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      Characteristics of Secondary, Primary, and Compensated Hypogonadism in Aging Men: Evidence from the European Male Ageing Study

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          Abstract

          The diagnosis of late-onset hypogonadism (LOH) in older men with age-related declines in testosterone (T) is currently not well characterized. Our objective was to investigate whether different forms of hypogonadism can be distinguished among aging men. The study was a cross-sectional survey on 3369 community-dwelling men aged 40-79 yr in eight European centers. Four groups of subjects were defined: eugonadal (normal T and normal LH), secondary (low T and low/normal LH), primary (low T and elevated LH), and compensated (normal T and elevated LH) hypogonadism. Relationships between the defined gonadal status with potential risk factors and clinical symptoms were investigated by multilevel regression models. Among the men, 11.8, 2.0, and 9.5% were classified into the secondary, primary, and compensated hypogonadism categories, respectively. Older men were more likely to have primary [relative risk ratio (RRR) = 3.04; P < 0.001] and compensated (RRR = 2.41; P < 0.001) hypogonadism. Body mass index of 30 kg/m(2) or higher was associated with secondary hypogonadism (RRR = 8.74; P < 0.001). Comorbidity was associated with both secondary and primary hypogonadism. Sexual symptoms were more prevalent in secondary and primary hypogonadism, whereas physical symptoms were more likely in compensated hypogonadism. Symptomatic elderly men considered to have LOH can be differentiated on the basis of endocrine and clinical features and predisposing risk factors. Secondary hypogonadism is associated with obesity and primary hypogonadism predominately with age. Compensated hypogonadism can be considered a distinct clinical state associated with aging. Classification of LOH into different categories by combining LH with T may improve the diagnosis and management of LOH.

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          Most cited references30

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          The clinical significance of subclinical thyroid dysfunction.

          Subclinical thyroid disease (SCTD) is defined as serum free T(4) and free T(3) levels within their respective reference ranges in the presence of abnormal serum TSH levels. SCTD is being diagnosed more frequently in clinical practice in young and middle-aged people as well as in the elderly. However, the clinical significance of subclinical thyroid dysfunction is much debated. Subclinical hyper- and hypothyroidism can have repercussions on the cardiovascular system and bone, as well as on other organs and systems. However, the treatment and management of SCTD and population screening are controversial despite the potential risk of progression to overt disease, and there is no consensus on the thyroid hormone and thyrotropin cutoff values at which treatment should be contemplated. Opinions differ regarding tissue effects, symptoms, signs, and cardiovascular risk. Here, we critically review the data on the prevalence and progression of SCTD, its tissue effects, and its prognostic implications. We also examine the mechanisms underlying tissue alterations in SCTD and the effects of replacement therapy on progression and tissue parameters. Lastly, we address the issue of the need to treat slight thyroid hormone deficiency or excess in relation to the patient's age.
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            Prevalence of symptomatic androgen deficiency in men.

            Despite recognition that androgen deficiency in men should be defined according to biochemical and clinical criteria, most prevalence estimates are based on low testosterone levels alone. The objective of this study was to examine the association between symptoms of androgen deficiency and low total and calculated free testosterone levels and estimate the prevalence of symptomatic androgen deficiency in men. This study was a population-based, observational survey. A total of 1,475 Black, Hispanic, and white men, between the ages of 30-79 yr, with complete data on testosterone, SHBG, and symptoms of androgen deficiency, and who are not taking medications that impact sex steroid levels were randomly selected from the Boston Area Community Health Survey. Outcomes were measured as symptomatic androgen deficiency, defined as low total (<300 ng/dl) and free (<5 ng/dl) testosterone plus presence of low libido, erectile dysfunction, osteoporosis or fracture, or two or more of following symptoms: sleep disturbance, depressed mood, lethargy, or diminished physical performance. Mean age of the sample was 47.3 +/- 12.5 yr. Approximately 24% of subjects had total testosterone less than 300 ng/dl, and 11% of subjects had free testosterone less than 5 ng/dl. Prevalence of symptoms were as follows: low libido (12%), erectile dysfunction (16%), osteoporosis/fracture (1%), and two or more of the nonspecific symptoms (20%). Low testosterone levels were associated with symptoms, but many men with low testosterone levels were asymptomatic (e.g. in men 50+ yr, 47.6%). Crude prevalence of symptomatic androgen deficiency was 5.6% (95% confidence interval: 3.6%, 8.6%), and was not significantly related to race and ethnic group. Prevalence was low in men less than 70 yr (3.1-7.0%) and increased markedly with age to 18.4% among 70 yr olds. Projection of these estimates to the year 2025 suggests that there will be as many as 6.5 million American men ages 30-79 yr with symptomatic androgen deficiency, an increase of 38% from 2000 population estimates. Prevalence of symptomatic androgen deficiency in men 30 and 79 yr of age is 5.6% and increases substantially with age. The aging of the U.S. male population will cause a large increase in the burden of symptomatic androgen deficiency. Future work should address the clinical significance of low testosterone levels in asymptomatic men.
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              Association of specific symptoms and metabolic risks with serum testosterone in older men.

              Although attention and concern about health disorders in aging men have been growing, the structure of psychological and somatic complaints of actual patients, not population-based cohorts, has not been elucidated in relation to sex hormone patterns and metabolism. The objective of the study was investigation of factors influencing complaint structures in aging male patients. This was a cross-sectional cohort study. The study was conducted in an andrological outpatient department. Subjects included 434 consecutive male patients aged 50-86 yr. The following hypotheses were measured: 1) psychosomatic complaints and metabolic factors in aging male patients are related to sex hormone levels in a symptom-specific manner, and 2) patients form subcohorts. A clear-cut threshold for late-onset hypogonadism was not found; rather, prevalence of psychosomatic symptoms and metabolic risk factors accumulated with decreasing androgen levels. For example, androgen-induced prevalence of loss of libido or vigor increased below testosterone concentrations of 15 nmol/liter (P < 0.001), whereas depression and diabetes mellitus type 2 (also in nonobese men) were significantly more present in men with testosterone concentrations below 10 nmol/liter (P < 0.001). Erectile dysfunction was identified as a composite pathology of metabolic risk factors, smoking, and depressivity, whereas only testosterone concentrations below 8 nmol/liter contributed to that symptom (P = 0.003). Cluster analysis revealed aging men to present within three independent groups characterized by psychosomatic complaints, metabolic disorders, and sexual health problems. These subgroups of patients exhibit distinct features in terms of androgen levels, age, and body mass index. There is no evidence that a uniform structure of testosterone concentrations and complaints exists within the cohort of elderly male patients. Rather, in aging male patients, psychosomatic complaints and metabolic risk relate to testosterone in a symptom-specific manner.
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                Author and article information

                Journal
                The Journal of Clinical Endocrinology & Metabolism
                The Endocrine Society
                0021-972X
                1945-7197
                April 01 2010
                April 01 2010
                : 95
                : 4
                : 1810-1818
                Affiliations
                [1 ]Arthritis Research Campaign Epidemiology Unit (A.T., T.W.O., D.M.L., A.J.S., J.D.F.), The University of Manchester, Manchester M15 6PB, United Kingdom
                [2 ]Andrology Unit (G.F.), Department of Clinical Physiopathology, University of Florence, I-50019 Florence, Italy
                [3 ]Department of Obstetrics, Gynaecology, and Andrology (G.B.), Albert Szent-György Medical University, H-6725 Szeged, Hungary
                [4 ]Department of Andrology and Endocrinology (S.B., D.V.), Katholieke Universiteit Leuven B-3000 Leuven, Belgium
                [5 ]Department of Medicine (F.F.C.), Santiago de Compostela University, Complejo Hospitalario Universitario de Santiago, Centro de Investigación Biomedical en Red de Fisiopatología Obesidad y Nutrición (CB06/03), Instituto Salud Carlos III, 15076 Santiago de Compostela, Spain
                [6 ]Scanian Andrology Centre (A.G.), Department of Urology, Malmö University Hospital, University of Lund, SE-205 06 Malmö, Sweden
                [7 ]Department of Endocrinology (T.S.H.), Royal Free and University College Medical School, Royal Free Hospital, London NW3 2QG, United Kingdom
                [8 ]Department of Andrology and Reproductive Endocrinology (K.K.), Medical University of Łódź, 90-419 Łódź, Poland
                [9 ]Laboratory of Molecular Endocrinology and Oncology (F.L.), Laval University, Quebec City, Quebec, Canada G1V 0A6
                [10 ]Division of Developmental Medicine (M.E.J.L.), Human Nutrition Section, University of Glasgow, Glasgow G12 8QQ, Scotland, United Kingdom
                [11 ]Clinical Gerontology (N.P.), The University of Manchester, Hope Hospital, Salford M6 8HD, United Kingdom
                [12 ]Andrology Unit (M.P.), United Laboratories of Tartu University Clinics, 50406 Tartu, Estonia
                [13 ]Department of Reproductive Biology (I.T.H.), Imperial College London, Hammersmith Campus, London W12 0HS, United Kingdom
                [14 ]The University of Manchester (F.C.W.W.), Manchester Academic Health Science Centre, Department of Medicine, Manchester Royal Infirmary, Manchester M13 9WL, United Kingdom
                Article
                10.1210/jc.2009-1796
                20173018
                929f0df8-bcc0-47ff-82da-b406046f241b
                © 2010
                History

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