Dr. Brendan McCarthy

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!

In this episode of the podcast, Dr. Brendan McCarthy—Chief Medical Officer of Protea Medical Center in Tempe, Arizona—continues his in-depth progesterone series with a deep dive into reverse responders and an often-overlooked mechanism: hormone sulfation. Many women take progesterone expecting better sleep, calmer moods, and reduced anxiety—yet feel more alert, only mildly calmer, or see no benefit at all. This episode explains why that doesn’t mean progesterone is wrong for you. Dr. McCarthy breaks down: What progesterone reverse responding really is The difference between 5-alpha reductase pathways and sulfation How the brain uses sulfation to buffer stress and trauma Why progesterone may be stored instead of calming the nervous system The role of chronic stress, PTSD, perimenopause, and hormone volatility Why higher doses can make things worse How thoughtful, low-dose, individualized hormone therapy actually works 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 Episode 2 of this deep-dive hormone series, Dr. Brendan McCarthy—Chief Medical Officer of Protea Medical Center in Tempe, AZ—breaks down the part of progesterone almost no one talks about: its powerful role as a brain hormone. Most women are only taught that progesterone is about fertility and uterine lining. But the truth? Progesterone is a neurosteroid that influences your amygdala, hippocampus, and prefrontal cortex—three key brain regions that shape your stress response, emotional stability, sleep, memory, and self-trust. This episode covers: ✔️ Why perimenopause makes your brain feel “out of control” ✔️ The link between progesterone decline and anxiety, irritability, depression, night sweats, and brain fog ✔️ How progesterone converts to allopregnanolone (your brain’s natural calming signal) ✔️ Why women under chronic stress or in their late 30s–40s feel symptoms more intensely ✔️ How hormonal imbalance impacts memory, decision-making, and emotional regulation ✔️ Why you’re not broken—and what real validation and proper care looks like   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, pp. 10171–10179. Snyder, Jonathan S., et al. “Adult Hippocampal Neurogenesis and Stress Regulation.” Nature Reviews Neuroscience, vol. 12, 2011, pp. 1–9. Stanczyk, Frank Z., and Jerilynn C. Prior. “Progesterone and Progestins: A Review of Pharmacology, PK, and Clinical Use.” Steroids, vol. 82, 2014, pp. 1–8. Tu, Ming-Je, et al. “Oral, Vaginal, and Transdermal Progesterone: PK, Metabolism, and Tissue Distribution.” Drug Metabolism Reviews, vol. 52, no. 2, 2020, pp. 1–28. Wang, Jun, et al. “Stress, Amygdala Plasticity, and the Neuroendocrine Interface.” Nature Neuroscience, vol. 10, 2007, pp. 1093–1100. Weinstock, Marta. “The Hippocampus and Chronic Stress.” Neurochemical Research, vol. 42, 2017, pp. 1–12. World Health Organization. Progesterone and Reproductive Function: Clinical Perspectives. WHO, 2019.   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!