Clinical meaning
Male hypogonadism results from insufficient testosterone production due to testicular failure (primary) or hypothalamic-pituitary dysfunction (secondary). The hypothalamus secretes GnRH in pulsatile fashion, stimulating anterior pituitary gonadotrophs to release LH and FSH. LH acts on Leydig cells to produce testosterone via cholesterol conversion through the steroidogenic pathway. Testosterone exerts negative feedback on both hypothalamus and pituitary. Primary hypogonadism (hypergonadotropic) shows low testosterone with elevated LH/FSH, as seen in Klinefelter syndrome, orchitis, or testicular injury. Secondary hypogonadism (hypogonadotropic) shows low testosterone with low or inappropriately normal LH/FSH, caused by pituitary adenoma, hyperprolactinemia, obesity, opioid use, or exogenous androgen abuse. Diagnosis requires two morning fasting total testosterone samples below 8 nmol/L drawn before 1000, as testosterone exhibits diurnal variation with peak levels in early morning.
Diagnosis & workup
Diagnostics & workup: - Two fasting morning (0700-1000) total testosterone levels < 8 nmol/L - Free testosterone by equilibrium dialysis if total T borderline (8-12 nmol/L) - LH and FSH to differentiate primary vs secondary hypogonadism - Prolactin level (elevated in prolactinoma causing secondary hypogonadism) - CBC (baseline before testosterone replacement - monitor hematocrit) - PSA baseline before initiating testosterone replacement therapy