The Peter Attia Drive

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Renato Tomioka is a leading expert in reproductive medicine and gynecologic surgery whose unique skills allow him to diagnose and treat some of the most impactful yet frequently overlooked conditions affecting women's health. In this episode, Renato explores endometriosis and adenomyosis, explaining what these conditions are, why they often go undiagnosed for years despite affecting millions of women worldwide, and how advances in MRI and specialized ultrasound are transforming diagnosis beyond traditional surgical laparoscopy. He discusses the decision-making process behind hormonal therapy versus surgery, how treatment strategies change when fertility preservation is a priority, and where IVF fits into the care pathway for women with endometriosis, adenomyosis, or age-related fertility decline. Renato also examines the profound effects of female age on egg quality and quantity, including the accelerating rise in chromosomal abnormalities after age 35, highlights common mistakes in both surgical and fertility management, and shares promising developments on the horizon for treating these conditions and preserving fertility.
Follow Dr. Tomioka's work: Instagram: @dr.renatotomioka; Website: Renato Tomioka, M.D., Ph.D.
We discuss:
0:00:00 - Intro
0:00:11 - Endometriosis: definition, prevalence, infertility risk, and theories of disease development
0:09:03 - The biology of endometriosis: estrogen dependence, progesterone resistance, and tumor-like growth mechanisms
0:13:25 - Adenomyosis explained: how it differs from endometriosis, why it develops, and its impact on reproductive health
0:18:52 - Recognizing endometriosis and adenomyosis: the "6 Ds" of endometriosis and key differences in clinical presentation
0:22:09 - Uterine fibroids: classification, symptoms, and the importance of fibroid location for bleeding and fertility
0:24:09 - Understanding endometriosis pain: lesion-driven pain, nerve involvement, central sensitization, and the importance of early treatment
0:28:26 - Endometriosis in young women: rising prevalence, delayed diagnosis, and barriers to care
0:33:11 - Modern diagnosis of endometriosis: specialized ultrasound, MRI, and the decline of diagnostic laparoscopy
0:45:52 - Clinical case example #1: Managing endometriosis in a young woman seeking pain relief while preserving future fertility
0:54:10 - Clinical case example #2: Comparing treatment strategies for symptom control versus fertility
1:01:24 - Endometriosis and fertility: the roles of age, embryo quality, IVF, and surgery
1:11:50 - Clinical case example #3: Managing adenomyosis after failed IVF transfers to improve implantation and pregnancy outcomes
1:20:51 - The funding gap in endometriosis research: disease burden, economic impact, and growing awareness
1:22:01 - Clinical case example #4: Surgical decision-making in endometriosis—balancing pain relief, fertility preservation, and common treatment pitfalls
1:27:43 - Common misconceptions about fertility: maternal age, embryo aneuploidy, the inefficiency of human reproduction, and the limits of IVF
1:34:23 - Elective egg freezing: timing, success rates, the fertility funnel, and the tradeoffs of fertility preservation
1:45:49 - Emerging fertility technologies: mitochondrial replacement, ovarian tissue preservation, stem-cell-derived eggs, and current limitations
1:55:10 - The future of endometriosis treatment: new guidelines, biologic therapies, and unanswered questions about IVF
1:58:30 - Why earlier diagnosis matters: reducing years of suffering from endometriosis and adenomyosis
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In this episode, Peter explores the critical topic of breast cancer screening, examining why thousands of women continue to die from breast cancer each year despite the availability of effective screening tools. He explains the strengths and limitations of current screening strategies, reviews the recommendations from major medical organizations, and discusses why screening guidance can often seem confusing or contradictory. Peter outlines a practical framework for understanding breast cancer risk and personalizing screening decisions, including when to begin screening, how frequently to screen, and which imaging modalities may be most appropriate based on an individual's risk profile. Throughout the episode, he emphasizes that while population-based guidelines provide an important foundation, optimizing outcomes requires a more personalized approach aimed at helping women make informed screening decisions that can improve the chances of early detection and successful treatment.
We discuss:
Why women still die from breast cancer: the benefits of screening, the problem of under-screening, and the need for risk-based screening strategies [1:45];
Current screening recommendations, why they differ between organizations, and the importance of personalized screening decisions [6:30];
A framework for personalizing screening [8:45];
Assessing baseline breast cancer risk: genetics, family history, breast density, lifestyle factors, and the role of risk calculators in personalized screening [9:30];
Balancing cancer detection and false positives: how breast cancer risk influences screening intensity and imaging choices [17:45];
Mammography as the foundation of breast cancer screening: detecting ductal carcinoma in situ (DCIS) and the advantages of 3D versus 2D mammography [21:00];
MRI for high-risk women: the benefits of supplemental screening, abbreviated MRI, and the emerging role of contrast-enhanced mammography [23:00];
The role of ultrasound: supplemental cancer detection, diagnostic evaluation, and limitations compared with mammography and MRI [26:00];
Choosing the right breast cancer screening strategy: imaging modality selection, screening hierarchies, and the importance of imaging center quality [28:00];
How often should you screen for breast cancer? [30:15];
At what age should you start screening? [37:30];
Breast cancer in younger women: aggressive tumor biology, BRCA-related risk, breast density, and individualized decisions about when to begin screening [41:45];
Inflammatory breast cancer, the limitations of screening mammography for symptomatic disease, and the importance of promptly evaluating new breast symptoms in both women and men [44:45];
From risk assessment to personalized screening: a practical framework for reducing breast cancer mortality through earlier and more effective detection [46:30]; and
More.
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Tom Dayspring is a world-renowned lipidologist and one of the most thoughtful teachers in the field of lipid metabolism. In this episode, Tom returns to The Drive for a deep dive into the relationship between lipids and brain health, beginning with the fundamentals of cholesterol transport before exploring why the brain's cholesterol system operates almost entirely independently from the rest of the body. Tom examines the roles of apoB, apoA-I, and especially apoE in cholesterol homeostasis, discusses how APOE genotype influences Alzheimer's disease risk, and unpacks the complex links between cholesterol metabolism, amyloid, and tau pathology. He also reviews what is currently known—and still uncertain—about the effects of statins, ezetimibe, omega-3 fatty acids, and emerging CETP inhibitors on brain health and neurodegenerative disease risk. Although highly technical, this conversation provides an essential framework for understanding the nuanced relationship between lipid-lowering therapies, cardiovascular disease prevention, and neurodegenerative diseases in an area often clouded by misinformation.
We discuss:
The fundamentals of cholesterol transport in the body, and how peripheral cholesterol metabolism differs from cholesterol handling in the brain [2:45];
How cholesterol is transported through plasma and stored within cells, and why lowering LDL cholesterol does not deplete the body or brain of cholesterol [11:45];
How apoB particles drive atherosclerosis, why lowering lipids matters, and the factors that influence individual cardiovascular risk [20:00];
How the brain produces and transports its own cholesterol using apoE lipoproteins independently of circulating cholesterol and apoB-containing lipoproteins [29:00];
How apoB structure influences LDL receptor binding and LDL clearance [39:00];
How neurons acquire cholesterol from apoE-containing lipoproteins and why desmosterol serves as a unique marker of cholesterol synthesis in the brain [41:45];
The difference between the APOE gene and the apoE protein, the major APOE genotypes found in humans, and how APOE4 influences Alzheimer's disease risk [48:45];
HDL function beyond cholesterol: immune function, protein cargo, and communication with the brain [53:30];
How APOE4-associated defects in brain cholesterol transport may promote Alzheimer's disease: amyloid production, neuronal cholesterol homeostasis, and cholesterol clearance [58:00];
Statins and brain health: reviewing the evidence of the potential impact of statins on cognition and Alzheimer's disease risk [1:09:00];
Desmosterol and 24S-hydroxycholesterol as biomarkers of brain cholesterol metabolism and statin effects [1:17:15];
Possible cognitive benefits of ezetimibe beyond lowering apoB [1:19:30];
EPA, DHA, and the evidence for omega-3 fatty acids in brain health [1:23:15];
Obicetrapib: an emerging CETP inhibitor with potential implications for both cardiovascular and brain health [1:31:00]; and
More.
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In this episode, Peter dives into the pharmacology of sleep, exploring where sleep medications fit within the broader framework of achieving healthy, restorative sleep. He explains why sleep is a biological imperative, why behavioral and environmental interventions must remain the foundation of good sleep, and how medications can serve as useful tools when carefully matched to a person's specific sleep problem. Peter examines the major classes of prescription sleep medications, including how they work, their effects on sleep architecture, their duration of action, side effects, and risks of tolerance and dependence. He also discusses the dangers of using sleep drugs without a clear understanding of the underlying problem being treated, the role of medications as short-term bridges during periods of acute stress, pain, or anxiety, and the promise that newer drugs like DORAs may hold for Alzheimer's prevention in high-risk individuals. Finally, Peter reviews the evidence for select off-label medications and supplements commonly used for sleep.
We discuss:
The biological foundations of sleep, the major drivers of sleep dysfunction, and the role sleep medications can play when appropriately matched to specific sleep problems [1:00];
Sleep hygiene, circadian alignment, and the medical causes of insomnia: building the foundation for effective sleep treatment [7:15];
Understanding insomnia: hyperarousal, CBT-I, paradoxical insomnia, and why different sleep problems require different treatments [12:45];
The difference between sedation and physiologic sleep: sleep architecture, restorative sleep stages, and matching medications to specific sleep problems [17:00];
Benzodiazepines for insomnia: mechanisms, effects on sleep architecture, and the risks of long-term use [18:45];
Z-drugs for insomnia: how Ambien, Sonata, and Lunesta work, and the ongoing risks of sleep medications targeting GABA systems [23:00];
Dual orexin receptor antagonists (DORAs) and the future of sleep medicine: orexin signaling, sleep architecture, and the emerging connection between sleep and Alzheimer's disease [27:15];
Melatonin for circadian timing: how timing signals differ from sedatives in the treatment of sleep disorders [36:30];
Trazodone for insomnia: preserving deep sleep while minimizing the risks of traditional sedative-hypnotics [42:00];
First-generation antihistamines for sleep: short-term sedation, anticholinergic risks, and concerns about long-term cognitive health [44:00];
Sleep supplements and the evidence behind them: glycine, magnesium, ashwagandha, phosphatidylserine, and more [45:45];
Takeaways: supplement quality, individualized sleep treatment, and the importance of matching interventions to the biology of insomnia [52:00]; and
More.
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In this "Ask Me Anything" (AMA) episode, Peter explores how to think critically about medications and supplements by focusing not on whether an intervention is inherently "good" or "bad," but on whether it makes sense for a specific person with a specific problem. He explains why clearly defining the problem matters more than choosing the intervention itself, how the intended purpose of a medication or supplement should influence the standard of evidence required, and why mechanistic reasoning alone is rarely enough to justify taking something. Peter also examines how baseline risk shapes the true benefit of an intervention, why relative risk statistics can be misleading without proper context, and how to weigh not only side effects, but also cost, inconvenience, and opportunity cost when deciding whether something is worth taking. Additionally, he discusses practical ways to evaluate whether a supplement is actually having a meaningful effect, how to think about discontinuing therapies, why supplements deserve far more skepticism than they often receive, and the small group of over-the-counter supplements he believes may offer a reasonable risk-reward trade-off.
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We discuss:
How to properly define health problems before considering medications or supplements [1:45];
How the intended purpose of an intervention should determine evidence standards and risk tolerance [5:00];
Understanding the hierarchy of evidence for medications and supplements and avoiding the mistake of treating weak evidence as clinical proof [9:00];
Why mechanistic explanations can be misleading when evaluating longevity interventions [13:15];
How baseline risk—and the distinction between relative and absolute risk reduction—changes the real-world benefit of medications and supplements [18:15];
Thinking beyond side effects: the many forms of downside associated with medications and supplements [22:45];
Why medications and supplements require different standards of trust and evidence [26:00];
How to structure meaningful self-experiments with medications and supplements to determine if it's they're working [30:30];
How to monitor the effects of medications and supplements without fooling yourself [32:30];
How to periodically reevaluate and potentially discontinue medications and supplements [35:15];
The biggest risks and failure modes of over-the-counter supplements: efficacy, poor quality control, contamination, interactions, toxicity, and marketing-driven overuse [38:30];
Why the US supplement regulatory system creates unreliable products [41:45];
A practical framework for evaluating medications and supplements [46:30];
Over-the-counter supplements with the best balance of evidence and low downside risk [48:00]; and
More.
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