Phenotype-Specific Differences in Insulin Resistance and Androgenic Profiles in Polycystic Ovary Syndrome: A Prospective Observational Study

Background and Objectives: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder characterized by distinct phenotypic presentations. This study aimed to compare androgenic and metabolic characteristics across Rotterdam-defined PCOS phenotypes, with particular emphasis on insulin resistance. Materials and Methods: This prospective observational study included 261 nulliparous women with PCOS who were prospectively enrolled and classified according to the Rotterdam criteria as phenotype A (n = 101), B (n = 39), C (n = 55), or D (n = 66). Clinical hyperandrogenism, biochemical androgen parameters, hormonal parameters, lipid profiles, and insulin resistance assessed using the homeostasis model assessment of insulin resistance (HOMA-IR) were compared across phenotypes. Insulin resistance was defined as HOMA-IR ≥ 2.5. Multivariable logistic regression was performed to evaluate the association between PCOS phenotype and insulin resistance after adjustment for age and body mass index (BMI). Results: Significant differences were observed among phenotypes in sex hormone-binding globulin (SHBG), free androgen index (FAI), and Ferriman–Gallwey scores (p = 0.005, p < 0.001, and p < 0.001, respectively). Median HOMA-IR differed significantly among phenotypes (p < 0.001) and was lowest in phenotype D. The prevalence of insulin resistance was 58.3%, 56.4%, 49.1%, and 22.6% in phenotypes A, B, C, and D, respectively (p < 0.001). After adjustment for age and BMI, phenotypes A (adjusted odds ratio [aOR] 4.56, 95% CI 2.20–9.42), B (aOR 4.54, 95% CI 1.90–10.87), and C (aOR 3.29, 95% CI 1.47–7.38) were associated with higher odds of insulin resistance compared with phenotype D. HDL-C also differed among phenotypes (p = 0.006), whereas other conventional lipid parameters, the TG/HDL ratio, and AIP were comparable. Conclusions: Rotterdam-defined PCOS phenotypes exhibit distinct androgenic and metabolic profiles. Hyperandrogenic phenotypes, particularly A and B, were associated with greater insulin resistance, whereas phenotype D showed a more favorable metabolic profile. These findings reflect cross-sectional metabolic differences between PCOS phenotypes and should not be interpreted as evidence of future cardiometabolic risk.