The negative association between serum free testosterone and leptin is dependent on insulin-like growth factor-binding protein 1 in healthy young and middle-aged men

OBJECTIVE: Previous studies have shown that serum levels of testosterone correlate negatively with leptin and positively with insulin-like growth factor binding protein 1 (IGFBP-1). The present study examined whether these associations are linked. DESIGN AND PATIENTS: The association between serum levels of IGFBP-1, free testosterone and insulin on one hand and leptin on the other hand were investigated in 38 healthy men with a median age of 48 years (range 23-62 years). RESULTS: Univariate analyses revealed that serum levels of leptin correlated negatively with serum free testosterone (r = - 0.42, P = 0.008) and with serum IGFBP-1 (r = - 0. 45, P = 0.005) and positively with body mass index (BMI; r = 0.46, P = 0.003) and serum insulin (r = 0.45, P = 0.004). Serum free testosterone correlated with IGFBP-1 (r = 0.42, P = 0.008) but not with serum insulin (r = - 0.08, ns). The correlations between leptin and free testosterone and between leptin and IGFBP-1 remained significant after adjustement for the influences of BMI and insulin. Forward stepwise multiple regression when BMI, insulin, testosterone and IGFBP-1 were entered in a model as independent variables and leptin as the dependent variable showed that BMI and IGFBP-1 were independent predictors of circulating leptin. These two parameters yielded an r 2 of 0.38, thereby together explaining approximately 40% of serum leptin. CONCLUSION: Serum levels of free testosterone and IGFBP-1 correlate negatively with serum leptin in healthy nonobese men but this influence is dependent on the influence of IGFBP-1. The study therefore suggests an important impact of IGFBP-1 on the regulation of circulating leptin in young and middle-aged men.     

Serum testosterone levels correlate with haemoglobin in middle-aged and older men

Background: Lower testosterone levels are associated with anaemia in older men and women. The relation between testosterone and haemoglobin (Hb) in younger and middle-aged men is less well defined. The aim of the study was to examine the association between testosterone and Hb levels in men spanning middle to older ages.
Methods: A cross-sectional analysis of 492 men aged 30.7–94.5 years from the Busselton Health Survey, Western Australia, was carried out. Haemoglobin (Hb), early-morning serum total testosterone and sex hormone-binding globulin (SHBG) were measured. Free testosterone was calculated using mass action equations.
Results: Haemoglobin correlated to total and free testosterone concentrations ( r = 0.13, P = 0.003 and r = 0.20, P < 0.001, respectively). Hb and SHBG were inversely correlated ( r =−0.14, P = 0.001). Hb increased across lowest to highest quartiles of total testosterone ( P = 0.02) and free testosterone ( P < 0.001), but not SHBG. After adjusting for age, waist circumference, smoking status, alcohol consumption, renal function and ferritin, total testosterone was associated with Hb ( β = 0.037, P = 0.003) as was free testosterone ( β = 2.32, P < 0.001), whereas SHBG was not associated.
Conclusion: Testosterone concentration modulates Hb levels in community-dwelling men across a wide age range. Further studies are needed to clarify implications of this association between testosterone and Hb in men.     

Reduced sex hormone binding globulin and derived free testosterone levels in women with severe acne

Reduced circulating sex hormone binding globulin (SHBG) levels were found in 54% of a group of women with moderate to severe acne and in 60% of another group of twenty-three women who had acne complicated by hirsutism and/or irregular menstrual cycles. The concentrations of SHBG for the women with acne alone (mean 48 ± 24 nmol/l) and for those with acne and hirsutes (mean 39 ± 18 nmol/l) were compared with the SHBG concentrations of fifteen unaffected women with normal menstrual cycles (mean 70 ± 19 nmol/l). The differences in mean SHBG values for both groups of women with acne were significant ( P < 0·001) on comparison with the mean for the unaffected women.
Twenty-nine per cent of the women with acne had elevated testosterone values (mean testosterone concentration for the group 1·5 ± 0·3 nmol/l) and 41% had elevated'derived'free testosterone levels (mean 21 ± 6 pmol/l). Of the women with acne and hirsutes 65% had elevated plasma testosterone levels (mean 2·1 ± 0·6 nmol/l) and 89% had elevated free testosterone concentrations (mean 31 ± 10 pmol/l). The mean values for testosterone and free testosterone in the plasma of unaffected women (mean testosterone concentration 1·1 ± 0·3 nmol/l and free testosterone 13 ± 4 pmol/l) were significantly lower than in women with acne alone ( P < 0·01 and P < 0·001) and in women with acne and hirsutism ( P < 0·001).
This study indicates that a deficiency in SHBG and an elevation in'derived'free testosterone is a frequent finding in women with severe acne and may be a significant factor in the aetiology and/or perpetuation of this condition.     

Diurnal variation of sex hormone binding globulin and insulin-like growth factor binding protein-1 in women with polycystic ovary syndrome

OBJECTIVES The aim of this study was to examine (1) the diurnal variation In SHBG and (2) the Inter-relatlonshlps of Insulin, IGF-I, SHBG and IGFBP-1 over 24 hours In 10 women with anovulatory PCOS and compare them with weight-matched ovulatory controls. PATIENTS AND METHODS The two groups comprised 10 anovulatory women with PCOS (as defined by clinical, ultrasound and biochemical criteria) and 10 weight matched controls. Serum samples were taken at two-hourly Intervals for 24 hours and stored for measurement of SHBG, IGFBP-1, insulin and IGF-I. Differences between the groups were compared using the Wllcoxon ranked paired tests of the Individual peak and trough concentrations in each group. The variation In Insulin, IGFBP-1 and SHBG concentrations over 24 hours was tested using two-way analysis of variance with the factors time and subject. Spearman's correlation coefficient was calculated from the subjects’median value over 24 hours. RESULTS The median (interquartile range) body mass Index (BMI) was 25-2 (22-2-29-3) in the PCOS group and 24-3 (23-2-25-7) kg/m2 In the control group. Serum testosterone (T) and LH levels were significantly raised in the PCOS group compared to the control group; T 3-8 (2-9-5-6) vs 1-9 (1-9-2-5) nmol/l (P < 0-007) and LH 12 (10-15) vs 4-1 (3-6-4-5) IU/I (P< 0-005) respectively. There was no diurnal variation In SHBG. The median (interquartile ranges) of the peak SHBG concentrations was lower In the PCOS group: 29-4 (14-9-39-4) vs 52-1 (39-4-61) nmol/l In the control group (P < 0-01). The fasting levels of Insulin at 0600 h (median (Interquartile ranges)) were not significantly different between the groups; 6-6 (5-4-9-8) and 6-2 (1-9-7-6) mU/l, respectively, although the peak median concentrations were significantly different; PCOS 66-1 (50-9-129-2) vs 40 (36-1-74-2) mU/l (P<005). Two-way analysis of variance showed a diurnal variation In Insulin concentrations In the control group (P=0-001) but not in the PCOS group (P=0-1). The diurnal variation In IGFBP-1 was similar in the two groups but the peak median levels were lower In the women with PCOS 54-9 (22-3-79-2) vs 71-5 (60-5-99-3) μg/I (P<003). The decline In IGFBP-1 concentrations correlated with the increase In insulin concentrations. The IGF-I concentrations were similar In the two groups. There was a significant negative correlation between SHBG and insulin (P<0-05) and between Insulin and IGFBP-1 (P<001). CONCLUSION This study demonstrates that there Is no diurnal variation In SHBG concentrations and confirms the finding of a marked diurnal variation in the concentration of IGFBP-1. Women with PCOS who are anovulatory have an abnormal pattern of Insulin secretion with an absence of diurnal variation compared to weight matched controls. This provides further evidence of the relative Insulin resistance which is independent of weight found In women with anovulatory PCOS. The inverse correlations of insulin concentrations with SHBG and IGFBP-1 support the role of Insulin as a possible regulator of the circulating levels of these binding proteins although the difference in the time course of their response makes It unlikely that they are co-regulated.     

Age-related changes of serum sex hormones, insulin-like growth factor-1 and sex-hormone binding globulin levels in men: cross-sectional data from a healthy male cohort

The age-dependent decline of the gonadal and somatotopic axis has been causally linked to frailty in the elderly by their effects on muscle mass and bone mineral density. However, for healthy men data on serum oestrogens and androgens, as well as IGF-1, as a common outcome measure covering the whole adult age range are scarce. We therefore studied healthy, nonobese male subjects between 20 and 80 years of age to asses their morning concentrations of total (T), free (FT), bioavailable testosterone (bT), oestradiol (E2), bioavailable oestradiol (bE2), oestrone (E1), sex-hormone binding globulin (SHBG), and insulin-like growth factor 1 (IGF-1). Five hundred and seventy-two male healthy volunteers with a BMI < 30 kg/m2 recruited from regular blood donors and senior sports clubs participated in the study. Serum samples were obtained during morning hours and T, FT, E2, E1, SHBG, albumin and IGF-1 were measured by radio-immunoassay systems. In addition, bT and bE2 were calculated. A potential relationship between sex hormones and IGF-1 was tested by multiple regression analysis including age and BMI. Ageing was negatively related to serum levels of sex steroids and IGF-1 (both P < 0.0001) with a mean decrease (youngest vs. oldest) of 51% for T, 64% for FT, 78% for bT, 32% for E2, 62% for bE2, 29% for E1 and 51% for IGF-1 starting in early adulthood whereas SHBG increased after the 5th decade of life (ANOVA P < 0.001). The decline of sex hormones and IGF-1 remained relatively unchanged after adjustment for BMI. Multiple regression analysis revealed an age-and BMI- independent association between oestradiol and IGF-1. In contrast to the female situation sex hormones in healthy, nonobese men decline continuously with age. This process has already started in the third decade, and is paralleled by a decline of IGF-1 serum levels leading to a substantial proportion of elderly men with markedly lowered serum levels of bioavailable sex hormones and IGF-1 compared to the young adult male range. With the recent demonstration of beneficial effects of androgen replacement therapy in healthy males on general well being, muscle mass and bone mineral density the present data may underline the importance of more detailed studies on the biological significance of hormonal changes in men with age.     

Continuous subcutaneous infusion of low dose growth hormone decreases serum sex-hormone binding globulin and testosterone concentrations in moderately obese middle-aged men

OBJECTIVE   Sex-hormone binding globulin (SHBG) is a liver derived protein whose concentration has been shown to be affected by a number of factors. The aim of the present study was to investigate the possible effect of increased basal GH concentrations on serum concentrations of SHBG, testosterone and thyroid hormones.
DESIGNS  Recombinant human growth hormone (rhGH) was given as a continuous subcutaneous infusion in a low dose (0.02 U/kg/day) over a period of 14 days in an open study.
PATIENTS  Eight middle-aged (42–59 years) overweight (body mass index 26.1–33.8 kg/m²) but otherwise healthy men were studied.
MEASUREMENTS  Blood samples were obtained after an over-night fast before and after 2, 7 and 14 days of treatment. Serum was separated and stored at −20°C until assay.
RESULTS  Serum GH concentrations increased to a steady level of 2–4 mU/l. Serum SHBG concentration decreased between 2 and 7 days of treatment and serum testosterone concentration changed in parallel. There was no change in the ratio between serum SHBG and serum testosterone. Serum T4 and free T4 concentrations decreased, and that of T3 increased as a result of continuous GH infusion. Simple correlations between changes in SHBG concentrations and other hormonal changes showed positive significant correlations between changes of SHBG and of testosterone.
CONCLUSIONS  Low dose continuously infused GH resulted in a parallel decrease in serum SHBG and testosterone concentrations. Thyroid hormone concentrations were affected in a similar way to that previously demonstrated following daily injections of GH.     

Secular decline in male testosterone and sex hormone binding globulin serum levels in Danish population surveys

CONTEXT: Adverse secular trends in male reproductive health have been reported to be reflected in increased testicular cancer risk and decreased semen quality in more recently born men. These secular trends may also be reflected by changes in Leydig cell function. OBJECTIVE: The objective of the study was to examine whether an age-independent time trend in male serum testosterone levels exists. DESIGN AND SETTING: Testosterone and SHBG were analyzed in 5350 male serum samples from four large Danish population surveys conducted in 1982-1983, 1986-1987, 1991-1992, and 1999-2001. Free testosterone levels were calculated. The effects of age, year of birth, and time period on hormone levels were estimated in a general linear statistical model. MAIN OUTCOME MEASURES: Testosterone, SHBG, and calculated free testosterone levels in Danish men in relation to age, study period, and year of birth were measured. RESULTS: Serum testosterone levels decreased and SHBG levels increased with increasing age. In addition to this expected age effect, significant secular trends in testosterone and SHBG serum levels were observed in age-matched men with lower levels in the more recently born/studied men. No significant age-independent effect was observed for free testosterone. Adjustment for a concurrent secular increase in body mass index reduced the observed cohort/period-related changes in testosterone, which no longer were significant. The observed cohort/period-related changes in SHBG levels remained significant after adjustment for body mass index. CONCLUSIONS: The observed age-independent changes in SHBG and testosterone may be explained by an initial change in SHBG levels, which subsequently lead to adjustment of testosterone at a lower level to sustain free testosterone levels.     

Relations between sex hormones, sex hormone binding globulin, insulin-like growth factor-I and insulin-like growth factor binding protein-I in post-menopausal breast cancer patients

OBJECTIVE Oestrogens, androgens and anti-endocrine drugs such as tamoxifen and aminoglutethimide influence plasma Insulin-like growth factor-I (IGF-I). IGF-I, in turn, has been found to stimulate the peripheral aromatase in vitro. The aim of this study was to examine relations between sex hormones, IGF-I and insulin-like growth factor binding protein-1 (IGFBP-1) In post-menopausal women with breast cancer. DESIGN To measure plasma sex steroids, sex hormone binding globulin (SHBG), IGF-I, IGFBP-1, Insulin and urinary oestrogen metabolites In post-menopausal women with breast cancer not receiving any endocrine therapy. PATIENTS Thirty-two patients had fasting blood samples obtained between 0800 and 1000h. A sub-group of 10 patients had 24-hour urine oestrogen metabolites determined. MEASUREMENTS Plasma steroids and proteins were measured by radioImmunoassays. Urinary oestrogens were measured by GC-MS. RESULTS SHBG correlated negatively with plasma androstenedione (P < 0·001), insulin (P < 0·001), IGF-I, height and plasma oestrone sulphate (P < 0·025 for all), but positively with plasma IGFBP-1 (P < 0·025). IGFBP-1 correlated negatively with IGF-I (P < 0·001) and the testosterone/SHBG ratio (P < 0·05). Neither IGF-I nor IGFBP-1 correlated with any of the plasma or urinary sex hormones or with the oestrone/androstenedione and oestradiol/testosterone ratios. Multivariate analysis revealed plasma SHBG to correlate positively with IGFBP-1 (P= 0·029) and negatively with Insulin (P= 0·031). Plasma IGFBP-1 correlated negatively with IGF-I (P < 0·0001) but not with insulin. CONCLUSION Our results do not suggest any influence of plasma sex steroids in physiological concentrations on IGF-I or IGFBP-1 in post-menopausal breast cancer patients, nor do they indicate IGF-I at physiological concentrations Influences the ratios between plasma oestrogens and their androgen precursors.     

Serum sex hormone and plasma homocysteine levels in middle-aged and elderly men

OBJECTIVE: To investigate whether circulating levels of testosterone (total, bioavailable), estradiol (total, bioavailable), and DHEA sulfate (DHEAS) are associated with fasting plasma homocysteine (tHcy) levels in middle-aged and elderly men. DESIGN: A population-based sample of 400 independently living men between 40 and 80 years of age in a cross-sectional study. METHODS: Total testosterone, sex hormone binding globulin (SHBG), and total estradiol were measured by RIA methods and bioavailable testosterone and estradiol were calculated. DHEAS was measured using an immunometric technique. Fasting homocysteine was measured by fluorescence polarization immunoassay. Anthropometric characteristics were also measured and two standardized questionnaires completed, including life-style factors and diet. Linear regression analysis adjusted for age, body mass index (BMI), creatinine clearance, and mean visceral fat was used to assess the association of endogenous sex hormones and fasting plasma homocysteine levels. RESULTS: After adjustment for age, BMI, creatinine clearance, and mean visceral fat no statistically significant association was observed between testosterone (total, bioavailable), DHEAS, and estradiol (total, bioavailable)levels with natural log tHcy (beta = -2 x 10(-3); 95% confidence intervals (CI) -9 x 10(-3); 5 x 10(-3)), (beta = -4 x 10(-3); 95% CI -18 x 10(-3); 9 x 10(-3)), (beta = 3 x 10(-3); 95% CI -6 x 10(-3); 12 x 10(-3)), (beta = -9.3 x 10(-5); 95% CI -1 x 10(-3); 1 x 10(-3)), and (beta = 0.00; 95% CI -3 x 10(-3); 2 x 10(-3)) respectively. Additional adjustment for smoking, alcohol intake, daily physical activity, diabetes mellitus, and hypertension did not change these findings. CONCLUSION: The results of our study do not support a direct role for circulating sex hormone levels in the regulation of fasting plasma tHcy concentrations in middle-aged and elderly men.     

Serum insulin-like growth factor type 1, insulin-like growth factor-binding protein-1, and insulin-like growth factor-binding protein-3 concentrations in patients with thyroid dysfunction.

Thyroid hormones play a role in the regulation of insulin-like growth factor type 1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) expression, and both IGF-1 and IGFBPs have been shown to be related to the function and growth of the thyroid. Our aim was to evaluate serum concentrations of IGF-1, IGFBP-1, and IGFBP-3 in patients with thyroid dysfunction before and after normalization of thyroid function. The study was performed in 86 patients with thyroid dysfunction (43 hyperthyroid and 43 hypothyroid patients) and 17 euthyroid subjects. Serum growth hormone (GH), insulin, IGF-1, IGFBP-1, and IGFBP-3 were measured in all patients before and after normalizing serum thyroid hormone concentrations. Hyperthyroid patients showed IGF-1 (198.8 +/- 17.0 microg/L) and IGFBP-3 levels (4.2 +/- 0.2 mg/L) similar to those found in the control group (217.9 +/- 20.3 microg/L and 4.2 +/- 0.3 mg/L, respectively). After therapy these levels significantly decreased to 156.6 + 11.1 microg/L (p < 0.01) and 3.3 +/- 0.1 mg/L (p < 0.001), respectively. IGFBP-1 concentrations were clearly higher than those found in controls (22.7+/- 2.6 vs. 5.7 +/- 1.5 microg/L, p < 0.001) and exhibited a significant reduction after therapy for thyroid hyperfunction (11.0 +/- 1.7 microg/L, p < 0.001). Patients with hypothyroidism showed serum concentrations of IGF-1 (161.5 +/- 13.1 microg/L, p < 0.05) and IGFBP-3 (3.2 +/- 0.3 microg/L, p < 0.05) significantly lower than those found in healthy volunteers. However, replacement therapy with levothyroxine did not induce any significant modification of these concentrations (152.6 +/- 10.6 microg/L and 3.2 +/- 0.2 mg/L, respectively). Similarly, patients with thyroid hypofunction exhibited raised levels of IGFBP-1 (15.5 +/- 0.9 microg/L, p < 0.05 vs. control group) that were significantly decreased after therapy (8.8 +/- 1.4 microg/L, p < 0.01). The results of the present study show that thyroid status affects GH/IGF axis. Hypothyroidism is associated with significant reductions of IGF-1 and IGFBP-3, and IGFBP-1 is elevated in both hypothyroidism and hyperthyroidism.     

Serum growth hormone binding protein (GHBP) and insulin-like growth factor binding protein (IGFBP)]

Insulin--like growth factors bind to specific binding proteins (IGFBPs) in serum and tissues. At present, six different IGFBPs have been characterized. Recent studies suggest that IGFBPs act as a reservoir for IGFs but also modulate the bioavailability of IGFs. Binding protein for growth hormone (GH) in serum has been recognized recently. Interestingly, the high affinity GH binding protein (GHBP) is identical with the extracellular domain of GH receptor and is absent in patients with Laron-type dwarfism, suggesting that serum GHBP might serve as a marker for the GH receptor in tissue. In this short review, updated information on serum GHBP and IGFBP is presented.     

过敏性紫癜患儿血清胰岛素样生长因子及胰岛素样生长因子结合蛋白-3的变化

目的 探讨胰岛素样生长因子(IGF)-1及胰岛素样生长因子结合蛋白(IGFBP)-3在过敏性紫癜(HSP)中的作用.方法 采用放射免疫法方法测定45例HSP患儿不同时期的血清IGF-1及IGFBP-3、C反应蛋白(CRP)水平.采用t检验和直线相关关系.结果 HSP急性发作组血清IGF-1[(452±183)μg/L]、IGFBP-3[(13 897±3124)μg/L]及CRP[(20±8)mg/L]水平升高,与健康对照组和缓解组比较,差异均有统计学意义(t值分别为3.42、4.10、11.17、11.63、8.59、9.86.P均<0.01);HSP缓解组血清IGF-1、IGFBP-3及CRP与健康对照组比较,差异无统计学意义(t=0.3,4、0.34、0.52,P均>0.05).HSP急性期并发肾损害组血清IGF-1[(621±253)μg/L]、IGFBP-3[(18 763±3173)μg/L]水平升高,与无肾损害组比较,差异有统计学意义(t值分别为4.21、7.26,P均<0.01),有胃肠道症组血清IGF-1[(479±192)μg/L]、IGFBP-3[(13 986±3162)μg/L]水平与无胃肠道症状组比较,差异无统计学意义(t值分别为0.83、0.16,P均>0.05);血清CRP水平在肾损害组与非肾损害组及胃肠道症组与无胃肠道症状组问差异均无统计学意义(t值分别为0.56、0.32.P均>0.05).HSP急性期患儿血IGF-1、IGFBP-3与CRP浓度之间呈直线正相关(r值分别为0.624,0.672,JP均<0.01).结论 IGF-1、IGFBP-3参与了HSP疾病的病理生理过程,血清IGF-1、IGFBP-3测定对紫癜性肾损害的诊断、病情监测及预后判断有一定帮助.

Abstract：

Objecfive To investigate the role of serum Insulin-like growth factor(IGF)-1,insulinlike growth factor-binding potein(IGFBP)-3 in children with Henoch-Schonlein purpura(HSP).Methods The serum concentration of IGF-1,1GFBP-3 was measured by enzyme-linked immunosorbent assay(ELISA)method in 45 acute SHP patients,40 recoverv patients and 30 healthy controls.Results The serum levels of IGF-1 [(452±183)μg/L],IGFBP-3 [(13 897±3124)μg/L] and C-reactive protein(CRP)[(20±8)mg/L]in acute phase were significantly higher than those in healthy controls(P<0.0 1)and higher than those during recovery period.The serum level of IGF-1,IGFBP-3 for the HSP patients dropped back slowly and their levels during recovery period were the same as those in healthy controls(P>0.05).The serum levels of IGF-1[(621±253)μg/L] and IGFBP-3[(18 763±3173)μg/L] were higher in the renal damage group than in the non-renal damage group(P<0.01).and the same in patients with gastrointestinal symptoms group as in patients without gastrointestinal symptoms group(P>0.05).whereas the serum level of CRP was not significantly different(P>0.05).The serum levels of IGF-1,IGFBP-3 showed positive correlation with the level of CRP(r=0.624,0.672,P<0.01).Conclusion The IGF-1 and IGFBP-3 may play an important role in the pathological mechanism of HSP.The level of IGF-1 may be used as an indicator for HSP disease activity and progression.IGF-1 mav have a close relation with the damage"of renaJ system in HSP.     

Relationships of serum lipoproteins and apoproteins to sex hormones and to the binding capacity of sex hormone binding globulin in healthy Finnish men

We have determined the levels of serum sex hormones, the binding capacity of sex hormone binding globulin (SHBG), urinary estrogens, serum lipids, lipoproteins, and apolipoproteins A-I, A-II, and B in 30 healthy middle-aged Finnish men with similar dietary habits. Serum levels of total testosterone, free testosterone, 5 alpha-dihydrotestosterone (5 alpha-DHT), and the binding capacity of SHBG were all positively correlated to high density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apo A-I) (r = .43 to .80, P less than 0.05 to 0.001). Total testosterone and 5 alpha-DHT showed a positive correlation to the ratio of apo A-I to Apo A-II (r = .37, P less than 0.05 and r = .58, P less than 0.01, respectively). Serum estradiol levels were negatively correlated to serum total cholesterol, low density lipoprotein cholesterol (LDL), and Apo B (r = -.51 to -.56, P less than 0.01). Moreover, serum free estradiol was negatively correlated to HDL-C and Apo A-I (r = -.46 and r = -.50, P less than 0.01). In multiple linear regression analysis, 5 alpha-DHT was the most significant independent determinant of HDL-C and apo A-I levels when androgens, luteinizing hormone, estradiol, binding capacity of SHBG, and exogenous factors such as age, body mass index (BMI), smoking, alcohol consumption, and diet were taken into account. Multivariate analysis also demonstrated that both total and free estradiol were inversely related to serum Apo B levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship of high density lipoprotein cholesterol with total and free testosterone and sex hormone binding globulin

A cross-sectional study was performed to see if the previously described association between high density lipoprotein (HDL) cholesterol and plasma total testosterone concentration reflected a relationship with free testosterone or with sex hormone binding globulin (SHBG). In 295 employed middle-aged men, measurements were made of total testosterone and SHBG in serum and of testosterone in saliva, and also of plasma total and HDL cholesterol, plasma triglycerides and other factors which might influence HDL cholesterol levels such as body mass index, alcohol and smoking habits and thyroid hormone levels. In a multiple regression analysis using the GLIM package programme total testosterone concentrations had a persistent positive association with HDL cholesterol (t = 3.5, P less than 0.001) - this association was independent of SHBG (which had a negative association with HDL: t = -1.8, P less than 0.07. The association of HDL cholesterol with testosterone was independent of and stronger than the association of HDL cholesterol with body mass index, alcohol intake and cigarette smoking. Salivary testosterone (a measure of the circulating free hormone) also had a positive independent association with HDL cholesterol. The relationship between HDL cholesterol and testosterone thus appears to reflect an association with circulating hormone levels rather than with the hormone binding globulin.     

Serum lipoproteins, sex hormones and sex hormone binding globulin in middle-aged men of different physical fitness and risk of coronary heart disease

Serum concentrations of lipoproteins, apolipoprotein A-I (Apo A-I), androgens, including biologically active free testosterone (free T), and sex hormone binding globulin (SHBG) and their associations were studied in 3 groups of men of different physical fitness and risk of CHD, consisting of male CHD patients, joggers and healthy controls. Of the 3 study groups, men with angiographically assessed CHD had the lowest HDL-C (P less than 0.002) and highest LDL-C and triglyceride (TG) levels (P = 0.05 and P less than 0.001) and lower 5 alpha-dihydrotestosterone (5 alpha-DHT) levels than joggers (P less than 0.02). Joggers had the highest serum high density lipoprotein cholesterol (HDL-C), Apo A-I and SHBG levels and lowest serum low density lipoprotein cholesterol (LDL-C) compared to the other groups (P less than 0.01). In correlation analysis 5 alpha-DHT was the most significant positive determinant of HDL-C and Apo A-I levels in CHD patients (r = 0.56 and r = 0.55, respectively, P less than 0.05). Moreover, SHBG was significantly positively correlated to both HDL-C and Apo A-I levels in patients, in the whole study group and in healthy men separately (r = 0.37-0.52, P less than 0.01). These significant correlations were also confirmed when age variation and differences in body mass index and smoking were controlled in multivariate analysis and in addition, in multivariate analysis both serum free and total testosterone were inversely related to serum triglyceride (TG) levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Association of endogenous sex hormone with C-reactive protein levels in middle-aged and elderly men

BACKGROUND: In women, postmenopausal oestrogen supplementation increases levels of systemic markers of inflammation, which are important predictors of coronary heart disease (CHD) risk. Whether endogenous sex hormone levels in men are also related to systemic subclinical inflammation is still unknown. OBJECTIVE: We tested the hypothesis that higher endogenous sex hormones levels within the physiological range may be associated with systemic subclinical inflammation. METHODS: Circulating sex hormone and high-sensitivity C-reactive protein (hs-CRP) levels were determined in 400 apparently healthy men aged between 40 and 80 years. We used multivariate linear regression analysis with the various sex hormones as determinant, and natural log hs-CRP as outcome. RESULTS: Higher levels of total as well as bioavailable oestradiol (E2) were associated with increased natural log hs-CRP levels, which remained statistically significant after adjustment for age and cardiovascular risk factors. Natural log hs-CRP was 0.26 mg/l higher [95% confidence interval (CI) -0.02 to 0.54] in the fourth than in the first quartile of total E2; the P-value for linear trend was 0.05. For bioavailable E2, the difference in natural log hs-CRP between the fourth and the first quartile was 0.30 mg/l (95% CI 0.03-0.56; P-value for linear trend 0.04). After adjustment for age and cardiovascular risk factors, physiological levels of total (TT) or bioavailable testosterone or dehydroepiandrosterone sulfate (DHEAS) were not associated with hs-CRP. CONCLUSION: Endogenous total and bioavailable E2 levels are significantly associated with CRP among middle-aged and elder men.     

Role of growth hormone, insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 in development of non-alcoholic fatty liver disease

Background and aims Pituitary dysfunction including growth hormone (GH) deficiency may be associated with non-alcoholic fatty liver disease (NAFLD). Since the relationships among GH, IGF-1, IGFBP-3, and development of NAFLD without hypopituitarism are unclear, we examined the role of these hormones in the development of NAFLD based on clinical, laboratory and liver histology data. Patients and methods A total of 55 consecutive patients (20 males and 35 females) with NAFLD. Results Aspartate amino transferase (AST), AST/ALT, platelet count and IGF-1, levels were significantly associated with differences in fibrosis, since these variables differed between stage 0–1 and stage 2–3 NAFLD. In multivariate analysis, platelet count (P = 0.0223, relative risk (RR), 5.899; 95% confidence interval (CI), 1.288–27.017), and IGF-1 (P = 0.0363, RR, 4.568; 95% CI, 1.101–18.945) showed significant associations with stage 2–3 NAFLD. Additionally, hyaluronic acid levels had a negative relationship with IGF-1 and the IGF-1/IGFBP-3 ratio. There was no relationship of fibrosis with GH level, but decreased GH (P = 0.0414, RR, 0.199; 95% CI, 0.042–0.989) was significantly associated with steatosis of stage 2–3. Low GH/IGF-1 and GH/IGFBP-3 ratios were found in advanced steatosis. Conclusion GH, IGF-1 and IGFBP-3 are associated with hepatic fibrosis and steatosis in NAFLD. Low levels of IGF-1 might be associated with fibrosis while low level of GH with hepatic steatosis.     

Serum levels of the low molecular weight form of insulin-like growth factor binding protein in healthy subjects and patients with growth hormone deficiency, acromegaly and anorexia nervosa

The low molecular weight form of insulin-like growth factor binding protein (35 kD IGFBP), determined in serum by radioimmunoassay during non-fasting conditions, was high at birth and declined with increasing age during childhood and adolescence (N = 149). Inverse correlation was found between chronological age and 35 kD IGFBP values (r = -0.61, P less than 0.001) during childhood and adolescence, but no age dependency was found in adult subjects aged 20-66 years (N = 73). The mean and 95% confidence limits of immunoreactive 35 kD IGFBP were 34 micrograms/l and 15-79 micrograms/l, respectively, in healthy adults (N = 73) in whom the blood samples were drawn after a one-night fast. The mean level of the 35 kD IGFBP in patients with acromegaly (19 micrograms/l, N = 23) was decreased by 50% in comparison with healthy adults, whereas a 2-fold elevation of the mean levels was found in both anorexia nervosa patients (70 micrograms/l, N = 13) and adult patients with GH deficiency (69 micrograms/l, N = 22). In patients with anorexia nervosa, the 35 kD IGFBP levels were inversely related to the body mass index (r = -0.65, P less than 0.02).     

Elevated serum levels of free insulin-like growth factor I in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common cause of anovulation in women. Previous studies suggest that the pathogenesis of PCOS may involve interrelated abnormalities of the insulin-like growth factor (IGF) and ovarian steroidogenesis systems. We investigated this hypothesis in fasting serum samples from 140 women with PCOS (age, 27.4 +/- 0.4 yr; body mass index, 26.3 +/- 0.5 kg/m2; mean +/- SEM). IGF-related parameters were also studied in a group of normoovulatory women (n = 26; age, 26 +/- 4 yr; body mass index, 23.6 +/- 4.3 kg/m2). For the PCOS group, the mean testosterone (T) level was 2.5 +/- 0.1 nmol/L, and it was significantly correlated with LH (r = 0.41; P < 10(-6)), estrone (r = 0.33; P = 0.016), estradiol (r = 0.18; P = 0.04), and androstenedione (AD; P < 10(-6)), but not with dehydroepiandrosterone sulfate (P = 0.71), a marker of adrenal steroidogenesis. T and AD were also related to total ovarian follicle number and ovarian size, as previously found with normoovulatory women (1). There were no differences between the PCOS subjects and the normoovulatory group for total IGF-I, IGF-II, or IGF-binding protein-3 (IGFBP-3). However, IGFBP-1 levels were significantly decreased in the PCOS group (1.0 +/- 0.2 vs. 7.3 +/- 1.1 ng/mL; P < 0.001) and were inversely correlated with serum insulin levels (r = -0.50; P < 10(-8)). Serum levels of free IGF-I (fIGF-I) were elevated (5.9 +/- 0.3 vs. 2.7 +/- 0.3 ng/mL; P < 0.001) in inverse relation with IGFBP-1 (r = -0.31; P = 0.046). Serum fIGF-I levels were related to total follicle number (r = - 0.35; P < 10(-4)) and to the ratio of sex hormone-binding globulin to T (r = -0.23; P = 0.009). However, these relationships were not independent of other variables. Despite the more than 2-fold elevation in fIGF-I levels, significant relationships between fIGF-I and markers of ovarian steroidogenesis (T, AD, estradiol, and estrone) could not be demonstrated. In conclusion, although we confirmed correlations between LH and hyperandrogenemia and have found abnormalities in the IGF system in a large cohort of PCOS subjects, a direct relationship between hyperandrogenism and the IGF system could not be shown. Previous studies suggest that elevated LH and hyperinsulinemia lead to excess ovarian androgen synthesis in PCOS and that the intraovarian IGF system is important for normal follicle development and may be important in the arrested state of follicle development in PCOS. However, the data presented in this cross-sectional study suggest that insulin-related changes in circulating IGFBP-1 and subsequent elevation of fIGF-I reflect insulin resistance and have little enhancing effects on ovarian steroidogenesis in this disorder.