Can the so-called 'male menopause' be treated with H...

"New research suggests that testosterone deficiency in older men is much more prevalent than current screening methods suggest, and that more men would benefit from hormone treatment," The Daily Telegraph reports.

The male menopause, which remains controversial, is said to be a syndrome of associated symptoms linked to the fall of testosterone, which include:

The research behind the headlines involved more than 2,000 men given trials of testosterone therapy after attending private Men's Health clinics in the UK.

The men had an average age of 54, though some were aged 90. All the men reported symptoms associated with the so-called male menopause. Most (83%) had testosterone levels that would be considered to be in the normal range, but all were given trials of testosterone therapy.

The men reported a reduction in symptoms with treatment. However, there are risks associated with testosterone therapy, including an increased risk of prostate cancer and blood clots.

The study was an audit of men attending a clinic, so there was no control group. This and other factors mean the study's results are less reliable: a randomised controlled trial would have made the research more trustworthy.

It remains to be seen whether the benefits of testosterone therapy outweigh the risks for men currently considered to have testosterone levels within the normal range, and further studies are needed.

Where did the story come from?

The study was carried out by researchers from the Centre for Men's Health and University College Hospital, both in London, and Edith Cowan University in Australia.

Funding was not reported, but one of the three authors works for a private Men's Health clinic. The clinic offers treatments for male menopause, erectile dysfunction and prostate health – this represents a potential financial conflict of interest.

The study was published in the peer-reviewed journal The Aging Male on an open-access basis. The research is available to read for free online.

Headlines such as "Academics find the male menopause is real" from the Daily Mail are simply not true. This study was an audit of men prescribed testosterone after reporting symptoms such as difficulty getting an erection. This type of study cannot prove whether the male menopause is real or not.

Reassuringly, all of the UK media outlets that covered the study made it clear the implications of this research have been disputed by other experts.

Most sources quoted Professor Frederick Wu of Manchester University, who disputed the claims made by this research. He said, "In my opinion, this publication is not only misleading, but potentially dangerous, particularly when the author calls for many more men to be treated, inappropriately, with testosterone."

What kind of research was this?

This was a retrospective audit of men attending private Men's Health clinics in London, Edinburgh or Manchester since 1989 with symptoms of low testosterone.

This type of study can provide an insight into whether testosterone replacement provides symptom relief, but cannot prove cause and effect.

A prospective, double-blinded randomised controlled trial would be required to prove a causal relationship, as this eliminates potential biases and confounding factors.

What did the research involve?

The researchers reviewed the medical notes of 2,693 men who had attended private Men's Health clinics since 1989. Their symptoms, reported to be present for around three to five years before attending the clinics, included:

loss of libido
low energy
difficulty achieving and maintaining an erection
loss of morning erections
night sweats
joint pains
depression
irritability
impaired memory

The clinics diagnosed the majority of the men (2,247) with inadequate testosterone levels based on their symptoms alone: diagnosis was not based on measured testosterone levels.

The researchers said many men had been denied treatment before because their testosterone levels were in the normal range. This study questions the reliability of these tests.

All of the men diagnosed with low testosterone levels based on symptoms alone were offered testosterone therapy in different forms. These included:

pellet implants
oral testosterone
testosterone scrotal cream
scrotal gel

A symptom checklist called the Andropause Checklist assessed changes in symptoms before and during treatment. It uses 20 questions to derive a score from 0 to 80. In this study, a score of less than 10 was considered normal and was the target for treatment.

What were the basic results?

The average age of the men was 54, with a range from 24 to 90. The average length of follow-up to assess symptoms and testosterone levels was one to two years after treatment. Treatment lasted from 3 to 12 years depending on the testosterone delivery (implant, gel, pill or cream).

Symptomatic relief – defined as a symptom score of less than 10 on a 0 to 80 scale – was achieved for all testosterone therapies two years into treatment.

Some treatments led to symptomatic relief within a year. Men with more severe symptoms were less likely to respond well to the testosterone therapy.

None of the men were reported to have an increased prostate after testosterone treatment, but the average follow-up was just one year.

An unreported proportion of the men had an increased number of red blood cells (polycythaemia) – a known side effect of testosterone treatment that increases the risk of blood clots. These men had to be treated for this by having blood taken regularly to reduce the number back to safe levels.

How did the researchers interpret the results?

The researchers concluded that, "With appropriate and necessary monitoring of safety parameters, testosterone treatment appears safe and economic.

"Many men who could benefit in terms of symptom relief, with improvement in related clinical conditions and prevention of the long-term effects of testosterone deficiency, may remain untreated because of excessive reliance on laboratory measures of androgens for diagnosis and treatment alongside unwarranted safety concerns."

Conclusion

This study found that offering men testosterone when they reported symptoms usually described by men with low testosterone caused a reduction in their symptoms. This was despite 83% of the men having testosterone levels considered to be in the normal range, above 10nmol/l.

The authors say that treating people according to symptoms should be more important than basing it on testosterone blood levels alone. They say these blood levels may be inaccurate, and some individuals may naturally need higher levels of testosterone than others. This is an interesting concept worthy of further robust study.

However, there are potentially serious side effects reported with testosterone therapy, and this study does not address these risks or provide evidence that more people should be treated.

This study's findings have many limitations:

Because of the nature of the study, there was no placebo group to act as a control.
The study was retrospective, which is a less reliable type of study than prospective trials.
The men did not have a laboratory-confirmed diagnosis of low testosterone, and the research relied on self-reported symptoms. The authors say the men's blood results may have been in the normal range for their age, but this may be lower than their individual level used to be. While this is a plausible conclusion, it is not backed by the evidence – the study did not measure each man's testosterone levels when they had no symptoms. Additionally, guidelines recommend that men are only treated if their testosterone level is below 10nmol/l, which was only the case for 17% of these men. Some had four times this cut-off, with levels of up to 40nmol/l.
All men were advised to make lifestyle changes, including reducing their stress levels, alcohol intake and weight if necessary, and increasing how much exercise they did, which could have influenced the results.
Other interventions were also started where necessary, including treatment for high blood pressure, high cholesterol and diabetes, which may also have affected the results.
The authors concluded that testosterone is a safe treatment, saying they have treated men in this way over the course of 25 years and have not seen known problems such as increased prostate size or blood clots. However, the average length of follow-up in this study was just one year.

The US Food and Drug Administration (FDA) issued a warning in 2014 about the increased risk of blood clots with the use of testosterone replacement. They only recommend that testosterone is prescribed for men who do not produce testosterone or who have low levels as a result of a medical condition that requires treatment, such as chemotherapy.

In the UK there are no official NHS guidelines, but the Society for Endocrinology recommends that male patients are treated on a case-by-case basis, depending on their symptoms.

If you suffer from the symptoms described above, it may be worth seeing your GP – testosterone replacement therapy is effective for men who are found to have low testosterone levels.

It remains to be seen whether the benefits of testosterone therapy would outweigh the risks for men currently considered to have testosterone levels within the normal range.

Many problems with issues such as erectile dysfunction and loss of libido are often the result of psychological, rather than physical, issues. It may be unwise to seek out hormonal treatments without first speaking to a sex therapist or a similar type of counsellor. The College of Sexual and Relationship Therapists has contact details for accredited therapists.