Dr Poochellam Muthalagu looks the primary and secondary reasons for hypogonadism and examines the different treatments available in this country.

Male hypogonadism is a clinical syndrome defined by low testosterone levels associated with sexual dysfunction, particularly diminished libido, mood disturbances, reduced lean body mass and increased adipose tissue mass.

A wide range of effective and well-tolerated treatment options exist. These include testosterone (T) gels and T patches. There is also a mucoadhesive sustained-release buccal tablet, but this is not available in Ireland. Intramuscular testosterone injections and subcutaneous depot implants (T pellets) are still the standard therapy.

Testosterone replacement therapy (TRT) can be individualised to enhance patient health and wellbeing. Screening and ongoing monitoring are necessary to ensure both the efficacy and safety of TRT, particularly prostate safety. Investigational agents, including selective androgen receptor modulators, may offer new pharmacodynamic and/or pharmacokinetic properties that enhance outcomes of TRT.

Male hypogonadism is defined as the failure of the testes to produce androgen, sperm or both. Although the disorder is exceedingly common, its exact prevalence is uncertain.

Testosterone production declines with advancing age; some 20 per cent of men older than 60 years and 30-40 per cent of men older than 80 years have serum testosterone levels that would be subnormal in their younger adult male counterparts.

This apparent physiologic decline in circulating androgen levels is compounded in frequency by permanent disorders of the hypothalamic-pituitary-gonadal axis. These include the transient deficiency states associated with acute stressful illnesses, such as surgery and myocardial infarction, and the more chronic deficiency states associated with wasting illnesses, such as cancer and acquired immunodeficiency syndrome (AIDS).

Pathophysiology
Circulating testosterone is largely protein-bound — the major protein is sex hormone-binding globulin (SHBG) — with only 2 per cent present as the biologically active or free fraction. Hepatic SHBG production rises with ageing and thyroid hormone excess and declines in hyperinsulinemic states (obesity and type II diabetes), so that free testosterone values may not always be concordant with total testosterone values.

The biologic effects of testosterone may be mediated directly by testosterone or by its metabolites 5a-dihydrotestosterone or estradiol. The single decapeptide gonadotropin-releasing hormone (GnRH) stimulates the release of follicle-stimulating hormone (FSH) and luteinising hormone (LH).

Pulsatile GnRH is required. Chronic exposure down regulates the GnRH receptor and causes impaired FSH and LH release, the mechanism whereby pharmacologic GnRH agonists result in chemical castration. Prolactin excess also results in impaired GnRH pulse generator function and hypo-gonadotropic hypogonadism.

Feedback inhibition of LH secretion is a sex steroid–mediated event, whereas FSH secretion has dual feedback regulation involving inhibition by sex steroids and the Sertoli cell product inhibin. Accordingly, a monotropic elevation of the FSH level (normal LH and testosterone levels) may result from deficient Sertoli cell–spermatogenic function.

Major causes of primary (hypergonadotropic) hypo-gonadism include: genetic (Klinefelter’s syndrome, XX males, XYY syndrome); congenital (anorchia, Noonan syndrome, cryptorchidism, myotonic dystrophy); toxins (alcohol, heavy metals, antineoplastics, radion); orchitis; trauma; infarction; and ageing.

Major causes of secondary (hypogonadotropic) hypogonadism include: pubertal delay; hypogonadotropism (Kallman’s syndrome); congenital or acquired; isolated or combined pituitary disease; space-occupying lesions of pituitary, hypothalamus; hyperprolactinaemia per se; infiltrative, infectious; suppression; sex steroids; gonadotropin-releasing hormone analogues; and (possibly) ageing.

Clinical features
Manifestations in adults are generally more subtle. Perhaps the minor contribution of adrenal androgens (or androgenic precursors) may substitute for testicular deficiency once the target tissues have been fully developed. Moreover, ingrained behaviour patterns may be resistant to androgenic hormone deficiency.

Certainly, prolactin excess, testosterone deficiency, or both in men may result in impaired libido and erectile dysfunction. The yield of finding hyperprolactinaemia or testosterone deficiency, or both, in patients presenting with these symptoms is generally considered to be low, usually less than 5 per cent.

A. More specific symptoms and signs
•  Incomplete or delayed sexual development, eunuchoidism;
•  Reduced sexual desire (libido) and activity;
•  Decreased spontaneous erections;
•  Breast discomfort, gynaecomastia;
•  Loss of body (axillary and pubic) hair, reduced shaving;
•  Very small (especially <5 ml) or shrinking testes;
•  Inability to father children, low or zero sperm count;
•  Height loss, low trauma fracture, low bone-mineral density;
•  Hot flushes, sweats.

B. Other less specific symptoms and signs
•  Decreased energy, motivation, initiative, self-confidence;
•  Feeling sad or blue, depressed mood, dysthymia;
•  Poor concentration and memory;
•  Sleep disturbance, increased sleepiness;
•  Mild anaemia (normochromic, normocytic, in the female range);
•  Reduced muscle bulk and strength;
•  Increased body fat, body mass index;
•  Diminished physical or work performance.

The first manifestation of hypogonadism may be a consequence of a large space-occupying intrasellar or parasellar lesion manifested by headaches, bitemporal hemianopia, or extraocular muscle palsy. Galactorrhoea as a manifestation of hyperprolactinaemia is rare, but rarely sought.

'Associated conditions include diabetes, AIDS, chronic renal failure, RA, ageing and cancer cachexia'

Unexplained osteoporosis or mild anaemia sometimes is the clue to an underlying hypogonadal state.

Some common clinical conditions associated with male hypogonadism are: chronic illness; diabetes; AIDS; chronic renal failure; rheumatoid arthritis; ageing; and cancer cachexia.

Because of the well-known diurnal rhythm of serum testosterone, which appears to be lost with age (older than 60 years), with values 30 per cent or so higher near 8am versus the later-day trough, a testosterone value should be determined first thing in the morning. Normal ranges vary among laboratories. Although the usually quoted range for young men is 300-100 ng/dL, the lower limit is 220ng/dL. In general, values below 220-250ng/dL are clearly low in most laboratories; values between 250ng/dL and 350ng/dL should be considered borderline low.

Similarly, in some reference laboratories, the lower limit of the normal range for serum free testosterone level, measured by the equilibrium dialysis method, is 5–9pg/ml (0.17-0.31nmol/l). The clinicians should use the lower limit of normal range for healthy young men established in their laboratory.

Because the acute effect of stressful illness may result in a transient lowering of testosterone levels, a confirmatory early-morning specimen should be obtained. Measurement of free testosterone levels or bioavailable testosterone levels, determined adequately in select commercial laboratories, may provide additional information.

For example, free testosterone levels may be lower than expected from the total testosterone level as a result of ageing and higher than expected in insulin-resistant individuals, such as in obesity. In addition, serum FSH, LH and prolactin levels should be determined to help delineate the cause of the testosterone-deficient state.

If gonadotropin levels are not elevated, despite clearly subnormal testosterone values, anterior pituitary (thyroid-adrenal) function should be determined by measuring free thyroxine and thyroid-stimulating hormone levels, as well as an early-morning cortisol level. A magnetic resonance imaging (MRI) scan of the brain and sella should be considered.

An exception to this recommendation is the condition of morbid obesity, in which both total and free testosterone levels are typically low and gonadotropin values not elevated. Hyperprolactinaemia, even of a small degree, may also warrant ordering MRI, because interference of hypothalamic-pituitary vascular flow by space-occupying, stalk-compressing lesions will lead to disruption of the tonic inhibitory influence of hypothalamic dopamine, and result in modest hyperprolactinaemia (20- to 50ng/mL range).

Treatment
The ideal TRT should replace testosterone to physiologic levels using natural (unmodified) testosterone. The TRT should offer: safety, efficacy, value for money, convenience, a good release profile, dosing flexibility, and effective normalisation of testosterone levels.

TRT is relatively straightforward. Typically, the depot esters are administered by the deep intramuscular route once every two weeks at a dose of 200mg in adults. A usual dosage for the transdermal or the buccal preparations results in the systemic absorption of 2.5-10mg daily. If the parenteral route is chosen, patients should and can be taught to self inject.

The major disadvantage with the parenteral route is that testosterone levels exhibit a saw-toothed pattern, with high-normal or supranormal levels on days two to four and low-normal or borderline low trough values before the next injection. Mood, sense of wellbeing and libido may vary accordingly in some individuals.

Dosages may be adjusted by aiming for mid-normal (400-600ng/dL) testosterone levels after one week or at the low end (250-350ng/dL) just before the next injection is due at two weeks. Values are stable within a few days or weeks of the skin patch, gel, or newer buccal preparation.

It must be ascertained that the preparation was actually used on the day the sample was drawn; again, a value in the midnormal range (400-600ng/dL) is the goal. Although comparable testosterone levels are reached by the patch and the gels, skin reactions at the application site are much more common with the patch. Also, the buccal preparation is difficult for patients to get used to. Alkylated oral androgens should be viewed as potentially hepatotoxic and should not be used.

Testosterone preparations available in Ireland

• Oral – Restandol (testosterone undecanoate)
• Intramuscular – Undecanoate, Nebido
• Gel – Testogel, Tostran, Testim

Contraindications for testosterone replacement include: breast carcinoma (history or presence); prostate carcinoma (history or presence); severe benign prostatic hyperplasia; abnormal digital rectal examinations; elevated levels of prostate-specific antigen; age (no limit established, possibly older than 80 years); psychopathology; sleep apnoea (potential for worsening); hypercoagulable states; and polycythaemia (haematocrit >51 per cent).

In genuinely hypogonadal men, testosterone administration can be expected to result in improvements in a variety of clinical areas. These include: increase in lean body mass; decreased fat mass; increased bone density (no fracture data available); improved mood and wellbeing; improved sexual function; better cognitive function; better muscle strength, physical function. Least predictable of these are the effects on sexual function, cognitive function and muscle strength.

Summary
Male hypogonadism is defined as the failure of the testes to produce androgen, sperm, or both. Although the disorder is exceedingly common, its exact prevalence is uncertain.

Signs and symptoms vary, according to age.

Diagnosis requires the determination of low testosterone levels. Normal ranges vary among laboratories. Measurement of free testosterone levels or bioavailable testosterone levels (performed adequately in select commercial laboratories) may provide additional information, in addition to serum follicle-stimulating hormone, luteinising hormone and prolactin levels. MRI scans of the brain and sella should be considered.

Androgen replacement therapy is used for the treatment of male hypogonadism. In addition to monitoring testosterone levels periodically, prostate screening by digital rectal examination and prostate-specific antigen determinations at periodic intervals when the patient is on therapy should be carried out.

Haemoglobin and haematocrit levels should also be checked periodically.

References on request.

• Dr Poochellam Muthalagu, Consultant Physician/Endocrinologist, Cavan/Monaghan Hospital Group

A spot of regular ‘retail therapy’ really does seem to help people live longer, suggests new research — and it seems to benefit older men the most.

The authors of the study based their findings on almost 1,850 elderly (65+) Taiwanese people who were living independently at home, and included in the nationally representative Elderly Nutrition and Health Survey in Taiwan (NAHSIT Elderly), carried out in 1999-2000.

Participants were asked how often they went shopping, with options ranging from ‘never’ to ‘every day’. Intellectual and physical capacities were measured using validated questionnaires, and age, gender, education, ethnicity, financial and employment status, lifestyle factors and the prevalence of long-term conditions were also factored in.

The researchers then tracked how long each of the participants lived by linking individuals to national death registration data between 1999 and 2008.

Nearly half (48 per cent) of the participants never or infrequently shopped during the week, and around one in four (22 per cent) shopped between two and four times a week.

A further 17 per cent shopped every day, and the remainder shopped just once a week.

Almost two-thirds of respondents were under the age of 75. Just over half (54 per cent) were men. Most had a healthy lifestyle and three out of four were financially self-sufficient.

Almost two thirds (60 per cent) had up to two long-term conditions. Those who went shopping more than once a week tended to be at the younger end of the age spectrum, and male.

They also tended to be smokers and drinkers, have better physical and mental health, take regular exercise and have a network of dinner companions.

The researchers used different approaches to take account of physical limitations and cognitive impairment, but even so, those who shopped daily lived longer than those who shopped less frequently. Those who shopped daily were 27 per cent less likely to die, with male daily shoppers 28 per cent less likely to die, compared with female shoppers, who were 23 per cent less likely to die.

The authors acknowledged that shopping could be a surrogate for good health to begin with, but suggest that shopping itself may improve health, by ensuring a good supply of food to maintain a healthy diet, for example. Frequent shopping among the elderly may not always be about buying things, but about seeking companionship or taking exercise, which is easier to do than more formal exercise that usually requires motivation, they said.

The conventional view of health promotion focuses on physical activity, but engaging in social and economic activities in later life may also contribute to better health, they added.

“Shopping captures several dimensions of personal wellbeing, health and security, as well as contributing to the community’s cohesiveness and economy, and may represent or actually confer increased longevity,” they concluded.

J Epidemiol Community Health (2011). doi:10.1136/jech.2010.126698.

Mr Kilian Walsh takes a look at developments in prescribing and surgery for patients with benign prostatic hyperplasia.

Combination therapy is not a new concept in medical prescribing. Many examples are to be found in MIMS Ireland or in the British National Formulary. For example, these include: Seretide, which is a combination of an inhaler and a steroid; Beta-Adalat, which is a combination of atenelol and nifedipine; Centyl K, a combination of a thiazide and potassium; and Augmentin, which is a combination of a penicillin and clavulinic acid.

However, combination therapy is a new concept in urology and therefore, it is a welcome and exciting idea of combining an alpha blocker and a 5-alpha reductase inhibitor. This adds a new string to our bow in prescribing for patients with benign prostatic hyperplasia (BPH).

Background
Benign prostatic hyperplasia occurs within the prostate of all men as they age and indeed, it begins to develop from about the age of 30 years onwards. However, it is not usual for men to develop symptoms of BPH until they get into their late 40s or older.

The presenting complaints of men with BPH are called lower urinary tract symptoms, or LUTS for short. These can be divided into two categories: voiding symptoms i.e. poor flow, hesitancy and terminal dribbling; and storage symptoms i.e. frequency, urgency and nocturia.

Men usually present to their general practitioner and are often prompted to do so by their wives. The GP then takes a medical history from the patient, performs a digital rectal examination to assess the size and texture of the prostate and, after discussion with the patient, may check prostate-specific antigen (PSA).

If the PSA does not indicate a risk of cancer for the patient, using the age-specific nomograms, then the consultation will turn to the discussion of how to treat the LUTS.

Many GPs quite correctly offer conservative treatment, such as limiting fluids at night, avoiding excessive alcohol intake and limiting caffeine drinks. Sometimes these measures are successful but, if this is not the case, then we have traditionally turned to two well-recognised medical therapies.

The tablets with the fastest onset of action have been alpha blockers. These help dilate the prostate and therefore, allow urine to pass more easily through the prostate during voiding and help alleviate symptoms. However, the side effects of dizziness and postural hypotension have to be explained to the patient.

The alternative, which has a more durable effect on the prostate, has been the 5-alpha reductase inhibitors; these have worked by shrinking the prostate over time, therefore reducing BPH progression and relieving symptoms.

Study results
In 2005, a large randomised control trial run by the National Institute of Health in the United States published its findings on combining both of the above tablets.

The study was called the MTOPS (Medical Therapy of Prostatic Symptoms) study and after 3,000 patients were assessed over four years, the researchers concluded that combination therapy (i.e. an alpha blocker and a 5-alpha reductase inhibitor) reduced the progression of BPH.

A subsequent study called CombAT (Combination therapy with Avodart and tamsulosin), using Avodart and tamsulosin as the name suggests, was similarly run over four years. Again, it demonstrated a reduction in BPH progression as well as reduced requirements for surgical intervention and a lower risk of urinary retention in patients who were on treatment.

The reporting of these two studies led to the development of a combined tablet now called Combodart. In patients who have failed conservative management with LUTS, this is a suitable tablet for GPs to prescribe in order to help alleviate symptoms and reduce clinical BPH progression in patients.

When to refer
However, if patients have an elevated PSA, or fail medical therapy or are interested in a surgical option for their LUTS, I would recommend a referral to an urologist.

When seen by an urologist, they will usually be assessed by a medical history-taking and clinical examination. They will be asked to fill out a symptom questionnaire and the urologist will then arrange for a flow rate and bladder ultrasound in order to determine the strength of their flow and whether they are emptying their bladder.

All these tests allow an urologist to evaluate the severity of the patient’s LUTS and their suitability for an operation. If the PSA is elevated or a digital rectal examination is abnormal, the urologist will arrange for a transrectal ultrasound and biopsy to outrule a cancer.

Then, if no cancer is found, the urologist may recommend an operation for BPH if the patient has bothersome LUTS.

BPH surgery
The goal of a BPH operation is to widen the channel within the centre of the prostate, as opposed to removing the whole prostate during a cancer operation.

This can be achieved either by a TURP (transurethral resection of prostate), whereby an electric current passed through a loop allows the cutting of chips of tissue from the middle of the prostate to increase the size of the central cavity, or more recently where a laser fibre has been used to vaporise the tissue in the middle of the prostate and therefore create a cavity. This is also called a PVP (photoselective vaporisation of the prostate).

Some patients are more suited to TURP and others to a PVP and that is usually determined by the urologist. However, after these procedures, the patients will usually have a greatly improved flow rate and hopefully a significant improvement in their quality of life, which can often be severely impaired with BPH symptoms.

If a patient develops either acute or chronic retention, they usually do well from an operation such as a TURP or PVP as it decreases the risk of such an event happening again.

A TURP usually requires a three-night hospital stay and a PVP usually requires just one night, and although a laser can offer a more rapid return to work, occasionally prolonged dysuria can be bothersome. The selection of PVP versus laser procedure usually entails a detailed discussion between patient and surgeon.

Conclusion
BPH is a common disorder that can be treated conservatively, medically and surgically, matching the treatment to the patient is the art of good medicine. However, recent scientific evidence has shown us the benefit of combination medical treatment.

• Mr Kilian Walsh FRCSI (Urol) is a Consultant Urological Surgeon at University College Hospital Galway and Bon Secours Hospital, Galway.

Contact via website: www.urologywest.ie.

Higher serum uric acid levels in older men are strongly associated with increased bone mineral density (BMD) and markers of calcium homoeostasis and bone resorption, new research has shown.

A study led by Prof Markus Seibel at the ANZAC Research Institute in Sydney examined 1,705 community-dwelling men aged 70 or more who participated in the Concord Health and Ageing in Men Project (CHAMP).

After adjusting for possible confounders, BMD at all sites was significantly higher among those with uric acid levels above the group median.

Uric acid levels were also positively associated with serum calcium, parathyroid hormone and 25-hydroxy-vitamin D levels. They were negatively associated with urinary NTX-1, a marker of bone resorption.

Above-median uric acid levels were also associated with a lower prevalence of osteoporosis at the femoral neck and lumbar spine, and a lower prevalence of vertebral and non-vertebral fractures.

The researchers said their study was the first to examine links between uric acid levels and bone health.

Uric acid had traditionally been viewed as a waste product that caused gouty arthritis and kidney stones, and also led to endothelial damage and increased cardiovascular risk.

However, it was also thought to provide an evolutionary benefit by helping to maintain blood pressure under low-salt conditions.

Emerging evidence suggested that uric acid was a powerful antioxidant that could help protect against conditions including Alzheimer’s disease, and possibly osteoporosis.

The cross-sectional nature of the study did not allow any cause-and-effect mechanisms to be explored, but there were several other plausible explanations for uric acid’s apparent benefits, including a direct effect on bone resorption, the researchers said.

J. Bone Miner. Res.
DOI: 10.1002/jbmr.286

Badly fitting condoms are not only likely to split and break, but they may also reduce sexual pleasure for both partners, according to a new study.
Researchers based their findings on 436 men aged between 18 and 67, who were recruited via newspaper advertisements and a blog on the website of a condom sales company.

The men completed a questionnaire on the Kinsey Institute for Research in Sex, Gender and Reproduction website about the fit of condom they had most recently used for penetrative sex with a female partner.
Almost half the participants said that they had used a badly fitting condom when they had last had sex during the previous three months. They were more than 2.5 times as likely to report breakage or slippage as those whose condoms were a good fit, and five times as likely to report penile irritation.
They were around twice as likely to say that the poorly fitting condom made it difficult for them and/or their partner to reach orgasm and that this curbed sexual pleasure for both parties. They were also around twice as likely to say that their poorly fitting condom interfered with getting and maintaining an erection. And they were twice as likely to say they removed the condom before sex had ended.
The authors acknowledge that their study, which is the first of its kind to look at the impact of poorly fitting condoms on sexual functioning, is limited by its reliance on self report. Nevertheless, they say that the findings ‘emphasise the point that men and their female sex partners may benefit from public health efforts designed to promote the improved fit of condoms’.
Sexually Transmitted Infections 2010;86:36-38

Although alcohol consumption is known to be associated with chronic pancreatitis, new evidence indicates that a threshold of five or more drinks per day is required to significantly raise risk; however, most patients with chronic pancreatitis do not drink this amount, according to a new report.
The report followed a study in which doctors examined the current prevalence of alcohol use and smoking and their association with pancreatitis in 1,000 patients enrolled in the North American Pancreatitis Study 2.

About one-fourth of both controls and patients were lifetime abstainers. Among those with chronic pancreatitis, 38.4 per cent of men and 11 per cent of women were very heavy drinkers (five or more drinks per day), compared with 16.9 per cent of men and 5.5 per cent of women with recurrent acute pancreatitis and 10 per cent of men and 3.6 per cent of women in the control group.
“We found the threshold drinking amount for association between alcohol use and chronic pancreatitis to be five or more drinks per day,” the authors reported.
Compared with abstaining and light drinking (half a drink per day or less), very heavy drinking was associated with approximately triple the odds of developing chronic pancreatitis. However, fewer patients with chronic pancreatitis than expected – about one-fourth – drank at this level. Other factors, including genetic mutations, also contribute to pancreatitis risk.
Although many heavy drinkers also smoked, cigarette use was an independent risk factor for both chronic pancreatitis and recurrent acute pancreatitis. Among smokers, those with chronic pancreatitis tended to smoke more and had smoked for a longer period of time, suggesting a dose-dependent effect.
“In conclusion, only very heavy alcohol consumption and cigarette smoking are independent risk factors for chronic pancreatitis,” the authors concluded. “Risk for chronic pancreatitis from alcohol consumption occurs above a threshold level, while risk due to smoking is dose dependent. Drinking levels in subjects with recurrent acute pancreatitis are similar to controls. Only a minority of patients with recurrent acute pancreatitis and chronic pancreatitis currently seen at secondary or tertiary US centres could be categorised as very heavy drinkers.”
Archives of Internal Medicine 2009;169:1035-1045

Dr Liam O’Síoráin writes that investment in palliative care is not only in the best interests of patients, it is also cost-effective.
It is almost a national sport today for people to comment on how we squandered our wealth during the Celtic Tiger era. But the development of palliative care in Ireland in recent years is an example of money well spent.

In 1994, there were two consultants in palliative care, Dr Michael Kearney at Our Lady’s Hospice in Dublin and Dr Tony O’Brien of Marymount Hospice in Cork. There were only three inpatient units or hospices in the country. Palliative care had yet to become a recognised specialty and there were only a few hospice home-care teams.
h4. Structured development
In the autumn of 1994 the Minister of Health, Brendan Howlin launched a strategic plan, ‘Shaping a Healthier Future’. For the first time, palliative care was identified as an area for ‘structured development’.
Over the following years, successive plans on cancer strategy were published, culminating in the 2001 report from the National Advisory Committee on Palliative Care that laid out a blueprint for palliative care development in Ireland. This report was adopted as Government policy.
This internationally praised report continues to be the reference document for palliative care. Successive Ministers of Health supported the implementation of the plan and the Department of Health worked hard to ensure that hospice care would be available to everyone who needed it countrywide.
There have been enormous improvements in the delivery of hospice care and the continuing investment has paid dividends. In December 2007, there were 686 staff and 153 specialist palliative care beds.
Over 20 home-care teams nationwide were supporting patients in their own homes. A total of 25 palliative medicine consultants, leading multi-professional teams in acute hospitals, hospices and the community brought specialist palliative care to 6,000 patients last year.
New hospices have been built, often with huge community fundraising involvement. More people are cared for at home by their GP, supported by the palliative care community teams. The annual palliative care budget has reached €75 million.
An indication of what can be achieved by a visionary and universally accepted palliative care strategy, political leadership on a local and national level and goodwill in the community is the reality that Ireland’s palliative care service was ranked second in Europe last year.
The current centralisation of cancer services in large ‘centres of excellence’ is well under way, but there also needs to be investment closer to home for patients with advanced disease who are too sick to travel long distances.
The argument for critical mass and focused expertise has been well made and will lead in time to improved survival and remission in the centres of excellence. This is not in dispute, but the improved survival and longer remission does not translate into less work for palliative care services.
h4. Increased demand
As our ageing population’s cancer prevalence rises, palliative care services will be accompanied by the rising numbers of people dying with cancer and other non-malignant conditions. This demographic wave will mean that by 2016, up to 13,000 people will need hospice care. This leaves only a short time to plan for this increased demand.
In addition, specialist palliative care services have been looking after more people with non-malignant diagnoses, such as heart failure, chronic lung conditions, renal failure and progressive neurological conditions such as motor neurone disease and multiple sclerosis.
The importance of having an inpatient specialist palliative care hospice unit to allow admission of patients with complex problems at any stage of their illness, occasional respite admissions when families need a break, and admissions at the end of life for those who cannot be cared for at home is clear. The inpatient unit itself is a ‘centre of excellence’ supporting the home care teams and outpatient/day hospice facilities.
Currently there is a significant gap in inpatient hospice care in the north east, the midlands and the south east. Some 12 counties have no access to this specialist inpatient service.
h4. Urgent need
There is an urgent need for a hospice in Waterford, Tullamore and Drogheda. Units are also needed in Kilkenny, Castlebar, Wicklow, Roscommon, Tralee, Blanchardstown and Cavan.
These specialist units need to be built and staffed as recommended in the 2001 report to a defined standard to ensure delivery of specialist care as close as possible to the regional acute hospitals serving their local communities.
Figures in 2007 revealed there was a palliative care staff shortage of 610 and a bed deficit of 237 compared to the standards set in the 2001 report. Regional spending on palliative care varied from a high of €35 per head of population to just €7.90 per capita.
These huge regional variations mean some of our citizens are well served with palliative care services while others are not. This is unjust and unacceptable.
h4. Equity of access
There has been a strong commitment to continue the development of palliative care, and the Minister for Health and Children Mary Harney has committed to publish the National Framework for Palliative Care Services 2009-2013. This prioritises areas for development in an attempt to improve equity of access for all and to remove the current regional differences.
It is very difficult in the current economic crisis to argue for investment in services when the prevalent focus is on significant cutbacks. One argument for investment in palliative care is simply a value-for-money argument.
There is a growing body of literature showing just how cost-effective palliative care can be. Care at home, in particular, is not only better for the patient and their family, but is also more cost-effective.
h4. Greater comfort
International studies have found that patients using palliative care services have greater comfort and dignity and use 25 per cent less resources than those receiving ‘usual care’ who die in hospital. Research in the USA indicated that savings were made within 18 months when there was a reallocation of resources and structures in favour of palliative care.
One area where it is hard to deny investment is in the provision of palliative care for children. Some 1,369 children in Ireland have life-limiting illnesses. Over 350 children die each year. The Irish Hospice Foundation (IHF) has identified the provision of palliative care to children as an absolute priority.
h4. €2 million in funding
In the context of the current economic difficulties, the IHF has committed over €2 million in funding to allow the employment of a paediatrically trained palliative care consultant and a number of outreach nurses in Dublin, Cork, Galway, Limerick, Offaly, Waterford and Louth, who will support families to care for their children at home.
At present, this whole initiative is stalled in the current freeze on recruitment in the HSE. It beggars belief that, given that the funding will last for three years, there is not the confidence to give this project the go ahead. If nothing else, it creates employment and allows improved specialist care at home to vulnerable children and to families who are already dealing with the impending loss of a loved child.
The IHF is reviewing other ways of recruiting the outreach nurses but the paediatric palliative care consultant must be recruited by the HSE.
h4. Enormous increases
Palliative care services face enormous increases in workload in the coming years. Most services are already stretched and some areas of the country have limited or no access to specialist palliative care hospice beds.
It is a challenge to ensure that funding intended for these specialist services are correctly spent in the areas needed. The National Council on Palliative Care, which was set up on the recommendation of the 2001 report, performed this overseer function but its term has come to an end. There is a need to have a representative body to continue to advise and to plan the development of services.
h4. Fundraising support
It is also a challenge to continue to grow essential services in the current climate and communities can play their part, both in advising their local politicians of their importance and in practical fundraising support.
Local communities have shown their support for hospice care over the years — and this week on June 12 and 13, Sunflower Days will allow people to support the development of local hospice services.
Every one of us, irrespective of our age, diagnosis or where we live, should have access to the best palliative care available at our time of need.
* Dr Liam O’Síoráin is a Palliative Care Consultant and Chairman of the Irish Palliative Medicine Consultants Association.

Erica Mills reports from a recent conference that explored the divide between fact and fiction in the public’s perception of stem cell research and therapies.
Stem cell research is undoubtedly one of the most contentious and widely discussed subjects in medicine today. Bursting into the public perception in 1998 with the creation of the first stem cell line and further brought to public awareness by celebrities such as Michael J. Fox and the late Christopher Reeve, stem cell research has been sold in equal measures as a miracle treatment and as the unforgivable and inexcusable destruction of unborn human life.

Supporters of stem cell research and therapies argue that it has the potential to award sufferers of debilitating diseases and conditions a better quality of life; detractors are concerned with the moral implications of embryonic stem cell usage. With the cacophony of competing voices, how can the average person be expected to make sense of it all? How much of what they hear is fact and how much of it is half-truths or complete fiction?
This subject can be an overwhelming and confusing one. The need for clarification and honesty is what prompted Stephen McMahon of the Irish Patients’ Association (IPA) and Dr Stephen Sullivan of Trinity College to organise a conference to address some of the issues surrounding stem cell research. This conference attempted to debunk some of the common myths about the current trends in research and therapy and expose the ways in which patients could be potentially scammed.
h4. A wide range of experts
Chaired by Brock Reeve, Executive Director of the Harvard Stem Cell Institute and half-brother of Christopher Reeve, this conference included a wide range of experts on the subject including Dr Hiram Chipperfield, Regulatory Affairs Project Manager for ERA Consulting (UK) Ltd., Dr Orla Hardiman, consultant neurologist for Beaumont Hospital and Dr Fionnuala Gough from the University of Manchester. Also speaking was Dr Patrick Costello of the Irish Medicines Board.
Taking place in the Science Gallery of Trinity College Dublin on April 22, 2009, the conference saw the attendance of a large number of patients’ groups, particularly those with spinal injuries — and one person even travelled from France to hear the information on offer.
The conference’s timing coincided with another big story on stem cell therapy, the case of an Irish couple who are travelling to China to pursue stem cell therapy for their eight-month-old child. Maria Kieran and Tommy Cullen are hoping that stem cell therapy might help to restore the sight of their daughter, Gretta Kieran Cullen, who suffers from septo optic dysplasia.
Concerns were raised, however, when it emerged that this treatment was costing the family €60,000. So should a treatment cost that amount? Absolutely not, said Dr Sullivan and Dr Hardiman when asked by Stephen McMahon about the potential risk of patients and their family being scammed. “Clinical trials should not cost you money,” asserted Dr Hardiman.
Stem cell treatments in humans are still in the experimental phases according to Brock Reeve. None are further than Phase II, according to all the experts at the conference. Geron Corporation, one of the biotechnology companies at the forefront of research, is only at Phase II of clinical trials.
There is a danger that stem cell therapy is being sold as ‘snake oil’ and that the realities do not match the expectation. A quick search of the internet throws back the promise that stem cell therapy has ‘cured’ from 70 to 73 conditions. “Not so,” said Reeve when questioned about this by Stephen McMahon. According to Reeve, this number was arrived at by those who have an agenda to further.
A little research confirms that this is true. The common search result which states that adult stem cells have cured seventy-something conditions while embryonic stem cells have cured none is deliberately misleading. Many of the adult stem cell treatments listed are in fact autologous stem cell transplants — the practice of removing stem cells before treatments such as chemotherapy and then giving them back to the individual after treatment to promote cell growth. This practice has, of course, been used for many years and refers to haematopoietic cells rather than the induced pluripotent cells (iPS) which are currently being studied.
The research of iPS is still in its infancy and the effects of iPS are not fully known. This much-peddled promise of a cure is misleading. Adult stem cells have indeed helped in the treatment of patients for many years; however, there is no way they can be said to have ‘cured’ patients. Rather, they have aided their treatment by replenishing the body’s blood which may have been depleted by an aggressive therapy such as chemotherapy.
h4. Advances made in mice
The cells referred to are not cells which have been manipulated to pluripotency but are actually the same cells of which the body has been depleted — reinserted to promote growth. To point to this common treatment as a cure is to give hopeful patients false hope; in reality, we are far from administering iPS cells, tissue specific cells or embryonic stem cells as treatment. Currently, great advances have been made in mice. Is it unrealistic to expect that humans might soon be treated?
According to Stephen Sullivan, it is hard to speculate. “Sometimes in research mice can be good approximations. Ultimately, you need to go into bigger vertebrates like pigs. Just because it works in mice or pigs does not mean there is a correlation to humans,” he said.
Currently, patients are eager to put themselves forward for patient trials and Stephen McMahon proposed that the availability of clinical trials should be made public. Besides the issue of commercial confidentiality, Dr Orla Hardiman felt that too great an emphasis was given to clinical trials. So, are patients ill-advised to come forward for clinical trials?
Dr Sullivan and Dr Hardiman both agreed that people expect too much of clinical trials. There is no guarantee that a clinical trial may improve one’s quality of life — it could, in fact, worsen it. There is a danger that patients are disregarding their doctors’ advice in favour of an unproven treatment. “People are pushing for autonomy and doctors are derided for dissuading patients,” said Dr Gough.
Dr Hardiman pointed out that there is no advantage to a person going on a clinical trial. She pointed to trials for motor neurone disease where the patients in the trial were actually worse off than they would have been if they had remained under conventional care as the trials failed.
The stark reality is that 50 per cent of clinical trials fail in Phase III. It is also unclear what effect a stem cell may have on a condition or illness. “In Parkinson’s disease and Alzheimer’s, stem cells already exist but are not turned on,” she explained. “Why would we use more if these existing ones won’t work?”
The lack of legislation is also a potential quagmire. While both Dr Patrick Costello of the Irish Medicines Board and Dr Hiram Chipperfield from ERA outlined the strict protocols all medical testing should follow, the ethical origins of stem cells has not been addressed in this country. Even if an embryonic stem cell follows the strict demands of these protocols, it is neither legal nor illegal to carry out embryonic and stem cell research in Ireland. This leaves the research of stem cells open to ethically unsound practices.
According to Dr Gough, the in vitro embryo has no status under Irish laws. Thus, therapeutic and research applications may not be illegal as it is not covered under legislation (and has never been since IVF treatment was first administered here). Dr Gough further stated that politicians are loath to involve themselves in a bioethical debate on the subject with which the Church has concerned itself.
The experts also debated the advantages of ‘banking’ umbilical cords. While it is comforting to think that one has a ready supply of stem cells, it is unlikely at the moment that any use could be found for them. Stephen Sullivan agrees that while it sounds interesting, it is still experimental and more information is needed before any application can occur. Dr Hardiman is more damning in her assessment. She believes that storing and harvesting umbilical cord cells is a waste of time as they may be useless by the time we know what to do with them. The IPA, however, sees it as an insurance policy and welcomes it as a better alternative to having another child with a view to aiding an ill child.
The subject of stem cell research and therapies is a complex one. It is possible that with the increased funding under Barack Obama’s presidency (George W Bush imposed a ban on funding for embryonic stem cell research), stem cell research and therapy may make the quantum leap into being ready for practical administration.
As it is, however, patients need to be aware that it is not, at the moment, a miracle cure. Those hoping for it to cure injuries such as spinal cord injuries may be disappointed to discover that currently it is plausible only as a treatment for new injuries — it is nowhere near suitable at the moment to treat any injuries where scar tissue has formed.
At present, this is an exciting area of science — not of medicine and patients need to be aware of this fact. It is also not clear at the moment, whether the greatest use of stem cells will come from inserting them into the body or in their use for studying disease. The use of stem cells in studying why cells mutate into diseases is often overlooked. It is possible that the greatest application of stem cell research is in assessing how cells may react to different medications and treatments. What is clear is that stem cell research has the potential to greatly improve the quality of patients’ lives in the future.
h4. Overhyped by the media
According to the experts at the conference, stem cell therapies and research have been overhyped by the media. While it is illegal to advertise unproven treatments, the internet has now made it possible for any group with an ulterior motive to espouse any opinion — opinions that may be biased and unsubstantiated.
Patients should be advised to be wary of any internet site which includes ‘testimonials’ instead of any proof which may be confirmed by their doctor. Any doctor or patient who wishes to research this further can go to www.isscr.org, an organisation which advocates the free exchange of information regarding stem cell research, for practical and impartial information.
In closing the conference Stephen McMahon expressed a wish that such discussions should continue, free of bias and unsubstantiated science. “We have started a powerful conversation and we will continue to enable such conversations between all stakeholders and patients with the motto ‘Nothing about us, without us’.”
These conversations and debates should continue to ensure that the public can inform itself completely about this complex subject.

Current testosterone doping tests should be scrapped for international sport, because they ignore vital ethnic differences in hormone activity, according to new research from Switzerland.
Testosterone, and other hormones that boost testosterone levels, are among the most widely abused performance enhancers used in sport, according to the World Anti-Doping Agency. Evidence of abuse is determined by the testosterone to epitestosterone ratio, or T:E ratio, in the urine.

Researchers tested the steroid profiles of football players of different ethnicities, after they had deliberately added steroid to their urine samples. They used gas chromatography and took account of a variation in the UGT2B17 gene.
Previous research has indicated that variations in this gene account for some of the differences in the urinary T:E ratio between men of white and Asian ethnic backgrounds. The gene affects metabolism, and therefore the rate at which testosterone is passed out of the body into the urine. They included 57 men of Black African origin, 32 of Asian origin, 32 of Hispanic origin and 50 of Caucasian origin. All were aged between 18 and 36.
The results revealed the genetic variation in 22 per cent of the Africans, 81 per cent of the Asians, 10 per cent of the Caucasians, and 7 per cent of the Hispanics. Based on these findings, the Swiss researchers recalibrated the thresholds for each ethnic group.
The new T:E ratios were: 5.6 for men of African origin, 5.7 for white men and 5.8 for men of Hispanic origin. For men of Asian origin, the ratio was 3.8.
A single indiscriminate threshold to pick up steroid abuse in international sport is ‘not fit for purpose’, the study’s authors concluded. Instead, the reference ranges should be tailored to an athlete’s individual endocrinological passport. Such a passport ‘may detect modifications induced by abuse of testosterone and its precursors, but also alterations in the steroid profile caused by indirect androgen doping products’.
Online First edition of British Journal of Sports Medicine, available at:
http://press.psprings.co.uk/bjsm/march/sm56242.pdf

Older people who are cared for in specialist geriatric units have a better chance of returning home after discharge than those cared for in conventional hospital units, a Spanish study has found. The study’s authors also found that such elderly patients are more likely to remain mobile and be able to carry out usual daily activities, such as dressing, eating or bathing. Researchers in Madrid reviewed 11 studies that compared care provided in acute geriatric units (AGUs) run by specialist elderly care teams with conventional hospital units.
Patients were aged 65 and over and had acute medical problems such as pneumonia, heart failure, urinary tract infections or chronic obstructive pulmonary disease, which did not require treatment in other specialised units. The majority were followed for three months after discharge from hospital.

They found that AGU care reduced functional decline at discharge and increased the probability of returning home to live at discharge and remaining at home three months after leaving hospital. These benefits were not associated with increased fatalities or costs of hospital care. The authors suggested that the effectiveness of AGU care may be down to comprehensive geriatric assessment and care by specialised multidisciplinary teams and a focus on early discharge planning.
BMJ Online, available at: www.bmj.com/cgi/doi/10.1136/bmj.b50