Katsuyuki Baba

Clinical Practice Manual for Late-onset Hypogonadism Syndrome

With the aging of the population, the quality of life (QOL) of middleaged and elderly men has come into question and it has been taken up from an interdisciplinary standpoint in recent years. Partial androgen deficiency of the aging male (PADAM) or lateonset hypogonadism (LOH) is a syndrome consisting of symptoms caused by partial deficiency of androgens, but the time of onset varies and the epidemiological status is unclear. Therefore, in Japan to date, this syndrome has been considered as a general phenomenon associated with aging, the medical authorities have not reacted and patients are not being treated. In Western countries however, this phenomenon has attracted attention in relation to geriatrics and reproductive endocrinology since the 1980s. In 1998, the International Society for the Study of the Aging Male (ISSAM) was founded to conduct basic and clinical research, to provide postgraduate education and to engage in publicity activities for the enlightenment of the public. The social background is characterized by the appearance of a very rapidly aging society with longer average life spans. The importance of improving the health of the elderly and preventive medicine as government policy has increased. Improving the health of the elderly not only promotes self-reliance of the elderly but also increases the work force. A high QOL is also possible. The main topic for healthcare in the 21st century is how to maintain the QOL of the elderly. In women, hormone replacement therapy (HRT) is widely applied internationally, but specific healthcare for elderly men appears to be limited to the widespread use of phosphodiesterase type 5 (PDE5) inhibitors to treat erectile dysfunction (ED). Although the delay in healthcare policies for elderly men is not a direct reason, a large gap has appeared between the average life spans of men and women in recent years and in Japan, men have a shorter life span than women by about seven years. In response to this sense of crisis, the World Health Organization (WHO) issued the Geneva Manifesto in 1997 and ‘healthy aging for men’ became an international movement. ISSAM was established in 1998 with the goal of ‘aging male research on gender specific issues in male health’. The first meeting of the society in Asia was held in Malaysia in 2001 and this topic was adopted on an international level from an early stage. The reason appeared to be strong economic and social concern that Asian countries with a current pyramid-type population distribution will become aging societies with a lower birth rate than in developing countries. Japan has already become an aging society with a low birth rate. In the national census (summary) in 2005, the elderly population of 65 years and older accounted for about 21% of the total population, the highest in the developed world. In Japan, scientific research on the aging male started at about the same time as in the rest of Asia, and the Japanese Society for the Study of the Aging Male (JSSAM) was founded in November 2001 with Yoshiaki Kumamoto, professor emeritus of Sapporo Medical University, and Hajime Nawata, professor of Kyushu University as representative facilitators. The goal of this society is ‘undertaking basic, clinical and social research and surveys on policies for the diagnosis, treatment and prevention of male-specific medical problems, and contributing widely to men’s health by development, promotion and spread of proper healthcare’. As mentioned above, the concept of research on the aging male is being promoted as ‘healthy aging for men’ but almost no actual treatment for such patients has been performed. When the JSSAM was established , so-called ‘male climacteric symptoms’ or ‘male menopause’ was popular in the media, and when such treatment was started , many patients mainly with a chief complaint of climacteric symptoms appeared in medical practice. These patients included many with psychiatric problems such as depression and considerable confusion arose in clinics and hospitals. Based on this background , the Subcommittee on Endocrinology, Reproductive Function and Sexual Function of the Japanese Urological Association asked the Scientific Committee to prepare a clinical practice guideline, and a working group was organized to prepare the guideline by a collaborative team from the Japanese Urological Association and JSSAM after a review by the Board of Directors. In this clinical practice manual, the term ‘late–onset hypogonadism (abbreviation: LOH)’ syndrome was adopted as the term that best expresses this condition medically. In order to recommend standard procedures for diagnosis, treatment, prevention and monitoring of adverse reactions due to androgen replacement therapy (ART) and post-treatment assessments, a literature survey of clinical papers was performed , but since treatment of LOH Syndrome has just started , almost all papers had a low recommendation rank. Therefore, the name was changed to ‘Clinical Practice Manual for Treatment of Late-onset Hypogonadism (LOH) Syndrome’ (‘Manual’ hereinafter) instead of the initially planned ‘clinical practice guideline’. Care of LOH Syndrome is in its initial stages and such treatment requires careful consideration. Since many men visiting medical institutions at present complain of ‘climacteric symptoms’, measures must be taken to have this disease recognized in the mental health field. In the future, it will be necessary to establish evidence for treatment of LOH Syndrome from the broad perspective of promotion of ‘healthy aging for men.’ This ‘Manual’ is the first edition aimed at gathering evidence through future diagnosis and treatment of LOH and it is hoped that it will serve as a reference for routine medical practice. Correspondence: Eitetsu Koh MD, Department of Urology, Kanazawa University School of Medicine, 13-1 Takaramachi, Kanazawa 920-8641, Japan. Email: kohei@med.kanazawa-u.ac.jp This is an English translation of text originally published in Japanese in (LOH ) , 2007, Jihou

Conservative treatment of childhood phimosis with topical conjugated equine estrogen ointment

Purpose : To assess the application of topical conjugated equine estrogen for the treatment of boys with phimosis.

Semen quality of 1559 young men from four cities in Japan: a cross-sectional population-based study

Objectives To provide information of semen quality among normal young Japanese men and indicate the frequency of reduced semen quality. Design Cross-sectional, coordinated studies of Japanese young men included from university areas. The men had to be 18–24 years, and both the man and his mother had to be born in Japan. Background information was obtained from questionnaires. Standardised and quality-controlled semen analyses were performed, reproductive hormones analysed centrally and results adjusted for confounding factors. Setting Four study centres in Japan (Kawasaki, Osaka, Kanazawa and Nagasaki). Participants 1559 men, median age 21.1 years, included during 1999–2003. Outcome measures Semen volume, sperm concentration, total sperm count, sperm motility, sperm morphology and reproductive hormone levels. Results Median sperm concentration was 59 (95% CI 52 to 68) million/ml, and 9% and 31.9% had less than 15 and 40 million/ml, respectively. Median percentage of morphologically normal spermatozoa was 9.6 (8.8 to 10.3)%. Small, but statistically significant, differences were detected for both semen and reproductive hormone variables between men from the four cities. Overall, the semen values were lower than those of a reference population of 792 fertile Japanese men. Conclusions Assuming that the investigated men were representative for young Japanese men, a significant proportion of the population had suboptimal semen quality with reduced fertility potential, and as a group they had lower semen quality than fertile men. However, the definitive role—if any—of low semen quality for subfertility and low fertility rates remain to be investigated.

POLYMERASE CHAIN REACTION ANALYSIS OF THE Y CHROMOSOME LONG ARM IN AZOOSPERMIC PATIENTS : LACK OF THE Y CHROMOSOME RECOGNITION MOTIF (YRRM1) GENE

We analyzed DNA from a patient with azoospermia whose Y chromosome was cytogenetically normal. A total of 16 loci on the Y chromosome long arm were examined: 15 loci between DYS7E and DYZ1, and the Y chromosome RNA recognition motif (YRRM1) locus, a candidate gene for the azoospermic factor AZF. We did not detect the YRRM1 gene in this patient. This finding supports the theory that YRRM1 is an essential gene for spermatogenesis.

Semen quality of Japanese fertile men: A study of partners of pregnant women

During the recent years conflicting information on possible changes in semen quality has been published. These publications also indicate that geographical differences in semen quality may exist. However, no definitive evidence has been provided and additionally very little information regarding semen quality of Japanese men are available. Therefore, we undertook a cross‐sectional study of partners of pregnant women following the same protocol, which has already been used in four European cities. 351 male partners of pregnant women living in the Kawasaki/Yokohama area of Tokyo participated in the study. Of these 232 were recruited from 3 University Hospitals (UH) and 119 were recruited from 2 Private Hospitals (PH). The raw data of the median sperm concentrations were 92.4 (mill/ml) and 99.8 (mill/ml) for the participants from UH and PH respectively. In the analysis of the data the following parameters were taken into account as confounders: mens age, season of year, and abstinence period. We detected a clear seasonal variation in sperm counts with lowest sperm concentration and total sperm count in spring season and highest counts in autumn season with counts in summer and winter seasons being in between. We estimated the semen quality of a “standardised man” (30‐year‐old, fertile, ejaculation abstinence of 96 hours) for both autumn and spring season. The sperm concentration (mill/ml) for autumn/spring were: UH 89/54 and PH 105/63; for total sperm counts (mill): UH 282/151 and PH 315/169. As in the European study we detected a seasonal variation in sperm counts. However, in our study highest counts were detected in autumn season whereas the highest counts in the European study were detected in winter season. Likewise, the lowest counts were in spring and summer in Japan and Europe respectively. The estimated sperm counts of a “standardised Japanese fertile man” seem to be higher than counts in Denmark (Copenhagen) and France (Paris) but lower than counts in Scotland (Edinburgh) and Finland (Turku). It remains to be seen whether regional differences in semen quality exist in Japan.