Serum testosterone concentrations in males are regulated by a multilevel feedback loop system (hypothalamic pituitary testicular (HPT) axis).
The production of testosterone by the Leydig cells of the testis involves Kisspeptin and Gonadotropin-Releasing Hormone (GnRH) neurons in the hypothalamus and Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) cells in the anterior pituitary gland. Testosterone (T) is bio transformed in a tissue specific manner to oestradiol (E2) and dihydrotestosterone (DHT) by aromatase and 5 α-reductase respectively. T and E2 feedback to inhibit the GnRH and Kisspeptin secretion. Sex steroids circulate bound to proteins, predominantly sex hormone binding globulin (SHBG) which is produced by hepatocytes in the liver.
Under normal circumstances testosterone production begins to increase at the onset of slow wave sleep, peaking by the first REM episode, and decreases progressively after waking.
A low serum testosterone may result from an intrinsic abnormality in one of more components of the HPT axis or may be secondary to factors external to the HPT axis. The distinction is of importance because treatment with testosterone is invariably successful in the former but of limited benefit in the latter where treatment should be directed to the primary condition.
Symptoms are of limited utility in assessing the significance of a low serum testosterone concentration because of the non-specificity and considerable overlap of the symptoms with the disorders that result in a low serum testosterone concentration. Accordingly, the assessment of a male with a low serum testosterone concentration requires a comprehensive assessment the approach to which will be discussed in this presentation.