<p><a href="https://peterattiamd.com/joannmanson/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=230412-pod-joannmanson&utm_content=230412-pod-joannmanson-podfeed"> View the Show Notes Page for This Episode</a></p> <p><a href="https://peterattiamd.com/subscribe/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=230412-pod-joannmanson&utm_content=230412-pod-joannmanson-podfeed"> Become a Member to Receive Exclusive Content</a></p> <p><a href="https://peterattiamd.com/newsletter/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=230412-pod-joannmanson&utm_content=230412-pod-joannmanson-podfeed"> Sign Up to Receive Peter's Weekly Newsletter</a></p> <p>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.</p> <p><strong>We discuss:</strong></p> <ul type="disc"> <li>The Women's Health Initiative: the original goal of the study, hormone formulations used, and potential confounders [4:15];</li> <li>Study design of the Women's Health Initiative, primary outcome, and more [16:00];</li> <li>JoAnn's personal hypothesis about the ability of hormone replacement therapy to reduce heart disease risk prior to the WHI [26:45];</li> <li>The relationship between estrogen and breast cancer [30:45];</li> <li>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];</li> <li>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];</li> <li>HRT and bone health [56:00];</li> <li>The importance of timing when it comes to HRT, the best use cases, and advice on finding a clinician [59:30];</li> <li>A discussion on the potential impact of HRT on mortality and a thought experiment on a long-duration use of HRT [1:03:15];</li> <li>Moving toward better HRT practices, and the need for more studies [1:10:00]; and</li> <li>More.</li> </ul> <p>Connect With Peter on <a href="https://twitter.com/PeterAttiaMD">Twitter</a>, <a href="https://www.instagram.com/peterattiamd/">Instagram</a>, <a href="https://www.facebook.com/peterattiamd/">Facebook</a> and <a href="https://www.youtube.com/channel/UC8kGsMa0LygSX9nkBcBH1Sg">YouTube</a></p>
Actionable Insights
1. Personalize HRT Decisions
Make hormone replacement therapy (HRT) decisions based on an individualized assessment of benefits and risks, considering a woman’s age, time since menopause, and underlying health status, through shared decision-making with a clinician.
2. Ideal HRT Candidates
The best candidates for HRT are women in early menopause (40s-50s) who experience moderate to severe or bothersome hot flashes and night sweats and are in generally good health, as they derive quality of life benefits with minimal absolute risk.
3. Seek Expert Menopause Clinician
If seeking HRT or menopause management, find a certified menopause practitioner through menopause.org by using their ‘Find a Certified Menopause Practitioner’ tab with your zip code, to ensure expert guidance and informed discussion of options.
4. HRT Timing is Key
Understand that the timing of HRT initiation is critical; absolute risks are much lower and potential benefits (e.g., for heart disease with estrogen alone) are more favorable when started in early menopause (50s) compared to later menopause.
5. Distinguish Absolute, Relative Risk
When evaluating medical information, understand the difference between relative and absolute risk, as relative risk can sound alarming (e.g., 25% increase) while the absolute risk may be very low (e.g., one extra case per 1,000 women per year).
6. HRT for Symptoms Only
Use HRT for treating bothersome menopausal symptoms like hot flashes and night sweats, for which it is FDA-approved and effective, but avoid using it for chronic disease prevention in mid to later menopause (average age 63+), as risks outweighed benefits in that context.
7. Progestogen with Intact Uterus
Women with an intact uterus must take a progestogen along with estrogen to counteract estrogen’s effect on the uterine lining and prevent a very high risk of developing endometrial cancer.
8. Prefer Bioidentical Hormones
Prefer transdermal estradiol and micronized progesterone (FDA-approved bioidentical formulations) over oral conjugated estrogen and medroxyprogesterone acetate, due to their potentially more favorable effects on clotting and cardiometabolic health.
9. MPA Linked to Breast Cancer
Recognize that the increased breast cancer risk observed in the Women’s Health Initiative was primarily linked to medroxyprogesterone acetate (MPA) when combined with estrogen, not estrogen alone.
10. Estrogen Alone & Breast Cancer
Estrogen-alone therapy (specifically conjugated equine estrogen) did not show an increased risk of breast cancer in the WHI and even showed a reduction with longer follow-up.
11. Consider Non-Hormonal Options
If HRT is not suitable or desired, explore non-hormonal options like SSRIs, SNRIs, or gabapentin for hot flashes, as these medications have been found to be quite effective, reducing symptoms by 40-50%.
12. Respect Patient HRT Fears
Respect a patient’s strong reluctance to take HRT, even if data suggests favorable absolute risks, as their emotional well-being and anxiety are crucial factors in the overall benefit-risk equation.
13. Bone Benefits Not Sustained
Be aware that HRT benefits for bone density are not sustained long-term after stopping the therapy; continuous use into later life would be needed for fracture prevention, which carries other risks.
14. Recognize Healthy User Bias
Be aware of healthy user bias when interpreting observational health data, as apparent benefits might be due to other healthy lifestyle factors rather than the intervention itself.
Be cautious about breast cancer risk with longer duration of estrogen plus progestin, even with different progestogen formulations, due to limited large-scale randomized trial data on alternatives to medroxyprogesterone acetate.