What is the role of Mounjaro (tirzepatide) in treating patients with Polycystic Ovary Syndrome (PCOS)?

Tirzepatide (Mounjaro) for Polycystic Ovary Syndrome (PCOS)

Tirzepatide (Mounjaro) is not currently FDA-approved for PCOS treatment, but may be considered as an adjunctive therapy in PCOS patients with obesity and metabolic dysfunction due to its significant weight loss and metabolic benefits.

Current PCOS Treatment Guidelines

• First-line pharmacological treatment for PCOS in women not attempting to conceive remains combined oral contraceptives (COCs), which suppress ovarian androgen secretion and increase sex hormone binding globulin 1
• Weight loss (even modest 5% reduction) significantly improves both metabolic and reproductive abnormalities in women with PCOS 2
• Metformin is recommended for women with PCOS who have cardiometabolic features such as abdominal obesity and insulin resistance 3
• Insulin-sensitizing agents, including metformin and thiazolidinediones, can improve insulin sensitivity and may positively impact risk factors for diabetes and cardiovascular disease in PCOS 2

Potential Role of Tirzepatide in PCOS

• Tirzepatide is a dual GIP/GLP-1 receptor co-agonist currently FDA-approved only for type 2 diabetes treatment 4, 5
• Tirzepatide has demonstrated unprecedented reductions in both HbA1c (1.24-2.58%) and body weight (5.4-11.7 kg) in type 2 diabetes patients 5
• The mechanism of action of tirzepatide addresses key pathophysiological aspects of PCOS:
  • Improves insulin sensitivity 5
  • Promotes significant weight loss 5
  • May reduce hyperinsulinemia which drives ovarian androgen production 6

Evidence for GLP-1 Based Therapies in PCOS

• The 2023 International Evidence-Based Guideline for PCOS notes that GLP-1 receptor agonists (similar to tirzepatide) have shown benefits in PCOS patients with obesity 2
• Limited studies exist specifically examining tirzepatide in PCOS, but other incretin-based therapies have shown promise:
  • Exenatide (GLP-1 agonist) has demonstrated similar efficacy to metformin for anthropometric and metabolic outcomes in PCOS 2
  • Liraglutide and semaglutide appear superior to placebo for anthropometric outcomes in PCOS 2

Clinical Considerations for Tirzepatide Use in PCOS

• Tirzepatide would be most appropriate for PCOS patients who:
  • Have obesity (BMI ≥30 kg/m²) or overweight with comorbidities 2, 6
  • Show features of insulin resistance or metabolic syndrome 6
  • Have not achieved adequate response with first-line treatments 2
• Tirzepatide may not benefit PCOS patients of normal weight without metabolic dysfunction 6
• Common adverse effects include gastrointestinal symptoms (nausea, diarrhea, vomiting), though the dual receptor mechanism may potentially reduce these compared to GLP-1 agonists alone 6

Monitoring and Expectations

• Monitor for:
  • Weight reduction (primary indicator of response) 5
  • Improvements in insulin sensitivity parameters 5
  • Changes in menstrual regularity 2
  • Reduction in androgen levels 6
• Gastrointestinal side effects typically improve with continued use and dose titration 5

Limitations and Research Gaps

• No large randomized controlled trials specifically evaluating tirzepatide for PCOS currently exist 6
• The 2023 International Evidence-Based Guideline for PCOS identifies anti-obesity agents as a high priority for future research in PCOS 2
• Long-term effects on fertility and pregnancy outcomes remain unknown 6

While tirzepatide shows promise for addressing the metabolic aspects of PCOS, it should be considered an adjunctive therapy to established treatments like COCs and lifestyle modifications until more specific evidence emerges for its use in PCOS.