The Hormone Decision - Hardcover

Tara Parker-Pope has been a professional reporter for 20 years, currently serving as the weekly consumer health columnist for the Wall Street Journal. Her weekly Health Journal and Health Mailbox columns appear every Tuesday in the Wall Street Journal. Her special report on the findings of the Women's Health Initiative earned her the media award from the North American Menopause Society as well as the Second Century Award for Excellence in Health Care from the Columbia University School of Nursing. She is also the author of Cigarettes: Anatomy of an Industry from Seed to Smoke. A 1988 graduate of the University of Texas, she resides in southeastern Pennsylvania.

PART ONE

Untangling the Controversy

1

HORMONE CONFUSION: MAKING SENSE OF THE HEADLINES

On the morning of July 9, 2002, women woke up to some shocking news. The menopause hormones they had been taking to cope with hot flashes, improve their sex lives, strengthen their bones, and possibly help their hearts had turned against them. Or so it seemed.

The subject dominating the news over the next few days was the Women's Health Initiative (WHI), a government-funded study of 27,347 women that had set out to determine whether menopause hormones helped prevent heart disease, a benefit widely ascribed to hormone use. As it turned out, in the first group of 16,608 women to be tracked, the menopause hormone Prempro--a mixture of estrogens and a progestin made by pharmaceutical giant Wyeth-- hadn't helped. Women in this study who used the drug had more heart attacks and breast cancer than non-hormone users. They also had fewer hip fractures and lower risk of colon cancer, but that potential good news was eclipsed by the heart and breast worries. Government health officials had decided the risks to the women in the study outweighed the benefits, prompting them to take the unusual step of stopping the main part of the hormone study early.1

Within days of notifying the study participants, they held a hastily organized press conference to alert the public. Dozens of reporters attended the event at the National Press Club. Officials from the National Institutes of Health (NIH) and the study investigators hit the morning talk show circuit and evening news programs to spread the word.

The impact was immediate and lasting. For years, doctors had told us that menopause hormones protected women's hearts. Now some of the same doctors were on national television telling us just the opposite. Even veteran newscasters seemed flummoxed by the results, which ran counter to long-held beliefs about menopause hormones. "I tell you--women gotta go insane today," exclaimed CNN newswoman Paula Zahn.2

Hormone sales plummeted overnight as women threw out their pills. Going off hormones cold turkey made them miserable, but they were too scared to keep taking them, certain that heart attacks, breast cancer, and all sorts of other maladies were now lurking around the corner, all because of hormones. They tried calling their doctors for guidance, but the phones were busy, swamped with other equally terrified patients trying to make sense of the news. The women who got through eventually discovered that their own doctors didn't really know what to do either.

HYPING THE RESULTS

Over the ensuing weeks and months, it became apparent that something had gone terribly wrong with the WHI. Screaming matches and name-calling erupted at medical meetings. WHI investigators stood firm in their findings. The researchers believed that the real problem was not the study itself but the fact that hormone proponents had spent years touting the benefits of the drugs and now just didn't want to admit they were wrong.

Meanwhile, longtime believers in menopause hormones were convinced that the study itself was somehow flawed and that this was all an effort to undermine hormones in favor of other types of drug treatments. Some of the nation's top menopause experts accused the WHI scientists of misinterpreting the study data in a way that created hysteria and hype.

So who was right?

Years later, scientists are just starting to make sense of the data that have emerged from this important study. Many questions still aren't answered. But looking back, it's clear that the government's quick interpretation of the study and alarmist public announcements did mislead millions of American women. Subsequent analyses of the WHI hormone data have shown that the findings are not as clear-cut as they seemed on that summer day in Washington, DC.

A closer look at the study shows that key mistakes were made in the early design of the WHI. For a variety of reasons, the WHI was not a study of menopause but evolved as a study of older women who took menopause hormones. The average woman in the WHI was 63, and most women in the study started taking hormones at least 10 years past menopause. This fundamental flaw in the study design means the data are of limited use in trying to understand the full range of risks and benefits to the typical user of menopause hormones.

Today, the typical woman who is considering hormone therapy is in her late forties or early fifties. She's just beginning to experience the hormonal turmoil--the hot flashes, mood swings, and other changes--associated with the menopausal transition. Although few women in this age group were studied in the WHI, these are the women who have been most frightened and affected by the research.

In telling the public about the study findings, government health officials overstepped the scientific boundaries of the research, and the result was a much-exaggerated interpretation of the WHI data. One of the most egregious examples was the statement by Jacques Rossouw, MD, who at the time was acting director of the WHI. "The results have broad applicability," Dr. Rossouw told a roomful of reporters. "The study found no differences in risk by prior health status, age, or ethnicity."3 Subsequent scientific analyses, published in respected medical journals, showed that the data are far more complex than that. They strongly suggest that the results probably don't apply to every woman.

As mentioned earlier, most of the women in the WHI started taking hormones at least 10 years past menopause; some were even 20 years past menopause. Think about this. Most of the women in the WHI were long past the hot flashes, sleep problems, mood changes, and other symptoms that persist throughout the menopausal transition. They were done with it. But for the sake of the WHI, they started taking hormones anyway. The study clearly showed it's not a good idea to begin taking hormones a decade or more after menopause, but what about those women who start sooner? A closer look at both WHI hormone studies--one of estrogen plus progestin, the other of estrogen alone--shows that the women in the studies who took hormones closest to the time of menopause had far fewer health risks and may have even received additional heart protection from hormone use.4,5

What does all this mean to you today, as you are struggling with your own hormone decision? In trying to understand the latest science on hormones, it's important to know that most of the recent headlines and news reports came straight from the data in the WHI--and much of the current thinking about hormones has been shaped by the government's initial announcements about the first phase of the study. Virtually everything you will read about menopause hormones for the next decade will be based on the WHI.

What has become increasingly clear is that the WHI is not the definitive word on menopause hormones. The WHI simply wasn't designed to give us information about most of the women who use hormones to treat the symptoms of menopause. Top government health officials and many WHI investigators have become sharply critical of that July 2002 press conference that has scared so many women about hormones. "It was presented in a very dramatic fashion," says Barbara Alving, former acting director of the National Heart, Lung, and Blood Institute (NHLBI), who temporarily took over the WHI after the first results were announced. "There should have been less drama and more thought. What we learned is that we need to work much better in the communication of risk, so people can understand it."

None of this means that the WHI is a bad study. Far from it. The WHI is the result of years of painstaking and high-quality scientific research. It is packed with voluminous amounts of valuable data. Dismissing this research would also be a disservice to women. The WHI has given us more information about hormones than we've ever had before.

The challenge is trying to figure out what the WHI really taught us and what it didn't. To make sense of it, you have to go back to the beginning, to the early days when the WHI was just an idea and scientists were trying to come up with the best way to learn about the risks and benefits of menopause hormones.

HORMONES AND THE HEART

At the time the WHI was devised, doctors had set out to answer the question of whether hormones could protect women from heart attacks. Answering this question was the primary purpose of the study. In 1991 when the WHI started, the thinking about women, hormones, and heart health was very different than it is today. The medical community was (and, actually, still is) heavily influenced by a major study from Harvard researchers called the Nurses' Health Study, which has followed the habits, health, and lifestyles of 120,000 nurses. In 1985,6 health surveys from 32,000 of the nurses provided researchers with some surprising and convincing data. The nurses who used menopause hormones were 50 percent less likely to have a heart attack than nurses who didn't use hormones. A follow-up study in 19917 confirmed the findings.

The data generated much excitement in the women's health community. An intervention that could lower heart attack risk by half would have a dramatic impact on women's health and save tens of thousands of lives. There was a lot of excitement, but there were also caveats. The Nurses' Health Study wasn't a clinical trial where one treatment is tested against a placebo. It was an observational study--that is, the women's habits and health were subjected to scientific scrutiny, but the women themselves were making their own choices about treatments, exercise, and medical checkups. Scientists know that you have to be cautious about how you interpret data from such a study. Were the nurses having fewer heart attacks because they used hormones? Or were the nurses who used hormones just healthier to start with? The type of woman who seeks out hormone treatment likely is getting regular medical care and is proactive about her health in other ways as well.

The question was: Do hormones keep you healthy? Or do healthy women use hormones?

Despite the scientific community's reservations about the Nurses' Health Study data, doctors and patients got excited about hormones. Physicians began routinely prescribing them to women--and not just to those who were coping with menopause symptoms. The thinking was that if hormones helped protect women's hearts, they should be given to the women who needed them most--those who were older and at the highest risk for suffering a heart attack.

It seemed to make sense at the time, but today, it seems nothing short of bizarre. We're talking about 75-year-old women, long past menopause with no symptoms whatsoever, walking out of their doctors' offices with prescriptions for menopause hormones.

LOOKING FOR ANSWERS

In 1991, Bernadine Healy, MD, the first woman to run the NIH, decided to embark on a major clinical trial of women's health issues. The study would look at hormone use, calcium and vitamin D supplementation, and low-fat diets, attempting to measure how these interventions affected women's risk of heart attack, breast and colon cancer, and osteoporosis, among other things. But in designing the hormone portion of the study, the study investigators had two big problems.

First, most women who take hormones to treat the symptoms of menopause are in their late forties or early fifties. They typically are healthy. For most of them, it will be at least 20 years before any signs of heart trouble show up. In science, it's expensive to study a healthy young woman. The reason: A study of healthy menopausal women would take years--possibly decades--before the women would be old enough to start having enough heart attacks to produce any meaningful results.

To find out if hormones would lower heart attack risk, the scientists needed to study women who would actually have heart attacks. If hormones helped, then women in the placebo group (the study participants who weren't taking the real drug) would have more heart attacks than women taking hormones. But nobody in the study would have heart attacks if they weren't old enough to be at risk for heart trouble to begin with. Although men see a jump in heart attack risk around age 45, a woman's heart attack risk doesn't start to rise until age 55. Most women won't face any heart risk until they are past 70.

But the WHI investigators couldn't wait 20 years for a 50-year-old menopausal woman to have a heart attack. They wanted and needed the data much sooner than that. In order for the WHI to examine the heart effects of hormones, the investigators needed to recruit women who were at risk for heart attacks in the next 5 to 10 years. And they needed some of the women in the study to actually have heart attacks. If their theory held up, more heart attacks would happen to the women who weren't taking hormones.

The second dilemma was due to the fact that menopause can produce a variety of distressing symptoms--hot flashes, sleep disturbances, bleeding irregularities, and numerous other complaints. The WHI investigators worried that if they tried to look at the effect of hormones on women in the throes of menopause, the study probably wouldn't get far. That's because this was to be a random, blinded, controlled clinical trial-- considered the gold standard of scientific research. It meant that some women would get real hormones, and some would get placebos. And nobody--not the women, not the doctors treating them, not the investigators--was supposed to know who was getting what.

But imagine if you were a menopausal woman in the study. You are waiting for an appointment with study doctors, and other women from the study also happen to be there. These women are relaxing, flipping through magazines, or dozing in the waiting room. Meanwhile, you are flushed and miserable. Your body is dripping with sweat, you can't sleep, and your bleeding has become so irregular that you position yourself right next to the ladies room. It will take you about 2 seconds to figure out that the other women are getting the real thing, and the pill you've been taking every day is a fake. And the moment you walk into the exam room, your doctor will figure it out too. So much for a random, blinded study.