Investigation, treatment and monitoring of late-onset hypogonadism in males
Open accessAbstract
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, 2, 3, 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, 7, 8, 9, 10, 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. Recent guidelines for the testosterone treatment of younger hypogonadal men are available from professional societies (12, 13, 14). Recommendations on the diagnosis, treatment, and monitoring of late-onset hypogonadism (LOH) were published by International Society for the Study of Aging Male (ISSAM) in 2002 (15). In 2005, a writing committee formed by the International Society of Andrology (ISA), the ISSAM, and the European Association of Urology (EAU) prepared a set of recommendations specifically on the ‘Investigation, treatment and monitoring of LOH’. In order to reach a large audience, these recommendations were published in the International Journal of Andrology, the Journal of Andrology, the Aging Male, and European Urology (16, 17, 18, 19). In view of the growing interest from practitioners on the treatment of older men with testosterone, the ISA, ISSAM, EAU, European Academy of Andrology, and American Society of Andrology convened meetings of the writing group with expert representatives from each of the societies. The writing group membership from 2005 was expanded to include additional urologists. Members of the writing group met in Berlin 2007, Toronto 2007, and Tampa 2008 to revise these recommendations. There was no corporate funding or support for the development of these recommendations. The revised recommendations are supported by a selection of appropriate references and categorized by the level of evidence and grade of recommendation according to the US Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research (1992; Table 1). Level of evidence and grade of recommendation utilized in the recommendations. Level of evidence and grade of recommendation utilized in the recommendations. To ensure broad outreach to multidisciplinary audiences, these recommendations are published in several journals simultaneously. LOH, also referred to as age-associated testosterone-deficiency syndrome (TDS), is a clinical and biochemical syndrome associated with advancing age and characterized by symptoms and a deficiency in serum testosterone levels (below the young healthy adult male reference range) (16, 17, 18, 19, 20). This condition may result in significant detriment in the quality of life and adversely affect the function of multiple organ systems. 2.1. At present, the diagnosis of treatable hypogonadism requires the presence of symptoms and signs suggestive of testosterone deficiency (Level 3, Grade A) (12, 16, 17, 18, 19). The symptom most associated with hypogonadism is low libido (Level 3, Grade A) (21, 22). Other manifestations of hypogonadism include: erectile dysfunction, decreased muscle mass and strength, increased body fat, decreased bone mineral density and osteoporosis, and decreased vitality and depressed mood. None of these symptoms are specific to the low androgen state but may raise suspicion of testosterone deficiency. One or more of these symptoms must be corroborated with a low serum testosterone level (Level 3, Grade A) (1, 23, 24, 25). 2.2. Questionnaires such as Aging Male Symptom Score (AMS) (26, 27) and Androgen Deficiency in Aging Men (ADAM) (28) are not recommended for the diagnosis of hypogonadism because of low specificity (Level 3, Grade B) (24, 29, 30). 3.1. In patients at risk or suspected of hypogonadism, a thorough physical and biochemical work-up is necessary (Level 4, Grade A). Transient decreases of serum testostero
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Other studies have shown increased associations between free testosterone and comorbid conditions including depression and hypogonadal symptoms.
“Other studies have also demonstrated increased associations between fT and other comorbid conditions, including depression and hypogonadal symptoms.”
From Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials (2016) · cites this paper as [97]
There is a degree of consensus that elderly men with serum testosterone clearly below the reference ranges and persistent clear clinical signs of hypogonadism may justifiably be treated.
“There is a degree of consensus that elderly men with serum testosterone clearly below the reference ranges and persistent clear clinical signs of hypogonadism may justifiably be treated (98, 99)”
From Onset of effects of testosterone treatment and time span until maximum effects are achieved (2011) · cites this paper as [98]
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- Authors
- Wang, C., Nieschlag, E., Swerdloff, R., Behre, H. M., Hellstrom, W. J., Gooren, L. J., Kaufman, J. M., Legros, J.-J., Lunenfeld, B., Morales, A., Morley, J. E., Schulman, C., Thompson, I. M., Weidner, W., & Wu, F. C. W.
- Affiliations
- University of California, Los Angeles (US)
- University of Münster (DE)
- University Hospital in Halle (DE)
- Tulane University (US)
- Vrije Universiteit Amsterdam (NL)
- Ghent University Hospital (BE)
- University of Liège (BE)
- Bar-Ilan University (IL)
- St. Louis VA Medical Center (US)
- Université Libre de Bruxelles (BE)
- The University of Texas at San Antonio Health Science Center (US)
- Justus-Liebig-Universität Gießen (DE)
- Manchester Royal Infirmary (GB)
- Corresponding author
- Wang, C
- ORCID
- Venue
- European Journal of Endocrinology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-11
- Volume
- 159
- Issue
- 5
- Pages
- 507-514
- ISSN
- 0804-4643 (ISSN-L)
- 1479-683X
- PMC
- PMC2754376
- OpenAlex
- W2097830439
- Cited by
- 867
- References
- 102
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 13 · 2023: 15 · 2022: 24 · 2021: 25 · 2020: 31 · 2019: 33 · 2018: 22 · 2017: 39 · 2016: 43 · 2015: 58 · 2014: 88 · 2013: 89 · 2012: 106
- FWCI
- 60.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- European Journal of Endocrinology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, other-oa)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- andropause, male hypogonadism, testosterone replacement therapy, older men, androgen deficiency, prostate cancer risk, cardiovascular risk, treatment monitoring, quality of life, frailty, body composition, bone mass, European Association of Urology
- MeSH terms
- Aging, Endocrinology, Europe, Humans, Hypogonadism, Male, Age of Onset
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