The Hormone Decision

A smart woman’s guide to the medical minefield of menopause, written in Tara Parker-Pope’s straight-talk, no-spin’ style. At last, the truth that women have been waiting for!

—MARY LOU QUINLAN, author and CEO, Just Ask a Woman

For my mom. I miss you.

CONTENTS

INTRODUCTION

PART ONE: UNTANGLING THE CONTROVERSY

CHAPTER 1 Hormone Confusion: Making Sense of the Headlines

CHAPTER 2 Hormone History: The Pendulum Swings

CHAPTER 3 Hormones and the Symptoms of Menopause

PART TWO: UNDERSTANDING THE SCIENCE

CHAPTER 4 Hormones and Your Heart

CHAPTER 5 Hormones and Your Breasts

CHAPTER 6 Hormones and Your Bones

CHAPTER 7 Hormones and Your Vagina

CHAPTER 8 Hormones and Your Brain

CHAPTER 9 Hormones and Your Skin

CHAPTER 10 Hormones and Other Body Parts

PART THREE: MAKING YOUR OWN CHOICES

CHAPTER 11 The Progestin Question

CHAPTER 12 Prescription Hormones: Pills, Patches, Creams, and Rings

CHAPTER 13 Hormone Alternatives: Drugs, Supplements, and Other Options

CHAPTER 14 The Hormone Decision

ENDNOTES

ACKNOWLEDGMENTS

INDEX

INTRODUCTION

Confused about hormones? It’s no wonder.

For years, women have taken prescription hormones to boost their health before, during, and after that important life transition called menopause. It’s a time when hot flashes, mood swings, and other changes announce that our ovaries are shifting gears and getting out of the baby business. As our natural estrogen and progesterone levels wax and wane, hormones in a pill have been a way to calm the hormonal chaos going on inside our bodies and give us much-needed relief from the vexing symptoms of menopause.

But after years of feeling good about hormone drugs, today women are scared to death. Newspapers, magazines, and television shows are filled with frightening reports about menopause hormones and studies linking them to heart attack, stroke, breast cancer, and other health worries. The latest research has seemed to contradict decades of scientific study in which hormone drugs appeared to protect women’s hearts. The conflicting reports about hormones, heart attacks, and hot flashes are enough to leave your head spinning.

But you don’t have to be confused anymore. The purpose of this book is to tell you the facts about menopause hormones and the science behind all the recent publicity. Once you look behind the headlines, you’ll realize that much of what you’ve read about menopause hormones has been misleading or just plain wrong.

The reason the hormone debate seems so confusing is that the medical community itself is confused about hormones. Every new hormone study seems to contradict the previous one. But in recent years, scientists have begun to make sense of much of the new hormone research. They’ve discovered that while the answers aren’t always simple, they aren’t nearly as scary as we’ve been led to believe. Unfortunately, most of these new insights haven’t been widely reported, and many women and doctors haven’t gotten the message. No single study can provide all the answers we need about menopause hormones. But every new study, every new report—no matter how bad or good the news seems at first—is simply one more small piece of the puzzle.

This book will help you see how all these pieces fit together. It will serve as a step-by-step guide to understanding the hormones made by your body and the hormones made by drug companies. It will also shed light on the controversial history of hormone science and hormone drugs, giving you insight into the historical context that frames today’s debate.

In these pages, you will embark on a head-to-toe tour of how hormones affect various parts of your body, based on not one but hundreds of scientific studies. You will learn what scientists know about how hormones affect your heart, your brain, your bones, your breasts, and every other imaginable body part. You will learn about the laboratories at Wake Forest University where for years, scientists have studied how hormones influence the heart health of monkeys. You will visit 120,000 nurses who have selflessly given their time and their personal health information to create one of the largest and most important studies ever of women’s health. From the horse pee farms of Canada to pharmacies that peddle so-called natural hormones—you will understand the risks and benefits of all the various products now touted as options to relieve menopausal symptoms.

Most important, you will get an insider’s view of the now-famous Women’s Health Initiative (WHI), the government-sponsored study of more than 27,000 women that has produced the most-frightening reports about the risks and benefits of menopause hormones. As the health columnist for the Wall Street Journal, I have followed this ground-breaking study since the first WHI hormone results were announced in the summer of 2002. Since then, I have conducted extensive interviews with the scientists, medical doctors, and government health officials behind the WHI and spent countless hours poring over hundreds of pages of detailed scientific papers explaining the research. The WHI is the biggest-ever clinical trial evaluating women’s health, and the data it has produced have proved exceedingly difficult to interpret. What has emerged is a far more complicated hormone story than has been reflected in the headlines and sound bites that appeared after the WHI results were first announced. In reading this book, you will see the miscalculations and the missteps that the government and the WHI scientists have made along the way and how these decisions and hurdles have clouded the debate and confused women.

In July 2002, many of the scientists behind the WHI told women to stop taking hormones because of worries about heart attacks and breast cancer. Today, after a closer look at the study data, these same scientists have realized that hormones are likely safe—and in some cases, possibly even protective—for women seeking relief from menopausal symptoms. The WHI researchers continue to mine the data that are still pouring in from this important study. And some of the WHI’s top scientists are pursuing new research, trying to determine if there is a window of opportunity when menopause hormones are safest and most effective for women.

Over the years, many of my readers have asked me whether hormones are good for you or bad for you. Unfortunately, there’s no simple, onesize-fits-all answer to that question. A woman who chooses hormones must weigh all the risks and benefits. And a woman who chooses not to take hormones—opting instead for other drugs or treatments, or nothing at all—has her own set of risks and benefits to consider. Whatever the decision, the bottom line is that a woman needs to be fully informed about all the various medical technologies available to her throughout her life. And she needs to be smart about the hormone decision. A woman who decides not to take hormones needs to do it with the same level of information and insight as the woman who chooses to use these drugs.

Because hormones aren’t right for every woman, this book also includes information about other treatment options for menopausal women. The right answer for you depends on a variety of factors, including your own personal health risks and fears, the severity of your symptoms, your family history, and your own values about medicine, and your personal health. The good news is that today, the women now approaching menopause will be the first generation to benefit from the recent science.

Our mothers and grandmothers experienced menopause with little information about the changes in their bodies or the options available to them. They had no solid research data about the risks and benefits of hormones on which to base their decisions—only hype, conjecture, and speculation. You will be among the first generation of women to make a truly informed decision about the best choices during this important transition in life. In the end—whether you choose prescription hormones, herbal remedies, or nothing at all—the hormone decision you make will be the right one for you.

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.

Study investigators anticipated that women with bothersome menopause symptoms would quickly drop out of the study if the pills they took didn’t relieve their symptoms. The only way to solve the problem was to study hormone use in women who didn’t have menopause symptoms. Today, it may sound silly to give a menopause hormone to a woman who’s not experiencing menopause symptoms. But at the time, the widespread belief was that hormones helped protect the heart. It didn’t matter if you had symptoms or not; many doctors would put you on hormones anyway—just like they now advise men over age 50 to take a daily aspirin. Hormones were viewed as an all-purpose wonder drug. In fact, so strong was the belief in hormones that some WHI investigators worried that it would be unethical to give some women a placebo.

A CRITICAL ERROR

So here is the dilemma faced by the WHI design team: How do you study the connection between heart attacks and hormones in a way that women won’t figure out whether they are getting the real hormone or a placebo? And how do you study the drugs in the shortest possible time, making sure that enough heart attacks happen in order to produce meaningful data?

The answer was to study older women. Older women have heart attacks. Older women don’t have menopause symptoms. Problem solved.

But really, looking back, it’s clear that this is where the WHI’s problems started.

This major national study of menopause hormones was conducted primarily in older women who weren’t experiencing menopause. As mentioned earlier, the average age of the WHI participants was 63. That’s 10 to 15 years older than the typical woman who seeks advice about menopause hormones.

Further increasing the need to enroll older women was the fact that the WHI was supposed to study more than hormones. Other parts of the