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The Science of Optimal Hormone Health | Dr. Melanie Cree PHD

Episode 148, duration 1 hr 45 mins
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Episode 148

The Science of Optimal Hormone Health | Dr. Melanie Cree PHD

In this episode, I’m joined by Dr. Melanie Cree—physician-scientist, pediatric endocrinologist, and one of the leading researchers redefining how we understand and treat Polycystic Ovary Syndrome (PCOS). PCOS affects millions of women, yet it's still underdiagnosed, misunderstood, and often mistreated. Dr. Cree cuts through the confusion, offering a deeply scientific yet compassionate look at what’s really driving this complex condition—from insulin resistance and mitochondrial dysfunction to skeletal muscle quality and fertility trajectories across a woman’s lifespan.

We cover:

  • Why PCOS isn’t a single disease—and what two phenotypes may explain the full picture
  • How muscle, liver, and fat interact in PCOS
  • The misunderstood role of testosterone, insulin, and SHBG in diagnosis
  • What muscle biopsies reveal about teenage girls with PCOS
  • Intramuscular fat, mitochondrial impairment, and the true cost of sedentary muscle
  • How early lifestyle and exercise interventions could change the future of PCOS care
  • What GLP-1 agonists and amino acid supplements might offer for treatment
Whether you’re a clinician, patient, or advocate for women’s health, this episode will give you a whole new lens on PCOS—and why skeletal muscle may be the most overlooked (and powerful) organ in the conversation.

Who is Dr. Melanie Cree?

Dr. Melanie Cree is a board-certified pediatric endocrinologist and Associate Professor at the University of Colorado and Children’s Hospital Colorado, where she directs a leading multidisciplinary PCOS clinic. Her research bridges metabolic medicine and muscle physiology, with clinical trials exploring semaglutide, amino acid therapy, liver metabolism, and insulin resistance in adolescents.
Watch the Episode Episode Notes Timestamps Read the Blog Transcripts

In this episode, we discuss:
– Why PCOS isn’t a single disease—and what two phenotypes may explain the full picture
– How muscle, liver, and fat interact in PCOS
– The misunderstood role of testosterone, insulin, and SHBG in diagnosis
– What muscle biopsies reveal about teenage girls with PCOS
– Intramuscular fat, mitochondrial impairment, and the true cost of sedentary muscle
– How early lifestyle and exercise interventions could change the future of PCOS care
– What GLP-1 agonists and amino acid supplements might offer for treatment

00:00 – Intro to PCOS: Why most women still don’t get real answers

03:00 – Dr. Melanie Cree’s mission: Advocacy, research, and a new liver pathway

07:00 – PCOS isn’t one disease: Metabolic vs. reproductive phenotypes

12:00 – Why lifestyle changes work—and why “just lose weight” isn’t enough

16:00 – Fertility, follicle congestion, and why some women conceive more easily after 35

21:00 – Diagnosing PCOS in teens vs. adults—and why ultrasounds mislead

26:00 – Testosterone, SHBG, and the lab mess misdiagnosing women

36:00 – Muscle in PCOS: Why high testosterone ≠ more muscle

41:00 – Mitochondrial dysfunction and insulin resistance in teen girls

46:00 – IMAT, marbled muscle, and early cardiovascular risk

53:00 – How fat in and around muscle affects insulin signaling

1:06:00 – MPS, amino acids, and resistance training in obesity

1:16:00 – Lifestyle vs. semaglutide: Surprising results from Dr. Cree’s trial

1:22:00 – Low-glycemic diets, liquid sugar, and reactive hypoglycemia

1:26:00 – Protein, GLP-1s, and lean mass loss: What matters most

1:30:00 – GLP-1s vs. metformin—and their full-body metabolic effects

1:37:00 – Can PCOS be reversed? Why “lifestyle-managed” is more accurate

1:40:00 – Brain remodeling, hunger, and GLP-1s in teens vs. adults

1:43:00 – Compounded GLP-1s, insurance gaps, and what’s next in PCOS care

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by | Apr 15, 2025

Evy Poumpouras

Evy Poumpouras is a multi-platform journalist, host, and exclusive contributor to NBC across all their news platforms, covering national security, law enforcement, and crime. Evy’s book, BECOMING BULLETPROOF, was released by Simon & Schuster in 2020 and covers a wide range of topics, including personal protection, behavioral analysis, situational awareness, and how to live life fearlessly. Outside of her role as a journalist, Evy is a TEDx speaker whose expertise is sought worldwide.

 Dr. Susan Peirce Thompson

Susan Peirce Thompson, Ph.D. is a faculty member in brain and cognitive sciences at the University of Rochester, a multiple New York Times bestselling author, and a keynote speaker on how the brain supports human flourishing. In 2014, she founded Bright Line Eating, a worldwide movement dedicated to helping people achieve permanent weight loss maintenance. Over 115,000 people from more than 100 countries have taken her courses and you can find her online at BrightLineEating.com or SusanPeirceThompson.com.

Dr. Mark Hyman

Mark Hyman, MD, has devoted his life to helping others discover optimal health and address the root causes of chronic disease through the power of Functional Medicine. Dr. Hyman is a practicing family physician and an internationally recognized leader, speaker, educator, and advocate in the field of Functional Medicine. He is a co-founder and the Chief Medical Officer of Function Health, founder and Director of The UltraWellness Center, founder of Cleveland Clinic Center for Functional Medicine and Board Member for The Institute of Functional Medicine.

He is the founder and chairman of the Food Fix Campaign, dedicated to transforming our food and agriculture system through policy. Dr. Hyman is also the host of one of the leading health podcasts, The Dr. Hyman Show, with 300+ million downloads and a fifteen-time New York Times best-selling author. He is a regular medical contributor to several television shows and networks, including CBS This Morning, Today, Good Morning America, The View, Fox and CNN.


Jeff Cavalier

Jeff Cavalier is a fitness guru, social media star, personal trainer, and former head physical therapist of the New York Mets (professional baseball team). Jeff earned a Bachelor of Science in Physioneurobiology/Premedicine and a Master's degree in Physical Therapy from the University of Connecticut. He is a Certified Strength and Conditioning Specialist (CSCS) by the National Strength and Conditioning Association (NSCA). Jeff served as both the Head Physical Therapist and Assistant Strength Coach for the New York Mets during the National League East Championship 2006, 2007, and 2008 seasons. During this time, he coached some of the game’s most accomplished players, including future Hall of Fame pitchers Tom Glavine and Pedro Martinez, and perennial all-stars Carlos Delgado, Carlos Beltran, David Wright, Jose Reyes, and Billy Wagner, to name just a few. In addition to physiotherapy and training, Jeff is an author and lecturer speaking on topics such as baseball injury prevention, sport-specific conditioning, sports training, and injury rehabilitation and prevention. Jeff founded ATHLEAN-X Training System to share methods and techniques used by some of the greatest athletes to forge explosive and strong physiques. This is a science-based training system allowing anyone to get the same results as professional athletes.

Sal Di Stefano

Sal Di Stefano’s passion for fitness began when he picked up his first barbell at 13 years old. Any other teenager would have done a set of curls, but legend has it, Sal did squats. He was always different like that – and it wasn’t long before everyone would notice.

At age 18, Sal started working as a personal trainer, becoming the youngest general manager at 24 Hour Fitness by 19 years old. Not long after, he opened his own studio. Its reputation and success proved he was more than a personal trainer, but also a gifted businessman. And it was this entrepreneurial spirit that guided Sal to where we see him today.

He is the voice of Mind Pump, a published author, and one of the most trusted and respected faces in the fitness industry. Sal is an indispensable podcast host: the one who summarizes research when Justin and Adam trip over scientific words, the proverbial guinea pig when there’s a new peptide, and the conductor trying his best to keep conversation on track when we all know it’s headed off the rails.

Michelle Shapiro

Michelle Shapiro is an integrative/ functional Registered Dietitian in NYC who has, over the past decade, helped thousands of clients reverse their anxiety, heal long-standing gut and complex immune issues, and approach their weight in a loving way. Michelle has a virtual private practice with seven nutritionists who help clients work one-on-one towards these goals. She is the host of the Quiet the Diet Podcast, where she helps listeners bridge the gap between body positivity and functional nutrition.

Massy Arias

Massy Arias is a certified health and wellness coach, trainer, and entrepreneur. She is the founder of her own fitness and wellness brand, TRU Training and TRU Supplements. Through a transformative approach that unites purposeful movement with tools for mental and emotional strength, Massy inspires people to reclaim their power from the inside out. Her journey of overcoming personal obstacles and taking control of her life has shaped her into a leader whose knowledge, resilience, and authenticity resonate with people of all ages and backgrounds. Born in the Dominican Republic, Massy is bilingual and connects with her international community in both English and Spanish. She is a proud mother to her daughter, Indi, and currently serves as an athlete for the global brand Adidas, continuing to lead by example and inspire millions worldwide.

Jeff Cavalier

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Heidi Somers

Heidi Somers is an entrepreneur, creator, and coach who has dedicated the last decade to helping millions of women transform their bodies, their confidence, and their lives.

Originally studying biology to become a doctor, Heidi discovered her real calling after experiencing her own fitness and mindset transformation. What started with sharing simple tips online grew into two globally recognized brands: Buffbunny Collection, a leading women’s activewear company, and Grounds, a fitness app built to give women the tools, education, and community they deserve.

Alan Argon

Alan Aragon is a nutrition researcher and educator with over 30 years of success in the field. He is known as one of the most influential figures in the fitness industry’s movement towards evidence-based information. His notable clients include Stone Cold Steve Austin, Derek Fisher, and Pete Sampras. Alan has collaborated on over 30 peer-reviewed publications, and counting. He co-authored Nutrient Timing Revisited, the most-viewed article in the history of the Journal of the International Society of Sports Nutrition (JISSN). He also is the lead author of the ISSN Position Stand on Diets & Body Composition. Alan is the founder and Editor-In-Chief of Alan Aragon's Research Review (AARR), the original and longest-running research review publication in the fitness industry. Alan founded the Fit Advancement Mentorship (FAM), which is a multi-faceted educational hub for fitness professionals and enthusiasts.

Shade Zahrai

Dr. Shadé Zahrai is a behavioral researcher, award-winning peak performance educator, and leading authority on confidence and self-doubt. A former corporate lawyer with an MBA and background in psychology, she has designed and delivered transformative programs for Fortune 500 giants including Google, Microsoft, LVMH, JP Morgan, and McKinsey. Named one of LinkedIn’s Top Voices for career development, Shadé has taught over 7 million learners on LinkedIn Learning. Her TEDx talks and viral videos have amassed more than 300 million views, and her work has been featured in The New York Times, Adweek, CNBC, and Yahoo Finance.

Jocko Willink

Jocko Willink is a decorated retired U.S. Navy SEAL officer, co-author of the #1 New York Times bestsellers Extreme Ownership: How U.S. Navy SEALs Lead and Win and The Dichotomy of Leadership, and host of the top-rated Jocko Podcast. He is the co-founder and Chief Executive Officer of Echelon Front, a premier leadership consulting firm; the founder of Jocko Fuel, a performance nutrition and lifestyle company committed to clean, uncompromising quality; and the co-founder of Origin USA, a Made in America company producing apparel, boots, and gear. Across his ventures, Jocko serves as an instructor, speaker, executive coach, and strategic advisor.

Jocko spent 20 years in the SEAL Teams, serving in both enlisted and officer roles before rising to command SEAL Team Three’s Task Unit Bruiser during the Battle of Ramadi. There, he led combat operations that supported the U.S. Army’s 1st Armored Division “Ready First” Brigade in bringing stability to one of the most violent regions in Iraq. Task Unit Bruiser became the most highly decorated Special Operations unit of the Iraq War.

Following his combat deployments, Jocko served as Officer-in-Charge of training for all West Coast SEAL Teams, where he spearheaded the development of leadership training and personally mentored the next generation of SEAL leaders. His career awards include the Silver Star, the Bronze Star, and numerous other personal and unit commendations.

Since retiring from the Navy in 2010, Jocko has dedicated himself to sharing the leadership principles forged in combat to help leaders in business, government, education, and non-profits win on their own battlefields. He built Jocko Fuel after discovering harmful levels of heavy metals in a supplement he and his family once used daily, committing to a standard of only what you need—none of what you don’t. Through Origin USA, he champions American manufacturing, producing world-class apparel and gear entirely in the U.S.

Michelle Shapiro

Lorem Ipsum is simply dummy text of the printing and typesetting industry. Lorem Ipsum has been the industry's standard dummy text ever since the 1500s, when an unknown printer took a galley of type and scrambled it to make a type specimen book. It has survived not only five centuries, but also the leap into electronic typesetting, remaining essentially unchanged. It was popularised in the 1960s with the release of Letraset sheets containing Lorem Ipsum passages, and more recently with desktop publishing software like Aldus PageMaker including versions of Lorem Ipsum.

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Layne Norton

As a self-proclaimed nerd who lifts heavy things, Layne completed his PhD in Nutritional Sciences with honors from the University of Illinois in 2010. His competitive athletic career highlights include four USA Powerlifting National titles (93kg weight class), most recently winning gold at the 2024 International Powerlifting Federations M1 World Championship (93kg) and setting a new M1 world record deadlift at 328kg. Layne helped popularize flexible dieting and online nutrition coaching using evidence-based methods, coaching over 1700 clients. In recent years, Layne has focused on ways to share his knowledge with people on a wider scale, including building a coaching team, writing books, developing a nutrition coaching app and educational courses, and launching Outwork Nutrition, an evidence-based supplement company. Layne’s passion is helping others achieve their goals through education and hard work.

Arthur Brooks

Arthur Brooks is a professor at the Harvard Kennedy School and the Harvard Business School, where he teaches courses on leadership and happiness. He is also the host of the weekly podcast “Office Hours with Arthur Brooks,” and a columnist at The Atlantic, where he writes the popular weekly “How to Build a Life” column.

Brooks is the author of 15 books, including the #1 New York Times bestsellers, Build the Life You Want, co-authored with Oprah Winfrey, and From Strength to Strength: Finding Success, Happiness, and Deep Purpose in the Second Half of Life. His next book, The Meaning of Your Life: Finding Purpose in an Age of Emptiness, will be released on March 31, 2026.

Brooks is one of the world’s leading experts on the science of human happiness, appearing in the media and traveling the world to teach people in private companies, universities, public agencies, and faith communities how they can live happier lives and bring greater well-being to others.

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