TIRZEPATIDE AND GYNECOLOGICAL ASPECTS: IMPACTS ON THE MENSTRUAL CYCLE, POLYCYSTIC OVARY SYNDROME, AND CONSIDERATIONS REGARDING REPRODUCTIVE RISKS AND BENEFITS

Abstract

Tirzepatide, a dual agonist of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, has demonstrated high efficacy in glycemic control and promoting significant weight loss in individuals with type 2 diabetes mellitus and obesity. Given the close interaction between metabolic status and female reproductive function, the potential impact of this therapy on gynecological parameters, especially the menstrual cycle and polycystic ovary syndrome (PCOS), has been investigated. PCOS is characterized by hyperandrogenism, ovulatory dysfunction, and often insulin resistance, creating a scenario in which metabolic interventions can exert relevant indirect effects on ovarian function. In this context, tirzepatide, by improving insulin sensitivity and promoting body weight reduction, may contribute to decreasing compensatory hyperinsulinemia and, consequently, to reducing ovarian androgen production. These mechanisms may favor the restoration of ovulation and the regularization of the menstrual cycle, particularly in patients with a predominantly metabolic phenotype. Studies with GLP-1 receptor agonists, a related pharmacological class, have already demonstrated benefits in menstrual regularity and ovulation rate in women with PCOS, supporting the biological plausibility of similar effects with tirzepatide. However, direct clinical evidence is still limited, and most available data derive from extrapolations or indirect analyses. Additionally, changes in the menstrual cycle may occur, especially at the beginning of treatment, possibly related to rapid weight loss and adaptations of the neuroendocrine axis. From a reproductive point of view, the improvement in ovulatory function may increase fertility, implying a potential risk of unplanned pregnancies. It should be noted, however, that the safety of tirzepatide during pregnancy has not been established, and its discontinuation is recommended in the pre-conception period.