Dr. Brendan McCarthy

In this episode, Dr. Brendan McCarthy dives deep into the psychology of ultra-processed foods, compulsive eating, shame, and why so many people feel trapped in unhealthy food cycles. This conversation goes far beyond calories and willpower. Dr. McCarthy explains how ultra-processed and hyper-palatable foods are intentionally engineered to drive repeat consumption, how emotional memories and stress shape cravings, and why shame-based nutrition advice often makes the problem worse instead of better. Topics covered in this episode include: • How ultra-processed foods affect the brain• Why compulsive eating is learned — and can be unlearned• The connection between trauma, stress, and food cravings• The difference between guilt and shame• How marketing and emotional associations shape eating habits• Why “clean eating” language can be harmful• The neuroscience of cravings, dopamine, serotonin, and reward• What real freedom with food actually looks like• Why self-compassion matters in healing If you’ve ever felt trapped in cycles of emotional eating, binge eating, food guilt, or shame around nutrition, this episode is for you. 📚 Research & References Tangney, June Price, Jeff Stuewig, and Debra J. Mashek. “Moral Emotions and Moral Behavior.” Annual Review of Psychology, vol. 58, 2007, pp. 345–372. Nechita, Dan M., et al. “Shame and Eating Disorders Symptoms: A Meta-Analysis.” International Journal of Eating Disorders, vol. 54, no. 11, 2021, pp. 1899–1945. Tomiyama, A. Janet. “Weight Stigma Is Stressful. A Review of Evidence for the Cyclic Obesity/Weight-Based Stigma Model.” Appetite, vol. 82, 2014, pp. 8–15. Levinson, Julia A., et al. “A Systematic Review of Weight Stigma and Disordered Eating Cognitions and Behaviors.” Obesity Reviews, 2024. Kelly, Allison C., et al. “Self-Compassion and Shame in Eating Disorder Recovery.” International Journal of Eating Disorders, vol. 47, no. 5, 2014, pp. 512–515. 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. Schultz, Wolfram. “Dopamine Reward Prediction Error Coding.” Dialogues in Clinical Neuroscience, vol. 18, no. 1, 2016, pp. 23–32. 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. Morales, Irene, and Kent C. Berridge. “‘Liking’ and ‘Wanting’ in Eating and Food Reward: Brain Mechanisms and Clinical Implications.” Physiology & Behavior, vol. 227, 2020, article 113152. 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. Gearhardt, Ashley N., et al. “Social, Clinical, and Policy Implications of Ultra-Processed Food Addiction.” BMJ, vol. 383, 2023, p. e075354. Haedt-Matt, Alissa A., and Pamela K. Keel. “Revisiting the Affect Regulation Model of Binge Eating: A Meta-Analysis of Studies Using Ecological Momentary Assessment.” Psychological Bulletin, vol. 137, no. 4, 2011, pp. 660–681. Wagner, Heather S., Traci Mann, and Janet Tomiyama. “The Myth of Comfort Food.” Health Psychology, vol. 33, no. 12, 2014, pp. 1552–1557. Schaefer, Lauren M., et al. “Examining the Role of Craving in Affect Regulation Models of Binge Eating.” International Journal of Eating Disorders, 2023. Jansen, Anita, et al. “A Learning Model of Binge Eating: Cue Reactivity and Cue Exposure.” Behaviour Research and Therapy, vol. 88, 2016, pp. 75–84. Craske, Michelle G., et al. “Maximizing Exposure Therapy: An Inhibitory Learning Approach.” Behaviour Research and Therapy, vol. 58, 2014, pp. 10–23. Grilo, Carlos M. “Psychological and Behavioral Treatments for Binge-Eating Disorder.” Journal of Clinical Psychiatry, vol. 78, suppl. 1, 2017, pp. 20–24. Dr. Brendan McCarthy is the founder and Chief Medical

In this final episode of the Progesterone Promise series, Dr. Brendan McCarthy, Chief Medical Officer of Protea Medical Center, breaks down one of the most misunderstood hormones in women’s health: progesterone. Progesterone is not “good” or “bad.” It’s contextual. In today’s world of quick sound bites and social media medicine, hormones are often reduced to oversimplified claims like “progesterone fixes anxiety” or “progesterone causes breast cancer.” The truth? It depends on your body, your stress levels, your liver health, your inflammation, your delivery method, and whether you're using bioidentical progesterone or synthetic progestins. Citations: 1. Oral Progesterone → First-Pass Metabolism & Allopregnanolone Claim:Oral micronized progesterone undergoes significant hepatic first-pass metabolism, increasing neuroactive metabolites (especially allopregnanolone), which positively modulate GABA-A receptors and produce sedative/anxiolytic effects. Core Evidence: Simon et al., 1993; de Lignières et al., 1995; Freeman et al., 1990 — Oral progesterone produces measurable neuroactive metabolites. Paul & Purdy, 1992; Rupprecht et al., 2001 — Allopregnanolone enhances GABA-A receptor activity. Supports:Sedation variability by route • Neurosteroid generation • GABA-A modulation 2. Sulfation vs 5α-Reduction → Opposing Neurologic Effects Claim:Progesterone metabolites can produce calming (5α-reduced) or excitatory (sulfated) neurologic effects depending on enzyme routing. Core Evidence: Majewska et al., 1990 — Pregnenolone sulfate negatively modulates GABA-A. Wu et al., 1991 — Sulfated neurosteroids enhance NMDA signaling. Schumacher et al., 2007; Reddy, 2010 — Pathway reviews of sulfation vs 5α-reduction. Supports:Reverse responding hypothesis • Divergent neurologic experiences • Enzyme-dependent effects 3. Stress & Enzyme Modulation Claim:Chronic stress alters HPA axis tone and hepatic enzyme expression, influencing steroid metabolism balance. Core Evidence: McEwen, 1998 — Allostatic load model. Charmandari et al., 2005 — Cortisol’s systemic regulatory effects. Zanger & Schwab, 2013; Gibson & Skett, 2001 — Stress alters cytochrome P450 expression. Supports:Stress-biased metabolism • Context-dependent hormone response 4. Breast Tissue Signaling & Context Claim:Progesterone influences mammary differentiation and interacts with estrogen signaling in context-dependent ways. Core Evidence: Brisken & O’Malley, 2010 — Progesterone receptor biology in breast tissue. Beleut et al., 2010 — RANKL mediates progesterone-driven proliferation. Hofseth et al., 1999 — PR-ER signaling interaction. Stanczyk & Bhavnani, 2014 — Natural vs synthetic differences in breast effects. Supports:Lobuloalveolar differentiation • RANKL pathway • Context-dependent proliferation 5. Synthetic Progestins vs Bioidentical Progesterone Claim:Synthetic progestins differ structurally and bind off-target receptors, producing distinct tissue effects. Core Evidence: Stanczyk et al., 2013 — Receptor binding differences. Sitruk-Ware, 2004 — Biologic comparisons. Chlebowski et al., 2003 (WHI) — Breast cancer signal with CEE + MPA. Supports:Structural divergence • Receptor-level differences • WHI clarification 6. Route of Delivery Differences Claim:Oral, vaginal, transdermal, and sublingual progesterone produce distinct pharmacokinetic profiles and tissue targeting. Core Evidence: Simon, 1995 — Oral vs vaginal PK comparison. Cicinelli et al., 2000 — “First uterine pass effect.” Wren et al., 2003 — Route-dependent systemic levels. Supports:Uterine targeting • Neurosteroid variability • Sedation differences 7. Progesterone, PMS & Migraine Claim:Neurosteroid fluctuations influence GABAergic tone and may contribute to PMS and migraine susceptibility. Core Evidence: Backstrom et al., 2011 — Allopregnanolone fluctuations in PMS. Reddy & Rogawski, 2002 — Neurosteroids and seiz

Unexplained infertility, PMS, and low progesterone are often dismissed when labs fall “within range.” In this episode, Dr. Brendan McCarthy explains why prolactin may be the missing piece. Learn how mildly elevated prolactin can suppress ovulation, lower progesterone, and impact fertility—even when labs appear normal. We also discuss common causes, symptoms, the role of stress and medications, and why diet (including gluten sensitivity) may matter. This episode focuses on precision medicine, not fear—helping you understand what standard reference ranges often miss. Citations: Research — Prolactin and Breast Cancer Risk Below are key epidemiologic and review papers that inform the discussion in this episode regarding prolactin and breast biology. These studies look at associations, not simple cause-and-effect relationships, and help explain why prolactin shows up in breast health conversations. Meta-analysis: circulating prolactin and breast cancer risk Wang M, et al. (2016).Plasma prolactin and breast cancer risk: a meta-analysis.Cancer Causes & Control. This meta-analysis pooled data from multiple observational studies comparing women with higher versus lower circulating prolactin levels. Across studies, higher prolactin levels were associated with a modest but statistically significant increase in breast cancer risk. The association was most evident in postmenopausal women and in hormone-receptor–positive tumors. This helps explain why prolactin is considered a relevant growth signal in breast tissue rather than just a “lactation hormone.” Systematic review and meta-analysis: prolactin levels across breast cancer cohorts Aranha AF, et al. (2022).Impact of prolactin levels in breast cancer: a systematic review and meta-analysis.Endocrine-Related Cancer. This more recent systematic review and meta-analysis evaluated circulating prolactin levels across breast cancer populations and control groups. Elevated prolactin levels were associated with higher breast cancer occurrence, with stronger associations seen in invasive cancers and hormone-receptor–positive disease. This paper adds weight to the idea that prolactin participates in breast biology in ways that matter clinically, even outside of pregnancy and breastfeeding. Prospective cohort studies: prolactin measured before diagnosis Tworoger SS, et al. (2004; 2006).Prospective analyses from large cohorts including the Nurses’ Health Study. In these studies, prolactin was measured years before any breast cancer diagnosis. Women with higher prolactin levels had a higher likelihood of developing breast cancer later, particularly estrogen-receptor–positive tumors in postmenopausal women. Because prolactin was measured before cancer developed, these studies help clarify timing and reduce the concern that elevated prolactin is simply a consequence of disease. Mechanistic context (supportive background) Experimental and translational studies show that prolactin receptor signaling influences mammary epithelial cell growth, differentiation, and interaction with estrogen signaling pathways. This provides a biologic backdrop for why epidemiologic associations between prolactin and breast cancer risk keep appearing across different study designs. How to read this as a clinician or patient These data do not mean prolactin “causes” breast cancer in a simple or deterministic way. What they do show is that prolactin is an active hormone in breast tissue, and chronically higher levels are consistently associated with changes in breast risk profiles across large populations. That’s why prolactin deserves attention in conversations about fertility, breast symptoms, and long-term hormonal signaling—not fear, and not dismissal. 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 m

In this episode, Dr. Brendan McCarthy, Chief Medical Officer of Protea Medical Center, explains why progesterone delivery systems matter—and how different routes change what progesterone actually does in the body. Part 4 of the progesterone series covers oral, topical, vaginal, rectal, injectable, and sublingual progesterone, breaking down which methods affect the brain, uterus, and breast tissue—and why choosing the right route is critical. If progesterone hasn’t worked for you in the past, the issue may not be the dose, but how it was delivered. This episode focuses on education, patient agency, and thoughtful hormone care—no shortcuts, no selling. Subscribe for more in-depth conversations on hormones and women’s health, and share with someone who may benefit. 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-Swing-Hormones/dp/0999649604 📲 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!

Dr. Brendan McCarthy, Chief Medical Officer of Protea Medical Center in Tempe, Arizona, brings closure to an important and often misunderstood topic: progesterone reverse responders. Some women take progesterone expecting calm, better sleep, and emotional balance — but instead experience anxiety, irritability, agitation, or feeling “wired but tired.” These responses are real, not imagined, and not a personal failure. In this episode, Dr. McCarthy explains: What progesterone reverse responding actually is (and what it is not) Why this reaction is not an intolerance or allergy How progesterone’s downstream metabolites affect the brain The difference between the 5-alpha reductase pathway and sulfation pathways Why labs can look “normal” while symptoms feel anything but Common mistakes providers make (pushing the dose, “waiting it out,” or masking symptoms) Why stress physiology plays a major role How thoughtful, patient-centered medicine can help women heal Most importantly, this episode emphasizes listening to women, validating lived experiences, and practicing medicine with curiosity, humility, and care. 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-Swing-Hormones/dp/0999649604 📲 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!

Have you taken progesterone expecting calm, better sleep, or relief from PMS… only to feel more anxious, wired, or worse overall? You are not a failure—and progesterone is not failing you. Your body is responding exactly as physiology dictates. The issue is how progesterone is being delivered and metabolized. In this episode, Dr. McCarthy explains: What it means to be a progesterone reverse responder How progesterone normally supports mood and brain chemistry through allopregnanolone Why some women experience paradoxical anxiety, insomnia, or agitation The role of the 5-alpha reductase pathway in progesterone metabolism Why oral progesterone can overwhelm the brain in certain women How PCOS, topical testosterone, stress, insulin resistance, and ultra-processed diets can amplify reverse responses Why kinetics and delivery method matter just as much as dosage 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-Swing-Hormones/dp/0999649604 📲 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 today’s episode, I’m opening the first chapter of what I believe is the most important series I’ve ever created — a deep dive into progesterone and why it became the heart of my medical practice. For more than 20 years, I’ve watched this “simple, humble hormone” transform women’s lives in ways most conventional medicine overlooks. What started in two small treatment rooms has grown into a 25,000 sq ft facility, and the core of our success comes down to understanding progesterone’s impact on the female brain, stress response, and emotional resilience. In this episode, I break down: Why progesterone is far more than a reproductive hormone How it regulates the female stress response (amygdala, hippocampus, prefrontal cortex) Why anxiety, insomnia, irritability, and emotional overwhelm often map directly to progesterone decline Why so many women feel “unraveled” in their 40s — and why it’s not their fault The science behind oral vs. sublingual progesterone (and why I use troches) How conventional medicine often misses the root cause The importance of physicians showing their work, their data, and their citations The lived stories and clinical outcomes that changed how I practice medicine If you’ve ever felt dismissed, unseen, or told that your anxiety or mood changes are “just stress,” this episode is for you. This is the beginning of a 7-part series where I break down the neurobiology, endocrinology, testing, dosing, delivery methods, breast health, perimenopause, and more. Citations: Brinton, Roberta Diaz, et al. “Neurosteroids and Brain Function.” Steroids, vol. 81, 2014, pp. 61–78. Epperson, C. Neill, et al. “New Insights into Perimenopausal Depression: A Neuroendocrine Vulnerability Framework.” The Lancet Psychiatry, vol. 9, no. 2, 2022, pp. 110–118. Frye, Cheryl A. “Neurosteroids—Endogenous Modulators of GABA_A Receptors.” Pharmacology & Therapeutics, vol. 116, no. 1, 2007, pp. 58–76. Genazzani, Andrea R., et al. “Progesterone, Stress, and the Brain.” Human Reproduction Update, vol. 16, no. 6, 2010, pp. 641–655. Meeker, John D., et al. “Environmental Endocrine Disruptors: Their Effects on Human Reproduction and Development.” Reproductive Toxicology, vol. 25, 2008, pp. 1–7. Mellon, Stanley H. “Neurosteroid Regulation of Central Nervous System Development.” Pharmacology & Therapeutics, vol. 116, 2007, pp. 107–124. Mizrahi, Romy, et al. “The Role of Allopregnanolone in Stress, Mood, and Trauma.” Neurobiology of Stress, vol. 11, 2019, 100198. Paul, Steven M., and Graziano Pinna. “Allopregnanolone: From Molecular Pathways to Therapeutic Applications.” Current Opinion in Neurobiology, vol. 48, 2018, pp. 90–96. Pluchino, Nicoletta, et al. “Progesterone and Allopregnanolone: Effects on the Central Nervous System in the Luteal Phase and in Perimenopause.” Gynecological Endocrinology, vol. 36, no. 6, 2020, pp. 441–445. Rasgon, Natalie L., et al. “Perimenopausal Changes in the Brain and Mood: A Review.” Journal of Clinical Endocrinology and Metabolism, vol. 107, no. 4, 2022, pp. 1120–1134. Reddy, Doodipala Samba. “The Neurosteroid Allopregnanolone and GABA-A Receptor Modulation in Epilepsy and Mood Disorders.” Frontiers in Neuroscience, vol. 12, 2018, 933. Schiller, Crystal E., et al. “The Neuroendocrinology of Perimenopausal Depression.” Trends in Neurosciences, vol. 44, no. 2, 2021, pp. 119–135. Schumacher, Michael, et al. “Neuroprotective Effects of Progesterone and Its Metabolites.” Frontiers in Neuroendocrinology, vol. 33, 2012, pp. 415–439. Selye, Hans. “The General Adaptation Syndrome and the Diseases of Adaptation.” Journal of Clinical Endocrinology, vol. 6, no. 2, 1946, pp. 117–230. Sheng, Jun, and György Buzsáki. “Neuronal Firing and Theta Oscillations in the Amygdala During Fear Conditioning.” Neuron, vol. 53, 2007, pp. 653–667. Smith, Sheryl S. “Progesterone Withdrawal Increases Neuronal Excitability in the Hippocampus: A GABA_A Mechanism.” Journal of Neuroscience, vol. 28, 2008, p