Serum spexin levels in women with diminished ovarian reserve: a prospective case–control study

Background Spexin is a recently identified neuropeptide that modulates the hypothalamic–pituitary–gonadal axis and has been shown to regulate granulosa cell function. Although circulating spexin levels decline with age and metabolic dysregulation, its relationship with ovarian reserve has not been investigated. This study aimed to evaluate serum spexin concentrations in infertile women with diminished ovarian reserve (DOR) compared with those with normal ovarian reserve (NOR). Methods This prospective case–control study enrolled 90 infertile women (45 DOR, 45 NOR) presenting to the Infertility Outpatient Clinic at a tertiary care centre between May and October 2024. DOR was defined as serum anti-Müllerian hormone (AMH) < 1.1 ng/mL. Serum spexin was measured by ELISA on days 2–4 of the menstrual cycle. Group comparisons were performed using the independent samples t -test or Mann–Whitney U test, as appropriate. Diagnostic performance was assessed by ROC curve analysis. Correlations were evaluated using Spearman’s rank correlation coefficient. Results Serum spexin levels were significantly lower in the DOR group than in the NOR group ( p = 0.001). However, the DOR group was significantly older ( p < 0.001), and after adjustment for age, the between-group difference was no longer significant (ANCOVA, p = 0.292). Age-stratified analysis showed no significant difference in spexin within any age band. Spexin did not independently predict DOR in multivariable logistic regression (OR = 1.00, p = 0.406). Positive correlations between spexin and AMH (rho = 0.375, p < 0.001) and antral follicle count (AFC) (rho = 0.351, p = 0.001) in the overall population were attenuated and lost significance after age adjustment. Conclusion Serum spexin has not previously been evaluated in relation to ovarian reserve in women. Although spexin levels were lower in the DOR group, this difference was largely explained by age, and spexin did not independently predict DOR after age adjustment. These findings suggest that circulating spexin reflects age-related reproductive decline rather than serving as an independent marker of ovarian reserve. Age-matched studies are needed to clarify whether spexin has any DOR-specific role.