Beyond PCOS: hormonal determinants of insulin resistance in normal-weight women of reproductive age - a scoping review

Abstract

Background/Purpose: Insulin resistance (IR) in normal-weight women is poorly understood and traditionally associated almost exclusively with polycystic ovary syndrome (PCOS). We aimed to map the available literature on the hormonal determinants of IR in normal-weight women of reproductive age. Methods: The review is compliant with the PRISMA-ScR (2020) guidelines and the Joanna Briggs Institute methodology. PubMed and the Cochrane Library (March 2026) were searched, intentionally omitting the term "PCOS" from the search strategy to capture evidence relevant to women without this condition. The review included 30 studies (approximately 6,500 participants from 17 countries) covering androgens, adipokines, and other factors. Study quality (Newcastle-Ottawa scale) averaged 7.4 out of 9. Results: 29 of the 30 studies involved women with PCOS, indicating a narrowly defined research interest in this topic. Classic androgen markers - the free androgen index and sex hormone-binding globulin - lost their predictive value for IR in normal-weight women, unlike at higher body mass index (BMI), suggesting a different pathophysiological mechanism. Various adipokines and adipose tissue hormones maintained their association with IR regardless of BMI. The role of anti-Müllerian hormone remained ambiguous. In one study, thyroid-stimulating hormone emerged as an independent predictor of IR. IR was also observed in control groups without PCOS. Conclusions: A methodologically robust literature on the determinants of IR in normal-weight women is needed, especially beyond the context of PCOS. Filling this gap could lead to improved diagnosis and treatment in this overlooked population. The current literature is heterogeneous and draws primarily correlational conclusions.