A study presented at the European Congress of Endocrinology in Dublin suggests that some men suffering from testosterone deficiency may be missed under current clinical guidelines, while others are misdiagnosed with testosterone deficiency. 

Testosterone deficiency, also known as male hypogonadism, can lead to decreased libido and infertility, but it has also been associated with a higher risk of developing metabolic syndrome, diabetes and osteoporosis. In men, testosterone levels gradually decline with age. In recent years, an increasing number of aging men are presenting with symptoms suggestive of hypogonadism and testosterone levels that are around or below the lower limit for young men. To date, the diagnosis of hypogonadism in these middle-aged and elderly men and their management remains controversial.

 Testosterone exists in the body in two states; bound to proteins (98 % of total testosterone) and non-protein bound or free (2% of total testosterone), the latter being the biologically active fraction. Current clinical guidelines suggest that testosterone deficiency is diagnosed by measuring total testosterone levels but the new work says that levels of free testosterone are more informative. 

Researchers used data from the European Male Aging Study (EMAS) to determine the relative importance of total and free testosterone measurements in diagnosing testosterone deficiency in aging men.

Only free testosterone can enter cells and is responsible for testosterone action. When men get older, total testosterone levels decrease while the levels of the protein that binds it increases. This means that the level of free testosterone decreases more than the total testosterone with age.

“We show that middle-aged and elderly men with normal total testosterone levels but low free testosterone levels have more symptoms of hypogonadism compared to normal men than those with normal free but low total testosterone – these men currently miss out on treatment because they are not diagnosed with testosterone deficiency,” says
 Dr. Leen Antonio from the University of Leuven, Belgium. “On the other hand, men with low total testosterone but normal levels of free testosterone do not suffer from testosterone deficiency, yet are misdiagnosed with the condition and can be treated with testosterone inappropriately.”

Antonio and colleagues propose that new guidelines should recommend measuring free testosterone, in addition to total testosterone, in the evaluation of men with hypogonadal symptoms.