Correlations between serum testosterone, estradiol, and sex hormone-binding globulin and bone mineral density in a diverse sample of men

CONTEXT: The relationship between hormones and bone mineral density (BMD) in men has received considerable attention. However, most studies have been conducted in homogenous populations, and it is not known whether differences in hormones impact racial and ethnic differences in BMD. OBJECTIVE: Our objective was to examine associations of testosterone, estradiol, and sex hormone-binding globulin (SHBG) with BMD in a racially and ethnically diverse population. DESIGN: This was a population-based, observational survey. PARTICIPANTS: A total of 976 Black, Hispanic, and white randomly selected men ages 30-79 yr from the Boston Area Community Health/Bone Survey were included. OUTCOME: BMD at the hip, wrist, and spine were calculated. RESULTS: The mean age of the sample was 46.7 +/- 12.4 yr. BMD levels were highest in black men, followed by Hispanic and then white men. Associations between hormones and BMD were consistent across racial and ethnic groups. Total and free testosterone was not correlated with BMD in age- or multivariate-adjusted models. SHBG was inversely correlated with total hip and ultradistal radius BMD after age adjustment, but not with multivariate adjustment for age, lean mass, fat mass, physical activity, self-rated health, and smoking. Total and free estradiol levels were positively and significantly correlated with femoral neck and total hip BMD, even with multivariate adjustment (partial correlations ranged between 0.11 and 0.16). However, estradiol levels failed to account for racial and ethnic differences in hip BMD. CONCLUSIONS: In our diverse population, neither serum total nor free testosterone levels were associated with BMD. Correlations between BMD and estradiol were significant but did not appear to account for any of the observed racial and ethnic differences in BMD. These findings suggest that differences in hormone levels are not a major contributor to the observed differences in BMD between Black, Hispanic, and white men.     

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.     

Reproductive hormones in the early menopausal transition: relationship to ethnicity,body size,and menopausal status

We measured serum reproductive hormone concentrations in a community-based, multiethnic population of premenopausal and early perimenopausal women to determine whether there are ethnic differences in hormones that can be explained by host factors. We studied 2930 participants in the Study of Women's Health Across the Nation who were aged 42-52 yr and self-identified as African-American (27.6%), Caucasian (47.1%), Chinese (7.4%), Hispanic (8.8%), or Japanese (9.0%) at 7 clinical sites. Outcome measures from this baseline assessment of a longitudinal study were serum estradiol (E2), FSH, testosterone (T), dehydroepiandrosterone sulfate, and SHBG concentrations and calculated estimates of free steroid availability, free testosterone index, and free E2 index from serum collected primarily in the early follicular phase of a spontaneous menstrual cycle. The primary explanatory variables were race/ethnicity, menopausal status, age, body mass index, day of the cycle, smoking, alcohol use, and physical activity. Chinese women had lower unadjusted E2 and SHBG levels, and Hispanic women had lower unadjusted T levels than other ethnic groups. Unadjusted serum FSH levels did not differ by race/ethnicity. E2 levels adjusted for host characteristics, particularly body size, did not differ by race/ethnicity. Adjusted FSH levels were higher, and adjusted T levels were lower in African-American and Hispanic women. Serum E2 and FSH concentrations were highly variable. Serum FSH levels, but no other hormone concentrations, were positively correlated with menopausal status. Serum dehydroepiandrosterone sulfate levels were negatively correlated with age, but not menopausal status. All hormone concentrations were significantly correlated with body mass index. We conclude that serum sex steroid, FSH, and SHBG levels vary by ethnicity, but are highly confounded by ethnic disparities in body size.     

Reported condom use and condom use difficulties in street outreach samples of men of four racial and ethnic backgrounds

The epidemiology of the HIV/AIDS epidemic in the United States has focused research attention on lesbian, gay, bisexual and transgendered communities as well as on racial and ethnic minorities. Much of that attention has, however, been focused on specific racial and ethnic groups, and specific sexual minorities. We report on the results of a study that examined the association between condom use and partnership types among men from four major racial/ethnic groups. Self-reported data on sexual identity (homosexual, bisexual, and heterosexual) and condom use in the past three months were collected from 806 African Americans, Hispanic, Asian, and white men intercepted in public places in Houston, TX. Data indicated that condom use was lowest in African Americans and Hispanic men, bisexual men reported the highest levels of use, with heterosexual men reporting the lowest use. African Americans and Hispanic men reported generally that it was very difficult to use a condom during sexual contact, although the patterns for self-identified homosexual, heterosexual, and bisexual men varied across race/ethnicity. Homosexual African American men reported the least difficulty, and white homosexual men the most difficulty compared with heterosexual and bisexual peers. For homosexually identified men, there were considerable differences across race/ethnicity in the proportion of partners who never or rarely disagreed to use condoms, with Asians disagreeing least, and African Americans most. Within racial/ethnic groups, the levels of condom use and difficulty were similar for male and female partners, suggesting that it is sexual identity, rather than partner gender, that has impacted condom-use messages. These data suggest that racial/ethnic targeting of condom use is likely to be most efficacious in increasing condom use in men.     

Prevalence of symptomatic androgen deficiency in men

CONTEXT: Despite recognition that androgen deficiency in men should be defined according to biochemical and clinical criteria, most prevalence estimates are based on low testosterone levels alone. OBJECTIVE: The objective of this study was to examine the association between symptoms of androgen deficiency and low total and calculated free testosterone levels and estimate the prevalence of symptomatic androgen deficiency in men. DESIGN: This study was a population-based, observational survey. PARTICIPANTS: A total of 1,475 Black, Hispanic, and white men, between the ages of 30-79 yr, with complete data on testosterone, SHBG, and symptoms of androgen deficiency, and who are not taking medications that impact sex steroid levels were randomly selected from the Boston Area Community Health Survey. OUTCOME: Outcomes were measured as symptomatic androgen deficiency, defined as low total (<300 ng/dl) and free (<5 ng/dl) testosterone plus presence of low libido, erectile dysfunction, osteoporosis or fracture, or two or more of following symptoms: sleep disturbance, depressed mood, lethargy, or diminished physical performance. RESULTS: Mean age of the sample was 47.3 +/- 12.5 yr. Approximately 24% of subjects had total testosterone less than 300 ng/dl, and 11% of subjects had free testosterone less than 5 ng/dl. Prevalence of symptoms were as follows: low libido (12%), erectile dysfunction (16%), osteoporosis/fracture (1%), and two or more of the nonspecific symptoms (20%). Low testosterone levels were associated with symptoms, but many men with low testosterone levels were asymptomatic (e.g. in men 50+ yr, 47.6%). Crude prevalence of symptomatic androgen deficiency was 5.6% (95% confidence interval: 3.6%, 8.6%), and was not significantly related to race and ethnic group. Prevalence was low in men less than 70 yr (3.1-7.0%) and increased markedly with age to 18.4% among 70 yr olds. Projection of these estimates to the year 2025 suggests that there will be as many as 6.5 million American men ages 30-79 yr with symptomatic androgen deficiency, an increase of 38% from 2000 population estimates. CONCLUSIONS: Prevalence of symptomatic androgen deficiency in men 30 and 79 yr of age is 5.6% and increases substantially with age. The aging of the U.S. male population will cause a large increase in the burden of symptomatic androgen deficiency. Future work should address the clinical significance of low testosterone levels in asymptomatic men.     

Laboratory abnormalities at the onset of treatment of end-stage renal disease: are there racial or socioeconomic disparities in care?

BACKGROUND: Laboratory abnormalities at the start of treatment of end-stage renal disease (ESRD) have been reported as worse in racial/ethnic minorities than in white patients, suggesting racial disparities in care. It is not known whether these differences are attributable to racial/ethnic differences in socioeconomic status (SES). METHODS: We tested associations between race/ethnicity, SES, and type of medical insurance and serum creatinine level, estimated glomerular filtration rate, serum albumin level, and hematocrit at the start of treatment of ESRD and use of epoietin before ESRD treatment in a large national population-based sample. Data on 515 561 patients beginning ESRD treatment between January 1, 1996, and June 30, 2004, were obtained for this cross-sectional survey from the United States Renal Data System. RESULTS: Race/ethnicity had a much stronger association than SES with each laboratory measure. Adjusted mean serum creatinine levels were lowest in white patients (7.5 mg/dL [663.0 micromol/L]; 95% confidence interval [CI], 7.45-7.49) and highest in black patients (8.9 mg/dL [786.7 micromol/L]; 95% CI, 8.92-8.97) (P<.001 across racial/ethnic groups). Adjusted mean hematocrit for white patients (29.5%; 95% CI, 29.4%-29.6%) was significantly higher and for black patients (28.3%; 95% CI, 28.2%-28.4%) significantly lower than that of all other racial/ethnic groups (P<.001 across racial/ethnic groups). Less marked differences were present for estimated glomerular filtration rate and serum albumin level. In contrast, predialysis use of epoietin was associated with race/ethnicity (black vs white: odds ratio, 0.80; 95% CI, 0.78-0.81; Hispanic vs white: odds ratio, 0.87; 95% CI, 0.85-0.89) and showed a graded decrease with decreasing SES (odds ratio for the lowest vs highest socioeconomic quartile 0.68; 95% CI, 0.67-0.70). Patients without medical insurance had more abnormal laboratory values than those with insurance, but these associations were weaker than those of race/ethnicity. CONCLUSIONS: Minorities, particularly black patients, had more severe laboratory abnormalities at the start of ESRD treatment than white patients. These differences were not readily attributable to SES differences. Absence of medical insurance, SES, and race/ethnicity were associated with the likelihood of predialysis use of epoietin.     

Inverse association of testosterone and the metabolic syndrome in men is consistent across race and ethnic groups

Context: Low sex hormone levels have been associated with the metabolic syndrome (MetS). Objectives: Our objective was to determine whether the association between sex hormone levels and MetS varies by race/ethnicity among men and to investigate the relationship of sex hormones and individual components of MetS. Design: We conducted a population-based observational survey. Participants: A multistage stratified design was used to recruit a random sample of 2301 racially/ethnically diverse men age 30-79 yr. Blood samples were obtained on 1899 men. Analyses were conducted on 1885 men with complete data on total testosterone (T), free T, and SHBG. Interventions: There were no interventions. Main Outcome Measure: MetS was defined using a modification of the Adult Treatment Panel III guidelines. The association between MetS and sex hormone levels was assessed using odds ratios and 95% confidence intervals estimated using logistic regression models. Results: A strong inverse association was observed, in both bivariate and multivariate analyses, between hormone levels and MetS. The odds of MetS increased about two-fold with a 1 sd decrease in hormone levels. The association between sex hormones and MetS was statistically significant across racial/ethnic groups. Although the magnitude of this association was largest among White men, racial/ethnic differences were not statistically significant. The strength of the association of sex hormones with individual components of MetS varied; stronger associations were observed with waist circumference and dyslipidemia and more modest associations with diabetes and elevated blood sugar. Conclusions: A robust, dose-response relationship between sex hormone levels and odds of the metabolic syndrome in men is consistent across racial/ethnic groups.     

Significant ethnic variation in total and free testosterone concentration

OBJECTIVE: Measurement of serum testosterone is an integral part of the assessment of men presenting to endocrine clinics. Little is known about the variation of total bound or bioavailable testosterone by ethnic group. The principal determinant of testosterone bioavailability is SHBG, which itself is a marker for insulin sensitivity. Our aim was to examine variations in testosterone and SHBG levels across three ethnic groups in relation to ethnic differences in insulin sensitivity. DESIGN: Men of three ethnic groups living in Manchester, UK, were sampled randomly from population registers being of white European (n = 55), Pakistani (n = 50) and African-Caribbean (AfC) origin (n = 75). Circulating serum testosterone and SHBG concentrations were measured and free testosterone calculated. Insulin sensitivity (HOMA-S) and insulin secretory capacity (HOMA-B) were determined from fasting plasma intact insulin and glucose values. RESULTS: Testosterone levels were lower in Pakistani men (mean 14.6 nmol/l, 95% confidence interval 12.6-16.6 nmol/l) than in Europeans (18.7, 16.8-20.6 nmol/l) or AfCs (18.0, 16.4-19.6 nmol/l) (F = 4.8, P = 0.009). Despite SHBG levels also being lower in Pakistani men (22.9, 19.4-26.5 nmol/l) compared with Europeans (28.7, 25.7-31.8 nmol/l) and AfCs (26.9, 23.9-30.0 nmol/l) (F = 3.0, P < 0.05), circulating free testosterone was significantly lower in the Pakistani group (367, 326-408 pmol/l) than in Europeans (455, 416-494 pmol/l) or AfCs (458, 424-492 pmol/l) (F = 6.8, P = 0.001). Pakistani men were on average 4 cm shorter than other groups. However, the lower free testosterone persisted even when adjusted for height or waist-hip ratio. The lower SHBG in the Pakistani men was paralleled by a lower HOMA-S (0.40, 0.25-0.56) compared with Europeans (0.77, 0.61-0.93) and AfCs (0.80, 0.66-0.93) (F = 8.2, P < 0.0001). SHBG correlated positively with HOMA-S (rho = 0.28, P < 0.001) and strongly with total testosterone (rho = 0.54, P < 0.001). There was no difference in insulin secretory capacity (HOMA-B) in Pakistani men compared with Europeans and AfCs. Multiple linear regression analysis showed that total testosterone was independently and negatively related to ln fasting insulin (beta = -0.28, P < 0.001) and age (beta = -0.17, P = 0.02) and positively to ln SHBG (beta = 0.23, P < 0.001) and height (beta = 0.22, P = 0.001). There was no relationship with ethnicity or waist-hip ratio. CONCLUSION: Both total bound and calculated free testosterone were lower in Pakistani men. SHBG levels were also lower in Pakistani men, in keeping with poorer insulin sensitivity. We propose that further work is necessary to establish ethnic-specific ranges for the interpretation of total circulating and free testosterone levels in men.     

Acute asthma among adults presenting to the emergency department: the role of race/ethnicity and socioeconomic status

OBJECTIVES: To investigate racial/ethnic differences in acute asthma among adults presenting to the emergency department (ED), and to determine whether observed differences are attributable to socioeconomic status (SES). DESIGN: Prospective cohort studies performed during 1996 to 1998 by the Multicenter Airway Research Collaboration. Using a standardized protocol, researchers provided 24-h coverage for a median duration of 2 weeks per year. Adults with acute asthma were interviewed in the ED and by telephone 2 weeks after hospital discharge. PARTICIPANTS: Sixty-four North American EDs. RESULTS: A total of 1,847 patients were enrolled into the study. Black and Hispanic asthma patients had a history of more hospitalizations than did whites (ever-hospitalized patients: black, 66%; Hispanic, 63%; white, 54%; p < 0.001; patients hospitalized in the past year: black, 31%; Hispanic, 33%; white, 25%; p < 0.05) and more frequent ED use (median use in past year: black, three visits; Hispanic, three visits; white, one visit; p < 0.001). The mean initial peak expiratory flow rate (PEFR) was lower in blacks and Hispanics (black, 47%; Hispanic, 47%; white, 52%; p < 0.001). For most factors, ED management did not differ based on race/ethnicity. After accounting for several confounding variables, blacks and Hispanics were twice as likely to be admitted to the hospital. Blacks and Hispanics also were more likely to report continued severe symptoms 2 weeks after hospital discharge (blacks, 24%; Hispanic, 31%; white, 19%; p < 0.01). After adjusting for sociodemographic factors, the race/ethnicity differences in initial PEFR and posthospital discharge symptoms were markedly reduced. CONCLUSION: Despite significant racial/ethnic differences in chronic asthma severity, initial PEFR at ED presentation, and posthospital discharge outcome, ED management during the index visit was fairly similar for all racial groups. SES appears to account for most of the observed acute asthma differences, although hospital admission rates were higher among black and Hispanic patients after adjustment for confounding factors. Despite asthma treatment advances, race/ethnicity-based deficiencies persist. Health-care providers and policymakers might specifically target the ED as a place to initiate interventions designed to reduce race-based disparities in health.     

Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study

In both men and women, circulating androgen levels decline with advancing age. Until now, results of several small studies on the relationship between endogenous androgen levels and atherosclerosis have been inconsistent. In the population-based Rotterdam Study, we investigated the association of levels of dehydroepiandrosterone sulfate (DHEAS) and total and bioavailable testosterone with aortic atherosclerosis among 1,032 nonsmoking men and women aged 55 yr and over. Aortic atherosclerosis was assessed by radiographic detection of calcified deposits in the abdominal aorta, which have been shown to reflect intimal atherosclerosis. Relative to men with levels of total and bioavailable testosterone in the lowest tertile, men with levels of these hormones in the highest tertile had age-adjusted relative risks of 0.4 [95% confidence interval (CI), 0.2-0.9] and 0.2 (CI, 0.1-0.7), respectively, for the presence of severe aortic atherosclerosis. The corresponding relative risks for women were 3.7 (CI, 1.2-11.6) and 2.3 (CI, 0.7-7.8). Additional adjustment for cardiovascular disease risk factors did not materially affect the results in men, whereas in women the associations diluted. Men with levels of total and bioavailable testosterone in subsequent tertiles were also protected against progression of aortic atherosclerosis measured after 6.5 yr (SD +/- 0.5 yr) of follow-up (P for trend = 0.02). No clear association between levels of DHEAS and presence of severe aortic atherosclerosis was found, either in men or in women. In men, a protective effect of higher levels of DHEAS against progression of aortic atherosclerosis was suggested, but the corresponding test for trend did not reach statistical significance. In conclusion, we found an independent inverse association between levels of testosterone and aortic atherosclerosis in men. In women, positive associations between levels of testosterone and aortic atherosclerosis were largely due to adverse cardiovascular disease risk factors.     

Age, body mass index, race and other determinants of steroid hormone variability: the HERITAGE Family Study.

OBJECTIVE AND METHODS: To investigate from the HERITAGE Family Study database, 13 steroid hormones (androstane-3alpha, 17beta-diol glucuronide, androsterone glucuronide, cortisol, dehydroepiandrosterone (DHEA), DHEA ester (DHEAE), DHEA sulfate (DHEAS), dihydrotestosterone (DHT), estradiol, 17-hydroxyprogesterone, progesterone, pregnenolone ester, sex hormone binding globulin (SHBG) and testosterone in each sex for their relationships with age, body mass index (BMI), race and key lifestyle variables. Sample sizes varied from 676 to 750 per hormone. Incremental regression methods were used to examine the contributions of the variables to steroid hormone variability. RESULTS: Age was a major predictor for most steroid hormones. The greatest contribution of age was a negative relationship with DHEAS (R(2)=0.39). BMI was also associated with the variability of several steroid hormones, being the most important predictor of SHBG (R(2)=0.20) and of testosterone (R(2)=0.12) concentrations. When age and BMI were included, race still contributed significantly to the variations in cortisol (R(2)=0.02 for men and 0.04 for women), DHT (R(2)=0.02 for men and 0.03 for women), and progesterone (R(2)=0.03 for women). Nevertheless, race appeared to be less important than age and BMI. In addition, lifestyle indicators (food and nutrient intakes, smoking and physical activity) influenced steroid hormone variability. Their contributions, however, were minor in most cases once age, BMI and race had been taken into account. CONCLUSIONS: We conclude that age was the most important factor, followed by BMI, race and lifestyle factors in explaining steroid hormone variability.     

Testosterone, sex hormone-binding globulin, and body composition in young adult African American and Caucasian men

This study examined the diurnal variation in circulating total and free testosterone and sex hormone-binding globulin (SHBG) levels in young adult African American and Caucasian men in order to investigate whether there are differences in the secretion of these plasma hormones in populations at different risks of developing prostate cancer as they age. A significant and similar diurnal rhythm for total and free testosterone was found for both groups. Serum levels of total testosterone were 29.4% and 23.9% lower at 8:00 PM than at 8:00 AM in African American and Caucasian men, respectively. Significantly higher serum levels of total testosterone (P<.01) and SHBG (P <.02) were found in the African American than in the Caucasian men in both the morning and evening, whereas free testosterone levels were similar in both groups. The higher SHBG levels appear to have an environmental/metabolic basis in that the waist circumference, waist-to-hip ratio, and fasting insulin concentration were lower (P <.05) in African Americans than in Caucasians. In summary, these data indicate that racial differences in central adiposity in men are established in early adulthood and influence circulating SHBG and thereby testosterone levels. In light of the findings by others that SHBG increases cyclic adenosine monophosphate (cAMP) production in the prostate and that cAMP-dependent protein kinase A is a coactivator of the androgen receptor, these studies provide a possible mechanism by which circulating androgens may contribute to the increased risk for prostate cancer among African American men.     

Serum estrogen, but not testosterone, levels differ between black and white men in a nationally representative sample of Americans

CONTEXT: Higher testosterone in black compared with white men has been postulated to explain their higher prostate cancer incidence. Previous studies comparing hormone levels by race might have been limited by size, restricted age variation, or lack of representation of the general population. OBJECTIVE: Our objective was to compare serum testosterone, estradiol, and SHBG concentrations among non-Hispanic black, non-Hispanic white, and Mexican-American men. PARTICIPANTS, DESIGN, AND SETTING: A total of 1413 men aged 20+ yr and who attended the morning examination session of the Third National Health and Nutrition Examination Survey (NHANES III) in 1988-1991 were included in this cross-sectional study. MEASUREMENT: Serum hormone concentrations were measured by electrochemiluminescence immunoassays. RESULTS: After applying sampling weights and adjusting for age, percent body fat, alcohol, smoking, and activity, testosterone concentrations were not different between non-Hispanic blacks (n = 363; geometric mean, 5.29 ng/ml) and non-Hispanic whites (n = 674; 5.11 ng/ml; P > 0.05) but were higher in Mexican-Americans (n = 376; 5.48 ng/ml; P < 0.05). Non-Hispanic blacks (40.80 pg/ml) had a higher estradiol concentration than non-Hispanic whites (35.46 pg/ml; P < 0.01) and Mexican-Americans (34.11 pg/ml; P < 0.01). Non-Hispanic blacks (36.49 nmol/liter) had a higher SHBG concentration than non-Hispanic whites (34.91 nmol/liter; P < 0.05) and Mexican-Americans (35.04 nmol/liter; P < 0.05). CONCLUSIONS: Contrary to the postulated racial difference, testosterone concentrations did not differ notably between black and white men. However, blacks had higher estradiol levels. Mexican-Americans had higher testosterone than whites but similar estradiol and SHBG concentrations. Given these findings, it may be equally if not more important to investigate estradiol as testosterone in relation to diseases with racial disparity.     

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.     

HIV Prevalence Rates Among Men Who Have Sex with Men in the Southern United States: Population-Based Estimates by Race/Ethnicity

States across the U.S. lack effective ways to quantify HIV prevalence rates among men who have sex with men (MSM). We estimated population-based HIV prevalence rates among MSM in the 17 southern states by race/ethnicity. Through 2007, estimated HIV prevalence rates per 100,000 MSM ranged from 2,607.6 among white (non-Hispanic) MSM in Maryland to 41,512.9 among black (non-Hispanic) MSM in the District of Columbia. Black MSM rates significantly exceeded Hispanic and white MSM rates in each state. Significant racial/ethnic disparities in rates persisted in a sensitivity analysis examining the possibility that minority MSM populations had been underestimated in each state. Compared with black, Hispanic, and white non-MSM males, respectively, rates at the regional level were 25.2 times higher for black MSM, 43.0 times higher for Hispanic MSM, and 106.0 times higher for white MSM. State-level analysis of racial/ethnic-specific MSM HIV prevalence rates can help guide resource allocation and assist advocacy.     

Sex hormone levels and subclinical atherosclerosis in postmenopausal women: the Multi-Ethnic Study of Atherosclerosis

We examined cross-sectional associations between sex hormones and carotid artery intimal-medial thickness (cIMT) and coronary artery calcium in women in the Multi-Ethnic Study of Atherosclerosis. Serum testosterone, estradiol, sex hormone binding globulin (SHBG), and dehydroepiandrosterone levels were measured in 1947 postmenopausal women aged 45-84 years (30% White, 14% Chinese-American, 31% Black, and 25% Hispanic) and not on hormone therapy. Using multiple linear regression we evaluated associations between log(sex hormone) levels and log(cIMT) adjusted for age, ethnicity, body mass index (BMI) and cardiac risk factors. Associations between sex hormone levels and the presence and extent of coronary calcium were evaluated. Total and bioavailable testosterone were positively associated with common cIMT independent of age, BMI, hypertension, smoking, HDL-cholesterol, LDL-cholesterol and insulin sensitivity (p=0.009 and p=0.002, respectively). SHBG was negatively associated with common cIMT (p=0.001) but further adjustment for BMI, cardiovascular risk factors, and LDL- and HDL-cholesterol removed significance. Estradiol and dehydroepiandrosterone were not associated with common cIMT. Sex hormones were not associated with presence of coronary calcium. Among women with measurable coronary calcium, higher SHBG (p=0.012) and lower bioavailable testosterone (p=0.007) were associated with greater coronary calcium score. No heterogeneity by ethnicity was found. In postmenopausal women, testosterone is independently associated with greater common cIMT. SHBG is negatively associated and this may be mediated by LDL- and HDL-cholesterol. In contrast, SHBG and testosterone were associated with extent of coronary calcium but in the opposite direction compared to carotid intimal-medial thickness. These differences warrant further evaluation.     

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.     

Androgens are associated with hemostatic and inflammatory factors among women at the mid-life

GOAL: The goal of this study was to relate annually measured endogenous androgens to hemostatic and inflammation markers in women longitudinally. METHODS: A total of 3302 participants from the Study of Women's Health Across the Nation, aged 42-52 yr at baseline and self-identified as African-American (28%), Caucasian (47%), Chinese (8%), Hispanic (8%), or Japanese (9%) were evaluated for testosterone (T), dehydroepiandrosterone sulfate, and SHBG at four time points in 5 yr. Cardiovascular disease markers were fibrinogen, activated factor VII-c, C-reactive protein (hsC-RP), and the fibrolytic factors, plasminogen activator inhibitor type 1 (PAI-1), and tissue plasminogen activator [t(PA)]. RESULTS: T and free androgen index (FAI) were associated highly positively with PAI-1 and t(PA), and FAI was associated highly and positively with hsC-RP. Lower SHBG levels, associated with greater bioavailable T, were associated significantly with higher levels of PAI-1, t(PA), hsC-RP, and factor VII-c. SHBG was lower in Chinese and Japanese women markedly, resulting in FAI values that, on average, were higher among Chinese and Japanese women compared with African-American, Caucasian, and Hispanic women. IMPLICATIONS: There were strong, positive associations of androgens with fibrolytic and inflammation markers, even after considering age, body size, smoking, and race/ethnicity. It is important to study androgens, their precursors, and their carrier protein as part of the risk profile for heart disease in mid-aged women.     

Changes in BMI modulate age-associated changes in sex hormone binding globulin and total testosterone, but not bioavailable testosterone in young adult men: the CARDIA Male Hormone Study

OBJECTIVES: To compare age-associated 8-year changes in total testosterone, calculated bioavailable testosterone and sex hormone binding globulin (SHBG) across five groups of men stratified according to change in body mass index (BMI) (i.e., BMI stable (+/-0.69 kg/m(2)), decreased (-0.7 kg/m(2)), increased minimally (0.7-1.74 kg/m(2)), increased moderately (1.75-3.19 kg/m(2)) and increased most (> or =3.20 kg/m(2))). DESIGN: Eight-year longitudinal cohort study. SUBJECTS: Four hundred and seventy-four black and 695 white men, aged 24-31 years at the time of the first hormone measurement. MEASUREMENTS: Aging-related changes in serum SHBG, total testosterone and bioavailable testosterone. RESULTS: SHBG significantly increased with age for men whose BMI decreased, and there were progressively smaller increases for men whose BMI was stable, or whose BMI increased minimally or moderately (range 1.1-0.3 nM per year, P< or =0.03, respectively). There was no age relationship with SHBG among men whose BMI increased most. Total testosterone did not change with age for men whose BMI decreased, was stable or increased minimally, but for men whose BMI increased moderately and most there was a graded decrease in total testosterone with age (beta=-0.2 and -0.4 nM per year, respectively, P< or =0.005). However, bioavailable testosterone decreased with age to a similar extent across all groups. CONCLUSIONS: These results suggest that changes in BMI during young adulthood modulate age-related changes in SHBG and total testosterone, but not bioavailable testosterone.     

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.