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Biomedical subjects

E Barrett-Connor

Publications and source records attributed to E Barrett-Connor.

At least 55 records · Page 3Linked to original sources
PubMed2000

Birth weight as a predictor of adult bone mass in postmenopausal women: the Rancho Bernardo Study.

Understanding the determinants of adult bone mass may help to identify women for prevention of osteoporosis. We postulated that birth weight would predict low adult bone mass in old age. Subjects were 305 postmenopausal Caucasian women (mean age 70 years). Bone mineral content (BMC) and bone mineral density (BMD) were measured at the wrist, forearm, hip and lumbar spine. Birth weight was assessed by self-report. Birth weight was positively correlated with BMC at the forearm (r = 0.15), hip (r = 0.12) and lumbar spine (r = 0.18), and the age-adjusted mean BMC increased significantly from the lowest to the highest birth weight tertile. Adjusting for adult weight diminished this association at the forearm and hip, but not at the spine. Adjustment for multiple other covariates, including height, did not materially change these associations. Adult weight and height were significantly correlated with birth weight (r = 0.19 and r = 0.24, respectively). Birth weight was not independently correlated with BMD. Birth weight was thus positively correlated with adult weight and BMC 70 years later. These findings suggest that low birth weight may be a marker for future low bone mass and that different mechanisms exist for establishing the adult bone envelope (estimated by BMC) versus its density (estimated by BMD).

Absorptiometry, Photon↗
PubMed2000

Lower extremity arterial disease in older women: the Rancho Bernardo Study.

Most studies of lower extremity arterial disease (LEAD) have not included women. To study the frequency of LEAD and its association with cardiovascular disease risk factors and estrogen use in community-dwelling postmenopausal women, we conducted a cross-sectional study of LEAD in 826 women whose average age was 74 years. Cardiovascular disease risk factors and medical history, body mass index (BMI), blood pressure, glucose tolerance, lipids and lipoproteins, and current and past medication use were determined using a standard protocol. Ankle-brachial artery index (ABI) of systolic blood pressure was measured by a trained technician using Doppler ultrasound. LEAD was defined as ABI <0.8. LEAD prevalence increased with age from nearly 5% in the 60-69-year-old group to >25% in women aged 90 and older. In age-adjusted analyses, women with LEAD had significantly lower levels of high-density lipoprotein (HDL) cholesterol, were less likely to exercise regularly, and were less likely to have ever used estrogen replacement therapy. They also had significantly higher levels of blood pressure, low-density lipoprotein (LDL) cholesterol, triglycerides, glucose, and insulin. In multivariate analyses, high HDL cholesterol, regular exercise, and estrogen use were each associated with a reduced risk of LEAD, whereas age, high blood pressure, and abnormal glucose tolerance were each associated with increased risk. Few women (6%) were smokers, but they had twice the risk of LEAD compared with nonsmokers. Estrogen was independently associated with LEAD in a model containing all covariates except LDL and HDL, and this association was no longer significant in a second model adjusting for these lipoproteins. LEAD is common in older women and associated with modifiable risk factors. The apparent protection associated with estrogen should be studied in clinical trials.

Age Distribution↗
PubMed2000

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.

Aged↗
PubMed2000

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.

Aged↗
PubMed2000

Higher basal cortisol predicts verbal memory loss in postmenopausal women: Rancho Bernardo Study.

BACKGROUND: In animals, higher endogenous or exogenous corticosteroids cause neuronal dysfunction, damage, and loss, especially in the hippocampus. In humans, high cortisol levels have been linked to memory impairment. OBJECTIVE: To prospectively examine the relation between morning basal cortisol level and change in cognitive performance during an average follow-up of 2 years. DESIGN: Longitudinal cohort. SETTING: Geographic community in southern California. MEASUREMENTS: Between 1984 and 1987, blood for basal morning cortisol was obtained along with pertinent medical, behavioral, and physical covariates from 749 post-menopausal women, mean age 72 years, who were not taking corticosteroids or postmenopausal hormones. Cognitive function was assessed in 502 women in the period from 1988 to 1991 and repeated in 136 women in the period from 1991 to 1993. RESULTS: In both age- and multiply adjusted linear regression models, higher baseline cortisol was a significant predictor of worsened category fluency. No other cognitive domain tested was related to cortisol. CONCLUSIONS: These results support the hypothesis that subtle dysregulation of cortisol axis is related to memory loss. Interventions that block this pathway may provide new therapeutic options to prevent cognitive decline.

Aged↗
PubMed2000

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.

Age Factors↗
PubMed2000

Sexual dimorphism in the influence of advanced aging on adrenal hormone levels: the Rancho Bernardo Study.

In recent years, adrenal function and aging has been the subject of intense interest. This cross-sectional study examines age and gender differences in plasma levels of cortisol, dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEAS), and the molar ratio of cortisol/DHEAS in 50-89-yr-old community-dwelling adults. Plasma hormone levels were assayed in samples obtained between 0730 h and 1100 h from 857 men and 735 nonestrogen-using, postmenopausal women. Hormone levels were stratified by 10-yr age groups and compared by two-factor (gender and age) ANOVA. Overall, age and BMI-adjusted DHEA and DHEAS [collectively DHEA(S)] levels were 40% lower and cortisol levels 10% higher in women than men, resulting in a 1.7-fold higher cortisol/DHEAS molar ratio for women (both, P < 0.001). Cortisol levels increased progressively (20% overall) with age in both men and women (both, P < 0.01). Although DHEA(S) levels declined 60% and the cortisol/DHEAS ratio increased 3-fold across the 40-yr age range for both men and women (all P < 0.001), the pattern of the change differed (all P < 0.01 for interaction). For men, DHEA(S) fell in a curvilinear fashion, with the degree of change decreasing with each decade. In contrast, DHEA(S) levels in women fell 40% from the 50s to 60s, were unvarying from 60-80 yr of age, and declined an additional 18% in the 80s. The cortisol/DHEAS ratio increased in a linear fashion for men, but was flat during the 60-80-yr age range for women. Despite these differences in the effect of aging, levels of DHEA(S) remained lower and cortisol and the cortisol/DHEAS ratio higher, in women than men throughout the 50-89-yr age range. These results were independent of adiposity, smoking, and alcohol consumption. In summary, among older, healthy adults DHEA(S) levels are lower and cortisol levels higher in women than men. The age-related decline in adrenal androgens persists into advanced age for both men and women, but exhibits a sexually dimorphic pattern. In contrast, cortisol levels in men and women show a parallel, linear increase with aging. These findings may have important implications for a host of age-related processes that exhibit gender differences, including brain function, bone metabolism, and cardiovascular disease.

Adrenal Cortex Hormones↗
PubMed2000

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.

Aged↗
PubMed2000

Sex differences in the association of endogenous sex hormone levels and glucose tolerance status in older men and women.

OBJECTIVE: Some evidence suggests an inverse association between type 2 diabetes and androgens in men and a positive association between type 2 diabetes and androgens in women. The purpose of this community-based study was to evaluate sex differences in the association between endogenous total and bioavailable estrogen and testosterone levels and glucose tolerance status. RESEARCH DESIGN AND METHODS: We included in this study 775 men and 633 postmenopausal non-estrogen-using women, all > or =55 years of age (mean ages 72 and 75 years, respectively). A 75-g oral glucose tolerance test (OGTT) was administered to fasting subjects from 1984 to 1987, when sera were frozen for measurement of total and bioavailable hormone levels. Total testosterone and estradiol levels were measured by radioimmunoassay, and bioavailable hormone levels were determined using a modified ammonium-sulfate precipitation method. The association between steroid hormones and glucose tolerance status was tested. RESULTS: In sex-specific age- and BMI-adjusted analyses, men with impaired glucose tolerance (IGT) had significantly lower total testosterone levels. Women with IGT or type 2 diabetes had significantly higher bioavailable testosterone and total and bioavailable estradiol levels than those with normal glucose tolerance. Total testosterone and fasting plasma glucose were inversely associated in men (P = 0.0001), whereas bioavailable testosterone and estradiol were positively associated with fasting plasma glucose in women (P = 0.0001 and 0.001, respectively). CONCLUSIONS: Additional studies are needed to further develop the hormone-diabetes connection.

Aged↗
PubMed1999

Effect of postmenopausal hormones on inflammation-sensitive proteins: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Study.

BACKGROUND: Observational studies in healthy women suggest postmenopausal hormone therapy reduces risk of coronary events. In contrast, in a recent clinical trial of women with coronary disease, a subgroup analysis demonstrated increased risk during the early months of therapy. Because higher levels of inflammation factors predict vascular disease outcomes, the effect of hormones on these factors is of interest. METHODS AND RESULTS: Four inflammation-sensitive factors, C-reactive protein, soluble E-selectin, von Willebrand factor antigen, and coagulation factor VIIIc were measured at baseline, 12, and 36 months in 365 participants of the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial, a randomized, placebo-controlled trial of the effects of 4 hormone preparations on cardiovascular disease risk factors. Compared with placebo, all 4 active preparations resulted in a large sustained increase in the concentration of C-reactive protein and a decrease in soluble E-selectin (P=0.0001). There were no effects of treatment on concentrations of von Willebrand factor or factor VIIIc. There were no differences in effects among treatment arms. Relative to placebo, when combining active treatment arms, final concentrations of C-reactive protein were 85% higher whereas E-selectin was 18% lower compared with baseline. CONCLUSIONS: Postmenopausal hormones rapidly increased the concentration of the inflammation factor C-reactive protein. Such an effect may be related to adverse early effects of estrogen therapy. In contrast, hormones reduced the concentration of soluble E-selectin, and this might be considered an anti-inflammatory effect. Because PEPI was not designed to assess clinical endpoints, studies of the impact of hormone-mediated changes in inflammation on risk of subsequent coronary events are needed.

Antigens↗
PubMed1999

Effects of estrogen and estrogen-progestin on mammographic parenchymal density. Postmenopausal Estrogen/Progestin Interventions (PEPI) Investigators.

BACKGROUND: In longitudinal studies, greater mammographic density is associated with an increased risk for breast cancer. OBJECTIVE: To assess differences between placebo, estrogen, and three estrogen-progestin regimens on change in mammographic density. DESIGN: Subset analysis of a 3-year, multicenter, double-blind, randomized, placebo-controlled trial. SETTING: Seven ambulatory study centers. PARTICIPANTS: 307 of the 875 women in the Postmenopausal Estrogen/Progestin Interventions Trial. Participants had a baseline mammogram and at least one follow-up mammogram available, adhered to treatment, had not taken estrogen for at least 5 years before baseline, and did not have breast implants. INTERVENTION: Treatments were placebo, conjugated equine estrogens (CEE), CEE plus cyclic medroxyprogesterone acetate (MPA), CEE plus daily MPA, and CEE plus cyclic micronized progesterone (MP). MEASUREMENTS: Change in radiographic density (according to American College of Radiology Breast Imaging Reporting and Data System grades) on mammography. RESULTS: Almost all increases in mammographic density occurred within the first year. At 12 months, the percentage of women with density grade increases was 0% (95% CI, 0.0% to 4.6%) in the placebo group, 3.5% (CI, 1.0% to 12.0%) in the CEE group, 23.5% (CI, 11.9% to 35.1%) in the CEE plus cyclic MPA group, 19.4% (CI, 9.9% to 28.9%) in the CEE plus daily MPA group, and 16.4% (CI, 6.6% to 26.2%) in the CEE plus cyclic MP group. At 12 months, the odds of an increase in mammographic density were 13.1 (95% CI, 2.4 to 73.3) with CEE plus cyclic MPA, 9.0 (CI, 1.6 to 50.1) with CEE plus daily MPA, and 7.2 (CI, 1.3 to 40.0) with CEE plus cyclic micronized progesterone compared with CEE alone. CONCLUSIONS: Further study of the magnitude and meaning of increased mammographic density due to use of estrogen and estrogen-progestins is warranted because mammographic density may be a marker for risk for breast cancer.

Breast↗
PubMed1999

Larger increases in bone mineral density during alendronate therapy are associated with a lower risk of new vertebral fractures in women with postmenopausal osteoporosis. Fracture Intervention Trial Research Group.

OBJECTIVE: To investigate whether the incidence of vertebral fractures is related to the magnitude of change in bone mineral density (BMD) during alendronate treatment. METHODS: Women in this study were age 55-81 years (n = 2,984). While participating in the Fracture Intervention Trial, they received 5 mg/day of alendronate for 2 years followed by 10 mg/day for the remaining 12-30 months of the study. Their BMD was measured at baseline and at 12 and 24 months, and spine radiographs were obtained at baseline and again at 36 or 48 months to identify new vertebral fractures. RESULTS: After 12 months of alendronate treatment, 35% of participants had increases of > or =3% in total hip BMD, and 21% had either decreased total hip BMD or no change. Women who had larger increases in total hip BMD during the first 12 months had a lower incidence of new vertebral fractures during the entire followup period. Only 3.2% of women with increases of > or =3% in total hip BMD experienced new vertebral fractures, whereas twice as many women (6.3%) whose BMD declined or stayed the same experienced new fractures (adjusted odds ratio 0.45, 95% confidence interval 0.27-0.72). Similar patterns were observed for spine BMD at 12 months, and for both sites using change in BMD at 24 months. CONCLUSION: Women with increases of > or =3% in BMD during the first 1 or 2 years of alendronate treatment had the lowest incidence of new vertebral fractures. These findings suggest that, among women taking antiresorptive agents, greater increases in BMD are associated with lower risk of new vertebral fractures.

Aged↗
PubMed1999

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.

Absorptiometry, Photon↗