A simple method for estimating equilibrium constants for serum testosterone binding resulting in an optimal free testosterone index for use in elderly men

Author(s):  
H. Alec Ross ◽  
Eric J. Meuleman ◽  
Fred C. G. J. Sweep

AbstractAn algorithm was developed to evaluate equilibrium constants for testosterone (Te) and sex hormone-binding globulin (SHBG) or albumin from serum free testosterone (FTe) measurements performed in a panel of 30 healthy elderly men by means of a near-reference method, i.e., symmetric dialysis (affinity constants: SHBG-Te, 1.13×10

2008 ◽  
Vol 159 (4) ◽  
pp. 459-468 ◽  
Author(s):  
B Lapauw ◽  
S Goemaere ◽  
H Zmierczak ◽  
I Van Pottelbergh ◽  
A Mahmoud ◽  
...  

ObjectiveThis study was designed to assess longitudinal changes in serum testosterone levels, explore relationships with aging, genetic-, health-, and lifestyle-related factors, and investigate predictors of changes in healthy elderly men.DesignPopulation-based, longitudinal, 4-year observational study in 221 community-dwelling men aged 71–86 years at baseline.MethodsHormone levels assessed by immunoassay, anthropometry, questionnaires on general health, and genetic polymorphisms. Predictors of changes in testosterone levels explored using linear mixed-effects modeling for longitudinal analyses.ResultsTotal testosterone (TT), free testosterone, and bioavailable testosterone (BioT) levels decreased with aging, decreases in BioT being most marked. No changes in sex hormone-binding globulin (SHBG) or estradiol (E2), while LH and FSH levels increased during follow-up. Subjects who gained weight displayed a greater decline in TT levels, mainly due to decreasing SHBG levels. However, baseline body composition was not predictive of subsequent changes in testosterone levels. Baseline E2 (P=0.023 to 0.004), LH (P=0.046 to 0.005), and FSH (P<0.002) levels were independently positively associated with a faster decline in testosterone fractions, although only FSH remained significant when adjusting for baseline testosterone (P=0.041–0.035). Carriers of a ‘TA’ haplotype of the estrogen receptor α gene (ERα) PvuII and XbaI polymorphisms displayed a slower decline of TT and BioT (P=0.041–0.007).ConclusionsIn elderly men with already low serum testosterone levels, a further decline was observed, independent of baseline age. The identification of FSH levels as a predictor of this decline appears to reflect the testicular mechanisms of aging-related changes in testosterone production, whereas associations with E2 and ERα polymorphisms are suggestive of estrogen-related processes, possibly related to changes in the neuroendocrine regulation of testosterone production.


2008 ◽  
Vol 54 (3) ◽  
pp. 512-516 ◽  
Author(s):  
Kristofer S Fritz ◽  
Alastair J S McKean ◽  
Jerald C Nelson ◽  
R Bruce Wilcox

Abstract Background: Analog-based free testosterone test results, sex hormone binding globulin (SHBG) concentrations, and total testosterone concentrations are somehow related. This study used new experiments to clarify these relationships. Methods: An analog-based free testosterone immunoassay and a total testosterone immunoassay were applied to well-defined fractions of serum testosterone. First, they were applied to the 2 fractions (retentate and dialysate) of normal male serum obtained by equilibrium dialysis. Second, they were applied to covaried concentrations of SHBG and total testosterone. Third, they were applied to decreasing concentrations of SHBG and protein-bound testosterone, offset by increasing concentrations of protein-free testosterone, while total testosterone was held constant. Results: The analog-based free testosterone assay and the total testosterone assay detected and reported serum testosterone test results from serum retentate, whereas neither assay detected the free testosterone in serum dialysate. Test results reported by the analog-based free testosterone assay followed varied concentrations of SHBG and total testosterone. When total testosterone was held constant, however, analog-based free testosterone test results did not follow varied concentrations of serum proteins or of free testosterone. Conclusion: An analog-based free testosterone immunoassay reported free testosterone test results that were related to total testosterone concentrations under varied experimental conditions. This alleged free testosterone assay did not detect serum free testosterone (the test results it reported were nonspecific) and should not be used for this purpose.


1997 ◽  
pp. 670-674 ◽  
Author(s):  
Y Sahin ◽  
F Kelestimur

OBJECTIVE: To determine the frequency of late-onset adrenal hyperplasia (LOCAH) due to 21-hydroxylase (21-OH) and 11 beta-hydroxylase (11 beta-OH) deficiency in women with clinical and biochemical features of polycystic ovary syndrome (PCOS). DESIGN: Eighty-three consecutively selected women with PCOS and eighteen normal women were included in the study. METHODS: Ultrasound, clinical and hormonal parameters were used to define PCOS. Basal FSH, LH, testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG) and cortisol levels were measured. Serum 17-hydroxyprogesterone (17-OHP) and 11-deoxycortisol (11-DOC) levels were also measured before, 30 and 60 min after a single bolus injection of 0.25 mg ACTH (1-24) at 0900 h during the mid-follicular phase of the cycle. ACTH-stimulated 17-OHP levels > 30 nmol/l were considered as the criteria of 21-OH deficiency. The diagnosis 11 beta-OH deficiency was made if the adrenal 11-DOC response to ACTH stimulation exceeded threefold the 95th percentile of controls. RESULTS: Basal serum testosterone, free testosterone, androstenedione, DHEA-S, cortisol and 11-DOC levels were significantly higher in PCOS than in control subjects. ACTH-stimulated 17-OHP (P < 0.05) and 11-DOC (P < 0.0005) levels were found to be significantly higher in patients with PCOS than in controls. Seven (8.4%) patients had an 11-DOC response to ACTH higher than threefold the 95th percentile of controls, while no patients showed evidence of 21-OH deficiency. CONCLUSIONS: We have found that 8.4% of the women with clinical and biochemical features of PCOS could be presumed to have 11 beta-OH deficiency. No patients among the women with PCOS showed evidence of 21-OH deficiency. 11 beta-OH deficiency is unexpectedly more common than 21-OH deficiency in women with PCOS.


Author(s):  
Joško Osredkar ◽  
Ivan Vrhovec ◽  
Niko Jesenovec ◽  
Andreja Kocijančič ◽  
Janez Preželj

A sensitive, specific and accurate direct radioimmunoassay of testosterone in human saliva is described. A single salivary testosterone result is shown to be of greater diagnostic use in hirsutism than any of the currently used serum androgen assays. Thus, of 50 hirsute patients, salivary testosterone (Sa-T) was elevated in 34 patients, sex hormone-binding globulin (SHBG) was decreased in 30 women, serum testosterone (S-T) elevated in 13, dehydroepiandrosterone sulphate (DHEA-S) was elevated in 14, and androstenedione in three of the investigated group.


2004 ◽  
pp. 539-546 ◽  
Author(s):  
EJ Duschek ◽  
LJ Gooren ◽  
C Netelenbos

OBJECTIVE: To explore effects on serum lipids, pituitary-gonadal axis, prostate and bone turnover of the administration of the mixed oestrogen agonist/antagonist raloxifene in healthy elderly men. PARTICIPANTS: Thirty healthy men aged 60-70 years randomly received raloxifene 120 mg/day (n=15) or placebo (n=15) for 3 months. MEASUREMENTS: In this double-blind, placebo-controlled study, serum gonadotrophins, sex hormones, prostate specific antigen (PSA), a marker of bone turnover, urinary hydroxyproline (OHPro) and cholesterol were measured at baseline and after 3 months. RESULTS: Raloxifene significantly increased serum concentrations of LH and FSH (by 29% and 21%), total testosterone (20%), free testosterone (16%) and bioavailable testosterone (not bound to sex hormone-binding globulin (SHBG; 20%). In parallel with testosterone, 17 beta-oestradiol also increased by 21%. SHBG increased by 7%. Total cholesterol (TChol) decreased significantly, from 5.7 to 5.5 mmol/l (P=0.03). Low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) showed a trend to decrease. Overall, there was no change in urinary OHPro/creatinine ratio as a marker for bone resorption. However, the raloxifene-induced increases in both serum testosterone and 17 beta-oestradiol were significantly related to a lower OHPro/creatinine ratio. Total PSA increased by 17% without significant changes in free PSA or free/total PSA ratio. Participants reported no side effects and raloxifene was well tolerated. CONCLUSION: In healthy elderly man, raloxifene 120 mg/day for 3 months increased LH, FSH and sex steroid hormones. Potentially beneficial effects were the small but significant decrease in TChol and the trend towards a decrease in LDL-c. Negative effects were the trend towards a decrease in HDL-c and the significant increase in serum PSA. A decrease in markers of bone resorption during raloxifene treatment was found only in men with relatively high increases in serum testosterone and 17 beta-oestradiol. Overall, there were no clear beneficial effects of administration of raloxifene to ageing men in this preliminary investigation.


2010 ◽  
Vol 162 (4) ◽  
pp. 737-745 ◽  
Author(s):  
Liesbeth Vandenput ◽  
Dan Mellström ◽  
Magnus K Karlsson ◽  
Eric Orwoll ◽  
Fernand Labrie ◽  
...  

ObjectiveAssociation studies in men have shown that androgens are inversely related to fat measures, while the relation between sex steroids and lean mass remains unclear. We, therefore, investigated the associations between serum sex steroid levels and body composition in elderly men with a main focus on lean mass measures.Design and methodsA cross-sectional survey of a population-based cohort of 3014 elderly men, aged 69–80 years (Osteoporotic Fractures in Men study, Sweden). Serum levels of testosterone and estradiol (E2) were measured by mass spectrometry, sex hormone-binding globulin (SHBG) levels were measured by IRMA, and measures of body composition were obtained by dual-energy X-ray absorptiometry.ResultsTotal as well as free serum testosterone associated independently inversely (P<0.001), while total as well as free serum E2associated independently directly (P<0.001) with total body fat mass and trunk fat mass. Serum SHBG associated independently inversely with central fat distribution. Serum E2and free E2but not serum testosterone or free testosterone levels associated positively with lean mass (P<0.01). Elderly men within the lowest quartile of free E2had 0.5 kg less lean mass in the legs than subjects within the highest quartile, while the subjects in the different quartiles of free testosterone did not differ in lean mass.ConclusionsSerum E2, but not serum testosterone, is directly associated with lean mass in this large study of elderly Swedish men. In addition, serum SHBG is associated with central fat distribution and we confirmed that serum testosterone is inversely associated with fat mass.


Author(s):  
C Wang ◽  
K Wakelin ◽  
J White ◽  
P J Wood

In the biochemical evaluation of hirsutism, 50% or less of patients have an elevated total serum testosterone. Recent work has suggested that measuring salivary testosterone or a derived serum ‘free testosterone index’ may be of use in the evaluation of hyperandrogenism. We have measured serum total, derived serum free indices and salivary concentrations of testosterone and 5α-dihydro-testosterone in an unselected group of hirsute patients in order to assess their value in the routine evaluation of hirsutism. The assays were performed using a novel oxidation procedure to overcome the need for chromatographic separation. The ‘free testosterone index’ gave the best discrimination. Salivary androgen concentrations were comparatively poor and cannot be recommended for routine use.


1982 ◽  
Vol 37 (3) ◽  
pp. 288-293 ◽  
Author(s):  
P. D. Tsitouras ◽  
C. E. Martin ◽  
S. M. Harman

2006 ◽  
Vol 154 (1) ◽  
pp. 125-129 ◽  
Author(s):  
Malene Boas ◽  
Kirsten A Boisen ◽  
Helena E Virtanen ◽  
Marko Kaleva ◽  
Anne-Maarit Suomi ◽  
...  

Objective: Infant boys show a brief activation of their hypothalamic–pituitary–gonadal axis shortly after birth, the physiological significance of which is poorly understood. The objective of the study was to investigate the correlation between endogenous testosterone levels and penile size and growth. Design: Prospective, longitudinal population-based study taking place at two large primary obstetric centres at the University Hospitals of Copenhagen, Denmark, and Turku, Finland. Methods: Infant boys, 728 Danish and 1234 Finnish, underwent clinical examinations at 0, 3, 18 and 36 months in Denmark and at 0, 3 and 18 months in Finland with blood samples taken at 3 months (n = 630). Penile length and growth were registered and reproductive hormones (testosterone, sex hormone binding globulin, oestradiol) were analysed. Results: Penile length increased from birth (3.49±0.4 cm) to 3 years of age (4.53±0.51 cm) with the highest growth velocity from birth to 3 months (1.0 mm/month). Penile length and growth were significantly, positively correlated to serum testosterone (r = 0.31 and 0.076, P = 0.006 and 0.001 respectively) and to free testosterone index (r = 0.385 and 0.094, P = 0.0001 and 0.0001 respectively). Conclusions: We found that endogenous testosterone was significantly associated with penile size and growth rate in infant boys. Thus, the postnatal surge in reproductive hormones appears to be important for genital growth. Our data may serve as an updated reference for normal penile length in Caucasian boys up to 3 years of age.


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