Why did Peter Attia dedicate an entire episode to HRT, a topic often seen as only relevant to women?

Peter Attia believes this topic has generated significant confusion and bad information in medicine. He emphasizes its importance for men to understand, particularly if they know or care about women, drawing parallels to past nutritional guidelines and highlighting the polarizing, almost 'religious' nature of the debate.

How do breast cancer and prostate cancer treatments for men and women compare historically?

Historically, both metastatic prostate cancer in men and breast cancer in women were treated with forms of castration to reduce sex hormones. However, Avrum Bluming notes a significant gender disparity: women often underwent more extreme procedures like adrenalectomy or pituitary gland removal, which were never performed on men for prostate cancer.

What common symptoms of menopause are often overlooked or dismissed?

Beyond hot flashes and night sweats, menopause symptoms can include palpitations, cognitive decline, joint pains, and sleep disturbances. These symptoms often last for seven and a half years on average, and in some women, for decades—far longer than the commonly perceived 'year or two'.

How significant is the drop in estrogen levels during menopause?

In menopause, estrogen levels plummet to approximately 1% of what they were before. This dramatic drop often contributes to various symptoms, including depression, which can be misattributed to a 'midlife crisis' rather than estrogen depletion.

What was the initial rationale for the Women's Health Initiative (WHI) study?

The WHI was primarily undertaken to determine if hormone replacement therapy had beneficial effects on the heart, brain, and bones, as suggested by prior studies like the Nurses' Health Study. It was not initially designed to investigate an increased risk of breast cancer.

What were the key criticisms of the Women's Health Initiative (WHI) study's methodology?

Critics point out that the average age of participants was 63 (10 years post-menopause), with 70% being overweight or obese, and many being smokers. Also, women with significant menopausal symptoms were excluded to prevent high dropout rates, leading to an inability to assess HRT's quality-of-life benefits accurately.

How was the increased breast cancer risk from the WHI study misrepresented?

The initial reported 26% increase in breast cancer risk among women taking estrogen and progesterone was not statistically significant. This finding was based on a lower-than-expected risk in the placebo group—an artifact possibly due to the exclusion of women who had previously taken hormones, not a true increase in risk from HRT.

Does HRT increase the risk of dying from breast cancer?

Surprisingly, studies, including subset analyses of the WHI, have shown that women diagnosed with breast cancer while on hormones have a better prognosis (stage for stage) and a lower risk of dying from breast cancer compared to women not taking hormones.

What is the recommended period for women to start HRT to minimize cardiovascular risks?

The ideal time to start HRT is around the onset of menopause or within the first ten years of cessation of periods, assuming no pre-existing cardiovascular disease. When started in this 'window of opportunity,' there is no increased risk of cardiovascular disease. Starting HRT older than 10 years after menopause might carry a temporary, small increased risk in the first year.

How effective is HRT in preventing osteoporosis and hip fractures?

Estrogen can decrease the risk of osteoporotic hip fracture by up to 50%, outperforming other long-term treatments. Unlike calcium and Vitamin D which primarily affect bone density, estrogen helps preserve bone elasticity and the internal collagen network, which are crucial for fracture resistance.

What are the acknowledged downsides of hormone replacement therapy?

The credible downsides of HRT include a small, statistically significant increase in the incidence of pulmonary embolism and venous thromboembolism, particularly in women with pre-existing conditions. There is also an increased incidence of gallbladder disease, often leading to stone formation and cholecystectomy.

Why is there reluctance to revisit large-scale HRT research?

Repeating a study of the magnitude of the Women's Health Initiative is seen as prohibitively complex and costly. There's also a prevailing idea that truth can only be determined by prospective double-blind randomized studies, which limits funding for other valuable research methods like well-conducted observational studies.

How should women approach their physicians about HRT given conflicting information?

Women should view Avrum Bluming and Carol Tavris's book 'Estrogen Matters' as a tool to become better healthcare consumers. The goal is to be empowered with data to engage in a collaborative discussion with their physician to work out the best, personalized program, rather than accepting a 'take no one's word for it' approach.

Key Moments

#42–Avrum Bluming, M.D. and Carol Tavris, Ph.D.: A compelling case for hormone replacement therapy

Q: What is the primary argument of a podcast episode about 'Estrogen Matters'?

The episode, built around the book 'Estrogen Matters,' argues that hormone replacement therapy (HRT) for women, especially post-menopause, has been unfairly maligned due to misinterpretations of scientific data, particularly from the Women's Health Initiative. The authors contend that the benefits of HRT often far outweigh the risks for most women.

Peter Attia MD

People & Blogs4 min read141 min video

Jan 8, 2020|21,553 views|566|52

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Key Moments

TL;DR

Critique of WHI study reveals HRT benefits for menopausal women outweigh risks.

Key Insights

The Women's Health Initiative (WHI) study's methodology and reporting were flawed, leading to an overestimation of HRT risks and underestimation of benefits.

Estrogen replacement therapy (ERT) alone does not increase breast cancer risk and may even decrease it, while the combination with synthetic progestin (MPA) showed a statistically insignificant increase.

HRT offers significant benefits beyond symptom relief, including substantial reductions in heart disease, Alzheimer's disease, osteoporosis, and hip fractures.

The prevailing advice of 'lowest dose for the shortest time' for HRT lacks empirical evidence and may deprive women of crucial health benefits.

Women experiencing menopausal symptoms, regardless of age or history, should have a thorough discussion with their physicians about personalized HRT options.

The historical and ongoing mistreatment of women in medical research has contributed to widespread fear and skepticism regarding HRT.

THE HISTORY OF MISUNDERSTANDING AND MISTRreatment

The conversation begins by highlighting the historical mistreatment of women in medical practice, including the unnecessary removal of ovaries and adrenal glands, and the routine hysterectomy with oophorectomy. This sets the stage for understanding the societal context surrounding hormone replacement therapy (HRT) and the deep-seated skepticism many women hold towards medical advice on reproductive health. The authors, Carol Tavris and Avrum Bluming, emphasize that their book, 'Estrogen Matters,' aims to challenge established beliefs and present a more nuanced view based on scientific research.

CRITIQUE OF THE WOMEN'S HEALTH INITIATIVE (WHI) STUDY

A central theme is a detailed critique of the 2002 Women's Health Initiative (WHI) study, which significantly influenced public and medical opinion against HRT. The authors argue the study's methodology was flawed: it used an older, less healthy population (average age 63), excluded symptomatic women, and its findings were sensationalized without statistical significance. The initial reporting of a 26% increased breast cancer risk with combination HRT was statistically insignificant and potentially skewed by a lower-than-expected risk in the placebo group, particularly among women who had previously used hormones.

BENEFITS OF ESTROGEN BEYOND SYMPTOM RELIEF

The discussion emphasizes that HRT's benefits extend far beyond alleviating menopausal symptoms like hot flashes. Estrogen can significantly reduce the risk of cardiovascular disease by up to 50%, lower the incidence of Alzheimer's disease by 20-50%, and decrease the risk of osteoporotic hip fractures by 50%. While the WHI study focused on risks, other studies and anecdotal evidence suggest these profound long-term health advantages are often overlooked or dismissed.

DECODING THE STATISTICS: RELATIVE VS. ABSOLUTE RISK

A crucial insight shared is the distinction between relative and absolute risk. The alarmingly-cited '26% increase in breast cancer risk' from WHI was a relative risk, translating to a very small absolute increase (less than 1% or about 9 cases per 10,000 woman-years). The authors stress the importance of understanding these numbers to avoid fear-mongering and to enable informed decision-making. They also highlight contraindications, such as pre-existing cardiovascular disease when starting HRT after menopause.

ADDRESSING SPECIFIC HEALTH OUTCOMES

The conversation delves into specific health outcomes, noting that estrogen alone showed no increased risk of breast cancer and may even decrease it. The potential role of synthetic progestins (MPA) is questioned, as separate analyses did not show increased risks with estrogen alone. Furthermore, HRT appears to reduce the risk of colon cancer and diabetes. While gall bladder disease and pulmonary embolism were noted as potential downsides, their absolute risks are considered very small compared to the overall benefits.

REDEFINING 'NATURAL' AND EMPOWERING WOMEN

The concept of 'natural' is challenged, questioning why a woman living beyond her reproductive years is considered unnatural. The authors advocate for a personalized approach, encouraging women to become informed consumers of healthcare. They argue that the benefits of HRT, when properly considered and discussed with a physician, far outweigh the perceived risks for many women, empowering them to seek treatment that improves their quality of life and long-term health.

THE CONTROVERSIAL CASE OF BREAST CANCER SURVIVORS

The discussion touches upon the complex issue of HRT use in breast cancer survivors. While acknowledging it's an open question, the authors cite studies suggesting that HRT does not necessarily increase recurrence risk, and in some cases, may even be associated with a better prognosis. This challenges the widespread assumption that any estrogen exposure is detrimental post-diagnosis, advocating for individualized risk-benefit analysis even in this sensitive population.

MOVING FORWARD: RESEARCH AND INDIVIDUALIZED CARE

The podcast concludes by emphasizing the need for more nuanced research, beyond large-scale, potentially flawed trials like WHI. The authors highlight the value of well-conducted observational studies and the convergence of evidence from multiple sources. They advocate for open discussion, challenging established dogmas, and empowering women and their physicians to make informed decisions based on comprehensive data, ultimately aiming for longer, healthier lives.

Mentioned in This Episode

●Organizations

●Books

●Drugs & Medications

●Studies Cited

●People Referenced

Lifetime Mortality Risk: Cardiovascular Disease vs. Breast Cancer in Women

Data extracted from this episode

Age	Mortality Ratio (Heart Disease / Breast Cancer)
25	3.5x
30	2.4x
35	2.1x
40	2.3x
45	2.5x
50	2.8x
55	4.1x
60	5.6x
65	8.1x
70	12.4x

Questionable 'Increased Breast Cancer Risk' Findings from Badly Analyzed Studies

Data extracted from this episode

Factor	Reported Increase in Breast Cancer Risk
Fish intake	14%
French fries (one additional serving per week in preschool population)	27%
Grapefruit (half a grapefruit)	30%
Scandinavian flight attendant (Finnish)	1.87x
Scandinavian flight attendant (Icelandic)	4.1x
Electric blanket (African-American, used >10 years, <6 months/year)	5x

Common Questions

The episode, built around the book 'Estrogen Matters,' argues that hormone replacement therapy (HRT) for women, especially post-menopause, has been unfairly maligned due to misinterpretations of scientific data, particularly from the Women's Health Initiative. The authors contend that the benefits of HRT often far outweigh the risks for most women.

Topics

Alzheimer'S Disease Health & Longevity Neuroscience & the Brain Mental Health & Psychology Breast Cancer Hormone Replacement Therapy Women's Health Cardiovascular Disease Medicine & Clinical Menopause Management Medical Bias Clinical Trials Critique

Mentioned in this video

People

Robert Langer

One of the Women's Health Initiative investigators who later revealed background information about the study's controversial publication process.

Carol Tavris

A social psychologist and co-author of 'Estrogen Matters' and 'Mistakes Were Made (But Not by Me)'. She focuses on bringing scientific research to public attention and understanding barriers to critical thinking.

Rowan Chlebowski

A professor at UCLA and one of the three principal authors of the initial WHI publication, who notably stated 'the statistical police have to leave the room' when discussing the study's findings.

Joann Manson

A Women's Health Initiative investigator known for attempting to course-correct previous HRT recommendations, stating that the initial recommendations went too far.

Avrum Bluming

A hematologist and medical oncologist, emeritus clinical professor at USC, and former senior investigator at the National Cancer Institute. Co-author of 'Estrogen Matters' and a key guest on the podcast, challenging assumptions about estrogen and breast cancer.

Bernard Fisher

Revolutionized breast cancer treatment by advocating for less disfiguring surgeries, moving away from radical mastectomies.

Jacques Rossouw

The cardiologist who led the Women's Health Initiative, who allegedly had a pre-existing bias against HRT and published an article expressing a desire to halt the 'HRT bandwagon'.

Steven Rosenberg

A mentor of Peter Attia and a prominent oncologist, co-author of 'Cancer: Principles & Practice of Oncology'.

Leslie Turnberg

The president of the Royal Society of Medicine in England who endorsed 'Estrogen Matters'.

Milton Weinstein

Co-author (as Tosteson) of a 1991 New England Journal of Medicine article that stated women taking estrogen would live longer and healthier, advocating for HRT.

John Ioannidis

An epidemiologist who has described nutritional epidemiology as 'garbage,' highlighting issues with its methodology.

Phyllis Greenberger

The CEO of the Women's Science Cooperative who endorsed 'Estrogen Matters'.

Garnet Anderson

The statistician for the Women's Health Initiative, who stated that for an issue as important as breast cancer, 'we intentionally set the bar low' regarding statistical significance.

Lee Goldman

Co-author of a 1991 New England Journal of Medicine article that stated women taking estrogen would live longer and healthier, advocating for HRT.

Mark Hegsted

A figure involved in setting dietary guidelines in the mid-80s, who argued that with high stakes, one doesn't have time to wait for definitive answers.

Peter Attia

Host of The Drive podcast, focused on optimizing performance, health, longevity, and critical thinking.

Katie Taylor

A woman mentioned in the book who blogged about experiencing severe perimenopausal symptoms and depression at 42, which were initially misdiagnosed.

Barbara Sher

A psychologist at McGill University who studied the benefits of estrogen on the brain and argued that taking HRT for prolonged healthy mental functioning in later years is not 'unnatural' if women live longer.

Samuel Hellman

A radiation oncologist, co-author of 'Cancer: Principles & Practice of Oncology'.

Organizations

New England Journal of Medicine

A prominent medical journal that published an article in 1991 by Goldman and Tosteson encouraging estrogen use, and later published articles related to the Women's Health Initiative.

National Cancer Institute

The organization where Dr. Avrum Bluming formerly served as a senior investigator.

University of Southern California

The institution where Dr. Avrum Bluming holds an emeritus clinical professorship.

Journal of the American Medical Association

A medical journal that published the initial controversial 2002 Women's Health Initiative study, issuing a press release before the article was fully available.

National Institutes of Health

Mentioned in the context of setting dietary guidelines in the mid-80s through a consensus that allegedly forced agreement amongst participants, and as the potential entity to fund large-scale studies.

Drugs & Medications

Premarin

An estrogen derived from pregnant mare urine, historically and currently a dominant form of estrogen in HRT, and the most studied form with 60 years of data.

Medroxyprogesterone Acetate

A synthetic progestin used in the Women's Health Initiative because it was the most widely prescribed progestin at the time. Its role in breast cancer risk is debated.

Micronized Progesterone

A form of bioidentical progesterone that appears to be the safest form of progesterone administration, mentioned in contrast to synthetic progestins.

Tamoxifen

A drug used to treat breast cancer, compared to progesterone in early trials, where progesterone performed slightly better.

Books

Feminine Forever

A book written in the 1940s by Dr. Robert Wilson, which oversold estrogen as an 'eternal Fountain of Youth' and was funded by a drug company.

Emperor of All Maladies

A book by Sid Mukherjee, mentioned as providing eloquent insights into medical history, including radical mastectomy practices.

Estrogen Matters

The book discussed in the podcast, co-authored by Dr. Avrum Bluming and Dr. Carol Tavris, making a case for hormone replacement therapy in women.

Mistakes Were Made

A book co-authored by Carol Tavris, recommended by Peter Attia as one of his absolute favorites, exploring why people resist new information.

Cancer: Principles & Practice of Oncology

Referred to as the 'Bible on oncology,' a very important book endorsed by notable oncologists.

Studies & Research

Nurse's Health Study

A large cohort-based epidemiological study from Harvard following 120,000 nurses for up to 30 years, which found no increased risk of breast cancer with HRT.

Women's Health Initiative

A large-scale randomized clinical trial that significantly impacted the perception and prescription of hormone replacement therapy in 2002. It is critically analyzed throughout the podcast for its methodology and interpretation.

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