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The impact of utilizing both symptoms as well as biochemically confirmed androgen deficiency in diagnosis of hypogonadism among type 2 diabetic men is relatively less studied. Furthermore, various determinants of hypogonadism in these men especially the role of insulin resistance and hypogonadism were studied. This is a cross sectional study of 353 T2DM men aged 20–70 years of age. Hypogonadism was defined by taking both symptoms as well as calculated testosterone levels. Symptoms were defined using androgen deficiency in ageing male (ADAM) criteria. Various metabolic and clinical parameters were assessed and evaluated with regards to presence or absence of hypogonadism. Among 353 patients, 60 had both symptoms as well as biochemical evidence of hypogonadism. Assessment of calculated free testosterone but not total testosterone identified all such patients. Body mass index, HbA1c, fasting triglyceride level and HOMA IR inversely correlated with calculated free testosterone. We found that insulin resistance (HOMA IR) was independently associated with hypogonadism (odds ratio=1.108). Assessment of both symptoms of hypogonadism and calculated free testosterone represents a better way for correct identification of hypogonadal diabetic men. Insulin resistance has a strong association with hypogonadism independent of obesity and complication status of diabetes. • Hypogonadism is very common in T2DM men. • 1003 subjects were screened for the study. • A total of 353 patients were taken for final assessment. • The prevalence of hypogonadism as per total testosterone was 13%. • The prevalence of hypogonadism as per calculated free testosterone was 17%. • Insulin Resistance was found to be independently associated with hypogonadism. [ABSTRACT FROM AUTHOR]

Objective: Sociodemographic, lifestyle, and medical variables influence total testosterone (T) and sex hormone-binding globulin (SHBG) concentrations. The relationship between these factors and "free" T remains unclear. We examined 21 sociodemographic, lifestyle, and medical predictors influencing calculated free T (cFT) in community-dwelling men across ages., Design: This is a cross-sectional analysis in 20 631 participants in the Androgens in Men Study., Methods: Individual participant data (IPD) were provided by 9 cohorts. Total T was determined using mass spectrometry, SHBG using immunoassays, and cFT using the Vermeulen formula. Associations were analyzed using 2-stage random effects IPD meta-analyses., Results: Cohort median ages ranged from 40 to 76 years and median cFT concentrations from 174.3 to 422.8 pmol/L. In men aged 17-99 years, there was a linear inverse association of cFT with age (-57.2 pmol/L [95% confidence interval, -69.4, -44.9] per 1 SD increase in age). Calculated free T increased with increasing baseline body mass index (BMI) among men with BMI < 23.6 kg/m2, but decreased among men with BMI > 23.6 kg/m2 (-24.7 pmol/L [-29.1, -20.3] per 1 SD increase in the 25.4-29.6 kg/m2 BMI range). Calculated free T was lower in younger men, who were married or in a de facto relationship (-18.4 pmol/L [-27.6, -9.3]) and in men who formerly smoked (-5.7 pmol/L [-8.9, -2.6]), were in poor general health (-14.0 pmol/L [-20.1, -7.8]), and had diabetes (-19.6 pmol/L [-23.0, -16.3]), cardiovascular disease (-5.8 pmol/L [-8.3, -3.2]), or cancer (-19.2 pmol/L [-24.4, -14.1])., Conclusions: Calculated free T was most prominently associated with age and BMI. The linear, inverse association with age, nonlinear association with BMI, and presence of diabetes, cancer, and sociodemographic factors should be considered when interpreting cFT values., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology.)

This study aimed to propose an operational definition of late-onset hypogonadism (LOH) that incorporates both clinical symptoms and serum testosterone measurements to evaluate the prevalence of LOH in aging males in China. A population-based sample of 6296 men aged 40 years–79 years old was enrolled from six representative provinces in China. Serum total testosterone (TT), sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were measured and free testosterone (cFT) was calculated. The Aging Males' Symptoms (AMS) scale was used to evaluate the LOH symptoms. Finally, 5078 men were included in this analysis. The TT levels did not decrease with age (P = 0.59), and had no relationship with AMS symptoms (P = 0.87 for AMS total score, P = 0.74 for ≥ 3 sexual symptoms). The cFT levels decreased significantly with age (P < 0.01) and showed a negative association with the presence of ≥ 3 sexual symptoms (P = 0.03). The overall estimated prevalence of LOH was 7.8% (395/5078) if a cFT level

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. [ABSTRACT FROM AUTHOR]

Objective: Serum testosterone concentrations are affected by factors unrelated to hypothalamo‐pituitary‐testicular axis pathology. We evaluated the impact of sociodemographic, lifestyle and medical factors, on serum testosterone and sex hormone–binding globulin (SHBG) in men aged 40‐69 years. Design: Cross‐sectional analysis of 208,677 community‐dwelling men from the UK Biobank. Measurements: We analysed associations of different factors with serum testosterone and SHBG (immunoassays) and calculated free testosterone (cFT), using smoothed centile plots, linear mixed models and effect size estimates. Results: Median (interquartile range) for serum testosterone was 11.6 (9.4‐14.1) nmol/L, SHBG 36.9 (27.9‐48.1) nmol/L and cFT 213 (178‐255) pmol/L. Age and BMI were inversely associated with testosterone and cFT, while SHBG was associated with age and inversely with BMI (all P <.001). Living with a partner, (South) Asian ethnicity, never or previous smoker and some medical conditions were associated with lower testosterone. Poultry or fish eater, and higher physical activity were associated with higher testosterone (all P <.001). Testosterone was lowered by ~0.5 nmol/L across ages, ~1.5 nmol/L for BMI 30 vs 25 kg/m2, ~2 nmol/L for (South) Asian ethnicity, living with partner, college/university qualifications, low red meat eater, insufficient physical activity and 0.3‐1.0 nmol/L with cardiovascular disease or diabetes. Different combinations of these factors varied serum testosterone by ~4 nmol/L, SHBG by ~30 nmol/L and cFT by ~60 pmol/L. Conclusions: The identified modifiable risk factors support lifestyle‐based interventions in men with low testosterone concentrations. Considering sociodemographic, lifestyle and medical factors facilitates more personalized interpretation of testosterone testing results with respect to existing reference ranges. [ABSTRACT FROM AUTHOR]

• Free testosterone may complement the measurement of serum T, but this is controversial and is not universally accepted. • Equilibrium dialysis methods are too complex for routine clinical use. • Equations for calculating free testosterone are inaccurate because they were founded on faulty models of T binding to SHBG. • The free androgen index is not reliable for use in men or women because of inaccuracy when the SHBG concentration is low. • Better equations are needed to calculate free testosterone, based on detailed knowledge of testosterone binding to SHBG. Testosterone (T) is strongly bound to sex hormone binding globulin and measurement of free T may be more appropriate than measuring total serum T, according to the free hormone theory. This view remains controversial and it has its detractors who claim that little extra benefit is gained than simply measuring total T, but it is endorsed by recent clinical practice guidelines for investigation of androgen disorders in both men and women. Free T measurement is very challenging. The gold standard equilibrium dialysis methods are too complex for use in routine clinical laboratories, assays are not harmonized and consequently there are no common reference intervals to aid result interpretation. The algorithms derived for calculating free T are inaccurate because they were founded on faulty models of testosterone binding to SHBG, however they can still give clinically useful results. To negate the effects of differences in binding protein constants, some equations for free T have been derived from accurate measurement of testosterone in large population studies, however a criticism is that the equations may not hold true in different patient populations. The free androgen index is not recommended for use in men because of inaccuracy at extremes of SHBG concentration, and in women it can also give inaccurate results when SHBG concentrations are low. If the free hormone hypothesis is to be believed, then calculated free testosterone may offer the best way forward but better equations are needed to improve accuracy and these should be derived from detailed knowledge of testosterone binding to SHBG. There is still much work to be done to improve harmonization of T and SHBG assays between laboratories because these can have a profound effect on the equations used to calculate free testosterone. [ABSTRACT FROM AUTHOR]

Nowadays, obesity and metabolic syndrome are considered as symptoms of male hypogonadism, which underlines the need for hormonal screening in these patients. However, remain unsolved some questions of laboratory diagnostics testosterone deficiency. In particular, there are contradictions in the choice of research method of free testosterone. The objectives of our work was to conduct a comparative evaluation of methods for studying androgen status of young and middle-aged men with obesity and metabolic syndrome, and determining the relationship between hormonal indicators and metabolic profile, blood pressure, anthropometric characteristics of obesity. The study included 51 patients with symptoms of obesity and metabolic syndrome, aged from 20 to 50 years, the control group consisted of 19 equal-age men with normal body weight. A significant decrease in total testosterone in men with metabolic syndrome was revealed. The dependence of the concentration of total testosterone with age and content sex-steroid-binding globulin was found. The role of free testosterone in the formation of the metabolic syndrome was shown. It was found that free saliva testosterone significantly correlated with the level of calculated serum free testosterone. In patients with obesity and metabolic syndrome there are a statistically significant increase in saliva testosterone indicators compared to calculated serum free testosterone, while at normal body weight differences are absent. It is concluded that saliva testosterone is more sensitive and appropriate marker for obesity and metabolic syndrome.

Summary: Objective/Context: The free androgen index (FAI) is known to give erroneous results in men, but it is still a commonly used test for the investigation of hyperandrogenism in women. This study aimed to compare the results of the FAI with the gold standard equilibrium dialysis method for free testosterone in women. Design/Patients: Free serum testosterone T (ED‐T) and total serum T (T) were measured by equilibrium dialysis and LC‐MS/MS in patients with polycystic ovarian syndrome (n = 130), normal female controls (n = 53) and normal males (n = 120). Calculated free T (cFT) and free androgen index (FAI) were also measured in these patients. In addition, cFT was retrospectively calculated in 4223 female patients with a normal T (<1.6 nmol/L) routinely investigated for hyperandrogenism. Results: The cFT showed good agreement with measured ED‐T, and the ratio cFT/ED‐T was stable across all SHBG concentrations. In contrast, the FAI/ED‐T ratio and the FAI/cFT ratio increased when the concentration of SHBG fell below 30 nmol/L. Conclusions: The FAI is not a reliable indicator of free T when the SHBG concentration is low and would give misleading information in a large number of women being investigated for hyperandrogenism. [ABSTRACT FROM AUTHOR]

The article presents an updated reference interval (RI) dataset for calculated testosterone indices in a pediatric cohort from birth to l8 years of age. Topics include the Canadian Laboratory Initiative in Pediatric Reference (CALIPER) intervals, the study's focus on the free testosterone (FT), bioavailable testosterone (BAT) and the free androgen indices (FAI) not covered in CALIPER studies, and the importance of detailed RIs in assessing androgen disorders in children and adolescents.

Background: Calculated 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. Materials: 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. Methods: Agreement between the two measures was assessed with Lin's concordance coefficient. Statistical analyses were performed using R software version 2.12.1. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Objectives: There are technical limitations for the currently available methods of measuring serum total and free testosterone in females. The study objectives were to evaluate the usefulness of serum total testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), and calculated free testosterone (CFT) in the assessment of androgen status in women investigated for suspected hyperandrogenism. Methods: This is a case control study that was conducted during the period from 1st May 2011 to 31st October 2011 on 122 patients aged (18-45 years) whom were referred to the Clinical Biochemistry Laboratory from the Endocrinology and Gynecology Clinics, Royal Hospital, Oman. Women with no clinical feature or laboratory data indicative of hormonal dysfunction and with midluteal progesterone >30 nmol/L were selected as controls (group 1; n=18). The patients were divided into subgroups based on the clinical/laboratory diagnosis of polycystic ovary syndrome (PCOS [group 2; n=19), hirsutism (group 3; n=18), menstrual disturbances (irregularities) or infertility (group 4; n=49), as well as combination of PCOS or hirsutism and menstrual disturbances or infertility (group 5; n=18). Serum total testosterone and SHBG were measured, FAI was calculated as percentage ratio of total testosterone to SHBG values, and CFT was calculated according to Vermeulen equation. Results: There was a statistically significant difference in the mean levels of testosterone, FAI and CFT in each patient group compared with the control group. For diagnosing hyperandrogenism, each indicator was selected at the recommended cut-off: testosterone >3.0 nmol/L, SHBG <30 nmol/L, FAI >5%, and CFT >32 pmol/L. In group 2, 89.5% and 94.7% of the patients had increased FAI and CFT, respectively; compared with 36.4% for increased testosterone. In group 3, 88.9% and 88.9% of the patients had similarly increased FAI and CFT, respectively; compared with 66.7% for testosterone. In group 4, patients had 63.3% and 73.5% elevated FAI and CFT, respectively; compared with 53.1% for testosterone, while in group 5, patients had 83.3% and 88.9% elevated FAI and CFT, respectively, compared with 61.1% for testosterone. Conclusion: The diagnosis of hyperandrogenism was most obvious when using CFT or FAI than testosterone alone. It is thus recommended to include these calculated parameters (CFT and/ or FAI) in the routine investigation and assessment of women with disorders related to clinical or biochemical hyperandrogenism. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the relationship among aFT, cFT, and total testosterone (TT) and the best method in diagnosing subnormal levels of TT. Methods: A total of 213 men were analyzed. Fasting blood samples were drawn for the determination of the lipid profile as well as of plasmatic glucose and serum levels of albumin, TT, aFT, and sex hormone-binding globulin (SHBG). The values of cFT were determined by Vermeulen's formula. Results: No correlation between aFT and cFT was observed ( r = 0.062; P = 0.368), except after controlling for confounders ( r = 0.188; P = 0.007). Only 44.8% of hypogonadal men (TT ≤ 300 ng/dL) were classified by aFT, whereas 72.4% of hypogonadal men were classified by both TT and cFT. Sensitivity, specificity, positive and negative predictive values, and positive likelihood ratio were greater in cFT when compared with aFT. Conclusions: Our results suggest that cFT is more accurate in diagnosing subnormal levels of TT. Furthermore, we do not recommend using aFT due to its lack of accuracy. Further studies should be performed in order to evaluate the correlation between aFT and cFT with clinical signs and symptoms of androgen deficiency. [ABSTRACT FROM AUTHOR]

Abstract: Background: Total and free testosterone decrease gradually in men with advancing age but it is not completely known how lower levels of testosterone are related with various cardiovascular risk factors. We studied the levels of total testosterone, calculated free testosterone and sex hormone-binding globulin (SHBG), and their relations with cardiovascular risk factors in young Finnish men. Methods: The study cohort consisted of 24–45-year-old men participating the Cardiovascular Risk in Young Finns Study in the follow-up surveys performed in 2001 (N =1024) and 2007 (N =991). Levels of total testosterone, SHBG, lipids, glucose, insulin, blood pressure and anthropometric factors were measured and free testosterone was calculated. Results: In multivariable analyses adjusted for age, body mass index and life-style factors (alcohol consumption, smoking and physical activity), total and calculated free testosterone were inversely correlated with triglycerides (both P <0.0001), insulin (P =0.0004 and P =0.01), systolic blood pressure (P =0.007 and P =0.01), and directly with high-density lipoprotein (HDL) cholesterol (P <0.0001 and P =0.003). SHBG was inversely correlated with triglycerides and insulin, and directly with HDL-cholesterol (all P <0.001). In longitudinal analyses, lower levels of testosterone and SHBG were associated with higher levels of triglycerides and insulin six years later (all P <0.01). Baseline level of SHBG was directly associated with HDL-cholesterol (P <0.0001). Conclusion: In young and middle-aged men, higher levels of testosterone and SHBG are associated with favourable cardiovascular risk profile characterized by lower levels of triglycerides, insulin and systolic blood pressure, and higher levels of HDL-cholesterol. [Copyright &y& Elsevier]

Introduction. Hypogonadism is common in human immunodeficiency virus (HIV)-infected men; the high concentration of sex hormone binding globulin (SHBG) in this population, induces a “false increase” in total testosterone (TT) values. Aims. To validate the determination of TT and measured free testosterone (FT [radioimmunoassay {RIA} ] ) for hypogonadism diagnosis in an HIV-infected population using calculated free testosterone (CFT) as reference method; and also to determine the prevalence and identify the risks factors of hypogonadism. Methods. Cross-sectional, observational study. Ninety HIV-infected males (42 ± 8.2 years), not HCV coinfected, antiretroviral therapy (ART)- naive (14 patients), on current ART with enhanced protease inhibitor (PI) (39 patients), or patients on PI- naive ART (NN) (37 patients). Main Outcome Measures. CFT was calculated by determining TT, SHBG, and albumin (Vermeulen's formula); hypogonadism was defined as CFT <0.22 nmol/L (reference range for young healthy males in our laboratory); sensitivity of TT and FT (RIA) for hypogonadism diagnosis was calculated. Results. Twelve patients (13.3%, 95% confidence interval [CI] 7.8–21.9) by CFT presented hypogonadism. TT and FT (RIA) presented a sensitivity of less than 30% in the diagnosis of hypogonadism. Logistic regression multivariate analysis confirmed an independent association between hypogonadism, the patient's age per decade, odds ratio (OR) 6.9 (CI 1.9–24.8; P = 0.003), and longer duration of HIV infection per decade, OR 13.1 (CI 1.3–130.6; P = 0.02). Hypogonadism was associated with erectile dysfunction. Conclusions. TT and FT (RIA) are not useful in the differential diagnosis of hypogonadism in HIV-infected males. There is a significant prevalence of hypogonadism in HIV-infected males, with the patient's age and duration of the disease being the only identifiable risk factors. Moreno-Pérez O, Escoín C, Serna-Candel C, Portilla J, Boix V, Alfayate R, González-Sánchez V, Mauri M, Sánchez-Payá J, and Picó A. The determination of total testosterone and free testosterone (RIA) are not applicable to the evaluation of gonadal function in HIV infected males. J Sex Med 2010;7:2873–2883. [ABSTRACT FROM AUTHOR]

Introduction. The most widely used method for measuring free testosterone (FT) is by analog immunoassay (aFT); however, this assay has been criticized as unreliable based on laboratory studies in small groups of men. Calculated FT (cFT), derived from total testosterone (TT) and sex-hormone binding globulin (SHBG) values has been recommended in its place. There are limited data comparing aFT and cFT in clinical populations. Aim. The purpose of this study was to compare aFT with cFT in a population of ambulatory men in a clinical setting. Methods. Medical records were reviewed for 100 randomly selected men in a urology practice, yielding 140 test results complete for TT, aFT, and SHBG. Calculated FT was determined via an online calculator. Comparisons were made with Pearson rank coefficients. Main Outcome Measures. Pearson rank correlation between aFT and cFT. Results. Mean patient age was 52.3 ± 14.3 years (range 24–80). Mean TT was 443.0 ± 208.3 ng/dL (range 110–1276). Mean aFT was 1.22 ± 0.54 ng/dL (range 0.24–3.8) and mean cFT 9.4 ± 4.5 ng/dL (range 1.8–27.8). Mean SHBG was 34.2 ± 19.5 nmol/L (range 9–127). A strong correlation was observed for aFT and cFT ( r = 0.88, P < 0.0001), particularly at low concentrations. Significant correlations were also noted between aFT and TT ( r = 0.73, P < 0.0001), and between cFT and TT ( r = 0.82, P < 0.0001). Numerical values for aFT were approximately one-eighth of the values obtained for cFT. Neither aFT nor cFT correlated with SHBG. Conclusions. A strong correlation was observed between aFT and cFT in this clinical population of ambulatory men. Different sets of reference values must be applied for each of these tests. Moreno SA, Shyam A, and Morgentaler A. Comparison of free testosterone results by analog radioimmunoassay and calculated free testosterone in an ambulatory clinical population. J Sex Med 2010;7:1948–1953. [ABSTRACT FROM AUTHOR]

BACKGROUND: Erectile dysfunction (ED) has a profound impact on the quality of life of many men. Many risk factors are associated with ED, such as aging, sex hormone levels, hypertension, cardiovascular diseases, and diabetes mellitus. Arsenic exposure could damage peripheral vessels and increase the risk of cardiovascular disease. However, the relationship between arsenic exposure and ED has seldom been evaluated. OBJECTIVES: In this study we aimed to investigate whether exposure to arsenic enhances the risk of ED. METHODS: We recruited 177 males ≥ 50 years of age through health examinations conducted in three hospitals in Taiwan. We used a questionnaire (International Index of Erectile Function-5) to measure the level of erectile function. Sex hormones, including total testosterone and sex hormone- binding globulin, were determined by radioimmunoassay. We used another standardized questionnaire to collect background and behavioral information (e.g., cigarette smoking; alcohol, tea, or coffee drinking; and physical activity). RESULTS: The prevalence of ED was greater in the arsenic-endemic area (83.3%) than in the non- arsenic-endemic area (66.7%). Subjects with arsenic exposure > 50 ppb had a significantly higher risk of developing ED than those with exposure ≤ 50 ppb, after adjusting for age, cigarette smoking, diabetes mellitus, hypertension, and cardiovascular disease [odds ratio (OR) = 3.4]. Results also showed that the risk of developing severe ED was drastically enhanced by arsenic exposure (OR = 7.5), after adjusting for free testosterone and traditional risk factors of ED. CONCLUSIONS: Results suggested that chronic arsenic exposure has a negative impact on erectile function. [ABSTRACT FROM AUTHOR]

The purpose of this study was to elucidate correlations between different biochemical measurements of androgen deficiency and clinical symptoms in male residents of Taiwan. An investigation of the serum biochemical markers for androgen deficiency in 650 males, including total testosterone, calculated free testosterone, and bioavailable testosterone, was conducted. Measurements of clinical symptoms were obtained using a questionnaire of the androgen deficiency in the aging male (ADAM) by St Louis University (SLQ). Correlations among the biochemical markers, correlations of the biochemical markers and age, and relationships between the biochemical markers and the SLQ were evaluated. The sensitivity and specificity of the SLQ were determined. Bioavailable and calculated free testosterone correlated better with age than did total testosterone. Eighty percent of the men had a positive SLQ, and 20% had a negative SLQ. The percentage of positive SLQ results increased with age. No statistically significant difference was noted between the biochemical markers of bioavailable and calculated free testosterone levels and the SLQ status except for men aged over 70 years. The SLQ in this study showed an acceptable sensitivity of about 80%, but the specificity was poor (about 20%). In conclusion, bioavailable testosterone and calculated free testosterone were more-closely correlated with age and may be better biochemical markers for androgen deficiency. SLQ might not be a suitable single measurement for androgen deficiency and should be used together with biochemical markers.International Journal of Impotence Research (2006) 18, 343–347. doi:10.1038/sj.ijir.3901417; published online 17 November 2005 [ABSTRACT FROM AUTHOR]

Objective . To investigate the age-related change of serum androgen levels in healthy men and to define a cut-off value of serum testosterone for the diagnosis of androgen deficiency in the aging male. Method . 1080 healthy men aged 20 to &geqslant;70 years old were enrolled in Beijing, Shanghai, Xian and Chongqing. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (T), calculated free testosterone (cFT), sex hormone binding globulin (SHBG), 17beta-oestradiol (E2), the T/LH ratio, and T/SHBG as a free testosterone index (FTI) were all determined. Results . Serum total T did not significantly decline, but the cFT, T/LH and FTI progressively decreased with aging. To determine androgen deficiency, the 10th percentile value of men 70 years. Conclusions . (i). While serum total T values do not decline with aging, the levels of cFT gradually decline with aging; (ii) when using the value of cFT of the 10th percentile of men aged 20 to 39 years as the cut-off point, the prevalence of androgen deficiency was <15% before the age of 50 years, and about 30% thereafter, approaching 45% after the age of 70 years; and (iii) in this study the values of T/LH paralleled those of cFT closely; therefore, T/LH could serve as a surrogate for cFT. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article on determining calculated free testosterone reference intervals in a normal adult male population.

This study aimed to propose an operational definition of late-onset hypogonadism (LOH) that incorporates both clinical symptoms and serum testosterone measurements to evaluate the prevalence of LOH in aging males in China. A population-based sample of 6296 men aged 40 years-79 years old was enrolled from six representative provinces in China. Serum total testosterone (TT), sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were measured and free testosterone (cFT) was calculated. The Aging Males' Symptoms (AMS) scale was used to evaluate the LOH symptoms. Finally, 5078 men were included in this analysis. The TT levels did not decrease with age (P = 0.59), and had no relationship with AMS symptoms (P = 0.87 for AMS total score, P = 0.74 for ≥ 3 sexual symptoms). The cFT levels decreased significantly with age (P < 0.01) and showed a negative association with the presence of ≥ 3 sexual symptoms (P = 0.03). The overall estimated prevalence of LOH was 7.8% (395/5078) if a cFT level <210 pmol l -1 combined with the presence of ≥ 3 sexual symptoms was used as the criterion of LOH. Among them, 26.1% (103/395) and 73.9% (292/395) had primary and secondary hypogonadism, respectively. After adjustment for confounding factors, primary and secondary hypogonadism was positively related to age and comorbidities. Body mass index was an independent risk factor for secondary hypogonadism. The results suggest that the AMS total score is not an appropriate indicator for decreased testosterone, and that the cFT level is more reliable than TT for LOH diagnosis. Secondary hypogonadism is the most common form of LOH., Competing Interests: None

Background: Although erectile dysfunction (ED) has been associated with low circulating total testosterone (TT) levels, the utility of free testosterone (FT) over TT is debatable., Aim: To assess the relative impact of low TT and low calculated FT (cFT) on androgen-related sexual symptoms in men with ED., Methods: Data from 485 men were analyzed. Comorbidities were scored with the Charlson Comorbidity Index (CCI). Patients completed the International Index of Erectile Function (IIEF) and the Beck Inventory for Depression (BDI). Descriptive statistics tested differences between patients with normal TT levels (>3 ng/mL) and normal cFT levels (>65 pg/mL; group 1) and men with normal TT and low cFT (group 2), low TT and normal cFT (group 3), and low TT and low cFT (group 4). Linear regression models tested the association between clinical predictors and sexual function impairment., Outcomes: We assessed the impact of different hormonal categories on androgen-related symptoms and the clinical utility of measuring cFT in men with ED., Results: Groups 1, 2, 3, and 4 were composed of 338 (69.6%), 44 (9.1%), 34 (7.0%), and 69 (14.3%) patients, respectively. Compared with group 1, patients in group 2 were older (P < .001), had a higher body mass index (P < .01), and had a larger proportion with CCI scores of at least 1 (P = .006). Likewise, group 2 presented lower scores for the IIEF erectile function (P = .07), sexual desire (P = .04), and orgasmic function (P = .007) domains and lower BDI scores (P = .02) than group 1. Similar findings were found for group 4 vs 1. Conversely, patients in group 3 had similar scores on the questionnaires to those in group 1. Low cFT and normal or low TT achieved independent predictor status for pathologic IIEF domains and BDI scores after accounting for age, CCI, and body mass index. Conversely, low TT and normal cFT status was not associated with pathologic scores on the questionnaires., Clinical Implications: The inclusion of cFT in the first-line assessment of hypogonadal symptoms in men with ED has major clinical utility., Strengths and Limitations: This is the first study evaluating the concomitant impact of TT and cFT on men with ED using well-validated instruments to assess patients' sexuality and depressive symptoms. Limitations are the retrospective nature of the study and lack of physical function data and bone ultrasound measurements., Conclusions: Although normal cFT was not associated with signs and symptoms suggestive of testosterone deficiency, even when concomitant with low TT or low cFT irrespective of TT values, it was indicative of poorer clinical profiles and impaired sexual and depressive parameters compared with normal TT and normal cFT in a cohort of patients with ED. Boeri L, Capogrosso P, Ventimiglia E, et al. Does Calculated Free Testosterone Overcome Total Testosterone in Protecting From Sexual Symptom Impairment? Findings of a Cross-Sectional Study. J Sex Med 2017;14:1549-1557., (Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study is to compare calculated free testosterone (cFT) and total testosterone (T) in predicting late-onset hypogonadism (LOH) in middle-aged and elderly males., Methods: We surveyed a random sample of 608 males between the ages of 45 and 87 years from Shanghai, China. The Aging Male Symptoms (AMS) questionnaire and the Androgen Deficiency in Aging Male (ADAM) questionnaire were completed by the subjects. Testosterone (T), sex hormone-binding globulin (SHBG), albumin, and other blood biochemical indexes were measured in 332 males. The corresponding cFT was obtained using the Vermeulen formula and the correlations between T and cFT were analyzed by SPSS statistical software., Results: Among the 332 males who underwent biochemical evaluation, 289 males (87.0%) was positively screened by the ADAM questionnaire and 232 males (69.9%) by the AMS questionnaire. As suggested by linear regression, cFT exhibited a negative correlation with age in both ADAM+ and AMS+ group, whereas T did not appear to have significant correlation with age. Besides, there were statistically significant differences in cFT (P<.001) in the AMS questionnaire., Conclusions: Calculated free testosterone levels are more reliable than T levels for diagnosing LOH in middle-aged and elderly males., (© 2016 Wiley Periodicals, Inc.)