Thursday June 17 2010
Late-onset hypogonadism is a rare condition
“Chaps feel the change too,” reported the Daily Mail. The newspaper said that some doctors have believed in the male menopause for years, but until now the condition has not been properly defined. It said a recent study confirms that some men may benefit from hormone therapy, but that the number is much smaller than expected.
This was a cross-sectional study in middle aged and older men. It found that a combination of at least three symptoms of sexual problems (poor morning erection, low sexual desire and general erectile difficulties) and lower testosterone levels can be used to diagnose late-onset hypogonadism, in which the testes produce few or no hormones.
This condition is not a male equivalent of the menopause. It is rare, affecting just over 2% of men in this study. Importantly, there were only small differences in average testosterone levels between men with symptoms and men without them, suggesting that there may be other, age-related reasons for these sexual symptoms in older men, unrelated to hormone levels.
This study supports previous research suggesting that hypogonadism in older men is relatively rare. Establishing criteria for this condition is important to prevent over-diagnosis and unnecessary hormone treatment.
Where did the story come from?
The study was carried out by researchers from a number of centres at universities in the UK, Europe and Canada. In the UK, centres included the Universities of Manchester, Glasgow, University College London and Imperial College London. It was funded by the European Community and published in the peer-reviewed New England Journal of Medicine.
The Mail’s headline could be misleading, as it implies that most men experience a condition similar to the female menopause, when the study found the opposite to be true. However, the story goes on to point out that the “male version”, (i.e. late onset hypogonadism) is rare, and the rest of the newspaper’s report is generally correct.
What kind of research was this?
The aim of this cross-sectional study was to investigate and define the clinical symptoms associated with late-onset hypogonadism, a condition in which the sex glands produce few or no hormones, in middle-aged and elderly men. There is little data on hypogonadism in ageing men. The researchers set out to define the symptoms associated with low testosterone levels and to identify the level of testosterone below which health is affected.
Cross-sectional studies involve surveying a population at one point in time. They are often used for assessing the prevalence of a particular health condition, but they cannot indicate causation.
The researchers point out that the possible association between age-related reductions in testosterone levels and clinical symptoms is controversial.
What did the research involve?
Researchers took a random sample of men participating in another study called the European Male Ageing Study (EMAS). EMAS is the largest ever study of ageing men in the world and its aim is to identify the symptoms of ageing in men and the possible association of these ageing symptoms with hormonal changes and other factors.
The researchers invited a random sample of men between the ages of 40 and 79 from EMAS to take part. Of the 8,416 men invited, 3,369 were recruited (43% of the sample), with an average age of nearly 60 years. Of these, 150 were excluded because of disorders or medications that could have affected the results.
The participants were asked to complete a questionnaire about their social and economic status, general health, medical conditions, medications and lifestyle. They were also asked detailed questions about sexual function and assessed for symptoms of depression. Physical tests (height, weight and body mass index) and cognitive performance tests were carried out. Blood tests were taken to measure biochemical and hormone levels. Tests were carried out to determine how much free testosterone they had available in their bodies.
The men were then divided into a “training set” and a “validation set”. The training set was the first group in which associations between 32 symptoms for hypogonadism and lower testosterone levels were evaluated. Any significant associations identified in the training set were then independently evaluated in the validation set.
The researchers used validated statistical methods to identify significant associations between symptoms and testosterone levels. They adjusted their findings to take into account other possible influences, such as age, BMI and co-existing illnesses.
What were the basic results?
- In both the training and validation sets, three particular sexual symptoms had a consistent association with reduced testosterone levels: poor morning erection, low sexual desire and general erectile difficulties. The greater the number of sexual symptoms, the lower the testosterone levels.
- Other symptoms, such as lack of energy, “sadness” and inability to engage in strenuous activity had some links with low testosterone, but the association was not consistent.
- The researchers also identified the range of testosterone levels that were linked to symptoms. It found that, overall, sexual problems were associated with total testosterone levels of less than 11nmol per litre.
- On the basis of this study, the prevalence of late-onset hypogonadism is about 2.1%, a proportion that gradually increases with age to 5.1% for men aged 70 to 79 years of age.
How did the researchers interpret the results?
The researchers say that, based on these findings, late-onset hypogonadism can be defined by the presence of at least three sexual symptoms, associated with a total testosterone level of less than 11nmol per litre.
They say that using this combination of sexual symptoms and testosterone level to diagnose hypogonadism should guard against “excessive diagnosis” and prevent unnecessary testosterone therapy in older men.
This study was of a relatively under-researched subject. The findings suggest that few older men experience negative symptoms from reduced testosterone levels. The main aim and result of the study was to identify evidence-based criteria for diagnosing late-onset hypogonadism.
Calling hypogonadism the “male menopause”, as the newspapers have done, is potentially misleading. The female menopause is a natural event experienced by all women. There is no such recognised equivalent in men.
It should be noted that the study has some limitations:
- Its results are based on cross-sectional data from questionnaires that rely on self-reporting and so introduce the possibility of error.
- Only one measure of testosterone was taken. Confirmation of low testosterone levels requires repeated measurements.
- It cannot be concluded from this study that low testosterone levels are the cause of sexual symptoms. Although the researchers took some other factors that can influence sexual function into account, such as the presence of health problems, there are many things that can affect sexual function. One of the most important of these unmeasured confounders is whether the man is single, married, widowed or separated, and how happy he is in his current relationship. The researchers themselves suggest that even where symptomatic elderly men have low testosterone levels, a general assessment is required to look at potential alternative causes.
- The difference in average testosterone levels between men with and without symptoms, although significant, was generally very small.
The study did not look at whether testosterone treatment can help with sexual or any other symptoms associated with ageing, in fact, it warns against “injudicious use” of hormone therapy in men.
The researchers say that many of the symptoms of late-onset hypogonadism “substantially overlap” some general signs of ageing. As such, they suggest that “testosterone treatment may only be useful in a relatively small number of cases where androgen (male hormone) deficiency is suspected, since many candidate symptoms of classic hypogonadism were not associated with decreased testosterone levels in older men”.