Dr. Brendan McCarthy

Why Progesterone Makes Some Women Feel Worse

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!

Progesterone & Your Brain: The Missing Link

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!

Progesterone: The Breakthrough Women Deserve

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!

The Truth About Estrone: What Your Lab Work Isn’t Telling You

Join Dr. Brendan McCarthy, Chief Medical Officer at Protea Medical Center in Tempe, Arizona, for a deep, practical breakdown of estrone—one of the most misunderstood and under-tested hormones in women’s health.
In this episode, Dr. McCarthy explains:
Why estrone matters far more than most routine labs suggest
How estrone relates to inflammation, insulin resistance, body fat, and chronic disease
What your estrone actually tells you about your metabolic load
How phase 1 and phase 2 liver detox pathways determine whether estrogen becomes helpful or harmful
How to use food, supplements, and prescriptions appropriately based on your labs
Red flags to watch for with boutique labs, overpriced clinics, and “hormone hacks”
You’ll learn exactly how clinicians should evaluate estrone, how to interpret the estrone–estradiol ratio, and how to identify where estrogen metabolism is blocked so you can take meaningful steps toward better health.
If you find this helpful, please subscribe and share it with someone who wants real, evidence-based hormone education.
 
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!

The Estrone Pathways That Predict Your Health: Labs Your Doctor Isn’t Running

In this episode, Dr. Brendan McCarthy, Chief Medical Officer at Protea Medical Center in Tempe, Arizona, takes you deep into the science of Estrone metabolism, why it becomes dominant during perimenopause and menopause, and the exact lab tests that uncover real root causes of symptoms like weight gain, mood swings, breast tenderness, irritability, fatigue, and sleep disruption.
This is Part 4 of our Estrone Series — and today’s focus is the real, science-based pathways behind estrone dominance:
Estrone : Estradiol ratios
2-, 4-, and 16-hydroxyestrone pathways
COMT function and methylation
Liver health and detoxification capacity
The nutrients and lifestyle factors that shift estrogen metabolism
How to interpret patterns your regular doctor may overlook
If you’ve ever been dismissed, told your symptoms are “normal,” or felt like something is wrong that no one is addressing — this episode gives you the tools, the labs, and the language to advocate for your health.
 
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!

Estrone & Cancer: The Truth About “The Forgotten Estrogen”

In Part 3 of the Forgotten Estrogen series, Dr. Brendan McCarthy—Chief Medical Officer of Protea Medical Center in Tempe, Arizona—dives deep into the misunderstood relationship between estrone and cancer.
For decades, women have been told to fear estrogen. But is estrogen really the enemy—or is it the environment within the body that determines risk?
Dr. McCarthy explains:
How estrone functions after menopause
Why estrogen became wrongly vilified after the 2002 Nurse’s Health Study
The truth about inflammation, insulin resistance, and detox pathways
The role of methylation, glutathione, and liver detox in estrogen metabolism
What lab markers actually matter (and how to interpret them)
Practical ways to support your hormones through nutrition, sleep, and lifestyle
This episode is about empowerment through knowledge, not fear.If you’ve ever been confused or afraid of estrogen, this conversation will change how you understand your body and your hormones.
 
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!

Estrone Explained (Part 2): The “Forgotten Estrogen” and Why It’s Not the Bad Guy

In this episode — Part 2 of our Estrone Series — Dr. McCarthy takes a deeper dive into estrone, the often misunderstood and overlooked estrogen. Learn:
Why estrone isn’t the “bad” estrogen it’s made out to be
How body fat, inflammation, and lifestyle influence estrone levels
The connection between estrone, insulin resistance, and breast health
Why oral estrogen can worsen symptoms for some women
Natural ways to support estrogen balance, including diet, nutrients, and detox pathways
Dr. McCarthy explains how understanding estrone can empower women through perimenopause and menopause — and why context and comprehensive lab work matter more than quick fixes.
💬 Have questions about estrone or hormone balance?Drop them in the comments — your feedback helps shape future episodes!
 
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!

Estrone Explained: How Lifestyle & Hormones Impact Women’s Health

In this episode, Dr. Brendan McCarthy, Chief Medical Officer of Protea Medical Center, dives deep into estrone, one of the three key estrogens, and explains why understanding it is crucial for women’s health.
Learn about:
The differences between estradiol, estriol, and estrone
How estrone levels shift during perimenopause and menopause
Why oral estrogen can dramatically increase estrone
The impact of lifestyle factors like diet, body fat, stress, alcohol, and sedentary behavior on estrogen balance
Practical tips to support healthy estrogen metabolism naturally
Dr. McCarthy breaks down complex biochemistry in a clear, actionable way so you can take charge of your hormonal health.
 
Citations: 1. Bulun, Serdar E., et al. “Aromatase and Estrogen Biosynthesis in Adipose Tissue.” Endocrine Reviews, vol. 23, no. 3, 2002, pp. 305–342. 2. Labrie, Fernand, et al. “Importance of the Intracrinology of Estrogen Synthesis in Peripheral Tissues in Postmenopausal Women.” Journal of Steroid Biochemistry and Molecular Biology, vol. 118, nos. 4–5, 2010, pp. 273–279. 3. Sasano, Hironobu, and Toshihiko Harada. “Differential Expression of Aromatase and 17β-Hydroxysteroid Dehydrogenase Isoenzymes in Human Tissues.” Journal of Steroid Biochemistry and Molecular Biology, vol. 86, no. 3–5, 2003, pp. 327–333. 4. Yager, James D., and Nancy E. Davidson. “Estrogen Carcinogenesis in Breast Cancer.” New England Journal of Medicine, vol. 354, no. 3, 2006, pp. 270–282. 5. Cavalieri, Ercole L., and Eleanor G. Rogan. “Depurinating Estrogen-DNA Adducts, Mechanisms of Formation, and Prevention.” Clinical Cancer Research, vol. 16, no. 3, 2010, pp. 596–602. 6. Suba, Zsuzsanna. “Circulating Estrogens and Estrogen Metabolism in Obese Women.” Journal of Clinical Endocrinology and Metabolism, vol. 98, no. 11, 2013, pp. 4336–4344. 7. Simpson, Evan R., and Konstanze C. Pike. “Aromatase Expression in Adipose Tissue: Relationship to Obesity and Insulin Resistance.” Endocrinology, vol. 156, no. 9, 2015, pp. 3422–3435. 8. Key, Timothy J., et al. “Circulating Sex Hormones and Breast Cancer Risk Factors in Postmenopausal Women: Reanalysis of 13 Studies.” British Journal of Cancer, vol. 105, no. 5, 2011, pp. 709–722. 9. Stanczyk, Frank Z., et al. “Oral, Transdermal and Injectable Hormone Therapy: Pharmacokinetics and Effects on Estrone/Estradiol Ratios.” Menopause, vol. 24, no. 9, 2017, pp. 1080–1090. 10. Santen, Richard J., et al. “Estrogen Bioidentical Hormone Therapy: Route of Administration and Risk.” Journal of Clinical Endocrinology and Metabolism, vol. 105, no. 7, 2020, pp. 2062–2074. 11. Zeleniuch-Jacquotte, Anne, et al. “Postmenopausal Levels of Estrone, Estradiol, and Estrone Sulfate and Breast Cancer Risk.” Cancer Epidemiology, Biomarkers & Prevention, vol. 23, no. 8, 2014, pp. 1531–1539. 12. Dall, Gabriella V., and Christine L. Clarke. “Local Estrogen Biosynthesis and Signaling in Breast Cancer Progression.” Steroids, vol. 78, no. 7, 2013, pp. 639–646. 13. Heald, Anthony H., et al. “Relationships Between Serum Estrone, Insulin Resistance, and Adiposity in Postmenopausal Women.” Clinical Endocrinology, vol. 67, no. 3, 2007, pp. 340–345. 14. Kuiper, George G. J. M., et al. “Estrogen Receptor β Selectivity of Estriol and Implications for Tissue-Specific Effects.” PNAS, vol. 94, no. 17, 1997, pp. 9105–9110. 15. Michnovicz, Joseph J., et al. “Dietary Indoles and Estrogen Metabolism: Effects of Cruciferous Vegetable Intake.” Journal of Nutrition, vol. 134, no. 12, 2004, pp. 3479S–
 
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!