European researchers have for the first time identified the symptoms of late-onset hypogonadism, also termed “male menopause“, a condition that follows reductions in the male hormone testosterone in older men, and suggest that unlike the female menopause it is quite rare.

You can read about these findings in the 16 June online issue of the New England Journal of Medicine, NEJM. The authors were from The University of Manchester, Imperial College London, UCL (University College London), both in the UK, and other European research establishments.

The link between aging-related drops in testosterone and late-onset hypogonadism in men is a controversial topic in medicine, and the researchers hope their findings will help guide doctors prescribing male testosterone therapy, the practice of which has gone up by 400 per cent in the US in the last decade.

Lead author Dr Fred Wu, a professor at The University of Manchester’s School of Biomedicine, and colleagues suggest that unlike the female menopause which generally affects all women, the male menopause only affects about 2 per cent of elderly men and is often associated with obesity and poor general health.

Because of the controversy over the link between symptoms and low levels of the male hormone, the researchers decided to look for hard evidence in the general population to help produce a list of criteria for late-onset hypogonadism.

For the study, which is part of the European Union-funded European Male Ageing Study, they surveyed a random population sample of 3,369 men aged from 40 to 79 at eight European centres.

The men completed questionnaires about their general, sexual, physical and psychological health and also gave blood samples from which the researchers were able to assess levels of testosterone (they actually measured total and free testosterone).

From a potential list of 32 candidate symptoms, the researchers found that only nine (three sexual, three physical and three psychological) were actually linked in any significant way with low testosterone.

But the strongest links were with the three sexual symptoms: decreased frequency of morning erection, erectile dysfunction, and decreased frequency of sexual thoughts (“sex drive”). The researchers wrote:

“Only the three sexual symptoms had a syndromic association with decreased testosterone levels.”

They also observed that the lower the testosterone levels, the more sexual symptoms there were.

Wu and colleagues concluded that:

“Late-onset hypogonadism can be defined by the presence of at least three sexual symptoms associated with a total testosterone level of less than 11 nmol per liter (3.2 ng per milliliter) and a free testosterone level of less than 220 pmol per liter (64 pg per milliliter).”

The other six symptoms, three physical and three psychological symptoms, that were only weakly related to low testosterone, were: an inability to walk more than 1 km; an inability to engage in vigorous activity (eg lifting heavy objects, running); an inability to bend, kneel or stoop; loss of energy; sadness; and fatigue.

Wu and colleagues also ruled out some symptoms that are often linked with male menopause: changes in sleeping pattern, feelings of worthlessness, poor concentration, anxiety, nervousness, and difficulty getting out of a chair. These were in the candidate symptom list but they did not show any significant links with low testosterone.

Wu said in a statement that:

“The diagnosis of classical hypogonadism is corroborated by underlying diseases affecting the testes or pituitary gland, which controls testicular function, but this well-practiced diagnostic approach is frequently found wanting when dealing with the age- related decline of testosterone in elderly men who are prone to have a significant background of non-hormone-related complaints.”

He said their findings have for the first time identified the key symptoms of late-onset hypogonadism and suggest that:

“Testosterone treatment may only be useful in a relatively small number of cases where androgen deficiency is suspected, since many candidate symptoms of classic hypogonadism were not associated with decreased testosterone levels in older men.”

However, he added a cautionary note, emphasizing the difficulty of diagnosing this condition:

“The long list of nonspecific symptoms that have a potential association with testosterone deficiency makes it difficult to establish a clear diagnosis of late-onset hypogonadism.”

“This situation is further complicated when you consider that even the most specific sexual symptoms of androgen deficiency was relatively common among men with normal testosterone levels,” he added.

He stressed the importance of establishing the presence of all three of the sexual symptoms from the nine that they found to be linked to low testosterone, plus the presence of low testosterone, to increase the likelihood of correctly diagnosing late-onset hypogonadism.

“The application of these new criteria should guard against the excessive diagnosis of hypogonadism and curb the unwise use of testosterone therapy in older men,” said Wu.

“Identification of Late-Onset Hypogonadism in Middle-Aged and Elderly Men.”
Wu, Frederick C.W., Tajar, Abdelouahid, Beynon, Jennifer M., Pye, Stephen R., Silman, Alan J., Finn, Joseph D., O’Neill, Terence W., Bartfai, Gyorgy, Casanueva, Felipe F., Forti, Gianni, Giwercman, Aleksander, Han, Thang S., Kula, Krzysztof, Lean, Michael E.J., Pendleton, Neil, Punab, Margus, Boonen, Steven, Vanderschueren, Dirk, Labrie, Fernand, Huhtaniemi, Ilpo T., the EMAS Group.
N Engl J Med, Published online 16 June 2010.
DOI: 10.1056/NEJMoa0911101

Source: University of Manchester.

Written by: Catharine Paddock, PhD