MEN'S HEALTH: AN EMERGING CONCEPT CHALLENGES FOR MEN TODAY

The challenges ahead with regard to the aging male are tremendous. In the year 2000, there were more than 400 million people aged 65 and over in the world - rojected to increase to almost 1.5 billion by the year 2050 - close to fourfold increase compared to the 50 % increase for the global population as a whole. More than 25 % of these 1.5 billion elderly people are projected to be "oldest-old" (aged 80 and over). Global ageing is a two edged sword: a triumph and a concern of immense proportions. As we have entered the 21st century, it will put increased economic and social demands on all countries. But if more and more individuals reach older age in good health - and remain healthy for longer - the benefits will be shared by all. Therefore, the promotion of healthy ageing and the prevention of disability in all older people must assume a central role in medical care and research as well as in the formulation of national health and social policies. Effective programs promoting healthy ageing will ensure a more efficient use of health and social services and improve the quality of life in older persons by enabling them to remain independent and productive. With prolonged life expectancy, men and women can expect to live one-third of their lives with some form of hormone deficiency. Life expectancy differences between men and women exist in various regions of the world with a mean of 4.2 years, and is projected to increase to 4.8 years by the year 2050. The ageing male, in particular, has the risk of developing gender-specific urological diseases, such as prostate cancer, benign prostate hyperplasia continence disorders (generally ignored by men) and erectile dysfunction. Hormonal changes in the ageing male are associated with changes in the body mass index, osteoporosis, and sleep and mood disorders. A significant relationship between body fat mass and both cardiovascular and overall mortality in men has been demonstrated. Men die on average 4-5 years earlier than women and cardiovascular diseases manifest themselves earlier than in women. Health education is of utmost importance and can be done at low cost. In the words of Bruno Lunenfeld, it is to be hoped that our endeavours allow us to help to improve the quality of life, prevent the preventable, and postpone and decrease the pain and suffering of the inevitable.

TESTOSTERONE REPLACEMENT THERAPY: CURRENT AND FUTURE

Ronald S. Swerdloff, Christina Wang

The currently available methods of androgen delivery systems are shown in the table. The injectable testosterone enanthate has been the most widely used preparation in many countries and is administered IM as 200 or 250 mg every two to three weeks. In subjects who may complain of fluctuations in mood and response, the dose may be reduced to 100 mg once every 7 to 10 days. Oral 17 alkylated androgens are not recommended for long term replacement therapy because of possible liver toxicity and significant lowering of HDL- and increases in LDL- concentrations. Oral testosterone undecanoate has long term safety and efficacy data but has to be administered at least twice per day and together with food. Large inter- and intra- subject variability in serum testosterone levels have been reported. The newer transdermal preparations when applied daily allows achieving steady delivery of testosterone within the physiological range. The reservoir and matrix skin patches may cause skin irritability in about 10 to 30 percent of patients and may not be tolerated or may have problem with adhesiveness. Testosterone gel delivers testosterone to reach relatively constant concentration of testosterone and allows more flexibility in doses. Short term (6 months) studies show that daily testosterone gel application results in improved sexual function, mood, lean body mass, bone mineral density and decreases in fat mass with minimal skin irritation. Long term (24 months) study in hypogonadal men demonstrates persistence of the benefits of androgen replacement therapy. With testosterone gel, transfer of the steroid at close skin contact can be avoided by clothing or showering. A new bioadhesive buccal tablet is being investigated in Europe and United States and preliminary data show that physiological serum testosterone levels can be achieved. Testosterone undecanoate is also formulated in oil as an injectable to be administered IM once in 12 weeks and has undergone clinical trials. Though approved in China, this preparation is awaiting approval in Europe. The future of testosterone delivery relies on the development of selective androgen receptor modulators with the benefits of testosterone but without its potential adverse effects.

PROSTATITIS: NEW CONCEPTS IN DIAGNOSIS AND THERAPY

Introduction: Prostatitis represents a source of intense frustration for patients and clinicians. This presentation outlines evidence-driven recommendations, current controversies and research directions.

NIH Classification of Prostatitis Syndromes.
I. Acute bacterial prostatitis
II. Chronic bacterial prostatitis
III. Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)

A. Inflammatory subtype
B. Non-inflammatory subtype
IV. Asymptomatic inflammatory prostatitis

Diagnostic Recommendations (2002 International Consensus)
Basic investigations
History
Physical examination, including digital rectal examination
Urinalysis
Urine culture

Further evaluations to define and direct therapy
Lower urinary tract localization test
National Institutes of Health Chronic Prostatitis Symptom Index
Flow rate
Residual urine determination

Evaluations in selected patients
International Prostate Symptom Score
Semen analysis/culture
Urethral swabs
Pressure flow studies/urodynamics
PSA
Urine cytology
Pelvic Imaging
Cystoscopy

Treatment Recommendations:
The evidence supporting current recommendations is considered.
Natural approach
Non-drug approach
Medical therapies
Surgical therapies
A therapeutic approach is then suggested for each prostatitis syndrome.

Research agenda:
The critical questions are considered, emphasizing the prominent role of Asian investigators.

SEXUALLY TRANSMITTED DISEASES: PRACTICAL MANAGEMENT UPDATE

Since antiquity, urologists have diagnosed and treated sexually transmitted diseases (STDs). STDs remain important today with more than 15 000 000 new cases each year in the U.S. The standard approach is based on traditional divisions among the medical microbiologists: bacterial, viral, protozoan, fungal infections, etc. This works very well for the microbiologists and for textbooks that emphasize the similarities and differences among organisms in each category. Unfortunately, this traditional approach does not work well for most urologists. We see patients with specific problems, or syndromes. Many syndromes can be caused by a variety of infections. These organisms often have little in common from a microbiological perspective other than a propensity to be transmitted by sexual contact. To present a practical review, we will take a syndromic approach, emphasizing diagnosis and treatment guidelines and new concepts.

Genital ulcers
Herpes
Syphilis
Chancroid
Lymphogranuloma venereum
Granuloma inguinale

In the US, genital herpes is the most common cause of genital ulcers. However, more than one disease may be present simultaneously. Each of the causes of ulcerative STDs has been associated with an increased risk of HIV infection. There are five important considerations in the differential diagnosis of a genital ulcer: genital herpes, syphilis, chancroid, lymphogranuloma venereum, and granuloma inguinale. Because diagnosis based on the history and physical examination if often inaccurate, laboratory confirmation is desirable. The recommended diagnostic evaluation includes: culture or antigen test for genital herpes virus. Darkfield and/or immunofluorescence test for Treponema pallidum, culture and/or polymerase chain reaction based testing for Haemophilus ducreyi, and an HIV test.

Genital herpes simplex virus (HSV) infections. In the US, >50 000 000 people are infected. New data suggest that most infected people are never diagnosed because they suffer mild or subclinical infections. However, such asymptomatic persons still shed HSV in their genital tracts and they can transmit infection. There are two genital HSV viruses, HSV-1 and HSV-2. HSV-2 is responsible for most recurrent genital infections. HSV-1 is responsible for 5 % - 30 % of initial infections but recurrence is much less common. Thus, viral typing is useful for both prognosis and counseling.

Systemic antiviral therapy provides partial control of HSV signs and symptoms but it does not eradicate the virus. Treatment does not change the recurrence rate after treatment is discontinued. Three antiviral drugs have proven effective for treatment of HSV infections: acyclovir, valacyclovir, and famciclovir. Most first HSV infection episodes should be treated. Treatment for recurrent HSV can be prescribed for symptomatic episodes or on a daily basis to reduce the frequency of recurrences. Treatment also reduces the frequency of transmission to uninfected partners.

Genital exudates. The exudative STDs include urethretis (both gonococcal and non-gonococcal), mucopurulent cervicitis, and vaginitis. Since most considerations in diagnosis and therapy were covered in the previous presentation. Therefore, we will concentrate on management of important urological complications. In men, the most important complications include epididymitis and Reiters syndrome. In women, the most important complications include pelvic inflammatory disease, ectopic pregnancy and infertility. Particular emphasis is placed on treatment guidelines for diagnosis and management of patients with persistent urethritis and epididymitis.

Human papillomavirus (HPV) infection. More than 20 HPV genotypes infect the genital tract. Most infected people have asymptomatic, subclinical, or unrecognized infections. Visible warts are usually caused by types 6 or 11. Other types, e.g., types 16, 18, 31, 33, and 35, are associated with cervical dysplasia, cervical carcinoma, genital squamous intraepithelial neoplasia and squamous cell carcinoma.

The primary goal of therapy for HPV is removal of symptomatic lesions. Currently there is no evidence that treatment changes the natural history of infection of that it eradicates infection. Treatment may decrease infectivity. It is also important to remember that warts may resolve spontaneously. Currently, there is no evidence that screening for subclinical infection offers any benefit to patients.

Many treatments are available but none is ideal. Recommendations are discussed for both patient-applied and provider-applied therapies. Surgical procedures, such as curettage, cautery, or laser therapy are recommended for treatment failures or where accurate diagnosis is in question (e.g., possible carcinoma, carcinoma in situ, or squamous intraepithelial neoplasia).

S02

IMPACT OF MODIFYING LIFE-STYLE ON SEXUAL FUNCTION

Some years ago, the World Health Organization has identified erectile dysfunction (ED) as an important quality of life health issue. Subsequently, many multi-national, multi-centric studies have been conducted to determine the incidence of ED in different populations and the important factors in its causation. Broadly, these can be classified as socio-economic factors, lifestyle factors, and co-morbid medical factors (as opposed to other causal factors such as spinal cord injury, prostatectomy, etc).

Socio-economic factors include education levels, occupation, ethnicity, sexual orientation, marital status and relationship problems. The incidence of ED is higher in the less educated, blue collar as opposed to white collar workers, blacks as opposed to whites (in one Brazilian study), homosexuals and bi-sexuals as opposed to heterosexuals, and among the unmarried and those with relationship difficulties.

Co-morbid medical conditions frequently associated with ED include diabetes, hypertension, other cardiovascular diseases, depression, obesity, prostatic diseases, LUTS, concomitant medication, and indeed the aging process itself.

The important lifestyle factors in ED are smoking, alcohol, substance abuse, sedentary occupations and practices (including TV viewing !), and that villain of modern living - stress.

Of these, socio-economic and co-morbid factors are not always modifiable. While one can try and work on one's relationships and diabetes control, for instance, it is not easy to change one's ethnicity or sexual orientation.

Lifestyle factors are the factors in ED that are totally modifiable and within one's control. Many of these cause ED by aggravating existing co-morbid conditions, if not per se. Modification of lifestyle must be begun early and preferably prophylactically to confer results, since it has been shown in some studies that waiting until middle age or after ED has set in, might be a bit too late. Physical exercise and maintenance of ideal body weight confer appreciable improvement in all, especially the sedentary and obese.

In recent years, the author has been strongly advocating yoga and meditation as a lifestyle practice for males, to be begun early. Tremendous mind-body health benefits can accrue from this, not just in sexual function, but in overall well-being.

DRUG INDUCED SEXUAL DYSFUNCTIONS: PREVENTION AND MANAGEMENT

Many prescription drugs are commonly implicated with ED and other forms of SD. These include antihypertensives, antidepressants, antiandrogens, anticholinergics, hormones, diuretics, cardiac drugs, H2 receptor antagonists, cytotoxic agents and tranquilizers.

In most cases, sexual dysfunction is reversible on drug discontinuation; dosage reduction in combination with appropriate lifestyle modification can also be effective. If an agent causes or worsens existing ED, it may help to switch patients to different drug. For instance, among antihypertensives, switching from a non-selective to a selective b-blocker can help resolve ED. Ca²⁺ channel blockers such as diltiazem and verapamil are associated with least ED. Cloxazocin or terazocin has been recommended in lieu of the a1 blocker prazocin. When ACE inhibitors and angiotensin receptor blockers induce ED, intraclass switching is unlikely to resolve ED. In some cases, low dose combination therapy may minimize ED. Commonly used lipid lowering drugs such as statins and fibrates may also cause ED. Statins inhibits the synthesis of steroid hormones including testosterone from cholesterol. Switching to alternative lipid lowering drugs of the same or different class may resolve the problem of ED.

In addition to depression per se, all four groups of antidepressant medications, namely tricyclic, heterocyclic, SSRI, MAOI can also precipitate ED. Their mechanisms of action include anticholinergic, sympathomimetic and altered serotoninergic activities. Together with ED, the antidepressants can also cause loss of libido and arousal, delayed or absent orgasm and ejaculatory dysfunction. Management includes dose reduction (for those who are stable and compliant) or switching to agents without these effects. Drug induced hypogonadism with testosterone lowering effect will be reflected through fewer nocturnal erections, decreased libido and decreased ejaculate volume. It is important for physicians treating patients with ED and other sexual dysfunctions to recognize these side effects for better patient care and management.

AN UPDATE ON THE PATHOPHYSIOLOGY OF ERECTILE DYSFUNCTION (ED): ED- AN IMPORTANT DISEASE

The human penis is a masterpiece of hydraulics capable of unique complex erectile function. It is flaccid in its basal physiological state of detumescence, but may quickly become firm and turgid in response to central and peripheral neuro-psychic signaling from amorous or erogenic stimulation.

Central to penile flaccidity/detumescence and penile rigidity/erection is the physiology of the smooth muscle cell (SMC) in the corpora cavernosa (CC). This has become much better understood in recent years as a result of biotechnological advances, accelerated by the serendipitous discovery that phosphodiesterase-5 inhibition was beneficial for ED.

The cavernosal trabecular and vascular SMCs regulate respectively the capacity of the sinusoids and the arterial blood flow in the helicine arteries. SMC contraction is modulated via the a-adrenergic pathway, and by endothelin, noradrenaline, neuropeptide Y and prostanoids. The principal mediator of SMC relaxation has been identified as nitric oxide (NO), which is produced under the influence of neuronal, endothelial and inducible nitric oxide synthase (NOS). Vasoactive intestinal polypeptide, calcitonin gene related peptide and prostanoids too contribute to SMC relaxation.

ED may result from impaired SMC relaxation or augmented SMC contraction. Numerous conditions are associated with ED with the majority having an organic aetiology most of which is vasculogenic. There is increasing evidence that impaired NO-mediated endothelial vasodilatation in vasculogenic ED is indicative and predictive of endothelial dysfunction, which correlates closely with most cardiovascular risk factors.

ED is indeed not just a lifestyle inconvenience but an important disease with far-reaching implications.

S06

HOW SHOULD ED BE MANAGED: THE ASIA PACIFIC CONTEXT INCLUDING THE ROLE OF THE TRADITIONAL THERAPIST

Aim: After the effective oral medications for the ED appeared in market, the management for this old human's disability is needed to be adjusted, especially in some traditional Asia-pacific societies. This review is aimed to discuss how the ED patients should be dealt as "goal directed therapy" and how the traditional measures to be a role as an adjuvant therapy for the modern treatment of ED. Methods and Results: We investigated those patients who failed to respond well after a long-term Sildenafil (Viagra) taken. Some of the patients only accepted oral medication and could not consider further invasive treatment such as intracavernosal injection or penile prosthesis implantation. It is also true that some patients did receive the traditional alternative therapy with some effect. The traditional therapy is including Phytopharma-ceuticals, chinese herbal wine or medication, acupuncture, Chi-Gung or other meditation-like therapy. In a study of sildenafil (Viagra) taker's life satisfaction, we found sexual counseling as well as sexual therapy is still needed to increase in overall life satisfaction for the couple even after effective oral medication. Some traditional therapy also had the concept to enhance the self-confidence and improve the life style of the patients. So we believe they still had a place to contribute for the modern ED treatment. Conclusion: In the new era of ED treatment, we believe that many traditional therapists in the Asia-pacific oriental society still can play a role for the patients either responsive or non-responsive to the effective oral medications.

ERECTILE DYSFUNCTION AND ASIAN AGING MALE

The prevalence of erectile dysfunction(ED) rises rapidly with age and is a frequent complaint presented in clinical practice. The pathophysiology of erectile dysfunction in the aging male mainly includes chronic ischaemia, which triggers the deterioration of cavernosal smooth muscle and the development of corporeal fibrosis.

The etiology of erectile dysfunction is multifactorial. A wide variety of conditions are diagnosed in the majority of patients presented with ED. The incidence of hypertension, cardiovascular diseases, and diabetes mellitus was associated with the incidence and severity of ED, as with age. The risk of ED increases with the presence of these conditions, which are very commonly seen in aging male. Therefore, we address other systemic pathology, requiring a multi-disciplinary approach.

The Asia region is home to the largest proportion of the world's population and has an integral part in the health of the global community. This continent has its unique life style. As such, profiles of diseases in Asia, which are regarded as risk factors of ED may differ from reported one of western countries.

In this opportunity, author will present ED and Asian aging male, focusing on ethnic variation in risk factors of ED.

S09

ERECTION AND CENTRAL NERVE SYSTEM IN HUMAN

Y. Miyagawa¹, A.Tsujimura¹, J. Hatazawa², A. Okuyama¹

Recent neuroimaging studies are providing insights into the issue about the role of central nerve system (CNS) in sexual function in human males. However the processing in CNS of sexual arousal and penile erection is found to be complicated and still to be elucidated precisely. The present study investigates the areas of brain activation during maintaining the penile erection evoked by viewing erotic film excerpts and try to observe the possible lesion of psychogenic erectile dysfunction.

We used H₂15O-PET to analyze the functional neuroanatomy of five healthy volunteer males. The penile rigidity of these subjects, all adult and right-handed, was assessed with the RigiScan^®. Four scans were performed as they viewed three categories of audiovisual presentations: sexually explicit clips (A), emotionally neutral control clips (M) and nonsexual control clips (N). The images were analyzed by statistical parametric mapping software (SPM99, Wellcome Department of Cognitive Neurology, London, UK). Height threshold was set at P<0.05, corrected for multiple comparison.

In 17 out of 20 scans, the subjects showed significant erection. These positive scans were analyzed. In contrast A-M, bilateral (but right dominant) occipital lobule (BA18/19), right temporal lobule (BA7) and right putamen, as well as right middle temporal gyrus (BA21) were activated. In contrast A-N, only right occipital lobule (BA19) activation was significant. On the other hand, left superior frontal lobule (BA6) and left superior/medial temporal gyrus (BA38/21) were activated in contrast M-A and contrast N-A respectively.

Penile erection correlated with increased brain activity mainly in the right occipital lobule. And also the activation of right temporal lobule and right putamen was noted during erection. Interestingly different areas of left brain activated according to the kinds of control clips to inhibit penile erection. These findings indicate that highly advanced function of brain cortex coordinates the visually evoked sexual arousal and penile erection in human males.

S10

ED AND CARDIOVASCULAR DISEASE

The association between ED and cardiovascular disease is not new. However, it has received attention only after the launch of sildenafil - especially after some sudden deaths and serious cardiovascular side effects were reported in some patients receiving the drug. Subsequently, several studies and investigations have been conducted to determine the relationship between ED, cardiovascular disease (CVD) and the newer drugs used for the treatment of ED.

ED occurring before any manifest CVD can be considered a reliable harbinger of impending CVD. Studies have strongly suggested that an abnormality in the systemic NO-cGMP vasodilator system may result in ED as the first clinical manifestation of CVD. ED can coexist with hypertension, myocardial infarction, atherosclerosis, hyperlipidemia, peripheral vascular disease, angina and stroke. The prevalence can vary from 39 % to 64 %. Depression often coexists with ED and CVD, forming a well-recognized clinical triad. Psychogenic factors are common in CVD patients with ED, especially say, after a myocardial infarction (MI). Many of these patients also receive multiple concomitant drugs for coexisting conditions. These can affect libido and erection. Especial care should be employed in patients receiving nitrates (with PDE5 inhibitors and apomorphine) and warfarin (injection, MUSE, vacuum device).

Patients with CVD and ED are often afraid to have sex. They should be reassured that sex is safe by and far, as is medication (and other treatment) administered carefully, and should be encouraged to go ahead with it. The Princeton and UK consensus panels have enunciated clear guidelines for the safe use of PDE5 inhibitors in these patients.

CVD certainly does not mean the end of a man's sex life. Except where clear contraindications or risks exist, healthy sexuality should be encouraged after the critical phase of CVD passes. Treatment should not be denied to patients because physicians are afraid to treat these patients. If in doubt about the safety of orally effective drugs, the cardiologist should participate in the decision-making. It must be remembered that other treatment options exist even if these are contraindicated.

S11

OBESITY AND MEN'S HEALTH

• Obesity is a complex and interrelated disease state internationally. The global epidemic is compared between different countries.

• Caveats in assessing obesity in older men will be high-lighted, explaining the J- curve phenomenon in older men.

• Metabolic syndrome will be introduced to the audience. The N.C.E.P. definition will be explained to the audience.

• Differences in fat distribution & cell type between men & women will be explained.

• The N.I.H. stepwise approach to management will be explained, with attention to diet and physical activity.

• FDA approved obesity agents will be introduced to the participants & they include sibutramine and orlistat.

• The effects of testosterone on obesity in aging men will be expounded as well. The evidence from scientific trials will be presented.

• The relationship between leptin, exercise and testosterone will also be highlighted.

OSTEOPOROSIS AND ANDROGEN DEFICIENCY IN MEN

Ronald S. Swerdloff , Christina Wang

Osteoporosis is an age-dependent risk factor for morbidity and mortality in both genders. Peak bone mineral density occurs in early adulthood. Thereafter, bone is lost progressively with age with men losing 30 % of their trabecular and 20 % of their peak cortical bone in their lifetime. While the prevalence rate for fractures is lower in men than women, men have higher mortality rates after hip, vertebral, and other fractures. Factors that influence bone loss include: genetic factors, age of puberty, smoking, and alcohol abuse, calcium intake, physical activity, androgen and estrogen deficiency, growth hormone deficiency, glucocorticoid excess, and medications that negatively influence calcium metabolism. Hypogonadism is frequently associated with osteopenia and osteoporosis but circulating and bone estradiol levels are the major determinate of bone loss. Testosterone treatment will increase bone mineral density in hypogonadal men but the effect is not dependent on 5" reduced metabolites as 5'-reductase-2 inhibitors do not greatly diminish the testosterone beneficial effects. Estrogen deficiency induced by aromatase and estrogen receptor loss of function mutations result in osteoporosis. Testosterone treatment increases trabecular bone > cortical bone density although the benefits of testosterone treatment in older hypogonadal men may be less than that of younger hypogonadal men. Despite the positive effects of T treatment on BMD there are inadequate data on fracture rates after T treatment. Men with osteoporosis should be investigated for cause and treatment options are multiple. Hypogonadal osteoporotic men should be treated with aromatizable androgens and patients should receive calcium supplementation and vitamin D. In all male patients with osteoporosis bisphosphates are first line treatment although when hypogonadism is associated with manifestations other than osteopenia androgen treatment alone or in combination with bisphosphates is appropriate. PTH treatment is reserved (at present) for men and women with high risk of fracture.

S14

IS ANDROPAUSE A DISTINCT ENTITY?

• There have been debates about the existence of andropause. This lecture sets out to prove the existence of androgen decline in aging males and the relationship to symptoms.

• Andropause and menopause will be compared and defined.

• The issue of declining fertility in older men will be discussed. Data on increased sperm DNA damage with age will be examined.

• Often overlooked conditions that may pose, as andropause will be discussed in detail: in particular clinical depression, obesity, metabolic syndrome & chronic disease states and their treatments.

• Limitations of screening questionnaires such as the A.D.A.M. & A.M.S. will be highlighted.

• Laboratory assessments of different fractions of testosterone such as free, total and bioavailable testosterone will be discussed.

• There will be highlights on the effects of testosterone on the different organ systems e.g. cardiovascular, bone and brain.

• Managing low testosterone will be summarized.

S15

ANDROGEN REPLACEMENT: THE KOREAN EXPERIENCE

Young Chan Kim¹, Moon Jong Kim², Jong Cheol Woo³, Young Jin Lee²

The age related changes in men over 50 years of age have created an intense world-wide interest in hormonal supplementation in the aging male. Among hormones responsible for some of the manifestations associated with aging, testosterone has been widely used for hormone supplementation in men as it has been widely investigated, and its beneficial and adverse effects on male bodily systems are relatively well established.

Testosterone supplementation has not been a principal treatment modality for alleviation of climacteric symptoms in aging male as well as treatment of erectile dysfunction in Korea for last 50 years. After non-scorotal patch preparation was introduced in Korea in 1996, prescription of testosterone has rapidly risen in Korea.

In Korean 7 years?experience, the authors usually measure the followings in order to know whether patients have contraindications for treatment and in order to optimally evaluate outcome and adverse effects of testosterone supplementation: The basic laboratory evaluation includes urinanalysis, liver function test, measurement of hematological parameters and lipid profile. Evaluation of body composition and bone mineral density were performed using Bioelectrical impedance analyzer and bone densinometer, respectively. For prostate safety, we measured Prostate Specific Antigen (PSA) and International Prostate Symptom Score (IPSS), and preformed digital rectal examination(DRE). Sexual functions were evaluated using IIEF(International Index of Erectile Function). Duration of treatment was at least for 3 months. In some patients, supplementations continued for more than 3 months up to 6 years. The changes in subjective symptoms were evaluated by the Korean climacteric symptom scale (KCSC), which was created by Korean Society for Aging Male Research (KOSAR). All parameters that were observed before initiation of supplementation were monitored during the testosterone replacement at a regular interval. The outcome of the treatment and events during treatment such as complications and suppression of endogenous hormonal secretion will be presented.

S16

MEDICO-LEGAL ASPECTS OF ANDROGEN REPLACEMENT

Plasma testosterone levels decline in the aging male and ageing men show signs of androgen deficiency, similar in symptoms found in hypogonadal men. Several studies show that androgen replacement ameliorates signs of ageing in men. These studies have not been sufficiently powerful (in terms of number of participants and duration of androgen administration) to prove that long-term androgen administration to ageing men is safe, particularly with regard to prostate disease. Some members of the medical profession will regard androgen administration to ageing men as an unproven treatment carrying high risks. Prostate cancer is an androgen related disease, though there is no proof that androgens are the causal factors for prostate cancer. There is no evidence that there is a positive relation between plasma testosterone levels and the occurrence of prostate cancer.

The incidence rate of prostate cancer increases dramatically with age and if an ageing men receives testosterone replacement it may well happen that a prostate carcinoma becomes manifest. Medicolegally the following points are pertinent:

• Post aut propter? Is this prostate carcinoma incidental, not related to androgen treatment or is there a causal relationship? Expert witnesses may argue that androgen treatment was unwarranted and not proven safe.

• Document that the patient is hypogonadal by clinical and laboratory criteria justifying androgen replacement.

• It is important to ask the patient for informed consent providing information that there is as yet no consensus on treatment indication and safety stressing the need for regular check-ups requiring the cooperation of the patient, thus sharing responsibility.

• A painstaking documentation of medical procedures, precautions and information provided to the patient, particularly when results of investigations are abnormal.

S17

EXPERIENCE WITH ANDROGEL

Christina Wang, Ronald S. Swerdloff

We have previously demonstrated that testosterone (T) gel (AndroGel^® T gel 1 % CIII, Solvay Pharmaceuticals, Marietta, GA.) provided steady serum T concentrations within the physiological range with proportional increases in serum free T, 5 alpha-dihydrotestosterone (DHT) and estradiol (E₂) concentrations. Over 150 hypogonadal men who received the AndroGel?/FONT> replacement for 6 months showed significant improvement in sexual function, mood, lean mass and muscle strength and decreases in fat mass and percent body fat . Furthermore, assessment of bone turnover markers indicated an initial, transient increase in bone formation markers and more sustained decreases in bone resorption markers. In subjects receiving AndroGel^®, 10 g per day, bone mineral density increased by about 2 % in the vertebrae by 6 months. The adverse effects were those anticipated of T replacement in hypogonadal men with minimal skin irritation. The compliance rate was good and the patient acceptance rate of this route of T delivery was high.

We then followed 122 hypogonadal men who applied 5, 7.5 or 10 g AndroGel^® per day in a long-term study for up to 42 months. Transdermal AndroGel^® application continued to normalize mean serum T and free T levels in hypogonadal men. Mean serum DHT concentrations and DHT to T ratio were slightly increased, mean serum E₂: T ratio doubled, and mean serum FSH and LH levels were suppressed by the continuous T replacement. Sexual function and mood parameters improved rapidly with treatment and were maintained throughout T replacement. Lean body mass increased (P=0.0001) and fat mass decreased (P=0.0001) and these changes were maintained throughout the treatment period. The increase in lean mass was not accompanied by significant increases in muscle strength. The changes in bone formation and resorption markers suggested an increase in bone formation that was followed by gradual and progressive increases in BMD more in the spine (P=0.0001) than the hip (P=0.0004). Mild local skin irritation occurred in 12 subjects, but only one subject discontinued treatment because of skin irritation. Except for the anticipated increase in hematocrit and hemoglobin, there were no clinically significant changes in blood counts or biochemistry. One subject had benign prostatic hyperplasia requiring surgery. In three subjects (1.8 %) with elevated serum PSA, prostate biopsies showed cancer. We conclude that continued application of AndroGel^® resulted in beneficial effects similar to those with injectables and other transdermal preparation. Monitoring for prostatic disease, serum PSA and hematocrit and hemoglobulin levels is essential to insure the safety of T replacement in hypogonadal men.

CLINICAL GUIDELINES FOR GROWTH HORMONE REPLACEMENT IN ELDERLY MALES

Growth hormone treatment in adults with GH-deficiency on the basis of pituitary disease, has been rewarding: anabolic effects on bone and muscle are apparent, associated with a reduction in fat mass. Exercise capacity improves along with cardiac functions. GH induces improvements in body composition but this improvement does not universally translate into improved function. As for aging subjects, there is, in principle, no reason to withhold GH treatment from elderly subjects in whom GH deficiency has been diagnosed.

For the time being, the combination of signs and symptoms potentially attributable to GH deficiency and an IGF-1 level and IGF-binding protein-3 in the lowest tertile provides a reasonable first indication of (relative) GH deficiency. The diagnosis should preferably be ascertained with provocation tests, such as the arginine or growth hormone-releasing hormone provocation tests(for review: Bengtson et al: Treatment of growth hormone deficiency in adults. Journal of Clinical Endocrinology and Metabolism, 2000; 85: 933-42). The starting dose of GH administration is not well established but a dose of 0.05?.1 U/kg subcutaneously seems reasonable. Once placed on GH administration, individual dose titration must be done on the basis of the IGF-1 levels resulting from GH administration and the occurrence of side effects. The aim is to produce IGF-1 levels in the normal range or only slightly above normal (0-1 standard deviation above mean levels of IGF-1).

The symptoms of prolonged GH excess as they occur in acromegalic patients, are well documented. Hyperinsulinaemia, impaired glucose tolerance and eventually type 2 diabetes develop in a large number of acromegalic patients. Joint deformities are also common. Side effects are common among patients on GH replacement, both in GH-deficient patients and elderly subjects receiving GH and include edema resulting from sodium/water retention, arthralgia, carpal tunnel syndrome and impairment of glycaemic control. A concern with the longer-term administration of GH is the theoretical possibility of stimulating tumour growth. In particular, benign and malignant polyps of the colon have been found among patients with an overproduction of GH. Patients with a high concentration of GH-derived IGF-1 are 2-4 times more likely to develop prostate cancer. But a recent study did not find an increase of serum prostate-specific antigen in men over 50 years receiving GH treatment (Le Roux et al: Growth hormone replacement does not increase serum prostate-specific antigen in hypopituitary men over 50 years. European Journal of Endocrinology 2002; 147: 59-63).

If side effects occur (flu-like symptoms, myalgia, arthralgia, carpal tunnel syndrome, oedema, impairment of glucose homeostasis), GH dosage is reduced in steps of 25 %. Contra-indications against GH use include type I diabetes, active (or a history of) cancer, intracranial hypertension, diabetic retinopathy or carpal tunnel syndrome and severe cardiac insufficiency.

It seems there is a place for GH administration in aging subjects at this point in time, primarily to gather more and better information as to whether there are groups that might benefit from its supplementation. In view of the narrow dose limits and potential side effects, treatment should be reserved for patients with certain GH deficiency and it is not advisable at present to administer GH to aging patients outside a clinical context capable of providing intensive guidance and safeguards to patients. A protocol of GH administration to aging subjects provides also legal safeguard in case a carcinoma develops in a patient on GH treatment.

RECENT PROGRESS AND FUTURE DIRECTIONS IN PROSTATE CANCER TREATMENT IN ASIA

The optimal form of therapy for all stges of prostate cancer remains a subject of great debate. Currently, treatment decisions are based on the grade and stage of the tumor, the life expectancy of the patient, the ability of each theapy to ensure disease-free survival, its associated morbidity, and patient and physician prefernces.

For localized prostatic cancer, radical prostatectomy is the gold standard therapeutic option while external beam radiational therapy (EBRT), brachytherapy, cyrosurgery, and thermoablation could be also an option. The reported incidence of clinically diagnosed prostate cancer in Asia is much lower than Western countries, which is an important factor to late development of modern treatment, in addition, more conservative attitudes towards radical treatment. However, the cases of radical prostatectomy has recently increased in Asia, although still much less in number compared with Western countries. Laparoscopic radical prostatectomy has been standardized during the last years in Western countries, and is a developing surgery in Asian countries. The first laparoscopic radical prostatectomy in Japan, China, and Korea was preformed in January 2000, November 2000, July 2001, respectively. Since then, more than 250 cases in Japan, more than 10 cases in China, and more than 40 cases in Korea were performed for about 2 years. Recently, robot-assisted laparoscopic radical prosttectomy is a new procedure for treating prostate cancer. Many centers in western countries are attempting this new modality but 5 centers in Japan and 1 in Singapore to my knowledge.

In 1995, 34.1 % of all patients diagnosed with clinically localized disease in USA underwent radcical prostatectomy, and 26.3 % were treated with EBRT. The radiotherapy is not familiar to Asian urologists. In Singapore, however, a relatively high number of patients receive radiation therapy alone as an initial treatment in comparison with that in other Asian countries (15 % vs 2 %-3 %). Currently, the interest in brachytherapy has resurrected because of the technologic developments making it possible to place radioactive seeds under TRUS guidance. The number of patients who receive this treatment has been continuously growing in the USA. The brachytherapy in China began in mid-1990 and recently, about 200 cases a year done while not so much in other Asian countries including Japan.

There has been a resurgence of interest in cryosurgery as a treatment for localized CaP in the past several years. However, currently, very few cryosurgeries are being performed, because other minimally invasive therapies are becoming more popular like brachytherapy. HIFU is a treatment option achieving similar results to those of other non-surgical treatments for prostate cancer. More than 40 centers in Europe are attempting HIFU but only 1 center in Singapore and Korea, respectively.

For the endocrine therapy, treatment choices in Western countries are based on evidence based medicine. However, in Asian countries, doctors tend to select the treatment modality according to culture, patients' economic status, and physician's experience. Immediate hormone therapy is frequently selected, even for patients with localized or locally advanced disease. In Korea, 56 % of all patients receiving endocrine monotherapy as an initial treratment were stage T2, while the figure is only 18 % in Japan. In Japan, Korea, and Singapore, almost all stages of the disease may be treated with hormone therapy. In Indonesia, orchiectomy is most usual, with antiandrogen therapy prescribed only following pregression of PSA. In Japan and Singapore, LHRH agonist therapy is the most usual option. In Taiwan, orchiectomy is rarely conducted. MAB is not popular in Singapore and Taiwan. Intermittent therapy and watchful waiting for metastatic prostatic cancer is not well accepted in all Asian countries.

In future, Asian countries will follow the principle for management of the prostate cancer adopted in Western countries. Laparoscopic surgery and other less invasive optional treatments will become more and more popular. However, a strategy for an optimal management of prostate cancer for Asian, particularly for hormonal therapy will be established, based on differences in culture, economy, life expectancy, biology in prostate cancer. Asian-specific gene therapy also could be expected.

S23

LAPAROSCOPIC RADICAL PROSTATECTOMY

The goal of radical prostatectomy is cancer control with total removal of organ confined cancers and functional preservation of continence and potency. The potential benefit of Laparoscopic radical prostatectomy (LRP) compared to conventional radical prostatectomy are:

1 Shorter hospital stay
2 Decreased pain and analgesic requirements
3 Rapid return to normal activities
4 Better preservation of continence and potency
5 Shorter catheterization time

The options of open radical prostatectomy include retropubic and perineal routes while laparoscopic prostatectomy include transperitoneal and retroperitoneal routes with or without some form of robotic assistance.

Thus far results available for scrutiny are mostly single centre non randomized reports. Considering the difficulties with randomized controlled trials comparing different surgical approaches, there may never be conclusive evidence favoring one option over the rest. Case selection and surgical experience may impact more on outcomes than the surgical alternatives. Taken in this light, the key question is whether the newer modalities are better in cancer control and functional outcome.

Long term survival data comparing LRP and RRP are not available. Using margin positive rates as proxy, the results of RRP ranges from 10 %-60 % while most LRP margin positive rates fall somewhere in between. Likewise continence rates of RRP series vary from 90% full continence at 1 year at the best centres to less than 50 % elsewhere, The LRP continence rates are comparable although many report shortened catheterization days. The best LRP potency results are also comparable to those of the RRP. In conclusion, there has not been good evidence that LRP delivers better cancer control or functional outcome currently. As longer term experience accumulate, these questions may be better answered.

S24

RADICAL PERINEAL PROSTATECTOMY IN JAPAN

Akio Matsubara, Hiroaki Yasumoto, Kazuaki Mutaguchi, Kouji Mita, Mitsuhiro Seki, Tsuguru Usui

There is growing interest in radical perineal prostatectomy (RPP) for treating localized prostate cancer, from both a cost-benefit viewpoint and its high degree of radicality with minimal invasiveness. RPP is understandably one of the least aggressive surgical techniques, considering that the prostate gland, which lies only 5-6 cm beneath the perineal skin, can be removed through only a small perineal incision. Patients therefore experience less postoperative pain and require a shorter period of convalescence. RPP is even carried out as an outpatient procedure in some hospitals in the USA.

RPP also has many technical advantages: the urethra and the posterior surface of the prostate are well visualized, thereby facilitating an easy nerve-sparing operation, a precise urethral incision, and a secure vesicourethral anastomosis. The dorsal vein complex can be separated from the prostate without hemorrhage. In addition, RPP can be mastered more easily and with less complication than radical retropubic prostatectomy (RRP), and offers a curability rate equal compared to RRP. Thus, RPP is a superior surgical method for localized prostate cancer.

However, RPP is still performed less often than RRP, probably because most urologists are unfamiliar with the technique. In this symposium, we will describe our techniques for RPP, and report the results of our RPP series with the aim of making the perineal approach more comprehensible.

GENETIC ASPECT OF MALE INFERTILITY

Male infertility is classified four general causes: spermatogenic disorder, obstruction of the seminal tract, inflammation, sexual disorders. Idiopathic spermatogenic disorder accounts for more than 50 % of all of them. The cause of spermatogenic disorder is not yet identified. In recent years it has become obvious that some of the crucial genes expressed during male germ cell differentiation exist on the long arm of Y chromosome (Yq). The azoospermia factor (AZF) regions in the Yq are now thought to show a major correlation with spermatogenesis.

In this symposium, we discuss about two subjects, the microdeletions of genome and the expression of specific genes in AZF regions. The microdeletions within each AZF region are detected among idiopathic infertile men by means of sequence-tagged site (STS)-PCR. The total incidence of microdeletions was approximately 7 % in Japanese infertile male. In recent paper, the AZFc region is conserved in a highly palindromic sequence. Therefore, the PCR based STS could not be accurately decided their unique position. This time we screened using the PCR STS probes using their proven position and the order of STS (http://www.genome.ucsc.edu/).

Furthermore, we investigate the expression of Y specific genes in azoospermia male undergoing testicular biopsy. RNA was reverse-transcribed and amplified with specific eleven primers. All patients were also performed the genome screening for STS markers. Although there was not a high incidence of microdeletion of genome, the absence of expression in AZF genes were shown relatively high. This discrepancy is probably due to disorder of transcription mechanism.

THE POSSIBILITY OF GENE THERAPY IN MALE INFERTILITY

Approximately half of infertile unions involve male-factor infertility, often resulting from spermatogenic disruption. Spermatogenesis, which includes proliferation, meiosis, and differentiation, is tightly controlled by cellular interactions. Hepatocyte growth factor (HGF), originally identified as a mitogen for mature hepatocytes, is a multifunctional growth factor showing mitogenic, motogenic, and morphogenic activities in various cell types. In the reproductive tissues, HGF protein is detected in the human and rat ductus deferens, seminal vesicle, epididymis, and Leydig cells of the testis. The HGF receptor, c-Met, is expressed on the surface membranes of spermatogonia, primary spermatocytes, spermatids, and spermatozoa. In the testis, HGF/c-Met interaction appears to be involved in spermatogenesis and tubulogenesis. In the present study, to determine whether HGF overexpression by gene transfer could restore spermatogenesis or testicular mass, we adenovirally transferred the HGF gene into the testis of rats, with surgically induced cryptorchidism and subsequent orchidopexy. Replication-deficient recombinant adenoviral vectors containing the CAG promoter driving rat HGF (pAxCAHGF) and LacZ (pAxCALacZ) were constructed. Sprague-Dawley rats surgically induced unilateral cryptorchidism and subsequent orchidopexy were divided into three groups: control (PBS), pAxCALacZ and pAxCAHGF by intratesticular injection. At week 2 and week 4 after subsequent orchidopexy, testes were removed and weighed. These specimens were analyzed histopathologically, and examined for cell apoptosis. HGF expression in these specimens associated with c-Met receptor-mediated signal molecules was examined by reverse transcription-polymerase chain reaction (RT-PCR), Western blot or immunohistochemical study. Adenovirus-mediated HGF gene transfer induced overexpression of HGF in some seminiferous epithelial cells and interstitial cells, increased the phosphorylation of ERK and Akt, and decreased the number of apoptotic cells of germ cells. HGF transduction also significantly increased the number of germ cells and testicular weight by 4 weeks compared to the other control groups.

In conclusion, adenoviral-mediated HGF gene transfer into the testis in the cryptorchidism rats inhibited germ cell apoptosis and restored the spermatogenesis. Therefore, the gene transfer of HGF may be a useful tool to treat the spermatogenic dysfunction.

CFTR MUTATION OF TAIWANESE PATIENTS WITH CONGENITAL ABSENCE OF BILATERAL VAS DEFERENS HAN-SUN CHIANG

Aim: In Taiwan, an area with a very low incidence of cystic fibrosis (CF), we first screened for the most common mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and clinical correlations in 27 patients with clinically diagnosed congenital bilateral absence of the vas deferens (CBAVD). Methods and Results: The clinical results showed that none of the 27 patients had CF symptoms. We did not detect any definite renal anomaly ultrasonographically. Mutation analysis was done on these 27 cases with a negative control of 46 normal fertile males. No mutations of DF508 or R117H were identified in any of the samples analyzed. In the screening of IVS8-poly T, 5 of the 27 CBAVD patients showed the homozygous genotype for 5T/5T, 14 of them showed the heterozygous genotype for 5T/7T, and 8 of them showed the homozygous genotype for 7T/7T. The frequency of 5T alleles was 44.4 %, which was significantly higher than that in the 46 normal fertile males for which there was a 5T frequency of
5.4 %. Conclusion: The absence of major mutations of CFTR genes could be related to the much low CF incidence; further investigations into differences in the mutation spectrum of other CFTR genes are needed for a better understanding of the development of Taiwanese-Oriental CBAVD.

S30

RECENT DEVELOPMENTS IN MALE CONTRACEPTION

Currently about 10 % of men are using male contraceptive methods that include condoms and vasectomy. Condoms, which protect against sexually transmitted diseases and prevent pregnancies, may not be generally acceptable and also are associated with a high user failure rate of about 12 % to 14 %. Vasectomy, including no-scalpel vasectomy and other vas occlusion methods, involve a surgical procedure. These procedures have low complication rates and high efficacy rates but are considered irreversible. It is generally agreed that vasectomy is not associated with increased health risk for atherosclerosis, genital cancers or other diseases. Refinement of vas occlusion methods are currently under study in an attempt to make this procedure easier and with higher efficacay.

Hormonal male contraceptive methods under study since the 1970s have the advantage of reversibility and of employing available agents with well-known effects. Hormonal contraception for men is based on induction of marked suppression of the pituitary secretion of the gonadotropins FSH and LH and by the exogenous administration of androgens, progestins and/or gonadotropin releasing hormone (GnRH) antagonists. In clinical trials of hormonal contraception for men, an androgen has been an essential component. Androgens when administered exogenously exert their effects not only by suppressing endogenous LH and FSH but also by replenishing the androgen deficiency that would have accompanied the suppression of endogenous testosterone (T) production.

The efficiency of hormonal contraception in men was demonstrated in two multicenter studies sponsored by the World Health Organization. These studies showed that an androgen T enanthate (TE) administered in supraphysiological doses (200 mg in every week) resulted in azoospermia or severe oligozoospermia (<310⁶/mL) in 97 % of the treated men. Once azoospermia or oligozoospermia was achieved, the efficacy of TE-induced suppression of spermatogenesis was 1.4 per 100 person years-a contraceptive efficacy rate that was equivalent to female hormonal methods. Results of the studies also showed that suppression appeared to be more complete in Asian men, the occurrence of which indicated a geographical or ethnic variation in the suppression of spermatogenesis in response to exogenous hormone.

Androgens currently in development include testosterone and 7a methyl-19 nor-testosterone (MENT) implants; long acting injectables such as T undecanoate, decanoate and microspheres; transdermal T preparations; and selective androgen receptor modulators. Because androgen-alone regimens may prove to be efficacious in Asian men, a large-scale contraceptive efficacy study using T undecanoate is currently in progress in China. In non-Asian countries, studies are focused on the combination of androgens with progestins such as oral levonorgestrel and desogestrel; injectable depot medroxyprogesterone acetate or norethisterone enanthate; and implants of levonorgestrel or desogestrel. These androgen/progestin combination trials have shown that the addition of the progestagen reduces the required dose of androgens, increases the efficacy of suppression of spermatogenesis, and may increase the rapidity of onset of azoospermia/oligozoospermia compared with androgen-alone regimens. In most studies the efficacy of suppression of spermatogenesis was increased to more than 90 % with the combination of progestins and T while reducing the T dose to a more physiologic level.

Other studies have used GnRH antagonists as the potent gonadotropin suppressor and T as replacement therapy to prevent hypogonadism. Though effective, the problems with GnRH antagonists are administration by daily sc injections and cost, which may be prohibitive. New developments may include longer delivery systems for GnRH antagonists and orally active non-peptide GnRH antagonists. Reported studies also have shown that once azoospermia or severe oligospermia is achieved with a combination of an androgen with a progestagen or GnRH antagonist, the suppression could be maintained by androgens alone. In 5 to 10 years, an androgen-alone regimen may become available as a male contraceptive in Asian countries and an androgen /progestagen combination may be an option for men in non-Asian countries. The reversible male contraceptive that will most likely be available is a monthly or bi-monthly injectable, followed by long-acting implants. The future of male contraceptive development lies in the availability of orally active or long-acting injectable or implantable androgens, modified androgens and progestins with selective target organ actions and non-peptide orally acting GnRH antagonist. Long-term potential health benefits or risks of male hormonal contraceptive agents cannot be assessed until such agents are available for use by large numbers of men in follow-up and epidemiological studies.

AW01

MEN AND MALE AGING: A PSYCHOSOCIAL EVALUATION OF A STUDY IN SINGAPORE

S. H. Teoh, P. H. C. Lim, T. K. Gan, C. K. S. Yeo

Aim: To make a psychosocial evaluation of the knowledge, perception and attitudes of men in Singapore towards andropause, Hormone Replacement Therapy in men and erectile dysfunction. Methods: A national survey on Knowledge, Attitudes and Practices towards Male Aging in Singapore was started in 2001. This is an on-going nation-wide, prospective, cross-sectional study on a random sample of 1000 men who were 45-70 years old. The respondents were directly interviewed and a total of 495 completed records were presented in a preliminary report. A psychosocial evaluation is made on data presented in this preliminary report. Results and Discussion: Only 39.5 % of men sampled have heard of "Male Menopause" or "Andropause" While
65.3 % (Figure 2) of men sampled claimed seeking help and more than 90 % believed that treatment improved health and quality of life, only 0.9 % was on HRT. Other forms of treatment for andropausal symptoms included taking multivitamins or herbs. 5 % of the men on other forms of treatment were receiving some form of treatment for erectile dysfunction (Viagra, PGE1 injections etc). 41.7 % of men sampled said they were not bothered to get any information on HRT. Men's health is increasingly being recognized as an issue that is socially constructed. The data above are discussed from a psychosocial viewpoint. Conclusion: Health professionals can contribute to the improved care of men, from childhood to old age, by adopting an approach that takes into consideration the impact of gender on the health of men and women.

AW02

EFFICACY AND TOLERABILITY OF COMBINATION OF SILDENAFIL CITRATE AND APOMORPHINE IN SUBLINGUAL TABLET FORM BY E.I.P.I.CO.-EGYPT

A. El-Taweel, O. Esawy , A. Waly ,

Aim: Sildenafil citrate (Viagra) is a potent selective inhibitor of phosphodiesterase type 5 proposed for the oral treatment of erectile dysfunction (ED). Apomorphine HCL is the first centrally acting nonselective (D1/D2) dopamine receptor agonist with more potent D2-like effects. The aim of this study was to evaluate the efficacy and tolerability of a fixed dose of combination of sildenafil citrate and apomorphine HCL sublingual tablet in men with ED of various causes (organic or psychogenic). Methods: In this double-blind, placebo-controlled, cross-over, fixed dose, clinical trial study, 60 patients (mean age 47.039.84) were classified according to history, examination and other diagnostic procedures into two main groups, psychogenic and organic. Each patient was given in randomized pattern SL combination of sildenafil citrate and apomorphine HCL E.I.P.I.CO.-EGYPT. Efficacy was determined by responses to the International Index of Erectile Function (IIEF-5). At each study visit, adverse events reported by the patient were recorded and assessed. Results: At the end of our study, 80 % of the total patients who received this new formulation shows very high significant improvement. With regard to etiology of erectile dysfunction 36 patients (60 %) were psychogenic, 86.1 % shows very high significant improvement. While 24 patients (40 %) were organic, only 70.8 % shows very high significant improvement. The incidences of side effects reported were: headache (11.7 %), flushing (10 %), nausea (8.3 %), dyspepsia (5 %) and visual disturbance (3.3 %). Conclusion: SL combination is an effective treatment for ED. The erectile efficacy of SL combination occurs irrespective of the presence of mild, moderate or severe ED at baseline, or the presence of co-morbidities and has mild side effects. So SL combination is therefore suitable as a first-line therapy.

LEYDIG CELL DYSFUNCTION IN VARICOCELE

A. M. Elkamshoushi¹, O. Sharaki², A. Salah¹

Aim: It is generally believed that varicocele impairs tubular function and spermatogenesis. It is, however, unclear whether or not the Leydig Cell (LC) function also decreases. This study was designed to evaluate the LC function by studying the changes in spermatic & peripheral testosterone levels in varicocele patients; and also to correlate between these changes and the grade of varicocele. This may clarify the LC dysfunction in varicocele and its role in inducing subfertility. Methods: This study is performed on 30 infertile patients with left primary varicocele, and 15 fertile males undergoing herniorraphy as a control group (age 20-40 years). Peripheral and spermatic vein testosterone was measured by ECLIA method in all subjects during either high spermatic vein ligation in infertile group, or herniorraphy in control group. Serum LH level is estimated in all patients. Results: Peripheral LH and testosterone were normal in all studied subjects. The mean level of spermatic testosterone in varicocele group (317.9159 ng/mL) was significantly lower than its mean value (506.4104.6 ng/mL) in control patients (t = 4.15 at p 0.05). There is a significant inverse relationship between the grade of varicocele and the mean levels of spermatic and peripheral testosterone (Table 1). Conclusion: Decreased Spermatic blood testosterone with normal LH in infertile patients with varicocele suggested diminished testicular androgen production due to Leydig Cell dysfunction. The severity of LC dysfunction is directly related to the degree of varicocele. The direct local effect of varicocele on the testes is the mechanism responsible for LC dysfunction. This study provides evidence that altered testosterone androgen production may explain the abnormal semen parameters in varicocele, due to defective spermatogenesis and epididymal dysfunction.

AW04

HOW DO MEN PERCEIVE ERECTILE DYSFUNCTION? A QUALITATIVE STUDY ON OPINIONS OF MEN

Wah-Yun LOW¹, Chirk-Jenn NG², Wan-Yuen CHOO³, Hui-Meng TAN³

Aim: Erectile dysfunction (ED) is one of the common chronic medical disorders affecting the aging male. Men's perception of a disease affects his health seeking behaviour. This study aimed to explore and compare perceptions of ED among men with and without ED and how these perceptions came about. Methods: This qualitative study utilized focus group discussions and in-depth interviews involving a convenient sample of 73 urban men, aged between 40 - 75 years old. One-to-one in-depth interviews of 17 men with ED and 7 focus group discussions consisting of 56 men without ED were conducted. The discussions and interviews were all carried out based on a self-developed semi-structured discussion guide. Transcripts of the discussions and interviews were performed via NUD*IST qualitative software. Results: The study found that different terminologies of ED existed among different cultures and most agreed that ED is prevalent among men. Misconceptions exist as to what ED was about. Men with ED also misconstrued the real meaning of ED. Most participants tend to perceive impotence as a more serious problem than ED, although both "impotence" and "ED" were used synonymously. There are similarities between men with ED and men without ED in terms of their perceived causes of ED, i.e. mainly due to medical conditions as well as psychosocial factors such as life stresses, and relationship problems. Interestingly, the 'overuse of the penis' was also mentioned to be a cause of ED in both groups. Men with ED noted the significant impact on their manhood and its effects on their relationship. Men without ED viewed a man with ED with sympathy and fear for their relationship. Nevertheless, some men perceived ED as not important compared to other medical conditions. For men without ED, the main sources of information pertaining ED were from the mass media, followed by friends and doctors, whereas for men with ED, their main source of information was from their doctors. Conclusion: One's personal experience of a disease certainly affects one's perception of that disease. Men's perception about ED played an important role in determining whether they would seek treatment for their ED. Public education would be useful to influence some of the negative perception and views about ED.

AW05

HEALTHY AGING: THE CONCERN OF SEXUAL HEALTH AS AN IMPORTANT ELEMENT IN THE MAINTENANCE OF TOTAL HEALTH IN THE AGED COUPLES: THE MALAYSIAN PERSPECTIVE

Sexual Health is the integration of the somatic, emotional, intellectual, and social aspects of sexual being, in ways that are positively enriching and that enhance personality, communication and love. Fundamental to this concept are the right to sexual information and the right to pleasure. According to Mace, Bannerman, and Burton the concept of sexual health includes three basic elements:
1. a capacity to enjoy and control sexual and reproductive behavior in accordance with a social and personal ethic.
2. freedom from fear, shame, guilt, false beliefs, and other psychological factors inhibiting sexual response and impairing sexual relationship.
3. freedom from organic disorders, diseases, and deficiencies that interfere with sexual and reproductive functions.

To ensure that the average aging couples?sexual needs are appropriately addressed the Ministry of Women and Family Development of Malaysia conducted a survey about sexual behavior, attitude and perception among those 50 years and above in the Klang Valley, in the Capital City which represents the principal population.The10 main questions that were asked to the couples included the following: Do you think sex is important at your age? Are you satisfied with your sex life? How frequent you have sex? Who initiated sexual intercourse? Do you have a problem with your sex life? Have you received any treatment/ help? Name the type of treatment/help received? Do you agree for someone to have another partner/wife due to sexual dissatisfaction? Are you on hormonal replacement therapy? Are you hoping for a satisfying sexual life at this age and in the future?

A total of 473 respondents were involved in the survey received and their answers were evaluated. The highlights of the findings are as follows. On the question of whether sex is important in the old age, 28 % responded as not important and 72 % responded positively. 87 % were satisfied with their sexual relationship as compared to 13 % that were not. 39 % had once to twice sexual relations a week and a good majority decline to give the detail. 34 % indicated that both couple actively initiate sexual relationships, whereas 29 % initiated by the respondents and 28 % by their partners. 83 % informed that they experienced no sexual problems compared to 17 that experience sexual problems. 5 % of those that experience sexual problems seek help as compared to 17 % that did not do anything and the remaining is silent about this!52 % of those that have sexual problems do not know whom to approach as compared to 45% who know where to get assistance.27 % would seek modern treatment as compared to 6 % that would seek traditional therapy. The rest remain silent with regards to treatment seeking behaviour. 76 % respondent did not agree with the suggestion of looking for a new partner when the existing partner is no longer sexually active as compared to 14 % that agreed to the suggestion. With regards to HRT, 93 % were not on HRT as compared to 5 %. 69 % of the respondents expressed that their sex lives are better now as compared to 30 % that were not. 61 % of the respondents were free from chronic illness as compared to 31 % and the usual medical conditions experienced include heart problems, followed by diabetes and hypertension

The survey has given some insights of the sexual health scenario of the aged couples and the main issues that may need to be addressed. Aged couples still feel uncomfortable to discuss their sexual problems openly and would not do anything to overcome their dilemma. Sexual Health should not be shrouded as sensitive issues but to be discussed openly so that total life can be cherished even in old age.

Sexual Health counseling has now been included in the various Family Care Centers under the Ministry and for start IEC Programs on Sexual Health are conducted through the local mass media and electronic media as well as in public seminars and community health workshops.

AW06

THE PREVALENCE OF VOIDING PROBLEMS IN AN ELDERLY IBAN COMMUNITY, SARAWAK, MALAYSIA ?A PILOT STUDY

T.A. Ong¹, G.C. Teh², C.C.M. Lei³, F.R. Belansai¹, B.P.P. Kho¹

Introduction: The prevalence of voiding problem in the elderly population of Iban, the largest indigenous ethnic group of Sarawak, Malaysia, had not been studied previously. Aim: To do a pilot study to assess the prevalence of voiding problems in an elderly Iban community with emphasis on lower urinary tract symptoms (LUTS) in male and incontinence in female. Methods: All residents above 60 year-old in an Iban resettlement area of Sekuau (total population: 2625; residents >60 year-old: 217), Sibu, Sarawak, were invited by oral and written methods. International Prostate Symptoms Score (I-PSS), quality of life score (QOL), maximum urinary flow rate (Qmax), post-void residual urine volume (PVR) were determined for male. For female, the Medical Epidemiologic Social Aspects of Aging (MESA) urinary incontinence questionnaire was administered. Results: A total of 120 (53 male & 67 female) subjects were recruited (representing 56.4 % & 54.5 % of the male & female above 60 year-old respectively in the resettlement area). For male, the mean age was 69.6 years (SD: 7.9; range 60-86). The mean I-PSS score was 5.6 (SD: 8.2). The percentage of subjects with moderate to severe symptoms (I-PSS score >7) was 21.2%. The mean QOL score was 2.0 (SD: 1.4). The mean Qmax was 13.1 mL/s (SD: 4.9) whereas the mean PVR was 43.8mL(SD: 42.3). Significantly worse QOL score was noted in subjects with moderate to severe symptoms compared to those with mild symptoms (mean 3.6 vs. 1.6; P=0.006; t-test). However, I-PSS scores did not correlate with both Qmax and PVR. For female, the mean age was 68.3 years (SD: 5.7; range: 60-80). The average number of children was 5. Only 9 subjects (13.4 %) reported episode(s) of urinary incontinence in the past 1 month. The symptoms were mainly of stress incontinence which were mostly mild. There was no significant difference between symptoms of incontinence with grand-multiparity (P=0.16; Fisher's exact test). Conclusion: The prevalence of LUTS in this group of elderly Iban male was consistent with the reported prevalence in other studies. However, the prevalence of incontinence in elderly Iban female was low.

STANDARDIZED INDICATION & SURGICAL APPROACH FOR PENILE IMPLANTATIONS

A. A.Yassin¹, F. Schukfeh²

It took time to gradually realize that there is no penile prosthesis that can be used for the same indication; e.g. patients with erectile dysfunction resists to oral agent treatment.

In the age of modern oral therapies, the indication for penile implants is limited indeed, however, the following conditions are strongly indicated, such as venous reflux (or leakage), multiple penile lesions and penile deformities (Peyronie's disease). Nowadays there's an enhanced advantage for inflatable prostheses by means of penoscrotal approach instead of infrapubic or sulcus approach. This procedure allows to implant 3 pieces-device through one inch incision; moreover, makes the fluid reservoir easily implanted perivesically. In patients with penile fibrosis and penile deviation, the implantation of "prosthesis-Mentor" has been a success. Because its material deserves the quality that is more solid and more inflatable than that of AMS 700, the "Mentor" prosthesis is more suitable for penile modelling.

MYCOTIC SEMINAL INFECTION AS A RESERVOIR FOR HARD RECURRENT VAGINAL MYCOSES

Keywords: Vaginal Mycoses; Semen; Sexual Habits; lazy sperms

Aims: Assessing and exploring reasons for hard recurrent vaginal mycoses in couples of certain patient's clientele. Detection of seminal / genital mycoses in male partners, as a mycoses "reservoir". Methods: Within 6 years - until June 2003 - 228 cases (males) whose wives/partners suffered from rec. hard vaginal mycoses had been examined by seven gynaecologists and three urologists. Considering 101 pathogen cases (44 %) in 100 of them candidiasis was found and aspergillosis in one case. The fungus cultures had been exclusively made for sperm- resp. prostate specimen. Profile of symptoms: a slight baroreception in the lower abdomen in just 17 cases, diffuse body complaints in 4 cases or ejaculatory burning to a medium-light extent. Conclusion: In abt. 50 % of rec. vaginal mycoses the blame attaches to men. It's easy for mycoses to establish and grow in the male genitalia. Assisted by provisory infections or immunodefficiency mycoses could be carried retroactively and may later infect the partner by means of the seminal fluid. Sexual habits like cunnilingus/fellatio and anal intercourse may help the spreading of this. Last but not least: with each spermiogram a fungus culture should be made as the mycosis is the reason for the phenomenon of "lazy sperm" too.

PP03

ECTOPLASMIC SPECIALIZATION DYNAMICS IN THE TESTIS IS REGULATED BY PHOSPHINOSTITIDE 3-KINASE VIA THE b1-INTEGRIN/PFAK/P13K/PKB SIGNALING PATHWAY

M. K. Y. Siu¹, C. Y. Cheng², W. M. Lee¹

Introduction: Like other tissues, the mammalian testis contains three types of cell junctions that stick cells together: the gap junctions, tight junctions and anchoring junctions [1]. The ectoplasmic specialization (ES) is a testis-specific anchoring junction (AJ) found between Sertoli cells and elongate spermatids. It provides mechanical adhesion of spermatids onto Sertoli cells and plays a crucial role in germ cell development in the testis. Recent studies in our laboratories have shown that AJ dynamics in the seminiferous epithelium, in particular at the site of ES, are regulated by focal adhesions complex (FAC)-associated proteins such as b1-integrin, focal adhesion kinase (FAK) and vinculin [2]. In the present study, we have investigated the role of phosphatidylinositol 3-kinase (PI3K), another FA component and a putative binding partner of p-FAK, on ES dynamics using both an in vitro model and an model. Methods and Results: When germ cells were cocultured with Sertoli cells, functional actin-based ES structures were formed as demonstrated by electron microscope. The events of Sertoli-germ cell ES assembly were associated with an induction of PI3K and its upstream signaling molecules, and an increase in the kinase activity and phosphorylation of protein kinase B (PKB, a downstream signaling molecule of PI3K) and extracellular signal regulated kinase (ERK). Immunohistochemistry and immunofluorescent microscopy revealed that these molecules were co-localized to the same site in the testis consistent with their presence in the ES. Co-immunoprecipitation have further confirmed that PI3K could form complexes with b1-integrin, p-FAK, vinculin, paxillin, p130 Cas and gelsolin (all are ES components), but not with N-cadherin or nectin-3. When adult rats were treated with AF-2364 to perturb Sertoli-germ cell AJs in vivo, an induction of PI 3-kinase, R-Ras, p-PKB, p-ERK and the kinase activity of PKB were also detected. Moreover, the use of a specific PI3K inhibitor, wortmannin, could effectively delay the AF-2364-induced spermatid loss from the epithelium. Conclusion: These studies suggest that PI 3-kinase is a crucial molecule in regulating ES dynamic possibly via the b1-integrin/p-FAK/PI3K/PKB/ERK signaling pathway and open an area for designing male contraception methods via this paracrine approach.

This work was supported in part by grants from the Hong Kong Research Grant Council (HKU 7194/01M) and the University of Hong Kong (CRCG).

1. Lui WY, Mruk D, Lee WM and Cheng CY (2003) Adherens junctions dynamics in the testis and spermatogenesis. Journal of Andrology 24: 1-14.
2. Siu MKY, Mruk D, Lee WM and Cheng CY (2003). Adhering junction dynamics in the testis are regulated by an interplay of b1-integrin and focal adhesion complex-associated proteins. Endocrinology 144: 2141-63.

PP04

TOXIC EFFECT OF CIPROFLOXACIN, AN ANTI-INFLAMMATORY DRUG ON TESTICULAR STEROIDOGENESIS AND GONADOTROPHINS

G. Vanithakumari, C. Anbalagan, R. Deivendran

Ciprofloxacin, at two different doses (250 mg and 400 mg respectively/60 kg body weight) given for seven days (short duration) to male albino rats, caused significant alteration in testicular steroidogenesis and gonadotrophins. Vitamin A, C and E were given as supplements individually to high dose drug treated group to screen for recovery from drug toxicity. A significant increase in FSH and LH levels was observed in all experimental groups including vitamins supplemented groups. Withdrawal of the drug could restore the FSH levels to normalcy but not the LH levels. A similar dose dependent decrease was shown by serum testosterone and this was due to an inhibition of the steroidogenic pathway enzymes 3b - hydroxysteroid dehydrogenase and 17b - hydroxysteroid dehydrogenase. Vitamins A, C and E could only partially (50 %) restore the testosterone levels. However, only vitamin E supplementation could raise the steroidogenic enzymes to normal levels. Neither vitamin A or C, the anti oxidants, nor the drug withdrawal were effective in raising the above enzyme levels to control values. Thus, Ciprofloxacin at shorter duration exerted toxic effects on the testicular hormones and gonadotrophins.

PP05

RESTORATIVE ROLE OF VITAMINS A, C AND E ON CIPROFLOXACIN ALTERED OXIDATIVE ENZYMES IN MALE REPRODUCTIVE ORGANS OF RATS

G. Vanithakumari, R. Deivendran, C. Anbalagan

The adverse effect of NSAID drug Ciprofloxacin in two different doses (250 mg and 400 mg/ 60 kg body weight/ 12 hours interval, respectively for seven days) was screened in male albino rats with special rteference to lipid peroxidation, oxidative enzymes like catalase and superoxide dismutase and non-enzymatic anti-oxidant glutathione in epididymis and seminal vesicle. The drug had caused a significant decrease in the enzymatic and non-enzymatic anti-oxidants in all treatments. The level of lipid peroxidation was high in all drug treatments when compared to the control. Similar changes have been noted in glutathione level also. The known vitamins A, C and E as restorative agents were given as individual supplements to highdose ciprofloxacin treated groups. These vitamin supplemented groups had induced many restorative changes in these enzyme activities. Among these three vitamins, vitamin C acted as an effective anti-oxidant which caused 75 % restoration. withdrawal of drug for further 14 days had caused a partial restoration only. Thus, the NSAID drug ciprofloxacin appears to exert an adverse effect on the enzymatic and non-enzymatic anti-oxidants in the reproductive tissues and vitamins supplementation acted as an effective rescue agent.

PP06

ADVERSE EFFECTS OF DICLOFENAC SODIUM ON CAUDA EPIDIDYMAL HISTOARCHITECTURE IN ADULT MALE ALBINO RATS

M. Selvaraj¹, G. Vanithakumari², R. Maheswari³

Diclofenac sodium, a non steroidal anti inflammatory drug was injected intramuscularly at 1.5 mg and 3.0 mg/kg body weight respectively and Vitamin E was administered orally at 4.0 mg/kg body weight for a period of 8 weeks to adult male albino rats. Eight weekly doses of low dose diclofenac administration caused deleterious changes in the caudal segments. The reductions in the sperm concentrations, their accumulation near the luminal surface and the abnormal severing of the head and flagellum of many sperms were evident in this tissue. There was desquamation of the pseudo-stratified epithelial cells in many tubules. Vitamin E supplementation to these animals could bring back the sperm concentrations to a limited extend. However, the sperm concentration did not recover to control levels.

High dose of diclofenac administered for 8 weeks led to an alteration in the number and distribution of cell types in cauda epididymis. The sperm concentration was further reduced considerably suggesting the adverse effect of the drug. Vitamin E supplementation to these group of animals partially restored the histoarchitecture of the pseudo stratified epithelium. The distribution of the cell types were the same like the control. The sperm density with in the lumen was increased. The histological appearance resembled the controls. Thus, diclofenac sodium exerted an adverse effect on the cauda epididymal structure and function.

PP07

CRYOPRESERVATION OF VERY SMALL NUMBER OF SPERMATOZOA IN A MICROPIPETTE

M. Miyake, T. Kasai, M. Suzuki, K. Suzuki, T. Shima, Y. Shimadu , M. Wada, M. Fujie, M. Hashi, S. Hirata, K. Hoshi

Department of Obstetrics & Gynecology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan

Aim: When very small number of testicular spermatozoa cryopreserved with normal procedures are thawed, we can not recover the spermatozoa without spending time and efforts. So we tried to make an efficient method for cryopreservation of very small number of spermatozoa in a micropipette, and investigated that whether it was available or not. Methods: The motile spermatozoa mixed with the freezing media were aspirated into the STRIPPER^® Micropipette Tips (MXL3-100, I.D. 100 micron) fitted to an ICSI microtool. The freezing procedure was based on a simple standard semen cryopreservation protocol. The micropipette covered with its case was exposed to liquid nitrogen vapor for 30 minutes and then plunged into liquid nitrogen. For thawing, the micropipette was taken out of liquid nitrogen and placed into a 37 water bath for 25 to 30 seconds. The micropipette was fixed to an ICSI microtool again. The sperm suspension was released into a HEPES-buffered HTF. Recovered motile spermatozoa were injected into mouse metaphase II eggs. The recovery rates of motile spermatozoa and rates of mouse egg activation by ICSI were investigated. Results: The recovery rates of motile spermatozoa and rates of mouse egg activation were 80 % and 66.7 %,respectively. Conclusion: It is suggested that this new method might be simple and efficient for cryopreservation of very small number of spermatozoa.

Sequential Male Orgasm

In a group of 2060 men with average median age of thirth nine years old. We divided this sample into two groups: one older with age around 40 years old and one younger with age around 16 years old. From this two groups, we found that 13 % of them have more than two orgasm with only one coitus and with only one erection.

PP09

FIBROSIS OF THE CAVERNOUS BODY OF PENIS RESULTING FROM PAPAVERINE INJECTION IS A CONTRAINDICATION TO HYDROFLEX INFLATABLE PENILE IMPLANT

Two patients who had self-injected papaverine presented priaprism. Following the usual treatment for this condition, laboratory blood tests and X-rays were conducted. The X-rays showed radiological alterations in the cavernous body of the penis. After a few months, an inflatable hydroflex prosthesis was implanted. In both patients, during the surgical procedures, it was possible to implant the prosthetic tube only in one side. In the other, dilation was impossible due to extensive fibrosis in the right side in the first case, and in the second case we found an extensive annular plate. After 6 months, the implants were not functioning anymore. X-rays and laboratory tests were performed. A new surgery was carried out, replacing the Hydroflex prosthesis with a semi-rigid one. We were then able to observe that, when not in contact with the fibrous cavernous body of penis, the prosthesis pump mechanism functioned regularly well.

PP10

Tonus of Cavernous Penile Muscles and ErectilE Disfunction

The group studied at nucleo de estudos de sexologia in curitiba - paran - brasil, consists in 150 men with age between 18 and 54 years old. These individuals were submitted to the contraction exercises from pelvics and perineal muscles.

These ones that involve the penis cavernous body (muscle bulb spongiosous) besides the muscle contraction anus elevator. They were submitted to an exercise contraction from penis and a pubococcigious muscles for 6 months.

Results: Note that after an exercise program for 6 months,
70 % from the subjects who presented an angle of 90º with erectile disfunction, they decrease the angle to 45º whith an environment rigidity from 50 mm Hg to 100 mm Hg. The young group of 18 to the 25 years that passed by the exercises program and that make part of standard sample, they proceeded having longer orgasm (35 s) and an orgasm quality increased, relating inclusive more widespread orgasms.

SEXUAL INTERCOURSE FREQUENCY IN THE OLD WOMEN

We observed in our study at the clinic Ncleo de Esdudos de sexologia e Geriatria, that the old women have a same sexual response as the young, if we consider one group of womam with age superior a 40 years, and another with age below this period. Our research compared this results with Kinsey one, abd Rischfield quantum the SIF for humans around 70 years.

The average of coitus that we find in our sample it's the same for the age 40 till 70 years old (12.2 times/month).

Between the age 61 till 70 this SIF increases to 17 times a months. The young group with age below 40 years have sexual intercourse 20.3 times a months, less than Rischfield and more than Kinsey.

PP12

THE EFFECT OF ORAL PENTOXYFILLINE ON SPERM MOTILITY IN INFERTILE MEN WITH ASTHENOSPERMIA

M. R. Moein, M. A.Khalili , A. Aflatoonian

Aim: To determine the effect of oral Pentoxyfilline on sperm motility in infertile men with Asthenospermia. Methods: Ninety-four infertile men who were referred to Andrology clinic and had isolated Asthenospermia with or without other sperm abnormalities were selected randomly. Physical examination was done for all of them. Patients with high grade varicocele were excluded from study and only patients without varicocele or those with low grade varicocele who refused varicocelectomy were selected. Sixty-eight patients included in our study and oral Pentoxyfilline with dose of 800 mg daily were started for them. Patients were followed by semen analysis 3 months after treatment. Sperm progressive motility and percentage of fast and slow moving spermatozoa were measured. Results: Mean sperm progressive motility was 25.82 and 29.60 percent before and after treatment respectively which showed no significant difference (P=0.077). But the number of fast motile sperms were increased from 6.14 before treatment to 9.62 after treatment which showed significant improvement (P=0.015).Although mean sperm motility was improved better in patients with isolated Asthenospermia but it was not statistically significant (P=0.08). Conclusion: Our study showed that oral form of Pentoxyfilline can improve percentage of fast moving spermatozoa that is more prominent in patients with isolated Asthenospermia.

PP13

PERCEPTIONS OF MALE SEXUAL DYSFUNCTION MANAGEMENT AMONG GENERAL PRACTITIONERS IN SOUTH AFRICA

Basil J. Pillay¹, Mohamed H. Cassimjee², P. Ramlachan³

Introduction: Sexual dysfunction (SD) is a common disorder presenting first to the general practitioner. While recent pharmacological advances have increased public interest and demand for treatment of SD, to a considerable extent, effective treatment is dependent on the quality of the interaction between the doctor and the patient. Medical practitioners attitudes and perceptions directly influence this interaction. It is therefore important to understand the role of the general practitioner in facilitating effective management of SD. Aim: To evaluate the attitudes, perceptions and management of sexual dysfunction in general practitioners. Methods: Semi structure interviews and questionnaires was used to elicit the experiences of general practitioners in the treatment of SD in a male cohort. Results and Conclusion: The results on data obtained nationally are discussed indicating the approach general practitioners use to screening for sexual problems (33 % female & 60 % male); the comfort of the general practitioner in treating SD (11 % female & 35 % male) and management challenges (8 % - 36 % female & 1 % - 17 % male). In addition, the challenges they face working in a multicultural context is discussed.

PP14

EFFECTIVENESS OF VITAMIN E SUPPLEMENTATION ON DICLOFENAC INDUCED CHANGES IN LIPOGENIC ENZYMES OF RATS

Shree K. Sakthi¹, G. Vanithakumari

The restoration of adverse changes in the activities of lipogenic enzymes on vitamin E (an-anti-oxidant) supplementation in albino rats, brought about by diclofenac, in short and long duration treatments, were studied. Wistar strain albino rats of 200-240 gm bodyweight were used. Diclofenac at a dosage of 3 mg/kg body weight was given im. as weekly dose for 2 weeks (short) and 8 weeks (long) duration and supplementation with 4 mg/kg body weight of vitamin E, along with the drug was also undertaken for the above mentioned durations. The activities of lipogenic enzymes were studied. A stimulated response to diclofenac was exhibited in the activities of NADP+ isocitrate dehydrogenase, ATP-citrate lyase, malic enzyme, G-6-PD and 6-phosphogluconate dehydrogenase enzymes, but inhibited the activity of malic dehydrogenase in short duration of treatment. Longer duration of treatment further potentiated the stimulated activities of the above enzymes, except for ATP-citrate lyase and malic enzyme, which were inhibited along with malic dehydrogenase enzyme. Vitamin E supplementation resulted in a partial restoration of the changed status of the enzyme activities to near normal levels, in short as well as long duration of treatments, thus indicating its beneficial effect on testicular lipogenic enzymes in rats.

PP15

THE PRESENT CONDITIONS OF INTRACAVERNOUS INJECTION OF PGE1 IN OUR INSTITUTIONS (YOKOHAMA, JAPAN)

Aim: A diagnosis procedure varied with abstract sildenafil citrate release dramatically, and the frequency of an ICI test decreased in comparison with the past, but importance as the diagnosis did not change. Therefore, we report the present conditions of an intracavernous injection test of PGE1 (ICI test) in our institutions. Methods: The patient who had a checkup with a specialized outpatient of our institutions was 278 impotent male, and the number that performed an intracavernous injection of PGE1 20 mg as purpose for ED diagnosis was 52 patients (18.7 %). Results: The erectile reaction to an ICI test was divided into 5 categories , one patient for Response 0, 13 for Response I, 7 for Response II, 31 for Response III and Response IV was not appeared. In other words, 21 patients (40.4 %) of Response 0~II are thought to be vasculogenic ED, on the other hand, 31 patients (59.6 %) of Response III are regarded that vascular system is normal and the etiology of these patients is psychogenic ED or neurogenic ED. And further evaluation, we are able to diagnose the etiology of some patients , 11 out of 21 patients of Response 0~II were arterial erectile dysfunction. On the other hand, in 31 patients of Response III, the cause of 5 patients is psychogenic factor and 11 patients are neurogenic ED (5 for the pelvic major surgery / 2 diabetes mellitus / 2 spinal cord injury / one pelvic fracture / one penile injury).

THE RELATIONSHIP BETWEEN SPERM KINETICS ASSESSED BY THE COMPUTER-AIDDED SPERM ANALYSIS (CASA) AND THE PREGNANCY RATE IN INTRAUTERINE INSEMINATION (IUI)

K. Suzuki, T. Kasai, M. Fujie, M. Suzuki, S. Hirata, K. Hoshi

Recent years, CASA is performed in many institutions to estimate the sperm kinetics using various parameters. This study was carried out to investigate the relationships between the CASA estimates and pregnancy rates in IUI by using ROC curve. The study was performed to patients who experienced IUI during the period January 2000-April 2003 whose semen analysis did not fulfill the WHO criterion. After sperm preparation, sperm motion kinetics was measured by CASA (curvilinear velocity [VCL], straight-line velocity [VSL], average path velocity [VAP], Burkman index [BI]). We compared the diagnostic power of inseminated sperm concentration, total number of inseminated sperm, and other sperm parameters, by ROC curve analysis. During the study period, we analyzed 166 IUI cycles. When looking at the area under the curve, there were no significant differences between the reference line and the seven parameters. Of the seven parameters, VSL showed the lowest P-value (0.051). Specificity of slow sperm was high, but both sensitivity and specificity of inseminated sperm concentration were low. It is difficult to predict pregnancy in IUI, because pregnancy rate of IUI is very low. Results of this study suggest the parameter which reflect the straight kinetics, especially VSL, is more useful to predict pregnancy than inseminated sperm concentration. And in spite of sperm preparation, when sperm speed is slow, we should consider to shift to IVF-ET therapy.

PP17

THE PROGNOSTIC POWER OF THE COMPUTERIZED POST-COITAL TEST FOR NATURAL CONCEPTION AND INTRAUTERINE INSEMINATION

T. Kasai, M. Fujie, M. Suzuki, K. Suzuki, T. Shima, Y. Shimazu, M. Wada, M. Miyake, M. Hashi, S. Hirata, K. Hoshi

Aim: The value of the conventional post-coital test (PCT) is controversial. We determined the relationship between the sperm motile parameters in the late follicular cervical mucus measured with a computer assisted semen analyzer (CASA) and male fertility in subfertile couples due to unexplained causes. Methods: A retrospective study relates the result of the computerized PCT to the occurrence of a spontaneous pregnancy and pregnancy by intrauterine insemination (IUI). Sperm motility parameters in the cervical mucus was evaluated by CASA as follows; number of motile sperm, average path velocity, straight line velocity, curvilinear velocity, amplitude of head displacement (ALH), and beat cross frequency (BCF). Patients were divided into four groups as follows: group A; spontaneous pregnancy (n=16), group B; no achieved spontaneous pregnancy (n=16), group C; achieved pregnancy by IUI (n=4), group D; no achieved pregnancy by IUI (n=10). Statistical analysis was performed using unpaired t-test and the receiver operating characteristic (ROC) curve. Results: ALH was significantly lower in group C than that in group A, B (P<0.05). BCF was significantly lower in group C than that in group D (P<0.05). No significant differences were found in other parameters. When the prognostic power of sperm motility parameters for pregnancy was analyzed by means of the ROC curve, only BCF was a predictor for the negative IUI pregnancy, with an area under the ROC curve of 0.138 (P<0.05). Conclusion: These results indicate that IUI might be considered for unexplained infertile couples when values of ALH or BCF of sperm in the cervical mucus were low.

PP18

EXPRESSION ANALYSIS OF AZF(AZOOSPERMIA FACTOR) GENES ON THE Y CHROMOSOME REVEALED A MAJOR ROLE FOR BPY 2 (BASIC PROTEIN Y 2) IN GERM CELL LINE

Eitetsu Koh, Masato Fukushima, Mikio Namiki, Atsumi Yoshida¹

Aim: Genes on the long arm of Y are believed to play a crucial role in human spermatogenesis. In this study, we investigated the expression of Y specific genes in azoospermia men undergoing testicular biopsy. We determined whether Y specific genes were transcripted in germ cell line. Methods: The patients who elevated levels Serum FSH more than 30 mIU/ml (normal; 2.7-8.9) were selected. A high level of FSH is involved in spermatogenesis impairment. All of subjects were undergoing a testicular biopsy. Patients with obstructive azoospermia and normal histology served as control. RNA was reverse transcribed and PCR amplified using specific primers, namely DFFRY, DBY, UTY, TB4Y, TTY2, XKRY, eIF-1AY, RBM , DAZ, BPY2 CDY. All patients were also performed the genome screening for fifty STS markers. Results: We chose twenty-four patients with azoospermia. Seventeen patients (71 %) had Sertoli cell only and seven patients (29 %) had no cell components in the seminiferous tubules (hyalinization). None of the patients showed microdeletions in any these genes on Y chromosome by means of STS-PCR. In expression study, all patients lacked BPY2 transcript. A lack of expression in RBM and DAZ was 67 % and 71 %, respectively. A large proportion of Y specific genes were showed the various expression pattern exceptBPY2, DAZ and RBM. Conclusion: BPY2 transcript is encoded by the AZFc of the human Y chromosome and is expressed specifically in the male germ cells. The pattern of expression of BPY2 correlated with the pattern of transcriptional activity during spermatogenesis.

PP19

SCANNING ELECTRON MICROSCOPE ANALYSIS OF PERINATAL EVENTS IN GUBERNACULUM TESTIS

Aymen A. Warille, Lakshmi Selvaratnam, Normadiah M. Kassim

Aim: From the time of Hunter (1762), a mesenchymal condensation referred to as gubernaculum testis (Gb), has been associated with playing a key role in guiding testicular descent. Moreover, Gb malformation has been strongly implicated in the pathogenesis of cryptorchidism and its sequelae, including infertility and testicular cancer. Thus, a morphological correlative study was carried out to determine alterations in Gb during the critical perinatal period of testicular development. Methods: Male foetuses were harvested from pregnant Sprague Dawley rats at 20 days gestation, at birth and at 4 days postnatally. The reproductive systems including Gb were dissected in situ and processed for light microscopy (LM; n=6/stage) & scanning electron microscopy (SEM; n=2/stage). Results: At prenatal day 20, the testis was comparatively large in size, but immature, depicted by its reduced seminiferous tubule density. Gb growth was maximal with much mitotic cellular activity. At birth, the testis exhibited enhanced differentiation and increased 3? fold in size, with more mature seminiferous tubules concentrated peripherally. At this stage, Gb demonstrated involution into the inguinal canal region and also displayed reduced mitotic activity and other signs of regression. By postnatal day 4, Gb showed degenerative changes and testis descended further towards the scrotal region. Conclusion: This study clearly demonstrates specific alterations in Gb structure and activity closely correlated with simultaneous testicular maturation and descent.

FP01

ERECTILE DYSFUNCTION AND LUTS AT THE CELLULAR LEVEL: IMPACT OF AGING AND/OR HYPOGONADISM ON PROSTATE & CAVERNOSAL TISSUES

A. A. Yassin¹, A. M. Traish²

The change impacts on body, power and mind in Aging Male are:

• Shrinking of Pituitary Gland

• Aging dependent decrease in testosterone level 1% and DHT 0.4 every year up age 40

• Increasing of certain "fibrosing" Growth Factors such as VEGF

That is consequently leading to macro-, micro-antomical & histochemical changes in target organs: here Prostate and penile cavernosal tissues.

We were more determined in our research group to study the impact on sexuality in this population not only as the result of impaired QoL due to voiding disturbances or nocturia (tiredness, lack of sleep etc.) but also to look for the reasons in the microanatomy and histo-chemistry, due to aging process and/or hypogonadism.

The hormonal imbalance (aging related Lack of Testosterone and DHT) can give a chance for ?Aging Changes ?in the whole male organism including the tissues of Prostate and Corpus cavernosum stromas. The connective collagen stroma will increase, enhancing the compartments of Alpha-1 Adrenoceptors 1 & 2. More collagen means less vascular compartment, less leukocytes, but in consequence less Nitric Oxide (NO). Besides blood vessels and leukocytes, the third source for NO are the nerves, which are also less under the dominance of connective tissues in organs concerned in this case.

The fibrosing role of certain growth factors like VEGF plays the integral part in increasing the collagen. Recovery process, correction or tissue rejuvenation, especially the trabecular tissues, can be reached in most cases under Androgen replacement therapy (ART).

FP02

HOW DO MEN COPE WITH ED ?A QUALITATIVE STUDY ON MENS HEALTH-SEEKING BEHAVIOUR

Wah-Yun LOW¹, Chirk-Jenn NG¹, Wan-Yuen CHOO¹, Hui-Meng TAN²

Aim: This study aimed to explore men's behaviour when they were faced with erectile dysfunction. Methods: This qualitative study utilized in depth interviews of 17 ED sufferers, whose health-seeking behaviours were explored based on a semi-structured guide. The key themes include their timing of seeking help, who they consulted and how they coped before seeking formal treatment. Results: This study revealed that men either did not seek help at all, delayed in seeking help or, less often, sought help immediately for ED. These behaviours were not permanent and changed with time and if opportunities of treatment arose. Some would self-medicate based on their own readings and experiences, while others would ask their spouses, relatives and friends for help. Modern medicine and traditional medicine were important but usually not the initial sources of help. Some men coped by rationalising their illness and accepting it without asking for help. This was the group of men that did not seek treatment, or delay their treatment for a long period of time. Another group of men would cope by self-stimulation, or by asking their partners to perform oral sex on them. Conclusion: In this study, men coped with ED in different manners. Understanding their health-seeking behaviours is important for targeted patient education and timely intervention by the doctors.

TADALAFIL AND a1-ADRENOCEPTOR BLOCKADE: COMBINATION ED-THERAPY IN BPH-POPULATION

A. A. Yassin¹, H. E. Diede²

Keywords: a1-Adrenoceptor; ED; BPH; Tadalafil

Aim: To assess/investigate the efficacy and safety of Tadalafil combination with Alfuzosin for treatment of ED in non-responders to Tadalafil mono-therapy. To create an integral treatment concept related to co-morbidity; such as the BPH in this study. Methods: In retrospective open label study we enrolled 42 BPH patients with IPSS > =18 and moderate to severe ED, according to IIEF surveys. Average age: 60 years. Duration: 6 months, till end of July 2003. Hormonal status was normal. PSA range 1.1 - 3.6 mg/L (average 2.1 mg/L). All patients were non-responders to PDE-5 inhibitors. After completing diagnostics procedures to BPH, Blood Pressure and ED, we put them all on Alfuzosin 10mg OD daily. They received Tadalafil 20mg on need (20 - 60 minutes before sexual intercourse), twice a week, max.. The results had been individually assessed by means of IPSS & IIEF one month after starting the therapy. Post-therapeutic data showed a clear correlation regarding improvement between IPSS and IIEF. In 30 patients (71 %) this combination therapy had been a success. There was no significant alteration in blood pressure. Side effect profile did not remarkably deviate from that of mono-therapy of each medicament. 12 patients reported no advantage regarding their ED situation. 7 of them were suffering from arterial hypertension for several years. Conclusion: Despite the fact that Alpha-1 Adrenoceptor antagonists are not adequate for ED treatment as mono-therapy, the study results proved the synergistic effect of Tadalafil and Alfuzosin in treatment of ED in BPH-Population. The blockade of Alpha adrenergic receptors reduces the sympathetic vasocon-strictive and smooth muscle tone in the penile cavernosal tissues, and enhances the vasoactive influence of Tadalafil. No blood pressure alteration or different side effect profile was noticed.

FP04

EXPLORING THE FACTORS INFLUENCING HEALTH-SEEKING BEHAVIOUR OF MEN WITH ED

Chirk-Jenn NG¹, Wah-Yun LOW¹, Wan-Yuen CHOO¹, Hui-Meng TAN²

¹Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
²Subang Jaya Medical Centre, Kuala Lumpur, Malaysia

Aim: This study aimed to explain the health-seeking behaviour of men with erectile dysfunction. Methods: Seventeen in-depth interviews were conducted among ED sufferers in Klang Valley, Malaysia. A semi-structured guide was used to explore key factors influencing men's health-seeking behaviours. Results: This study identified many influencing factors which are classified into personal factor, social factor, disease and treatment factor, and health care provider/ health care system factor. Personal factor stood out as one of the most important variables influencing men's health-seeking behaviour. Manhood, relationship and communication with wives, Asian culture, perception of sex in terms of age and needs were common themes. Partner's sexual dissatisfaction was the main motivating factor for men to seek help. Partners' sexual needs and willingness to discuss sex also affected men's enthusiasm to seek help. Their perception of the severity of ED also played an important role. Most men were not aware of where to go and who to seek help from. This significantly hampered their initial help-seeking process. Once they sought help, they preferred healthcare providers who would listen and understand their problems, and offer appropriate advice. Confidentiality was considered crucial. Conclusion: Understanding these determinants would help the healthcare providers to offer more patient-centred and holistic management of this gender-sensitive condition.

PP19

COMBINATION THERAPY OF TADALAFIL & TESTOSTERONE IN HYPOGONADAL NON-RESPONDERS

A. A. Yassin¹, A. M. Traish², F. Saad³,  H. E. Diede⁴

Keywords: ED; Hypogonadism; Testosterone; PDE-5- inhibitors; Tadalafil

Aim: To investigate the efficacy and safety of Tadalafil in combination with Androgen Replacement Therapy (ART)/Testosterone, for the treatment of Non-responders to Tadalafil mono-therapy in ED patients. To create an integral indication-related treatment. Methods: 35 % of DM patients and 23 % of others suffering from ED, are initially non-responders to therapy with PDE- inhibitors including Tadalafil. Upon discovering of DM,

42 % of DM population has already got a primary hypogonadism. A half of non-DM, non-responders to Tadalafil, show a kind of Androgen insufficiency. We divided our 69 non-responders into two homogeneous groups. Average age was 59 years. First group: 35 patients received ART for 4 weeks, then we started Tadalafil 20 mg therapy with measuring T-Testosterone level 3-4 ng/mL. 15 patient (40 %) reported sexual satisfaction, IIEF and spontaneous or nocturnal erections. Second group: 34 patients received Tadalafil 20 mg 10 weeks after Testosterone therapy with significantly higher response 22 pat. (65 %). They showed a significant increase in IIEF and spontaneous or nocturnal erection as well. Conclusion: This study is proving the essential role of Testosterone not only in male desire but erection as well. The recovery process at the penile cellular level due to androgen deficiency, is starting with good?Testosterone level in serum, but it takes more time than four weeks to reach significant satisfaction. Studies have shown that sexual desire and spontaneous erection (morning, nocturnal) are clearly testosterone-dependant and are correlating with normal Testosterone level 2-4 ng/mL. Nocturnal erection seems always impaired when Testosterone under 1.5 ng/mL, whereas sexual activity is always impaired if Testosterone lower than 2 ng/mL. There is also a correlation between Testosterone and parameter of Penile Vascular Function in men. The therapy with Tadalafil and Testosterone in Diabetes- and/or hypogonadal patients is a safe and effective combination for ED in this clientele for whom Tadalafil alone failed.