Reproductive Endocrinology Reference Intervals for Transgender Women on Stable Hormone Therapy

2020 ◽  
Author(s):  
Dina N Greene ◽  
Robert L Schmidt ◽  
Gabrielle Winston McPherson ◽  
Jessica Rongitsch ◽  
Katherine L Imborek ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Hormone Therapy ◽  
Free Testosterone ◽  
Reference Intervals ◽  
Transgender Women ◽  
Reproductive Hormones ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Significant Variable ◽  
Reproductive Endocrinology

Abstract Background Transgender women and nonbinary people seeking feminizing therapy are often prescribed estrogen as a gender-affirming hormone, which will alter their reproductive hormone axis. Testosterone, estradiol, and other reproductive hormones are commonly evaluated to assess therapy, but reference intervals specific to transgender women have not been established. The objective of this study was to derive reference intervals for commonly measured analytes related to reproductive endocrinology in a cohort of healthy gender nonconforming individuals on stable feminizing hormone therapy. Methods Healthy transgender individuals who had been prescribed estrogen (n = 93) for at least a year were recruited from internal medicine and primary care clinics that specialize in transgender medical care. Total testosterone and estradiol were measured using immunoassay and mass spectrometry; LH, FSH, sex hormone binding globulin, prolactin, progesterone, anti-mullerian hormone (AMH), and dehydroepiandrosterone sulfate (DHEAS) were measured using immunoassay; free testosterone was calculated. Reference intervals (central 95%) were calculated according to Clinical Laboratory Standards Institute guidelines. Results The distribution of results for transgender women was different than what would be expected from cisgender men or women across all measurements. Use of spironolactone was associated with changes in the result distribution of AMH, FSH, LH, and progesterone. Compared to liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS), immunoassay was sufficient for the majority of estradiol and total testosterone measurements; free testosterone added little clinical value beyond total testosterone. Conclusion Reference intervals specific to transgender women should be applied when evaluating reproductive endocrine analytes. Spironolactone is a significant variable for result interpretation of some tests.

scholarly journals Reference Intervals of Total Testosterone in Adult Filipino Men

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Myrna Buenaluz‐Sedurante ◽  
Mark Isaiah K. Co ◽  
Daryl Jade T. Dagang ◽  
Racquel G. Bruno ◽  
Annie Jane N. Sarmiento ◽  
...  
Keyword(s):  
Young Adult ◽  
Reference Range ◽  
Clinical History ◽  
Free Testosterone ◽  
Reference Intervals ◽  
The Philippines ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Reference Ranges ◽  
Healthy Young Adult

Background. The reference range of total testosterone needs to be established locally as ethnic differences in adiposity, insulin sensitivity, and sex hormone-binding globulin (SHBG) levels may affect total testosterone levels. The aim of this study is to establish the reference intervals of total testosterone from healthy, young adult Filipino males. Methods. The study included 110 healthy, Filipino male volunteers aged 21–40, studying or working at the University of the Philippines Manila. Clinical history, height, weight, body mass index (BMI), and blood pressure (BP) were obtained, and blood for total testosterone, SHBG, albumin, insulin, fasting blood sugar (FBS), and total cholesterol was collected. Free testosterone was calculated using Vermeulen’s formula. The 2.5th to 97.5th percentiles of subjects for total testosterone were used as the normative range for Filipino men. Results. The reference range of total testosterone is 7.33–53.01 nmol/L. Conclusion. The present study derived reference ranges of total testosterone using data from apparently healthy, young adult men to support clinical services.

scholarly journals MANAGEMENT OF ENDOCRINE DISEASE Hyperandrogenic states in women: pitfalls in laboratory diagnosis

2018 ◽  
Vol 178 (4) ◽  
pp. R141-R154 ◽  
Author(s):  
Michel Pugeat ◽  
Ingrid Plotton ◽  
Aude Brac de la Perrière ◽  
Gérald Raverot ◽  
Henri Déchaud ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Limit Of Detection ◽  
High Specificity ◽  
Free Testosterone ◽  
Laboratory Diagnosis ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Adrenal Androgen ◽  
Androgen Excess ◽  
Specificity And Sensitivity

Measuring total testosterone level is the first-line approach in assessing androgen excess in women. The main pitfalls in measuring testosterone relate to its low concentration and to the structural similarity between circulating androgens and testosterone, requiring accurate techniques with high specificity and sensitivity. These goals can be achieved by immunoassay using a specific anti-testosterone monoclonal antibody, ideally after an extraction step. Liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS) will be commonly used for measuring testosterone, providing optimal accuracy with a low limit of detection. Yet, the pitfalls of these two techniques are well identified and must be recognized and systematically addressed. In general, laboratories using direct testosterone immunoassay and mass spectrometry need to operate within a quality framework and be actively engaged in external quality control processes and standardization, so as to ensure appropriate interpretation irrespective of the particular laboratory. Circulating testosterone is strongly bound to sex-hormone-binding globulin (SHBG), and SHBG levels are typically low in overweight hyperandrogenic patients. Thus, low SHBG may decrease circulating testosterone to normal values, which will mask androgen excess status. One way to avoid this pitfall, awaiting direct free testosterone assays that are yet to be developed, is to measure SHBG and calculate free testosterone. A few other pitfalls will be discussed in this review, including those of adrenal androgen exploration, with the aim of helping clinicians to better handle laboratory investigation of androgen excess disorders in women.

Reproductive Endocrinology Reference Intervals for Transgender Men on Stable Hormone Therapy

2020 ◽  
Author(s):  
Dina N Greene ◽  
Robert L Schmidt ◽  
Gabrielle Winston-McPherson ◽  
Jessica Rongitsch ◽  
Katherine L Imborek ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Laboratory Tests ◽  
Clinical Laboratory ◽  
Free Testosterone ◽  
Dehydroepiandrosterone Sulfate ◽  
Reference Intervals ◽  
Total Testosterone ◽  
Primary Care Clinics ◽  
Endocrine Hormones ◽  
Transgender Men

Abstract Background Gender-affirming therapy with testosterone is commonly prescribed to aid in the masculinization of transgender men. Sex-hormone concentrations are routinely measured, but interpretation of results can be difficult due to the lack of published reference intervals. Methods Healthy transgender individuals who had been prescribed testosterone (n = 82) for at least a year were recruited from internal medicine and primary care clinics that specialize in transgender medical care. Total testosterone and estradiol were measured using immunoassay and mass spectrometry; LH, FSH, SHBG, prolactin, progesterone, anti-Müllerian hormone (AMH), and dehydroepiandrosterone sulfate (DHEAS) were measured using immunoassay; free testosterone was calculated. Reference intervals (central 95%) were calculated according to Clinical Laboratory Standards Institute guidelines. Results When evaluating general endocrine laboratory tests in people using masculinizing hormones, reference intervals for cisgender men can be applied for total and free testosterone and SHBG and reference intervals for cisgender women can be applied for prolactin. Reference intervals for estradiol, LH, FSH, AMH, and DHEAS differ from those used for cisgender men and cisgender women, and therefore should be interpreted using intervals specific to the transmasculine population. For testosterone and estradiol, results from immunoassays were clinically equivalent to mass spectrometry. Conclusion Masculinizing hormones will alter the concentrations of commonly evaluated endocrine hormones. Providers and laboratories should use appropriate reference intervals to interpret the results of these tests.

scholarly journals Hypogonadism and liver fibrosis in HIV-infected patients

2021 ◽  
Author(s):  
E. Quiros-Roldan ◽  
T. Porcelli ◽  
L. C. Pezzaioli ◽  
M. Degli Antoni ◽  
S. Paghera ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Univariate Analysis ◽  
Free Testosterone ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Cross Sectional ◽  
Pituitary Dysfunction ◽  
Consequent Reduction ◽  
Secondary Hypogonadism ◽  
The Relationship

Abstract Purpose Hypogonadism is frequent in HIV-infected men and might impact on metabolic and sexual health. Low testosterone results from either primary testicular damage, secondary hypothalamic-pituitary dysfunction, or from liver-derived sex-hormone-binding-globulin (SHBG) elevation, with consequent reduction of free testosterone. The relationship between liver fibrosis and hypogonadism in HIV-infected men is unknown. Aim of our study was to determine the prevalence and type of hypogonadism in a cohort of HIV-infected men and its relationship with liver fibrosis. Methods We performed a cross-sectional retrospective study including 107 HIV-infected men (median age 54 years) with hypogonadal symptoms. Based on total testosterone (TT), calculated free testosterone, and luteinizing hormone, five categories were identified: eugonadism, primary, secondary, normogonadotropic and compensated hypogonadism. Estimates of liver fibrosis were performed by aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) scores. Results Hypogonadism was found in 32/107 patients (30.8%), with normogonadotropic (10/107, 9.3%) and compensated (17/107, 15.8%) being the most frequent forms. Patients with secondary/normogonadotropic hypogonadism had higher body mass index (BMI) (p < 0001). Patients with compensated hypogonadism had longer HIV infection duration (p = 0.031), higher APRI (p = 0.035) and FIB-4 scores (p = 0.008), and higher HCV co-infection. Univariate analysis showed a direct significant correlation between APRI and TT (p = 0.006) and SHBG (p = 0.002), and between FIB-4 and SHBG (p = 0.045). Multivariate analysis showed that SHBG was independently associated with both liver fibrosis scores. Conclusion Overt and compensated hypogonadism are frequently observed among HIV-infected men. Whereas obesity is related to secondary hypogonadism, high SHBG levels, related to liver fibrosis degree and HCV co-infection, are responsible for compensated forms.

scholarly journals Hyperandrogenism by Liquid Chromatography Tandem Mass Spectrometry in PCOS: Focus on Testosterone and Androstenedione

2020 ◽  
Vol 10 (1) ◽  
pp. 119
Author(s):  
Giorgia Grassi ◽  
Elisa Polledri ◽  
Silvia Fustinoni ◽  
Iacopo Chiodini ◽  
Ferruccio Ceriotti ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Polycystic Ovary ◽  
Free Testosterone ◽  
Reference Intervals ◽  
Model Assessment ◽  
Homeostatic Model Assessment ◽  
Liquid Chromatography Tandem Mass ◽  
And Control ◽  
The Impact

The identification of hyperandrogenism in polycystic ovary syndrome (PCOS) is concerning because of the poor accuracy of the androgen immunoassays (IA) and controversies regarding which androgens should be measured. The aim of our study was to evaluate the impact of the assessment of testosterone (T) and androstenedione (A) by liquid chromatography in tandem with mass spectrometry (LC/MS-MS), in the diagnosis of PCOS. We evaluated 131 patients referred for suspected PCOS. Fourteen patients in total were excluded, some because of other diagnosis (n = 7) or incomplete diagnostic workup (n = 7). We measured T and A both by IA and LC-MS/MS in the 117 subjects included. We calculated free T (fT) by the Vermeulen formula and recorded clinical and metabolic data. 73 healthy females served as controls to derive immunoassays (IA) and LC-MS/MS reference intervals for T, fT and A. PCOS was confirmed in 90 subjects by IA and in 93 (+3.3%) by LC-MS/MS. The prevalence of biochemical hyperandrogenism in PCOS by LC-MS/MS increased from 81.7% to 89.2% if A was also considered. The most frequently elevated androgens were fT (73.1%) and A (64.5%) and they had similar levels of accuracy in differentiating PCOS and controls (0.34 ng/dL, Sn 91% Sp 89%; 1.16 ng/mL, Sn 91% Sp 88%, respectively). Free testosterone correlated with body mass index (BMI), homeostatic model assessment (HOMA)-index, glycated hemoglobin (HbA1c), and sex-binding globulin (SHBG). The results confirm that LC-MS/MS is slightly more sensitive than IA in the diagnosis of PCOS with LC-MS/MS detecting higher levels of fT and A. Moreover, assessment of fT and A by LC-MS/MS had a similar level of accuracy in discriminating between PCOs and control subjects. Lastly, fT by LC-MS/MS correlates with adverse metabolic parameters.

scholarly journals In men older than 70 years, total testosterone remains stable while free testosterone declines with age. The Health in Men Study

2007 ◽  
Vol 156 (5) ◽  
pp. 585-594 ◽  
Author(s):  
Bu B Yeap ◽  
Osvaldo P Almeida ◽  
Zoë Hyde ◽  
Paul E Norman ◽  
S A Paul Chubb ◽  
...  
Keyword(s):  
Free Testosterone ◽  
Older Men ◽  
Early Morning ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Limited Data ◽  
Cross Sectional ◽  
Testosterone Concentration ◽  
Age Related ◽  
Clinical Consequences

Objective: An age-related decline in serum total and free testosterone concentration may contribute to ill health in men, but limited data are available for men > 70 years of age. We sought to determine the distribution and associations of reduced testosterone concentrations in older men. Design: The Health in Men Study is a community-representative prospective cohort investigation of 4263 men aged ≥ 70 years. Cross-sectional hormone data from 3645 men were analysed. Methods: Early morning sera were assayed for total testosterone, sex hormone binding globulin (SHBG) and LH. Free testosterone was calculated using the Vermeulen method. Results: Mean (± s.d.) serum total testosterone was 15.4 ± 5.6 nmol/l (444 ± 162 ng/dl), SHBG 42.4 ± 16.7 nmol/l and free testosterone 278 ± 96 pmol/l (8.01 ± 2.78 ng/dl). Total testosterone correlated with SHBG (Spearman’s r = 0.6, P < 0.0001). LH and SHBG increased with age (r = 0.2, P < 0.0001 for both). Instead of declining, total testosterone increased marginally (r = 0.04, P = 0.007) whilst free testosterone declined with age (r = −0.1, P < 0.0001). Free testosterone was inversely correlated with LH (r = −0.1, P < 0.0001). In multivariate analyses, increasing age, body mass index (BMI) and LH were associated with lower free testosterone. Conclusions: In men aged 70–89 years, modulation of androgen action may occur via an age-related increase in SHBG and reduction in free testosterone without a decline in total testosterone concentration. Increasing age, BMI and LH are independently associated with lower free testosterone. Further investigation would be required to assess the clinical consequences of low serum free testosterone, particularly in older men in whom total testosterone may be preserved.

scholarly journals The importance of SHBG and calculated free testosterone for the diagnosis of symptomatic hypogonadism in HIV-infected men: a single-centre real-life experience

Infection ◽  
2020 ◽  
Author(s):  
Letizia Chiara Pezzaioli ◽  
Eugenia Quiros-Roldan ◽  
Simone Paghera ◽  
Teresa Porcelli ◽  
Filippo Maffezzoni ◽  
...  
Keyword(s):  
Life Experience ◽  
Real Life ◽  
Free Testosterone ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Sexual Symptoms ◽  
Low Testosterone ◽  
Gonadal Status ◽  
Spearman’S Correlation

Abstract Purpose The prevalence of low testosterone and symptoms of hypogonadism in HIV-infected men is still debated. We aimed to estimate the prevalence and type of hypogonadism in HIV-infected males complaining about sexual symptoms, and to evaluate the role of calculated free testosterone (cFT) vs total testosterone (TT) for diagnosis. Furthermore, we evaluated relationship between sex hormone-binding globulin (SHBG), gonadal status and clinical and virologic parameters. Methods We retrospectively evaluated 169 HIV-infected men with sexual symptoms, with TT available. Among them, we selected 94 patients with TT, SHBG, cFT, and luteinizing hormone (LH) available, and classified hypogonadism into overt (low TT and/or low cFT) and compensated (high LH, normal TT and cFT). Comparison was performed by non-parametric Kruskal–Wallis test and Spearman’s correlation was calculated to verify the possible associations. Results Overt and compensated hypogonadism were found in 20.2% and 13.8% of patients, respectively. With reliance on TT alone, only 10.6% of patients would have met diagnosis. SHBG values were elevated in one third of patients, and higher in men with compensated hypogonadism. Significant positive correlation was found between SHBG and HIV infection duration, TT and LH. Conclusion Only a complete hormonal profile can properly diagnose and classify hypogonadism in HIV-infected men complaining about sexual symptoms. TT alone reliance may lead to half of diagnoses missing, while lack of gonadotropin prevents the identification of compensated hypogonadism. This largely comes from high SHBG, which seems to play a central role in the pathogenesis of hypogonadism in this population.

scholarly journals The analog free testosterone assay: are the results in men clinically useful?

1998 ◽  
Vol 44 (10) ◽  
pp. 2178-2182 ◽  
Author(s):  
Stephen J Winters ◽  
David E Kelley ◽  
Bret Goodpaster
Keyword(s):  
Free Testosterone ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Serum Concentrations ◽  
Testosterone Concentration ◽  
Low Testosterone ◽  
Relationship Of ◽  
The Relationship ◽  
Constant Percentage

Abstract Men with low testosterone concentrations are usually hypogonadal. However, because variations in the testosterone transport protein, sex hormone-binding globulin (SHBG), directly influence the total testosterone concentration, confirmation of a low testosterone with a measurement of free testosterone or “bioavailable” testosterone (BAT) is recommended. In the present study, we examined the relationship of SHBG with free testosterone (Coat-A-Count assay, Diagnostic Products) and with BAT in men (n = 29) and women (n = 28) who participated in a study of the metabolic determinants of body composition. As expected, total testosterone was strongly positively correlated with SHBG among men (r = 0.68; P &lt;0.01). Although the BAT was independent of SHBG in men (r = 0.02), SHBG was an important predictor of free testosterone (r = 0. 62; P &lt;0.01). In contrast, in women serum concentrations of total testosterone (r = −0.26; P = 0.17), free testosterone (r = −0.30; P = 0.17), and BAT (r = −0.46; P = 0.013) all tended to be lower with increasing SHBG. Free testosterone was nearly perfectly positively correlated with total testosterone (r = 0.97) in men, among whom free testosterone represented a relatively constant percentage of the total testosterone (0.5–0.65%), and the percentage of free testosterone was unrelated to SHBG. Thus the Coat-A-Count free testosterone concentration in men, like the total testosterone concentration, is determined in part by plasma SHBG. Accordingly, androgen deficiency may be misclassified with this assay in men with low SHBG. Moreover, the previous findings of reduced free testosterone concentrations with hypertension or hyperinsulinemia or as a risk factor for developing type 2 diabetes, conditions in which SHBG is reduced, may have been methodology-related.

scholarly journals Exercise training improves free testosterone in lifelong sedentary aging men

2017 ◽  
Vol 6 (5) ◽  
pp. 306-310 ◽  
Author(s):  
Lawrence D Hayes ◽  
Peter Herbert ◽  
Nicholas F Sculthorpe ◽  
Fergal M Grace
Keyword(s):  
Interval Training ◽  
Free Testosterone ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
High Intensity Interval Training ◽  
Baseline Phase ◽  
Aging Men ◽  
High Intensity Interval ◽  
The Impact ◽  
Older Males

As the impact of high-intensity interval training (HIIT) on systemic hormones in aging men is unstudied to date, we investigated whether total testosterone (TT), sex hormone-binding globulin (SHBG), free testosterone (free-T) and cortisol (all in serum) were altered following HIIT in a cohort of 22 lifelong sedentary (62 ± 2 years) older men. As HIIT requires preconditioning exercise in sedentary cohorts, participants were tested at three phases, each separated by six-week training; baseline (phase A), following conditioning exercise (phase B) and post-HIIT (phase C). Each measurement phase used identical methods. TT was significantly increased following HIIT (~17%; P < 0.001) with most increase occurring during preconditioning (~10%; P = 0.007). Free-T was unaffected by conditioning exercise (P = 0.102) but was significantly higher following HIIT compared to baseline (~4.5%; P = 0.023). Cortisol remained unchanged from A to C (P = 0.138). The present data indicate a combination of preconditioning, and HIIT increases TT and SHBG in sedentary older males, with the HIIT stimulus accounting for a small but statistically significant increase in free-T. Further study is required to determine the biological importance of small improvements in free-T in aging men.

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