Metformin dosage and galectin-3 levels: insights from PCOS patients preparing for IVF

Abstract

This study explores the impact of metformin dosage and hyperprolactinemia on galectin-3 levels in women with Polycystic Ovary Syndrome (PCOS), providing novel insights into their roles in the metabolic and hormonal management of the condition. A cohort of 53 women, diagnosed using the Rotterdam criteria and undergoing in vitro fertilization (IVF) preparation, was analyzed to determine how these factors influence galectin-3, a biomarker in PCOS. Using high-performance liquid chromatography to measure metformin concentrations and ELISA for galectin-3, our results revealed that both metformin dosage and hyperprolactinemia significantly statistically associated with galectin-3 levels, while body mass index (BMI) showed no significant association. These findings challenge prior assumptions and suggest that galectin-3 may be regulated via pathways independent of metformin pharmacokinetics. Notably, the correlation between galectin-3 levels and metformin concentration was either absent or weak after adjusting for the daily dose, indicating that treatment duration and dosage, rather than absolute drug levels, may more critically influence galectin-3. This study offers deeper insights into the role of personalized metformin dosing in managing PCOS, enhancing the understanding of metabolic and hormonal regulation in this condition, and laying the groundwork for future targeted therapies.

Keywords: body mass index; galectin-3; hyperprolactinemia; insulin resistance; metabolic pathways; metformin; polycystic ovary syndrome (PCOS).

FIGURE 1

Effect of Metformin Dosage on Galectin-3 Levels in PCOS Patients with and without Hyperprolactinemia. This figure compares average galectin-3 concentrations and metformin dosages in PCOS patients with and without hyperprolactinemia. The bar heights represent mean galectin-3 levels, while the overlaid lines indicate mean metformin dosages.

FIGURE 2

Key Factors Influencing Galectin-3 Levels in Women with PCOS and Their Impact on Clinical Outcomes. This diagram illustrates the complex relationships between factors that influence galectin-3 levels in women with PCOS and their impact on clinical outcomes. PCOS increases galectin-3 levels by elevating inflammation and insulin resistance (red arrow 1) and exacerbates clinical symptoms, leading to poorer reproductive outcomes (red arrow 2). Metformin, at higher dosages, reduces galectin-3 levels (blue arrow 3) and improves clinical outcomes both by lowering galectin-3 and through additional pathways, including enhanced insulin sensitivity (blue arrow 4). BMI also plays a significant role by reducing dose-corrected metformin plasma concentrations (red section of arrow 6), while higher metformin doses increase plasma concentrations (blue section of arrow 5), illustrating the need for personalized dosing in PCOS treatment. Hyperprolactinemia further elevates galectin-3 levels (red arrow 7) and negatively impacts reproductive outcomes (red arrow 8). Finally, potential Galectin-3 inhibitors could reduce galectin-3 levels (red arrow 10), indirectly improving clinical outcomes (dashed blue arrow 11). Fire icon: Represents inflammation, a key factor driving increased galectin-3 levels in PCOS; Sugar cube with a keyhole: Symbolizes insulin resistance, another major contributor to elevated galectin-3 levels; Unbalanced scales: Illustrates hormonal imbalance associated with hyperprolactinemia, affecting galectin-3 levels in certain patients; Crossed molecular structure icon: Represents the potential therapeutic galectin-3 inhibitor, a molecule that specifically blocks or reduces galectin-3 levels, which could help alleviate inflammation, improve insulin sensitivity, and enhance reproductive outcomes in women with PCOS. Arrow colours: Blue arrows indicate positive effects, where interventions like metformin or galectin-3 inhibitors contribute to better clinical outcomes or reduce galectin-3 levels; Red arrows indicate negative impacts, such as factors like PCOS and BMI increasing galectin-3 levels or reducing metformin efficacy.