A prospective study of uric acid by glucose tolerance status and survival: the Rancho Bernardo Study.

OBJECTIVES: Little is known about uric acid (UA) levels and mortality in the context of glycaemia. We examined whether serum UA levels predict all-cause and cardiovascular disease (CVD) mortality differentially in older adults by glucose tolerance status. DESIGN AND METHODS: Between 1984 and 1987, 2342 community-dwelling men and women had an oral glucose tolerance test, UA measurement, and assessment of traditional CVD risk factors. We defined glucose tolerance status as normoglycaemia (NG), pre-diabetes (pre-DM), and type 2 diabetes mellitus (T2DM). Ninety per cent were followed for vital status up to 23 years. Death certificates were coded using the Ninth International Classification of Diseases. RESULTS: Baseline age was 69.5 years; 44.4% were men. At baseline 939 had NG, 957 pre-DM, and 446 T2DM. The mean UA by glucose tolerance status was 327.1, 362.8, and 374.7 micromol L(-1). During follow-up, there were 1318 deaths 46.8% attributed to CVD. In Cox-regression analysis, each 119 micromol L(-1) (2 mg dL(-1)) increment in UA levels predicted an increased hazard ratio (HR) for all-cause deaths independent of age, smoking, body mass index, alcohol, physical activity, diuretic use and estimated glomerular filtration rate in all groups (NG: HR 1.25 95% CI 1.06-1.47, P =0.005; pre-DM: HR 1.20 95% CI 1.06-1.37, P = 0.04; T2DM: HR 1.20 95% CI 1.01-1.47, P = 0.04). After adjusting for CVD risk factors, the UA association with CVD mortality was significant only in the pre-DM and T2DM groups. CONCLUSION: All-cause mortality was independently associated with UA in all groups, but UA predicted CVD mortality only in those with abnormal glucose tolerance.

Mid-life blood pressure levels and the 8-year incidence of type 2 diabetes mellitus: the Rancho Bernardo Study.

Type 2 diabetes mellitus (T2DM) and hypertension frequently occur together. We examined whether blood pressure (BP) levels predict 8-year incident diabetes. Participants were community-dwelling older adults who had BP measured twice and an oral glucose tolerance test at baseline and again 8.3 years later. At baseline, participants were classified as normotensive (systolic blood pressure (SBP) <120 mm Hg and diastolic blood pressure (DBP) <80 mm Hg; n=242); prehypertensive (SBP>or=120 and <140 mm Hg or DBP>or=80 and <90 mm Hg; n=426); or hypertensive (SBP>or=140 mm Hg or DBP>or=90 mm Hg or using anti-hypertensive medication; n=457). There were 1125 participants (mean age 66.0 years; 44.3% men) who attended the baseline and follow-up visit, of whom 85 had new onset T2DM. Participants who developed T2DM had higher mean body mass index (BMI) and BP levels than those who did not develop diabetes. In logistic regression models adjusted for age, sex, BMI, and physical activity, the odds of incident T2DM was greater in prehypertensives (odds ratio (OR) 2.32 95% confidence interval (CI) 1.05-5.1, P=0.03) and hypertensives (OR 3.5 95% CI 1.50-8.0, P=0.002) compared with normotensives. Excluding participants who used anti-hypertensive medications did not change results. In conclusion, mid-life hypertension and prehypertension predicted future diabetes, independent of BMI. Glucose surveillance should be encouraged in adults with prehypertension or hypertension.

Adipocytokines, sex hormones, and cardiovascular risk factors in postmenopausal women: factor analysis of the Rancho Bernardo study.

Steroid sex hormones modulate the expression of adipocytokines implicated in the pathogenesis of athero-thrombotic cardiovascular disease. We used exploratory factor analysis to search for latent associations between circulating sex steroid hormones, adipocytokines, and cardiovascular risk factors in a well-characterized cohort of postmenopausal women. Among participants in the Rancho Bernardo community study we identified 515 Caucasian women with a mean age of 74+/-8 years and mean body mass index of 24.2+/-3.7 kg/m(2). All had intact ovaries and none was using estrogen therapy. We constructed models aiming for structural clarity and high loading of variables on individual factors. Total adiponectin loaded with major lipid subfractions (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and fasting triglycerides) and with sex hormone-binding globulin. Leptin loaded with central obesity (waist circumference) and fasting insulin levels. Neither adipocytokine loaded with total or bioavailable testosterone or with estradiol or dehydroepiandrosterone sulfate. Sex hormones consistently loaded together on a separate factor; this co-segregation was not influenced by body mass index. Exclusion of women with diabetes did not alter these observations. In conclusion, we identified evidence of latent associations between adipocytokines and a range of cardiovascular risk factors in postmenopausal women. Our results suggest that cardiovascular risk in older women may be modulated through a hitherto unrecognized association between adiponectin, lipid subfractions, and sex hormone bioavailability.

Peripheral arterial disease and osteoporosis in older adults: the Rancho Bernardo Study.

SUMMARY: We examined the association between peripheral arterial disease (PAD) and bone health in 1,332 adults. We found a weak association between PAD and osteoporosis and bone loss only in women, but the association was not independent of age. PAD was not associated with fractures in this community-based population. INTRODUCTION: Increased rates of osteoporosis have been reported in patients with cardiovascular disease, suggesting a link between osteoporosis and atherosclerosis. METHODS: We examined the association between PAD and bone health in 1,332 adults who attended a research visit in 1992-1996, when the ankle-brachial index (ABI), bone mineral density (BMD), and spine X-rays were obtained. A total of 837 participants attended a follow-up visit in 1997-2000. RESULTS: PAD defined by an ABI < or = 0.90 was present in 15.4% of the women and 13.3% of the men. Prevalence of osteoporosis was significantly higher in women with PAD compared to women without PAD (p < 0.05). During an average 4-year follow-up, women with PAD had a significantly higher rate of bone loss than women without PAD (p = 0.05). The associations were no longer significant after age adjustment. In men, PAD was not associated with osteoporosis, but men with PAD had lower BMD at the femoral neck than men without PAD (p = 0.03). PAD was not associated with osteoporotic fractures in either sex. CONCLUSION: We found a weak and age-dependent association between PAD and osteoporosis in women but not men. PAD was not associated with fractures in this community-based population.

Sex-specific association of serum vitamin D levels with physical function in older adults.

UNLABELLED: In women, but not men, lower 25-hydroxyvitamin D [25(OH)D] levels were associated with impaired performance on two lower extremity function tests in both cross-sectional and prospective analyses. INTRODUCTION: Preserved physical function may explain how 25(OH)D supplementation reduces falls and fractures. METHODS: A total of 1,065 community-dwelling men and women (mean age 74.6 years) with 25(OH)D levels and performance on timed up and go (TUG) and timed chair stand (TCS) were seen in 1997-1999; 769 (72%) participants returned for follow-up. Associations were examined using generalized linear models. RESULTS: 25(OH)D levels were higher in men than women, but the prevalence of vitamin D insufficiency defined as 25(OH)D <75 nmol/L was 14%. There were no baseline sex differences in TUG or TCS. However, after 2.5 years, decline in TCS and TUG was greater in women than men (11% vs. 3%; p < 0.001). Women in the lowest 25(OH)D quartile (<80 nmol/L) compared to the highest quartile had an accelerated rate of functional decline on the TUG and TCS independent of covariates. No significant associations were seen in men. CONCLUSION: In women, but not men, lower 25(OH)D levels were associated with impaired performance on two lower extremity function tests in both cross-sectional and prospective analyses. These results provide additional evidence that 25(OH)D is associated with physical function, which may explain how vitamin D supplementation reduces falls and fractures.

Effect of dehydroepiandrosterone supplementation on bone mineral density, bone markers, and body composition in older adults: the DAWN trial.

UNLABELLED: We present results of a randomized, placebo-controlled trial to examine the effect of 50 mg daily oral DHEA supplementation for one year on bone mineral density (BMD), bone metabolism and body composition in 225 healthy adults aged 55 to 85 years. INTRODUCTION: Dehydroepiandrosterone (DHEA) levels decline dramatically with age, concurrent with the onset of osteoporosis, suggesting a role for DHEA supplementation in preventing age-related bone loss. METHODS: We conducted a randomized, placebo-controlled trial to examine the effect of 50 mg daily oral DHEA supplementation for one year on bone mineral density (BMD), bone metabolism and body composition in 225 healthy adults aged 55 to 85 years. RESULTS: DHEA treatment increased serum DHEA and DHEA sulfate levels to concentrations seen in young adults. Testosterone, estradiol and insulin-like growth factor (IGF-1) levels increased in women (all p < 0.001), but not men, receiving DHEA. Serum C-terminal telopeptide of type-1 collagen levels decreased in women (p = 0.03), but not men, whereas bone-specific alkaline phosphatase levels were not significantly altered in either sex. After 12 months, there was a positive effect of DHEA on lumbar spine BMD in women (p = 0.03), but no effect was observed for hip, femoral neck or total body BMD, and no significant changes were observed at any site among men. Body composition was not affected by DHEA treatment in either sex. CONCLUSION: Among older healthy adults, daily administration of 50 mg of DHEA has a modest and selective beneficial effect on BMD and bone resorption in women, but provides no bone benefit for men.

Associations between the metabolic syndrome and bone health in older men and women: the Rancho Bernardo Study.

UNLABELLED: We examined the associations of metabolic syndrome (MS) with BMD, osteoporosis, and osteoporotic fractures in 417 men and 671 women from the Rancho Bernardo Study. After adjusting for BMI, MS was associated with lower, not higher BMD. Incidence of osteoporotic non-vertebral fractures was higher in participants with MS. MS may be another risk factor for osteoporotic fractures. INTRODUCTION: The metabolic syndrome (MS) is a cluster of risk factors, including abdominal obesity, high glucose, triglycerides, hypertension and low HDL levels, associated with cardiovascular disease morbidity. The association between components of the MS and bone mineral density (BMD) has been researched, but results are contradictory. METHODS: We used multivariate regression models to examine the cross-sectional associations of MS defined by NCEP-ATP III criteria with BMD and osteoporosis, and the longitudinal association of MS with fractures in 420 men and 676 women from the Rancho Bernardo Study. RESULTS: Prevalence of MS at baseline was 23.5% in men and 18.2% in women. In age-adjusted analyses, men and women with MS had higher BMD at total hip when compared to those without MS (p < 0.001 and p = 0.01, respectively). Men but not women with MS also had higher BMD at femoral neck (p = 0.05). After adjusting for BMI, these associations were reversed, such that MS was associated with lower and not higher BMD. CONCLUSION: Incidence of osteoporotic non-vertebral fractures was higher in participants with MS. MS may be another risk factor for osteoporotic fractures. The association of MS with higher BMD was explained by the higher BMI in those with MS.

Serum 25-hydroxyvitamin D, parathyroid hormone, and bone mineral density in men: the Rancho Bernardo study.

INTRODUCTION: This study examined the distribution and determinants of serum 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) and their associations with bone mineral density (BMD) at the hip and spine in 414 older men (mean age 74 years) living in southern California. METHODS: At a clinic visit (1997-2000), demographic and lifestyle information, fracture history, and medication use were recorded; venous blood for serum 25OHD and PTH was obtained; and BMD was measured at the hip and spine. RESULTS: Only one man had vitamin D deficiency (25OHD <20 nmol/l), but 15.5% of the men had high parathyroid levels (PTH >or=65 pg/ml). The mean 25OHD and PTH levels were 109.0 nmol/l and 50.3 pg/ml, respectively. Overall, 21.5% used calcium and 9.7% used vitamin D supplements. Serum 25OHD decreased with age and was lowest in the winter; levels were higher in supplement users (vitamin D and/or calcium; p<0.01). Serum PTH did not vary by age or season, and it was lower in supplement users (p<0.01). After excluding 12 men who were outliers for serum 25OHD and PTH, there was no significant correlation between serum 25OHD and PTH (r=-0.05, p=0.3). In multiple adjusted models, serum 25OHD was positively associated with BMD at the hip (p=0.01) and spine (p=0.001). Serum PTH was moderately and inversely associated with BMD at the hip (p=0.04) but not at the spine (p=0.77). CONCLUSION: We conclude that serum 25OHD is associated with bone health in older, community-dwelling men.

Low testosterone levels are associated with carotid atherosclerosis in men.

OBJECTIVE: To study the relationship between endogenous sex hormone levels and intima-media thickness (IMT) of the carotid artery measured by ultrasonography. DESIGN: Population-based cross-sectional study. METHODS: Sex hormone levels measured by immunoassay, anthropometric measurements and IMT was studied in 1482 men aged 25-84 years participating in the 1994-1995 Tromsø study. The data were analysed with partial correlation, multiple linear regression and logistic regression analysis. RESULTS: Linear regression models showed that total testosterone and sex hormone-binding globulin levels, but not calculated free testosterone, serum oestradiol or dehydroepiandrosterone sulphate levels were inversely associated with the age-adjusted IMT (P = 0.008 and P < 0.001 respectively). These associations were independent of smoking, physical activity, blood pressure and lipid levels, but were not independent of body mass index (BMI). Excluding men with cardiovascular disease (CVD) did not materially change these results. In a logistic regression model adjusted for the confounding effect of CVD risk factors, men with testosterone levels in the lowest quintile (<9.0 nmol L(-1)) had an independent OR = 1.51 (P = 0.015) of being in the highest IMT quintile. CONCLUSIONS: We found an inverse association between total testosterone levels and IMT of the carotid artery in men that was present also after excluding men with CVD, but was not independent of BMI. The clinical relevance of this, however, is uncertain and needs to be investigated in a clinical setting.

A comparison between peripheral BMD and central BMD measurements in the prediction of spine fractures in men.

INTRODUCTION: Most of the research on osteoporosis has been conducted on women. Few studies have compared central and peripheral densitometry and their association with vertebral fractures in men. The present study was designed to compare peripheral bone mineral density (BMD) measurements with central BMD measurements, and to examine their association with radiographic spine fracture in men. METHODS: We studied 402 community-dwelling men aged 45-92 years (mean: 70 years) from the Rancho Bernardo Study cohort who attended a clinic visit between 1988 and 1992 when BMD measurements of the midshaft radius, ultradistal wrist, lumbar spine, and total hip were obtained, and who returned for lateral X-rays of the thoracic and lumbar spine an average of 4 years later. Logistic regression, T-scores, and quintiles were used to analyze BMD and its association with vertebral fractures. RESULTS: The prevalence of osteoporosis defined by the National Osteoporosis Foundation criteria (for women) was 14.2% at the spine and 13% at the hip. Because there are no validated definitions of osteoporosis based on the ability to predict fracture risk for peripheral densitometry, the frequency of overlap by bone site was calculated among men in the lowest quintile of each site. Of the 402 men, 82 men (20.3%) had at least two sites with BMD measurements in the lowest quintile. After an average of 4 years, 33 (8.2%) men had at least one radiographic vertebral fracture, and ten (2.5%) men had at least two vertebral fractures. Low BMD at the spine (with and without covariate adjustment) was associated with having one or more vertebral fractures, whether using NOF T-score-defined osteoporosis [Odds ratio (OR): 3.81; confidence interval (CI): 1.52, 9.57] or the lowest quintile versus all others (OR: 2.53; CI: 1.03, 6.19). After age and/or other covariate adjustments, neither BMD at the total hip nor at the peripheral sites was associated with spine fractures using either NOF women-based criteria or male quintiles from this cohort. CONCLUSION: Although different men had osteoporosis defined by quintiles at different sites, only low BMD at the spine was associated with vertebral fracture.

Osteoporosis and apolipoprotein E genotype in older adults: the Rancho Bernardo study.

Recent studies reported an association between apolipoprotein E (ApoE) 4 and osteoporosis. We examined the association of ApoE 4 genotype with bone mineral density (BMD), bone loss and fracture risk in 596 men and 332 community-dwelling women aged 45-95 years. Women were postmenopausal and not using estrogen. At the baseline visit, BMD was measured at the ultradistal and midshaft radius using single photon densitometry, and at the hip and lumbar spine using dual-energy X-ray absorptiometry. Hip and lumbar spine BMD levels were remeasured 4 years later. Self-reported fractures were confirmed by radiology reports in 95% of cases. ApoE allele distribution did not vary by age; 25% of men and 20% of women had one ApoE 4 allele. There were no differences in BMD at the lumbar spine, total hip, ultradistal or midshaft radius in men or women with the ApoE 4 allele compared with men or women without the ApoE 4 allele. After an average 4 year interval, there were also no differences in the annualized percent change in BMD at the hip or lumbar spine in men or women with or without an ApoE 4 allele. One or more clinical fractures were reported by 55 men and 109 women. Fewer, not more, clinical fractures were reported in men and women with an ApoE 4 allele; these differences were not statistically significant (p = 0.21 and p = 0.62, respectively). These data do not support the hypotheses that there is an association between ApoE genotype and BMD, bone loss or osteoporotic fractures in older community-dwelling men or women.

Prevalence and clustering of menopausal symptoms in older women by hysterectomy and oophorectomy status.

This study examines the association of hysterectomy and oophorectomy with the prevalence and clustering of menopausal symptoms in a large population-based sample of older women. Subjects were 1121 women aged 50-89 from the Rancho Bernardo Study. Information on menopause, hysterectomy, oophorectomy, estrogen use, and other covariates was obtained in 1984-1987. A 1989 mailed survey obtained information on menopausal symptoms. In this sample, 22.1% reported hysterectomy with bilateral oophorectomy, and 25.3% reported hysterectomy with ovarian conservation. Mean time since hysterectomy was 26 (+/-12) years. Overall, 37% reported current estrogen use, and 40% reported past use. The duration of estrogen use was longer for women who had a hysterectomy (p < 0.001). Age-adjusted comparisons indicated that more women who had a hysterectomy, with or without bilateral oophorectomy, reported greater energy after menopause (p = 0.003 and p = 0.001, respectively), and more women with bilateral oophorectomy reported greater interest in sex (p = 0.007) and that life was getting better (p = 0.012) than women with natural menopause. Principal components factor analysis of the symptom data for all women yielded four factors: psychological, vasomotor, positive feelings, and self-image. Analyses performed within each group of women yielded similar factors and loadings. Adjusted comparisons of factor scores indicated that positive feelings were significantly higher in women who had a hysterectomy, with or without bilateral oophorectomy (p < 0.01) than in women with natural menopause. This difference was limited to current estrogen users. Vasomotor symptoms, psychological symptoms, and negative self-image did not differ by hysterectomy or oophorectomy status before or after stratification for estrogen use (p > 0.10). This study found after a hysterectomy, women are more likely to recall positive feelings about their menopause than women with natural menopause. Relief from symptoms leading to hysterectomy and use of replacement estrogen may be partly responsible. Results do not support the thesis that surgical menopause is associated with a sustained increased prevalence of vasomotor, psychological, or other symptoms.

Vasomotor symptoms are not associated with reduced bone mass in postmenopausal women: the Rancho Bernardo Study.

The association of menopause-related vasomotor symptoms with later bone mineral density (BMD) at axial and appendicular sites was examined in community-dwelling older women. Subjects were 894 postmenopausal women from the Rancho Bernardo Study who had BMD measured in 1988-1991 and responded to a 1989 mailed survey that included questions about menopause symptoms. Mean age was 73 years (SE +/- 9.5, range 47-97), and mean age at menopause was 47 years (SD +/- 6.8, range 21-62). Vasomotor symptoms were recalled by two thirds (68%) and night sweats by 36% of all women, with no significant differences in symptom frequency by age or type of menopause. Postmenopausal estrogen (PME) had been used by 644 women (72%) for an average duration of 12.3 (+/-11) years. Among women who reported current estrogen use with a duration >3 years, those who experienced vasomotor symptoms had significantly higher BMD at the lumbar spine (p = 0.01), femoral neck (p = 0.05) and midshaft radius (p = 0.05) compared with women who did not experience symptoms. Vasomotor symptoms were not associated with BMD among past or never PME users or among women who reported current PME use for 3 or fewer years. Analyses stratified by age, type of menopause, or when PME use began showed similar results. Women who reported night sweats also had no difference in BMD compared with women without night sweats. In conclusion, vasomotor symptoms are not a marker for low BMD years after menopause in women with access to healthcare. Vasomotor symptoms significantly increased the likelihood of continued use of PME, which was in turn associated with higher BMD levels.

Hysterectomy, oophorectomy, and endogenous sex hormone levels in older women: the Rancho Bernardo Study.

This study examines the cross-sectional association of hysterectomy and oophorectomy status, chronological age, and years since menopause with plasma levels of total and bioavailable testosterone and estradiol, androstenedione, estrone, and sex hormone-binding globulin (SHBG) in community-dwelling postmenopausal women who were not using estrogen replacement therapy. Six hundred and eighty-four women, aged 50-89 yr, were surveyed for hysterectomy and oophorectomy status and had plasma obtained between 1984-1987. Of these, 438 (67%) had not undergone hysterectomy or oophorectomy (intact), 123 (18%) reported hysterectomy with bilateral oophorectomy, and 123 (18%) reported hysterectomy with conservation of 1 or both ovaries. After adjustment for age and body mass index, both total and bioavailable testosterone levels were reduced by more than 40% (P < 0.001) in hysterectomized women with bilateral oophorectomy compared to those in intact women, with intermediate levels observed in hysterectomized women with ovarian conservation. Androstenedione levels were about 10% lower in hysterectomized women with or without ovarian conservation compared to those in intact women (P = 0.039). Total estradiol levels tended to be lower (P = 0.095) in bilaterally oophorectomized women. Levels of bioavailable estradiol, estrone, and SHBG did not differ by hysterectomy and oophorectomy status. Among intact women, total, but not bioavailable, testosterone levels increased with age (P = 0.015), reaching premenopausal levels for the 70-79 decade with relatively stable levels thereafter. Among oophorectomized women, total and bioavailable testosterone levels did not vary with age and were 40-50% lower than those in intact women throughout the 50-89 yr age range. Androstenedione levels decreased 27% and SHBG levels increased 30% (P < 0.001) with age in intact, but not oophorectomized, women. Levels of other hormones did not vary with age. Stratification by years since menopause or surgery yielded similar results. These results demonstrate that the postmenopausal ovary remains a critical source of androgen throughout the lifespan of older women. The clinical consequences of lower testosterone levels years after oophorectomy are unknown. Reconsideration of prophylactic oophorectomy and clinical trials to evaluate the effects of androgen replacement after oophorectomy are needed.

Low levels of estradiol are associated with vertebral fractures in older men, but not women: the Rancho Bernardo Study.

This longitudinal study included 288 postmenopausal women without estrogen use (median age, 72 yr) and 352 men (median age, 66 yr). All were community-dwelling, ambulatory, and Caucasian. Blood for hormone assays (total and bioavailable estradiol and testosterone, estrone, androstenedione, dihydrotestosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate) was obtained in 1984-1987, and vertebral fractures were diagnosed from lateral spine radiographs obtained in 1992-1996. At least one vertebral fracture was found in 21% of women and 8% of men. Among men, age-adjusted hormone levels differed by fracture status only for total (64.1 vs. 75.4 pmol/L, P = 0.012) and bioavailable (43.0 vs. 51.4 pmol/L, P = 0.008) estradiol. There was a graded association between higher concentrations of total and bioavailable estradiol and lower fracture prevalence (trend P<0.01 for both hormones). Men with total testosterone levels compatible with hypogonadism (<7 nmol/L) were not more likely to have vertebral fractures. In women, none of the measured sex hormones was associated with vertebral fractures. There was also no increased prevalence of fractures in women with estradiol levels below the assay sensitivity (<11 pmol/L). These data suggest that estrogen plays a critical role in the skeletal health of older men and confirm other studies showing no association of postmenopausal endogenous estrogen levels with vertebral fractures in older women.

Evaluation of the simple calculated osteoporosis risk estimation (SCORE) in older Caucasian women: the Rancho Bernardo study.

Osteoporosis is a major health problem in older women. A risk assessment tool, the Simple Calculated Osteoporosis Risk Estimation (SCORE), has been developed to identify postmenopausal women likely to have low bone mass who should be referred for bone densitometry. The objective of this study was to calculate the sensitivity, specificity and predictive values of SCORE in a community-dwelling sample of older women. A total of 1013 postmenopausal Caucasian women aged 44-98 years provided a standard medical history including history of osteoporotic fractures and medication use. Bone mineral density (BMD) was measured at the femoral neck using dual-energy X-ray absorptiometry. In accordance with the SCORE protocol, low BMD was defined as 2 or more standard deviations below the mean BMD in healthy young women. Among these older women (mean age = 72.5 years), 67% had low BMD. Using the recommended SCORE cutpoint of 6, the sensitivity of SCORE was 98% but the specificity was only 12.5%. The positive predictive value (PPV) and negative predictive value (NPV) were 69% and 75%, respectively, meaning that all but 5.5% of the women would be recommended for bone densitometry. Increasing the cutpoint of 11, based on ethnicity and the receiver operating characteristic (ROC) curve, reduced sensitivity to 80% but improved specificity to 46%. The PPV and NPV were 75% and 53%, respectively, meaning that bone scans would not be recommended for 28% of the women. However, 13% of the women with low BMD would be missed. Analyses restricted to women <74 years of age reduced the rate of recommended bone densitometry but increased the number of women with low BMD who would be missed. We conclude that SCORE has limited value as a method for appropriately referring older ambulatory women for bone densitometry.

Endogenous levels of dehydroepiandrosterone sulfate, but not other sex hormones, are associated with depressed mood in older women: the Rancho Bernardo Study.

OBJECTIVE: The purpose of this study was to determine whether endogenous steroid hormone levels are associated with depressed mood in community-dwelling older women. DESIGN: A cross-sectional population-based study. SETTING: Rancho Bernardo, California PARTICIPANTS: A total of 699 non-estrogen using, community-dwelling, postmenopausal women (aged 50 to 90 years) from the Rancho Bernardo cohort who were screened for depressed mood and had plasma obtained for steroid hormone assays in 1984-1987. MEASUREMENTS: Plasma levels of total and bioavailable (non-SHBG-bound) estradiol and testosterone, estrone, androstenedione, cortisol, dehydroepiandrosterone, and (DHEA) and its sulfate (DHEAS) were measured by radioimmunoassay. Mood and depression were assessed using the Beck Depression Inventory. RESULTS: Only DHEAS levels were significantly and inversely associated with depressed mood, and the association was independent of age, physical activity, and weight change (P = .0002). Age, sedentary lifestyle, and weight loss were positively associated with depressed mood. Alcohol intake, cigarette smoking, marital status, type of menopause, and season of testing were unassociated with depressed mood. A subset of 31 women with categorically defined depression had lower DHEAS levels compared with 93 age-matched nondepressed women (1.17 +/- 1.08 vs 1.57 +/- .98 micromol/L; P = .01). CONCLUSIONS: These results add to the evidence that DHEA/S is a neuroactive steroid and point to the need for careful long-term clinical trials of DHEA therapy in older women with depressed mood.

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.

A community-based study of menopause symptoms and estrogen replacement in older women.

This study examines the symptoms after a natural menopause recalled by women aged 50-89 years. We determined the frequency and clustering of symptoms, the effect of age on symptoms, and the relation of symptoms to the use of estrogen therapy in a cross-sectional, community-based study of 589 Caucasian, middle- to upper-middle-class women from Rancho Bernardo, California. At the time of menopause, 55% of the women reported that they felt life was getting better and 57% were more cheerful. The most frequently recalled symptoms were hot flushes (74%), propensity to weight gain (45%), night sweats (35%), tiredness (32%), and insomnia (28%). Irritability was reported by one-fourth, depression by one-fifth. Nearly 11% reported anxiety about looking older. The recalled prevalence of hot flushes, irritability, weepiness and tiredness did not vary by current age, but younger women were significantly more likely than older women to have experienced night sweats, visible flushes, depression, anxiety about looking older and insomnia. Principal components factor analysis yielded four main independent factors: psychological symptoms (21% of the variance), vasomotor symptoms (14%), positive feelings (11%), and negative self-image (8%). The four symptom groupings suggest different causal mechanisms. Forty-two percent reported past, and 27% reported current use of estrogen therapy. Both past and current hormone users were significantly more likely to report menopause symptoms than non-users. Estrogen use was not associated with positive feelings or self-image at the time of menopause. Although three-quarters experienced symptoms, the majority of women reported positive feelings about menopause.