The Role of Equine Estrogen in Breast Cancer Risk

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The same conjugated equine estrogen was used with the MPA that found a clinically irrelevant, but statistically significant increase in the incidence of breast cancer. The increased risk of breast cancer seen with estrogen plus progestin was mostly attributable to the progestin and Madroxyprogesterone acetate. There are no large-scale randomized clinical trials that have done head-to-head comparisons or even really tested long-term the effects of other formulations of progestogen on breast cancer risk.

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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.