Aging men - Challenges ahead

Bruno Lunenfeld

Faculty of Life Sciences, Bar-Ilan University, Israel

Asian J Androl  2001 Sep; 3: 161-168

Keywords:  aging; life expectancy; health expectancy; fertility;  HRT  (hormone replacement therapy); quality of life; preventive strategies

Abstract

1 An aging world

First we were obsessed with the challenge of  population explosion, then we shifted our concern to the problems of global aging, and only now do we start to grasp the future consequences of a rapid fertility decline.  E. Diczfalusy, 2000.

The human race entered the 19th century with a global population of 978 million, the 20th century with 1650 million and the 21st century with a worldwide population of 6168 million. The estimates and projections of the United Nations indicate that between 1900 and 2100, world population will increase seven-fold, from 1.65 billion to 11.5 billion: an increase of almost 10 billion people.  This rapid increase in world population is in spite the fact that effective family planning has significantly reduced fertility rates. In 1970, there were 22 countries with a total fertility rate at or below the replacement of 2.1.  In the year 1999 it was 68 countries, and it is projected that by 2020, 121 countries representing 75% of the global population will have birthrates below the replenishment level.

Human had a life expectancy of about 30 years for about 99.9% of the time we inhabit this planet. Today more then 75% of all human death in developed countries occur after the age of 75. The last century has been marked by the triumph of partially preventing the premature termination of life. During the past 50 years infant mortality rates declined from 155/1000 to 52/1000 in the world and from 72/1000 to 11/1000 in Europe^[1]. During the same time frame, a significant decline in over all mortality rates was also seen. This declines was mainly due to the development of antibiotics, vaccines, safer water, better sanitation and personal hygiene^[2]. These events were responsible for the decrease in the appearance of epidemics and the control of most infectious diseases. Acute disease is not any more the major cause of death. Today one dies from or with chronic illnesses, degenerative diseases, metastatic cancer, immune-deficiencies and other diseases which prolong disability, immobility and dependency.  Dying has become in most instances a long, painful, and expensive procedure^[2].

The worldwide prolongation of the mean life expectancy and the drastic reduction of fertility rate resulted in a rapidly aging world population (Fig.1).  Table 1 describes the total fertility rates in Europe and Table 2 demonstrated the effect of decrease in fertility rates and increase in life expectancy in selected Asian countries/district on the increase of its population above the age of 65. It is projected that in general, the elderly (above 65) will increase within the next 25 years by 82%, whereas the new born only by 3%. The working age population will increase by only 46%. The UN^[3] projects that by 2050, the proportion of  persons above 60 will exceed for the first time the proportion of children below 15, and  13 countries will iave more than 10% of the oldest old (> 80 years old) in their population. Italy will be leading with 14%.

Figure 1.  Aging population.

By the year 2050 Asia will be inhabited by almost 1 billion people aged 65 and above. China (including Hong Kong and Macao), Japan and Singapore will have become members of the club of 14 with more than 10% of their population aged 80 and above. Since the last years of life are accompanied by an increase of disability and sickness, the demand to the social and health services will increase immensely. The high cost in relation to these services will strain to the limit the ability of health, social and even political infrastructures. By the year 2050 Asia will be inhabited by almost 1 billion people aged 65 and above. China (including Hong Kong and Macao), Japan and Singapore will have become members of the club of 14 with more than 10% of their population aged 80 and above. Since the last years of life are accompanied by an increase of disability and sickness, the demand to the social and health services will increase immensely. The high cost in relation to these services will strain to the limit the ability of health, social and even political infrastructures.

Table 1. Total Fertility rates in Europe 1995.

Table 2. Effects of decrease in fertility rate and increase in life expectancy.

Table 3. Life expectancy of males at different ages.

Courtesy of the Registrar General for Scotland (From cheating time by Roger Gosden).

Table 4. Occupational handicap-free life expectancy in Canada (Wilkins & Adamas  1983).

Table 5. Health expectancy (WHO 2000).

The majority of older men today reside in developing countries. As the demographic transition gathers pace in the poorer regions of the world, an even greater proportion of the world's older men will live in countries and regions that have the least resources to respond to their needs.

The communication revolution and its consequence globalization which started at the end of the last century will peak during this century. But if we will not learn to share the resources and wealth of mother earth, poverty will remain enemy number one. It must be our honest aim to achieve the goal that every human being on this earth should be able to age in health and with dignity. The cost of caring for the increasing population of senior citizens will become prohibitive with its attendant socio-economic consequences. To the prudent health care administrators, the establishment of preventive measures, rather than concentration on interventive care is an important strategic thrust in overall management of the aging population^[4]. Frailty, disability and dependency will increase immensely the demand to the social and health services. The very high cost in relation to these services may strain to the limit the ability of health, social and even political infrastructures not only of developing but also of the most developed and industrialized nations. The ability to permit men to age gracefully, maintain independent living, free of disability, for as long as possible is a crucial factor in aging with dignity and would furthermore reduce health service costs significantly. To achieve this objective, a holistic approach to the management of aging has to be adopted^[4].

The promotion of healthy aging and the prevention, or drastic reduction of morbidity and disability of the elderly must assume a central role in the formulation of the health and social policies of many, if not all, countries in the next century. It must emphasize  an all encompassing  life long approach to the aging process  beginning with pre-conceptual events and focus on appropriate interventions at all stages of life.

Life-history studies of childhood and adolescence demonstrate clearly that social factors probably operate in a cumulative fashion.  There are significant social class differences in height growth and other aspects of physical development, as well as in incidence of infectious and other diseases and risk of injury.  For example, the nutritional status of the mother is now known to influence intrauterine growth rates, birth weights, and the later life risks of several important health problems. In addition, a whole host of factors influence growth and development and in turn these factors influence the health status of men in the latter decades of their lives. Vulnerability to physical ill health in childhood and later adult life is associated with poor parental socio-economic circumstances and low levels of parental education and concern.  Cross-sectional studies show differences in mortality and morbidity as a function of socio-economic status, across various disease categories throughout the life span. Poverty has a significant impact on both life and health expectancy. It should not only be measures in terms of property, employment, wages and income, but also in terms of basic education, healthcare nutrition, water and  sanitation. Educational attainment and marital status have also been shown in several longitudinal studies to be powerful predictors of morbidity, health expectancy and mortality.  In addition, age, gender and socio-economic status influence disability-free life expectancy. The economic consequences of retirement place many older citizens in positions of financial vulnerability. As populations age, in both the developing and the developed worlds, the issue becomes how to keep older persons economically viable within their respective societies. No community is exempt from the financial hardships experienced by aging populations.

The life course perspective leads to important policy and strategy decisions. Firstly, it is clearly possible and desirable to improve the health status of men when they are old, although this approach is still not fully implemented. Secondly, a complementary approach to improving the health of older men would focuson appropriate interventions at all stages of their lives. The determinants of aging and of life expectancy extend from genetic and molecular determinants to the increasingly powerful forces of environmental, economical, technological and cultural globalization. Specific measures for the promotion of healthy aging should include:
1. the promotion of a safe envirment,
2. healthy lifestyle including proper nutrition, 
3. appropriate exercise, 
4. avoidance of smoking, 
5. avoidance of drug and alcohol abuses,
6. social interactions to maintain good mental health, 
7. and medical health care including the control of chronic illnesses. 

If done effectively, it should result in a significant reduction of the health and social costs, reduce pain and suffering, increase the quality of life of the elderly and enable them to remain productive and contribute to the well-being of society. The medical and socioeconomic implication of a demographic reality of a new world, will be very different from all preceding epochs in history, indeed so new that most people, their governments, national and private pension funds as well as most health insurers did not yet have sufficient time vision, determination or courage to face up to this immediate challenge. The medical profession, pharmaceutical and health industries are not yet prepared for these emerging markets.

2 Men, aging and health

Before a thing has made its appearance, order should be secured before this order has begun.  Lao Zi

It is impossible to understand aging and health without a gender perspective. Both from a physiological and from a psychosocial point of view, the determinants of health as we age are intrinsically related to gender.  There is increasing recognition that unless research and programmes-on both clinical science and public health - acknowledge these differences, they will not be effective.  While women experience greater burdens of morbidity and disability, men die earlier, yet the reasons for such premature mortality are not fully understood.  The rapidity with which the world-wide population is aging will require a sharp focus on gender issues if meaningful policies are to be developed.  Yet so often gender in the health context is taken as being synonymous only with women's issues^[8].

In contrast  to the recent and much needed attention to the social position and health status in women, men health concerns have been relatively neglected. Men continue to have a higher morbidity and higher mortality rate^[8]. Life expectancy for men is significant  shorter then that for women in most regions of the world^[2].  The course of disease, response to disease and societal response to illness exhibit gender differences and often result in different treatments and different access to health care. The conventional  approach   of  the medical,  behavioral  and social sciences  to  the problem of male aging has been for a  long  time subject of oversight, absence of focusing, disconnection and most of all lack of interdisciplinary  collaboration.

The major causes of morbidity and mortality all take effect over extended periods. DNA is constantly  being damaged and being repaired,  Bones are constantly worn away and rebuilt and atheromas  are constantly  accumulating in side arteries, and are constantly being removed . If the rate of decay is faster then the rate of repair, healthy tissue will be lost  until damage will  produce in symptoms and finally  result in disease. Therefore, primary prevention strategies will be most effective when initiated at the earliest opportunity. Prevention of ischemic heart disease, hypertension and stroke as well as lung cancer, are diseases which primary prevention needs to be addressed.  When problems are more prevalent at older ages, as with prostate and colorectal cancers and osteoporosis early diagnostic tests, such as appropriate  and periodic  use  of  laboratory  tests (e.g. PSA) and screening  procedures can play an important role  in secondary prevention and self care strategies^[9].

Significant numbers of male related  health  problems such as:

• changes  in body  constitution,

• fat distribution, 

• muscle  weakness,

• urinary incontinence, 

• loss of cognitive functioning, 

• reduction in well being, 

• depression,

• as well as  sexual dysfunction,  could  be  detected and  treated in  their  early  stage if  both physicians and public   awareness of  these  problems  was  more pervasive. This could effectively decrease morbidity, frailty and dependency, increase quality of life and reduce health service costs. Women visit the doctor 150% as often as men, enabling them to detect health problems in their early stages. However usually men cost the health services more then women since they seek the medical services  at a more  advanced stage of disease. While women are geared to preventive care, men generally come for reparation.

When discussing age related problems, it is often difficult to separate and to distinguish between
1) the natural aging process, primarily genetically determined (which today can not be changed), 
2)  aging amplifiers determined by environmental and developmental factors (which can be  modified) and 
3)  an acute or chronic illness or intercurrent diseases (which can be prevented, delayed or  cured). 

It must not be forgotten, that aging by itself is associated with reduced productivity, decreased general vigor (frailty of the aged) as well as with increased incidence of defined diseases.  These include:

• cardiovascular diseases,

• malignant neoplasm,

• chronic obstructive pulmonary diseases;

• degenerative and metabolic diseases (arthrosis, diabetes, osteoporosis, etc.)

• visual  loss (macular degeneration, cataract)

• hearing loss

• anxiety,  mood, depression and sleep disorders

• sexual dysfunction

• various dementia (i.e., Alzheimer disease).

• Endocrine deficiencies

Five of six men in their sixties have one or more of these diseases. The chronic degenerative diseases have a long latency period before symptoms appear, and adiagnosis is finally made. Once the diagnosis is made, drugs may alleviate symptoms, but are not very effective to alter the underlying disease which unfortunately usually continues to deteriorate.

Heart disease and stroke are the major causes of death and disability in aging men. Approximately 52 million deaths occur worldwide each year; 39 million occurring in developing countries. About one-quarter of all deaths in developing countries and half of all deaths in developed countries are attributed to cardiovascular disease (CVD). Globally, there are more deaths from coronary heart disease (5.2 million) than from stroke (4.6 million). Age specific death rates from cardiovascular disease increase dramatically with age. Within each country, age-specific death rates for all cardiovascular diseases increase at least twofold between the age groups 65- 74 years and 75-84 years in both sexes, with consistently at least 50% higher rates for elderly men then for women. Morbidity and disability from these diseases are also high. For example, the Global Burden of Disease project estimates that by 2020, coronary heart disease and stroke will be the first and second leading cause of death. Lack of exercise, smoking and obesity are recognized risk factors for CVD. A significant relationship exists between body fat mass and both cardiovascular and overall mortality in men. The increased mortality as observed in obese men was inversely related with physical fitness.

Worldwide, more than nine million people developed cancer in 1997 and more than six million died of cancer. Cancer deaths increased from 6% to 9% of total deaths from 1985 to 1997 in developing countries, but remained about constant at 21% of total deaths in developed countries. The highest mortality rate was observed for lung cancer with approximately 790,000 deaths in 1997, followed by stomach, liver, colorectal, esophageal, and prostate cancer.

For men, prostate cancer is the most prevalent malignancy and the third leading cause of cancer death. In 1990, worldwide, there were 193,000 deaths from prostate cancer, with 127,000 of those deaths occurring amongst those aged 70 years and over and 51,000 amongst those aged 60-69. Since prostate cancer is primarily a disease affecting men over 50, the worldwide trend towards an aging population means that the number of prostate cancer deaths is predicted to increase markedly.

In the year 2020, a global increase of 393,000 deaths is expected with 359,000 of those deaths among men >70 years and 103,000 deaths among men aged 60-69.

Chronic obstructive pulmonary diseases and lung cancer is not only one of the most frequent problems among men, but are the most preventable. In men, 90% of all cases are attributable to cigarette smoking. These data suggest that almost every male lung cancer patient could have prevented his disease. Strategies to promote smoking cessation should be a top public policy priority, especially in those developing countries where aggressive marketing by the tobacco industry is not counterbalanced by adequate public health information advertisements.

The loss of vision, hearing and other senses should be recognized as more than physical problems. Such conditions have profound effects on social and personal interactions, economic viability, and mental health of those affected, and should be treated seriously.

Depression is the most common functional mental disorder affecting aging males, it is under-diagnosed and under-treated. It has a high rate of recurrence and is associated with significantly increased mortality. Depression is closely linked in this group with physical illness and altered presentation can make diagnosis difficult. Thorough holistic assessment and good communication skills are of utmost importance. Nurses and medical professionals can improve the mental health of these patients with therapeutic attitudes and actions. It must be remembered that about 90% of older men who attempt or complete suicide have depression either not diagnosed or inadequately treated. If men continue to under-report depression, the morbidity of this condition will continue to increase. Proper identification and treatment of depression will have significant public health implications.

Cognitive decline with age is inevitable but the global impairment of the higher cortical functions can be delayed. Estrogen specifically maintains verbal memory in women and may prevent or forestall the deterioration in short-  and long-term memory that occurs with normal aging. There is also evidence that estrogen decreases the incidence of Alzheimer disease or retards its onset or both^[10]. The delayed onset of Alzheimer disease in men may be due to the fact that estrogen levels are significantly higher in aging men then in post-menopausal women. In women HRT was shown to delay the onset of Alzheimer disease.  There is an urgent need to obtain such information also  in men. Dementia is a major public health issue accounting for significant morbidity, loss of independence, loss of dignity and eventual institutionalization.  The prevalence of severe dementia increases from 1% at ages 65-74,  7% at ages 75-84 and 25% after the age of 85. 37% of patients with Alzheimer's disease lived in institutions compared   with 1.7% of subject without dementia.

Sexual desire, sexual arousal, sexual performance and sexual activity decrease significantly with aging  with a striking increase in the prevalence of impotence in men over 50.  Reasons for decreased sexual activities include loss of libido (partially due decreased androgen production), lack of partner, chronic illness and/or various social and environmental factors, as well as erectile dysfunction (ED). It was found that sexual information significantly and independently contributed to sexual enjoyment and satisfaction. Persistent interest in sexual activity results in positive mental and physical healthy benefits. The frequency, duration and degree of nocturnal penile tumescence decrease significantly with age.  These events are concomitant with a significant decrease in bio-available testosterone and a compensatory increase in LH showing that aging is associated with decreased gonadal activity. Worldwide more than a 100 million men are estimated to have some degree of ED. Erection is a neuro vascular phenomenon under hormonal control and includes arterial dilatation, trabecular smooth muscle relaxation and activation of the corporeal occlusive vein mechanism. Some of the major etiologies of ED are hypertension, diabetes and heart disease. Depression, a disease frequently accounted in aging men, is  an important etiology for ED. Furthermore the anti-depressants  administered may alleviate the symptoms of depression but may by  themselves increase ED.  Therefore,  the antidepressant to be used should be carefully considered, weighing the cost and benefit for each product and each individual patient.  It should also be remembered that genitourinary and colon surgery very often cause ED. Nerve-sparing surgery, which may reduce the incidence of ED, should be used whenever possible. Patients should be counseled prior to such interventions.

Many drugs, particularly anti-  hypertensive and psychotropic drugs may cause various degrees of ED.    When focusing on the maintenance of quality of life among aging men, efforts to maintain, restore or improve sexual function should not be neglected.  Recent advances of basic and clinical research has led to the development of  new treatment options for ED, including new pharmacological agents for intra-cavernosal, intra-urethral and oral use .  Orally acting preparations with either central action (apomorphine) or peripheral action (Sildenafil) alone or in concert with androgens have significantly improved the fate of men with erectile and or sexual dysfunction. The management of ED should only be performed following proper evaluation of the patient and only by physicians with basic knowledge and clinical experience in diagnosis and treatment of ED.

Partial  endocrine  deficiencies of aging are associated with a decrease in the peripheral levels of  testosterone,  dehydroepiandrosterone (DHEA) and its sulphate (DHEAS),  growth hormone (GH),  IGF1, and melatonin.  There is also a concomitant increase in LH and FSH.  In addition sex hormone binding globulin (SHBG) increases with age resulting in further lowering the oncentrations of  free biologically active testosterone With aging there is a loss of circadian rhythmicity of testosterone. These changes are associated with:

A decrease in general well being                
A decrease in sexual pilosity 
A decrease in libido
A decrease in cognitive function
A decrease of red blood cell volume
A decrease in muscle strength
A decrease in bone mass (osteoporosis) with an increased fracture risk
A decrease in immune-competence
An increase in fat mass, with a change in fat contribution and localization
An increase in cardiovascular accidents
An increase in mood disorders, 
An increase in sleep disorders.

With prolonged life expectancy, men and women live today one third of their life with some hormone deficiency. In cases of endocrine deficiencies, irrespective of age, traditional endocrinology aims to replace the missing hormone or hormones with substitutes. The decision to start hormone replacement therapy in men should only be taken after obtaining objective evidence of hormone deficiencies, after exclusion of secondary causes of endocrine dysfunction and after making the balance of risks and expected benefits of the replacement therapy.  When data of long-term well-controlled studies will have become available, long-term substitution therapy with one or more  hormonal preparations will most probably, if used correctly, improve the quality of life of aging men and may even delay the aging process.  It is probably  not unrealistic that in the future  HRT in men will become as common as in women today. It has been demonstrated that interventions, such as hormone replacement therapies, the use of anti-oxidant drugs, proper and personally tailored nutrition, with vitamin supplements when ever necessary, as well as individually adjusted regular physical activity (aerobic, anaerobic and stretching) has significant physiological, psychological and social benefits for older persons and may favorably influence some of the symptoms of aging as well as some of the pathological conditions in aging men.

The correct strategies in the management of aging should permit men to age in health and dignity improving their quality of life by preventing the preventable and postpone, delay and decrease the pain and suffering of the inevitable. Educating both the public and health-care providers about the importance of early detection of male health problems will result in reducing rates of morbidity, mortality, as well as health costs for many age-related diseases. Many men are reluctant to visit their health center or physician for fear, lack of information and psychological reasons For more than 100 years, gynecologists have been specialized physicians for the medical care of the woman. About 50 years ago, gynecologists understood that the women's health physician is more then an obstetrician and an "oncology oriented surgeon", and slowly the "medical oriented gynecologist evolved, trained  in reproductive endocrinology, in peri-neonatology, in ultrasound, in family planning and recently in assisted reproductive procedures. The training curricula (specially in The USA and the UK) where constantly modified and adapted to the needs of women's health. The modern gynecologist is not only cure-oriented, but has been trained in preventive strategies and in the maintenance of health and well being. He will take care of women from adolescence to menopause. Today in most part of the world enough gynecologists have been trained to take care of women's health.

The present day surgically oriented urologist has arrived at the same cross road gynecologists reached 50 years ago. They are today highly specialized surgeons for the prostate, kidney, bladder and the urinary tract. They have become highly specialized oncologists and diagnosticians in their field of specialization and many have also specialized in the diagnosis and treatment of ED. Some have become nephrologists and some have specialized in transplantation. A few have become androlgist specialized in gonadal physiology and pathology and in the treatment of infertility, mostly in collaboration with gynecologists, extracting sperm from testis or epydydemis or diagnosing and managing varicoceles. Training in urology is extremely long. With surgical procedures decreasing and being replaced by medical interventions the idea of the Medical Urology evolved.  The number of urologists worldwide today is far to small to take care of all men. To become the man's health physician they will have to receive sufficient training in endocrinology, internal medicine, especially cardiology, and psychology/psychiatry; they will have to be trained to manage nutrition, aerobic and anaerobic exercise and have a solid understanding in gerontology. The International Society for the Study of the Aging Male (ISSAM) is working together with the diverse urological and andrological associations to obtain this goal. However, until this goal will be achieved, and until sufficient urologists/andrologists will have been trained, a gate keeper will be required to serve and manage men's health. Who can take the role of gate keeper for men's health will depend on the specific training, culture, and the medical services of each geographical area and country. Men's Health could be managed by an interdisciplinary group practice, or by the primary health worker, the family physician, the general practitioner, the endocrinologist or a specialist in internal medicine or gerontology. Each member of this profession can be trained to become a gate keeper for men's health and learn to screen men for their most probable risk factors, advise them on life style and whenever necessary refer the man to the specialist he may need. Men usually do not consult a doctor except if they have an acute illness. When a man comes to see his family doctor for a common cold, a gastrointestinal disorder or any other acute infection, the physician should according to the family history, body constitution, life style and risk factors, advise the patient on preventive strategies or refer him to consult the correct specialist. 

3 Strategies to improve and maintain aging men's health

Men who are educated about the value that preventative health care can play in prolonging their life span and increasing the quality of life and their role as productive family members, will be more likely to participate in health screening. To obtain this goal it will be necessary:

1) to make available a group of trained medical professionals who can understand, guide, educate and manage the problems of the aging men.
2) to provide more information about the normal male aging process and to advertise and promote aging in a positive and active way.  Men should receive education and be prompted to take on teaching roles themselves, leading self-help groups and advocating on behalf of their aging communities.
3)   to established programs empowering men to become well-informed, active managers of their own health and the health of their surrounding social environments
4)  to obtain essential epidemiological data and  to intensify basic and clinical research on aging men,  
5) to assess age-related nutritional needs
6) to develop strategies for physical exercise (aerobic for maintaining cardiac function, anaerobic - targeted to specific muscle groups and stretching)
7)   to develop and assess new and improved drugs for prevention and treatment of pathological changes related to aging. 

To this end, the efforts of all governmental and non-governmental organizations to promote aging men's health on local, national and international levels must be strongly encouraged.  A holistic approach to this new challenge of the 21st century will necessitate a quantum leap in multidisciplinary and internationally coordinated research efforts, supported by a new partnership between industry and governments, philanthropic and international organizations.

It is my sincere hope that the next few years will enrich us with facts and clarify  the state  of our present knowledge  permit us to recognize  some  of the missing links and give us the tools and methodology to design and  plan ways to understand aging of men, permit us to help  to improve  the  quality  of  life, prevent  the  preventable, and postpone and decrease the pain and suffering of the inevitable.

References

[1] United Nations Secreteriat Department of Economic and Social Affairs Population Division. World Population Prospects, The 1998 Revision. ESA/P/WP 150, New York: United Nations; 1998. 
[2] Lunenfeld B. Aging male, The Aging Male 1998; 1: 1-7.
[3] United Nations, World Population Prospects, The 1998 Revision. New York: United Nations; 1999.
[4] Lunenfeld  B. Hormone replacement therapy in the aging male. The Aging Male 1999; 2: 1-6. 
[5] WHO.  International Classification of impairments, disabilities and handicaos. Geneva: WHO; 1980.
[6] WHO. Jakarta Declaration on Leading Health Promotion into the 21st Century. Geneva: WHO; 1997.
[7] Wilikins R, Adams OB.  Health expectancy in Canada,  demographic, regional and social dimensions. Am J Public Health 1983; 73: 1073-80.
[8] Kalache A, Lunenfeld B. Health and the aging Male. The Aging Male  2000; 3: 1-36. 
[9] Tremblay RR, Morales AJ.  Canadian practice recommendations for screening monitoring and treating men affected by andropause or partial androgen deficiency.The Aging Male  1998; 1: 213-21.
[10] Sherwin BB. Can estrogen keep you smart? Evidence from clinical studies. J Psychiatry Neurosci 1999; 24: 315-21.

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Correspondence to: Prof. Burno Lunenfeld, President, ISSAM, 7 Rav Ashi St., 69395 Tel Aviv, Israel.
E-mail: blunenf@attglobal.net
Received 2001-06-06    Accepted 2001-06-19