The Hypothalamus–Pituitary–Testicular Axis in a Healthy Aging Male

The exact points of weakness along the aging hypothalamus–pituitary–testicular (HPT) axis remain undetermined. In this review, the HPT axis in healthy older males will be analyzed and compared to that in younger males. A systematic review of published literature related to “aging males” and the “hypothalamus–pituitary–testicular axis” was conducted using the PubMed, Web of Science, Google Scholar, and Embase online databases for articles published between January 1, 2003, and December 31, 2023. Gonadotropin-releasing hormone (GnRH) exhibits increased potency and a lower maximal effect on luteinizing hormone (LH) secretion with age. Serum LH, follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), and estradiol levels increase with age while the serum LH and testosterone (T) coordination desynchronize. Serum total testosterone (TT) levels decrease, and serum free testesterone(FT) and serum bioactive testesterone(FT) levels decrease even more. Indicators of Leydig and Sertoli cell function respectively, insulin-like 3 peptide decreased, and inhibin-B remained stable. Aging hypogonadism is a primary hypogonadism because serum gonadotropin levels increase as serum T levels decrease. However, there is also evidence that GnRH and LH stimulation decrease with age. A loss of Leydig cell function and a decrease in Sertoli cell count is observed via serum indi cators. Additionally, SHBG is implicated in the difference between serum TT and serum FT and BT. Due to the numerous influences on aging hypogonadism in men without comorbid endocrine disorders, it may be more accurate as global hypogonadism. Further study is needed for the various locations of desynchrony, hopefully leading to treatment and prevention options. Cite this article as: Goldblatt J, Dalloul M, Muneyyirci-Delale O. The hypothalamus pituitary–testicular axis in a healthy aging male. Endocrinol Res Pract. 2025;29(3):261-266.