Menopause and Misinformation: Real Consequences of Fake News

Blog: Exploring the "WHY" in the WHI

Hi Beautiful Friends,

While “fake news” has been around since, well, news, it feels like a more recent phenomenon. In 2016, Trump popularized the term when he slapped it on any negative press coverage of himself leading up to the election.  Facebook and other social media platforms facilitated the spread of misinformation at a volume and speed never seen before.  Add in the isolation of the pandemic, which funneled many of us through online algorithms chasing dopamine splurge clickbait, then sprinkle some AI deep fakes on top and, voila! The perfect recipe for zero trust. 

If you were lucky enough to hit perimenopause right around this time, we’re in the same boat rowing trepidatiously into meno-land asking “what and who should I believe?” This hormonal shift, confusing and disorienting enough on its own, seems doubly unfair in the context of the troubled history of misinformation that continues to plague it.

Being the obsessive type, I began a search-and-consume mission for as much information on the topic as possible. As sleep became more elusive, I had more time to obsess. I devoured books, podcasts, videos, documentaries, and hundreds of articles from news and medical journals; had conversations with NAMS-certified doctors, pelvic floor PTs, nurses, nutritionists, and peers; and scoured various websites of telehealth, beauty, and supplement companies.  The deeper I dove, the more I found the data, interpretations of the data, and the expert opinions were anything but clear-cut. The amount of misinformation was overwhelming. 

Intent Matters

There are three types of “information disorder”: misinformation, disinformation, and malinformation, each of which carries a different level of intent.  The good news is that the type most ubiquitous in meno-land seems to be misinformation, or “the spread of false information without intent to cause harm.”  The bad news is that profit seems to be the prime motivator. 

Everywhere I turn I’m inundated by ads for pharmaceuticals, beauty products, supplements, and services making grand cure-all promises.  When the provision of information, goods, and services is motivated first by profit, truth and health fall by the wayside.  Misinformation becomes the means for companies and individuals to serve up snake oil to a population of which 85% are experiencing distressing (beyond “bothersome,” a word I’ve grown to loathe) symptoms, and who are vulnerable to fears of aging and other insecurities.  We are the prey. I can feel the teeth as I scroll through my Instagram feed. 

Many companies will take your money in exchange for nothing more than placebo effect, which at 20-66% isn’t nothing. In another post, I explore misinformation sold to us under the label of “natural” remedies. But first, I want to dive deeper into a monumental piece of fake news brought to us by the institutions we most trusted, and which struck fear in the hearts of doctors and women worldwide.  

Fake News: The WHI Press Release of 2002

The initial press release on the morning of July 9th, 2002, was followed by headlines in the New York Times that read “Hormone Replacement Study a Shock to the Medical System” and “Study is Halted Over Rise Seen in Cancer Risk” and  “Hormone Therapy Woes,” while The Washington Post proclaimed “So much for Hormone ‘Salvation’.” Given the design flaws, the misrepresentation of data, and the twenty-year non-alarming follow-up, these overwrought headlines qualify as fake news.

Headlines—and the articles beneath them—have real consequences. In a matter of days, Premarin, the oral hormone therapy and once top-selling prescription drug, was brought to its knees. When estrogen levels drop, women tend to experience an increase in heart disease and osteoporosis. Without the help of hormone therapy, doctors turned to other medications to treat these diseases. Drug sales for heart and bone medications (statins, and bisphosphonates) went up. (Note: While there is a bulk of evidence suggesting that estrogen protects against both heart disease and osteoporosis, it is currently FDA approved solely for the prevention of osteoporosis.)

Fake news is often profit-driven but when I attempt to follow the money, I can’t find a single clear competitor to step in for hormone therapy, certainly not for the treatment of hormonal symptoms of menopause for which hormone therapy is still the most safe and effective treatment. 

Get a WHI(FF) of this!

I’m not conspiratorially minded, but after probing into the matter, I struggle to understand why a small group of principal investigators performed statistical gymnastics in order to link hormone therapy to breast cancer. I say “small group” because many of the principal investigators of the WHI across the nation were not included in writing the initial report for the Journal of American Medical Association in time for their concerns and proposed changes to be considered. The report, created by a small group of people, was already printed at the warehouse and ready to distribute. One investigator, Robert Langer MD, has been outspoken on the harm of the WHI. In a recent 2022 interview, he explains that the “Data, Safety and Monitoring Committee” stopped the study prematurely because a predetermined “conservative monitoring boundary” for breast cancer had been reached. He asserts that breast cancer incidence never reached statistical significance.

It’s one thing to stop a study because ethically you want to be extra careful that you aren’t harming participants. It’s a whole other thing to publish those statistically insignificant findings as though they are significant to the general population. In this case, the conservative monitoring boundary may have been reached because the placebo control group used in comparison to the estrogen and progestin group happened to have a lower than normal incidence of breast cancer. None of the other placebo groups in other arms of the study had such a low incidence. In fact, one of the possible reasons for that low incidence may have been the fact that women within that arm had taken hormone therapy previously before the start of the study. It would take years for the investigators to find and publish the result of lower incidence of breast cancer in the estrogen-only group. This benefit of hormone therapy along with other revisions over the years, didn’t make headlines.

So all in all, the WHI just smells bad.

Dr. Peter Attia expresses this shared feeling in his interview with Dr. Avrum Bluming and Carol Tavris, authors of Estrogen Matters, an excellent read when trying to make sense of the WHI and hormone therapy. The interview, episode #42 of thedrive podcast, is a detailed overview of the book and my favourite podcast on this issue.

The Villain

The bad smell infected my imagination, which turned cardiologist Jacques Rossouw, the acting director of the WHI at the time, into a villain. (Ok, here’s a neurotic aside. If you’re like me and can’t pronounce a name that you keep having to read, it royally screws up reading rhythm. “Rossouw” is pronounced like Rousseau, but the “ou” is in the second half of the word and if you ask me there aren’t enough vowels in the first half of the word to make the sound “oo.” To make matters worse, the whole mess ends in a “w.” I may be just as peeved at his name as I am at the damage he’s caused. Not really. But every time I write his name, I have to stop and look it up, which screws up my writing rhythm. Now it’s occurring to me that long parenthetical breaks probably wreak havoc on reading rhythm. I blame Jacques.)

Rossouw wrote an article in the journal for the American Heart Association in 1996 stating that estrogen was over-prescribed without adequate investigation of its risks and benefits. He wrote, “It is time to put the brakes on the hormone bandwagon while pushing ahead with the randomized trials that will provide definitive data on benefit and risk.”  Interestingly, his article also mentions both the heart and bone medications I refer to above, which he claims are “better choices.” Rossouw was a key player not just in interpreting the WHI data in the initial report but also in the initial media response.

I pictured a villain suited to a name that broke all sorts of pronunciation rules drumming his bony fingers together as he conspired to put two generations of women through misery by depriving them of hormones.  I looked him up and found an interview he gave on Charlie Rose (@15:25) the week after the WHI press release. To my surprise, he had no monocle or curly mustache. His fingers may have been bony. They were off camera. Instead he presents as a metered, soft-spoken doctor with a charming South African (ahhhh….that explains it) accent and a genuine concern about the impact of hormone therapy on women.

Quite quickly he explains in the interview that the 26% relative increase in breast cancer that had been found actually translates to a 0.1% increase in a given year to an individual woman, or 8 additional cases per 10,000 women per year. What he did not adequately explain is why they chose to present relative risk rather than absolute risk to the public. Twenty-six is a lot bigger than 0.1.

While no monster, Rossouw does say things in this interview that are refuted elsewhere. He says the press release and the publication in JAMA were made public at the same time. In fact, the press release came out 7 days before the medical journal publication.

He also describes the participants of the study as “very healthy,” while other sources reveal many of the women were smokers, on blood pressure medication, and overweight (which in and of itself is not an indication of poor health but is often associated with chronic disease). The participant group included few women under the age of fifty-five, or 3,425 of the total 24, 347. (The Hormone Decision, p. 33) The average age of participants was sixty-three and some were as old as seventy-nine. It made sense that many had already begun to develop chronic diseases of aging. Rossouw’s statement to reporters in 2002 that “the study found no differences in risk by prior health status, age, or ethnicity” (The Hormone Decision, p. 23) didn’t line up with the evidence from years of follow-up, investigation, and reporting. While studies before the WHI suffered from “the healthy woman bias” (women who choose to take hormones tend to be healthier to begin with), the WHI went in the other direction. Given the majority of participants were well past menopause and not in particularly good health, Rossouw’s statement that age and health had no bearing on outcomes for taking hormone therapy just doesn’t make sense.

What was clear from the interview is that Rossouw, rather than acknowledging the study’s flaws, oddly believed the WHI’s new and different findings were to become the new and broadly applicable truth on hormone therapy. He boasted, “We’re the only game in town with definitive data.” After all, his study was the biggest, best study ever done, a large randomized control trial, “the gold standard* for evidence based medicine.” Unfortunately, he failed to recognize that his large, expensive, gold standard study, collected definitive data for an older, less healthy population, not those women most likely seeking treatment for the relief of hormonal symptoms of menopause. However, as far as he was concerned, the WHI put the much needed brakes on the party bus, that hormone bandwagon that had been “picking up in speed and volume” for decades.

The bandwagon comes to a halt!

Rossouw wasn’t wrong that many physicians were over-prescribing hormone therapy to treat heart disease in older women without adequate evidence. The WHI certainly demonstrated not only that women over sixty-three do not benefit from hormone therapy but that, when administered late, it can increase certain health risks. The belief driving the bandwagon was that estrogen protects the heart no matter what age. In an effort to save time and money, the study tested older women more likely to suffer heart attacks. From a design standpoint, older women mostly no longer having symptoms preserved the double blind requirement of the gold standard trial, where highly symptomatic women would know they were receiving the placebo and so would their investigators. In fact, symptomatic women who would jeopardize this important aspect of the gold standard trial did not participate. The WHI succeeded in bringing the hormone therapy bandwagon to a grinding halt not only for older women who received prescriptions for an untested benefit of heart disease prevention that was not demonstrated, but also for every woman regardless of age and health.

In retrospect, knowing a little more now about hormones than we did in the nineties, it seems strange that a medical doctor couldn’t predict that re-introducing hormones to bodies that had been without them for over a decade would have the same or similar results as in bodies that were still producing those hormones. This 2017 abstract from Climacteric, the official journal of the International Menopause Society, identifies this failing of the WHI. I can’t help but think this oversight must have been somewhat embarrassing, at least in the long run. Perhaps knowledge of women’s physiology was just that lacking. I address the historical reasons for that problem in another post.

Male Bias in Medical Research:

Confirmation Bias

While profit is often the motivation, especially if a drug company is involved, the driver that makes the most sense here seems to be confirmation bias, “a response in which individuals, consciously or unconsciously, allow emotion-loaded motivational biases to affect how new information is perceived.”  This bias leads people to view evidence in a way that supports prior, personal beliefs and to reject evidence that contradicts those beliefs. They may manipulate, mine, cherry pick, and interpret data in such a way that supports personal attitudes.

In an interview in 2006, Tara Parker-Pope, (Wall Street Journal and NYTimes health journalist who may have written as much on the WHI as some of its principal investigators), explains how influences other than money can impact bias.  She says: 

“...just because somebody does not have drug company funding does not mean that they don’t have an agenda or a bias. People have invested huge amounts of money and careers in a certain way of thinking…You can’t just assume that because somebody doesn’t have ties to the drug industry that they’re always right.” 

Given the size, expense, and importance of the WHI, one would hope that, bandwagons aside, the investigators could maintain objectivity, stay diligent to the scientific process, and be curious to find actual results. 

Rossouw, who had published his hunch that estrogen wasn’t as beneficial as everyone believed, clearly had strong opinions on hormone therapy beginning many years before the halting of the study. Perhaps he saw himself as a breast cancer prophet and crusader for women. This randomized control trial was going to show the world he was right!

Regardless, mistakes in design and data interpretation of the WHI were then exacerbated by irresponsible representation and translation of the findings by the media to the public.

In a void of explanation, a little more speculation

People are often motivated by their own personal, anecdotal experiences. I don’t know if Rossouw’s mother, sister, or wife died of breast cancer while on hormone therapy. I do know that because my grandmother developed breast cancer and had taken hormone therapy, my mother believes there is a direct cause and effect between hormone therapy and breast cancer for all women.

Truthfully, some women will get breast cancer when on hormone therapy. Some women will die of breast cancer, although that happens less now than ever. Due to regular screenings and advancements in surgery and treatment.  And yet we certainly don’t have clear evidence to point to the use of hormone therapy as a direct cause of breast cancer. Conversely, alcohol, (a group 1 carcinogen), has a much greater causal link, a risk most of us rarely consider; we’re just not willing to give up the juice. Additionally, 90% of women diagnosed with breast cancer today will survive.  Not only that, but prognosis is better for those on hormone therapy.

Risk aversion is a real factor in decision-making. Why not include all considerable risks when making risk:benefit calculations for hormone therapy? Why not include risks of heart attacks, broken hips, and colon cancer, all of which estrogen seems to protect against and all of which kill many more women than breast cancer?

Bad News Makes Good News

It makes some sense that because the study was so large and expensive, principal investigators and the NIH wanted something to show for it.  Knowing health announcements often get lost in the 24-hour news cycle, Rossouw told Tara Parker-Pope that the WHI was going for “high impact” in order to “shake up the medical establishment and change the thinking about hormones.” (The Hormone Decision, p. 37). 

Mission accomplished!

Turns out breast cancer gets our attention.  The press nightmare initiated by the NIH was compounded by the media’s overreaction.  Hormone therapy was dropped like a carcinogenic hot potato by women and doctors alike, causing devastating and sometimes fatal withdrawal symptoms like heart attack and stroke.  (Note:  potatoes are NOT carcinogenic but are a good source of vitamin C, potassium, vitamin B6, and fiber.  Stay tuned for more on nutrition in other posts.) While many news outlets ran fearful headlines, Parker-Pope began responding rationally and immediately, and she ultimately wrote a balanced, well-researched book, The Hormone Decision, in 2008. But she was just one voice in the wilderness.

Dr. Mary Jane Minkin, a practicing OB-GYN and clinical professor at the Yale School of Medicine, interested in cognitive benefits of hormone therapy, got more calls the day of the WHI press release than she’d ever gotten before. On a podcast that addresses all things perimenopause (“Perimenopause, WTF?” with host Rachel Hughes), Dr. Minkin describes the shock of the WHI announcement: “I remember where I was when John Kennedy was shot. I remember where I was on 9/11. And I remember where I was when the W.H.I. findings came out.”

My personal OB-GYN was in residence at the time. She began frantically searching the literature for answers for her terrified aunt who had been on hormone therapy and was now convinced she was heading toward an early grave. Unprecedented in medical literature, the report wasn’t available for a whole week after the press release.  When you believe you’re on medication that is killing you, waiting seven days to investigate feels too long.  

The Real Bad News

“The excessive conservatism engendered by the presentation to the media of the first results of the WHI in 2002 has disadvantaged nearly a decade of women who may have missed the therapeutic window to reduce their future cardiovascular, fracture, and dementia risk.”  -International Menopause Society 2011

Some studies have demonstrated an increase in hip fractures and death associated with hip fracture due to women halting their hormone therapy, which makes sense given that estrogen protects against osteoporosis.  Death after hip fracture kills more women than breast cancer.

There was also a Yale School of Medicine study published in 2013 that estimated approximately 50,000 unnecessary deaths over the previous 10 years among women aged 50 to 69 who, after hysterectomies, were deprived the protection against heart disease and breast cancer that estrogen therapy provides. This estimation was based on evidence from the WHI in the subgroup given estrogen alone.

Stuck in “Post-Truth”

In the pivotal year of 2016, the Oxford Dictionary chose “post-truth” as its word of the year.  Post-truth is where "objective facts are less influential in shaping public opinion than appeals to emotion and personal belief."  Not much appeals more to the emotion of fear, especially for women, than fear of breast cancer.  Breasts have long been the feminine symbols of both sexuality and motherhood.  Double mastectomy was once the common surgical solution to breast cancer, involving the complete removal of a body part intimately tied to sense of identity. This procedure provokes a completely understandable fear, not to mention the painful post-op treatments of radiation and chemotherapy that often accompany the diagnosis of breast cancer. I do not blame women for their fear; I share it.  However, the incitement of fear without enough evidence is reprehensible.  Expensive eye creams make me cringe, but the spread of misinformation that was provided by the NIH and media breaks my heart, even if the intent was never to harm.

In my utopia, the NIH and the press would get together again to speak to the public and set the record straight in a way that would have a real impact. On Dr. Peter Attia’s podcast thedrive #317 where he interviews Marty Makary MD from Johns Hopkins who speaks on uncovering blind spots in medicine. He says he hunted down the principal investigator of the WHI and said that he got “that guy” without naming him (maybe he couldn’t pronounce his name) and got him to confess reluctantly that the WHI demonstrated no increases in breast cancer deaths with hormone therapy.

Some Good News!

The initial interpretation of data from the WHI has been quietly revised over the years, including the finding that the group who had had hysterectomies and were on estrogen alone experienced a decrease in breast cancer and an overall reduction in colon cancer. The subgroup aged 50-59 on hormone therapy had healthier hearts and a 30% lower risk of dying.  

In the past two years the New York Times has published at least nine articles on menopause including one entitled, “Women Have Been Misled About Menopause.”  They might have added “by Us.” I know, they were just reporting what the experts were telling them. Tara Parker-Pope was the one health journalist who was able to carve out truth from hysteria. Her book, The Hormone Decision, remains a terrific, well-researched book that helps the reader with exactly what the title says.

While Dr. Jacques Rossouw has since retired, Dr. Joann Manson, another principal investigator for the WHI, admits in interview with Dr. Attia that the initial findings should never have been extrapolated to all women given the older median age of participants.  She also agrees that absolute risk rather than relative risk should have been used when presenting the findings to the public. Dr. Manson admits that younger women between the ages of 50-59 who are healthy have very low absolute risk of adverse events from hormone therapy.  She expresses regret over the fact that so many women were denied a safe treatment for “distressing” (not bothersome- thanks for that, Joann!) symptoms of menopause. You can hear the whole interview on Attia’s podcast thedrive, episode #253.

What are we to do?

Unfortunately, the damage done in 2002 moved us to a place post-truth where objective facts don’t matter as much as feelings and anecdotal experiences.  This human tendency explains why, when a patient worried about osteoporosis and suffering hormonal symptoms asks her family doctor about hormone therapy, the doctor may respond, “Well, would you rather have a broken leg or cancer?”

Fear of hormone therapy is the legacy of the WHI, which remains the unfortunate bias of most doctors who have not delved deeper into this problematic study (many have not even read it), but remain fearful from a panic induced by fake news. The problem with fake news, misinformation, and personal bias, is that it is fueled by emotion, not reason. You just can’t argue with feelings.  But you can talk about the data and share it. So please do!

*The gold standard for medical research is RCTs (randomized control double blind placebo trials). Some have started to put this into question, believing other types of research such as epidemiological reviews and observational studies have strong validity in the field of hormone therapy. Interestingly, results for risks and benefits of hormone therapy from follow up from the WHI are consistent with many of the preceding, concurrent, and recent observational studies on hormone therapy.