Dr. Brendan McCarthy

Many women are prescribed oral estrogen without ever being told what happens after it enters the body. In this episode, Dr. Brendan McCarthy takes a deeper look at estrone, the estrogen metabolite created when estradiol is taken orally, and explains why the delivery method of hormone therapy matters.

You'll learn:

The difference between estradiol and estrone

Why oral estrogen creates significantly higher estrone levels

How estrone may contribute to inflammation and insulin resistance

The connection between estrogen metabolism and weight gain during perimenopause and menopause

Why monitoring labs is essential when using hormone therapy

The importance of understanding risks, benefits, and treatment options before starting hormones

Dr. McCarthy also discusses the role of inflammation, body fat, metabolic health, and hormone delivery systems in creating long-term outcomes for women navigating menopause.

This episode is about education, informed consent, and helping women better understand the science behind their care.

 

Citations: There is more than one estrogen; after menopause, estrone dominates Kuhl, Herbert. “Pharmacology of Estrogens and Progestogens: Influence of Different Routes of Administration.” Climacteric, vol. 8, no. S1, 2005, pp. 3–63. Body fat is an endocrine organ — aromatase converts androstenedione into estrone, and adipose becomes the dominant post-menopausal estrogen source Lee, Angel A., and Laura J. Den Hartigh. “Metabolic Impact of Endogenously Produced Estrogens by Adipose Tissue in Females and Males across the Lifespan.” Frontiers in Endocrinology, vol. 16, 2025, article 1682231. Inflamed fat raises IL-6; IL-6 tracks the insulin-resistant state Kern, Philip A., et al. “Adipose Tissue Tumor Necrosis Factor and Interleukin-6 Expression in Human Obesity and Insulin Resistance.” American Journal of Physiology-Endocrinology and Metabolism, vol. 280, no. 5, 2001, pp. E745–E751. IL-6 is part of the insulin-resistance machinery — it correlates with impaired insulin-stimulated glucose uptake Bastard, Jean-Philippe, et al. “Adipose Tissue IL-6 Content Correlates with Resistance to Insulin Activation of Glucose Uptake Both In Vivo and In Vitro.” The Journal of Clinical Endocrinology & Metabolism, vol. 87, no. 5, 2002, pp. 2084–2089. Inflammation amplifies aromatase — IL-6 raises aromatase via COX-2/PGE2 Bowers, Laura W., et al. “Obesity-Associated Systemic Interleukin-6 Promotes Pre-Adipocyte Aromatase Expression via Increased Breast Cancer Cell Prostaglandin E2 Production.” Breast Cancer Research and Treatment, vol. 149, no. 1, 2015, pp. 49–57. Human-tissue confirmation: HOMA-IR, IL-6, insulin, leptin, hsCRP track breast aromatase after menopause Brown, Kristy A., et al. “Menopause Is a Determinant of Breast Aromatase Expression and Its Associations with BMI, Inflammation, and Systemic Markers.” The Journal of Clinical Endocrinology & Metabolism, vol. 102, no. 5, 2017, pp. 1692–1701. Iyengar, Neil M., et al. “Effects of Obesity on Breast Aromatase Expression and Systemic Metabo-Inflammation in Women with BRCA1 or BRCA2 Mutations.” npj Breast Cancer, vol. 7, no. 1, 2021, article 18. The molecular crux: estrone drives ERα/NF-κB inflammatory signaling while estradiol opposes it Qureshi, Rehana, et al. “The Major Pre- and Postmenopausal Estrogens Play Opposing Roles in Obesity-Driven Mammary Inflammation and Breast Cancer Development.” Cell Metabolism, vol. 31, no. 6, 2020, pp. 1154–1172.e9. Estrone as a metabolic-risk signal — prospectively associated with diabetes (note: male cohort) Jasuja, Guneet Kaur, et al. “Circulating Estrone Levels Are Associated Prospectively with Diabetes Risk in Men of the Framingham Heart Study.” Diabetes Care, vol. 36, no. 9, 2013, pp. 2591–2596.

 

Dr. Brendan McCarthy is the founder and Chief Medical Officer of Protea Medical Center in Arizona. With over two decades of experience, he’s helped thousands of patients navigate hormonal imbalances using bioidentical HRT, nutrition, and root-cause medicine. He’s also taught and mentored other physicians on integrative approaches to hormone therapy, weight loss, fertility, and more.

If you’re ready to take your health seriously, this podcast is a great place to start.

👇 Tap Subscribe to learn more about what’s actually happening in your body, and what to do about it.

📘 Read Dr. McCarthy’s Book:
Jump Off the Mood Swing – A Sane Woman’s Guide to Her Crazy Hormones
https://www.amazon.com/Jump-Off-Mood-...

📲 Follow Dr. McCarthy:
Instagram: @drbrendanmccarthy
TikTok: @drbrendanmccarthy
Website: www.protealife.com

💬 Got a question or topic for a future episode? Let us know in the comments!

In this episode, Dr. Brendan McCarthy breaks down one of the most misunderstood topics in hormone replacement therapy: estradiol.

Not all estrogen is the same—and how estradiol is delivered can dramatically affect hormone balance, inflammation, clotting risk, testosterone levels, and overall health outcomes.

Dr. McCarthy discusses:

• Why route of administration matters (oral, patch, injectable, topical, vaginal, pellet)
• How oral estradiol converts to estrone
• The differences between estradiol (E2), estrone (E1), and estriol (E3)
• Estrone's relationship to inflammation and metabolic health
• Oral estrogen and clotting risk
• Oral estrogen's effect on SHBG and free testosterone
• The impact of oral estrogen on IGF-1 and growth hormone signaling
• Why informed consent should be central to hormone therapy
• Benefits and limitations of pellets, patches, creams, and injections
• Estriol and emerging research in autoimmune conditions such as multiple sclerosis

At Protea Medical Center, our philosophy is simple: patients deserve complete information so they can make empowered decisions about their health.

📍 Protea Medical Center
Tempe, Arizona

👍 If you found this episode helpful, please like, subscribe, and share it with someone who may benefit.

⚠️ This podcast is for educational purposes only and does not constitute medical advice. Always consult your healthcare provider before making changes to your treatment plan.

REFERENCES (Abbreviated)

• Kuhl H. Climacteric. 2005.
• O'Connell MB. J Clin Pharmacol. 1995.
• Canonico M et al. Circulation. 2007.
• Vinogradova Y et al. BMJ. 2019.
• Weissberger AJ et al. JCEM. 1991.
• Bellantoni MF et al. JCEM. 1996.
• Kam GY et al. JCEM. 2000.
• Brown KA et al. JCEM. 2017.
• Iyengar NM et al. npj Breast Cancer. 2021.
• Bowers LW et al. Breast Cancer Res Treat. 2015.
• Lee AA & Den Hartigh LJ. Front Endocrinol. 2025.
• Kern PA et al. Am J Physiol Endocrinol Metab. 2001.
• Bastard JP et al. JCEM. 2002.
• Qureshi R et al. Cell Metab. 2020.
• Cushman M et al. Circulation. 1999.
• Key TJ et al. J Natl Cancer Inst. 2002.
• Sicotte NL et al. Ann Neurol. 2002.
• Voskuhl RR et al. Lancet Neurol. 2016.
• Soldan SS et al. J Immunol. 2003.
• Taylor MB & Gutierrez MJ. Pharmacotherapy. 2008.
• FDA Drug Safety Communication. 2010.
• Greenblatt RB & Suran RR. Am J Obstet Gynecol. 1949.

 

Dr. Brendan McCarthy is the founder and Chief Medical Officer of Protea Medical Center in Arizona. With over two decades of experience, he’s helped thousands of patients navigate hormonal imbalances using bioidentical HRT, nutrition, and root-cause medicine. He’s also taught and mentored other physicians on integrative approaches to hormone therapy, weight loss, fertility, and more.

If you’re ready to take your health seriously, this podcast is a great place to start.

👇 Tap Subscribe to learn more about what’s actually happening in your body, and what to do about it.

📘 Read Dr. McCarthy’s Book:
Jump Off the Mood Swing – A Sane Woman’s Guide to Her Crazy Hormones
https://www.amazon.com/Jump-Off-Mood-...

📲 Follow Dr. McCarthy:
Instagram: @drbrendanmccarthy
TikTok: @drbrendanmccarthy
Website: www.protealife.com

💬 Got a question or topic for a future episode? Let us know in the comments!

After 16 episodes exploring food, metabolism, cravings, and health, Dr. Brendan McCarthy shares the most important lesson of all:

Your body is not broken.

Too often, health conversations focus on calories, diets, lab results, and willpower. But lasting change isn't just about what you eat—it's about understanding why you eat, what your body is responding to, and replacing shame with compassion.

In this powerful conclusion to the series, Dr. McCarthy reflects on years of working with women who have been told they are the problem, only to discover that healing begins when someone finally listens.

In this episode:
✔ Why comfort foods affect more than hunger
✔ How food impacts brain chemistry and emotional regulation
✔ The hidden reason diets often fail long-term
✔ Why shame keeps people stuck in unhealthy cycles
✔ The importance of self-compassion and sustainable change
✔ "We don't attack the person. We repair the protocol."

If you've ever felt frustrated by your health journey, struggled with food cravings, or blamed yourself for not being able to "stick with it," this episode is for you.

 

Dr. Brendan McCarthy is the founder and Chief Medical Officer of Protea Medical Center in Arizona. With over two decades of experience, he’s helped thousands of patients navigate hormonal imbalances using bioidentical HRT, nutrition, and root-cause medicine. He’s also taught and mentored other physicians on integrative approaches to hormone therapy, weight loss, fertility, and more.

If you’re ready to take your health seriously, this podcast is a great place to start.

👇 Tap Subscribe to learn more about what’s actually happening in your body, and what to do about it.

📘 Read Dr. McCarthy’s Book:
Jump Off the Mood Swing – A Sane Woman’s Guide to Her Crazy Hormones
https://www.amazon.com/Jump-Off-Mood-...

📲 Follow Dr. McCarthy:
Instagram: @drbrendanmccarthy
TikTok: @drbrendanmccarthy
Website: www.protealife.com

💬 Got a question or topic for a future episode? Let us know in the comments!

This episode is about more than food.

It's about understanding why we reach for certain foods, creating a realistic off-ramp from ultra-processed eating, and giving your body a chance to reset.

If you've ever felt like you're doing everything right but still struggling with weight, energy, inflammation, or cravings, this episode is for you.

 

Citation:

Hall, Kevin D., et al. “Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake.” Cell Metabolism, vol. 30, no. 1, 2019, pp. 67–77.e3. https://doi.org/10.1016/j.cmet.2019.05.008

— This is the cornerstone. Same calories, sugar, fat, fiber, and macros on both diets; people ate ~500 kcal/day more on the ultra-processed one and gained weight. It’s the strongest evidence that the processing, not just the nutrients, changes intake.

Why fat + sugar together hijack reward more than either alone (the “hyperpalatable” mechanism)

DiFeliceantonio, Alexandra G., et al. “Supra-Additive Effects of Combining Fat and Carbohydrate on Food Reward.” Cell Metabolism, vol. 28, no. 1, 2018, pp. 33–44.e3. https://doi.org/10.1016/j.cmet.2018.05.018

McDougle, Molly, et al. “Separate Gut-Brain Circuits for Fat and Sugar Reinforcement Combine to Promote Overeating.” Cell Metabolism, vol. 36, no. 2, 2024, pp. 393–407. https://doi.org/10.1016/j.cmet.2023.12.014

— Together these support your point that engineered fat-plus-sugar foods (the Doritos idea) light up reward pathways more than natural foods, because fat and sugar run on separate gut-brain circuits that combine.

Why “glycemic velocity” matters — hidden refined starches like maltodextrin

Hofman, Denise L., et al. “Nutrition, Health, and Regulatory Aspects of Digestible Maltodextrins.” Critical Reviews in Food Science and Nutrition, vol. 56, no. 12, 2016, pp. https://doi.org/10.1080/10408398.2014.940415

— Supports the egg-bite/maltodextrin point: maltodextrin is a refined starch with a glycemic index around 85–110, higher than table sugar, hiding on labels as “modified food starch.” Backs your “what the calories came from” framing.

Why these foods genuinely relieve stress (your central, original thesis)

Ulrich-Lai, Yvonne M., et al. “Pleasurable Behaviors Reduce Stress via Brain Reward Pathways.” Proceedings of the National Academy of Sciences, vol. 107, no. 47, 2010, pp. https://doi.org/10.1073/pnas.1007740107

Tomiyama, A. Janet, et al. “Comfort Food Is Comforting to Those Most Stressed: Evidence of the Chronic Stress Response Network in High Stress Women.” Psychoneuroendocrinology, vol. 36, no. 10, 2011, pp. 1513–1519. https://doi.org/10.1016/j.psyneuen.2011.04.005

— This is the science behind “the food was doing something right.” Palatable food measurably dampens the HPA (cortisol) stress axis through reward pathways — which is exactly why pulling it without replacing the stress tool fails.

Why cravings are state-dependent and rise with stress (the “urge depends on the state of your blood / stress level” claim)

Adam, Tanja C., and Elissa S. Epel. “Stress, Eating and the Reward System.” Physiology & Behavior, vol. 91, no. 4, 2007, pp. 449–458. https://doi.org/10.1016/j.physbeh.2007.04.011

Darcey, Valerie L., et al. “Brain Dopamine Responses to Ultra-Processed Milkshakes Are Highly Variable and Not Significantly Related to Adiposity in Humans.” Cell Metabolism, vol. 37, no. 3, 2025, pp. 616–628. https://doi.org/10.1016/j.cmet.2025.02.002
 (edited) 

 

 

WHAT TO EAT FOR THE NEXT SIX WEEKS — Protein. Plant. Potato. (P³)

The formula for every meal: one protein + one plant + one starch (potato, or beans and rice). Add fat — olive oil, butter, avocado, cheese, nuts. Add flavor — salt, pepper, garlic, lemon, vinegar, salsa, hot sauce, herbs. This is not the meal you dreamed of. This is the meal that sets you free.

BREAKFAST

Eggs + sautéed vegetables + fruit on the side

Plain Greek yogurt + berries + a handful of nuts

Leftover chicken or beef + potato + vegetables (last night’s dinner works)

LUNCH

Chicken + roasted potato + green salad with olive oil and lemon

Tuna + white beans + cucumber + tomato, dressed with olive oil and vinegar

Beef + potato + peppers + salsa

DINNER

Sheet-pan chicken + potatoes + green beans

Instant Pot chicken + potato + a vegetable

Burger patty (no bun) + potato + salad

Batch chili (beef + beans + tomato) over rice

Baked fish + sweet potato + roasted broccoli

Pork + beans and rice + sautéed greens

THE DURESS PLATE — for when the day collapses
One protein + one plant + one starch, zero cooking. Examples:

• Hard-boiled eggs + apple + handful of nuts
• Tuna + canned beans + cucumber, with olive oil
• Pre-cooked/frozen ground beef + frozen vegetables + microwave potato
• String cheese + fruit + a few nuts (in a real pinch)

SIMPLE RECIPES
Sheet-Pan Chicken & Potatoes (serves 4)
Toss chicken thighs and quartered baby potatoes in olive oil, salt, pepper, garlic. Roast at 425°F (220°C) ~35–40 min. Add green beans for the last 15 min.

Batch Chili (serves 6)
Brown 2 lb ground beef with chopped onion. Add 2 cans diced tomatoes, 2 cans beans (drained), garlic, cumin, chili powder, salt. Simmer 30+ min. Freezes well — make once, eat all week. Serve over rice.

Instant Pot Chicken
Chicken breasts + ½ cup broth + salt, garlic, paprika. Pressure cook 10 min, natural release 5. Shred. Pairs with any potato + vegetable.

The 5-Minute Tuna Bean Bowl
Can of tuna + can of white beans (rinsed) + diced cucumber and tomato. Dress with olive oil, lemon or vinegar, salt, pepper.

Microwave Potato, Done Right
Pierce a potato, microwave 5–7 min. Split, add butter or olive oil, salt, pepper. The reliable, universal starch.

Remember: Don’t aim for one perfect week repeated six times. Just follow the basic protocol the best you can for six weeks. When a craving hits, run the nine-minute interrupt from Episode 14.
 

Dr. Brendan McCarthy is the founder and Chief Medical Officer of Protea Medical Center in Arizona. With over two decades of experience, he’s helped thousands of patients navigate hormonal imbalances using bioidentical HRT, nutrition, and root-cause medicine. He’s also taught and mentored other physicians on integrative approaches to hormone therapy, weight loss, fertility, and more.

If you’re ready to take your health seriously, this podcast is a great place to start.

👇 Tap Subscribe to learn more about what’s actually happening in your body, and what to do about it.

📘 Read Dr. McCarthy’s Book:
Jump Off the Mood Swing – A Sane Woman’s Guide to Her Crazy Hormones
https://www.amazon.com/Jump-Off-Mood-...

📲 Follow Dr. McCarthy:
Instagram: @drbrendanmccarthy
TikTok: @drbrendanmccarthy
Website: www.protealife.com

💬 Got a question or topic for a future episode? Let us know in the comments!

Most diets fail because they never address what the food was doing for you emotionally.

In this episode, Dr. Brendan McCarthy explains the stress-craving loop behind emotional eating, why ultra-processed foods feel impossible to resist, and how shame actually reinforces the cycle.

You’ll learn:
• Why cravings feel automatic
• How stress drives food urges
• The “cue → urge → reward” loop
• A simple 9-minute method to interrupt cravings

This isn’t about perfection or willpower. It’s about understanding the pattern so you can finally begin to change it.

 

Citations: 

Boswell, Rebecca G., and Hedy Kober. “Food Cue Reactivity and Craving Predict Eating and Weight Gain: A Meta-Analytic Review.” Obesity Reviews, vol. 17, no. 2, 2016, pp. 159–177. doi:10.1111/obr.12354.
Use for: Food cues can trigger craving and eating even without true hunger.

Berridge, Kent C., and Terry E. Robinson. “Liking, Wanting, and the Incentive-Sensitization Theory of Addiction.” American Psychologist, vol. 71, no. 8, 2016, pp. 670–679. doi:10.1037/amp0000059.
Use for: “Wanting” food is not the same as true pleasure.

Schultz, Wolfram, Peter Dayan, and P. Read Montague. “A Neural Substrate of Prediction and Reward.” Science, vol. 275, no. 5306, 1997, pp. 1593–1599. doi:10.1126/science.275.5306.1593.
Use for: Dopamine helps encode reward prediction and learning.

Wood, Wendy, and Dennis Rünger. “Psychology of Habit.” Annual Review of Psychology, vol. 67, 2016, pp. 289–314. doi:10.1146/annurev-psych-122414-033417.
Use for: Habits form through repeated cue-context loops.

Laborde, Sylvain, et al. “Effects of Voluntary Slow Breathing on Heart Rate and Heart Rate Variability: A Systematic Review and a Meta-Analysis.” Neuroscience & Biobehavioral Reviews, vol. 138, 2022, article 104711. doi:10.1016/j.neubiorev.2022.104711.
Use for: Slow breathing supports parasympathetic regulation and stress reduction.

Lieberman, Matthew D., et al. “Putting Feelings into Words: Affect Labeling Disrupts Amygdala Activity in Response to Affective Stimuli.” Psychological Science, vol. 18, no. 5, 2007, pp. 421–428. doi:10.1111/j.1467-9280.2007.01916.x.
Use for: Naming emotions can reduce emotional reactivity.

Gollwitzer, Peter M. “Implementation Intentions: Strong Effects of Simple Plans.” American Psychologist, vol. 54, no. 7, 1999, pp. 493–503. doi:10.1037/0003-066X.54.7.493.
Use for: “If-then” plans improve behavior change under stress.

Forman, Evan M., et al. “A Comparison of Acceptance- and Control-Based Strategies for Coping with Food Cravings: An Analog Study.” Behaviour Research and Therapy, vol. 45, no. 10, 2007, pp. 2372–2386. doi:10.1016/j.brat.2007.04.004.
Use for: Acceptance and urge-surfing strategies help cravings pass without acting on them.

Hall, Kevin D., et al. “Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake.” Cell Metabolism, vol. 30, no. 1, 2019, pp. 67–77.e3. doi:10.1016/j.cmet.2019.05.008.
Use for: Ultra-processed foods increase intake and reinforce overeating patterns.

 
Dr. Brendan McCarthy is the founder and Chief Medical Officer of Protea Medical Center in Arizona. With over two decades of experience, he’s helped thousands of patients navigate hormonal imbalances using bioidentical HRT, nutrition, and root-cause medicine. He’s also taught and mentored other physicians on integrative approaches to hormone therapy, weight loss, fertility, and more.

If you’re ready to take your health seriously, this podcast is a great place to start.

👇 Tap Subscribe to learn more about what’s actually happening in your body, and what to do about it.

📘 Read Dr. McCarthy’s Book:
Jump Off the Mood Swing – A Sane Woman’s Guide to Her Crazy Hormones
https://www.amazon.com/Jump-Off-Mood-...

📲 Follow Dr. McCarthy:
Instagram: @drbrendanmccarthy
TikTok: @drbrendanmccarthy
Website: www.protealife.com

💬 Got a question or topic for a future episode? Let us know in the comments!