Biomarkers of Iron Are Associated with Anterior-Pituitary-Produced Reproductive Hormones in Men with Infertility

Abstract

Approximately 16% of North American couples are affected by infertility, with 30% of cases being attributable to male factor infertility. The regulation of reproductive hormones via the hypothalamic-pituitary-gonadal axis is important for spermatogenesis and subsequently male fertility. Maintaining iron homeostasis is critical to normal reproductive physiological function. This cross-sectional study's objective was to determine the association between serum biomarkers of iron and reproductive hormones. Men experiencing infertility (n = 303) were recruited from Mount Sinai Hospital, Toronto. Serum was analyzed for iron and ferritin as biomarkers of iron status and reproductive hormones (follicle-stimulating hormone, luteinizing hormone, testosterone, estradiol, and prolactin), which were the primary outcome. Associations were determined using non-parametric Spearman's rank correlation coefficient, linear regressions, and logistic regressions. A significant independent monotonic inverse relationship between serum iron and prolactin (p = 0.0002) was found. In linear regression analyses, iron was inversely associated with luteinizing hormone (unadjusted p = 0.03, adjusted p = 0.03) and prolactin (unadjusted p = 0.001 and adjusted p = 0.003). Serum ferritin was inversely associated with both gonadotropins, follicle-stimulating hormone (adjusted p = 0.03), and luteinizing hormone (adjusted p = 0.02). These findings suggest that biomarkers of iron are associated with pituitary-produced reproductive hormones, which play a role in the hypothalamic-pituitary-gonadal signaling pathway involved in spermatogenesis, testicular testosterone production, and male fertility.

Keywords: estradiol; ferritin; follicle-stimulating hormone; iron; luteinizing hormone; male infertility; pituitary gland; prolactin; reproductive hormones; testosterone.