A Novel Marker in Hypogonadal Hypogonadism: Apelin

Apelin is a recently identified adipokine with pleiotropic actions in cardiovascular regulation, metabolic homeostasis, bone remodeling, and reproductive physiology. Through binding to the apelin receptor (APJ), apelin has been shown to influence gonadotropin-releasing hormone (GnRH) secretion, which is essential for the production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Given its potential role in the hypothalamic-pituitary-gonadal (HPG) axis, alterations in circulating apelin may contribute to hypogonadotropic hypogonadism (HH). This study aimed to investigate whether serum apelin concentrations are altered in patients with HH and to evaluate its potential relevance as a complementary biomarker in the diagnostic approach to HH.

A total of 60 participants were enrolled: 30 newly diagnosed HH patients (untreated for at least one year, with no comorbid chronic diseases) and 30 age- and body mass index (BMI)-matched healthy controls. Individuals with BMI<20 or BMI>30 were excluded to minimize confounding metabolic influences on apelin secretion. Following overnight fasting, venous blood samples were obtained for complete biochemical and hormonal profiles. Serum apelin levels were measured using a validated human ELISA kit (SunRed Biotechnology, China; intra- and inter-assay coefficients of variation<10%). Statistical analysis was performed using SPSS 17.0.

Apelin concentrations were significantly lower in HH patients compared with healthy controls (median 35.2ng/L vs. 63.3ng/L, p=0.046). ROC analysis yielded an area under the curve (AUC) of 0.65, with a sensitivity of 76% and a specificity of 64%.

These findings demonstrate reduced circulating apelin concentrations in HH, supporting the hypothesis of its involvement in GnRH regulation and the pathogenesis of hypogonadism. Although its diagnostic accuracy is modest, apelin may complement traditional hormonal markers. Further multicenter studies and mechanistic research are required to validate these observations.