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Longitudinal analysis of the T-cell receptor (TCR)-VA and -VB repertoire in CD8+ T cells from individuals immunized with recombinant hepatitis B surface antigen.

Recent studies have suggested that vaccination induces alterations in the T cell receptor (TCR) repertoire. We investigate the diversity of the TCR repertoire after immunization with a recombinant hepatitis B surface vaccine in seven healthy subjects in CD8+ T cells in peripheral blood lymphocytes. Cellular immune responses were monitored over time by sorting CD8 T cells followed by TCR-VA and -VB complementarity determining region 3 (CDR3) analysis. Frequency of individual VB families was determined by flow cytometry. TCR-VA/VB repertoires obtained from CD8+ T cells drawn after vaccination were compared to the TCR repertoire determined prior to vaccination. Monoclonal TCR transcripts could be detected exclusively in CD8+, but not in CD4+ T cells. Such monoclonal TCR transcripts were either stable in some individuals, or could only be detected at certain time points after vaccination. Sorting of monoclonal TCR-VB3+ T cells, which constituted up to 5% of the CD8+ T cell population from one individual, revealed that this T cell clone recognizes an epitope provided by the recombinant hepatitis B vaccine presented by MHC-class I on autologous antigen-presenting cells. Examination of the structural anatomy, defined by the TCR, and the frequency of T cells responding to the immunizing antigen may be helpful to provide surrogate markers to monitor cellular immune responses induced by protein antigens utilized for vaccination.

Adult↗

[Longitudinal analysis of factors associated with participation in community-based mass screening for the frail elderly in need of care].

PURPOSE: To examine factors associated with participation in a community based comprehensive health check to screen frail elderly before they become in need of long-term care. METHODS: All residents aged 70 years and over living in Kusatsu, Gumma prefecture were surveyed for their sociodemographics, and physical, mental and social functioning through in-person interview in the years 2001 and 2003. In the following years--in 2002 and 2004, respectively--mass screenings were conducted to detect early signs of need for care among the elderly. Using the baseline interview information as explanatory variables, we performed multiple logistic regression analysis in order to examine the social determinants of participation in the mass-screening. RESULTS: For the first mass-screening, having high blood pressure and poor subjective health decreased the likelihood of attending the screening by 34% and 65% respectively. In contrast, one point increases in IADL, mobility and social-role score increased the probability of attendance by 27%, 26% and 26% respectively. After the screening was re-conducted, the factors influencing attendance appeared to have changed. With a third mass-screening, while the IADL and mobility score still had significant effects, elderly having excellent subjective health were less likely to go by some 48%. It was also found that not having visual impairment had a significantly positive effect on attendance. CONCLUSION: If local government conducts community-based mass screening aiming to screen the frail elderly in need of care, it is likely that there are high risk elderly among the non-participants. It is very important to follow up those non-participants using an attendance roll and provide appropriate advice. It is also worth discussing mass screening that focuses more on health promotion than on "screening" itself.

Activities of Daily Living↗

A longitudinal analysis of risk factors for child maltreatment: findings of a 17-year prospective study of officially recorded and self-reported child abuse and neglect.

OBJECTIVE: To identify demographic, family, parent, and child factors prospectively associated with risk for child abuse and neglect among families in the community, using data on child maltreatment obtained from both official records and youth self-reports. METHOD: Surveys assessing demographic variables, family relationships, parental behavior, and characteristics of parents and children were administered to a representative sample of 644 families in upstate New York on four occasions between 1975 and 1992. Data on child abuse and neglect were obtained from New York State records and retrospective self-report instruments administered when youths were > or = 18 years old. RESULTS: Logistic regression analyses indicated that different patterns of risk factors predicted the occurrence of physical abuse, sexual abuse, and neglect, although maternal youth and maternal sociopathy predicted the occurrence of all three forms of child maltreatment. In addition, the prevalence of child abuse or neglect increased from 3% when no risk factors were present to 24% when > or = 4 risk factors were present. State records and self-reports of child maltreatment did not correspond in most cases when maltreatment was reported through at least one data source, underlining the importance of obtaining data from both official records and self-reports. CONCLUSIONS: Assessment of a number of risk factors may permit health professionals to identify parents and children who are at high risk for child maltreatment, facilitating appropriate implementation of prevention and treatment interventions.

Child↗

Gender, psychosocial factors and the use of medical services: a longitudinal analysis.

Many researchers have reported gender differences in levels of reported symptoms, morbidity, mortality and medical care utilization, but the debate continues about the underlying causes of these differences. Some have argued that women use more medical services because they are more sensitive to symptoms and interested in health, while others believe that women's greater service utilization arises from the fact that women experience more morbidities than do men. To date, these questions have not been studied prospectively. Using data from a household interview survey carried out in 1970-1971 and linked to 22 years of health services utilization records, we explored the effects of gender, self-reported health status, mental and physical symptom levels, health knowledge, illness behaviors and health concerns and interest on the long-term use of health services. After controlling for the aforementioned factors, female gender remained an independent predictor of higher utilization over the 22-year period studied, and psychosocial and health factors measured at the initial interview predicted service use even 19-22 years later. Controlling for factors identified as likely causes of gender-related differences in healthcare utilization, gender remains an important predictor of medical care use before and after removing sex-specific utilization. In addition, the consistent predictive ability of attitudinal and behavioral factors, combined with the finding that health knowledge did not predict utilization, indicates that efforts to help patients assess their service needs should target the attitudinal and behavioral factors that vary with gender, rather than health-related knowledge alone.

Adolescent↗

Longitudinal analysis of Prototheca zopfii-specific immune responses: correlation with disease progression and carriage in dairy cows.

In order to characterize the humoral and cellular immune responses to bovine mammary protothecosis, serum and whey samples obtained from 72 dairy cows assigned to four different clinical stages of infection were examined for specific antibodies by indirect enzyme-linked immunosorbent assay techniques. Milk samples were analyzed for the total numbers of excreted algal cells and somatic cells. After characterization of the course of immune induction in bovine protothecal mastitis, a long-term sentinel study was performed in an affected herd in order to investigate disease progression. A total of 61 dairy cows with protothecal mastitis were examined for shedding of algae cells and for local immune responses three times in 6-month intervals. During acute and chronic stages of protothecosis, significantly elevated specific antibody activities in sera were detected. A strong correlation of whey immunoglobulin A (IgA) and whey IgG1 antibody activity with the total counts of somatic cells in milk was observed, whereas only a weak correlation of whey IgA and whey IgG1 concentrations to the number of algal cells excreted with the milk was seen. Our results from the sentinel long-term study of infected cows revealed that 70.5% of the persistently infected animals were continuously shedding the pathogen. About 4.9% of the animals showed an intermittent shedding, whereas 18% of the cows were tested culturally negative throughout the study. It can be assumed that Prototheca zopfii mastitis in dairy cows is maintained on the herd level by subclinically infected alga-shedding cows.

Animals↗

Longitudinal analysis of MART-1/HLA-A2-reactive T cells over the course of melanoma progression.

An HLA-A2-positive patient with advanced stage IV melanoma was vaccinated with dendritic cells (DCs) pulsed with melanoma antigens, whereby the rapid progression of disease stalled for a period of 10 months. Monitoring of the cellular immune response against one of the vaccinated HLA-A2-restricted epitopes demonstrated both induction and subsequent decline in the number of interferon-gamma (IFN-gamma)-producing MART-1-reactive cells present in the blood. Enumeration of reactive T cells by MART-126-35/HLA-A2 tetramer staining revealed an induction of such cells after three vaccinations and a subsequent decline that most prominent at times of rapid disease progression. However, a substantial number of reactive cells were present even when no MART-1 reactivity was detectable by functional assays. Isolation of such MART-126-35-reactive T cells by means of peptide/HLA-A2-coated magnetic beads demonstrated the persistence of a TCRVbeta14+ T-cell clone in this population over the whole observation period. Intracellular fluorescence-activated cell sorter staining of such TCRVbeta14+ T cells for IFN-gamma and interleukin-2 after maximal stimulation with phorbol 12-myristate 13-acetate/ionomycin revealed an impairment in their capacity to produce cytokines at the end of the observation period. Thus, functional changes of individual T-cell clones, e.g. clonal exhaustion, seem to be responsible for the known discrepancy between functional and phenotype assays for immune monitoring of tumour patients.

Antigens, Neoplasm↗

Drink-driving and DUI recidivists' attitudes and beliefs: a longitudinal analysis.

OBJECTIVE: Cross-sectional survey research has shown correlations between drink-driving behavior and people's beliefs concerning the riskiness, social acceptability and morality of driving under the influence of alcohol. The current study examines the association between such beliefs and subsequent alcohol-impaired driving in a sample of offenders who were driving under the influence (DUI). METHOD: Repeated interviews were conducted with 182 multiple DUI offenders. Baseline data included measures of moral and prescriptive beliefs concerning alcohol-impaired driving (internal behavioral controls), perceived risks of criminal punishment and crashes associated with alcohol-impaired driving (external behavioral controls) and perceived peer-group attitudes toward alcohol-impaired driving (social control). The dependent variable in the study was a measure of self-reported alcohol-impaired driving over the preceding 2 years, collected at 2-year follow-up from baseline. RESULTS: Results from multiple regression modeling showed significant protective effects associated with the beliefs that driving after drinking is immoral and that random police sobriety checks are a good idea (internal control items). Results also showed that a social desirability control measure was predictive of increased risk, at follow-up, for driving after drinking. CONCLUSIONS: These results suggest that internal controls may protect against alcohol-impaired driving behavior, even in a high-risk sample of repeat DUI offenders. The results also suggest that future policy interventions to curtail drink-driving might profitably be designed to promote these sorts of behavioral controls.

Adult↗

Couples' adjustment to breast cancer and benign breast disease: a longitudinal analysis.

A comprehensive comparison of couples' adjustment to benign (n = 73 couples) and malignant breast disease (n = 58 couples) at the time of diagnosis and at two follow-up assessments at 60 days and 1 year is reported. Specific objectives were to: (a) compare the concurrent stress, resources, appraisal, and patterns of adjustment of couples in the benign and malignant groups; (b) compare the psychosocial responses of patients versus spouses; and (c) determine the amount of correspondence in levels of adjustment reported by patients and their husbands over time. Multiple instruments with reported reliability and validity were used to measure study variables: Smilkstein Stress Scale, Dyadic Adjustment Scale, Family APGAR, Social Support Questionnaire, Mishel Uncertainty in Illness Scale, Beck Hopelessness Scale, Brief Symptom Inventory, and Psychosocial Adjustment to Illness Scale. Mixed design analyses of covariance (ANCOVA) were used to assess differences between and among couples and examine changes in study variables over time. Significant differences were found in the resources, appraisal, and patterns of adjustment reported by couples in the benign and malignant groups. Couples facing breast cancer reported greater decreases in their marital and family functioning, more uncertain appraisals, and more adjustment problems associated with the illness. In addition, there was a high degree of correspondence between the levels of adjustment reported by women with breast cancer and their husbands over time. Couples who reported high distress or a high number of role problems at diagnosis were likely to remain highly distressed at 60 days and 1 year. Study findings underscore the importance of assisting couples, not just patients, to manage the adjustment difficulties associated with breast cancer.

Adaptation, Psychological↗

[Longitudinal analysis of glucose metabolism in recurrent meningioma].

We repeatedly measured kinetic rate constants and glucose metabolic rate (kinetic rCMRG1) using dynamic positron emission tomography (PET) and autoradiographic rCMRG1 in a patient with recurrent meningioma. A 50-year-old woman who presented with a left visual disturbance was admitted to our hospital. MR images revealed a mass lesion occupying the left middle fossa. The patient underwent Simpson grade IV surgery. The histological diagnosis was meningothelial meningioma. One year later the tumor had grown back to almost the same size as before treatment and was removed again by Simpson grade IV procedure. Postoperatively, the patient underwent radiation therapy (54 Gy). Two years after the second operation, the tumor was found to have invaded the left orbit and was resected by Simpson grade IV procedure. After additional radiation therapy, the patient was discharged. The rate constants were analyzed preoperatively and whenever the tumor recurred according to the three compartment 18F-fluorodeoxyglucose (FDG) model. Preoperative PET indicated tumor k1 and k2 values higher than in the contralateral gray matter, suggesting high permeability due to absence of the blood-tumor barrier and an abundant blood supply. The tumor k3 value, an indicator of hexokinase activity, was as high as in the contralateral gray matter. When the tumor recurred, the tumor k1, k2 and k3 values remained consistently high, indicating high proliferative activity. In contrast, the contralateral gray matter k1, k2 and k3 values decreased to some extent, suggesting effects of surgery or radiotherapy. Tumor rCMRG1 values, both autoradiographic and kinetic, were enhanced markedly.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoradiography↗

Black-white differences in risk of becoming disabled and recovering from disability in old age: a longitudinal analysis of two EPESE populations.

This study compared the odds of becoming disabled and recovering from disability among blacks and whites aged 65 years and over in two sites of the Established Populations for Epidemiologic Studies of the Elderly (EPESE) project. The authors examined the influence of mortality differences, socioeconomic status, and health-related factors on racial differences in risk of disability and recovery. A Markov model was employed using nine waves of data from the New Haven, Connecticut, site (529 blacks, 2,219 whites) and seven waves of the North Carolina (Piedmont) site (2,260 blacks, 1,876 whites), collected between 1982 and 1992. Blacks below age 75 years had an increased risk of developing disability relative to whites in New Haven (odds ratio (OR) at age 65 years = 3.33, 95% confidence interval (CI) 2.13-5.22) as well as in North Carolina (OR at age 65 years = 1.58, 95% CI 1.25-1.99). This excess risk diminished with increasing age, and crossed over in New Haven (OR at age 85 years = 0.45, 95% CI 0.22-0.95), but not in North Carolina (OR at age 85 years = 1.22, 95% CI 0.98-1.51). Adjustment for socioeconomic and health-related factors only partially reduced the excess disability risk among blacks below age 75 years in New Haven, but eliminated the difference in disability risk between blacks and whites in North Carolina. Blacks below age 75 years also had higher mortality risks at both sites. There were no consistent racial differences in recovery from disability.

Black or African American↗

Longitudinal analysis of the association between depressive symptomatology and cognitive deterioration.

Although many studies have found a cross-sectional relation between depression and dementia or depressive symptomatology and cognitive functioning, the direction of the association is still unknown. The purpose of this analysis was to determine whether high depressive symptomatology is predictive of cognitive deterioration among the elderly 3 years later. Data came from a community-based prospective cohort study of noninstitutionalized and nondemented subjects aged 65 years and over living in the Gironde department in southwest France (1,600 subjects were interviewed at both study entry in 1989 and 3-year follow-up). Cognitive functions were assessed with the Mini-Mental State Examination (MMSE), and cognitive deterioration was defined as an MMSE score decrease of at least five points between two assessments. The Center for Epidemiologic Studies Depression (CES-D) Scale was used to evaluate the level of depressive symptomatology. The present study reports that a high level of depressive symptomatology is not predictive of cognitive deterioration 3 years later (relative risk = 0.8, 95% confidence interval 0.3-2.1). The authors observed that the risk of cognitive deterioration was associated with the concomitant level of depressive symptomatology at the 3-year follow-up, independent of depressive symptoms at entry. These results indicate that the association between high depressive symptomatology and poor cognitive functioning is cross-sectional, and they illustrate the importance of adjusting for depressive symptomatology in epidemiologic studies assessing cognitive functions.

Aged↗

A longitudinal analysis of methicillin-resistant Staphylococcus aureus in a Hong Kong teaching hospital.

OBJECTIVES: To review the incidence and trends of MRSA during a 12-year (1989-2000) period at a university teaching hospital and the relationship between strain distribution by antibiogram and molecular typing. DESIGN: Retrospective review of laboratory-based surveillance records on MRSA isolation and characterization of strains by antimicrobial susceptibility and PFGE. A patient episode was counted at the time when MRSA was first isolated. SETTING: A 1,350-bed university teaching hospital in Hong Kong. PATIENTS: Those with clinical isolates of MRSA. RESULTS: During 1989 to 2000, the hospital recorded 1,203,175 deaths and discharges (D&D) and encountered 5,707 patient episodes of new MRSA isolation. The overall incidence of patient episodes of MRSA was 0.47/100 D&D. In 1989, the incidence was 0.81/100 D&D and fell to a low of 0.33/100 D&D in 1995, but then rose to 0.50/100 D&D in 2000. Antibiogram and DNA typing identified 5 major types. PFGE type A constituted 68% (211/312) of isolates and was present throughout the 12-year period. PFGE type B constituted 13% (40/312) of isolates and was only present from 1995 to 2000. These isolates form a distinct clone and had unique antibiotic resistance profiles. CONCLUSIONS: The study showed the establishment of a dominant MRSA clone (PFGE type A group) in the intensive care, medical, and surgical units and the appearance of a new MRSA strain in 1995 (PFGE type B), which partly explained the rise in incidence of MRSA cases and a disproportionate rise in MRSA bacteremia from 1995 to 2000.

Electrophoresis, Gel, Pulsed-Field↗

Longitudinal analysis of human immunodeficiency virus type 1 RNA in breast milk and of its relationship to infant infection and maternal disease.

Transmission of human immunodeficiency virus type 1 (HIV-1) via breast-feeding can occur throughout lactation. Defining both fluctuation in breast-milk virus level over time and how breast-milk virus correlates with mother-to-child transmission is important for establishing effective interventions. We quantified breast-milk HIV-1 RNA levels in serial samples collected from 275 women for up to 2 years after delivery. Higher maternal plasma virus load, lower maternal CD4 T cell count, and detection of HIV-1 DNA in maternal genital secretions were significantly associated with elevated breast-milk HIV-1 RNA. Within women who breast-fed, median virus load in colostrum/early milk was significantly higher than that in mature breast milk collected 14 days after delivery (P< or =.004). Breast-feeding mothers who transmitted HIV-1 to their infants had both significantly higher breast-milk viral RNA throughout lactation and more-consistent viral shedding, compared with mothers who did not transmit HIV-1. In breast-feeding women, a 2-fold-increased risk of transmission was associated with every 10-fold increase in breast-milk virus load (95% confidence interval, 1.3-3.0; P<.001). These results indicate that the risk of infant infection from breast-feeding is influenced by breast-milk virus load, which is highest early after delivery.

Breast Feeding↗

A longitudinal analysis of antihypertensive drug interactions in a Medicaid population.

BACKGROUND: Drug interactions are a frequent cause of adverse drug events. We evaluated whether the frequency of previously reported antihypertensive drug-drug interactions could be reduced by pharmaceutical case management. METHODS: Patients >30 years of age with hypertension who were enrolled in the Iowa Pharmaceutical Case Management (PCM) program were evaluated. All prescription claims for patients were obtained on their date of eligibility and again 9 months later. A drug interaction database was developed to examine potential drug interactions in each patient's regimen. RESULTS: Antihypertensive drugs were taken by 1377 patients at baseline and at 9-month follow-up. Highly significant antihypertensive drug interactions were observed at baseline in 35% of patients (0.47 per patient), and interaction prevalence did not change over time. Decreases in the number of drug interactions tended to occur more commonly among patients of pharmacies that provided the highest intensity of service (11.5% in high-intensity pharmacies v 9% in low- or zero-intensity pharmacies, but this did not achieve statistical significance). Nearly 75% of patients had an interaction of any significance level, and the total number of interactions increased over time (P =.0067). CONCLUSIONS: This Medicaid population with hypertension had a very high prevalence of potential drug interactions. The prevalence of interactions did not change, but the mean number of all interactions actually increased over time. There was some suggestion that higher-intensity pharmacies might be more successful in minimizing the risk of clinically significant drug interactions when compared with lower-intensity pharmacies.

Adrenergic beta-Antagonists↗

Longitudinal analysis of T-helper cell phenotypes in renal-transplant recipients undergoing growth hormone therapy.

BACKGROUND: Treatment with recombinant human growth hormone (rhGH) in growth-retarded children after renal transplantation is effective, but there have been concerns regarding the safety of rhGH because of its possible immunomodulatory actions. We therefore evaluated the immune phenotypes of pediatric renal-transplant recipients and controls in response to rhGH with regard to a possible shift toward a T-helper (TH)1-type response. METHODS: Intracellular cytokines, activation markers, costimulatory, and adhesion molecules were studied in 13 children after renal transplantation (Tx+GH). Children with chronic renal failure (CRF+GH, n=11) before and under rhGH therapy and pediatric renal-transplant recipients without rhGH therapy (Tx, n=33) served as controls. Measurements were performed by four-color flow cytometry before and 4, 12, 18 and 24 weeks after initiation of rhGH therapy. RESULTS: Under baseline conditions, Tx+GH patients did not differ from Tx patients. During rhGH therapy in children with transplants, interleukin (IL)-2 production increased threefold at 4 weeks, and IL-4 and IL-13 increased by 70% at 12 weeks. All three cytokines returned to baseline after 18 weeks. No patient experienced rejection. In CRF+GH patients, baseline values for all investigated cytokines were higher than in patients with transplants but did not change in response to rhGH therapy. CONCLUSION: Our data indicates that rhGH therapy in stable, pediatric renal-transplant recipients has a mild and transient immunostimulatory effect in vivo. Immunosuppression and graft function in patients with transplants undergoing rhGH treatment should therefore carefully be monitored.

Adolescent↗

One-year reduction and longitudinal analysis of carotid intima-media thickness associated with colestipol/niacin therapy.

BACKGROUND AND PURPOSE: The Cholesterol Lowering Atherosclerosis Study has reported significant reduction of coronary artery disease and of carotid arterial intima-media thickness (IMT) at 2 and 4 years with colestipol/niacin therapy. We now report on treatment effects on carotid IMT at 6 months and 1 year. METHODS: One hundred eighty-eight nonsmoking men, aged 40 to 59 years, with prior coronary artery bypass graft surgery were randomized to colestipol/niacin plus diet therapy or placebo plus diet therapy. Computerized image processing of carotid ultrasound films was used to measure IMT in the right common carotid artery. Treatment group comparisons were made at 6 months and 1 year (46 and 33 subjects, respectively, with baseline and 6-month or 1-year ultrasound measures). The time course of the treatment effect on carotid IMT was estimated using the complete sample of 78 subjects with baseline and on-trial data. RESULTS: No significant treatment group differences on carotid IMT were found at 6 months. At 1 year, the treated group showed significant reduction of carotid IMT (P = .01 between groups). The placebo group showed continuing progression of IMT during the 4-year study period (estimated progression rate, 0.018 mm/y). The treated group showed reduction of IMT during the first 3 years and a plateau during the remainder of the study. CONCLUSIONS: Reduction of carotid IMT was found with aggressive lipid-lowering therapy. Ultrasound measures of IMT offer a noninvasive and precise measure of early carotid atherosclerosis that will decrease sample size requirements, potentially decrease dropout rates, and widen the study population of antiatherosclerotic clinical trials.

Adult↗

Longitudinal analysis of bacterial vaginosis: findings from the HIV epidemiology research study.

OBJECTIVE: To determine the natural history of bacterial vaginosis in women with or at risk for human immunodeficiency virus (HIV). METHODS: A cohort of 854 HIV-infected women and 434 HIV-uninfected women from four US sites was followed prospectively with gynecologic exams every 6 months over a 5-year period. The prevalence, incidence, persistence, and severity of bacterial vaginosis, which was defined using a Gram-staining scoring system, were calculated using generalized estimating equation methods. RESULTS: In adjusted analyses, HIV-infected women had a higher prevalence of bacterial vaginosis than HIV-uninfected women (adjusted odds ratio [OR] 1.29; 95% confidence interval [CI] 1.08, 1.55). Although HIV-infected women were not more likely to have incident infections, they were more likely to have persistence of their infections (adjusted OR 1.49; 95% CI 1.18, 1.89). Similarly, immunocompromised women (CD4+ cell count less than 200 cells/microL) were more likely than HIV-infected women with higher CD4+ cell counts (more than 500 cells/microL) to have prevalent (adjusted OR 1.29; 95% CI 1.03, 1.60) and persistent (adjusted OR 1.38; 95% CI 1.01, 1.91) bacterial vaginosis infections, but not more likely to have incident infections. Immunocompromised women had more severe bacterial vaginosis by both clinical criteria (adjusted OR 1.40; 95% CI 1.08, 1.82) and by Gram-staining criteria (adjusted OR 1.50; 95% CI 1.12, 2.00). CONCLUSIONS: Bacterial vaginosis is more prevalent and persistent among HIV-infected women, particularly among those who are immunocompromised. Immunocompromised women are more likely than HIV-infected women with higher CD4+ cell counts to have severe bacterial vaginosis.

AIDS-Related Opportunistic Infections↗

Modeling women's health during the menopausal transition: a longitudinal analysis.

OBJECTIVE: There has been controversy about the relative effects on various health outcomes of hormonal, psychosocial, and lifestyle changes during the menopausal transition. In previous studies the risk factors for one particular health endpoint have been analyzed separately. Separate analyses do not provide an overall view of the relationships between all the variables or the relative importance of different factors. Thus, the objective of this study was to provide an overall analysis of the influence of hormonal changes during the menopausal transition on a range of health outcomes while simultaneously considering all the available predictors and all the endpoints and to test the hypothesis that prior health status predicts current health status. DESIGN: This was a 9-year prospective observational study of 438 Australian-born women, who at baseline were aged 45 to 55 years and had menstruated in the prior 3 months. Interviews were conducted and fasting blood and physical measurements were performed annually. RESULTS: Main outcome measures were hormone levels, sociodemographic variables, attitudes and lifestyle variables, self-rated health and well-being, bothersome symptoms, coronary heart disease risk, bone mineral density, and sexuality. Data from 336 women, 77% of the original sample, were analyzed. Statistical modeling using structural equations showed that for all health endpoints, the prior level of that variable was the most important predictor. Declining levels of estradiol during the menopausal transition affected certain health outcomes: bone mineral density, coronary heart disease risk, vasomotor symptoms, vaginal dryness, and sexual response. Well-being is negatively affected by symptoms, hassles, and stress. Exercise has beneficial effects on hot flushes, well-being, body mass index, and coronary heart disease risk. Relationship factors and mood affect sexual response. CONCLUSIONS: This observational study provides a conceptual data-based framework for understanding changes in women's health during the natural menopausal transition.

Estradiol↗