If progesterone makes you feel wired, anxious, angry, emotional, or unable to sleep, this episode is for you.

In this deeply important continuation of our reverse responding series, Dr. Brendan McCarthy—Chief Medical Officer of Protea Medical Center—returns to clarify what was missing in Episode 3C and to walk you through the real physiology, compassion, and treatment strategy behind reverse responding.

Reverse responding is not intolerance, weakness, anxiety, noncompliance, or failure. It is an adaptive response rooted in threat-state physiology, chronic stress, and lived experience. Your body is not broken—it is protecting you.

In this episode, Dr. McCarthy covers:

What reverse responding actually is (and what it is not)

The difference between sulfation and 5-alpha pathways

Why labs often miss this entirely

Why “just more progesterone” makes things worse

How trauma, chronic stress, and safety shape hormone response

The importance of earning permission from the nervous system

Practical treatment pillars:

Glycemic stability

Circadian safety and sleep rhythm

Reducing inflammatory load

Gentle nervous system regulation

Slow, low, respectful progesterone onboarding

Supplement strategies used clinically (and what to avoid)

Most importantly, this episode is a reminder:

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!

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?

This episode covers:

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!

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!

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!

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.

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 — 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?

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!