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On “Blind Spots”
Dr. Makary’s new book is taking the country by storm. He is being interviewed everywhere. I tried to order a hard copy of his book from Amazon, but it is sold out and on backorder. So I ordered it on Kindle and have started reading it. I confess that the chapter on the WHI (on hormone replacement therapy, HRT, in post-menopausal women) is the first chapter I read.
I find it interesting that if one is able to hang around long enough, some mistakes eventually get corrected.
Let me explain.
In Nov 2015, I incurred the ire of Russ Roberts, the conservative or libertarian economist (at least I think he is conservative; he may disagree). He had an episode of EconTalk with a guest, Robert Aronowitz, a physician at the University of Pennsylvania, who had just written a book, “Risky Medicine” regarding medical screening and attempts at risk reduction through screening, which is a fraught endeavor. The episode was very good, and I listened with great interest. The difficulty in making decisions on screening for various diseases (mammograms, PSAs, etc.) was explored in considerable detail.
Toward the end of the podcast, Roberts asked his guest if any study in medicine gave us a completely solid answer to what should be done in a given medical decision process. To my great surprise and chagrin, Dr. Aronowitz said, yes, there is. He then cited the Women’s Health Initiative study that he said definitively showed that we should avoid the use of HRT, except for as short a time as possible to treat severe menopausal symptoms. Roberts noted his response and did not challenge it in any way. That was some 13 years after the WHI had been stopped and the study published. I read the study when it was published. It had so many flaws it was hard to know where to begin. Not only was it not THE definitive study to guide medical recommendations on Menopause, but it was also one of the worst studies ever done. In my opinion, the study methods constituted medical malpractice.
I placed a comment to that effect, detailing the study’s vast shortcomings, stating that I felt the guest, and Dr. Roberts by extension, were guilty of promulgating false and misleading information.
To wit: The study participants’ average age was 62, a decade or more post-menopausal. It was not applicable to women a decade younger early in menopause. The study was stopped before statistical significance was reached regarding breast cancer, but the study was promulgated as if it had proved that estrogens cause breast cancer. (Never proven before or since). The study did not report the weights of the participants. Obesity is associated with a higher risk of breast cancer. No information could be gleaned from the study regarding the relation between obesity, HRT, and breast cancer. Premarin was used, which had been pretty much supplanted by estradiol when the study was undertaken. Topical estrogens were not considered, despite the common use of transdermal or vaginal estrogens at the time the study was done. Could there be a difference between the route of delivery of the estrogen? In reading the study, it appeared that women who were smokers were not required to quit smoking before being placed on HRT. This is medical malpractice, as HRT and smoking increase the risk of vascular events. Further, no one was starting women in their mid-60s on HRT.
Why was this older cohort selected for this study? Perhaps because the question of menopausal symptoms was no longer a consideration in whether to start HRT and would not be a factor in a blinded prospective study. But that decision compounded the whole problem with the study.
I received a rather harsh private reprimand from Russ Roberts (justified? Probably.) for my supposed lack of civility, with a threat to ban me from the site if such behavior continued. No mention of any response to the issues I had raised. The guest posted a note that cardiovascular events were shown to increase with HRT but elided the issue of starting HRT early post-menopausally vs. a decade later. That makes all the difference. But it was true that cardiovascular problems increased when HRT was started a decade after menopause, and that is a solid conclusion from the study.
I was practicing in the 1990s when the Study was underway. It was not a minor or trivial study. It was the largest study ever done on women’s health. It had been started with great fanfare. Bernadette Healy was the head of the NIH, the first woman (a cardiologist) to achieve that distinction. There was an intense discussion about the fact that women’s health issues had been neglected in Medicine, that research had not been oriented toward women’s health. This was the study that was going to end that discrepancy, that unfairness, that “blind spot.” (As an aside, the current issue of Endocrinology Today features Monica M. Latonia, PhD, and Jane E Reusch, MD. Their work on women’s health issues and reproductive medicine, and their attendance at Joe and Jill Biden’s White House Initiative on Women’s Health Research meeting at the University of Colorado, was ostensibly part of an initiative to “fundamentally change how our country approaches and funds research on women’s health”–as if that had not been thought of or done before).
There was at the time of the WHI study a distinctly feminist trope to the study. Women were in charge and were going to right the wrongs; that women, just like men, were able to control their own fate and the resources of society to their advantage.
There was also a considerable consensus in the medical literature and among medical academics that it was obvious to them that estrogens caused breast cancer, and that HRT caused breast cancer. They were sure that adequate studies to prove the causality had not been done. This study was going to correct that deficiency.
That bias persists, although neither the WHI study nor any other study or set of studies has demonstrated it. Some studies show the opposite (as Dr. Makary notes in his book). It was an academic article of faith.
I stopped listening to EconTalk podcasts then.
Out of interest, I checked to see if Dr. Roberts, now President of Shalem College in Jerusalem and a Fellow of the Hoover Institution, had a podcast with Dr. Makary, and sure enough, he did. So I listened and heard Dr. Makary thoroughly deconstruct the WHI study and note how wrong the conclusions drawn from the study were, and how harmful those conclusions have been to women’s health in the U.S. A very good presentation.
To counter that just a bit: There have been a lot of practitioners in the US who understood from the outset that the study was bunkum and had no application to HRT in menopausal women, but just to women a decade or more past menopause. Indeed, there is no time constraint on how long HRT can be used if started early in menopause, as long as untoward events do not supervene. I would say that the majority of Gyn physicians in my experience have ignored the study, even if not from the outset.
To make it personal, my wife required a full hysterectomy at age 50 and has been on estrogen transdermally ever since (e.g., for 28 years). Our daughter, an OB-GYN physician trained at USC fully agrees with that treatment. Yearly mammograms have been OK (perhaps because she is on estrogen). She had severe osteoporosis at age 50, having grown up in utter poverty in the northeast of Brazil, with marginal nutrition as a child. A 2-year course of Forteo (teriparatide) corrected her osteoporosis, and estrogen treatment has maintained her bone density stable for the subsequent 25 years. (In fact, her bone density has gradually improved over that time.)
I was hoping that Dr. Roberts might mention his prior podcast with Dr. Aronowitz in 2015. He made no mention of it… But it is in the archive of EconTalk podcasts.
Dr. Roberts got it right now, somewhat belatedly, and has corrected a long-ago mistake.
Published in General
Do you have any way of posting a comment there now, or whatever, asking if Roberts has any recollection of your previous criticism?
Yes, but like Bartley, I prefer not.
Okay, but sometimes just a bit of “neener neener!” can be good.
Could genetic screening for breast, ovary & cervical cancer factors help to show which women should avoid HRT and which should go ahead with it?
The notion that women who smoked were not told to quit smoking or at least taper the habit down is disturbing.
Women who do well with HRT also have glossy skin, look younger longer and it is said their sex drive does not plummet. But no med treatment is not without some risks.
I’m a regular listener. I heard the episode. To be frank, when it comes to highly complicated subjects like medicine, I’m from Michael Chrichton’s “wet streets cause rain” school of listening.
Makary, who seems very sincere and makes logical arguments came off as a bit of a self righteous jerk. Maybe I’m out of step with the zeitgeist, but I don’t think most people are acting out of malice. No doubt like many other industries, medicine has a “that’s the way we’ve always done it” challenge. It probably takes either professional courage or obstinacy to deviate from accepted practice. Unfortunately, medical advances sometimes evolve at the expense of patients.
I remember the study and the hoopla quite well. I had minor symptoms with menopause and never started. My skeptic’s antenna just alerted when I read that the lead on the study was the “first woman cardiologist at the NIH.” I wonder how much of that distinction led to reluctance to critique the study framework even before it began. Had I tried to use a data set with as many uncontrolled variables as evidence in a tax case I’d have lost quicker than quick, with prejudice. It also seems that the ‘90’s was, if not the start of then full swing into, to never speaking ill of the obese. Did they start the study with women in their ‘60’s because that’s how old Healy was?
Now do the same for Covid – there’s some irony about blind spots in real time. Those spots weren’t actually blind though, so different.
Back in the day, I asked my OB-GYN about the study. I was on HRT, and wondered if I should be concerned. My periods had nearly stopped a couple of years before, I was on a low dose of estrogen and progresterone. She said the choice was mine. ( She appeared to have read the study.)So I stopped, gradually reducing my intake. What’s interesting is that I worried about having hot flashes (which I’d had before I started the regimen). The hot flashes never returned. Sometimes we can trust our own judgment.
Good post!
Thank you for an outstanding deconstruction of the WHI. I made my living for twenty years dealing with the wretches whose internists ignored the study’s flaws and took them immediately off of HRT. The long term followup studies, which show the safety of continuous HRT, are very reassuring.
Genetic screening is usually focused on those with family histories and has not supplanted mammograms and Pap smears. It is certainly relevant in the individual decision making process. Individualization is the key.
The new finding that ovarian cancer is actually fallopian cancer is a stunning game changer on that dire type of cancer.
You make excellent points.
Mrs. Pessimist has downloaded the audible version of ‘Blindspot’ that we will listen to together on a trip to South Carolina in few weeks. I think Makarry is brighter than most of the TV medical analysts. None of them want to be controversial but from what I have heard Makarry say, I think he knows how broken our medical care system is. I look forward to his thoughts.
The only thing I know about female hormone treatment is that hormones are very complicated. I have avoided any hormone treatments so far. Menopause was hard on me when Mrs. Pessimist went through it despite aggressive HRT.
The amazing thing about menopausal symptoms is how varied they are between individuals, both in severity and duration.