Dr Malcolm Carruthers writes that testosterone deficiency is the most common endocrine disorder in the adult male, yet is the least commonly diagnosed and treated of these disorders.
This millennium has seen rapidly growing awareness of the important role that testosterone plays in maintaining men’s health and quality of later life. Testosterone deficiency syndrome (TDS) is now recognised as a very real and increasing problem for several reasons.
Global ageing is occurring rapidly, in both developed and in developing countries, but an increased life expectancy is not unfortunately being accompanied by a greater health expectancy – the gap between the two is widening.
With age, testosterone levels fall and there is greater resistance to its action, partly due to rising levels of the binding protein, sex hormone binding globulin (SHBG), which causes a more marked drop in bioavailable and free testosterone. This reduction in testosterone is made worse by illness and the drugs used to treat it, especially in diabetes and metabolic syndrome, both of which are increasing exponentially.
There is also some recent evidence that testosterone levels are decreasing generally in men, as seen in populations in Denmark and the USA, and this is attributed to both lifestyle and environmental factors. Included in the environmental causes are likely to be the increasing effects of xenoestrogens and anti-androgens, which in younger men appear also to be having a disastrous effect on reproductive health.
Not only is the quality of a man’s life greatly reduced by the characteristic symptoms of testosterone deficiency (which include loss of energy and libido, erectile dysfunction, irritability, joint pains and stiffness, memory impairment, irritability and depression), but there is well documented associated morbidity and mortality in relation to a wide range of serious conditions.
There are many epidemiological, theoretical and therapeutic studies linking low androgen levels in men with cardiovascular disease, metabolic syndrome, diabetes, osteoporosis, frailty and Alzheimer’s disease. As might be concluded from these now well-recognised associations, life expectancy is also decreased by androgen deficiency.
Awareness of the effects of testosterone deficiency is also increasing as the general public surfs the oceans of information available on the internet, but still the condition remains largely unrecognised and untreated.
The symptoms of testosterone deficiency syndrome, as it has come to be called in preference to andropause or late-onset hypogonadism, were considered relatively rare in the 1940s when it was recognised as the ‘male climacteric’, but are now frequently seen in middle-aged and older men.
So how many men have TDS? Some say 0.5 per cent, others 50 per cent. The answer depends on the population of men studied, their age and whether symptoms alone are considered diagnostic or additional laboratory criteria such as testosterone levels are required.
These polar views both need to be considered, since the biochemical criteria can be questioned on the grounds of the doubtful validity of androgen assays, and their significance in the light of the concept of androgen resistance, akin to that seen with insulin in type 2 diabetes mellitus.
Using the best validated and most widely studied questionnaire, the Ageing Male Symptoms (AMS) scale, Heinemann found a prevalence of moderate and severe symptoms of testosterone deficiency in around 20 per cent for European men over 50 from an aggregate of studies in Germany, the UK, France, Spain, Portugal, Italy and Sweden.
Because it is fully recognised that the current consensus view of the major societies in the field require biochemical confirmation of the diagnosis, figures for those with additional biochemical evidence at around five per cent, as well as those with symptoms alone at 20 per cent, will be given later.
h4. Men getting testosterone treatment
The table shows that only a very small proportion of the men with TDS are receiving treatment. Assuming that 20 per cent of men over the age of 50 are testosterone deficient, in most of Europe for example, including Ireland, less than one per cent of these cases are being treated. Germany fares better at nearly twice this level, and the USA, which accounts for 90 per cent of the market in testosterone, is up to nearly eight per cent.
Even when additional biochemical confirmation of the diagnosis is required, the prevalence is likely to be five per cent or higher, giving treatment rates of less than four per cent of cases in Europe, eight per cent in Germany and 30 per cent in the USA.
These figures make testosterone deficiency, other than type 2 diabetes in which it also plays a part in up to 50 per cent of cases, the most common endocrine disorder in the adult male, and yet the least commonly diagnosed and treated.
h4. Causes of failure to treat androgen deficiency
h4. 1. Missing the diagnosis
It is suggested that given characteristic symptomatology, particularly in the presence of medical conditions known to be associated with TDS, setting arbitrary cut-off points for total testosterone (TT) or calculated free testosterone (CFT), above which androgen deficiency can be definitely excluded is both scientifically and clinically unjustified.
This contention is supported by the existing evidence on the inconsistencies in sampling procedures, laboratory analyses and uncertainties about the interpretation and significance of so-called ‘normal ranges’ of androgens.
These problems surrounding the laboratory-based diagnosis of TDS are compounded by the evidence that there can be both insufficient production, and variable degrees of resistance to the action of androgens operating at several levels in the body simultaneously.
These factors become progressively worse with ageing, adverse lifestyle, other disease processes, and a wide range of medications.
h4. 2. Unfounded concerns about treatment side-effects
Concern about causing prostate cancer (pCA) is combined with unfounded concerns over the possible adverse effect on benign enlargement of the prostate, and also lack of awareness of the important role of testosterone in erectile dysfunction. It is suggested that physicians need to be updated on all these points.
The current state of knowledge on testosterone (T) and pCA is best summarised by the statement in the article that ‘current literature does not provide any evidence of a cause-effect relationship between endogenous T or T treatment and prostate cancer development’. Further, the concerns about any such link been declared to be ‘a modern myth’ by the American urologist Morgentaler who goes as far as to state ‘that there is not now – nor has there ever been – a scientific basis for the belief that T causes pCA to grow’.
h4. 3. Lack of awareness of disorders related to testosterone deficiency
As indicated above, androgen deficiency has been linked epidemiologically and clinically to many of the commonest, most severely debilitating and distressing afflictions of ageing men, including cardiovascular disease, metabolic syndrome, diabetes, osteoporosis and Alzheimer’s disease.
As well as its overall health benefits, sexual health is improved by increased libido, and testosterone is increasingly recognised as a adjunct to PDE5 inhibitors in treating erectile dysfunction. Finally, testosterone treatment can reduce the distressing and expensive period of frailty and dependency at the of end life.
h4. 4. Lack of training in safe and effective treatment
Guidelines for this have now been provided by many leading endocrine societies and are remarkably uniform in their safety recommendations.
An on-line training course based on these guidelines has recently been established by the Society for the Study of Androgen Deficiency and for the first time, makes the theoretical and practical information needed to diagnose and treat androgen deficiency available to physicians anywhere in the world (www.andropause.org.uk).
h4. 5. Concerns about cost
There is a lack of awareness of recent advances in safe and economic forms of androgen treatment, and the continuing availability of toxic products such as methyl testosterone e.g. in France and Russia. This has tended to over-shadow the economic as well as the medical burden of TDS in terms of both morbidity and mortality.
In well-developed healthcare systems such as the USA’s, there is an emphasis on the concept of ‘preventive care’ in limiting spiraling costs in this major segment of the economy, though there is considerable debate over which clinical interventions actually save money.
These authors raise the key point that ‘findings that some cost-saving or highly efficient measures are underused would indicate that current practice is inconsistent with the efficient delivery of healthcare’.
Since testosterone treatment can safely provide short and long-term improvement in the quality of life, and be of benefit in many serious and debilitating conditions, when carefully targeted it could be considered a strong candidate for providing cost-effective preventive medical care.
International action is urgently needed in making these problems known to the medical profession in each country, and overcoming the obstacles to treatment by educating and motivating them and those regulating the healthcare systems, as well as encouraging the public to be aware of symptoms of TDS and its importance.
The proposed sequence of events is firstly that primary care physicians should be made aware that androgen deficiency is important, frequently occurring, easily diagnosed by questionnaires such as the AMS, and safe, simple and economic to treat. Without this initial stage, many patients with diagnostic symptoms will continue to go unrecognised and untreated. This is one of the main aims of the conference on ‘Testosterone in Men’s Health’ to be held at The Royal College of Physician’s in Dublin on 1 November.
Secondly, urologists, especially those treating erectile dysfunction, andrologists, endocrinologists seeing patients with diabetes and metabolic syndrome, cardiologists, psychiatrists and gerontologists should all be more aware of the need to recognise and treat the condition.
Last but not least, by unsensational but authoritative TV programmes and articles in the press, we can educate the general public, increasing their awareness that testosterone deficiency is a common and serious condition in men which can and should be treated.
The economic case that it could be an important part of preventive medical care, especially in ageing men, needs to be developed and publicised.
References on request.
* Dr Malcolm Carruthers, MD, FRCPath., MRCGP, Centre for Men’s Health, 20/20 Harley Street, London.
About Gary Culliton
Loading ...
