some, however, stopping is not an easy option.

Ms. Kipfer began taking the hormone combination in April 1991, when she was 44.

"I was going through incredible hot flashes and could not get a good night's sleep," she said. Two years later, when she had an X-ray for other reasons, a doctor noticed that the bones in her back looked thin, as if she had osteoporosis. She went to Dr. J. Christopher Gallagher, an osteoporosis expert at Creighton University, who confirmed the other doctor's suspicions: her spine had 18 percent less bone than was normal for her age. He discovered that she was continuing to lose bone on the usual dose of estrogen, .625 milligrams a day, so he increased her dose to .9 milligrams a day.

Ms. Kipfer has also been lifting weights at a gym, which Dr. Gallagher told her would improve her muscle strength and might improve the quality of her bones. But the benefits of weight training are still unclear: there are no randomized trials that show it increases bone density, and several trials that show no effect.

With the higher estrogen dose, she gained bone in her spine. Now, she said — and Dr. Gallagher confirmed — she has the bone density of a 62-year-old. Her goal is to maintain it.

"She's much better," Dr. Gallagher said. Estrogen, he added, "has made a huge difference."

The problem, he explained, is that Ms. Kipfer has no good alternative if she wants to prevent further bone loss. While there are effective drugs for osteoporosis, known as bisphosphonates, he worries about giving one to a 56-year-old woman who would have to take it for decades to prevent her bones from deteriorating. These are drugs, like Fosamax and Actonel, that protect against osteoporosis by permanently binding to the surface of bone and slowing the activities of osteoclasts, cells that break bone down.

"Nobody knows about the long-term safety of bisphosphonates," Dr. Gallagher said. "It gets into the bones and stays there a long time, and nobody knows the long-term implications." But, he said, he cannot recommend that Ms. Kipfer simply do nothing for her bones. "If she discontinues estrogen," he said, "she will lose everything she gained within two to three years."

Ms. Kipfer says she knows what a fractured bone in her back feels like, because she once broke a spinal bone in an accident and the pain was excruciating. Her husband told her he thought the choice was clear: the osteoporosis benefit was not worth the risk of cancer and heart attacks. "Don't you think you'd rather have a little pain than die?" Ms. Kipfer said he asked her. Recalling what that spinal pain felt like, she said she was not so sure.

"You don't want to make a mistake you can't correct," she said.

Other women want to stop taking the hormones, but worry about how they can tolerate the severe symptoms of menopause that the hormones have squelched.

About two-thirds of women have symptoms at menopause. Of that total, about a third have them severely, with at least five to seven disabling hot flashes a day, said Dr. Wulf Utian, the executive director of the North American Menopause Society. Their symptoms last from about a year to many years, he said, adding that he had a few patients in their 60's and 70's who had not taken hormones for their symptoms and were continuing to have hot flashes.

"We just don't understand at all why some women's symptoms go on and on," Dr. Utian said.

There is also no way to predict when a woman's symptoms will end, Dr. Grady of the University of California said. When a woman starts having symptoms like flushes and sweating, she said, "we have no way of estimating if they will last three months or two years."

Dani Danzig, a 56-year-old technical writer and editor who lives in Newton, Mass., is, by anyone's definition, one of those women whose symptoms go on and on.

She began taking the hormone combination when she was 49, to control the symptoms of menopause. "I was taking it quite contentedly," she said. "I took it as I took my vitamins every morning for about five years." Then she began to worry. Studies were suggesting that the pills might increase a woman's risk of heart attacks and strokes. Her doctor suggested she stop using them, and so she tapered off. After six months, she thought she had done it — she was no longer taking the pills and she was no longer suffering from hot flashes and night sweats.

Then they returned, as disabling as ever.

"I would have three or four hot flashes every day and they disrupted whatever I was doing," Ms. Danzig said. "They stopped me dead, they made me leave the room to change my clothes. It was a real show-stopper." The night sweats disrupted her sleep, leaving her soaked several times a night. "I felt as though my whole system was being whipped around," she said.

Her doctor, Maureen Connelly, an internist at Harvard Vanguard Medical Associates, a group practice in Boston, suggested she start taking the hormones again and then try to stop. But, Ms. Danzig said, "every time I tried to back off completely, the symptoms came back."

"It happened again this year," she said. "I backed off of a smaller dose and, whammo, the symptoms were back. Now I'm back on a full dose."

"I am worried," Ms. Danzig said. "I'm still living with having taken it for five or six years, and I don't know what negative effect that has had." She said she wanted an alternative that would control her symptoms, but did not know what to do. "I go to health food stores and there are things on the shelf, but I know nothing about them."

"I looked at my vitamins this morning and my two hormone replacement pills were there," Ms. Danzig said. "I said, `Boy, am I taking poison!' "

Dr. Marcie Richardson, a gynecologist who is Dr. Connelly's partner — the two direct the Harvard Vanguard Menopause Consultation Service — said that, in fact, there are few alternatives for patients like Ms. Danzig. Dr. Richardson and others have begun giving some women antidepressants like Effexor, of a class known as selective serotonin reuptake inhibitors. She has also used the anti-epilepsy drug Neurontin to control hot flashes and night sweats. Both treatments "work about 50 to 60 percent of the time," Dr. Richardson said.

Asked if women will have to take those drugs for the rest of their lives to prevent menopausal symptoms, Dr. Richardson and others said no one knows because there is too little experience with them.

Doug Petkus, a spokesman for Wyeth, which makes Effexor, said he knew of no studies on the uses of the drug to treat menopause symptoms. He added that although some doctors say it works, the drug was not approved for that use. The same is true for Neurontin, said Dr. Eric Grossman, senior medical director at Pfizer, the drug's maker. "We would caution people not to use preparations that have not been adequately studied," Dr. Grossman said.

Dr. Richardson said she mostly gives antidepressants or Neurontin to breast cancer patients who have severe symptoms of menopause and are willing to take a chance that the drugs might be safe over the long term. But these are desperate women, she said. "When you are waking up four times a night soaking wet, you'll take anything."

"It is very important for women to understand that there isn't a right answer," Dr. Richardson said.

Some doctors are finding there are so many answers that each woman who comes into their office will leave with different advice.

That happened to Dr. Utian of the North American Menopause Society on Wednesday, the day after the Women's Health Initiative study came to a halt. He saw 10 women who were going through or had gone through menopause. Each wanted to discuss the question: Should she take hormones? Each left his office with a different recommendation.

One woman who had been taking the hormones for four years said her biggest worry was heart disease. "She said: `I know what it's like to come off it. I'm going to feel terrible,' " Dr. Utian said. Then she asked him what the actual risks were. He pulled out Table 4 from the publication of the study data in The Journal of the American Medical Association. In Year 4, he told her, 25 women taking hormones had heart attacks, compared with 24 taking a placebo; the risk was low.

"Table 4 is going to be on my desk from now on," Dr. Utian said.

Another woman had taken the drugs for about the same amount of time. She was at high risk for colon cancer and osteoporosis. "Her risk-to-benefit ratio turns out to be favorable if I keep her on it," he said.

A third woman had started taking the drugs to reduce her risk of heart disease. "I told her I don't see any reason to stay on them," he said.

Other patients have had very emotional reactions to the drugs.

One woman who had come in on Monday afternoon was 70 years old and had been taking hormones for 30 years. The few times she had tried to stop taking them, her menopause symptoms had returned.

"I said, `Don't you think you've been on it long enough?' " Dr. Utian said. "She said: `Why would I come off it? I'd rather be dead.' "

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