Adiposity-related gradients of follistatin, leptin, and visfatin contrast with differential six-month inhibin B changes in women with endocrine infertility

Background Obesity-associated endocrine infertility involves interacting metabolic and ovarian disturbances that are not fully captured by conventional hormonal assessment. We characterized circulating adipokine and reproductive peptide profiles across adiposity strata and evaluated six-month changes during routine treatment. Methods This prospective observational study included 114 women: 43 with overweight-associated endocrine infertility, 51 with obesity-associated endocrine infertility, and 20 controls documented as having normal weight at enrollment; paired follow-up data were available for 80 patients. Seven biomarkers were measured at baseline, and follistatin, leptin, visfatin/nicotinamide phosphoribosyltransferase, and inhibin B were reassessed after six months. Analyses incorporated false-discovery-rate control, body mass index-adjusted correlations, bootstrap receiver operating characteristic analysis, log-scale mixed-effects models, inverse-probability weighting, and sensitivity analyses. Results Follistatin, leptin, and visfatin increased progressively across controls, overweight, and obesity groups (all q<0.001). Per 5-kg/m² higher body mass index, concentrations were 40.0%, 22.6%, and 18.2% higher, respectively, whereas inhibin B showed no graded association. Visfatin provided the strongest exploratory separation of obesity from overweight (area under the curve, 0.920; 95% confidence interval, 0.863–0.964). The ROC cut-offs were derived and evaluated in the same cohort and therefore remain strictly exploratory. At six months, follistatin, leptin, and visfatin decreased similarly in both patient groups. Inhibin B increased by 60.1% in the overweight group and 133.9% in the obesity group (interaction q<0.001), with consistent sensitivity analyses. No biomarker change remained associated with restoration of ovulation after multiplicity correction. Conclusion The panel identified distinct adiposity-associated and granulosa-cell-related biomarker domains, but neither sample-derived thresholds nor longitudinal changes are validated diagnostic or reproductive-response markers and neither should be used for clinical decision-making without independent validation.