Hormone dependency of breast tumours developing in the Guernsey Cohort study.

The aim of this study was to determine whether endogenous estradiol levels in postmenopausal women helped determine the estrogen receptor status of subsequent breast cancers. Within the Guernsey Cohort study of 6127 women, 140 have been diagnosed with breast cancer of whom 59 had estradiol assays performed and ER status available. Estradiol levels in serum and urine were measured by radioimmunoassay and ER status of tumours by immunohistochemistry. Of the individuals in the highest tertile of serum estradiol 35% had ER+ve tumours compared with 27% in the lowest tertile. In terms of 16hydroxyestrone excretion the proportions ER+ve tumours were 22% in the lowest tertile and 38% in the highest tertile. This suggests that endogenous estrogen levels do impact on the phenotype of subsequent breast cancer.

Hormone replacement therapy use and menopausal symptoms among women participating in a behavioral lifestyle intervention.

BACKGROUND: The decision to take hormone replacement therapy (HRT) is a choice many women encounter when entering menopause. The purpose of this study was to examine the choice to take HRT while participating in a lifestyle intervention to reduce cardiovascular risk through the menopause. METHODS: The Women's Healthy Lifestyle Project is a randomized clinical trial designed to examine whether a behavioral lifestyle intervention can decrease the expected rise in cardiovascular risk through the menopause. Participants (N = 535) completed questionnaires and were interviewed regarding menopausal symptoms, menopausal status, hot flashes, and HRT use at baseline and 54 months. RESULTS: The intervention was successful in preventing risk elevation through the 54-month visit. At the final visit, there was no difference between the intervention and control groups in the percentage who had become postmenopausal (32.9% vs 35.0%, respectively), there was no difference between control and intervention with HRT use, with 31.2% reporting use of HRT, and there was no difference between groups with menopausal symptoms. The women started HRT an average of 6 months after they missed a period. Baseline risk factors did not predict HRT use at the 54-month visit. CONCLUSIONS: A sizable number of women reported HRT use. The decision to use HRT was not influenced by the lifestyle intervention or their baseline cardiovascular risk, and these women started HRT very early in the peri- to postmenopause. Further, weight loss in the perimenopause did not affect menopausal symptoms.

Post-menopausal hormone therapy and concentrations of protein C and antithrombin in elderly women.

The effects of post-menopausal hormone therapy (HRT) on blood coagulation in elderly women are not well defined. We studied associations of HRT use with levels of natural anticoagulant proteins in a cross-sectional study of 3393 women > or = 65 years of age participating in the Cardiovascular Health Study. Protein C antigen and antithrombin were measured in all users (n = 230 unopposed oestrogen; 60 oestrogen/progestin) and a comparison group of 196 age- and race-matched non-users. Compared with non-users, oestrogen use was associated with higher protein C (4.80 vs. 4.30 microg/ml, P < 0.01). Results were similar for oestrogen/progestin (P > 0.05). In both user groups, antithrombin was lower than in non-users (109% for each vs. 115% in non-users, P < 0.001). Adjustment for factors related to prescription of HRT and to anticoagulant protein levels had little impact on the results. For antithrombin, associations with HRT were larger for thinner Caucasian women and black women. Venous thrombosis from HRT may be mediated partly by alterations in antithrombin, but not protein C concentrations. This study extends previous observations to older women, the group at highest risk of venous thromboembolism. Studies of HRT-induced alterations in anticoagulant function in relation to the occurrence of thrombosis with HRT are required.

Serum levels of C-reactive protein are associated with obesity, weight gain, and hormone replacement therapy in healthy postmenopausal women.

The authors evaluated the cross-sectional and prospective associations between the serum concentration of C-reactive protein and measures of obesity and fat distribution, hormone replacement therapy (HRT) use, and serum sex hormones in postmenopausal women from the Healthy Women Study (Allegheny County, Pennsylvania, 1998). The authors tested the hypothesis that C-reactive protein levels would be higher among HRT users and among women with greater body mass index, waist circumference, or visceral fat. There were 207 women in the study who were > or =8 years postmenopausal (101 HRT users and 106 HRT nonusers). The median levels of C-reactive protein were 3.01 mg/liter in HRT users compared with 1.74 mg/liter in nonusers (p = 0.002). C-reactive protein levels were strongly positively correlated with measures of body size, fatness, fat distribution, and weight gain among HRT users and nonusers. C-reactive protein was also positively correlated with serum estrone levels (r(s) = 0.38) among HRT nonusers. The highest level of C-reactive protein was found among HRT users in the highest quartile of visceral fat (4.29 mg/liter) compared with women not on HRT and in the lowest quartile of visceral fat (0.96 mg/liter). The use of HRT and measures of overall body fatness are important correlates of C-reactive protein among postmenopausal women.

Women's Healthy Lifestyle Project: A randomized clinical trial: results at 54 months.

BACKGROUND: The Women's Healthy Lifestyle Project Clinical Trial tested the hypothesis that reducing saturated fat and cholesterol consumption and preventing weight gain by decreased caloric and fat intake and increased physical activity would prevent the rise in LDL cholesterol and weight gain in women during perimenopause to postmenopause. METHODS AND RESULTS: There were 275 premenopausal women randomized into the assessment only group and 260 women into the intervention group. The mean age of participants at baseline was 47 years, and 92% of the women were white. The mean LDL cholesterol was 115 mg/dL at baseline, and mean body mass index was 25 kg/m(2). The follow-up through 54 months was excellent. By 54 months, 35% of the women had become postmenopausal. At the 54-month examination, there was a 3.5-mg/dL increase in LDL cholesterol in the intervention group and an 8.9-mg/dL increase in the assessment-only group (P:=0.009). Weight decreased 0.2 lb in the intervention and increased 5.2 lb in the assessment-only group (P:=0.000). Triglycerides and glucose also increased significantly more in the assessment-only group than in the intervention group. Waist circumference decreased 2.9 cm in the intervention compared with 0.5 cm in the assessment-only group (P:=0.000). CONCLUSIONS: The trial was successful in reducing the rise in LDL cholesterol during perimenopause to postmenopause but could not completely eliminate the rise in LDL cholesterol. The trial was also successful in preventing the increase in weight from premenopause to perimenopause to postmenopause. The difference in LDL cholesterol between the assessment and intervention groups was most pronounced among postmenopausal women and occurred among hormone users and nonusers.

Estrogen replacement therapy and MRI-demonstrated cerebral infarcts, white matter changes, and brain atrophy in older women: the Cardiovascular Health Study.

OBJECTIVE: We studied the relationship between the use of estrogen replacement therapy (ERT) and cerebral magnetic resonance imaging (MRI) abnormalities among older women. DESIGN: A population-based prospective study (Cardiovascular Health Study). SETTING: Four regions in the United States. PARTICIPANTS: A total of 2133 (62.9% of the eligible) women aged 65 to 95 years (mean age 74.8), on whom MRI was performed in 1992-1994. MEASUREMENTS: Presence of global brain atrophy, white matter changes, small infarct-like lesion (ILL) (<3 mm), MRI infarcts (> or =3 mm, mostly small and asymptomatic), and cognitive function as measured by Mini-Mental State Exam (MMSE), and by ERT use (current/past/never), adjusted for a number of socioeconomic, lifestyle, and reproductive covariates. RESULTS: Current use of ERT was reported by 15% and past use by another 23% of participants; 35% of all women had MRI infarcts. The prevalence of MRI infarcts did not differ in current or past users from those who had never used ERT (nonusers). Bifrontal distance, the largest distance between frontal horns, and the size of ventricles were larger among current ERT users compared to past users or nonusers (P (trend) = .01), adjusted for all other covariates, but no dose-response relationship to current or past ERT use was found. Duration of estrogen use was not associated with any atrophy measure. Cortical atrophy measure, sulcal widening, or white matter disease did not differ significantly by ERT use or duration of use. Central measures of atrophy, bifrontal distance, and ventricular size were significantly associated with cognition as measured by MMSE. CONCLUSIONS: Current ERT users had much more clinically significant central atrophy than nonusers, but the implications remained unclear.

Estrogens and women's health: interrelation of coronary heart disease, breast cancer and osteoporosis.

The determinants of blood levels of estrogen, estrogen metabolites, and relation to receptors and post-transitional effects are the likely primary cause of breast cancer. Very high risk women for breast cancer can now be identified by measuring bone mineral density and hormone levels. These high risk women have rates of breast cancer similar to risk of myocardial infarction. They are candidates for SERM therapies to reduce risk of breast cancer. The completion of the Women's Health Initiative and other such trials will likely provide a definite association of risk and benefit of both estrogen alone and estrogen-progesterone therapy, coronary heart disease, osteoporotic fracture, and breast cancer. The potential intervention of hormone replacement therapy, obesity, or weight gain and increased atherogenic lipoproteinemia may be of concern and confound the results of clinical trials. Estrogens, clearly, are important in the risk of bone loss and osteoporotic fracture. Obesity is the primary determinant of postmenopausal estrogen levels and reduced risk of fracture. Weight reduction may increase rates of bone loss and fracture. Clinical trials that evaluate weight loss should monitor effects on bone. The beneficial addition of increased physical activity, higher dose of calcium or vitamin D, or use of bone reabsorption drugs in coordination with weight loss should be evaluated. Any therapy that raises blood estrogen or metabolite activity and decreases bone loss may increase risk of breast cancer. Future clinical trials must evaluate multiple endpoints such as CHD, osteoporosis, and breast cancer within the study. The use of surrogate markers such as bone mineral density, coronary calcium, carotid intimal medial thickness and plaque, endothelial function, breast density, hormone levels and metabolites could enhance the evaluation of risk factors, genetic-environmental intervention, and new therapies.

High blood pressure and bone-mineral loss in elderly white women: a prospective study. Study of Osteoporotic Fractures Research Group.

BACKGROUND: High blood pressure is associated with abnormalities in calcium metabolism. Sustained calcium loss may lead to increased bone-mineral loss in people with high blood pressure. We investigated the prospective association between blood pressure and bone-mineral loss over time in elderly white women. METHODS: We studied 3676 women who were initially assessed in 1988-90 (mean age 73 years [SD 4, range 66-91 years]; mean bodyweight 65.3 kg [11.5]; blood pressure 137/75 mm Hg [17/9]) who were not on thiazide diuretics. Mean follow-up was 3.5 years. Anthropometry, blood pressure, and bone-mineral density at the femoral neck were measured at baseline and bone densitometry was repeated after 3.5 years by dual-energy X-ray absorptiometry. FINDINGS: After adjustment for age, initial bone-mineral density, weight and weight change, smoking, and regular use of hormone-replacement therapy, the rate of bone loss at the femoral neck increased with blood pressure at baseline. In the quartiles of systolic blood pressure, yearly bone losses increased from 2.26 mg/cm2 (95% CI 1.48-3.04) in the first quartile to 3.79 mg/cm2 in the fourth quartile (3.13-4.45; test for heterogeneity, p=0.03; test for linear trend, p=0.01), equivalent to yearly changes of 0.34% (0.20-0.46) and 0.59% (0.49-0.69; test for heterogeneity, p=0.02; test for linear trend, p=0.005). There was no significant interaction with age. The exclusion of women on antihypertensive drugs did not alter the results. For diastolic blood pressure, there was an association with bone loss in women younger than 75 years. INTERPRETATION: Higher blood pressure in elderly white women is associated with increased bone loss at the femoral neck. This association may reflect greater calcium losses associated with high blood pressure, which may contribute to the risk of hip fractures.

The relationship of fibrinogen and factors VII and VIII to incident cardiovascular disease and death in the elderly: results from the cardiovascular health study.

Little is known about the prospective associations of fibrinogen, factor VII, or factor VIII with cardiovascular disease (CVD) and mortality in the elderly. At baseline in the Cardiovascular Health Study (5888 white and African American men and women; aged >/=65 years), we measured fibrinogen, factor VIII, and factor VII. We used sex-stratified stepwise Cox survival analysis to determine relative risks (RRs) for CVD events and all-cause mortality (up to 5 years of follow-up), both unadjusted and adjusted for CVD risk factors and subclinical CVD. After adjustment, comparing the fifth quintile to the first, fibrinogen was significantly associated in men with coronary heart disease events (RR=2.1) and stroke or transient ischemic attack (RR=1.3), and also with mortality within 2.5 years of follow-up (RR=5.8) and later (RR=1.7). Factor VIII was significantly associated in men with coronary heart disease events (RR=1.5) and mortality (RR=1.8), and in women with stroke/transient ischemic attack (RR=1.4). For both factors, values were higher in those who died, whether causes were CVD-related or non-CVD-related, but highest in CVD death. Factor VII exhibited associations with incident angina (RR=1.44) in men and with death in women (RR, middle quintile compared with first=0.66). However, in general, factor VII was not consistently associated with CVD events in this population. We conclude that, if confirmed in other studies, the measurement of fibrinogen and/or factor VIII may help identify older individuals at higher risk for CVD events and mortality.

Hormone replacement therapy, inflammation, and hemostasis in elderly women.

Lipid-lowering by postmenopausal hormone therapy (HRT) explains only partly the assumed coronary risk reduction associated with therapy. To explore other possible mechanisms, we studied associations of HRT use with inflammation and hemostasis risk markers in women >/=65 years of age. Subjects were selected from 3393 participants in the fourth year examination of the Cardiovascular Health Study, an observational study of vascular disease risk factors. After excluding women with vascular disease, we compared levels of inflammation and hemostasis variables in the 230 women using unopposed estrogen and 60 using estrogen/progestin, with those of 196 nonusers selected as controls. Compared with nonusers, unopposed estrogen use was associated with 59% higher mean C-reactive protein (P<0.001), but with modestly lower levels of other inflammation indicators, fibrinogen, and alpha-1 acid glycoprotein (P<0.001). Factor VIIc was 16% higher among estrogen users (P<0.001), but this was not associated with higher thrombin production (prothrombin fragment 1-2), or increased fibrin breakdown (D-dimer). Concentration of plasminogen activator inhibitor-1 was 50% lower in both using groups (P<0.001) compared with nonusers, and this was associated with higher plasmin-antiplasmin complex: 8% higher in estrogen and 18% higher in estrogen/progestin users (P<0. 05). Relationships between the markers and hormone use were less pronounced in estrogen/progestin users, with no association for C-reactive protein except in women in upper 2 tertiles of body mass index (P for interaction, 0.02). The direction and strength of the associations of HRT use with inflammation markers differed depending on the protein, so it is not clear whether HRT confers coronary risk reduction through an inflammation-sensitive mechanism. Associations with hemostasis markers indicated no association with evidence of procoagulation and a possible association with increased fibrinolytic activity.

Do urinary oestrogen metabolites predict breast cancer? Guernsey III cohort follow-up.

This is the first prospective study of urinary measures of the two major competing pathways of oestrogen metabolism, 16alpha-hydroxyoestrone (16alpha-OHE1) and 2-hydroxyoestrone (2-OHE1), in relation to incident breast cancer risk. Experimental and case-control study results suggest that metabolism favouring the more oestrogenic 16alpha-OHE1 pathway may be linked to higher breast cancer risk. Women aged 35 and older from Guernsey (n = 5104) were surveyed in 1977-85 and have been continuously monitored for breast cancer and mortality up to the present (Guernsey III, Imperial Cancer Research Fund). Incident cases of breast cancer were matched to three control subjects for comparison of urinary oestrogen metabolite levels measured by enzyme immunoassay (EIA) in spot urine samples collected at baseline and stored frozen for up to 19 years. Consistent with case-control study results, post-menopausal (but not premenopausal) women at baseline who went on to develop breast cancer showed about a 15% lower 2:16alpha-OHE1 ratio than matched control subjects. Further, subjects with metabolite ratios in the highest tertile of 2:16alpha-OHE1 had about a 30% lower risk than women with ratios in the lowest two-thirds, although results were not statistically significant (OR = 0.71, 95% CI = 0.29-1.75). It is of potential importance that, in contrast to most risk factors for breast cancer, such as late age at first birth, oestrogen metabolism appears to be modifiable via diet and exercise, offering women the possibility of lowering breast cancer risk through non-pharmacological measures, although this remains to be tested.

Maintenance of cardiovascular risk factor changes among middle-aged women in a lifestyle intervention trial.

The Women's Healthy Lifestyle Project is a 5-year randomized clinical testing whether a behavioral intervention aimed at lifestyle changes in diet and physical activity can prevent the rise in weight and low-density lipoprotein cholesterol (LDL-c) observed during menopause. Cardiovascular risk factor and behavioral data from 489 participants (intervention group n = 236; control group n = 253) who attended baseline, 6-month, and 18-month clinical assessments were analyzed to determine how well initial improvements achieved at 6 months were maintained over the subsequent year of follow-up. Results indicated that the treatment effect persisted at 18 months for weight, body mass index, total cholesterol, LDL-c, systolic blood pressure (SBP), and glucose levels. Intervention participants maintained improvements in physical activity, caloric intake, dietary cholesterol, SBP, and glucose levels between 6 and 18 months, although weight, total cholesterol, and LDL-c began to rise during this period. Eighty percent of intervention participants compared to 45% of controls were at or under baseline weight at 18 months, suggesting that promoting modest weight loss may be an effective approach to preventing weight gain in these women.

Carotid atherosclerosis in premenopausal and postmenopausal women and its association with risk factors measured after menopause.

BACKGROUND AND PURPOSE: In women, symptoms of coronary artery disease are delayed by 10 to 15 years in comparison with men, most likely because of the protective effect of ovarian hormones. This report compares the prevalence and degree of carotid atherosclerosis between 292 premenopausal women and 294 women at 5 to 8 years after menopause. METHODS: Scans were performed in the same laboratory over the same time period for both groups. Intima-media thickness (IMT) was averaged across the common, bulb, and internal carotids. The plaque index summarized degree of focal plaque based on the size and number of plaques throughout both carotid systems. RESULTS: Mean IMT was 0.69 mm for premenopausal women and 0.77 mm for postmenopausal women (P < 0.001). Prevalence of plaque was 25% among premenopausal women and 54% among postmenopausal women (P < 0.001). In both premenopausal and postmenopausal women, risk factors measured before menopause were associated with carotid atherosclerosis. Premenopausal risk factors independently associated with IMT were higher pulse pressure (P < 0.001), triglycerides (P = 0.002), body mass index (P < 0.001), and study group (a surrogate for both age and menopausal status; P < 0.001). Premenopausal risk factors independently associated with focal plaque were ever smoking (P = 0.002), higher pulse pressure (P = 0.028), higher LDL (P = 0.003), age at baseline (P = 0.050), and study group (P < 0.001). CONCLUSIONS: Subclinical carotid atherosclerosis can be observed in middle-aged women. Risk factors measured before menopause are clearly associated with subclinical disease measured both concurrently and at 5 to 8 years after menopause.

Smoking cessation, weight gain, and changes in cardiovascular risk factors during menopause: the Healthy Women Study.

OBJECTIVES: The relationship between smoking cessation, subsequent weight gain, and cardiovascular disease risk factors from premenopause to postmenopause was studied. METHODS: Healthy Women Study participants were assessed for changes in coronary heart disease risk factors from a premenopausal baseline assessment to first- and second-year postmenopausal assessments. RESULTS: Although ex-smokers gained substantially more weight than nonsmokers and smokers, they did not experience a greater increase in cardiovascular risk factors. In fact, the results indicated a trend toward ex-smokers' high-density lipoprotein cholesterol levels increasing slightly more than those of nonsmokers and smokers. CONCLUSIONS: Smoking cessation in perimenopausal to postmenopausal women is associated with greater weight gain but appears to be modestly associated with certain positive changes in cardiovascular risk factors.

Thyroid function and perimenopausal lipid and weight changes: the Thyroid Study in Healthy Women (TSH-W).

We designed a prospective observational trial to study the relationship of thyroid function to cholesterol and weight changes at menopause. Subjects were participants in the ongoing Healthy Women Study, a prospective study of cardiovascular risk factor change through menopause. Healthy premenopausal women were recruited from a random sample of licensed drivers in selected ZIP codes of Allegheny County, Pennsylvania. Participants had to be 42-50 years of age, have menstruated within the last 3 months, not have had surgical menopause, have diastolic blood pressure < 100 mm Hg, and not be taking medications (including insulin, estrogen, lipid-lowering drugs, or thyroid or antihypertensive medications) at the baseline examination. The substudy included three groups of women who were premenopausal at baseline and were categorized according to change noted at follow-up regarding menopausal status and use of hormone replacement therapy (HRT). The groups comprised 95 women who remained premenopausal, 96 postmenopausal women not on HRT, and 61 postmenopausal women using HRT. The main outcome measures were baseline and follow-up measurements for serum levels of thyroid-stimulating hormone (TSH), thyroid peroxidase, and thyroglobulin, as well as serum cholesterol, total high-density lipoprotein (HDL) cholesterol, triglycerides, and calculated low-density lipoprotein (LDL) cholesterol, height, and weight. Covariates included cigarette smoking and alcohol intake. The prevalence of thyroid antibodies in this healthy population was high at both time points (range 27%-31%) and did not differ by menopausal status. The presence of thyroid antibodies was associated with increased TSH concentration. Women with antibodies at both time points had lower levels of total and LDL cholesterol compared with those with no antibodies, significant only for those women who remained premenopausal during the follow-up period. Thyroid function during menopause in this healthy population is unlikely to account for the observed changes in levels of serum lipoprotein and body weight. The presence of thyroid antibodies may be associated with lower total and LDL cholesterol, possibly through an underlying inflammatory disorder.

Relationship of C-reactive protein to risk of cardiovascular disease in the elderly. Results from the Cardiovascular Health Study and the Rural Health Promotion Project.

Markers of inflammation, such as C-reactive protein (CRP), are related to risk of cardiovascular disease (CVD) events in those with angina, but little is known about individuals without prevalent clinical CVD. We performed a prospective, nested case-control study in the Cardiovascular Health Study (CHS; 5201 healthy elderly men and women). Case subjects (n = 146 men and women with incident CVD events including angina, myocardial infarction, and death) and control subjects (n = 146) were matched on the basis of sex and the presence or absence of significant subclinical CVD at baseline (average follow-up, 2.4 years). In women but not men, the mean CRP level was higher for case subjects than for control subjects (P < or = .05). In general, CRP was higher in those with subclinical disease. Most of the association of CRP with female case subjects versus control subjects was in the subgroup with subclinical disease; 3.33 versus 1.90 mg/L, P < .05, adjusted for age and time of follow-up. Case-control differences were greatest when the time between baseline and the CVD event was shortest. The strongest associations were with myocardial infarction, and there was an overall odds ratio for incident myocardial infarction for men and women with subclinical disease (upper quartile versus lower three quartiles) of 2.67 (confidence interval [CI] = 1.04 to 6.81), with the relationship being stronger in women (4.50 [CI = 0.97 to 20.8]) than in men (1.75 [CI = 0.51 to 5.98]). We performed a similar study in the Rural Health Promotion Project, in which mean values of CRP were higher for female case subjects than for female control subjects, but no differences were apparent for men. Comparing the upper quintile with the lower four, the odds ratio for CVD case subjects was 2.7 (CI = 1.10 to 6.60). In conclusion, CRP was associated with incident events in the elderly, especially in those with subclinical disease at baseline.

Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study.

The authors ascertained cardiovascular events (myocardial infarction and angina pectoris) in 498 women with systemic lupus erythematosus seen at the University of Pittsburgh Medical Center from 1980 to 1993 (3,522 person-years). Subjects were stratified by age, and cardiovascular event incidence rates were determined. The authors compared these rates with cardiovascular event rates were determined. The authors compared these rates with cardiovascular event rates occurring over the same time period in 2,208 women of similar age participating in the Framingham Offspring Study (17,519 person-years). Age-specific rate ratios were computed to determine whether the cardiovascular events in the lupus cohort were greater than expected. The risk factors associated with cardiovascular events in women with lupus were determined. There were 33 first events (11 myocardial infarction, 10 angina pectoris, and 12 both angina pectoris and myocardial infarction) after the diagnosis of lupus: two thirds were under the age of 55 years at the time of event. Women with lupus in the 35- to 44-year age group were over 50 times more likely to have a myocardial infarction than were women of similar age in the Framingham Offspring Study (rate ratio = 52.43, 95% confidence interval 21.6-98.5). Older age at lupus diagnosis, longer lupus disease duration, longer duration of corticosteroid use, hypercholesterolemia, and postmenopausal status were more common in the women with lupus who had a cardiovascular event than in those who did not have an event. Premature cardiovascular disease is much more common in young premenopausal women with lupus than in a population sample. With the increased life expectancy of lupus patients due to improved therapy, cardiovascular disease has emerged as a significant threat to the health of these women. The impact of this problem has been underrecognized, with little focus placed on aggressive management of hypercholesterolemia and other possible risk factors.

Prospective study of the determinants of age at menopause.

The authors prospectively studied the effect of demographic, reproductive, stress-related, and health behavior factors measured at study entry on age of natural menopause in 185 healthy US women. At study entry, women were 42.5-47.5 years old and premenopausal. After a baseline examination (1983-1985), women were followed for 7-9 years, during which time they reported on a monthly basis their menstrual status and whether they were taking hormones. Menopausal age was defined as age at the last menstrual period prior to stopping menstruation for 12 months (and not taking hormones). Estimated median age at menopause was 51.5 years for the whole sample. Median age at menopause was earlier for women who reported irregular menstrual cycles at study entry (50.2 years), were African-American (49.3 years), were smokers (50.6 years), or were currently on a weight reduction diet (50.5 years). Psychosocial stress was predictive of an even earlier median age at menopause in African Americans (48.4 years) and in those with irregular cycles at baseline (49.4 years). Results suggest that premenopausal women in their forties who are experiencing irregular menstrual cycles, are smokers, are dieting, or are African-American are likely to reach menopause earlier than their contemporaries. African-American women may have a different "biological clock" than white women, especially when under stress, or they may experience more stress of longer duration.

Relation of C-reactive protein and coronary heart disease in the MRFIT nested case-control study. Multiple Risk Factor Intervention Trial.

The authors measured the relation between C-reactive protein, alpha 1 acid glycoprotein and albumin, an acute phase protein, and subsequent risk of myocardial infarction and coronary heart disease death in a nested case-control study among the Multiple Risk Factor Intervention Trial (MRFIT) participants. There were 98 myocardial infarction cases, 148 coronary heart disease deaths, and 491 controls. The cases and controls were followed for up to 17 years for deaths and 6-7 years for myocardial infarction cases and controls. There was a significant association between available distribution of C-reactive protein and subsequent coronary heart disease mortality. For smokers at baseline, the risk of coronary heart disease deaths in quartile 4 of C-reactive protein as compared with quartile 1 was 4.3 (95% confidence interval 1.74-10.8). The association persisted when adjusted for characteristics related to smoking and smoking cessation during the trial and to pulmonary function. There was no relation between alpha 1 acid glycoprotein and either myocardial infarction or coronary heart disease death. Albumin was inversely related to coronary heart disease death only for deaths that occurred between 7 and 13 years after baseline, consistent with previous MRFIT analyses. This is the first prospective study in "healthy but high risk individuals" to document the relation between C-reactive protein and coronary heart disease mortality.

Risk factors for cardiovascular disease among women.

The studies of risk factors for cardiovascular disease among women have changed over the past few years because of: (1) the further development and evaluation of noninvasive methods of measuring subclinical atherosclerosis, (2) the availability of potent drugs that substantially lower LDL-cholesterol levels, (3) improvement in the methods of measuring factors related to clotting and fibrinolysis and inflammation, (4) better methods of quantifying obesity, fatness and body fat distribution, (5) increasing interest in the interrelationship between endogenous sex-steroid hormone metabolism, risk factors and disease, (6) the relationship of new metabolic risk factors and cardiovascular disease and (7) the use of molecular genetics to identify specific genotypes of risk factors.