Diagnosis of male hypogonadism: what is low testosterone

Abstract

In contrast to primary hypogonadism, whereby the rise of gonadotropin levels helps establishing a diagnosis, the diagnosis of secondary hypogonadism relies for the most part, on the identification of a low testosterone level in the right clinical context. Establishing that a patient indeed has a low testosterone level requires taking into account several physiological as well analytical aspects. The vast majority of testosterone in men circulates in plasma bound to albumin (50%), sex-steroid binding globulin (SHBG) (44%) and other proteins (4%), while only 2% is found free. The biologically active fraction consists of the free and the albumin-bound fractions. Testosterone levels are highest in the early morning and lowest during the summer. Both total and free testosterone decline with age, as SHBG levels increase. Conditions such as obesity and diabetes also result in diminished testosterone concentrations, while they are accompanied by low SHBG levels. Currently, measurement of total testosterone in hospital laboratories is usually performed on fully automated immunoassay analyzers. Although tandem mass spectrometry methods after gas or liquid chromatography are the most accurate means for testosterone measurement, they are still not widely available in most clinical laboratories. In some cases the concentration of total testosterone may not always represent a true reflection of the patient androgen status and therefore an estimate of the non-SHBG or bioavailable fraction may be a more appropriate measure. Methods of assessment of the non-SHBG-bound fraction of testosterone include estimation of the free concentration by methods including the calculation of the free androgen index (FAI), equilibrium dialysis, centrifugal ultrafiltration, direct analog RIA or calculation of the free fraction.