Low Serum Testosterone Concentration in Middle-aged Men with Type 2 Diabetes
Michiaki FukuiJintetsu SohMuhei TanakaYoshihiro KitagawaGoji HasegawaToshikazu YoshikawaTsuneharu MikiNaoto Nakamura
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Low concentrations of endogenous androgens have been linked with insulin resistance and atherosclerosis. Men with diabetes have been reported to have lower serum testosterone concentration than non-diabetic men; however, there has never been a large study. The aim of this study was to investigate if endogenous androgen concentration is certainly lower in a relatively large number of Japanese patients with type 2 diabetes compared with healthy men, and to identify what factors may be associated with low serum testosterone concentrations in men with type 2 diabetes. Serum free testosterone concentrations were measured in 524 healthy men and in 331 consecutive Japanese men with type 2 diabetes between 40 and 69 years old. In addition, we investigated the relationships between serum free testosterone concentration and luteinizing hormone (LH) concentration as well as major cardiovascular risk factors including age, blood pressure, plasma lipid concentration, glycemic control (HbA(1c)), and BMI. Serum free testosterone concentrations were lower in men with type 2 diabetes than in healthy men in the 40-49 years group (10.9 +/- 3.3 vs. 14.0 +/- 3.6 pg/ml, P<0.0001), in the 50-59 years group (10.4 +/- 3.2 vs. 12.1 +/- 2.9 pg/ml, P<0.0001), and in the 60-69 years group (9.5 +/- 2.6 vs. 10.5 +/- 2.9 pg/ml, P = 0.0104). A negative correlation was found between serum free testosterone and LH concentrations (r = -0.326, P<0.0001). In conclusion, serum free testosterone concentration is certainly lower in a relatively large number of Japanese patients with type 2 diabetes compared with healthy men with each decade of life between 40 and 69 years old.Keywords:
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For the purpose of investigating a possible correlation between the genesis of breast cancer and the serum contents of free (non-protein-bound) estradiol (E2) and free testosterone (T) in Japanese women, the distributions of free and total E2 and T and the binding capacity of sex hormone-binding globulin (SHBG) in serum were compared for 39 patients with preoperative breast cancer and 40 normal women (controls). The patients were found to have significantly higher free E2 and free T (in terms of the percentage of the total) than did controls. Conversely, percentages of SHBG-bound E2 and albumin-bound E2 were not significantly different for patients and controls. The SHBG binding capacity was significantly smaller in postmenopausal, but not in premenopausal, patients. Free E2 and free T were found to be negatively correlated with the SHBG binding capacity in both patients and controls. A significant negative correlation also was noted between the percentage of free E2 or free T and the age of controls. The percentage of free T was positively correlated with body weight for both premenopausal and postmenopausal patients. These results suggest a possibility that the elevation of free E2 in the serum may be one of the potential risk factors for genesis of breast cancer in Japanese women.
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To investigate the relation between free testosterone (T) and binding capacity of sex-hormone-binding globulin (SHBG-BC) and a degree of hirsutism, 34 women were classified into 3 groups according to the criteria of Ferriman and Gallway on the degree of the hirsutism; 11 patients with a total score of 1 to 3 (group 1), 8 patients with a total score of 4 to 10 (group 2), and 15 patients with a total score of 11 or more (group 3). Total plasma T, SHBG-BC, and free plasma T were measured in each group, and they were compared with those of controls. In groups 1 and 2, mean levels of total T were slightly higher than in controls but the differences were not significant. Total T levels were extremely elevated in group 3. Mean level of SHBG-BC in group 1 was slightly lower than in controls but was not statistically significant. SHBG-BC was drastically reduced in groups 2 and 3. The percent free T levels and free T concentrations were significantly higher than those of controls in groups 2 and 3, but not in group 1. The results suggested that decreased SHBG-BC and increased free T might be the cause of hirsutism in women with normal total T levels.
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We would like to follow up our 2014 publication in this journal (1) by submitting further validation data to support the measurement of salivary testosterone (T), highlighting its independence from variations in circulating sex hormone-binding globulin (SHBG), unlike serum total T which is positively correlated with SHBG.All analyses were performed as previously described (1).In addition, further samples were collected from, 48 males and 38 females, healthy volunteers (mean age 32 y, range 18-66).Ethical committee approval was granted from Ghent University Hospital.These samples were analysed for salivary T, total T and equilibrium dialysis using liquid chromatography-tandem mass spectrometry (2).
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Abstract An algorithm was developed to evaluate equilibrium constants for testosterone (Te) and sex hormone-binding globulin (SHBG) or albumin from serum free testosterone (FTe) measurements performed in a panel of 30 healthy elderly men by means of a near-reference method, i.e., symmetric dialysis (affinity constants: SHBG-Te, 1.13×10
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The clinical relevance of the free androgen index (FAI), a ratio of total testosterone (T) to sex-hormone binding globulin (SHBG), was investigated in a regional population of men (n = 40) and women (n = 30). The FAI correlated well with free testosterone (T) in both men (r = 0.551, p < 0.001) and women (r = 0.454, p < 0.01). However, there was considerable variability among individual patients. Moreover, the FAI showed no association with sperm parameters in male patients, although total T and free T showed weak associations. The FAI may be a cost-effective alternative to free T measurement in the diagnosis of oligomenorrhea and hirsutism in women as previously shown, but may have little relevance in men.
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To determine whether menstrual status had an effect on plasma sex hormone-binding globulin (SHBG) capacity and nonprotein-bound estradiol (% free E2) and testosterone (% free T), we measured these as well as plasma FSH, total E2, and T and the MCRs of E2 and T in a group of 78 perimenopausal women. The women were allocated to 4 groups: women with cycles whose plasma FSH level was less than 40 mlU/mL (A; n = 16), women with cycles whose plasma FSH level was greater than 40 mlU/mL (B; n = 19), Women who were amenorrheic for less than 1 yr (C; n = 13), and women who were amenorrheic for more than 1 yr (D; n = 30). The mean plasma SHBG values were 51.4 ± 5.7 (±se), 48.3 ± 4.3, 45.9 ± 5.4, and 51.1 ± 3.7 nM in groups 1–4 respectively, and were not significantly different from one another. The mean % free E2 and % free T values also were not different between the groups. However, the mean total E2 and free E2 (% free E2 × E2/100) concentrations were significantly (P < 0.05) higher in both groups A and B than in groups C and D. The E2 concentration was also higher in group A than in group B. There were strong correlations between the E2 and free E2 concentrattions between the T and free T (% free T × T/100); (P < 0.0001) concentrations, between SHBG capacity and weight, and between the MCRs of both E2 and T and % free E2 and % free T. In normal women, the menopause is not associated with changes in SHBG or % free steroids. Hence, the measurement of E2 could be used to predict the mass of free E2 in these women.
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Objective Sex hormone-binding globulin (SHBG) is a glycoprotein which binds hormones such as testosterone. Around 97% of circulating testosterone is bound to SHBG or albumin and is therefore biologically unavailable; 2–3% of testosterone is free. Free testosterone is very technically challenging to quantify; in order to circumvent this problem, equations using testosterone and SHBG are used to estimate free testosterone. We decided to determine the effect of using different SHBG immunoassays on calculated free testosterone results. Design Anonymized surplus serum samples were analysed for SHBG on four different immunoassay platforms (Abbott Architect, Roche, Beckman and Siemens). The SHBG results were used to generate a Vermeulen calculated free testosterone. Results Beckman Access and Siemens Centaur both gave results close to the overall mean. Roche gave the highest SHBG concentrations with Abbott Architect producing the lowest results. Abbott Architect gave the highest calculated free testosterone results, followed by Beckman. Roche gave the lowest results. Sixty-five per cent of male samples had low calculated free testosterone and 27.5% of the females had high calculated free testosterone using the SHBG from the Abbott assay compared with 69% low male calculated free testosterone and 20% high female calculated free testosterone with the Roche assay. Conclusion Our results have shown significant differences in SHBG results produced by different analysers and subsequently the calculated free testosterone, which may affect result interpretation if method-specific reference ranges for calculated free testosterone are not used. Care should be taken to ensure reference ranges are appropriate for the analyser used to avoid misdiagnosis of hypo or hyperandrogenism, and ensure patients get the most appropriate treatment.
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Objective To investigate the correlation of waist-hip ratio( WHR) with sex hormone binding globulin( SHBG) and free testosterone in perimenopausal women with obesity. Methods Eighty obesity women aged 40 ~50 years old were divided into group Ⅰ and group Ⅱ according to WHR,with 40 cases in each group,and the serum levels of free testosterone,SHBG were detected,and body mass index( BMI) was calculated. The free androgen index( FAI) was used as the indicator of androgen activity. Results FAI and WHR in group Ⅰ were higher than those in group Ⅱ( all P 0. 05),while the level of SHBG was lower than that in group Ⅱ( P 0. 05); WHR negatively correlated with SHBG( P 0. 05),and positively correlated with FAI and BMI among perimenopausal women with obesity( P 0. 05).Conclusion WHR negatively correlates with SHBG while positively correlates with FAI and BMI among perimenopausal women with obesity.
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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 <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 <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.
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