The role of Spexin and Phoenixin-20 in girls during puberty

Spexin has an inhibitory effect on the hypothalamus (GnRH expression), pituitary (LH and FSH expression) and ovary (estradiol expression). However, Phoenixin potentiate GnRH-stimulated GnRH receptor expression. Our aim is to assess the role of these two functionally opposite peptides in girls with Central Precocious Puberty (CPP). This prospective study was conducted on three groups of patients (CPP: 33 patients, premature thelarche (PT): 57 patients, and healthy controls: 53 patients). The patients’ anthropometric measurements, pubertal stage, bone age, basal FSH, LH, and estradiol, and peak FSH and LH values obtained from the LH-RH stimulation test were evaluated. The primary aim was to compare Spexin and Phoenixin-20 measurements between groups. Median (Q1–Q3) Spexin levels were 502 pg/mL (314–1434) in the CPP group, 530 pg/mL (234–820) in the PT group, and 626 pg/mL (379–1298) in the control group, with no statistically significant difference between groups (p = 0.177). Median (Q1–Q3) Phoenixin-20 levels were 264 ng/L (206–383) in the CPP group, 252 ng/L (177–383) in the PT group, and 199 ng/L (139–273) in the control group. A statistically significant difference was observed between groups (p = 0.009). Nevertheless, statistical significance between the Phoenixin-20 level of the CPP group and the PT group disappeared after post-hoc analysis. Although Spexin levels tended to be lower and Phoenixin-20 levels higher in the CPP group compared to PT and control groups, the difference was not statistically significant. Correlation analysis demonstrated a weak positive correlation between Phoenixin-20 levels and Tanner stage (r = 0.190, p = 0.023). Although patients with CPP had a lower Spexin and higher Phoenixin-20 level compared to PT and controls, their diagnostic performance was found poor in distinguishing the CPP from PT and healthy controls. Therefore, measurement of these peptides did not find as a diagnostic tool for the diagnosis of CPP and its differentiation from PT. This study was retrospectively registered at ClinicalTrials.gov (NCT07359092). Unique Protocol ID: SPX-PNX-CPP-2024, Last Update: 01/14/2026