First Asian ISSAM Meetinh on The Aging Male, Kuala Lumpur, Malaysia, 1-3 March 2001 C an overview

Renate Leimller, Bruno Lunenfeld¹

International Society for the study of the Aging Male ( ISSAM ), CH-1211, Geneva 1,Switzerland

1 Aging in Asia-an avalanche starts to form

More than 400 delegates heard that Indonesia has the fastest growing aging population (65 years) and in 2025 it will be increased by 414%, followed by Kenya (347%), Brazil (255%), China (220%) and Japan (129%). The greater part of those seniors of tomorrow will be women, since they survive longer than men for roughly seven years. The reasons for this fact are not entirely clear, but indisputably female care more for health, and seek medical advice more often. Whereas postmenopausal hormone replacement therapy is widely accepted, the consequences of the gradual decrease of male sexual hormones did not attract serious attention in Asia. This attitude is hopefully bound to change, as the key lectures suggest that the replacement of testosterone in proven cases of androgen deficiency can contribute to improve the quality of life of the individual.

2 Integration instead of separation

To make this dream reality, the nowadays picture of the forever young society has to be changed; old persons are often felt as a burden for the state, the insurers, the employers, and as soon as disabled, even for the children. As the overwhelming part of old people traditionally are supported by the family, big problems will emerge in the near future especially in China with regard to the longstanding policy of the one-child-family. Where can the old ones go? Family structures have also changed in the rest of Asia, with women being integrated in the working process to earn money for the family which makes family support of the aged complicated.

What can be done? For Dr. Tan Hui Meng (Malaysia), a retraining and redirecting of the human resources is mandatory: special programmes for the period of pre-retirement and for older people should be created. There they could learn about what they can do themselves for healthy aging, what they can do for other members of the society, how to pass on their skills according to their physical and mental strength, and to culture and customs. Professor Vinod Kumar, WHO-Delegate from New Delhi, focused this aspect in the words the old people shall be givers, not takers.

With regard to the male perspective, Professor Poo Chang Tan from the University of Malaya (Malaysia) proposed a prolonged working life in no way in the traditional sense with just doing the same job only for a longer time and so blocking the way for the young. Instead she favours new models, where the skills and favoured occupations of the young old can be used-working as a consultant, or in a post of honour, teach calligraphy or tai chi, care for children, etc. We have to think in new schemes to keep people engaged, abolish age discriminating practices, and start in young age, she summarised.

3 Holistic approach needed

The shift in paradigms inevitably requires a holistic approach to manage active aging, Professor Victor Goh from Singapore University supported his colleague, comprising not only economic and social aspects but health care, too. Today people face six to twelve years of disability, but depending on the access to care systems with growing longevity this time span will increase to twelve to 30 years. Facing this prospect, Dr. Goh underlined the need for prevention, which is never too late, but ideally should start in younger days. Active aging involves anindividual decision, over and over again, he noted. The prerequisite is information on nutrition and healthy lifestyle, including exercise appropriate to age and culture. The health care systems have to be adapted to the growing rate of old people and their special needs; complimentary medicine can be helpful, but has to be evaluated on a scientific basis. This holds true for replacement therapies as well, he said.

As most of the data on aging processes so far have been accumulated in the western world, Dr. Goh started a longitudinal research study on natural aging (RNA) in Singapore, a city with a well known mix of Chinese, Indians and people of other Asian countries. It is planned to enrol 1,500 persons aged 30 to 70 for several years, to assess the normal range of many different parameters like body composition, lipid profiles, hormones, as well as the age related amount of diabetics, or people at risk of heart disease or osteoporosis. For the future, different intervention arms are planned, e.g. HRT for female and male.    Preliminary results from 500 patients revealed an astonishing high number of women at risk of osteoporosis even in younger age: 9% of the women aged 40 to 50 showed bone mineral density below 70% of the reference normal range of young reference women. These rates increased in the following decades, reaching 15% to 27% in the mid-sixties. In Taiwan, China 12% of the male and 18% of the women over 65 suffer from vertebral fractures, while over the age of 70 the rates for both genders are equal.

4 Growing need for trained geriatric staff and departments

As the examples show, a pressing topic to attend to is the future need for trained geriatric staff and well equipped geriatric departments to enable adequate therapy and avoid prolonged hospitalisation for elderly patients. In the financially better off Taiwan, China and in Singapore these problems have been mastered, whereas the rapidly growing Indonesia today has only one  single geriatric clinic. In the Philippines, where 16% of the female and 11% of the male elderly persons are underweight, a great proportion is suffering from anemia, and deficits in vitamins, the access to medical care is limited and most of the clinics are without gerontologists. With respect to the knowledge and care for the aging male, the situation is not much better: trained andrologists are very rare in most of the Asian countries.

5 Biostimulators or testosterone replacement? 

Aphrodisacs manufactured from the plant Tibulus Terrestris L. Bulgaricum are sold in high quantities, as is an extract of the roots of  Eurycoma Longifolia (Jack). Both claim to be biostimulators, naturally increasing the androgen levels in hypogonadal or testosterone-deficient men. Despite no solid proof, both are widely used. Malaysia had to protect the Eurycoma Longifolia tree to prevent excessive root-collecting. Nevertheless, with better knowledge of the effective compounds and the clear-cut pharmacological action, some Asian scientists would prefer the natural stimulation of androgens to the substitution with testosterone derivatives, which, when given in excess, may suppress the endogenous androgen production.

Although many symptoms of aging are reminiscent of symptoms of androgen deficiency, in contrast to hormone replacement therapy in menopausal women, androgen substitution in aging male has not been well documented. Moreover, symptoms frequently show only  a weak but significant correlation with (free) testosterone levels, as Professor Alex Vermeulen from Ghent (Belgium) told the audience. A role of decreased testosterone levels in this symptomatology is likely, although the symptoms have a multifactorial origin, he added deliberately. Replacement therapy therefore requires a thorough physical examination including a digital rectal examination and the estimation of prostate specific antigen (PSA), as prostate carcinoma is an absolute contraindication for androgen administration. The well-known andrologist stated: "Androgen replacement therapy should only be considered if: 

*clinical examination indicates an androgen deficiency,
* laboratory findings confirm a testosterone deficit, 
* and if absolute contraindications have been ruled out.

These include chronic obstructive lung disease, sleep apnoea, severe lower urinary tract symptoms, and hyperlipidaemia.

6 Who is androgen-deficient?

The problem is: there is no convincing evidence of an altered androgen requirement in elderly men. Hence western andrologists apply the same biochemical criteria for subnormal testosterone levels in young and in elderly men: 11 nmol/L for testosterone and 0.225 nmol/L for free testosterone (determined by dialysis or calculation). In using these criteria, more than one forth of the men aged 70 and above are androgen deficient, Dr. Vermeulen said.

The experience with replacement therapies is relatively limited in the number of patients and length of treatment. It appears that if selectively and properly administered, most side effects of replacement therapy can be avoided. But long-term studies are urgently needed before these therapies can be generally advised, the speaker cautioned. The important issues to clarify include:

* the definition of objective criteria for androgen deficiency
* the definition of the specific androgen levels required for each end-organ
* the special role of androgen deficiency in aging symptoms, and
* the risks of concomitant diseases.

7 Old fears and new perceptions

At least in two points the fear of a negative impact of androgen replacement seems to be questionable: androgens probably are not the bad guys with respect to cardiovascular functions and they could even be beneficial in males with a testosterone deficiency. Although the evidence is far from hard at the moment, pilot studies with male volunteers indicate comparable effects of testosterone with respect to arterial vessels as are established for estrogens in women. Several small studies conducted by the cardiologist Dr. Peter Collins at the Imperial College School of Medicine in London propose even an antiischemic effect of testosterone: men with established androgen deficiency as well as coronary heart disease had an exercise ECG after withdrawal of the anti-ischemic medication, and addition of either placebo or high dose testosterone intravenously. Given the hormone, the test persons were able to exercise significantly longer, as measured by the time to ST segment depression, a well known marker of ischemia. With these promising results Collins group is planning to start a long term study with oral testosterone to clarify the possible  beneficial effects for coronary patients.

The other point of concern with androgen replacement therapy is the induction of an inappropriate growth of the prostate. Also this  assumption seems not to be true, as Professor Louis Gooren from Amsterdam (The Netherlands) told the audience. Studies so far show a growth of the comparably small prostate of hypogonadal men, but only to the volume the organ normally reaches in eugonadal men. Most probably androgens do not initiate malignant prostate growth, but seem to be essential for the development of prostate cancer, the specialist stated.

For the replacement therapy itself a broad range of testosterone formulations are on the market. Costs are differing widely, but the experts heavily discouraged from prescribing the cheap methylated esters because of their liver toxicity. Parenteral application does not seem the ideal solution because of excessive androgen peaks soon after the injection  and  very low testosterone levels prior to the next administration. Oral preparations such as testosterone undecanoate  (absorbed via the lymphatic system) taken in the morning and evening give more constant hormone profiles, and are best resorbed when taken with the meals, Gooren explained. The other choices are implants, patches and gels.

For the future, new substances will enrich the selection to choose from, Professor Alvaro Morales from Kingston (Canada) said. He hopes for designer androgens acting as selective androgen receptor modifiers (SARMs). Ideally these drugs should:

* have no effect on the prostate, 
* stimulate libido, sex function, hair growth (in the desired places), 
* increase muscle and lean body mass, and 
* also influence the lipid profile positively. 

Despite popular beliefs, testosterone replacement will not ameliorate erectile dysfunction (ED), unless it is basically a brain problem, which holds true for only around three percent of the cases in the western world, or is due to decreased libido. For the broad majority of elderly ED patients, the dysfunction is due to underlying diseases such as diabetes, hypertension, benign prostate hyperplasia, neural or vascular problems. A survey in Singapore revealed a very high incidence of ED in Chinese men (81.3%) compared to Malay (6.6%), Indian (6.7%) and other Asian elderly patients (4.2%), the origin of the ED being predominantly physical in origin.

Given the wide variety of potent new drugs and devices on top of the traditional medications most of the patients nowadays can be helped-bearing in mind a documented placebo effect in the range of 30%.  

Practical Tips

As risk factors for erectile dysfunction are in part similar to those known for cardiovascular disease, prevention is possible by not smoking, and control and therapy of hypertension and diabetes. Besides a healthy lifestyle, daily exercise keeps muscles, heart, and lungs in form, helps to prevent bone loss, and thereby helps to grow old in a healthy state. It is also a well known fact, that females keep males young. And how to elevate testosterone was an open secret already in the old days in China: coitus and scrotum massage. In men with symptoms of benign prostate hyperplasia, adequate treatment not only improves quality of life, but patients will feel less fear and anxiety. Both are known to be a potent predictors of sexual dysfunction.

Correspondence to: Dr. Renate Leinmller, Taunusstr. 14, 63067 Offenbach, Germany.
Tel: +49-69-88 4593   Fax: +49-69-88 8901
E-mail: RLEINMUE@aol.com
¹Prof. Bruno Lunenfeld, President, ISSAM, 7 Rav Ashi St., 69395 Tel Aviv, Israel.