Podcast Summary: The Dr. Gabrielle Lyon Show – "GLP-1 & PCOS Breakthroughs: How Ozempic is Changing Women’s Health | Dr. Melanie Cree"

Introduction

In the April 15, 2025 episode of The Dr. Gabrielle Lyon Show, host Dr. Gabrielle Lyon welcomes Dr. Melanie Cree, a distinguished pediatric endocrinologist and leading researcher in the treatment of Polycystic Ovary Syndrome (PCOS). The episode delves into the latest advancements in PCOS management, challenging traditional perceptions, and exploring groundbreaking treatments like GLP-1 agonists, particularly Ozempic, and their impact on women's health.

Understanding PCOS

Dr. Cree begins by clarifying that the term "Polycystic Ovary Syndrome" is a misnomer, as most women with PCOS do not have cysts on their ovaries. She emphasizes the syndrome's broad spectrum, highlighting two primary phenotypes:

1. Reproductive Phenotype: Characterized by hormonal imbalances, particularly elevated luteinizing hormone (LH) leading to increased testosterone production. This phenotype is closely linked to infertility issues.
2. Metabolic Phenotype: Strongly associated with insulin resistance and an elevated risk of type 2 diabetes, especially in individuals with obesity.

Key Insights:

• Prevalence and Impact: PCOS affects millions of women globally and is the leading cause of female infertility in the United States. The prevalence is increasing in tandem with rising obesity rates.
• Genetic and Environmental Factors: Dr. Cree explains that PCOS likely comprises two distinct conditions based on their phenotypic presentations, influenced by genetic predispositions and insulin sensitivity.

Notable Quote:

"PCOS is the leading cause of female infertility in the United States, and its prevalence is rising as obesity rates climb." – Dr. Melanie Cree [07:49]

Latest Breakthroughs in PCOS Management

Dr. Cree shares her pioneering research on a newly discovered metabolic pathway involving glycerol and glutathione in the liver. This pathway plays a crucial role in preventing liver fibrosis by neutralizing reactive oxygen species generated from excess fat combustion.

Key Points:

• New Metabolic Pathway: Glycerol, the backbone of fat, can be converted into glutathione, a compound that mitigates liver fibrosis.
• Research Collaborations: Dr. Cree collaborates with leading organizations like PCOS Challenge to advocate for patient education, funding, and clinical trials aimed at improving PCOS treatment.

Notable Quote:

"We found that glycerol can be turned into glutathione, which mops up reactive oxygen species, preventing fibrosis in the liver." – Dr. Melanie Cree [04:40]

Muscle and Insulin Resistance in PCOS

A significant portion of the discussion centers on the relationship between skeletal muscle function and insulin resistance in individuals with PCOS. Dr. Cree presents findings from her studies showing that young individuals with PCOS exhibit lower rates of oxidative phosphorylation in muscles, leading to heightened insulin resistance regardless of their weight.

Key Points:

• Skeletal Muscle Insulin Resistance: Girls with PCOS, both overweight and lean, demonstrate impaired mitochondrial function in skeletal muscles, contributing to systemic insulin resistance.
• Intramuscular Adipose Tissue (IMAT): Elevated IMAT is associated with increased insulin resistance and cardiovascular risks. Dr. Cree highlights the distinction between IMAT and intramyocellular lipids (IMCL), noting that IMAT is detrimental to metabolic health.

Notable Quote:

"Girls with PCOS had lower rates of oxidative phosphorylation than girls of the same weight without PCOS." – Dr. Melanie Cree [43:54]

Treatment Approaches: Lifestyle Changes and Medications

Dr. Cree underscores the primacy of lifestyle modifications in managing PCOS, emphasizing that these interventions are beneficial irrespective of the patient's weight. She discusses the role of medications like Metformin and emerging treatments involving GLP-1 agonists.

Key Points:

• Lifestyle Interventions: Focus on reducing sugar intake, particularly liquid calories, and increasing physical activity to enhance insulin sensitivity.
• Metformin Usage: Traditionally used to improve insulin sensitivity, Metformin remains a cornerstone in PCOS treatment but has limitations in efficacy.
• GLP-1 Agonists (e.g., Ozempic): These medications have shown significant promise in managing PCOS by facilitating weight loss and improving metabolic profiles.

Notable Quote:

"Lifestyle changes are recommended for every patient with PCOS, regardless of body size, because even those who don't have extra weight have insulin resistance." – Dr. Melanie Cree [09:54]

GLP-1 Agonists in PCOS: A Game Changer

The conversation delves deep into the transformative potential of GLP-1 agonists like Ozempic in treating PCOS. Dr. Cree shares insights from her recent trials, highlighting the efficacy of these medications in promoting weight loss and improving hormonal and metabolic parameters.

Key Points:

• Efficacy of GLP-1s: Dr. Cree's studies indicate that GLP-1 agonists lead to substantial weight loss and improvement in testosterone and cholesterol levels, comparable to lifestyle interventions.
• Sustainability Challenges: While GLP-1s are effective, their benefits are often contingent on continued usage, as discontinuation can lead to weight regain and a resurgence of PCOS symptoms.
• Regulatory Hurdles: Dr. Cree discusses the challenges in obtaining approval for trials involving adolescents and the complexities of navigating FDA regulations.

Notable Quote:

"Even in the absence of weight loss, by eating a healthier diet, you can improve your PCOS." – Dr. Melanie Cree [78:59]

Diagnostic Challenges and Misconceptions

Dr. Cree addresses the difficulties in diagnosing PCOS accurately due to variability in hormone assays and inconsistent diagnostic criteria. She advocates for standardized testing methods, including liquid chromatography-mass spectrometry (LC-MS/MS), to ensure reliable measurement of testosterone levels.

Key Points:

• Hormone Assay Variability: Different laboratories use varying cutoff points for testosterone levels, leading to inconsistent diagnoses.
• Importance of Free Testosterone: In patients with obesity, total testosterone may appear normal due to low sex hormone-binding globulin (SHBG). However, free testosterone, which is bioactive, remains elevated and is a more accurate indicator of PCOS.
• Recommendations for Accurate Diagnosis: Dr. Cree advises testing testosterone levels in the morning during menstrual bleeding and ensuring the use of LC-MS/MS methods.

Notable Quote:

"If a patient is having testosterone drawn, they should ask for a testosterone panel in the morning during menstrual bleeding and ensure it's run by LC-MS/MS." – Dr. Melanie Cree [29:20]

Muscle Quality and Body Composition

The discussion explores how PCOS affects muscle mass and quality. Contrary to expectations, individuals with the metabolic phenotype of PCOS do not exhibit increased muscle mass despite elevated testosterone levels. This paradox is attributed to impaired muscle protein synthesis and the detrimental effects of IMAT.

Key Points:

• Muscle Mass Discrepancies: Women with PCOS, especially those with obesity, do not have more muscle mass compared to their lean counterparts.
• Impact of IMAT: Excess fat within and around muscle cells hampers muscle function and contributes to insulin resistance.
• Exercise and Muscle Health: Dr. Cree emphasizes the role of physical activity in reducing IMAT and improving muscle quality, thereby enhancing insulin sensitivity.

Notable Quote:

"Individuals with excess weight do not have more muscle than individuals of the same BMI who don't have PCOS." – Dr. Melanie Cree [18:36]

Dietary Interventions and Protein Intake

Dr. Cree highlights the significance of dietary modifications in managing PCOS. She advocates for a low glycemic diet, reducing liquid and simple carbohydrates, and increasing protein intake to support muscle maintenance and improve metabolic health.

Key Points:

• Low Glycemic Diet: Eliminating liquid calories and simple carbohydrates helps stabilize insulin levels, reducing testosterone production.
• Protein Consumption: Ensuring adequate protein intake is crucial for protecting lean muscle mass during weight loss.
• Dietary Trials: Recent studies indicate that dietary changes alone, even without significant weight loss, can lead to improvements in hormonal and metabolic parameters comparable to medication.

Notable Quote:

"Even in the absence of weight loss, by eating a healthier diet, you can improve your PCOS." – Dr. Melanie Cree [78:59]

Challenges and Future Directions

Despite promising advancements, Dr. Cree points out the ongoing regulatory and systemic challenges in PCOS research and treatment. She calls for better education, standardized diagnostic criteria, and increased funding to explore innovative treatments like amino acid supplementation.

Key Points:

• Regulatory Barriers: Obtaining approval for novel treatments involves navigating complex FDA requirements, often delaying essential research.
• Educational Gaps: There is a significant misconception among the public and healthcare providers that lifestyle changes are ineffective for PCOS, leading to underdiagnosis and inadequate treatment.
• Research Needs: Dr. Cree emphasizes the necessity for extensive studies to establish normative data for hormone levels and further investigate the role of muscle and metabolic health in PCOS.

Notable Quote:

"The biggest misconception is that lifestyle doesn't work and people give up." – Dr. Melanie Cree [94:43]

Conclusion

Dr. Melanie Cree's insights shed light on the intricate mechanisms underlying PCOS and the transformative potential of GLP-1 agonists like Ozempic in its management. By bridging clinical practice with cutting-edge research, Dr. Cree advocates for a holistic approach that combines lifestyle modifications with targeted pharmacological interventions to empower women in managing their health effectively.

Final Quote:

"PCOS can be lifestyle managed. The relationship between weight and insulin resistance is inherently tied, especially in the metabolic PCOS." – Dr. Melanie Cree [95:47]

Resources and Further Reading

For listeners interested in exploring Dr. Cree's research and accessing resources on managing PCOS, additional information can be found through the podcast's description links.

This summary encapsulates the core discussions, insights, and conclusions from the episode, providing a comprehensive overview for those who haven't listened to the full podcast.