GLP-1 Medications and Brain Connectivity

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.

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Find Dr. Melanie Cree at:

University of Colorado - https://som.cuanschutz.edu/Profiles/Faculty/Profile/22449

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Timestamps:

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

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

pathway

07:00 – PCOS is not one disease: Metabolic vs. reproductive phenotypes

12:00 – Why lifestyle changes work—and why the messaging around “just lose weight” is

all wrong

16:00 – Fertility, follicle congestion, and why some women with PCOS conceive more

easily at 35+

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

26:00 – Testosterone testing: The lab mess, SHBG, and how women are misdiagnosed

36:00 – Muscle in PCOS: Why women with high testosterone don’t have more muscle

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

46:00 – IMAT, marbled muscle, and early signs of cardiovascular disease

53:00 – How fat inside and around muscle impacts insulin signaling and metabolic

health

59:00 – Targeting IMAT: What biopsies reveal, and why location of fat matters more

than total %

1:06:00 – Muscle protein synthesis, amino acids, and resistance training response in

obesity

1:16:00 – Lifestyle vs. semaglutide: Surprising diet findings from Dr. Cree’s recent

trial

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

1:26:00 – Protein, GLP-1s, and lean mass loss: What matters more than the drug itself

1:30:00– Why GLP-1s may eventually replace metformin—and the organ-wide benefits

emerging

1:37:00 – Can PCOS be reversed? Why Dr. Cree says “lifestyle managed” is more accurate

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

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

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