Bruno Lunenfeld

Investigation, Treatment, and Monitoring of Late-Onset Hypogonadism in Males: ISA, ISSAM, EAU, EAA, and ASA Recommendations

The new ISA, ISSAM, EAU, EAA and ASA recommendations on the investigation, treatment and monitoring of late-onset hypogonadism in males provide updated evidence-based information for clinicians who diagnose and treat patients with adult onset, age related testosterone deficiency.

Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA and ASA recommendations

Demographic data clearly demonstrate that the percentage of the population in the older age group is increasing. Androgen deficiency in the aging male has become a topic of increasing interest and debate throughout the world. Cross-sectional and longitudinal data indicate that the testosterone falls progressively with age and that a significant percentage of men over the age of 60 years have serum testosterone levels that are below the lower limits of young adult (age 20–30 years) men (1–4). The principal questions raised by these observations are whether older hypogonadal men will benefit from testosterone treatment and what will be the risks associated with such intervention. The past decade has brought evidence of benefit of androgen treatment of hypogonadal men on multiple target organs and the recent studies show short-term beneficial effects of testosterone in older men that are similar to those in younger men. This has been comprehensively reviewed and summarized by the Institute of Medicine in ‘Testosterone and Aging: Clinical Research Directions’ (5). Long-term data on the effects of testosterone treatment in the older population are limited mainly to effects on body composition and bone mass (6–11). Key questions of the effects of testosterone on patient reported outcomes and functional benefits that may retard physical or mental frailty of the elderly or improve the quality of life are not yet available. Specific risk data on the prostate and cardiovascular systems are needed.

Follicular development and its control

The female reproductive cycle is based on a co-ordinated function of several regulatory elements and signalling systems. Of the approximately 7 million oocytes present in the human fetal ovary, only 475 will eventually ovulate. In the human, the development of a primordial follicle into a dominant one takes about 10 weeks. Approximately 300 follicles are recruited initially for growth and development, 30 of them are likely to become gonadotropin-dependent and enter competition for dominance and, finally, only one will achieve ovulation. The mechanisms by which follicle stimulating hormone, luteinizing hormone, growth factors and steroids may promote or disrupt follicular development are discussed in detail. Possible implications of these new facts on diagnosis and treatment of ovulatory disturbances are described.

Investigation, treatment and monitoring of late-onset hypogonadism in males.

*Corresponding Author Androgen deficiency in the aging male has become a topic of increasing interest and debate throughout the world. The demographics clearly demonstrate the increasing percentage of the population that is in the older age groups. The data also support the concept that testosterone falls progressively with age and that a significant percentage of men over the age of 60 years have serum testosterone levels that are below the lower limits of young adults (age 20-30 years) men. The principal questions raised by these observations are whether older hypogonadal men will benefit from testosterone treatment and what will be the risks associated with such intervention. The past decade has brought evidence of benefit of androgen treatment on multiple target organs of hypogonadal men and recent studies show short-term beneficial effects of testosterone in older men that are similar to those in younger men. Long-term data on the effects of testosterone treatment in the older population are limited and specific risk data on the prostate and cardiovascular systems are needed. Answers to key questions of functional benefits that may retard frailty of the elderly are not yet available. The recommendations described below were prepared for the International Society of Andrology (ISA) and the International Society for the Study of the Aging Male (ISSAM) following a panel discussion with active participation from the audience sponsored by the ISA on the topic at the 4th ISSAM Congress in Prague in February 2004. The ISA Member Societies were requested to comment on the draft recommedations. Representatives of the European Association of Urology (EAU) participated in the final draft of this document. This document is not intended to provide evidence for each recommendation as review of pertinent studies have recently been comprehensively summarized in the Clinical Research Directions on “Testosterone and Aging” by the Institute of Medicine (Washington 2004). The recommendations will be subject to revision as larger-scale and longer-term data become available. In order to reach a large audience these recommendations are published in the International Journal of Andrology,the Journal of Andrology, The Aging Male and in European Urology. E Nieschlag * Institute of Reproductive Medicine University of Münster, Germany Email: eberhard.nieschlag@ukmuenster.de

ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males

Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center and Los Angeles BioMedical Research Institute, Torrance, CA, USA, Centre for Reproductive Medicine and Andrology, University of Muenster, Muenster, Germany, Center for Reproductive Medicine and Andrology, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Halle, Germany, Department of Urology, Tulane University, New Orleans, LA, USA, Department of Endocrinology, VU University Medical Center, Amsterdam, The Netherlands, Department of Endocrinology, Academish Ziekenhuis, Gent, Belgium, Centre Hospitalier Universitaire, Sart-Tilman, Liege, Belgium, Faculty of Life Science, Bar-Ilan University, Ramat-Gan, Israel, Centre for Applied Urological Research, Queen’s University, Kingston, Canada, Division of Geriatric Medicine, St. Louis University and GRECC, St. Louis VA Medical Center, St. Louis, MO, USA, Department of Urology, Erasme Hospital, University Clinics Brussels, Brussels, Belgium, Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA, Department of Urology and Pediatric Urology, University Hospitals, Justus-Liebig-University, Giessen, Germany, and Department of Endocrinology, University of Manchester, Manchester Royal Infirmary, Manchester, UK

Infertility therapy associated-multiple pregnancies (births): an ongoing epidemic

Multiple gestation is now recognized as a major problem associated with both assisted reproductive technologies (ART) and also with ovulation induction therapies. Although some countries are beginning to adopt measures to address this issue, either through legislation or the development of clinical guidelines, there is a clear need to ensure recognition and a consistent approach to this problem worldwide. In particular, there is a need to educate both healthcare professionals and the lay population that multiple gestations are not a desirable outcome for the infertile couple.

Recommendations on the diagnosis, treatment and monitoring of hypogonadism in men

Abstract Hypogonadism or Testosterone Deficiency (TD) in adult men as defined by low levels of serum testosterone accompanied by characteristic symptoms and/or signs as detailed further on can be found in long-recognized clinical entities such as Klinefelter syndrome, Kallmann syndrome, pituitary or testicular disorders, as well as in men with idiopathic, metabolic or iatrogenic conditions that result in testosterone deficiency. These recommendations do not encompass the full range of pathologies leading to hypogonadism (testosterone deficiency), but instead focus on the clinical spectrum of hypogonadism related to metabolic and idiopathic disorders that contribute to the majority of cases that occur in adult men.

Cancer incidence in a cohort of infertile women who underwent in vitro fertilization

OBJECTIVE To assess whether ovarian hyperstimulation and IVF increase the risk for cancer. DESIGN Historical cohort analysis. SETTING; IVF units of two medical centers in Israel. PATIENT(S) Five thousand twenty-six women who underwent IVF between 1981 and 1992. INTERVENTION(S); Cancer incidence rates were determined through linkage to the National Cancer Registry and were compared with expected rates with respect to age, sex, and place of birth. MAIN OUTCOME MEASURE(S) Development of cancer. RESULT(S) Twenty-seven cases of cancer were observed, and 35.6 were expected (standardized incidence ratio, 0.76 [95% CI, 0.50-1.10]). Eleven cases of breast cancer were observed, whereas 15.86 were expected (standardized incidence ratio, 0.69 [95% CI, 0.46-1.66]). One case of ovarian cancer and 1 case of cervical cancer were observed, compared with 1.74 and 1.73 cases expected, respectively. The type of infertility, number of IVF cycles, and treatment outcome did not significantly affect risk for cancer. CONCLUSION(S) In a cohort of women treated with IVF, no excess risk for cancer was noted.

ISA, ISSAM and EAU recommendations for the investigation, treatment and monitoring of late-onset hypogonadism in males: Scientific background and rationale

Prescription sales for testosterone products have substantially increased over the last several years reflecting the growing awareness of physicians for the potential benefits of testosterone replacement therapy in men with hypogonadism. Indiscriminate administration of testosterone poses a risk and has to be deprecated. Testosterone supplementation to treat late-onset hypogonadism (LOH), a term for androgen deficiency in elderly men, is still controversially discussed mainly due to a lack of large, controlled clinical trials on efficacy and safety. To provide guidance for physicians primarily dealing with aging men, ISSAM is periodically updating and publishing its recommendations as new data become available [Morales A, Lunenfeld B. International Society for the Study of the Aging Male. Investigation, treatment and monitoring of late-onset hypogonadism in males. Official recommendations of ISSAM. International Society for the Study of the Aging Male. Aging Male 2002;5:74–86 and Morales A, Lunenfeld B. Androgen replacement therapy in aging men with secondary hypogonadism. Draft recommendations for endorsement by ISSAM. Aging Male 2001;4:1]. Following a panel discussion at the 4th ISSAM Congress in Prague in February 2004, the International Society of Andrology (ISA), the International Society for the Study of the Aging Male (ISSAM) and the European Association of Urology (EAU) revised existing recommendations on the definition, diagnosis and management of LOH. The recommendations are based on the currently available scientific data on androgen supplementation therapy and should be regarded as provisional until larger-scale, long-term studies are available. While certainly not intending to be exhaustive, this review will highlight some relevant background information and provide the underlying scientific rationale for the ISA, ISSAM and EAU recommendations on LOH published in this issue.

An Aging World – demographics and challenges

The world has seen enormous changes over the past century, including historically unprecedented declines in mortality rates and increases in population, followed by equally unprecedented declines in fertility rates. This century will see a new set of demographic challenges, including a mix of falling fertility rates alongside persisting worldwide population growth, and the subsequent aging of populations in both developing and developed countries. The 20th century was the century of population growth; the 21st century will go into the history books as the century of aging. A holistic approach to this new challenge of the 21st century will necessitate a quantum leap in multidisciplinary and internationally coordinated research efforts, supported by a new partnership between industry and governments, philanthropic and international organizations. This collaboration we hope will enrich us with a better understanding of healthy aging, permit us to help to improve quality of life, prevent the preventable, and postpone and decrease the pain and suffering of the inevitable.