Testosterone and the Free Androgen Index (original) (raw)
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Oman Medical Journal, 2012
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 1 st May 2011 to 31 st 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 cutoff: 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.
International Urology and Nephrology, 2011
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 B 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.
The Journal of Urology, 2010
The diagnosis of testosterone deficiency syndrome is based on clinical manifestations and documentation of low testosterone. Which biochemical tests to use and the importance of morning sampling are still controversial. Biological variation (including interindividual and intraindividual biological variation) must be considered when interpreting individual results as it determines the usefulness of reference intervals and the change (reference change value) necessary for a significant difference between results. Materials and Methods: A total of 87 healthy men (50 to 70ϩ years old) provided blood in the morning of the first day, and 4 weeks later in the morning and afternoon. Samples were frozen (Ϫ70C) and analyzed in the same run for serum testosterone, sex hormone-binding globulin and albumin, and bioavailable testosterone and free testosterone were calculated. Results: Serum testosterone was lower in the afternoon by 1.5 nmol/l (43 ng/dl, p Ͻ0.05), with larger changes observed with higher morning values. However, this diurnal effect was dwarfed by the normal biological variation observed for repeat morning samples (serum testosterone Ϯ 4 nmol/l [115 ng/dl]). Between day intra-individual biological variation for morning serum testosterone was 18.7% while within day intra-individual biological variation was 12.9%. A change of 52% (reference change value) is necessary between serial morning results to confirm a significant difference. The biological variation parameters of calculated bioavailable testosterone and calculated free testosterone confer no advantage over total testosterone. Conclusions: Marked individuality of serum testosterone is evident even in healthy men. Because intraindividual biological variation is less than interindividual biological variation, reference intervals are marginally useful. The homeostatic set point of a patient could decrease by half and still be within the reference interval. Prospective establishment of an individual's baseline over repeated measurements or symptoms regardless of serum testosterone concentration should be used to guide clinical decisions.
European Journal of …, 2012
Background: The limitations of serum testosterone and estradiol (E 2) measurements using nonextraction platform immunoassays (IAs) are widely recognized. Switching to more specific mass spectrometry (MS)-based methods has been advocated, but directly comparative data on the two methods are scarce. Methods: We compared serum testosterone and E 2 measurements in a large sample of middle-aged/elderly men using a common platform IA and a gas chromatography (GC)-MS method, in order to assess their limitations and advantages, and to diagnose male hypogonadism. Of subjects from the European Male Aging Study (nZ3174; age 40-79 years), peripheral serum testosterone and E 2 were analyzed using established commercial platform IAs (Roche Diagnostics E170) and in-house GC-MS methods. Results: Over a broad concentration range, serum testosterone concentration measured by IA and MS showed high correlation (RZ0.93, P!0.001), which was less robust in the hypogonadal range (!11 nmol/l; RZ0.72, P!0.001). The IA/MS correlation was weaker in E 2 measurements (RZ0.32, P!0.001, at E 2 !40.8 pmol/l, and RZ0.74, P!0.001, at E 2 O40.8 pmol/l). Using MS as the comparator method, IA ascertained low testosterone compatible with hypogonadism (!11 nmol/l), with 75% sensitivity and 96.3% specificity. The same parameters with IA for the detection of low E 2 (!40.7 pmol/l) were 13.3 and 99.3%, and for high E 2 (O120 pmol/l) 88.4 and 88.6%. Conclusion: A validated platform IA is sufficient to detect subnormal testosterone concentrations in the diagnosis of male hypogonadism. The IA used for E 2 measurements showed poor correlation with MS and may only be suitable for the detection of high E 2 in men.
Steroids, 2010
Accurate measurement of testosterone concentration is of critical importance when diagnosing and treating male hypogonadism, congenital adrenal hyperplasia, premature or delayed puberty, and androgen excess in polycystic ovary syndrome or other virilizing conditions. However, some assays have inherent limitations and biases that affect measurement of low-testosterone values. Therefore, we developed a highly specific online mass spectrometry method. Sera were extracted online using high-turbulence flow liquid chromatography coupled to analytical HPLC and atmospheric pressure chemical ionization tandem mass spectrometry (HTLC-APCI-MS/MS). Analyte ions were monitored by multiple reaction monitoring (MRM). Total analysis time was 1.15 min per sample when using the multiplexing system. Testosterone concentrations were measured directly from 150 microL of serum or plasma without derivatization or liquid-liquid extraction. The lower limit of quantification was 0.3 ng/dL, and the assay was linear up to 2000 ng/dL. The method compared very well with an established RIA: y=1.02x+1.5, r(2)=0.994. Comparison with a platform immunoassay confirmed the previously reported ICMA positive bias at low concentrations. Male and female adult and pediatric reference ranges were developed for this very sensitive and accurate high-throughput LC-MS/MS method. This method is suitable for measuring the expected low-testosterone concentrations seen in women, children, and hypogonadal males and for monitoring testosterone suppressive therapy in prostate cancer patients.
European Journal of Endocrinology, 2012
Background: The limitations of serum testosterone and estradiol (E 2 ) measurements using nonextraction platform immunoassays (IAs) are widely recognized. Switching to more specific mass spectrometry (MS)-based methods has been advocated, but directly comparative data on the two methods are scarce. Methods: We compared serum testosterone and E 2 measurements in a large sample of middle-aged/elderly men using a common platform IA and a gas chromatography (GC)-MS method, in order to assess their limitations and advantages, and to diagnose male hypogonadism. Of subjects from the European Male Aging Study (nZ3174; age 40-79 years), peripheral serum testosterone and E 2 were analyzed using established commercial platform IAs (Roche Diagnostics E170) and in-house GC-MS methods. Results: Over a broad concentration range, serum testosterone concentration measured by IA and MS showed high correlation (RZ0.93, P!0.001), which was less robust in the hypogonadal range (!11 nmol/l; RZ0.72, P!0.001). The IA/MS correlation was weaker in E 2 measurements (RZ0.32, P!0.001, at E 2 !40.8 pmol/l, and RZ0.74, P!0.001, at E 2 O40.8 pmol/l). Using MS as the comparator method, IA ascertained low testosterone compatible with hypogonadism (!11 nmol/l), with 75% sensitivity and 96.3% specificity. The same parameters with IA for the detection of low E 2 (!40.7 pmol/l) were 13.3 and 99.3%, and for high E 2 (O120 pmol/l) 88.4 and 88.6%. Conclusion: A validated platform IA is sufficient to detect subnormal testosterone concentrations in the diagnosis of male hypogonadism. The IA used for E 2 measurements showed poor correlation with MS and may only be suitable for the detection of high E 2 in men.
Salivary testosterone: a reliable approach to the diagnosis of male hypogonadism
Clinical Endocrinology, 2007
Objective This study was to demonstrate that SalT is a reliable biomarker of androgen status in the diagnosis of male hypogonadism. Design In order to validate the salivary testosterone assay (Sal-T), its reproducibility, the agreement with serum free testosterone levels (Free-T), the correlation with other circulating androgen markers (bioavailable testosterone, total testosterone) and cutoff values were defined. Patients and methods We studied 52 eugonadic (E) and 20 hypogonadic (Hy) men. SalT was assayed using an adapted radioimmunoassay for serum testosterone. SalT concentrations were compared in nine cases before and after citric acid stimulation of salivary flow rate. Free-T and bioavailable testosterone (Bio-T) were calculated by Vermeulen equation and SHBG were determined by binding assay. Results SalT did not depend on salivary flow rate and morning samples from 07•00 h to 09•00 h were stable. Agreement between SalT and Free-T measurements was confirmed in all subjects. SalT levels correlated positively with all circulating androgens, showing the best correlation with Free-T in E (r = 0•92) as well as in Hy (r = 0•97). A cutoff value of SalT ≤ 0•195 n m showed 100% sensibility and specificity to rule out hypogonadism. Conclusions Our data showed that SalT is a reliable marker of testosterone bioavailability. The results support the inclusion of this biomarker as a noninvasive approach in the diagnosis of male androgen deficiency.
The journal of sexual …, 2010
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 Ϯ 14.3 years (range 24-80). Mean TT was 443.0 Ϯ 208.3 ng/dL (range 110-1276). Mean aFT was 1.22 Ϯ 0.54 ng/dL (range 0.24-3.8) and mean cFT 9.4 Ϯ 4.5 ng/dL (range 1.8-27.8). Mean SHBG was 34.2 Ϯ 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.