Seasonal variation of estradiol, follicle stimulating hormone, and dehydroepiandrosterone sulfate in women and men

CONTEXT: Seasonal variation in daylight regulates reproduction in animals living at higher latitude, but the influence of season on the sex hormones in humans remains unclear. OBJECTIVE, DESIGN, AND PARTICIPANTS: A cross-sectional population-based study in Troms?, Norway (70 degrees N) included 1651 women and 1540 men aged 25-84 yr. Circulating total estradiol (and calculated free levels), FSH, and dehydroepiandrosterone sulfate (DHEAS) were measured between September 1994 and September 1995 and provided a unique opportunity to study effects of extreme seasonal variations in the daylight on hormone levels in an arctic population. MAIN OUTCOME MEASURE: Circulating total and free estradiol, FSH, and DHEAS were measured. RESULTS: Total and free estradiol showed differences between monthly means, with peak in June in postmenopausal women (P < 0.001), and in May in men (P = 0.002 and P < 0.001) by analysis of covariance. By cosinor analysis, a seasonal variation in total and free estradiol was evident in women (P = 0.02 and P = 0.03) and men (P = 0.004 and P = 0.001), but only 0.2-0.9% of the variation in total and free estradiol was explained by season. FSH and DHEAS showed no obvious seasonal variation in either sex. CONCLUSIONS: Seasonal variations should be considered while designing studies and interpreting results of estradiol measurements to avoid bias in comparative studies.     

雄激素及其受体与老年男性冠状动脉粥样硬化性心脏病的相关性研究

目的 观察老年男性冠状动脉粥样硬化性心脏病(冠心病)患者性激素及雄激素受体水平的变化及相关性. 方法 横断面调查老年男性539例,其中健康人(对照组)400例,年龄62～92岁,平均(71.4±5.2)岁;冠心病患者139例,年龄60～88岁,平均(73.6±6.4)岁.测定总睾酮、游离睾酮、脱氢表雄酮硫酸酯(DHEAS)、性激素结合球蛋白(SHBG)、雌二醇、黄体生成素(LH)、卵泡刺激素(FSH)水平,同时采用流式细胞术检测外周血雄激素受体(AR)水平. 结果 老年男性冠心病患者DHAES、总睾酮、SHBG、游离睾酮、AR荧光强度均低于对照组(均为P<0.01),而FSH、E2高于对照组(均为P<0.01).年龄与总睾酮、游离睾酮呈负相关(r分别为-0.28、-0.17,P<0.01和P<0.05);与E2、SHBG呈正相关(r分别为0.33、0.14,P<0.01和P<0.05).AR荧光强度与收缩压呈负相关(r=-0.12,P<0.01).Logistic回归分析显示,总睾酮(OR=1.065,95%CI:1.012～1.121,P<0.05)、SHBG(OR=0.994,95%CI:0.990～0.998,P<0.01)和AR(OR=0.971,95%CI:0.956～0.986,P<0.01)与老年男性冠心病相关. 结论 老年男性冠心病患者存在低水平的DHEAS、总睾酮、SHBG、游离睾酮、AR,同时存在高水平的FSH、E2;低水平总睾酮、SHBG和AR可能是老年男性冠心病独立的危险因素.     

Relationship between endogenous sex hormone levels, lipoproteins and coronary atherosclerosis in men undergoing coronary angiography

This study was carried out in order to investigate the relationship between endogenous sex steroid hormones and coronary artery disease (CAD). Three hundred and thirty-seven men undergoing coronary angiography were enrolled in the study. Total testosterone, estradiol, free testosterone levels in men with CAD (n = 213) were compared to those of men without CAD (n = 124). No significant differences were found in the serum concentrations of estradiol, total and free testosterone and serum lipid profile between the two groups. Total and free testosterone were negatively (p < 0.05 to p < 0.001) and estradiol was positively (p < 0.05) correlated with age in both groups. Total cholesterol and low-density-lipoprotein levels were positively correlated with the level of free testosterone (r = 0.221, p < 0.01; r = 0.173, p < 0.05, respectively), and high-density-lipoprotein levels were negatively correlated with total testosterone in patients with CAD (r = -0.166, p < 0.05). The results of this study do not support the role of sex steroid hormones in CAD. However, the relationship between sex steroids and serum lipids needs further clarification.     

Endogenous sex steroid, GH and IGF-I levels in normal elderly men: relationships with bone mineral density and markers of bone turnover.

There are studies concerning the association among endogenous sex steroids, growth hormone (GH), insulin-like growth factor-I (IGF-I) and bone mineral density (BMD) in both men and women. However, little is known concerning the association of these parameters with markers of bone turnover in healthy elderly men. We studied the association of BMD (dual energy X-ray absorptiometry of spine, hip and forearm) and markers of bone turnover (bone-specific alkaline phosphatase, serum C-terminal propeptide of type I collagen, and serum osteocalcin reflecting formation, urine deoxypyridinoline and calcium excretion in relation to creatinine excretion reflecting resorption) with endogenous sex steroids, GH and IGF-I in 14 elderly normal men (age range 60-79 years). There was a negative correlation between age and dehydroepiandrosterone sulphate (DHEAS) (r=-0.60, p=0.022) and a positive correlation between GH and IGF-I (r=0.53, p=0.048). Serum estradiol concentrations correlated with BMD at distal 1/3 radius (r=0.41, p=0.1) and mid-radius (r=0.47, p=0.08), and negatively correlated with age (r=-0.45, p=0.09). There was no correlation of estradiol with bone turnover markers, testosterone, free testosterone, DHEAS, GH and IGF-I. Serum GH and IGF-I levels showed no correlation with BMD (all sites) and bone turnover markers. Serum total testosterone concentrations positively correlated with BMD at distal 1/3 radius (r=0.47, p=0.09), femoral neck (r=0.56, p=0.037) and Ward's triangle (r=0.49, p=0.07). These data suggest that serum estradiol and testosterone levels are associated with BMD in elderly men, possibly indicating their contribution to skeletal maintenance in old age. However, correlations of IGF-I, GH and DHEAS with BMD and bone turnover markers are lacking in the group studied.     

Low serum testosterone and high serum estradiol associate with lower extremity peripheral arterial disease in elderly men. The MrOS Study in Sweden.

OBJECTIVES: This study sought to determine whether serum levels of testosterone and estradiol associate with lower extremity peripheral arterial disease (PAD) in a large population-based cohort of elderly men. BACKGROUND: Few studies have explored the relationship between serum sex steroids and lower extremity PAD in men. METHODS: The Swedish arm of the MrOS (Osteoporotic Fractures in Men) study (n = 3,014; average age 75.4 years) assessed ankle-brachial index (ABI) and defined lower extremity PAD as ABI <0.90. Radioimmunoassay measured serum levels of total testosterone, estradiol, and sex hormone-binding globulin, and we calculated free testosterone and free estradiol levels from the mass action equations. RESULTS: A linear regression model including age, current smoking, previous smoking, diabetes, hypertension, body mass index, free testosterone, and free estradiol showed that free testosterone independently and positively associates with ABI (p < 0.001), whereas free estradiol independently and negatively associates with ABI (p < 0.001). Logistic regression analyses showed that free testosterone in the lowest quartile (vs. quartiles 2 to 4; odds ratio [OR] 1.65, 95% confidence interval [CI] 1.22 to 2.23, p = 0.001) and free estradiol in the highest quartile (vs. quartiles 1 to 3; OR 1.45, 95% CI 1.09 to 1.94, p = 0.012) independently associate with lower extremity PAD. CONCLUSIONS: This cross-sectional study shows for the first time that low serum testosterone and high serum estradiol levels associate with lower extremity PAD in elderly men. Future prospective and interventional studies are needed to establish possible causal relationships between sex steroids and the development of lower extremity PAD in men.     

性激素和雄激素受体与老年男性糖尿病的相关性研究

目的 研究老年男性糖尿病患者的性激素和雄激素受体水平的变化,探讨老年男性糖尿病患者性激素和雄激素受体与糖尿病的相关性. 方法横断面调查老年男性492例,其中健康对照组104例,平均年龄(71.4±5.2)岁;非糖尿病对照组259例,平均年龄(71.5±5.0)岁;糖尿病组129例,平均年龄(73.0±6.3)岁.测定总睾酮(TT)、游离睾酮(FT)、脱氢表雄酮硫酸酯(DHEAS)、性激素结合球蛋白(SHBG)、雌二醇(E_2)、黄体生成素(LH)、卵泡刺激素(FSH)水平,采用流式细胞术检测外周血白细胞雄激素受体(AR)水平. 结果糖尿病组TT水平显著低于两对照组,分别为(17.1±6.1)、(15.8±6.0)nmol/L和(13.8±4.7)nmol/L(P<0.01),FT、SHBG、AR阳性率、AR荧光强度健康对照组、非糖尿病对照组和糖尿病组3组间呈下降趋势.但差异无统计学意义.多元回归分析町见TT、E_2,E_2/T,SHBG与血糖水平呈负相关;SHBG与糖尿病病程呈正相关.TT和AR阳性率与糖尿病病程呈负相关.Logistic多元同归分析示年龄、腰臀围比、FSH、SHBG、AR阳性率是糖尿病的危险因素. 结论低水平的TT、SHBG和AR可能是糖尿病的危险因素,在老年男性糖尿病的发生和发展中起到一定作用.     

Dehydroepiandrosterone secretion in healthy older men and women: effects of testosterone and growth hormone administration in older men

CONTEXT: Aging is associated with diminished gonadal steroid and GH/IGF-I axis activity; whether these changes contribute to the parallel declines of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) production is unknown, as are the effects of sex steroid and/or GH administration on DHEA and DHEAS production. OBJECTIVE: Our objective was to evaluate morning DHEAS concentrations and nocturnal DHEA secretory dynamics in healthy older men and women, before and after chronic administration of sex steroid(s) alone, GH alone, sex steroid(s) combined with GH, or placebo alone. DESIGN: We compared nocturnal DHEA secretory dynamics (2000 h to 0800 h, sampling every 20 min, analyzed by multiparameter deconvolution and approximate entropy algorithms) in healthy older (65-88 yr) men (n = 68) and women (n = 36), both before and after 26 wk of administration of sex steroid(s) alone [testosterone (T) in men or estrogen/progesterone in women], GH alone, sex steroid(s) combined with GH, or placebo alone. RESULTS: Morning concentrations of DHEAS were lower; nocturnal DHEA pulsatile production rate, burst frequency, and amplitude were higher; and half-life was shorter in women (P < 0.05). Nocturnal integrated DHEA concentrations, total production rate, and approximate entropy did not differ significantly by sex. Because of small treatment group sizes in women, only hormone intervention results in men are presented. In men, T and T plus GH administration significantly decreased nocturnal integrated DHEA but not morning DHEAS concentrations. GH alone exerted no significant effects on nocturnal DHEA secretion or morning DHEAS. CONCLUSIONS: Spontaneous nocturnal DHEA secretion is sexually dimorphic in healthy older individuals, and T administration decreases nocturnal DHEA secretion in older men. The clinical significance of sex steroid modulation of DHEA secretion in older persons remains to be elucidated.     

Effect of moderate alcohol consumption on plasma dehydroepiandrosterone sulfate, testosterone, and estradiol levels in middle-aged men and postmenopausal women: a diet-controlled intervention study

BACKGROUND: Moderate alcohol consumption is inversely associated with cardiovascular diseases. Changes in hormone levels might in part help explain the positive health effect. This study was performed to examine the effect of moderate alcohol consumption on plasma dehydroepiandrosterone sulfate (DHEAS), testosterone, and estradiol levels. METHODS: In a randomized, diet-controlled, crossover study, 10 middle-aged men and 9 postmenopausal women, all apparently healthy, nonsmoking, and moderate alcohol drinkers, consumed beer or no-alcohol beer with dinner during two successive periods of 3 weeks. During the beer period, alcohol intake equaled 40 and 30 g per day for men and women, respectively. The total diet was supplied and had essentially the same composition during these 6 weeks. Before each treatment there was a 1 week washout period, in which the subjects were not allowed to drink alcoholic beverages. At the end of each of the two experimental periods, fasting blood samples were collected in the morning. RESULTS: Moderate alcohol consumption increased plasma DHEAS level by 16.5% (95% confidence interval, 8.0-24.9), with similar changes for men and women. Plasma testosterone level decreased in men by 6.8% (95% confidence interval, -1.0- -12.5), but no effect was found in women. Plasma estradiol level was not affected. Serum high-density lipoprotein cholesterol level increased by 11.7% (95% confidence interval, 7.3-16.0), with similar changes for men and women. The overall alcohol-induced relative changes in DHEAS, testosterone, and estradiol correlated positively with the relative increase in high-density lipoprotein cholesterol (adjusted for the relative change in body weight); however, findings were only borderline significant for DHEAS and estradiol (r = 0.44, p = 0.08; r = 0.32, p = 0.21; and r = 0.46, p = 0.06, respectively). CONCLUSIONS: A protective effect of moderate alcohol consumption for cardiovascular disease risk may in part be explained by increased plasma DHEAS level.     

Testosterone and estradiol among older men

CONTEXT: Testosterone and estradiol levels decline with age in men. This change may affect multiple clinical outcomes, but there have been few reports of the distribution and correlates of testosterone and estradiol concentrations in elderly men. OBJECTIVE: The purpose of these studies was to assess sex steroid levels in a large cohort of older men. DESIGN: We conducted a cross-sectional cohort evaluation. SETTING: Community-dwelling men were studied at six academic medical centers in the United States. PARTICIPANTS: The Osteoporotic Fractures in Men Study is a prospective cohort of men aged at least 65 yr. In these studies, a randomly selected stratified subsample of 2623 participants was analyzed. MAIN OUTCOME MEASURES: We assessed levels of total and free testosterone and estradiol and SHBG. Results: Age was inversely associated with free testosterone and free estradiol levels (P for trend = 0.001 for both). Notably, at any age, there was substantial variation in levels of each hormone. Free testosterone levels were lower in men with greater body mass index, lower SHBG, and poorer self-reported health status and in those of Asian race. Free estradiol concentrations were lower in men with lower body mass index and higher SHBG levels. Free estradiol and free testosterone were modestly correlated (r = 0.20; P < 0.001), but at any level of free testosterone, there was considerable variation in free estradiol levels. CONCLUSIONS: This is the largest cohort of older men in which sex steroid levels are available, and it demonstrates that testosterone and estradiol, and their free fractions, tend to decline with age even among older men. However, substantial variation is also present. The relationships between sex steroid levels and their consequences in aging are likely to be complex.     

Effect of sex hormones on lipid peroxidation in women with polycystic ovary syndrome, healthy women, and men.

Recently, the influence of free radicals and lipid peroxides on many diseases, the effect of sex hormones on lipid peroxidation and antioxidant effects of estrogens have received considerable interest. In the present study we aimed to investigate the relationship between sex hormones and both lipid peroxidation and glutathione content in women with polycystic ovary syndrome (POS), in healthy women and in healthy men. We measured levels of lipid peroxides and sex hormones in plasma and levels of glutathione in erythrocytes of all cases. We evaluated the level of thiobarbituric acid reactive substances (TBARS) as an index of lipid peroxides and erythrocyte glutathione level as an index of antioxidant. We found that plasma levels of free testosterone, dehydroepiandrosterone sulfate (DHEAS) and estradiol significantly higher in the women with POS group than in the healthy women group. There was no significant difference in the levels of both plasma TBARS and erythrocyte glutathione, between women with POS group and healthy women group. Plasma DHEAS levels of healthy men and women with POS were similar. Plasma TBARS level was higher and erythrocyte glutathione level was lower in the healthy men group than in both the healthy women group and in the women with POS group. These data imply that testosterone has an oxidant effect. DHEAS which is an antioxidant, has a protective role in females with POS. Estrogens have an antioxidant effect but this action changes according to its dominant degradation pathway.     

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.     

血清性激素水平与老年男性认知功能相关性研究

目的探讨老年男性血清性激素水平与认知功能的关系。方法选取2008年12月至2009年12月间在第六人民医院老科就诊的老年患者62例采用简易智能量表（MMSE）评估认知功能,男性患者按照MMSE测定分数分为认知功能正常组（30例）与认知功能障碍组（32例）。采用化学发光法测定所有患者血清总睾酮（TT）和性激素结合球蛋白（SHBG）及雌二醇（E2）水平,并根据Vermeulen公式计算游离睾酮（FT）,比较两组患者TT、E2和FT水平的差异,并分析TT、E2、FT与老年认知功能的相关性。结果老年男性中认知功能障碍组的雌二醇[（20．88±5．10）pmol／L vs（27．00±9．61）pmol／LP〈0．05]、总睾酮[（4．52±1．88）mmol／L vs（6．42±1．84）mmol／L P〈0．05]、游离睾酮[（0．043±0．022）nmol／L vs（0．092±0．034）nmol／L P〈0．05]水平较认知功能正常组低（P〈0．05）。结论老年男性认知功能障碍可能与性激素水平下降相关。     

Effects of transdermal testosterone on cognitive function and health perception in older men with low bioavailable testosterone levels

BACKGROUND: Many men older than 50 years have bioavailable testosterone levels below the reference range for young adult men. The impact of the decreased androgen levels on cognition and health perception has received little attention. METHODS: Sixty-seven men (mean age 76 +/- 4 years, range 65-87) with bioavailable testosterone levels below 128 ng/dl (lower limit for adult normal range) were randomized to receive transdermal testosterone (2-2.5 mg patches/d) or placebo patches for 1 year. All men received 500 mg supplemental calcium and 400 IU vitamin D. Outcome measures included sex hormones [testosterone, bioavailable testosterone, sex hormone binding globulin (SHBG), estradiol, and estrone], cognitive tests (Digit Symbol, Digit Span, Trailmaking A and B), health perception (Medical Outcome Survey Short-form 36 or SF-36), lower extremity muscle strength and power, and calcium intake. RESULTS: Twenty-three men (34%) withdrew from the study; 44 men completed the trial. Bioavailable testosterone levels increased from 93 +/- 34 (SD) to 162 +/- 100 ng/dl (p <.002) at 12 months in the testosterone group (n = 24) while no change occurred in the control group (n = 20). While there was no change in estradiol levels in either group, estrone levels increased in the testosterone group (28 +/- 7 to 32 +/- 9 pg/dl, p =.017). Scores on the Digit Symbol test improved in both the testosterone and placebo groups. Scores on Trailmaking B improved in men treated with testosterone (p <.005), although the changes were not statistically different from the changes seen in the placebo group. Twelve-month scores on Trailmaking B for the entire group were correlated with 12-month testosterone levels (p =.016). Scores for health perception measured by SF-36 did not change significantly, though scores of mental and general health declined in both groups during the 12-month intervention. Twelve-month bioavailable testosterone scores were directly correlated with scores for physical role (p =.022), vitality (p =.036), and the physical composite score (p =.010). CONCLUSIONS: Transdermal testosterone treatment in men with low bioavailable testosterone levels does not impair and may improve cognitive function. Treatment did not improve health perception but this may have been due to the side effects of skin irritation suggested by similar reactions in both the testosterone and placebo groups.     

Relationship of leptin and sex hormones to bone mineral density in men

Sex hormones are strongly associated with bone mineral density (BMD) in adult humans. Leptin, a hormonal product of the OB gene, also appears to be associated with BMD, but results from previous studies are conflicting. Most of the studies in this area have been in women and apparently none have simultaneously analyzed the relationship of estradiol, testosterone, and leptin with BMD in healthy men. To address these issues, serum sex hormones, sex-hormone-binding globulin (SHBG), leptin, dehydroepiandrosterone sulfate (DHEAS), and insulin were measured in 50 apparently healthy men, 18-66 years of age. After controlling for age and body mass index (BMI), BMD correlated positively with estradiol ( p=0.007) and testosterone ( p=0.019), but negatively with leptin ( p=0.001). No significant correlations between BMD and SHBG, DHEAS, or insulin were observed. In multiple regression analysis with age, BMI, estradiol, testosterone, and leptin as the independent variables, only age ( p<0.05), BMI ( p<0.001), and leptin ( p=0.004) were significantly related to BMD. These findings suggest that in men, leptin may have an important negative relationship with BMD.     

Body mass index, waist circumference and waist to hip ratio and change in sex steroid hormones: the Massachusetts Male Ageing Study

OBJECTIVE: Cross-sectional data suggest that obesity, particularly central obesity, may be associated with decreased production of sex steroid hormones in men. However, longitudinal hormone data on men in relation to obesity status are limited. Previous studies have not consistently demonstrated whether sex steroids are associated specifically to body mass index or to measures of central obesity. Our objective was to examine the relation of obesity (body mass index > 30 kg/m2), and of central obesity (waist circumference > 100 cm or waist to hip ratio > 0.95) to longitudinal change in sex steroid hormones in men. DESIGN: Prospective follow-up of a population-based sample of men in Boston. PATIENTS: Nine hundred forty-two (942) men in the Massachusetts Male Ageing Study with complete anthropometry and hormone data at baseline (1987-1989, ages 40-70) and follow-up (1995-1997). MEASUREMENTS: Free and total testosterone (FT and TT), dehydroepiandrosterone sulphate (DHEAS), and sex hormone-binding globulin (SHBG) were assessed using standardized methods. Health behaviours and medical history were obtained by structured interview. Repeated measures regression was used to describe trends in steroid hormones and SHBG in relation to obesity status, adjusting for age, smoking, alcohol, comorbidities, and physical activity. RESULTS: Obesity was associated with decreased levels of total and free testosterone, and of SHBG at follow-up relative to baseline. For any given baseline concentration of TT, FT or SHBG, follow-up levels were lowest among men who remained obese or who became obese during follow-up. This was true for all three indices of obesity. Central adiposity was associated with lower DHEAS levels at follow-up, while elevated body mass index was not. CONCLUSIONS: Obesity may predict greater decline in testosterone and SHBG levels with age. Central adiposity may be a more important predictor of decline in DHEAS than is body mass index.     

Endogenous sex hormones in relation to age, sex, lifestyle factors, and chronic diseases in a general population: the Tromsø Study

The role played by endogenous hormones in many diseases makes it important to understand factors influencing their levels. This study examined the distribution of total and free estradiol, FSH, and dehydroepiandrosterone sulfate (DHEAS) by age and sex and associations of these hormones with body mass index (BMI), lifestyle factors, and chronic diseases. Plasma samples taken from 1555 men and 1952 women 25-84 yr of age in 1994-1995 Troms? Study were analyzed in 2001. Total estradiol increased with age among men (P < 0.001), with or without adjustment for BMI and lifestyle factors. FSH increased with age both in men (P < 0.001) as well as pre- (P < 0.001) and postmenopausal women (P = 0.01) after similar adjustment, and DHEAS decreased with age in both sexes (P < 0.001). With increasing BMI, free estradiol increased in men (P = 0.004), total and free estradiol increased in postmenopausal women (P < 0.001), and FSH decreased in men (P = 0.03) and postmenopausal women (P < 0.001). Men with chronic diseases had lower levels of DHEAS, compared with healthy men (P < 0.001). Smokers had higher DHEAS levels than nonsmokers. Further studies are needed to confirm these hormonal changes with age and disease.     

Visceral and subcutaneous adipose tissue assessed by magnetic resonance imaging in relation to circulating androgens, sex hormone-binding globulin, and luteinizing hormone in young men

CONTEXT: No large studies of young men have examined circulating sex hormones in relation to visceral and sc adipose tissues. OBJECTIVE: The aim of this study was to investigate the role of visceral adipose tissue and sc adipose tissue on circulating sex hormones and the impact of obesity on sex hormone reference intervals. DESIGN, SETTING, AND PARTICIPANTS: Population-based study of 783 Danish 20- to 29-yr-old men was performed using dual-energy x-ray absorptiometry in all men and magnetic resonance imaging in 406 men. MAIN OUTCOME MEASURES: Total, bioavailable, and free testosterone, dihydrotestosterone (DHT), total and bioavailable estradiol, SHBG, and LH were measured. RESULTS: In multiple regressions, visceral adipose tissue was an independent, inverse correlate of bioavailable and free testosterone. Subcutaneous adipose tissue correlated negatively with SHBG and positively with bioavailable estradiol adjusted for total testosterone. Both visceral adipose tissue and sc adipose tissue correlated inversely with total testosterone and DHT. Adjusting for SHBG, only visceral adipose tissue remained significantly correlated. Low total testosterone in viscerally obese men was not accompanied by increased LH. The androgen reference intervals were significantly displaced toward lower limits in obese vs. nonobese men (total testosterone: 8.5-29.3 vs. 12.5-37.6 nmol/liter; bioavailable testosterone: 6.1-16.9 vs. 7.6-20.7 nmol/liter; free testosterone: 0.23-0.67 vs. 0.29-0.78 nmol/liter; and DHT: 0.63-2.5 vs. 0.85-3.2 nmol/liter), whereas total estradiol (36.5-166 pmol/liter) and bioavailable estradiol (23.4-120 pmol/liter) reference intervals were not. In obese men, 22.9% had total testosterone less than 12.5 nmol/liter. CONCLUSIONS: Visceral adipose tissues correlate independently with bioavailable and free testosterone in young men. The inverse relationship between total testosterone and sc adipose tissue seems to be accounted for by variations in SHBG. The reference intervals for total testosterone, bioavailable testosterone, free testosterone, and DHT are displaced toward lower limits in obese men.     

Circulating androgen levels are associated with subclinical atherosclerosis and arterial stiffness in healthy recently menopausal women

Although increasing evidence supports an association between endogenous sex hormones and cardiovascular disease, the results still remain controversial. This study aims to examine the association between endogenous sex hormones and indices of vascular function and structure. Serum follicle-stimulating hormone, luteinizing hormone, estradiol, testosterone, sex hormone-binding globulin, dehydroepiandrosterone sulfate (DHEAS), and Δ4-androstenedione were measured in 120 healthy postmenopausal women aged 41 to 60 years. Possible associations with surrogate markers of subclinical atherosclerosis, arterial stiffness, and endothelial function were investigated. Indices of arterial structure included carotid and femoral intima-media thickness and atheromatous plaques presence. Indices of arterial function included flow-mediated dilation of the brachial artery, carotid-femoral pulse wave velocity (PWV), and augmentation index. Total testosterone and free androgen index (FAI) were the most important predictors of common carotid artery intima-media thickness (β = 0.376 and β = 0.236, P < .001 and P = .014, respectively). Similarly, FAI was the only significant independent predictor of PWV (β = 0.254, P = .027) after adjusting for age, smoking, body mass index, homeostasis model assessment of insulin resistance, and blood lipids. Free estrogen index showed a positive association with PWV, independently of age, smoking, and body mass index, but not of homeostasis model assessment of insulin resistance and blood lipids. Age-adjusted levels of DHEAS exhibited a significant independent negative association with measures of augmentation index. Follicle-stimulating hormone, luteinizing hormone, estradiol, sex hormone-binding globulin, and Δ4-androstenedione were not associated with any of the vascular parameters independently of traditional cardiovascular risk factors. Higher serum testosterone and FAI are associated with subclinical atherosclerosis in healthy recently menopausal women. This association is independent of traditional cardiovascular risk factors or insulin resistance. On the contrary, serum DHEAS exhibits a negative association with arterial stiffness.     

Bioavailable testosterone and depressed mood in older men: the Rancho Bernardo Study

A cross-sectional population-based study examined the association between endogenous sex hormones and depressed mood in community-dwelling older men. Participants included 856 men, ages 50-89 yr, who attended a clinic visit between 1984-87. Total and bioavailable testosterone, total and bioavailable estradiol, and dihydrotestosterone levels were measured by radioimmunoassay in an endocrinology research laboratory. Depressed mood was assessed with the Beck Depression Inventory (BDI). Levels of bioavailable testosterone and bioavailable estradiol decreased with age, but total testosterone, dihydrotestosterone, and total estradiol did not. BDI scores increased with age. Low bioavailable testosterone levels and high BDI scores were associated with weight loss and lack of physical activity, but not with cigarette smoking or alcohol intake. By linear regression or quartile analysis the BDI score was significantly and inversely associated with bioavailable testosterone (both Ps = 0.007), independent of age, weight change, and physical activity; similar associations were seen for dihydrotestosterone (P = 0.048 and P = 0.09, respectively). Bioavailable testosterone levels were 17% lower for the 25 men with categorically defined depression than levels observed in all other men (P = 0.01). Neither total nor bioavailable estradiol was associated with depressed mood. These results suggest that testosterone treatment might improve depressed mood in older men who have low levels of bioavailable testosterone. A clinical trial is necessary to test this hypothesis.