Variability in total testosterone levels in ageing men with symptoms of androgen deficiency (original) (raw)
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The Journal of Clinical Endocrinology & Metabolism, 2004
The diagnosis of male hypogonadism requires the demonstration of a low serum testosterone (T) level. We examined serum T levels in pedigreed samples taken from 62 eugonadal and 60 hypogonadal males by four commonly used automated immunoassay instruments (Roche Elecsys, Bayer Centaur, Ortho Vitros ECi and DPC Immulite 2000) and two manual immunoassay methods (DPC-RIA, a coated tube commercial kit, and HUMC-RIA, a research laboratory assay) and compared results with measurements performed by liquid chromatography-tandem mass spectrometry (LC-MSMS). Deming's regression analyses comparing each of the test results with LC-MSMS showed slopes that were between 0.881 and 1.217. The interclass correlation coefficients were between 0.92 and 0.97 for all methods. Compared with the serum T concentrations measured by LC-MSMS, the DPC Immulite results were biased toward lower values (mean difference, ؊90 ؎ 9 ng/dl) whereas the Bayer Centaur data were biased toward higher values
European Journal of Endocrinology, 2012
Background: The limitations of serum testosterone and estradiol (E 2 ) measurements using nonextraction platform immunoassays (IAs) are widely recognized. Switching to more specific mass spectrometry (MS)-based methods has been advocated, but directly comparative data on the two methods are scarce. Methods: We compared serum testosterone and E 2 measurements in a large sample of middle-aged/elderly men using a common platform IA and a gas chromatography (GC)-MS method, in order to assess their limitations and advantages, and to diagnose male hypogonadism. Of subjects from the European Male Aging Study (nZ3174; age 40-79 years), peripheral serum testosterone and E 2 were analyzed using established commercial platform IAs (Roche Diagnostics E170) and in-house GC-MS methods. Results: Over a broad concentration range, serum testosterone concentration measured by IA and MS showed high correlation (RZ0.93, P!0.001), which was less robust in the hypogonadal range (!11 nmol/l; RZ0.72, P!0.001). The IA/MS correlation was weaker in E 2 measurements (RZ0.32, P!0.001, at E 2 !40.8 pmol/l, and RZ0.74, P!0.001, at E 2 O40.8 pmol/l). Using MS as the comparator method, IA ascertained low testosterone compatible with hypogonadism (!11 nmol/l), with 75% sensitivity and 96.3% specificity. The same parameters with IA for the detection of low E 2 (!40.7 pmol/l) were 13.3 and 99.3%, and for high E 2 (O120 pmol/l) 88.4 and 88.6%. Conclusion: A validated platform IA is sufficient to detect subnormal testosterone concentrations in the diagnosis of male hypogonadism. The IA used for E 2 measurements showed poor correlation with MS and may only be suitable for the detection of high E 2 in men.
The Journal of Urology, 2010
The diagnosis of testosterone deficiency syndrome is based on clinical manifestations and documentation of low testosterone. Which biochemical tests to use and the importance of morning sampling are still controversial. Biological variation (including interindividual and intraindividual biological variation) must be considered when interpreting individual results as it determines the usefulness of reference intervals and the change (reference change value) necessary for a significant difference between results. Materials and Methods: A total of 87 healthy men (50 to 70ϩ years old) provided blood in the morning of the first day, and 4 weeks later in the morning and afternoon. Samples were frozen (Ϫ70C) and analyzed in the same run for serum testosterone, sex hormone-binding globulin and albumin, and bioavailable testosterone and free testosterone were calculated. Results: Serum testosterone was lower in the afternoon by 1.5 nmol/l (43 ng/dl, p Ͻ0.05), with larger changes observed with higher morning values. However, this diurnal effect was dwarfed by the normal biological variation observed for repeat morning samples (serum testosterone Ϯ 4 nmol/l [115 ng/dl]). Between day intra-individual biological variation for morning serum testosterone was 18.7% while within day intra-individual biological variation was 12.9%. A change of 52% (reference change value) is necessary between serial morning results to confirm a significant difference. The biological variation parameters of calculated bioavailable testosterone and calculated free testosterone confer no advantage over total testosterone. Conclusions: Marked individuality of serum testosterone is evident even in healthy men. Because intraindividual biological variation is less than interindividual biological variation, reference intervals are marginally useful. The homeostatic set point of a patient could decrease by half and still be within the reference interval. Prospective establishment of an individual's baseline over repeated measurements or symptoms regardless of serum testosterone concentration should be used to guide clinical decisions.
Longitudinal Effects of Aging on Serum Total and Free Testosterone Levels in Healthy Men
The Journal of Clinical Endocrinology and Metabolism, 2001
Many studies have shown cross-sectional (and two small studies, longitudinal) declines in total and/or free testosterone (T) levels, with age, in men. The extent to which decline in T is the result of the aging process per se, as opposed to chronic illness, medication use, and other age-related factors, remains controversial. The frequency with which aging leads to T levels consistent with hypogonadism has also not been defined. These issues bear on the potential use of T replacement in aging men, because aging and hypogonadism have, in common, reduced bone and lean body mass and muscle strength and increased total and abdominal fat. We measured T and sex hormone-binding globulin (SHBG), by RIA, in stored samples from 890 men in the Baltimore Longitudinal Study on Aging. Using a mixed-effects model, we found independent effects of age and date of sampling to reduce T levels. After compensating for date effects, which investigation suggested was artifactual, we observed significant, independent, ageinvariant, longitudinal effects of age on both T and free T index (free T index ϭ T/SHBG), with an average change of Ϫ0.124 nmol/L⅐yr and Ϫ0.0049 nmol T/nmol SHBG⅐yr. T, but not free T index, also decreased with increasing body mass index. Use of Ϫblocking drugs was associated with higher T and higher free T index levels. Using total T criteria, incidence of hypogonadal T levels increased to about 20% of men over 60, 30% over 70 and 50% over 80 yr of age, and even greater percentages when free T index criteria were employed. Our observations of health factor independent, age-related longitudinal decreases in T and free T, resulting in a high frequency of hypogonadal values, suggest that further investigation of T replacement in aged men, perhaps targeted to those with the lowest serum T concentrations, are justified.
Age-Associated Discrepancy between Measured and Calculated Bioavailable Testosterone in Men
Clinical Chemistry, 2007
Background: Bioavailable testosterone (BT) concentration is considered the best marker for evaluating testicular function in men. The decrease of BT in older men is more pronounced than the decrease in total testosterone because of the parallel increase in sex hormone-binding globulin (SHBG) concentrations. Measurement of BT is therefore crucial for the diagnosis of hypoandrogenism in the aging male population.
Serum androgen levels in men: impact of health status and age
Urology, 2003
To investigate the impact of health status on androgen levels in men and to assess the age-related changes in androgen levels. Sera were obtained from 526 men (age 20 to 89 years) participating in a health screening project and 35 men selected according to the SENIEUR protocol, which excludes those with underlying disease. The health screening project participants were divided into two groups: healthy men (n = 133; group 1) and the remainder (n = 393; group 2). The total testosterone and sex hormone-binding globulin levels were quantified, and the amount of free testosterone (cfT) was calculated. The lowest annual declines in androgen level were observed in group 3 (testosterone 0.2%; cfT 0.4%), followed by group 1 (testosterone 0.4%; cfT 0.8%) and group 2 (testosterone 0.8%; cfT 0.9%). Body mass index and levels of cholesterol, triglycerides, and glucose correlated negatively (P <0.01) with testosterone and cfT. Decade-adjusted reference values (mean +/- 2 standard deviations) f...
The Laboratory Diagnosis of Testosterone Deficiency
Urology, 2014
Evaluation and treatment of hypogonadal men has become an important part of urological practice. Fatigue, loss of libido and erectile dysfunction are commonly reported, but non-specific symptoms of low testosterone (T) and laboratory verification of low testosterone is an important part of evaluation in addition to a detailed history and physical exam. Significant intra-individual fluctuations in serum T levels, biological variation of T action on end organs, the wide range of T levels in human serum samples and technical limitations of currently available assays have led to poor reliability of T measurements in the clinical laboratory setting. There is no universally accepted threshold of T concentration that distinguishes eugonadal from hypogonadal men, thus laboratory results have to be interpreted in the appropriate clinical setting. This review focuses on clinical, biological and technological challenges that affect serum T measurements to educate clinicians regarding technological advances and limitations of currently available laboratory methods to diagnose hypogonadism. A collaborative effort led by the American Urological Association (AUA) between practicing clinicians, patient advocacy groups, government regulatory agencies, industry and professional societies is underway to provide optimized assay platforms and evidence based normal assay ranges to guide clinical decision making. Until such standardization is commonplace in clinical laboratories, the decision to treat should be based on the presence of signs and symptoms in addition to serum T 2
European Journal of …, 2012
Background: The limitations of serum testosterone and estradiol (E 2) measurements using nonextraction platform immunoassays (IAs) are widely recognized. Switching to more specific mass spectrometry (MS)-based methods has been advocated, but directly comparative data on the two methods are scarce. Methods: We compared serum testosterone and E 2 measurements in a large sample of middle-aged/elderly men using a common platform IA and a gas chromatography (GC)-MS method, in order to assess their limitations and advantages, and to diagnose male hypogonadism. Of subjects from the European Male Aging Study (nZ3174; age 40-79 years), peripheral serum testosterone and E 2 were analyzed using established commercial platform IAs (Roche Diagnostics E170) and in-house GC-MS methods. Results: Over a broad concentration range, serum testosterone concentration measured by IA and MS showed high correlation (RZ0.93, P!0.001), which was less robust in the hypogonadal range (!11 nmol/l; RZ0.72, P!0.001). The IA/MS correlation was weaker in E 2 measurements (RZ0.32, P!0.001, at E 2 !40.8 pmol/l, and RZ0.74, P!0.001, at E 2 O40.8 pmol/l). Using MS as the comparator method, IA ascertained low testosterone compatible with hypogonadism (!11 nmol/l), with 75% sensitivity and 96.3% specificity. The same parameters with IA for the detection of low E 2 (!40.7 pmol/l) were 13.3 and 99.3%, and for high E 2 (O120 pmol/l) 88.4 and 88.6%. Conclusion: A validated platform IA is sufficient to detect subnormal testosterone concentrations in the diagnosis of male hypogonadism. The IA used for E 2 measurements showed poor correlation with MS and may only be suitable for the detection of high E 2 in men.
Age and Ageing, 2005
Background: relative androgen deficiency in ageing males is assumed to have adverse health effects. This study assessed the effect of 12 months' standard dose, oral testosterone, on symptoms attributed to testosterone deficiency in older men with plasma testosterone levels in the low-normal range for young men. Methods: testosterone undecanoate (TU, 80 mg bid) or placebo was administered for one year to 76 healthy men, 60 years or older, with a free testosterone index (FTI) of 0.3-0.5 and significant symptoms on a questionnaire designed to evaluate androgen deficiency (ADAM). The ADAM was completed at baseline, 6 and 12 months. Hormone and safety data were collected at baseline, 1, 3, 6 and 12 months. Results: after 12 months, plasma total testosterone was unchanged in both groups and sex hormone binding globulin decreased in the testosterone group (P = 0.01). FTI and calculated bioavailable testosterone (cBT) were greater in the testosterone group as compared with the placebo group (P = 0.021 and 0.025, respectively). There was no significant difference in total symptom score between testosterone and placebo groups after 12 months of oral TU. However, there were trends toward improvements in sadness/grumpiness (P = 0.063), reduced erection strength (P = 0.059) and decreased work performance symptoms (P = 0.077), particularly in men with baseline cBT levels below 3.1 nmol/l. Conclusions: this study concludes that 80 mg bid oral TU does not improve overall ADAM questionnaire scores in older men with low-normal gonadal status. Oral TU may preserve mood and erectile function, as assessed by this questionnaire, particularly in men with the lowest testosterone levels.