#253 ‒ 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.
The Women's Health Initiative (WHI) study showed that hormone replacement therapy (HRT), especially the combination of estrogen plus progestin, had potential risks, such as an increased risk of breast cancer, but the risks were relatively low and the decision to use HRT should be individualized based on a woman's symptoms, age, and overall health status.
HRT may be more beneficial in women in their 50s, with potential reductions in mortality and cardiovascular events, but the risks and benefits of HRT vary based on individual factors such as overall health, family history, and the severity of menopausal symptoms, so women should have informed discussions with their healthcare providers to weigh the potential benefits and risks based on their specific circumstances.
The combination of estrogen plus progestin therapy in HRT was found to be associated with a 25-30% increase in breast cancer risk, mainly attributed to the progestin component (MPA), while estrogen alone did not show a significant increase in breast cancer risk, highlighting the need for caution when interpreting the findings as they may not apply to all hormone formulations.
Deep dives
The Women's Health Initiative study was designed to test the benefits and risks of hormone replacement therapy (HRT) for chronic disease prevention
The Women's Health Initiative (WHI) study was a randomized clinical trial conducted in the early 1990s with the goal of examining the effects and risks of hormone replacement therapy (HRT) for preventing chronic diseases like heart disease, stroke, and cognitive decline. The study included over 27,000 women, and there were two separate trials: one for estrogen plus progestin and one for estrogen alone. The researchers wanted to assess the potential benefits of starting HRT in early menopause and determine the risks associated with long-term use.
Findings from the Women's Health Initiative study challenged previous assumptions about HRT's benefits and risks
The results of the WHI study generated surprising and often contradicting findings compared to previous observational studies. While previous studies suggested that HRT could reduce the risk of heart disease, cognitive decline, and even mortality, the WHI study did not find significant benefits for these outcomes. In fact, the study showed that HRT, especially the combination of estrogen plus progestin, had potential risks, such as an increased risk of breast cancer. However, it's important to note that the risks were relatively low, and the decision to use HRT should be individualized, considering a woman's symptoms, age, and overall health status.
Timing and personal factors play a crucial role in the decision to use HRT
The timing of HRT and personal factors are important considerations when deciding whether to use HRT. The study found that HRT may be more beneficial in women in their 50s, with potential reductions in mortality and cardiovascular events. However, the risks and benefits vary based on individual factors such as overall health, family history, and the severity of menopausal symptoms. Women should have open and informed discussions with their healthcare providers to weigh the potential benefits and risks of HRT based on their specific circumstances.
The impact of estrogen plus progestin on breast cancer risk
The podcast discusses the increased risk of breast cancer associated with estrogen plus progestin therapy. The Women's Health Initiative (WHI) study found that the combination of these hormones was linked to a 25-30% increase in breast cancer risk. However, it is important to note that the increased risk was mostly attributed to the progestin component, specifically medroxyprogesterone acetate (MPA). The study did not find a significant increase in breast cancer risk with estrogen alone. The podcast emphasizes the need for caution when interpreting these findings, as they may not apply to all formulations of estrogen alone or other types of progestogens.
Impact of the WHI study on hormone therapy practices
The podcast highlights the significant changes in hormone therapy practices that resulted from the WHI study findings. The study led to a significant reduction, around 70-80%, in the use of hormone therapy for the prevention of chronic diseases such as heart disease, stroke, and cognitive decline. This change was considered favorable as the risks were found to outweigh the benefits in the specific population studied by the WHI. However, the podcast also points out that the study results were inappropriately extrapolated to women in their 40s and 50s who were seeking hormone therapy for the treatment of bothersome symptoms like hot flashes and night sweats. The podcast suggests that women in early menopause, in generally good health and experiencing severe symptoms, should have a discussion with a healthcare professional knowledgeable in menopause management to explore their treatment options, including hormone therapy, and weigh the potential benefits against the risks.
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
