Hormone replacement therapy and the Women's Health Initiative: re-examining the results, the link to breast cancer, and weighing the risk vs reward of HRT | JoAnn Manson, M.D.

**Peter Attia** (0:11)
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My guest this week is Dr. JoAnn Manson. JoAnn is a professor of medicine and the Michael and Lee Bell Professor of Women's Health at Harvard Medical School, professor in the Department of Epidemiology, along with chief of the Division of Prevention Medicine at Brigham and Women's Hospital.
She is also a physician, epidemiologist, endocrinologist, and the principal investigator or co-PI of several research studies, including the Women's Health Initiative, which we of course discuss here in length, along with other studies such as the cardiovascular components of the nurse's health study, the vitamin D and omega-3 trials known as VITAL. Her primary research interests include randomized clinical prevention trials of nutrition and lifestyle factors related to heart disease, diabetes, cancer, and the role of endogenous and exogenous estrogens as determinants of chronic disease in women. JoAnn has received numerous honors, including the American Heart Association's Population Research Prize, the American Heart Association's Distinguished Science Award, the Research Achievement Award, election to the Institute of Medical of the National Academies and the National Academy of Medicine, membership in the Association of American Physicians, fellowship in the AAAS, and so many other awards that I could spend the rest of the introduction of this podcast going over them. She has published more than 1200 peer-reviewed articles in the medical literature and is the author or editor of several books and textbooks. She serves as the editor in chief of contemporary clinical trials and is the past president of the North American Menopause Society. She is one of the most highly cited researchers in the history of published research and one of the physicians who is featured in the National Library of Medicine's Exhibition, History of American Women Physicians.
In this episode with JoAnn, we spend the entire conversation focusing on one of her main projects, the study that she was involved in called The Women's Health Initiative, of which she was one of the principal investigators. In this discussion, we speak about the reasons for the study, the questions being examined, the study design, inclusion, exclusion criteria.
We then go into the nuances of the study, including why it was prematurely stopped and how it was interpreted. Of course, the most important part of this discussion is what the implications are for someone today listening to this. Hormone replacement therapy is potentially one of the most controversial bits of medicine today. And I would argue, and I make this point to JoAnn, that the misinterpretation of the Women's Health Initiative some 20 years ago may be one of the greatest missteps of medicine, and by extension, the medical press, in the past several decades. I make no bones about my bias here in this podcast, which is that I think the fears of hormone replacement therapy are completely overblown and are generally being propagated by people who are not familiar with the literature, which is why I wanted to sit down with JoAnn today. I could think of no better person to sit down with and go through the details of this study than the person who is more familiar with them than anyone else. So without further delay, please enjoy my conversation with Dr. JoAnn Manson. JoAnn, it is great to finally be sitting down with you. This is a topic that is arguably as important as any topic that we'll cover in this podcast, and there's probably no better person to speak with about HRT than you. So maybe just by way of background, well, maybe I'll introduce you with one interesting statistic. Do you know how to actually calculate the H index?

**JoAnn Manson** (4:38)
Yes.

**Peter Attia** (4:40)
So tell folks what the H index is, how it's calculated. I'll embarrass you by telling people how high you rank on that.

**JoAnn Manson** (4:47)
Okay, this is very embarrassing, Peter, but let me start by saying it's great to have a chance to talk with you. And I'm so glad that you're interested in the subject and providing more information to your audience on this subject. The H index is calculated from the number of publications you have that are highly cited. If, for example, you have an H index of 100, that would mean that you have at least, we have a hundred publications that have 100 or more citations each.