Referral bias in female functional hyperandrogenism and polycystic ovary syndrome

Objective: Women with polycystic ovary syndrome (PCOS) seeking health care in the United States may be more obese and hyperandrogenic than those present in the general population. We aimed to assess the impact of referral bias on European women with functional androgen excess disorders. Design: Cross-sectional study. Methods: We studied two groups of patients: i) 368 consecutive patients referred to our clinic for the study of functional hyperandrogenism (FH) (referral patients); ii) 57 consecutive premenopausal patients identified by screening during blood donation (unselected patients). We compared the anthropometric data from the groups of patients with those of two control populations: iii) a group of unselected premenopausal healthy female blood donors (unselected controls); and iv) data available from the local general premenopausal female population. Results: Referral patients with FH were more hirsute, had a higher percentage of hyperandrogenemia, and fulfilled PCOS criteria more frequently than unselected patients. The prevalence of obesity in unselected controls was similar to that observed in the general population, whereas referral patients and unselected patients were more frequently obese. The prevalence of obesity was also higher among referral patients compared to unselected patients. Conclusion: Referral bias influences the phenotype of patients with FH. Patients studied at the clinical setting may show more severe hyperandrogenic and obese phenotypes than patients from the general population, even though PCOS appears to be associated with weight excess also in the general European population. This fact should be considered when establishing reference values and control populations for clinical and research purposes.