Relationship between serum testosterone and sex hormone-binding globulin in adult men with intact or absent gonadal function

Serum levels of testosterone and sex hormone-binding globulin (SHBG) were determined in 80 apparently healthy men aged 25-85 years and in 23 patients with prostatic carcinoma (CAP) aged 60-75 years before and 6 months after orchidectomy. Serum levels of testosterone and SHBG were correlated positively in healthy men, in all subjects overall as well as within different age groups, and in CAP patients before, but not after, orchidectomy. These data are not consistent with the classical theory regarding SHBG regulation and also speak against an influence of SHBG binding on testosterone metabolism as a mechanism behind the observed positive association between testosterone levels and SHBG.     

性激素结合球蛋白与某些生殖系统疾病的相关性

性激素结合球蛋白(SHBG)是主要由肝细胞合成的一种多功能蛋白质,是运输性激素的重要载体,生理作用主要是运输性激素、调节性激素活性、降低性激素代谢清除速率、稳定血清中有活性的性激素水平,将性激素运输到靶组织。随着SHBG结构与功能、受体与信号传导、基因多态性研究的不断深入,许多生殖系统疾病与血清SHBG水平及其基因多态性有关。本文将对SHBG与生殖系统疾病的关联性研究作一综述。     

Reduction of testosterone availability to 5 alpha-reductase by human sex hormone-binding globulin in the rat ventral prostate gland in vivo

The present studies assess the effects of human sex hormone-binding globulin (SHBG) on the conversion of [3H]testosterone (T) into dihydrotestosterone (DHT) in rat ventral prostate gland in vivo using a constant aortic infusion technique. The DHT/T ratio was determined using two-dimensional thin-layer chromatography (TLC), and these results were confirmed with reverse-phase high-performance liquid chromatography. The prostatic gland DHT/T ratio was 2.1 +/- 0.4, 1.3 +/- 0.2, 0.24 +/- 0.02, or 1.1 +/- 0.2, following a 60 sec aortic perfusion of [3H]testosterone dissolved in either Krebs-Henselite buffer (KHB), 5 g/dl human serum albumin (HSA), human pregnancy serum (HPS), or heat inactivated HPS, respectively. Heat inactivation (60 degrees C, 60 min) selectively denatured SHBG in HPS. The distribution of [3H]testosterone in rat ventral prostate was examined with thaw-mount light in microscopic autoradiography. Following an aortic perfusion of [3H]testosterone in buffer alone, the radiolabeled steroid was uniformly distributed among the epithelial and stromal compartments. However, the [3H]steroid hormone was selectively sequestered in the stromal compartment following aortic perfusion of HPS. In conclusion, these studies demonstrate that human SHBG markedly restricts the availability of circulating testosterone to 5 alpha-reductase in the prostate gland in vivo and that the presence of SHBG in serum causes the selective sequestration of the steroid hormone within the stromal compartment of the gland in vivo.     

Serum estradiol and sex hormone-binding globulin and the risk of hip fracture in elderly women: the EPIDOS study.

It has been suggested that low serum 17beta-estradiol (E2) and sex hormone-binding globulin (SHBG) may predict hip fracture in postmenopausal women. We have investigated the predictive value of serum E2 and SHBG concentrations and urinary deoxypyridinoline (D-Pyr) and type I collagen breakdown products (CTX) in a large prospective cohort of 7,598 healthy elderly ambulatory women (EPIDOS study), aged 75 years or more. We performed a nested case control study, by matching 212 patients with incident hip fracture with 636 controls. Mean follow-up was 3.3 years (maximum, 4.9 years). Women having serum E2 below the limit of detection (3 pg/ml), that is, 2% of the population, were not at higher risk, with a relative hazard (RH) of 1.59 (95% CI = 0.45-5.55). Women having serum E2 below 5, 6, 7, or 8 pg/ml, in the lowest quartile, or below the median had no increased risk of hip fracture. In contrast, women having serum E2 in the highest quartile (i.e., > or = 10 pg/ml) were protected, with an RH of 0.66 (0.44-0.98) that did not remain significant after adjustment for weight (RH = 0.71 [0.47-1.06]). High serum SHBG values with different cut-offs tended to be associated with an increased risk of hip fracture. Women in the highest quartile had an RH of 2.5 (1.37-4.61), compared with those in the lowest quartile, that decreased markedly after adjustment for body weight (1.61 [0.99 -2.62]). The highest quartile of the ratio E2/SHBG, which is an index of free E2, was associated with a lower hip fracture risk (RH = 0.6 [0.4-0.91]) that was no longer significant after adjustment for weight. In contrast, urinary D-Pyr and CTX, when elevated above the upper limit of premenopausal values, were predictive of hip fracture, with an RH of 2.07 (1.49-2.9) and 1.67 (1.19-2.32), respectively, even after adjustment for body weight, serum E2, and SHBG. We conclude that in healthy elderly French women over 75 years of age, serum E2 and E2/SHBG in the highest quartile are associated with a lower risk of hip fracture and that this association is explained by a higher body weight. In addition, serum levels of E2 and SHBG do not account for the increased risk of hip fracture associated with high levels of bone resorption markers.     

Relationship of testosterone, sex hormone binding globulin, and calculated free testosterone to subsequent clinical progress in patients with carcinoma of the prostate treated with bilateral orchidectomy or estrogens

The concentration in serum of testosterone, sex hormone binding globulin (SHBG), and albumin has been measured, and from these measurements free testosterone has been calculated in 75 patients with carcinoma of the prostate treated with either bilateral orchidectomy, stilbestrol, or estramustine phosphate (Estracyt). After exclusion of 3 noncompliant patients, total testosterone did not differ significantly between treatments, but free testosterone was lower in estrogen-treated patients (5.9 +/- 0.9 (SEM) pmol/l, n = 28) compared with the orchidectomized patients (23 +/- 1.4 pmol/l, n = 44) (P less than 0.001); all of the estrogen-treated patients falling in the lower third of the range of the orchidectomized patients. Free testosterone did not change systematically during several years of treatment and there was no evidence of a rise with clinical deterioration. In the 33 patients with metastatic cancer treated with orchidectomy, the third with the lowest free testosterone or total testosterone showed a better survival over 2 years than the two-thirds with higher free or total testosterone; thereafter, the advantage was lost.     

Lower urinary-tract symptoms and testosterone in elderly men

OBJECTIVES: The objective was to examine the effects of testosterone administration on symptom scores of lower urinary tract symptoms (LUTS). METHODS: The literatures on the epidemiological association between the metabolic syndrome, erectile failure and (LUTS) were reviewed. RESULTS: In men with the metabolic syndrome and erectile failure, often lower-than-normal testosterone levels are found. This is less clear for men with LUTS, but the relationship between testosterone and LUTS might be indirect and based on the association of the metabolic syndrome with an overactivity of autonomic nervous system. This overactivity may play a key role in increasing the severity of LUTS above an intrinsic basal intensity that is determined by the genitourinary factors in aging men. Androgen receptors are present in the epithelium of the urethra and the bladder. Testosterone may play a role in the reflex activity of the autonomic nervous system in the pelvis, or may interact with postsynaptic non-genomic receptors suppressing detrusor activity. Human neurons in the wall of the bladder contain nitric oxide synthase. Similar to the penis, testosterone has an impact on nitric oxide synthase. CONCLUSIONS: Some studies investigating the effects of normalizing testosterone levels in elderly men have found a positive effect on variables of the metabolic syndrome and, simultaneously, on scores of the International Prostate Symptoms Score (IPSS) which is worthy of further investigation in randomized, controlled and sufficiently powered clinical trials.     

Sex hormones,sex hormone binding globulin,and vertebral fractures in older men

The association between sex hormones and sex hormone binding globin (SHBG) with vertebral fractures in men is not well studied. In these analyses, we determined whether sex hormones and SHBG were associated with greater likelihood of vertebral fractures in a prospective cohort study of community dwelling older men. We included data from participants in MrOS who had been randomly selected for hormone measurement (N = 1463, including 1054 with follow-up data 4.6 years later). Major outcomes included prevalent vertebral fracture (semi-quantitative grade ≥ 2, N = 140, 9.6%) and new or worsening vertebral fracture (change in SQ grade ≥ 1, N = 55, 5.2%). Odds ratios per SD decrease in sex hormones and per SD increase in SHBG were estimated with logistic regression adjusted for potentially confounding factors, including age, bone mineral density, and other sex hormones. Higher SHBG was associated with a greater likelihood of prevalent vertebral fractures (OR: 1.38 per SD increase, 95% CI: 1.11, 1.72). Total estradiol analyzed as a continuous variable was not associated with prevalent vertebral fractures (OR per SD decrease: 0.86, 95% CI: 0.68 to 1.10). Men with total estradiol values ≤ 17 pg/ml had a borderline higher likelihood of prevalent fracture than men with higher values (OR: 1.46, 95% CI: 0.99, 2.16). There was no association between total testosterone and prevalent fracture. In longitudinal analyses, SHBG (OR: 1.42 per SD increase, 95% CI: 1.03, 1.95) was associated with new or worsening vertebral fracture, but there was no association with total estradiol or total testosterone. In conclusion, higher SHBG (but not testosterone or estradiol) is an independent risk factor for vertebral fractures in older men.     

Assessment of sex hormone-binding globulin and osteocalcin in patients undergoing coronary artery bypass graft surgery

OBJECTIVE: To determine sex hormone-binding globulin (SHBG) and osteocalcin (OC) levels in patients undergoing coronary artery bypass graft surgery to clarify the status of peripheral thyroid metabolism and to correlate SHBG and OC with thyroid hormones and adverse postoperative events. DESIGN: Prospective study. SETTING: University medical center. PARTICIPANTS: Fifty randomly selected patients undergoing coronary artery bypass graft surgery. INTERVENTIONS: On the morning of surgery before induction of anesthesia; 30 minutes after cross-clamping of the aorta; 2 hours and 6 hours after aortic cross-clamp removal; and on the first, second, third, and seventh postoperative mornings, blood samples were drawn and analyzed for OC, SHBG, triiodothyronine (tT3), free T3 (fT3), thyroxine (tT4), free T4 (fT4), thyroid-stimulating hormone, and thyroid-binding globulin. Adverse postoperative events were recorded. MEASUREMENTS AND MAIN RESULTS: Mean tT3 and fT3 decreased on average by 35% and 18% but remained within the normal range perioperatively. Similarly, mean SHBG and OC remained within the normal range. More than half of the patients investigated (60%) had OC concentrations below the normal range. Patients with pathologically decreased tT3 (n = 6) and tT4 (n = 16) intraoperatively and postoperatively had SHBG and OC concentrations similar to those in patients with normal tT3 and tT4 levels. Patients with postoperative complications had significantly lower OC levels preoperatively and on the first postoperative morning than those with an uneventful postoperative recovery. CONCLUSION: Despite significant intraoperative and postoperative decreases in levels of thyroid hormones, low T3 syndrome was rare in this patient population. Unchanged concentrations of SHBG and OC in patients with pathologically decreased tT3 or tT4 suggest normal local thyroid exposure at the tissue sites in these patients. OC may act as a predictor for postoperative outcome.     

Evidence for association of sex hormone-binding globulin and androgen receptor genes with semen quality

The roles of androgen receptor AR(CAG)n gene polymorphisms and sex hormone-binding globulin SHBG(TAAAA)n gene polymorphisms on semen quality were studied. One hundred fourteen men were included in the study: 85 with normal sperm count and 29 oligospermic. The genotype analysis, on DNA extracted from spermatozoa, revealed five SHBG(TAAAA)n alleles with 6–10 repeats and 18 AR(CAG)n alleles with 12–32 repeats. The SHBG allelic distribution showed that in men with normal sperm count and motility, those with short SHBG alleles had higher sperm concentration than men with long SHBG alleles ( P  = 0.039). As concerns AR(CAG)n polymorphisms, men with short AR alleles had lower sperm motility compared to those with long AR alleles ( P  < 0.001) in both total study population and normal sperm count men. The synergistic effect analysis of the two polymorphisms revealed an association between sperm motility ( P  = 0.036), because of the effect of AR(CAG)n polymorphism on sperm motility. In conclusion, long AR alleles were found to be associated with higher sperm motility, while short SHBG alleles were associated with higher sperm concentration, supporting the significance of these genes in spermatogenesis and semen quality.     

Research progress on the relationship between sex hormone-binding globulin and male reproductive system diseases

Sex hormone-binding globulin, also known as testosterone–estradiol-binding globulin, is a multifunctional protein synthesised by hepatocytes. Sex hormone-binding globulin specifically binds and transports sex hormones to regulate plasma bioactive sex hormone levels and affects their bioavailability. As male sex hormone expression is dominated by testosterone, the binding of sex hormone-binding globulin with testosterone leads to the reduction in bioavailable testosterone, which cannot fulfil its physiological roles, thereby resulting in male infertility, erectile and gonadal dysfunction, prostate cancer and other male reproductive system diseases. Sex hormone-binding globulin may be involved in the pathogenesis of male reproductive system diseases, seriously affecting the quality of life of men. In this article, we review the association between sex hormone-binding globulin and male reproductive system diseases.     

The effect of exogenous testosterone on total and free prostate specific antigen levels in healthy young men

Purpose

We evaluated the effect of exogenous testosterone administration on serum total and free prostate specific antigen (PSA) in healthy young men.

Materials and Methods

Nine volunteers received either 100, 250 or 500 mg. testosterone by intramuscular injection each week for 15 weeks. Blood was drawn every other week for 28 weeks and at week 40. Serum total and free PSA, and total and free testosterone were measured and compared to baseline values.

Results

Significant elevations in total and free testosterone occurred but no significant change in serum total and free PSA was detected.

Conclusions

Serum PSA is not responsive to elevated serum testosterone levels in healthy young men. PSA metabolism in the normal prostate is unclear but our findings may have implications for differentiation of pathological conditions of the human prostate.     

Competitive binding assay with dextran-coated charcoal for measurement of sex hormone-binding globulin in breast cancer

A simplified method for determination of the binding capacity of the sex hormone binding globulin (SHBG-BC) in human serum and its clinical application are described. This method is based on the estimation of the amount of estradiol (E2) bound with SHBG which possessed binding sites with it. After removing the endogenous steroids from the serum-samples by adsorption with dextran coated charcoal, the value of SHBG-BC increased by 18% compared with that of untreated serum. In 48 patients of various ages with breast cancer, the value of SHBG-BC (34.6 +/- 11.1; mean +/- S.D.), expressed as pico mole per 1 ml serum, did not differ significantly from that of 12 healthy control women (29.6 +/- 6.6). However, in postmenopausal women, the value of SHBG-BC in 24 patients with breast cancer (33.4 +/- 12.2) differed from that of 6 controls (26.1 +/- 4.9; p less than 0.05). In addition, estrogen receptors (ER) were measured by using gel-filtration method in cytosols from the tissue of breast cancer. The value of SHBG-BC in 15 ER-positive cases (40.4 +/- 10.1) was significantly higher than that in 13 ER-negative cases (29.3 +/- 8.7; p less than 0.01), but the value of SHBG-BC and ER did not run parallel completely.     

Sex hormone-binding globulin is a significant predictor of extracapsular extension in men undergoing radical prostatectomy

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Previous reports showed controversial evidence supporting the role of sex steroids, mainly testosterone, in the etiology and pathogenesis of prostate cancer (PCa). The bioavailability of sex steroids is significantly regulated by sex hormone–binding globulin (SHBG). In this context, SHBG levels have been shown to be significantly higher in PCa patients than in controls. Likewise, SHBG was reported to serve as an independent predictor for extra‐prostatic extension of tumour [defined as cancer (≥pT3) with capsular penetration, seminal vesicle involvement, or lymph node invasion (LNI)] in patients with clinically localized PCa. The presence of non–organ‐confined disease is significantly associated with higher biochemical recurrence rates. This study provides novel evidence that SHBG might serve as a significant multivariate predictor of extra capsular extension (ECE) in PCa patients submitted to radical prostatectomy, after accounting for preoperative clinically available variables such as patient’s age, total PSA, clinical stage, biopsy Gleason sum, and BMI. Moreover, a clinical cut‐off for circulating SHBG allows using this easily quantifiable molecule as a novel clinical parameter in PCa patients.

OBJECTIVE

? To examine the association between sex hormone‐binding globulin (SHBG) and extracapsular extension (ECE) in men treated with retropubic radical prostatectomy (RRP).

PATIENTS AND METHODS

? Preoperative serum SHBG levels were measured in a cohort of 629 consecutive European Caucasian men [mean (range) age of 64 (41–78) years] who underwent RRP. ? No patient received any hormonal neoadjuvant treatment. SHBG levels were measured the day before RRP (08:00–10:00 hours) in all cases at the same laboratory. ? Logistic regression models tested the association between predictors [including age, prostate‐specific antigen (PSA) level, clinical stage, biopsy Gleason sum, body mass index (BMI), and SHBG] and ECE. ? Combined accuracy of predictors was tested in regression‐based models predicting ECE at RRP. SHBG was included in the model both as a continuous and categorized variable (according to the most informative threshold level of 30 nmol/L).

RESULTS

? In all, 92 patients (14.6%) had ECE. The mean (standard deviation; median) serum SHBG levels were significantly higher in men with ECE compared with those with no ECE at 41.1 (14.7; 37.5) vs 36.4 (16.7; 34) nmol/L (P= 0.007; 95% confidence interval ?8.00, ?1.29). ? Univariate analyses indicated that continuously coded SHBG was significantly [odds ratio (OR) 1.01; P= 0.03] associated with ECE, with a predictive accuracy of 60.1%. ? At multivariate analyses, both continuous (OR 1.01; P= 0.03) and categorical SHBG (OR 3.22; P < 0.001) were significantly associated with ECE, after accounting for age, PSA level, clinical stage, biopsy Gleason sum, and BMI. ? Addition of continuously coded SHBG slightly increased the predictive accuracy of the base model based on clinically established predictors from 63.3% to 65.5% (2.0% gain; P= 0.48). ? In contrast, a model based on categorized‐SHBG showed bootstrap‐corrected predictive accuracy of 68.4% (5.1% gain; P= 0.044).

CONCLUSION

? This study shows that SHBG might serve as a significant multivariate predictor of ECE in men with prostate cancer that undergo RRP.     

性激素结合球蛋白检测在评价多囊卵巢综合征治疗中的意义

目的探讨性激素结合球蛋白(SHBG)检测在评价治疗多囊卵巢综合征(PCOS)不育患者中的意义。方法将533例PCOS不育患者按体重指数(BMI)分为非肥胖组(424例)和肥胖组(109例)并再按是否存在胰岛素抵抗(IR)分为四组。A组:非肥胖无IR组(162例)、B组:非肥胖IR组(262例)、C组:肥胖无IR组(42例)、D组:肥胖IR组(67例)。测定黄体生成素(LH)、卵泡刺激素(FSH)、雌二醇(E_2)、总睾酮(T)、泌乳素(PRL)、SHBG、血糖(FBG)和胰岛素(FINS)水平,计算游离雄激素指数(FAI)及稳态模型指数(HOMA-IR)。A组、C组予达英-35;B组、D组予达英-35+盐酸二甲双胍,均治疗3月后复查各指标。停药后给予枸橼酸氯米芬(克罗米芬,CC)+人绝经期促性腺激素(HMG)促排卵治疗。比较各组排卵及妊娠情况。结果四组治疗后FAI均较治疗前降低,SHBG较治疗前升高差异有显著性;四组治疗后LH、LH/FSH比值、T较治疗前降低差异有显著性;但A组HOMA-IR、FINS较治疗前升高差异有显著性,B、D组HOMA-IR、FINS较治疗前降低差异有显著性。促排卵结果显示治疗后排卵率非肥胖组高于肥胖组(85.60%vs 68.69%,P0.01),两组治疗后有排卵患者SHBG较无排卵患者升高,FAI较无排卵患者降低;非肥胖组LH、LH/FSH比值、FINS降低(P0.05),而肥胖组FINS、HOMA-IR则降低(P0.05)。妊娠结局比较:非肥胖组和肥胖组妊娠分娩患者治疗后T、FAI、FINS、HOMA-IR较自然流产患者降低,SHBG升高(P0.05);此外肥胖组妊娠分娩患者治疗后BMI较自然流产患者降低。结论无论肥胖还是非肥胖的PCOS患者,无论是否存在胰岛素抵抗,SHBG及FAI均可作为评价治疗是否有效的指标之一,可提示促排卵治疗及妊娠结局。因此在PCOS患者治疗中检测SHBG及FAI能指导临床用药,降低流产率,对优生优育有重要指导意义。     

Sex hormone-binding globulin, estradiol, and bone turnover markers in male osteoporosis

The role of estrogen deficiency in male osteoporosis is still under discussion. One hundred five subjects, 65 of them suffering from osteoporosis (mean age, 53.9 years) and 40 age-matched controls were studied. Osteoporosis was defined by a T score < −2.5 in the lumbar spine or at the femoral neck. Forty-one (63.1%) of the subjects had a history of low-energy fractures, involving vertebrae in 33 cases (50.8%). Osteoporosis was considered to be idiopathic in 33 subjects (50.8%) for whom no etiology could be found. We measured levels of total estradiol (pg/ml, with a detection threshold of 4 pg/ml), total testosterone (ng/ml), and their carrier protein, that is, sex hormone-binding globulin (SHBG, pmol/ml). Various markers of bone remodeling were also measured. Two of them provide an estimate of bone formation—osteocalcin (OC) and bone alkaline phosphatase (BAP). Two others evaluate bone resorption—procollagen type I C-terminal telopeptide (ICTP) and serum C-telopeptide of type I collagen (sCTX).

There was no significant difference in estradiol levels between controls and osteroporosis patients. We did not find any significant correlation between estradiol levels and spinal bone mineral density (BMD) (r = 0.15, P > 0.05), and the relationship between estradiol levels and BMD at the femoral neck was weak (r = 0.25, P < 0.05). On the other hand, SHBG was significantly higher in the osteoporotic patients than in controls (P < 0.01). This difference persisted after adjustment for body mass index (BMI) and after exclusion of patients with a condition known to increase SHBG levels. Moreover, this carrier protein was negatively correlated with BMD at the femoral neck (r = −0.37, P < 0.01) and at the lumbar spine (r = −0.27, P < 0.05). SHBG also correlates strongly with sCTX (r = 0.37, P < 0.01). Finally, logistic regression analysis showed that serum SHBG concentration was significantly associated with the presence of fractures; the odds ratio of having a fracture was 2.04 [95% confidence interval (CI) 1.2–3.4, P < 0.01] for each increase of 1 standard deviation (SD) in the patient's SHBG level. The stronger relationship was nearly the same for the whole group and for patients with idiopathic osteoporosis.

This study therefore suggests that SHBG may play a key role in male patients with idiopathic or secondary osteoporosis. It shows that serum SHBG concentration is increased in middle-aged men with osteoporosis and is correlated with hip, spine BMD, and sCTX levels. Finally, our findings are in agreement with previous studies which suggest that serum SHBG is a new biological marker of fracture risk in men.     

Coffee and caffeine consumption in relation to sex hormone-binding globulin and risk of type 2 diabetes in postmenopausal women

OBJECTIVE

Coffee consumption has been inversely associated with type 2 diabetes risk, but its mechanisms are largely unknown. We aimed to examine whether plasma levels of sex hormones and sex hormone–binding globulin (SHBG) may account for the inverse association between coffee consumption and type 2 diabetes risk.

RESEARCH DESIGN AND METHODS

We conducted a case-control study nested in the prospective Women''s Health Study (WHS). During a median follow-up of 10 years, 359 postmenopausal women with newly diagnosed type 2 diabetes were matched with 359 control subjects by age, race, duration of follow-up, and time of blood draw.

RESULTS

Caffeinated coffee was positively associated with SHBG but not with sex hormones. Multivariable-adjusted geometric mean levels of SHBG were 26.6 nmol/l among women consuming ≥4 cups/day of caffeinated coffee and 23.0 nmol/l among nondrinkers (P for trend = 0.01). In contrast, neither decaffeinated coffee nor tea was associated with SHBG or sex hormones. The multivariable-adjusted odds ratio (OR) of type 2 diabetes for women consuming ≥4 cups/day of caffeinated coffee compared with nondrinkers was 0.47 (95% CI 0.23–0.94; P for trend = 0.047). The association was largely attenuated after further adjusting for SHBG (OR 0.71 [95% CI 0.31–1.61]; P for trend = 0.47). In addition, carriers of rs6259 minor allele and noncarriers of rs6257 minor allele of SHBG gene consuming ≥2 cups/day of caffeinated coffee had lower risk of type 2 diabetes in directions corresponding to their associated SHBG.

CONCLUSIONS

Our findings suggest that SHBG may account for the inverse association between coffee consumption and type 2 diabetes risk among postmenopausal women.Previous prospective studies have documented an inverse association between coffee consumption and type 2 diabetes risk (1,2), especially in women (2). Coffee intake may improve glucose tolerance via activation of energy metabolism and enhancement of insulin sensitivity and β-cell function (2,3)—although much of the molecular mechanism remains unknown. Previous cross-sectional studies have associated coffee intake with plasma levels of sex hormones or sex hormone–binding globulin (SHBG) (4,5). In addition, a large body of observational and experimental data has implicated the important roles of sex hormones in the development of type 2 diabetes (6–8). Notably, recent experiments indicate that SHBG not only regulates the biologically active fraction of sex hormones but may bind to its own receptors at the plasma membranes of a variety of cells, directly mediating intracellular signaling of sex hormones (9). More recently, prospective studies of men and women incorporating both genetic and phenotypic assessment of SHBG revealed a strong inverse association between SHBG levels and type 2 diabetes risk (10). However, no studies have comprehensively evaluated the interrelationships of coffee consumption in relation to sex hormones and SHBG with respect to type 2 diabetes risk. To examine whether and to what extent sex hormones or SHBG may account for the potential protective effect of coffee intake against type 2 diabetes, we analyzed data from a prospective case-control study of women. In particular, we evaluated the associations of coffee consumption with plasma levels of sex hormones and SHBG, as well as the direct association between coffee consumption and type 2 diabetes risk during a 10-year follow-up. Moreover, we investigated whether the association of coffee consumption with type 2 diabetes risk was attenuated by further adjusting for plasma sex hormones or SHBG. Finally, we examined whether coffee intake may interact with specific SHBG genotypes in affecting diabetes risk.     

Characteristics of sildenafil erections in healthy young men

Aim： To determine the effect of sildenafil citrate on the nocturnal penile erections （i.e. time to onset, the duration of erection, and the interval between first and second erections） of healthy young men. Methods： Twenty-two potent men, 23-29 years old, were recruited for the study. All subjects completed three sessions over consecutive nights using the RigiScan monitoring device （Dacomed, Minneapolis, USA）. After a first night of adaptation, night 2 records were their baseline values, and on night 3 they received 100 mg of sildenafil citrate. Statistical comparisons were done between the second and third night data. Results： The mean time to onset of the first erection with sildenafil citrate was （34 ± 18） min, whereas it was （74 ± 24） min （P 〈 0.001） without sildenafil citrate. The number of erections observed during the first 5 h after sildenafil citrate medication was 3.6 ± 0.5 in contrast to 2.4 ± 0.5 with no medica- tion （P = 0.001）. The interval between first and second erections was shorter with sildenafil citrate： （52 ± 26） min vs. （85 ± 34） min （P = 0.01）. The duration of the last erection was statistically significantly longer with the sildenafil citrate： （64 ± 33） min vs. （42 ± 28） min （P 〈 0.01）. Conclusion： Healthy young men achieved erection within 34 min after sildenafil citrate administration, which is shorter than the 1 h interval proposed by the manufacturer. The interval between the first and second erections was shorter and the duration of the last nocturnal erection was longer.     

Endogenous sex steroids and bone mineral density in healthy men

OBJECTIVE: To evaluate the role of endogenous sex steroids on bone mineral density (BMD) in healthy Turkish men. METHODS: Serum total testosterone (TT), free testosterone (FT), dehydroepiandrosterone sulfate and estradiol levels were assayed in 174 healthy men of 240 volunteers, aged 22-76 years. Dual-energy X-ray absorptiometry was used to measure the BMD (g/cm(2)) of lumbar spine, femoral neck and non-dominant proximal and distal radius-ulna sites. Linear regressions were conducted using each BMD site as the dependent variable and each sex steroid as the independent variable. Four models were run for each bone site and sex steroid; crude, age-adjusted, adjusted for age and body mass index (BMI), and adjusted for age, BMI and cigarette-smoking. RESULTS: The mean age and BMI of men enrolled in the study were 47.7 +/- 13.7 years and 26.9 +/- 3.6 kg/m(2). Log of FT was significantly associated with the BMD of distal forearm in all models analyzing the crude and adjusted effects. Dehydroepiandrosterone sulfate effect on BMD of proximal forearm came closer to the level of statistical significance when adjusted with age, BMI and cigarette-smoking. Estradiol and TT levels were not found to be associated with BMD of any sites measured. CONCLUSION: Among the endogenous sex steroids in men, predominantly FT seems to be one of the determinants of BMD. Therefore a decrease in serum levels of testosterone in aging male or secondary causes may negatively affect BMD.     

中老年男性血清睾酮与动脉粥样硬化的相关性研究

目的 :探讨中老年男性睾酮水平与动脉粥样硬化之间的相关性。方法:选取2012年10月至2013年3月40~75岁的广州男性居民413例作为研究对象,收集人口学资料、临床资料及身体测量指标,实验室检测性激素、血糖、血脂等指标,彩色多普勒超声诊断仪测定颈动脉内膜中层厚度(CIMT)。结果:以CIMT=0.9 mm作为切点将人群分为颈动脉硬化组与非硬化组,游离睾酮(FT)在两组间的中位数分别为57.41 pmol/L及59.72 pmol/L(P=0.005),总睾酮(TT)两组间未见差异。Spearman相关分析提示TT、FT与CIMT呈负相关,r分别为-0.126(P=0.011)和-0.188(P<0.01)。以四分位数点作为切点由低到高将FT分为Q1、Q2、Q3、Q4组,各组颈动脉硬化患病率分别为23.30%、13.46%、17.48%、7.77%(P for trend=0.008)。TT各组颈动脉硬化的患病率分别为17.48%、18.27%、16.50%、9.71%(P for trend=0.116)。多因素Logistic回归分析评估FT各组颈动脉硬化患病优势比(OR)提示,以Q4组作为对照,在校正了年龄、腰围、收缩压、糖基化血红蛋白的影响后,Q1组的患病风险明显增高(OR1=2.491,95%CI:1.01~6.149)。同样在TT的分组中采取Logistic回归分析,以Q4组作为对照,各组患病风险未见明显差异。结论:中国40岁以上男性,血清FT低下可能是动脉粥样硬化的危险因素。     

Postprandial triglyceride metabolism in elderly men with subnormal testosterone levels

Aim： To investigate the level of postprandial triglycerides （TG）s in elderly men with subnormal testosterone level （≤ 11.0 nmol/L） compared to men with normal testosterone level （〉 11.0 nmol/L）. Methods： Thirthy-seven men with subnormal and 41 men with normal testosterone aged 60-80 years underwent an oral fat load and TG levels were measured fasting and 2, 4, 6 and 8 h afterwards. Results： Men with subnormal testosterone had significantly higher body mass index （BMI） and waist circumference （P 〈 0.001） than men with normal testosterone. They had significantly higher area under curve （AUC, P = 0.037）, incremental area under curve （AUCi, P = 0.035） and TG response （TGR, P = 0.014） for serum-TG and significantly higher AUC （P = 0.023）, AUCi （P = 0.023） and TGR （P = 0.014） for chylomicron-TG compared to men with normal testosterone level. Adjusting for waist circumference erased the significant differences between the groups in postprandial triglyceridemia. Conclusion： Men with subnormal testosterone have increased postprandial TG levels indicating an impaired metabolism of postprandial TG-rich lipoproteins （TRL）, which may add to an unfavourable lipid profile and promote development of atherosclerosis.