scholarly journals SUN-066 Prenatal Sex Steroid Serum Concentrations in Relation to Sex-Typical Play Behavior at 4 Years of Age

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Swathi Sethuram ◽  
Shanna Swan ◽  
Christina C L Wang ◽  
Emily Barrett ◽  
Ruby Nguyen ◽  
...  
Keyword(s):  
Sex Steroids ◽  
Infant Development ◽  
Parental Attitudes ◽  
Equilibrium Dialysis ◽  
Objective Measure ◽  
Free Testosterone ◽  
Small Sample ◽  
Play Behavior ◽  
Total Testosterone ◽  
Quadratic Term

Abstract INTRODUCTION: Sex differences in play behavior have been seen in rodents, primates and humans with literature showing some associations with maternal sex steroids. The PreSchool Activities Inventory (PSAI) is a validated tool to assess sexually-dimorphic play behavior. We assessed the associations between prenatal maternal estradiol (E2), free testosterone (fT) and total testosterone (T) and children’s PSAI scores at age 4. METHODS: Data were collected in The Infant Development and the Environment Study (TIDES), a US-based multi-center pregnancy cohort. The analysis included 399 pregnant women with complete data on sex steroids, PSAI and covariates. Early pregnancy E2 and T were analyzed by liquid chromatography tandem mass spectrometry and fT by equilibrium dialysis using labeled testosterone. PSAI scores (masculine, feminine and composite) were calculated from questionnaires completed by mothers when child was approximately 4 years old. Covariates included: maternal age and education, child age at questionnaire completion, number of older brothers and sisters, infant race and parental attitudes towards sex-atypical play behavior. After demonstrating nonlinear associations between PSAI scores and sex steroids, we used multivariable sex-stratified quadratic regression to model these relationships. RESULTS: The analysis included 192 boys and 207 girls (mean age: 4.5 years). Sex steroids in serum collected at 6-20 weeks’ gestation (mean: 11 weeks) were similar in mothers of boys and girls. In girls, E2 showed a quadratic relationship with the masculine score (beta (E2) = 0.003, p = 0.002, beta (E22) = -7.3E-7, p <0.001). Masculine scores were lower among girls whose mothers had E2 above the 75th percentile (2160 pg/ml). In boys, we observed a positive linear association of borderline significance (beta (fT) = 9.11, p = 0.06) and a significant negative association for the quadratic term (beta (fT2) = -7.44, p = 0.04). PSAI measures were not associated with E2 in mothers of boys, fT in mothers of girls, or T in either sex. DISCUSSION: This study did not replicate previously reported associations between T and masculine scores in girls. However, we found that, while most maternal E2 levels were not associated with play behavior in either sex, levels above the 75th percentile were associated with reduced masculine scores in girls at age 4. Our data also suggest a somewhat reduced feminine scores in boys born to mothers with fT above the 75th percentile. These results, based on a small sample using a maternal assessment of play behavior, should be examined in a larger sample using an objective measure of play.

Health status is related to testosterone, estrone and body fat: moving to functional hypogonadism in adult men with HIV

2021 ◽  
Vol 184 (1) ◽  
pp. 107-122
Author(s):  
Sara De Vincentis ◽  
Maria Chiara Decaroli ◽  
Flaminia Fanelli ◽  
Chiara Diazzi ◽  
Marco Mezzullo ◽  
...  
Keyword(s):  
Body Composition ◽  
Health Status ◽  
Body Fat ◽  
Sex Steroids ◽  
Highly Active Antiretroviral Therapy ◽  
Free Testosterone ◽  
Total Testosterone ◽  
Male Hypogonadism ◽  
Cross Sectional ◽  
Highly Active

Objective Hypogonadism is common in HIV-infected men. The relationship between health status, sex steroids and body composition is poorly known in HIV. The aim was to investigate the association between health status (comorbidities/frailty), body composition, and gonadal function in young-to-middle-aged HIV-infected men. Design Prospective, cross-sectional, observational study. Methods HIV-infected men aged <50 years and ongoing Highly Active Antiretroviral Therapy were enrolled. Serum total testosterone (TT), estradiol (E2), estrone (E1) were measured by liquid chromatography-tandem mass spectrometry, LH and FSH by immunoassay. Free testosterone (cFT) was calculated by Vermeulen equation. Body composition was assessed by dual-energy X-ray absorptiometry and abdominal CT scan. Multimorbidity (MM) and frailty were defined as ≥3 comorbidities and by a 37-item index, respectively. Results A total of 316 HIV-infected men aged 45.3 ± 5.3 years were enrolled. Body fat parameters were inversely related to cFT and TT, and directly related to E1 and E2/testosterone (TS) ratio. Patients with MM had lower cFT (P < 0.0001) and TT (P = 0.036), and higher E1 (P < 0.0001) and E2/TS ratio (P = 0.002). Frailty was inversely related to cFT (R2 = 0.057, P < 0.0001) and TT (R2 = 0.013, P = 0.043), and directly related to E1 (R2 = 0.171, P < 0.0001), E2 (R2 = 0.041, P = 0.004) and E2/TS ratio (R2 = 0.104, P < 0.0001). Conclusions Lower TT and cFT, higher E1, E2/TS ratio and visceral fat were independently associated to poor health status and frailty, being possible hallmarks of unhealthy conditions in adult HIV-infected men. Overall, MM, frailty and body fat mass are strictly associated to each other and to sex steroids, concurring together to functional male hypogonadism in HIV.

In women, no significant variances of calculated free testosterone (cFT) are observed when a fixed value of albumin (Alb: 4.3 g/dL) is used instead of measured albumin values

2014 ◽  
Vol 20 (3) ◽  
Author(s):  
Dinamarie Garcia-Banigan ◽  
Andre Guay ◽  
Abdul Traish ◽  
Gheorghe Doros ◽  
John Gawoski
Keyword(s):  
Equilibrium Dialysis ◽  
Free Testosterone ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Hormone Binding ◽  
R Software ◽  
Significant Variance ◽  
Clinical Evaluations ◽  
Data Points ◽  
Two Measures

AbstractCalculated free testosterone (cFT) is determined from the values of total testosterone (TT), sex hormone binding globulin (SHBG), and albumin (Alb) using mathematical formulae. We evaluated any potential cFT variance when determined with fixed Alb (4.3 g/dL) compared to measured Alb, and the point at which low SHBG and Alb combinations produced significant cFT variance.We analyzed 2050 data points in 1222 women. cFT values with fixed vs. the actual measured Alb values were evaluated and contrasted. cFT levels were determined theoretically for all possible combinations of TT, SHBG, and Alb.Agreement between the two measures was assessed with Lin’s concordance coefficient. Statistical analyses were performed using R software version 2.12.1.Mean Alb was 4.05±0.30 g/dL. Mean SHBG 73.0±53.3 nmol/L. A fixed Alb of 4.3 g/dL produced no significant variance for most evaluations of cFT. The accuracy decreased with Alb ≤3.5 g/dL in combination with SHBG ≤30 nmol/L and exists in 1.0% of the samples.A fixed Alb of 4.3 g/dL is acceptable for most clinical evaluations. If Alb is ≤3.5 g/dL, along with SHBG ≤30 nmol/L, the variance increases and a free testosterone (FT) measurement by equilibrium dialysis is warranted for better accuracy.

scholarly journals Measurement of Free Testosterone in Serum Using Equilibrium DialysisCoupled With ID-UHPLC-MS/MS: Comparison Between Equilibrium Devices

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A760-A760
Author(s):  
Hui Zhou ◽  
Ashley Ribera ◽  
Amonae Dabbs-Brown ◽  
Uliana Danilenko ◽  
Hubert W Vesper
Keyword(s):  
High Throughput ◽  
High Performance ◽  
Equilibrium Dialysis ◽  
Internal Standard ◽  
Free Testosterone ◽  
Performance Comparison ◽  
Total Testosterone ◽  
Method Performance ◽  
Endocrine Society ◽  
Clinical Patient

Abstract Free testosterone (FT) has been used as a biomarker in clinical patient care and public health research to assess and manage patients with androgenic abnormalities. The latest Endocrine Society clinical practice guideline for testosterone therapy in men with hypogonadism recommends measuring FT for those with borderline and low total testosterone concentrations, or those who have conditions that change SHBG concentrations, such as some metabolic or hormonal diseases, certain medication use, or SHBG genetic polymorphisms. Measuring FT is technically challenging and shows high variability. The CDC clinical standardization program is developing a high throughput method using the gold-standard equilibrium dialysis (ED) procedure with isotope dilution ultra-high-performance liquid chromatography tandem mass spectrometry (ID-UHPLC-MS/MS). A serum sample was dialyzed against a protein-free HEPES buffer (pH 7.4) at 37 °C until equilibrium. After isolating endogenous FT from protein-bound testosterone by ED, isotope-labeled internal standard (13C3-testosterone) was added to the dialysate for quantification. Certified pure primary reference material (National Measurement Institute M914) was used to prepare calibrators, enabling traceable quantitation and ensuring measurement trueness. FT was further isolated from the dialysate matrix using supported liquid extraction and a chromatographic separation from interfering compounds and quantitation by tandem MS. The dialysis step requires maintaining the endogenous free hormone equilibrium so that results in dialysate reflect FT concentrations in the blood without influence from dilution, temperature, or pH. The dialyzer system has a 1:1 sample-to-buffer volume and has been used in reference measurement procedures for free hormone measurements, serving as the standard for method performance comparison. Four commercially available devices designed for high throughput in a multiple well-plate format, requiring respective sample-to-buffer ratios, were evaluated for their recovery, speed, ease of automation by a liquid handling system, repeatability, and robustness. Preliminary results showed that a device with 1:1 sample-to-buffer volume had the most comparable results to those obtained from the standard dialyzer, with the mean bias less than 15%. The device with the highest sample-to-buffer ratio showed bias as high as 50%. These data suggest that controlling sample-to-buffer ratio is a critical step in ED FT method.

An improved ultrafiltration method for determining free testosterone in serum.

1982 ◽  
Vol 28 (11) ◽  
pp. 2286-2291 ◽  
Author(s):  
I Vlahos ◽  
W MacMahon ◽  
D Sgoutas ◽  
W Bowers ◽  
J Thompson ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Equilibrium Dialysis ◽  
Free Testosterone ◽  
Total Testosterone ◽  
Unbound Fraction ◽  
Men And Women ◽  
Healthy Men ◽  
Centrifugal Ultrafiltration ◽  
Dialyzed Serum

Abstract In this method, we use the Amicon MPS-1 centrifugal ultrafiltration device and the YMB membrane in measuring free testosterone in serum. Two independent assays are combined: total testosterone and the ultrafiltrable fraction of added [3H]testosterone. The unbound fraction is determined in 0.15-0.5 mL ultrafiltrates of 0.6 to 1 mL of variably diluted serum that has been equilibrated with [3H]testosterone at 37 degrees C. The assay is rapid (less than 1 h), practicable (requires 0.6 mL of serum), and reproducible (CV 3.2% within assay, 3.9% between assays). Accuracy was evaluated as the fraction of free testosterone in the ultrafiltrate of dialyzed serum vs that in a prior dialysate; they were the same confirming the validity of the free testosterone measurement. Samples from ostensibly healthy men and women and from hirsute and pregnant women gave results that agreed with those obtained by equilibrium dialysis. Total testosterone concentrations for normal and hirsute women showed considerable overlap, but data on free testosterone concentrations in these populations were better resolved.

scholarly journals Validity of free testosterone calculation in pregnant women

2019 ◽  
Vol 8 (6) ◽  
pp. 672-679
Author(s):  
M P Schuijt ◽  
C G J Sweep ◽  
R van der Steen ◽  
A J Olthaar ◽  
N M M L Stikkelbroeck ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Equilibrium Dialysis ◽  
Free Testosterone ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Testosterone Concentration ◽  
Testosterone Levels ◽  
Liquid Chromatography Tandem Mass ◽  
Highly Correlated ◽  
Design And Methods

Objective Increased maternal testosterone concentration during pregnancy may affect the fetus. Therefore it is clinically relevant to have a quick and reliable method to determine free testosterone levels. Current calculators for free testosterone are suspected to perform poorly during pregnancy due to suggested competition between high levels of estradiol and free (bio-active) testosterone for sex hormone-binding globulin (SHBG) binding. Therefore, it is claimed that reliable calculation of free testosterone concentration is not possible. However, recent evidence on SHBG-binding sites questions the estradiol effect on the testosterone-SHBG binding during pregnancy. In this study, we investigated whether the free testosterone concentration can be calculated in pregnant women. Design and methods Free testosterone was measured with a specially developed equilibrium dialysis method combined with liquid chromatography tandem mass spectrometry (LC-MS/MS). Free testosterone was also calculated with the formulas of Vermeulen et al. and Ross et al. Results Total and free testosterone measured in healthy men and women were in good agreement with earlier reports. In pregnant women, total testosterone values were higher than in non-pregnant women, whereas free testosterone values were comparable. Calculated free testosterone levels in pregnant women were highly correlated, but marginally higher, compared to measured free testosterone levels. Conclusions We developed an equilibrium dialysis–LC-MS/MS method for the measurement of free testosterone in the low range of pregnant and non-pregnant women. Although during pregnancy total testosterone is increased, this is not the case for free testosterone. The free testosterone formulas perform well in pregnant women.

scholarly journals Analog-Based Free Testosterone Test Results Linked to Total Testosterone Concentrations, Not Free Testosterone Concentrations

2008 ◽  
Vol 54 (3) ◽  
pp. 512-516 ◽  
Author(s):  
Kristofer S Fritz ◽  
Alastair J S McKean ◽  
Jerald C Nelson ◽  
R Bruce Wilcox
Keyword(s):  
Serum Proteins ◽  
Equilibrium Dialysis ◽  
Serum Testosterone ◽  
Free Testosterone ◽  
Sex Hormone Binding Globulin ◽  
Normal Male ◽  
Total Testosterone ◽  
Test Results ◽  
Experimental Conditions ◽  
Serum Free

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.

scholarly journals Decreased serum levels of sex steroids associated with osteoporosis in a group of Romanian male patients

2016 ◽  
Vol 24 (1) ◽  
pp. 75-82
Author(s):  
Florina Ligia Popa ◽  
Mihaela Stanciu ◽  
Adrian Bighea ◽  
Mihai Berteanu ◽  
Ioan Gheorghe Totoianu ◽  
...  
Keyword(s):  
Sex Steroids ◽  
Free Testosterone ◽  
Serum Levels ◽  
Cross Sectional Study ◽  
Hormone Deficiency ◽  
Control Group ◽  
Total Testosterone ◽  
Mineral Density ◽  
Cross Sectional ◽  
Study Materials

Abstract Introduction. With age, sex hormone deficiency leads to reduced bone mineral density (BMD) in men. The aim of our research is to analyze the role of serum sex steroids in assessing BMD in the men included in this study. Materials and methods. This cross-sectional study included 146 men aged 65-85 years old with osteopenia or osteoporosis (study group) and 121 men with normal BMD (control group). Serum levels of total testosterone (Tt) and free testosterone (Tf) were measured by immunoassay, and estradiol (E2) levels were measured by the immunoenzymatic method. Femoral neck and lumbar spine BMD was examined by dual-energy X-ray absorptiometry. Results. Tf and E2 deficiency was significantly associated with low BMD (p=0.007). No association was found between Tt deficiency and reduced BMD. Tf levels (p<0.001) and E2 levels (p=0.003) were significantly lower in patients with reduced BMD compared to those with normal BMD. Significant more cases with low levels of Tf (p=0.015) and E2 (p<0.001) were found in patients with osteoporosis compared to those with osteopenia. Conclusions. Sex hormones deficiency in men was significantly correlated with the decrease of BMD. Determination of serum Tf and E2 levels is important in assessing the risk of osteoporosis in male subjects.

Prevalence of and Risk Factors for Low Free Testosterone Levels in Japanese Men with Well-controlled Human Immunodeficiency Virus Infection

2020 ◽  
Vol 18 (5) ◽  
pp. 381-386
Author(s):  
Yusuke Yoshino ◽  
Ichiro Koga ◽  
Yoshitaka Wakabayashi ◽  
Takatoshi Kitazawa ◽  
Yasuo Ota
Keyword(s):  
Risk Factors ◽  
Human Immunodeficiency Virus ◽  
Standard Deviation ◽  
Hiv Infection ◽  
Free Testosterone ◽  
Serum Levels ◽  
University Hospital ◽  
Rapid Decline ◽  
Total Testosterone ◽  
Immunodeficiency Virus

Background: The change in the prevalence of hypogonadism with age in men with human immunodeficiency virus (HIV) infection is subject to debate. Objective: To address this issue, we diagnosed hypogonadism based on serum levels of free testosterone (fTST) rather than total testosterone which is thought to be an inaccurate indicator. We also determined the relationship between age and fTST levels and identified risk factors for hypogonadism in men with HIV infection. Method: We retrospectively reviewed fTST levels and associated clinical factors in 71 wellcontrolled HIV-infected men who were treated at Teikyo University Hospital between April 2015 and March 2016 and who had data available on serum fTST levels, measured >6 months after starting antiretroviral therapy. fTST was measured using radioimmunoassay on blood samples collected in the morning. Risk factors for hypogonadism were identified using Welch’s t-test and multiple regression analysis. Results: The men had a mean (± standard deviation) age of 47.4 ± 13.6 years, and mean (± standard deviation) serum fTST level of 13.0 ± 6.1 pg/mL. Fifteen (21.1%) men had hypogonadism based on a fTST <8.5 pg/mL. Serum fTST levels significantly decreased with age (−0.216 pg/mL/year). Older age and low hemoglobin levels were identified as risk factors for hypogonadism. Conclusion: The men in the study experienced a more rapid decline in fTST levels with age than men in the general population (−0.161 pg/mL/year). Serum fTST levels in men with HIV infection should be monitored, especially in older men and those with low hemoglobin levels.

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