USE OF TIRZEPATIDE IN POLYCYSTIC OVARY SYNDROME: EFFECTS ON INSULIN RESISTANCE, HYPERANDROGENISM, AND FERTILITY

Abstract

Polycystic ovary syndrome (PCOS) is a complex endocrinopathy characterized by a variable combination of ovulatory dysfunction, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology. Insulin resistance, which is particularly common in overweight women, plays a significant role in the metabolic and reproductive pathophysiology of the disease. Tirzepatide—a dual agonist of the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors—promotes significant weight loss and improved insulin sensitivity in individuals with obesity and/or type 2 diabetes mellitus, sparking interest in its use for treating PCOS. However, its specific use for PCOS does not yet have the same level of evidence as established treatments. Evidence from studies on GLP-1 receptor agonists demonstrates reductions in body mass index, waist circumference, and insulin resistance, as well as potential benefits regarding menstrual regularity, sex hormone-binding globulin (SHBG) levels, and androgen indices. Recent meta-analyses, however, show heterogeneous results regarding testosterone reduction and reproductive outcomes. A randomized clinical trial involving 60 overweight or obese Chinese women with PCOS demonstrated that combining 5 mg/week of tirzepatide with metformin for 16 weeks resulted in significantly greater weight loss, reduced visceral fat, and improved metabolic and reproductive parameters compared to metformin alone. Menstrual cycle recovery and pregnancy rates were also higher in the combination group, although the small sample size and short duration preclude definitive conclusions regarding fertility and live birth rates. In conclusion, tirzepatide shows significant therapeutic potential for PCOS, particularly in women with obesity or excess weight associated with insulin resistance. However, it should not currently be considered a specific medication for ovulation induction or primary infertility treatment. Its potential effects on hyperandrogenism and fertility appear to be predominantly mediated by metabolic improvement and weight loss, although direct ovarian mechanisms remain under investigation.