Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age, with an estimated prevalence ranging from 5% to 21% depending on diagnostic criteria. It is characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology, and is strongly associated with obesity, insulin resistance, and cardiometabolic complications.
Obesity is a particularly important factor in the pathophysiology of PCOS. Between 40% and 90% of women with PCOS are overweight or obese, and excess adiposity amplifies insulin resistance, hyperandrogenism, and reproductive dysfunction. Increased adipocyte mass also enhances aromatization of androgens into estrogens, further disturbing the hypothalamic–pituitary–ovarian axis. As a result, weight gain worsens menstrual irregularities, infertility, and metabolic risks.
Lifestyle interventions remain the cornerstone of management; however, adherence is often challenging and pharmacological options are increasingly being explored. Among these, glucagon-like peptide-1 (GLP-1) receptor agonists have shown benefit in both weight reduction and metabolic improvement. Tirzepatide, a novel dual GLP-1 and glucose-dependent insulinotropic peptide (GIP) receptor agonist—or “twincretin”—offers enhanced metabolic benefits compared with GLP-1 agonists alone and is emerging as a promising therapeutic candidate for women with PCOS.
Evidence from a Retrospective Observational Study
A retrospective observational study was conducted between July 2024 and February 2025 to evaluate the role of tirzepatide in women with PCOS and obesity.
- Participants: 56 women over 18 years with PCOS and obesity (BMI ≥30 kg/m² or ≥27 kg/m² with obesity-related comorbidities).
- Treatment regimen: Tirzepatide once weekly, initiated at 2.5 mg for 4 weeks, escalated to 5 mg for 4 weeks, and then maintained at 7.5 mg for the remainder of the study period.
Key Outcomes
- Weight and BMI: Mean body weight decreased from 84.8 ± 12.7 kg to 76.7 ± 10.8 kg, reflecting a 9.5% reduction (p = 0.0004). BMI decreased from 36.5 ± 6.1 to 32.5 ± 4.7 kg/m² (p = 0.0002).
- Glycemic control: Fasting blood sugar improved from 6.89 ± 0.78 to 5.57 ± 0.42 mg/dL (p < 0.0001), and HbA1c decreased from 5.7 ± 0.6% to 4.9 ± 0.4% (p < 0.0001).
- PCOS symptoms:
- Irregular menstrual cycles decreased from 85.7% to 32.1% (p < 0.0001).
- Ovarian cyst prevalence declined from 89.3% to 41% (p < 0.0001).
- Insulin resistance improved from 80.4% to 50% (p = 0.0008).
- Acne, acanthosis nigricans, depression/anxiety, fatigue, and sleep apnea also showed significant reductions.
- Safety and tolerability: The most frequent adverse events were heartburn (42.9%), nausea/vomiting (39.3%), general weakness (33.9%), and injection-site pruritus (28.6%). Overall, 84% of participants reported satisfaction with treatment outcomes.
Clinical Implications
The findings suggest that tirzepatide may be a valuable addition to the therapeutic armamentarium for PCOS, particularly in women with obesity and insulin resistance. By targeting both weight and metabolic dysfunction, tirzepatide not only improves cardiometabolic risk factors but also alleviates core reproductive symptoms of PCOS, including menstrual irregularities and ovarian cyst burden.
While further prospective and long-term studies are needed to confirm these benefits and assess effects on fertility outcomes, current evidence positions tirzepatide as a promising therapeutic option in PCOS management.
Reference:
Ferdous J, Hossain MM, Faika MJ, Begum M, Mahjabeen S, Jahan IA, Khan MZ, Hossain MM. Role of Tirzepatide in Obesity Management Among Women with Polycystic Ovary Syndrome. International Journal of Diabetes and Endocrinology. 2025 Apr;10(2):37-44.
