Peter Attia MD253 ‒ Hormone replacement therapy and the Women’s Health Initiative: re-examining the results
At a glance
WHAT IT’S REALLY ABOUT
Dr. JoAnn Manson Re-examines Women's Health Initiative Findings on Hormone Therapy
- The WHI was launched in the early 1990s to test in randomized trials whether hormone therapy prevents heart disease and other chronic conditions, after observational studies suggested benefit that Manson suspected was partly confounded.
- Participants averaged 63 years old and were often more than a decade past menopause, and the estrogen-plus-progestin arm was stopped early after 5.6 years because of increased breast cancer, no heart disease reduction, and an unfavorable overall risk-benefit index.
- Attia and Manson agree the breast cancer increase with estrogen plus MPA was small in absolute terms (about one extra case per thousand women per year), and that estrogen alone did not raise breast cancer risk, but Manson cautions that estrogen's role in breast cancer is supported by other evidence and results may not generalize across formulations.
- Manson says the results were wrongly extrapolated to women in their 40s and 50s with bothersome hot flashes, who were denied treatment, while stopping hormone therapy for chronic disease prevention in older women was appropriate.
- Manson stresses individualized shared decision-making, favors transdermal estradiol and micronized progesterone, and says another WHI-scale trial is unlikely, while Attia argues long-term use for bone protection could outweigh risks but acknowledges that this can't be tested.
IDEAS WORTH REMEMBERING
5 ideasThe WHI tested prevention of chronic disease, not treatment of menopausal symptoms.
Manson explains that the trial addressed whether hormones prevent heart disease and cognitive decline, a different question from relieving hot flashes, for which hormone therapy is FDA approved.
The trial population was older than typical symptomatic women.
The average age was 63, and enrollment was by age 50 to 79 rather than time since menopause, so many women were well past early menopause when they began therapy.
The breast cancer signal was small in absolute terms and tied to the progestin combination.
Estrogen plus MPA showed roughly one extra case per thousand women per year, while estrogen alone showed no increase and later a reduction. Manson agrees MPA is likely responsible but says estrogen's role in breast cancer cannot be dismissed.
Results were over-extrapolated to younger women with symptoms.
Manson says use fell 70 to 80 percent after the findings, which was positive for prevention uses but wrongly denied treatment to healthy women in early menopause with distressing symptoms.
Timing matters for risks and benefits.
Absolute risks were lower in women in their 50s, with signals of lower heart disease and about 30 percent lower mortality that were not statistically significant, while estrogen alone in women 70 to 79 showed a possible mortality increase.
WORDS WORTH SAVING
5 quotesIt's amazing how the pendulum has swung. So in the 1980s, 1990s, the perception was that hormone therapy was good for all women. Then after the WHI in the early 2000s, the pendulum was in the opposite direction, that hormone therapy is bad for all women.
— JoAnn Manson
Women never should have been denied hormone therapy for the treatment of bothersome, distressing hot flashes, night sweats to improve their quality of life, especially generally healthy women in early menopause who have such low absolute rates of adverse events.
— JoAnn Manson
In many ways, timing is everything when it comes to hormone therapy because not only are the absolute risks, the risk of having adverse events on hormone therapy lower in the younger women, women in early menopause
— JoAnn Manson
The problem was it was overextrapolated. The results were extrapolated to women in early menopause taking hormone therapy for the hot flashes, night sweats.
— JoAnn Manson
I think there's a lost generation of women. I think there's 20 years of women who entered menopause who were denied HRT due to the ignorance of their physicians and the irresponsibility of the media.
— Peter Attia
High quality AI-generated summary created from speaker-labeled transcript.
