Estrogen Matters

Introduction

Who Killed HRT?

Avrum recently received an e-mail from a woman he did not know, referred to him by a mutual friend, who was agonizing over suspicious findings on her breast ultrasound. Her mammogram had shown a probable cyst, so the radiologist had ordered the ultrasound, and the results suggested a malignancy. The woman wrote that she was “freaking out,” feeling hopeless, and already anticipating a total mastectomy; she added that if she could have her whole torso surgically removed, she would. This woman was a fifty-year-old university professor of experimental psychology, yet she was completely panicked before a biopsy had even been performed.

Av is profoundly aware of the fear that accompanies even a suspicion of a breast cancer diagnosis. He has been a medical oncologist for many years, and about 60 percent of his practice has been devoted to the study and treatment of breast cancer. In 1988, his wife, Martha, was diagnosed with breast cancer at the age of forty-five. She had found a small nodule that seemed benign but nonetheless warranted removal, and he vividly remembers his own fear when the surgeon who removed the tumor said, “I’m sorry, Av. It was a carcinoma.” He felt as though he had been walking along a rocky path on a high mountain, holding Martha’s hand, and they had suddenly lost their footing. Two days later, the surgeon told them almost casually that the nodes he’d sent for biopsy when he removed the tumor appeared completely normal. Av regained his balance. Whatever else might turn up, there was now a good chance that Martha would be cured.

The often repeated statistic that one woman in eight (12 percent) will develop breast cancer at some point in her life should be understood in a broader context: That’s a woman’s risk of getting it, all right, but only if she lives to be eighty-five. As Patricia T. Kelly explained in Assess Your True Risk of Breast Cancer:

So where did that one-in-eight risk come from? It’s obtained by adding together the risks in each age category: 0.4 plus 1.5 plus 2.4 and so forth. But if you are a woman who has reached age sixty without a diagnosis of breast cancer, your risk in the coming decades is only 7.6 percent (12 percent less each decade’s risk that you have passed); the risk of breast cancer in any given decade of life never exceeds one in twenty-six. Yet by far the most important statistic is this one: over 90 percent of women currently diagnosed with early breast cancer will be cured, and most will not need disfiguring mastectomies or chemotherapy.

Martha’s cancer was diagnosed thirty years ago. After her lumpectomy, she received postoperative radiotherapy and chemotherapy and has had no recurrence of cancer since. The chemotherapy she received, however, pushed her into menopause; severe symptoms began and then continued unabated. She didn’t complain, understanding better than her husband did what women were expected to tolerate at that time as part of the “change of life.” But she was most definitely suffering. For years, the women under Av’s care had been reporting a variety of the same symptoms: hot flashes, loss of sexual desire, painful intercourse because of vaginal dryness, difficulty sleeping, palpitations, unexplained and uncharacteristic anxiety attacks, difficulty concentrating, and—the thing that especially bothered Martha—fuzzy thinking, such as trouble remembering phone numbers and even following the plot of a book.

And so Avrum delved more systematically into the world of menopausal symptoms and their treatments. At the time, and still today, the uncontested most effective treatment for these symptoms was—and is—estrogen. Because estrogen replacement therapy (ERT) alone is associated with an increased risk of endometrial cancer (cancer of the lining of the uterus), women who still have a uterus are given hormone replacement therapy (HRT)—estrogen plus progesterone—which provides the benefits of estrogen without the increased risk of endometrial cancer.^* Martha asked Av about prescribing estrogen for her. Many of his menopausal patients who had been treated for breast cancer over the years had asked for the same thing. They had complained of severe quality-of-life impairments that they hoped estrogen would alleviate. He had advised against it because of the prevalent concern that estrogen might increase the risk of cancer recurrence among women with previous breast cancer. (As you will learn in chapter 6, it does not.)

By the early 1990s, researchers had fifty years of evidence of estrogen’s benefits, all of it well documented in the medical literature. Estrogen not only successfully controlled menopausal symptoms in most women but also significantly reduced the risks of heart disease, hip fractures, colon cancer, and Alzheimer’s. A 1991 New England Journal of Medicine editorial, “Uncertainty About Postmenopausal Estrogen: Time for Action, Not Debate,” reported a 40 to 50 percent reduction in atherosclerotic heart disease, which was responsible for the deaths of more than eight times as many American women as breast cancer.² The long-running Framingham study reported a 50 percent drop in osteoporosis-associated hip fractures, which were linked to as many deaths every year as breast cancer.³ Two studies, one from the University of Wisconsin and one from the American Cancer Society, reported a 50 percent decrease in the risk of developing or dying of colon cancer. And a USC study reported a 35 percent decrease in the risk of Alzheimer’s. Among women with no history of breast cancer, studies found that estrogen did not increase the risk of developing it, even among women who had been taking estrogen for ten to fifteen years. Most remarkable, women taking estrogen were living longer than women who were not taking hormones. A 1997 report in the Journal of the American Medical Association stated that “HRT should increase life expectancy for nearly all postmenopausal women by up to 3 years.”⁴ Their analysis concluded that up to 99 percent of current postmenopausal women would benefit from taking HRT as measured by decreased rates of disease and improved longevity.

So it is no wonder that in the 1990s, the medical consensus was fairly strong about the benefits of ERT and HRT. In her 1995 book A New Prescription for Women’s Health: Getting the Best Medical Care in a Man’s World, Bernadine Healy, a cardiologist and the first (and thus far only) female director of the National Institutes of Health (NIH), observed that many of the major risks that women face as they age—heart disease, stroke, osteoporosis, and Alzheimer’s disease—“are or may well be reduced by hormone replacement therapy.” As a result of that data, she wrote, when she hit menopause, she planned to begin HRT “without a blink”:

And then she added: “A decision not to consider hormone replacement is a health decision, too, just as is the decision not to take a flu shot or get a hepatitis vaccination. As I see it, women have a competitive health and survival edge before menopause. Women during their childbearing years are protected against many problems that affect men. I see no reason to relinquish that advantage after menopause—not if I can help it.”

Today, more than twenty years after Bernadine Healy’s published advice, estrogen’s benefits have been drowned out by the alarms about its risks, which were inflamed by reports from the Women’s Health Initiative (WHI), initially published in 2002. Those reports claimed that HRT was flat-out dangerous, that it increased the risks of breast cancer, heart disease, stroke, and dementia, all leading to a shortened life expectancy. Hundreds of thousands of women, already frightened of breast cancer, went off hormone replacement immediately. Most of their physicians supported them. If you go online, you’ll see how many establishment medical centers to this day rely on the WHI and advise women not to take HRT at all or to take it only briefly.

Yet, as we will show in a close examination of the WHI studies, some of those claims were exaggerated, some were misleading, and some were just wrong—and several WHI investigators themselves eventually backed away from them. We realize what a stunning assertion this is. The Women’s Health Initiative, supposedly the gold standard of empirical research, funded by the National Institutes of Health to the tune of one billion dollars—and we are arguing that its findings can’t be trusted? Yes, we are, and we hope that by the time you finish this book, you will see why.

While we’re at it, we plan to shatter a widespread assumption underlying the concerns about HRT: that estrogen causes breast cancer. As Av began to question the received wisdom on estrogen, he found himself in the same position as the physicians who dared question the once universal belief in the benefits of radical mastectomy, promoted by the surgeon William Halsted in the late nineteenth and early twentieth centuries. Radical mastectomy was based in part on Halsted’s theory that breast cancer spread almost exclusively from the original site into contiguous areas. Find a tumor in the breast? Then it is essential to remove the tumor, the entire breast, and everything adjacent—a “radical” procedure.

Halsted’s assumption was logical, widely accepted, and wrong. In the fifty-four years between 1927 and 1981, twenty-four studies reported on more than four thousand patients with breast cancer who were treated with lumpectomy (removal of the tumor only) and, usually, subsequent radiation. In all but two of those studies, survival rates, even up to thirty years later, were similar to those of patients treated with variations of the radical mastectomy. Randomized trials and observational studies continue to show that breast-conserving surgery is almost always at least as effective as mastectomy. Yet rates of radical mastectomies, especially bilateral mastectomies, for treatment of localized breast cancer have been rising since 2006—another manifestation of the fear associated with breast cancer. In the overwhelming majority of these cases, mastectomy is not indicated and not recommended. Yet many patients, like the woman who wrote to Avrum, panic and say, “Just take it off—take them both off—so I don’t have to worry.” They would rather cope with the pain, discomfort, prolonged recovery, and physical impairments of extensive surgery than deal with anxiety, even though the more extensive surgery does not offer a greater chance for cure.

Like Halsted’s mistaken notion that breast cancer spreads from the original site to adjacent areas, the belief that estrogen causes breast cancer is logical, widely accepted, and wrong. Consider these findings, which you will learn more about in detail in this book:

We—Avrum and Carol—have been close friends for many years. We met when Avrum saved Carol’s sister-in-law’s life with a successful intervention for a rare blood disorder caused by a stroke medication. We discovered a mutual passion for following the data wherever it led and a shared commitment to debunking pseudoscience and fad therapies, Av in medicine, Carol in psychology. The story of HRT, a therapy designed to treat life changes that are specific to women—a therapy praised by some researchers, condemned by others, and eventually brought down by a large nationwide study—was fascinating in its own right but was also a perfect case study for Carol’s interest in gender biases in health care and cognitive biases in research.

And so, one afternoon more than a decade ago, Carol decided to attend Avrum’s talk about HRT at a continuing-medical-education seminar. She went mostly out of friendship. She was not an advocate of hormones, nor did she have a vested interest in them one way or the other; she had sailed through menopause with nary a symptom. In her 1992 book The Mismeasure of Woman, she included a chapter on hormone replacement, a therapy she didn’t wholly oppose but didn’t wholly endorse either. In those years, she shared the view of many women’s health activists that the idea of hormone “replacement” was itself problematic, implying that the normal changes of life automatically created deficiencies rather than being, well, normal changes of life.

And then she watched, riveted, as Avrum set about methodically dismantling the arguments stating that HRT was a serious risk factor in breast cancer. He presented a table of breast cancer risks (which you will see in chapter 1). At the lower end was taking Premarin—an insignificant risk. Riskier factors included eating fish, eating one additional serving of French fries per week during preschool years, and being a Scandinavian airline flight attendant. All of these associations were weak, unlikely, and meaningless in real life, and all were stronger than those with Premarin, but all of them found homes in medical journals.

Bingo! Carol realized that Avrum was doing in medicine what she loved doing in psychology: dealing with evidence that contradicted received wisdom and coming face-to-face with the exasperating reaction that most people have to such evidence. (They rarely say, “Thank you.” They don’t say much of anything.) She was therefore not surprised when Av told her how much trouble he was having in trying to persuade his colleagues that they might be wrong about the dangers of HRT and the reliability of the Women’s Health Initiative. Carol offered to collaborate with him on articles for his medical colleagues, and these were soon published by the Cancer Journal and Climacteric.⁷ The papers’ detailed examinations of the disgraceful data manipulations of the WHI were greeted by the medical establishment with… silence.

And so, this book. Just as decades of evidence eventually overturned the scientific justification for radical mastectomy, decades of evidence indicates that it is time to change medical professionals’ minds about estrogen too. We will show how the powerful belief that estrogen causes breast cancer has blinded otherwise reputable, serious investigators to what their own data actually reveals. And we will show how the powerful belief that advocates for estrogen are all in the pocket of Big Pharma—as, indeed, some of them are—has blinded many conscientious feminists, scientists, and health activists and kept them from taking that data seriously.

Accordingly, before we go any further, we want to make it clear that neither of us is a partially or wholly owned subsidiary of Wyeth (purchased by Pfizer in 2009) or any other drug company. Carol has long been an outspoken critic of the pharmaceutical industry, and Avrum does not and has not met with drug reps in his office, let alone accepted dinners, pens, speaking offers, writing assignments, pizzas, or any other bribe or inducement, in exchange for a prescription. In 2005, Avrum was contacted by a lawyer representing Wyeth, and he agreed to serve as an expert witness on a case, since his already published papers had questioned the role of hormones in the development of breast cancer. He was not hired to create an opinion.

Last year, Avrum got an e-mail from a former patient who had moved to another city.

As he read his patient’s letter, Av wondered how her otherwise competent young oncologist had become so adamantly opposed to hormone replacement therapy that she was unable to recognize its benefits in the patient sitting in front of her, a woman who had been on HRT for more than twenty years. To answer that question, we will consider the effects of hormone replacement therapy on menopausal symptoms, heart disease, bone health, overall survival, and cancer and conclude with recommendations of where we go from here. If a woman is trying to choose whether or not to take ERT or HRT, she owes herself a familiarity with its benefits and risks, and that is what this book is designed to provide.

Every action that human beings take involves risk: crossing the street, swallowing an aspirin, getting married. In the case of estrogen, yes, of course, there are some legitimate concerns about risks, and we will discuss them. But we will argue that medical professionals, in their concern about what turn out to be small risks for some women, are overlooking the overwhelming evidence of estrogen’s very large benefits for most women. Women have been scared away from estrogen by the fear of breast cancer—a fear so great that it made an educated woman like Avrum’s correspondent claim she would sacrifice her “whole torso” for a cure, even before she had an official diagnosis of cancer. We hope this book will replace that fear with a deeper understanding that will allow women, with guidance from informed physicians, to make decisions based on knowledge rather than on unfounded anxiety and false alarms.