Accounting for racial/ethnic variation in bone mineral content and density: the competing influences of socioeconomic factors, body composition, health and lifestyle, and circulating androgens and estrogens.

UNLABELLED: The relative importance of various contributors to racial/ethnic variation in BMC/BMD is not established. Using population-based data, we determined that body composition differences (specifically skeletal muscle and fat mass) are among the strongest contributors to these variations. INTRODUCTION: Racial/ethnic variation in fracture risk is well documented, but the mechanisms by which such heterogeneity arises are poorly understood. We analyzed data from black, Hispanic, and white men enrolled in the Boston Area Community Health/Bone (BACH/Bone) Survey to determine the contributions of risk factors to racial/ethnic differences in bone mineral content (BMC) and density (BMD). METHODS: In a population-based study, BMC, BMD, and body composition were ascertained by DXA. Socioeconomic status, health history, and dietary intake were obtained via interview. Hormones and markers of bone turnover were obtained from non-fasting blood samples. Multivariate analyses measured percentage reductions in estimated racial/ethnic differences in BMC/BMD, accompanying the successive removal of covariates from linear regression models. RESULTS: Black men demonstrated greater BMC than their Hispanic and white counterparts. At the femoral neck, adjustment for covariables was sufficient to reduce these differences by 46% and 35%, respectively. While absolute differences in BMC were smaller at the distal radius than femoral neck, the proportionate reductions in racial/ethnic differences after covariable adjustment were comparable or greater. Multivariate models provided evidence that lean and fat mass, serum 25(OH)D, osteocalcin, estradiol, and aspects of socioeconomic status influence the magnitude of racial/ethnic differences in BMC, with lean and fat mass providing the strongest effects. Results for BMD were similar, but typically of lesser magnitude and statistical significance. CONCLUSIONS: These cross-sectional analyses demonstrate that much of the racial/ethnic heterogeneity in measures of bone mass and density can be accounted for through variation in body composition, diet, and socio-demographic factors.

Serum 25-hydroxyvitamin D and bone mineral density among Hispanic men.

UNLABELLED: There are few data on the skeletal health of Hispanic men. We observed differences in vitamin D deficiency and low BMD between Hispanic ethnic subgroups that persisted with adjustment for risk factors. Our data indicate a substantial burden of low BMD and vitamin D deficiency among Hispanic men. INTRODUCTION: Disparities within ethnic groups are generally ignored, but in evolving populations they may have implications for public health. We examined ethnic variation in serum 25-hydroxyvitamin D [25(OH)D] and bone mineral density (BMD) among Hispanic American men. METHODS: Three hundred and fifty-eight Hispanic males 30 to 79 years of age were studied. Logistic regression models assessed variation in odds of vitamin D deficiency (<20 ng/mL) and low BMD (T-score<-1) by ethnicity, with and without adjustment for risk factors (age, smoking, occupation, physical activity, body mass index, and sunlight exposure). RESULTS: Vitamin D deficiency was most common among Puerto Rican (26%), compared with Dominican (21%), Central American (11%), and South American (9%) men. Percentages with low BMD were: South American (44%), Puerto Rican (34%), Dominican (29%), and Central American (23%). Adjustment for age and risk factors failed to account for Hispanic subgroup differences in vitamin D deficiency and low BMD. Population estimates indicate a substantial burden of low BMD and vitamin D deficiency among Hispanic men. CONCLUSIONS: Our findings underscore the importance of examining the skeletal health of Hispanic subgroups, and suggest that a considerable number of Hispanic men may be at elevated risk of fracture and vitamin D deficiency.

Relative contributions of multiple determinants to bone mineral density in men.

SUMMARY: Focus on individual risk factors for osteoporosis could allocate disproportionate attention to trivial relationships. We tested many recognized risk factors of osteoporosis for their association with bone mineral density (BMD) in multivariate models among men. Lean mass accounted for the most variance, with substantially less accounted for by demographic, strength, and health factors. INTRODUCTION: Osteoporosis in men has gained recognition as a public health problem, generating an interest in the search for risk factors. Isolation of individual risk factors could allocate disproportionate attention to relationships that may be of limited consequence. METHODS: The Boston Area Community Health/Bone (BACH/Bone) Survey is a population-based study of randomly selected community-dwelling men (age, 30-79 years). BMD and lean mass were measured by dual X-ray absorptiometry. Socioeconomic status, health history, and lifestyle factors were obtained via interview. Hormone levels and markers of bone turnover were obtained from non-fasting blood samples. Multivariate analyses measured relative contributions of covariates to femoral neck (hip), one-third distal radius (wrist), and lumbar spine BMD. RESULTS: Factors positively associated with BMD in multivariate models at the three sites were black race and appendicular lean mass. Asthma was consistently negatively associated. Various other risk factors also contributed significantly to each of the individual sites. R (2) values for the hip, wrist, and spine were 41%, 30%, and 24%, respectively. Lean mass accounted for the most explained variance at all three sites. CONCLUSIONS: These data emphasize the limitation of focusing on individual risk factors and highlight the importance of potentially modifiable lean mass in predicting BMD.

Sources of variation in physician adherence with clinical guidelines: results from a factorial experiment.

BACKGROUND: Health services research has documented the magnitude of health care variations. Few studies focus on provider level sources of variation in clinical decision making-for example, which primary care providers are likely to follow clinical guidelines, with which types of patient. OBJECTIVES: To estimate: (1) the extent of primary care provider adherence to practice guidelines and the unconfounded influence of (2) patient attributes and (3) physician characteristics on adherence with clinical practice guidelines. DESIGN: In a factorial experiment, primary care providers were shown clinically authentic video vignettes with actors portrayed different "patients" with identical signs of coronary heart disease (CHD). Different types of providers were asked how they would manage the different "patients" with identical CHD symptoms. Measures were taken to protect external validity. RESULTS: Adherence to some guidelines is high (over 50% of physicians would follow a third of the recommended actions), yet there is low adherence to many of them (less than 20% would follow another third). Female patients are less likely than males to receive 4 of 5 types of physical examination (p < .03); older patients are less likely to be advised to stop smoking (p < .03). Race and SES of patients had no effect on provider adherence to guidelines. A physicians' level of experience (age) appears to be important with certain patients. CONCLUSIONS: Physician adherence with guidelines varies with different types of "patient" and with the length of clinical experience. With this evidence it is possible to appropriately target interventions to reduce health care variations by improving physician adherence with clinical guidelines.

Testosterone, sex hormone-binding globulin, and the development of type 2 diabetes in middle-aged men: prospective results from the Massachusetts male aging study.

OBJECTIVE: The objective was to examine prospectively the association between low testosterone and sex hormone-binding globulin (SHBG) levels and the subsequent development of type 2 diabetes in men. RESEARCH DESIGN AND METHODS: Analyses were conducted on the cohort of the Massachusetts Male Aging Study, a population-based random sample of men aged 40-70. Of the 1,709 men enrolled in 1987-1989 (T1), 1,156 were followed up 7-10 years later (T2). Testosterone and SHBG levels at T1 were used to predict new cases of diabetes between T1 and T2. RESULTS: After controlling for potential confounders, diabetes at follow-up was predicted jointly and independently by lower baseline levels of free testosterone and SHBG. The odds ratio for future diabetes was 1.58 for a decrease of 1SD in free testosterone (4 ng/dl) and 1.89 for a 1SD decrease in SHBG (16 nmol/l), both significant at P < 0.02. CONCLUSIONS: Our prospective findings are consistent with previous, mainly cross-sectional reports, suggesting that low levels of testosterone and SHBG play some role in the development of insulin resistance and subsequent type 2 diabetes.

Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study.

To evaluate the hypothesis that endocrine profiles change with aging independently of specific disease states, we examined the age trends of 17 major sex hormones, metabolites, and related serum proteins in 2 large groups of adult males drawn from the Massachusetts Male Aging Study, a population-based cross-sectional survey of men aged 39-70 yr conducted in 1986-89. Group 1 consisted of 415 men who were free of obesity, alcoholism, all prescription medication, prostate problems, and chronic illness (cancer, coronary heart disease, hypertension, diabetes, and ulcer). Group 2 consisted of 1294 men who reported 1 or more of the above conditions. Each age trend was satisfactorily described by a constant percent change per yr between ages 39-70 yr. Free testosterone declined by 1.2%/yr, and albumin-bound testosterone by 1.0%/yr. Sex hormone-binding globulin (SHBG), the major serum carrier of testosterone, increased by 1.2%/yr, with the net effect that total serum testosterone declined more slowly (0.4%/yr) than the free or albumin-bound pools alone. Among the major androgens and metabolites, androstane-3 alpha,17 beta-diol (androstanediol; 0.8%/yr) and androstanediol glucuronide (0.6%/yr) declined less rapidly than free testosterone, while 5 alpha-dihydrotestosterone remained essentially constant between ages 39-70 yr. Androstenedione declined at 1.3%/yr, a rate comparable to that of free testosterone, while the adrenal androgen dehydroepiandrosterone (3.1%/yr) and its sulfate (2.2%/yr) declined 2-3 times more rapidly. The levels of testosterone, SHBG, and several androgen metabolites followed a parallel course in groups 1 and 2, remaining consistently 10-15% lower in group 2 across the age range of the study. Subgroup analyses suggested that obese subjects might be responsible for much of the group difference in androgen level. Serum concentrations of estrogens and cortisol did not change significantly with age or differ between groups. Of the pituitary gonadotropins, FSH increased at 1.9%/yr, LH increased at 1.3%/yr, and PRL declined at 0.4%/yr, with no significant difference between groups 1 and 2.(ABSTRACT TRUNCATED AT 400 WORDS)

Diet and sex hormone-binding globulin.

The serum concentration of sex hormone-binding globulin (SHBG) is inversely related to weight and in animal studies is inversely related to protein intake. As SHBG can affect the biological activity of testosterone and estradiol, we wished to determine the role of protein intake on SHBG levels in men. Using data from the Massachusetts Male Aging Study we examined cross-sectional relationships between dietary components and SHBG levels in 1552 men (aged 40-70 yr) for whom these factors were known. Analyzed by multiple regression, controlling for testosterone and estradiol levels, age (P<0.001) and fiber intake (P = 0.02) were positively correlated to SHBG concentration, whereas body mass index (P<0.001) and protein intake (P<0.03) were negatively correlated to SHBG concentration. The intakes of calories, fat (animal or vegetable), and carbohydrate were not related to SHBG concentration. We conclude that age and body mass index are major determinants of SHBG concentrations in older men, and fiber and protein intake are also significant contributors to SHBG levels, but total caloric intake and the intake of carbohydrate or fat are not significant. Thus, diets low in protein in elderly men may lead to elevated SHBG levels and decreased testosterone bioactivity. The decrease in bioavailable testosterone can then result in declines in sexual function and muscle and red cell mass, and contribute to the loss of bone density.

The relation of smoking, age, relative weight, and dietary intake to serum adrenal steroids, sex hormones, and sex hormone-binding globulin in middle-aged men.

The relationships of cigarette smoking, age, relative weight, and dietary intake to serum dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, cortisol, 3-alpha-androstanediol, 3-alpha-androstanediol-glucuronide, testosterone, albumin-bound testosterone, free testosterone, dihydrotestosterone (DHT), and sex hormone-binding globulin (SHBG) were examined cross-sectionally in 1241 randomly sampled middle-aged U.S. men. Compared with nonsmokers and independent of relative weight (body mass index) and age, cigarette smokers had increased serum levels of DHEA (18% higher, P = 0.0002), DHEAS (13% higher, P = 0.0007), cortisol (5% higher, P = 0.01), androstenedione (33% higher, P = 0.0001), testosterone (9% higher, P = 0.009), DHT (14% higher, P = 0.004), and SHBG (8% higher, P = 0.004). Androstenedione, total plasma testosterone, albumin-bound testosterone, DHT, and SHBG decreased with increasing relative weight. Age was positively associated with serum SHBG and negatively associated with albumin-bound testosterone, DHEA, and DHEAS. An association was found between alcohol intake and DHEA (r = 0.15; P = 0.0001), cortisol (r = 0.10; P = 0.0007), and 3-alpha-androstanediol-glucuronide (r = 0.08; P = 0.0004). Cortisol was the only hormone that was associated with carbohydrate intake (r = -0.09; P = 0.002). The only hormones associated with dietary lipids were DHT (for vegetable fat, r = 0.07; P = 0.02), cortisol (for total fat, r = 0.08; P = 0.007), and SHBG (for animal fat, r = -0.06; P = 0.05). In addition, SHBG was positively associated with dietary (r = 0.07; P = 0.008) and crude (r = 0.08; P = 0.007) fiber. These data suggest that serum adrenal steroid and sex hormone concentrations in middle-aged men are more influenced by cigarette smoking, age, and obesity than by dietary intake; however, serum adrenal steroids were influenced by alcohol intake.

Testosterone level, androgen receptor polymorphism, and depressive symptoms in middle-aged men.

BACKGROUND: Testosterone (T) level declines progressively with age. Psychiatric symptoms of T deficiency (e.g., dysphoria, fatigue, irritability, low libido) are also symptoms of depression, and appear to be variably expressed. METHODS: We assessed independent measures of hypothalamic-pituitary-gonadal axis functioning, i.e., total T level and androgen receptor (AR) CAG repeat length (CAG RL), a genetic trait marker associated with AR function; and depression (diagnosed by above-threshold score on the Center for Epidemiologic Studies-Depression Scale [CES-D]) in 1000 men (mean age = 62.6 years; SD = 8.3) who participated in the Massachusetts Male Aging Study. RESULTS: There were 110 (11%) men with "depression" (CES-D score > or = 16) in the analysis sample. Neither total T level nor CAG RL was associated with depression in bivariate analyses. Among men with shorter CAG RLs, the percentage of men with depression was 21.6% in the lowest subgroup of total T (defined by quintiles) and 4.2% in the highest subgroup of total T. This was confirmed in simple logistic regression models with depression as the dependent variable and continuous total T as the predictor, run separately within the three CAG RL subgroups: depression was significantly and inversely associated with total T in men with shorter CAG RLs but not in men with moderate and longer CAG RLs. CONCLUSIONS: CAG isotype, a genetic trait marker of androgen receptor function, may mediate the expression of the central nervous system effects of T deficiency in men.

Physician characteristics: do they influence the evaluation and treatment of breast cancer in older women?

BACKGROUND: To determine if physician specialty, length of time in practice, and fear of malpractice influence the diagnosis and management of breast cancer in older women. METHODS: We used a fractional factorial design that controlled for patient age (65 or 80 years), race, socioeconomic status, mobility, comorbidity, and assertive behavior through 2 videotaped scenarios (a potential breast cancer [no. 1] and a known stage IIA breast cancer [no. 2]). One hundred twenty-eight white male physicians equally divided by specialty (surgeon versus nonsurgeon) and time in practice (< or = 15 or >15 years) viewed the videotapes and made recommendations. RESULTS: The physician subjects saw 46 patients per week, 59% female, and 47% age > or = 65. Their concern over malpractice was 4.7 (on a 10-point Likert scale with a higher score indicating more concern) and did not differ by specialty or time in practice (P values > 0.7). After viewing scenario no. 1, surgeons were less likely than nonsurgeons to consider breast cancer as the principal diagnosis (odds ratio [OR] = 0.4, 95% confidence interval [CI] = 0.2 to 0.9) and to obtain a tissue diagnosis (OR = 0.3, 95% CI = 0.1 to 0.9). However, in scenario no. 2, surgeons were more likely to offer reconstruction (OR = 3.8, 95% CI = 1.4 to 10.4). Physicians in practice < or = 15 years were more likely than those in practice <15 years to obtain a tissue diagnosis in scenario no. 1 (OR = 6.1, 95% CI = 1.9 to 19.2) and to perform full primary therapy in scenario no. 2 (OR = 2.8, 95% CI = 1.2 to 6.9). Physicians who performed an extensive metastatic evaluation (bone or computer tomography [CT] scan) had greater concern over malpractice than those who did not, as did physicians who performed an axillary node dissection (OR = 2.1, 95% CI 1.3 to 3.4 and OR = 1.8, 95% CI = 1.1 to 3.0). CONCLUSIONS: With the uncertainty of how to diagnose and treat older women with breast cancer, physician specialty, length of time in practice, and concern over malpractice do influence clinical decisions.

Evidence that the CAG repeat in the androgen receptor gene is associated with the age-related decline in serum androgen levels in men.

In men over 30 years old, serum levels of testosterone (T) decrease with age. A shorter polymorphic CAG repeat length in exon 1 of the androgen receptor (AR) gene is associated with higher transcription activation by the AR. We determined the number of CAG repeats for 882 men aged between 40 and 70 years from the Massachusetts Male Aging Study (MMAS). MMAS is a population-based random sample survey of men for whom baseline (1987-1989, mean age 53+/-8 years) and follow-up (1995-1997, mean age 61+/-8 years) serum hormone levels were available. Multiple linear regression was used to determine if CAG repeat length would be predictive of hormone levels at follow-up. Hormone levels measured included T, free T, albumin-bound T, dihydrotestosterone (DHT), sex hormone-binding globulin (SHBG) and luteinizing hormone (LH). The CAG repeat length was significantly associated with T (P=0.041), albumin-bound T (P=0.025) and free T (P=0.003) when controlled for age, baseline hormone levels and anthropometrics. Follow-up levels of T decreased by 0.74%+/-0.36 per CAG repeat decrement. Likewise, the percentages of free and albumin-bound T decreased by 0.93%+/-0.31 and 0.71%+/-0.32 per CAG repeat decrement respectively. These results suggest that androgen levels may be modulated by AR genotype.

Low dehydroepiandrosterone sulfate and heart disease in middle-aged men: cross-sectional results from the Massachusetts Male Aging Study.

PURPOSE: Serum concentrations of the adrenal androgen dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS), both of which decline with age more markedly than other sex hormone levels, have been alternately credited and discredited as "protective" correlates of heart disease. Baseline data from the Massachusetts Male Aging Study (MMAS), collected in 1987-89, provided a large population-based random sample (n = 1709) in which to examine cross-sectionally the relation of DHEA and DHEAS levels to heart disease, while controlling for a comprehensive set of potential confounders including serum lipid and hormone levels as well as smoking, alcohol intake, obesity, hypertension, diabetes, diet, medication, physical activity, and psychological measures. METHODS: The subjects were men aged 40-70 years, randomly sampled from the Massachusetts state census listing, measured and interviewed at home. Nonfasting blood samples were assayed for hormones and lipids. RESULTS: In all strata of age, smoking, and alcohol intake, the age-adjusted odds ratio for self-reported heart disease was between 0.55 and 0.85 per standard deviation (SD) of log DHEA and DHEAS concentration. Multiple logistic regression analysis indicated a strong independent role for DHEAS as a predictor of self-reported heart disease, controlling for age and the potential confounders listed above. The multiply-adjusted odds ratio for heart disease was 0.64 per SD log DHEAS concentration, with 95% confidence interval (CI) 0.50-0.83 (P = 0.0002). The DHEAS effect was not diminished by controlling for use of cardiac, vasodilator, antihypertensive, or lipid-lowering medication. CONCLUSIONS: These findings suggest that serum DHEAS levels bear an inverse relationship to heart disease, independently of a large set of established cardiovascular risk factors. The cross-sectional nature of this study requires that the findings be interpreted with caution.

An examination of research design effects on the association of testosterone and male aging: results of a meta-analysis.

The study of testosterone is likely to be prominent in future epidemiological work on endocrine function and the clinical treatment of age-related diseases. Thus, understanding the hormonal changes involved in the normal male aging process will be critical. Using techniques of meta-analysis, the authors examined 88 published studies of the age-testosterone relation in men. These studies reported conflicting results: age-testosterone correlations ranged from -0.68 to +0.68. In cross-study comparisons, certain research design characteristics (e.g. time of day of blood sampling) and various sample characteristics (e.g. volunteers vs patients as subjects) were related to both mean testosterone level and the slope of the age-testosterone relation. For example, for subgroups of subjects that did not exclude ill men, the mean testosterone levels were low, and did not decline with age. Subgroups that included only healthy subjects, in contrast, had higher overall testosterone levels and showed a decline of testosterone with age. Implications of these results for design, analysis and reporting of future epidemiologic studies will be discussed. These results also illustrate the utility of meta-analysis for research with the aged.

A comparison of anlaytic methods for non-random missingness of outcome data.

Missing outcome values occur frequently in survey data and are rarely missing randomly. Depending on the pattern of missingness, the choice of analytic method has implications for accuracy of the estimated outcome distribution as well as multivariate models. Data from a study of patterns of care in disabled elders were used to evaluate several common methods when missingness of the outcome was nonrandom. Results from single and multiple model-based imputation were compared with results from complete-case analysis and mean imputation. By ignoring nonrespondents' covariate information, the latter two methods yielded biased estimates of population means. Mean imputation and single model-based imputation underestimated standard errors by treating imputed values as if they were observed. Mean imputation also distorted the relationship between the outcome and predictors. Multiple model-based imputation provided an easily implemented method of adjustment for non-random non-response in both univariate and multivariate analyses.

Reliability and physiologic correlates of the Harvard Alumni Activity Survey in a general population.

The reliability of the Harvard Alumni Activity Survey (HAAS) and its association with physiologic measures was assessed in a large sample of men and women aged 25-65 years residing in the Boston metropolitan area in 1987. Reliability was estimated by comparing HAAS energy expenditure reports (kcal/week) from two separate interviews conducted 7-12 weeks apart. The test-retest reliability coefficient was 0.58 for the entire sample, but was considerably higher (r = 0.69) for those whose activity patterns had not changed from one interview to the next. HAAS self-reports were compared to two physiologic measures known to be affected by physical activity: high density lipoprotein cholesterol (HDLC) and body mass index (BMI). The natural logarithm of weekly HAAS expenditures was positively correlated with HDLC (r = 0.14, p less than 0.01) and negatively correlated with BMI (r = 0.13, p less than 0.01) for all respondents. These statistically significant associations persisted when adjusted for other covariates influencing physiologic status. The reliability coefficients and physiologic correlations for the HAAS in this sample are comparable to those reported for physical activity instruments requiring more intensive data collection and scoring procedures.

Construction of a surrogate variable for impotence in the Massachusetts Male Aging Study.

Uncollected data must be filled in after the fact in many epidemiological studies. We compared several methods for constructing a surrogate variable for erectile potency, based on responses to related questions, in the Massachusetts Male Aging Study (MMAS). Quadratic discriminant analysis performed best among the procedures tested, achieving high rates of correct classification in cross-validation of training data and (according to posterior estimates) in classification of MMAS subjects. Two versions of the surrogate variable were constructed, one involving a discrete classification and the other involving a set of continuous probabilities. The two versions were used to investigate medical correlates of impotence in MMAS and produced similar results, although the continuous version appeared to provide higher statistical power. We conclude that construction of a surrogate variable is a viable and potentially beneficial option in epidemiological investigations.

A new surrogate variable for erectile dysfunction status in the Massachusetts male aging study.

Erectile dysfunction (ED) is the subject of a vast clinical literature, but little information has been gathered from random samples of the general public. The Massachusetts Male Aging Study (MMAS) addressed this important aspect of men's health. The MMAS was conducted in two waves, with baseline data collection in 1987-1989 and follow-up in 1995-1997. Subsequent to the baseline MMAS survey, a consensus developed that subjective measures are optimal for defining ED. Unfortunately, the baseline questionnaire did not ask subjects directly about their erectile functioning. Thus, we previously assigned the MMAS subjects a degree of impotence at baseline using a series of related questions, employing a discriminant formula constructed from a separate sample of urology clinic patients. At follow-up the men classified themselves directly in addition to answering the original series of related questions. In the present article, we report the results of a new discriminant function, based on the MMAS men at follow-up. We also compare the two methods and discuss our reasons for preferring the internally calibrated method.

Risk factors for clinical benign prostatic hyperplasia in a community-based population of healthy aging men.

We defined risk factors for a clinical diagnosis of benign prostatic hyperplasia (BPH) among subjects of the population-based Massachusetts Male Aging Study. In 1987-89 1709 men aged 40-70 provided baseline risk factor data and were followed for a mean of 9 years; 1019 men without prostate cancer provided follow-up data. We classified men with clinical BPH at follow-up if they reported (1) frequent or difficulty urinating and were told by a health professional that they had an enlarged or swollen prostate or (2) if they reported having surgery for BPH. At follow-up the prevalence of clinical BPH was 19.4%, increasing from 8.4% of men aged 38-49 years to 33.5% of men aged 60-70 years (P < 0.001 for trend). Elevated free PSA levels (age- and total PSA-adjusted OR, top vs. bottom quartile ng/mL 4.4, 95% CI 1.9-10.5), heart disease (age-adjusted OR 2.1, CI 1.3-3.3), and use of beta-blocker medications (OR 1.8, CI 1.1-3.0) increased odds for BPH, while current cigarette smoking (OR 0.5, CI 0.3-0.8) and high levels of physical activity (top vs. bottom quartile kcals/day OR 0.5, CI 0.3-0.9) decreased odds of BPH. All but the medication effects persisted in fully adjusted multivariable models. Total or fat calorie intake, sexual activity level, alcohol intake, body mass index, waist-hip ratio, diastolic blood pressure, a history of diabetes, hypertension, vasectomy, or serum levels of androgens or estrogens did not individually predict clinical BPH. We conclude that physical exercise and cigarette smoking appear to protect against development of clinical BPH. Elevated free PSA levels predict clinical BPH independent of total PSA levels. Risk associated with heart disease does not appear to be due solely to detection bias or to effects of heart disease medications. A wide variety of other characteristics appear to have no influence on risk for clinical BPH.

Relation of dehydroepiandrosterone and dehydroepiandrosterone sulfate with cardiovascular disease risk factors in women: longitudinal results from the Massachusetts Women's Health Study.

Low circulating levels of the adrenal steroids dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) are thought to be associated with increased risk of cardiovascular disease (CVD) in men. In women, either a positive or null association with CVD has been found. The nature of the relation between DHEAS and CVD risk factors in women is unclear and is based on cross-sectional data. We present results from a longitudinal investigation of serum DHEA and DHEAS and cardiovascular disease risk factors in 236 women, initially 50-60 years old, from a population-based prospective (1986-1995) study of the menopausal transition. We used generalized estimating equations to model the relation of serum DHEA and DHEAS to systolic and diastolic blood pressure and serum levels of total cholesterol, high density lipoprotein cholesterol, and apolipoproteins A and B, adjusting for other factors related to CVD. Both DHEA and DHEAS were positively related to diastolic and systolic blood pressure, and DHEAS was negatively related to apolipoprotein A. DHEA and DHEAS were also positively related to smoking, alcohol use, estrone, and estradiol levels, and inversely related to age. Our results suggest that higher levels of DHEA and DHEAS in middle-aged women may indicate increased CVD risk.

Does collecting repeated blood samples from each subject improve the precision of estimated steroid hormone levels?

Measuring levels of steroid hormones in epidemiologic studies is difficult because pulsatile release can cause the levels of many hormones to vary markedly over short intervals, leading to a loss of precision in between-subject comparisons. Clinicians often control this variation by collecting several samples from each subject at defined intervals and pooling these samples for assay. The number of samples per subject that would adequately control such variation in an epidemiologic study has not been fully investigated. This study examines the effects of collecting 1, 2, or 3 samples per subject on the variances of 11 hormones and sex hormone binding globulin in men and 6 hormones in women. Three samples were collected at 30-minute intervals from each of 20 men and 59 women and were assayed separately. Variances that would be obtained in studies collecting one, two, or three samples per subject were then estimated. Collecting more than one sample substantially reduced the variances of several hormones in men but not in women.