The Role of Hormone Therapy in Preventing Chronic Diseases

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In the 1980s and 1990s, there were several observational studies looking at women who chose to be on hormone therapy or whom doctors were prescribing hormone therapy for. And they did tend to have lower rates of heart disease in those studies compared to women not using hormone therapy. They also seem to have more favorable outcomes, such as less cognitive decline, lower all-cause mortality rates. But we often say that observational studies of this nature cannot prove a cause and effect relationship but can generate hypotheses to be tested in randomized clinical trials.

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JoAnn Manson is a world-renowned endocrinologist, epidemiologist, and Principal Investigator for the Women’s Health Initiative (WHI). In this episode, she dives deep into the WHI to explain the study design, primary outcome, confounding factors, and nuanced benefits and risks of hormone replacement therapy (HRT). JoAnn reflects on how a misinterpretation of the results, combined with sensationalized headlines regarding an elevated risk of breast cancer, led to a significant shift in the perception and utilization of HRT. From there, they take a closer look at the breast cancer data to separate fact from fiction. Additionally, JoAnn gives her take on how one should weigh the risks and benefits of HRT and concludes with a discussion on how physicians can move towards better HRT practices.

We discuss:

The Women’s Health Initiative: the original goal of the study, hormone formulations used, and potential confounders [4:15];
Study design of the Women’s Health Initiative, primary outcome, and more [16:00];
JoAnn’s personal hypothesis about the ability of hormone replacement therapy to reduce heart disease risk prior to the WHI [26:45];
The relationship between estrogen and breast cancer [30:45];
Why the WHI study was stopped early, and the dramatic change in the perception and use of HRT due to the alleged increase in breast cancer risk [37:30];
What Peter finds most troubling about the mainstream view of HRT and a more nuanced look at the benefits and risks of HRT [45:15];
HRT and bone health [56:00];
The importance of timing when it comes to HRT, the best use cases, and advice on finding a clinician [59:30];
A discussion on the potential impact of HRT on mortality and a thought experiment on a long-duration use of HRT [1:03:15];
Moving toward better HRT practices, and the need for more studies [1:10:00]; and
More.