Identification of Late-Onset Hypogonadism in Middle-Aged and Elderly Men

Andrology Research Unit, Developmental and Regenerative Biomedicine Research Group, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
New England Journal of Medicine (Impact Factor: 55.87). 07/2010; 363(2):123-35. DOI: 10.1056/NEJMoa0911101
Source: PubMed


The association between aging-related testosterone deficiency and late-onset hypogonadism in men remains a controversial concept. We sought evidence-based criteria for identifying late-onset hypogonadism in the general population on the basis of an association between symptoms and a low testosterone level.
We surveyed a random population sample of 3369 men between the ages of 40 and 79 years at eight European centers. Using questionnaires, we collected data with regard to the subjects' general, sexual, physical, and psychological health. Levels of total testosterone were measured in morning blood samples by mass spectrometry, and free testosterone levels were calculated with the use of Vermeulen's formula. Data were randomly split into separate training and validation sets for confirmatory analyses.
In the training set, symptoms of poor morning erection, low sexual desire, erectile dysfunction, inability to perform vigorous activity, depression, and fatigue were significantly related to the testosterone level. Increased probabilities of the three sexual symptoms and limited physical vigor were discernible with decreased testosterone levels (ranges, 8.0 to 13.0 nmol per liter [2.3 to 3.7 ng per milliliter] for total testosterone and 160 to 280 pmol per liter [46 to 81 pg per milliliter] for free testosterone). However, only the three sexual symptoms had a syndromic association with decreased testosterone levels. An inverse relationship between an increasing number of sexual symptoms and a decreasing testosterone level was observed. These relationships were independently confirmed in the validation set, in which the strengths of the association between symptoms and low testosterone levels determined the minimum criteria necessary to identify late-onset hypogonadism.
Late-onset hypogonadism can be defined by the presence of at least three sexual symptoms associated with a total testosterone level of less than 11 nmol per liter (3.2 ng per milliliter) and a free testosterone level of less than 220 pmol per liter (64 pg per milliliter).

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    • "The association between T deficiency and poor health status, in fact, has been recently described in men with obesity (Corona et al., 2011d) or with a history of previous CV diseases and hypogonadism resulted to be protective on further CV events (Corona et al., 2014a). An increasing body of evidence suggests that a low T syndrome is common especially in older frail men with multiple morbidities (Travison et al., 2007; Wu et al., 2010) and that the lowering of circulating T might be a protective mechanism in unhealthy conditions (Corona et al., 2011d, 2014a). This adaptive mechanism might avoid physiological conditions of high-energy expenditure that are potentially detrimental for the sick patient (e.g., reproductive behavior, vigorous physical activity, increased energy expenditure, and high CV rate), thus conferring advantage for both the patient (in terms of sparing energy) and the species (preventing fatherhood) (Corona et al., 2011d, 2014a; Rochira & Guaraldi, 2014). "
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    ABSTRACT: Men with human immunodeficiency virus (HIV) infection are often hypogonadal and develop several HIV-associated non-acquired immunodeficiency syndrome (AIDS) (HANA) conditions that impair overall health status. No studies explored the relationship between health status and serum testosterone (T) in HIV-infected men. This study aims to investigate the association between total serum T and HANA, multimorbidity, and frailty in a large cohort of 1359 HIV-infected men and to explore the relationship between patients' overall health status and serum T. Among biochemical and hormonal measurement performed the main are serum total T, free triiodothyronine (fT3), and luteinizing hormone. Other outcome measurements include anthropometry, assessment of comorbidities and disabilities, overall health status defined as the number of HANA and by the 38-item multimorbidity frailty index, anthropometry, and bone mineral density. The cumulative relative risk of comorbidities is increased in HIV-infected men with hypogonadism (p < 0.001) and hypogonadism is associated with several comorbidities. The prevalence of hypogonadism increases progressively with the increase of the number of comorbidities. Frailty index is inversely related to serum total T (age-adjusted r = 0.298, r(2) = 0.089, p < 0.0001). Serum fT3 levels are significantly lower in hypogonadal than eugonadal men (p = 0.022). This suggests that low serum T could be considered a sensitive marker of frailty and poor health status and that the latter might induce hypogonadism. The more HIV-infected men are frail the more they are hypogonadal. This suggests that hypogonadism might be a naturally occurring condition in unhealthy HIV-infected men and raises concern about the safety of T treatment. In conclusion, low serum T is associated with multimorbidity, HANA, and frailty in HIV-infected men and this association seems to be bidirectional. Given the wide attitude to offer T treatment to HIV-infected men, caution is needed when prescribing T to HIV-infected male patients, especially if the patient is unhealthy or frail. © 2015 American Society of Andrology and European Academy of Andrology.
    Andrology 02/2015; 3(2). DOI:10.1111/andr.310 · 2.30 Impact Factor
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    • "This empirical diagnostic approach is questionable when dealing with milder forms of androgen deficiency, especially the late-onset hypogonadism (LOH), where clinical features suggestive of hypogonadism could be caused by other prevalent disorders. In this regard, the minimum criteria for the identification of LOH emerged from the European Male Aging Study (EMAS): the presence of three sexual symptoms (lessened sexual thoughts, weakened morning erections and erectile dysfunction) in combination with biochemical androgen deficiency (Wu et al., 2010). According to the data from EMAS, it is possible to state almost categorically that if a man does not have sexual symptoms, he does not have LOH (Huhtaniemi & Forti, 2011). "
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    ABSTRACT: Although high rates of serum testosterone deficiency have been reported in men with spinal cord injury (SCI), its determinants and attributes are not yet established. The aim of this study was to recognize, among putative determinants and attributes of androgen deficiency, those significantly associated to low testosterone after adjustment for confounders recognizable in men with chronic SCI. A biochemical androgen deficiency (total testosterone <300 ng/dL) was exhibited by 18 of 51 patients (35.3%). Significant correlates of testosterone levels were as follows: weekly leisure time physical activity (LTPA) explored by the LTPA Questionnaire for people with SCI, body mass index (BMI), homeostatic model assessment of insulin resistance (HOMA-IR), triglycerides and sexual symptoms, explored by the aging males' symptom (AMS) questionnaire. At the multiple linear regression analysis, among putative determinants of low testosterone, only weekly LTPA and BMI exhibited a significant association with testosterone levels, explaining 54.2 and 9.0% of testosterone variability respectively. At the linear regression models, among various putative attributes of androgen deficiency, only lower sexual desire and, at a lesser extent, higher HOMA-IR, exhibited significant associations with lower testosterone levels, after adjustment for BMI, age, comorbidities and weekly LTPA. In conclusion, poor LTPA, high BMI and low sexual desire are independent predictors of low testosterone in men with chronic SCI. This is relevant to clinical practice, as all these features are routinely assessed in rehabilitation settings for SCI. As poor LTPA and high BMI are modifiable life-style related risk factors, prospective studies could clarify whether life-style modification could increase the level of testosterone and improve the low sexual desire, relevant clinical attribute of low testosterone in men with SCI.
    Andrology 06/2014; 2(5). DOI:10.1111/j.2047-2927.2014.00235.x · 2.30 Impact Factor
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    • "These can affect bones, muscles , and lipids, as well as cognitive function Testosterone Deficiency Syndrome (TDS) or Late Onset Hypogonadism which is defined on the basis of clinical symptoms associated with abnormal testosterone levels. The European Male Aging Study [3] (EMAS) studied 3369 men aged 40−79 at 8 "
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    International Journal of Endocrinology 04/2014; 2014:143763. DOI:10.1155/2014/143763 · 1.95 Impact Factor
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