The Skeptics Society & Skeptic magazine

This is a useful, readable book. It is co-authored by an oncologist and a social psychologist, each with decades of practice challenging the conventional wisdom of their respective fields. And although it provides important healthcare information and recommendations for millions of people, it goes far beyond that.

Estrogen Matters starts as a mystery story: Who killed hormone replacement therapy (HRT)? The book answers that question, which involves a range of people — researchers whose bias influenced both what they saw and what they ignored in their own data; journalists who reported scare stories without reading or understanding the data; and physicians too busy to read original research themselves. This story, sadly, is a familiar one: it’s about the power of a paradigm to blind people to evidence that doesn’t fit — or which disconfirms — what they think they know. The result is today’s public confusion about the role of estrogen in a healthy life. Estrogen Matters aims to end that confusion.

The book begins in 1988, when Dr. Bluming’s 45-year-old wife was diagnosed with breast cancer. After a lumpectomy, chemotherapy, and radiation, Martha was cancer-free (and remains so, past age 70). But the chemotherapy pushed her into menopause, with intense symptoms including hot flashes, sleep problems, and worst of all, difficulty concentrating. So Dr. Bluming set out to test — and ultimately to question — the assumption that estrogen causes breast cancer. What, he wondered, did the evidence say about giving estrogen to women who have survived breast cancer? Was it safe, or, as many assumed, just adding hormonal fuel to the malignancy’s fire?

At that time there was already a half-century of evidence of estrogen’s benefits for middle-aged women. And in addition to reducing the physical, emotional, and sexual symptoms of menopause, estrogen’s other benefits were also well-documented. The hormone significantly reduces the risks of heart disease, osteoporosis, and Alzheimer’s — all of which are far more common than breast cancer.

In 1991, Dr. Bernadine Healy, newly appointed the first female director of the National Institutes of Health, announced her plan for the Women’s Health Initiative (WHI). This was going to be a 15-year study with a projected budget of $625 million. Women’s health research was going major league.

Four years later, following the best medical knowledge at the time, Dr. Healy wrote a book describing how many of the major risks that women face as they age — heart disease, stroke, osteoporosis, and dementia — can be reduced by Hormone Replacement Therapy (HRT), a combination of estrogen and progesterone (women without a uterus are given estrogen on its own). Of her own future menopause, she wrote she planned to begin HRT “without a blink.”

But when the WHI started publishing its results in 2002, estrogen was the central villain. In a startling reversal of long-accepted (and, remember, long-documented) scientific fact, the reports claimed that HRT was dangerous, actually increasing various health risks (including breast cancer), shortening women’s life expectancy.

This report received enormous (and uncritical) press across the world. Hundreds of thousands of American women stopped taking estrogen or HRT, supported by their well-intentioned physicians. Many prestigious medical centers still rely on the WHI and advise women not to take HRT, or to do so only briefly. Huge numbers of both women and physicians are now persuaded that estrogen is harmful and a cause of breast cancer — and so they’re permanently turned off to this treatment.

It’s clear that Bluming and Tavris are both outraged by this development in medical practice. As a physician, Bluming must feel like he’s been watching a medical-cultural train wreck in slow motion. As a psychologist, Tavris must feel that the whole travesty exposes the faulty way ordinary humans make decisions. Having spoken with Tavris, I know she’s pretty angry about the way American journalism let down the public by uncritically echoing WHI press releases. As the authors say, “we will show, in a close examination of the WHI studies, that some of those claims were exaggerated, some were misleading, and some were just wrong.” Bluming and Tavris are honest about the dramatic statements they’re making: “we realize what a stunning assertion this is…that the Women’s Health Initiative’s findings can’t be trusted.”

With stunning effectiveness (and sharp-edged, easy-to-understand scientific tools), Estrogen Matters demonstrates this exactly. In chapter after chapter, the authors demonstrate that the WHI data was fundamentally flawed. Then they show it was badly reported to emphasize the alleged harms of estrogen. And then they reveal it was uncritically accepted by the medical profession and the mainstream press.

In 2002, the NIH stopped the highly touted WHI research project much sooner than expected, claiming that they’d discovered “an increased risk of invasive breast cancer” in women treated with estrogen. The Journal of the American Medical Association echoed the press release: “Hormone Therapy Study Stopped Due to Increased Breast Cancer Risk.” Together these announcements led to a world-wide avalanche of headlines. The executive director of the North American Menopause Society called it “The biggest bombshell that ever hit in my 30-something years in the menopause area.”

Within a short time, the prescription rate for HRT fell by more than half.

But Bluming and Tavris have actually read the voluminous WHI reports and its many follow-ups. Women randomly assigned to take estrogen alone had no increased risk of breast cancer; those who took estrogen and progestin had a small increased risk compared to women assigned a placebo. The report coyly stated the comparison “almost reached statistical significance” — meaning it didn’t. And that breast cancer rates in the estrogen plus progestin group involved a “marked increase,” which would scare the hell out of anyone. As it happens, the trivial increase in absolute numbers of women described as a “marked increase” was clinically meaningless.

So why stop the multi-year, billion-dollar research project over statistically insignificant results? According to Bluming and Tavris, the WHI press release said that “Because breast cancer is so serious an event, we set the bar lower to monitor for it.” Bluming and Tavris paraphrase the WHI this way: We set the bar low enough to monitor for non-significant results if we could squeak out any.

In a follow-up study four years later, the WHI reported no increased risk of breast cancer among women assigned to estrogen plus progestin treatment. But there were no headlines, no apology, no explanation for the contradictory findings. More astonishingly, when several WHI investigators themselves later backed away from the study’s claims, there was still no acknowledgement of any error.

As New York Times journalist Tara Parker-Pope noted in her 2007 book The Hormone Decision, the WHI “seemed to have a different standard for bad hormone news than it did for good hormone news.” Or as Bluming and Tavris ask, “Where was the ‘oops, we’re sorry to have scared you?’”

Estrogen Matters notes other shoddy features of WHI methodologies. To pick just one: incredibly, the median age of the study’s participants was 63 — long past the beginning of menopause. Therefore, the study’s results couldn’t be generalized to all postmenopausal women — but that’s exactly what WHI researchers and publicists did.

As a final note demonstrating the WHI’s violations of science’s best and expected professional practices, Estrogen Matters cites the 2017 publication by one of its principle investigators, Robert Langer. He revealingly wrote: “Highly unusual circumstances prevailed when the WHI trial was stopped prematurely in July 2002…[principal investigators] were actively excluded from the writing and dissemination activities.” In fact, the first primary results paper was written by only a few of those investigators, and published without their co-investigators’ approval.

And yet this publication drove an immediate, world-wide change in women’s and physicians’ health care decisions — to stop a valuable treatment option, increasing women’s risks of a variety of serious diseases.

Beyond investigating this little-known scandal, Estrogen Matters addresses additional fascinating public policy and behavioral science questions. These include:

People are afraid of the wrong things, and act accordingly. For example, many people are afraid to fly in commercial airplanes, not realizing that the drive to the airport is far more dangerous. I recall my own elderly parents’ only flight abroad from the U.S. many years ago. My highly anxious mother booked a flight with multiple stops so she could periodically “be safe on the ground” — ignoring the evidence that with each takeoff and landing, she increased the trip’s actual risk.

Another common thing that people worry about is their child being kidnapped by a stranger. According to the FBI, that happens to 0.001% of American children — still too many, but very, very rare. The most dangerous thing most kids do is texting while riding their bikes.

The structure of news. Television news prefers dramatic visual events, like fires and massive truck pileups, whose incidence people then overestimate. In general, the news ignores undramatic events (“study finds no correlation between taking vitamin D and strong bones”), while preferring dramatic man-bites-dog stories (“that drug/food/activity will kill you”).

We also know that conflict (real or imagined) entices viewers. People getting along doesn’t attract attention or eyeballs; good news rarely sells. But rivalry, hatred, “throwing shade,” a single study that seems to overturn decades (or centuries) of proven wisdom is automatic click-bait, meaning it will quickly march to the top of the day’s news pile. Consumers should be wary of being manipulated in this way. For example, when celebrities like Jenny McCarthy falsely claim that childhood vaccinations cause autism, it’s considered news; when literally thousands of doctors cite studies proving it doesn’t, it’s typically ignored.

The role of science in public policy. The scientific method exists to help us separate fact from coincidence, predictable pattern from anecdote, the world we inhabit from the world we wish we inhabited. What better foundation for public policy could there be?

Alas, Estrogen Matters shows how confirmation bias (and, presumably, a bit of institutional politics and professional self-interest) can shape public policy. We can all think of examples: gun ownership policy, drug criminalization policy, school curriculum policy. In this respect, Estrogen Matters is a cri de coeur for taking (good) science more seriously.

How bad most people are at making decisions. For example, having been scared about hormone replacement, most women still want relief from the symptoms that can last up to seven years: heart palpitations, vaginal dryness, joint pain, and many others. And so they desperately turn to other modalities such as “compounded bioidenticals,” which sound personal and organic, but are unregulated and unproven. And they buy bizarre “forever young” products, keeping celebrities like Suzanne Sommers and Gwyneth Paltrow rich and popular.

Statistical illiteracy. If only every adult could have a three-hour course on statistics. Four simple ideas would make a world of difference:

The normal distribution: how traits, behaviors, and other things cluster around a mean, and how extremes of these are progressively less likely in a random sample. The concept of a random or representative sample, and the extent to which any given research (or anecdotal) result is generalizable. Why there will always be outliers that contradict any statistic — and why they don’t disprove the statistic. The difference between a difference and a significant difference; and the difference between a significant difference and a meaningful difference.

You don’t need a college education to understand any of these. Unfortunately, political policymakers aren’t any more literate about these simple but crucial concepts than the rest of the population (well, there’s a testable hypothesis).

Estrogen Matters is a wonderful consumer guide to healthcare decisions for women of all ages, whether a reader’s interest is in heart disease (the leading killer of women in every decade of their lives), stroke, osteoporosis, Alzheimer’s, or longevity. And any woman interested in breast cancer — and most are — will be surprised, challenged, and ultimately relieved to find that estrogen and HRT remain important tools in creating better health outcomes, even for women diagnosed with breast cancer.

Peri-menopause usually starts around the early 40s, menopause around 50, and then most Western women live another 30 years. So the treatment regimen for menopausal symptoms is important for most women.

Bluming and Tavris have done a great public service in investigating and collecting excellent healthcare information about the benefits and risks of estrogen. Estrogen Matters also reminds us that both science and journalism need to serve the public better by being more skeptical, and that we consumers need to pay more attention to the research (as well as our personal biases) informing our own health care decisions.