Diagnosis of hypogonadism in the aging male

Abstract

The diagnosis of hypoandrogenism in the aging male is still difficult, since the symptomatology is aspecific and multifactorial, and it is unknown whether the androgen requirements of elderly men are the same as those of young men. Indeed, there are arguments for decreased (increased androgen feed-back sensitivity) as well as for increased (decreased concentration of androgen receptors) requirements in elderly men. In the absence of a reliable, clinically useful, parameter of androgen activity, we have to rely on plasma androgen level, an indirect parameter. In the absence of convincing arguments for altered requirements with age, we consider that the normal range of (free) testosterone levels in young adults is also valid for elderly men, the lower normal limit being 11 nmol/l for total testosterone and 0.225 nmol/l for free testosterone. There are indirect, suggestive clinical arguments for accepting these limit values. The diagnosis of hypoandrogenism in elderly males requires both the presence of clinical symptoms and decreased (free) testosterone levels. The best methods for determining free or bioavailable testosterone, are equilibrium dialysis and ammonium sulfate precipitation, respectively. They are, however, time-consuming techniques which are not easily automated. Calculation of the free androgen index (testosterone/sex hormone binding globulin (SHBG)) is not a valid method for male serum. Calculation of free testosterone from total testosterone, SHBG and albumin concentration, yields values that are in good agreement with values obtained by dialysis or ammonium sulfate precipitation. Several conditions should, however, be fulfilled: reliable methods for the determination of testosterone and SHBG, SHBG measurement in serum and not in plasma, use of fresh serum (not repeatedly frozen and thawed), absence of (exogenous) steroids competing for binding sites on SHBG and blood samples taken between 08.00 and 10.00 in the fasting state. Under these conditions an excellent correlation with dialysis and bioavailable testosterone (ammonium sulfate precipitation) is generally obtained.