Hysterectomy in a Danish population. Weight-related factors, psychological factors and life style variables

The aim was to assess risk factors for hysterectomy performed for benign conditions. In a prevalence study, 2301 Danish women were selected at random in 1982. Information about weight and slimming history, life-styles, psychological factors, gynaecological history, and social background were obtained. In an incidence study, the cohort was followed from 1982 to 1990 to assess the incidence of hysterectomy. In the prevalence study, weight cycling (recurrent weight loss and weight gain of more than 5 kg) was associated with hysterectomy for benign disease (adjusted odds ratio 1.77, 95% confidence interval 1.05-2.99) independently of overweight, smoking, oral contraceptives, psychological and social factors. In the incidence study, weight cycling was the only significant weight-related risk factor for hysterectomy performed for benign disease (adjusted relative risk 2.49, 95% confidence interval 1.10-5.60), explaining the relation between hysterectomy and psychological factors. Weight cycling might be an important risk factor for premenopausal hysterectomy performed for benign conditions.     

Calcium channel blockers, cancer incidence, and cancer mortality in a cohort of U.S. women: the nurses' health study

BACKGROUND: Some studies have suggested that the use of calcium channel blockers may increase the risk of cancer. A possible association of the use of calcium channel blockers with cancer incidence and cancer mortality was addressed using data from the Nurses' Health Study. METHODS: In this study, a total of 18,635 female nurses reported regularly taking at least 1 of 4 cardiovascular medications in 1988: diuretics, beta-blockers, calcium channel blockers, and/or angiotensin-converting enzyme (ACE) inhibitors. Cancer incidence and cancer deaths were ascertained until 1994. RESULTS: During 6 years of follow-up, 852 women were newly diagnosed with cancer and 335 women died of cancer. Women who reported the use of calcium channel blockers had no increased risk of newly diagnosed cancer compared with those taking other cardiovascular drugs (relative risk=1.02; 95% CI 0.83-1.26). The relative risk of dying from cancer associated with the self-reported use of calcium channel blockers was 1.25 (95% CI 0.91-1.72). Relative risks were adjusted for the following self-reported factors: age; weight; height; cholesterol level; systolic and diastolic blood pressure; smoking; alcohol intake; physical activity; menopausal status; postmenopausal hormone use; aspirin use; and history of diabetes, cancer, stroke, myocardial infarction, coronary artery bypass graft or percutaneous transluminal coronary angioplasty, angina, and hypertension. Regarding site specific cancer incidence and mortality, only lung cancer incidence was somewhat increased (RR=1.61; 95% CI 0.88-2.96). CONCLUSIONS: These data suggest no important increase in overall cancer incidence or cancer mortality related to the self-reported use of calcium channel blockers.     

Increased cancer mortality following a history of nonmelanoma skin cancer

CONTEXT: Cancer registries have reported an increased incidence of melanoma and certain noncutaneous cancers following nonmelanoma skin cancer (NMSC). Whether these findings were attributable to intensified surveillance, shared risk factors, or increased cancer susceptibility remains unclear. OBJECTIVE: To determine whether a history of NMSC predicts cancer mortality. DESIGN: Prospective cohort with 12-year mortality follow-up adjusted for multiple risk factors. SETTING: Cancer Prevention Study II, United States and Puerto Rico. PARTICIPANTS: Nearly 1.1 million adult volunteers who completed a baseline questionnaire in 1982. MAIN OUTCOME MEASURE: Deaths due to all cancers and common cancers. RESULTS: After adjusting for age, race, education, smoking, obesity, alcohol use, and other conventional risk factors, a baseline history of NMSC was associated with increased total cancer mortality (men's relative risk [RR], 1.30; 95% confidence interval [CI], 1.23-1.36; women's RR, 1.26; 95% CI, 1.17-1.35). Exclusion of deaths due to melanoma reduced these RRs only slightly. Mortality was increased for the following cancers: melanoma (RR, 3.36 in men, 3.52 in women); pharynx (RR, 2.77 in men, 2.81 in women); lung (RR, 1.37 in men, 1.46 in women); non-Hodgkin lymphoma (RR, 1.32 in men, 1.50 in women); in men only, salivary glands (RR, 2.96), prostate (RR, 1.28), testis (RR, 12.7), urinary bladder (RR, 1.41), and leukemia (RR, 1.37); and in women only, breast (RR, 1.34). All-cause mortality was slightly increased (adjusted men's RR, 1.03 [95% CI, 1.00-1.06]; women's RR, 1.04 [95% CI, 1.00-1.09]). CONCLUSIONS: Persons with a history of NMSC are at increased risk of cancer mortality. Although the biological mechanisms are unknown, a history of NMSC should increase the clinician's alertness for certain noncutaneous cancers as well as melanoma.     

Weight change between age 50 years and old age is associated with risk of hip fracture in white women aged 67 years and older

BACKGROUND: Although changes in body weight with aging are common, little is known about the effects of weight change on health in old age. OBJECTIVES: To study the effects of weight loss and weight gain from age 50 years to old age on the risk of hip fracture among postmenopausal white women aged 67 years and older and to determine if the level of weight at age 50 years modifies this risk. METHODS: The association between weight change and the risk of hip fracture was studied in 3683 community-dwelling white women aged 67 years and older from three sites of the Established Populations for Epidemiologic Studies of the Elderly. RESULTS: Extreme weight loss (10% or more) beginning at age 50 years was associated in a proportional hazards model with increased risk of hip fracture (relative risk [RR], 2.9; 95% confidence interval [CI], 2.0-4.1). This risk was greatest among women in the lowest (RR, 2.3; CI, 1.1-4.8) and middle (RR, 2.8; CI, 1.5-5.3) tertiles of body mass index at age 50 years. Among the thinnest women, even more modest weight loss (5% to < 10%) was associated with increased risk of hip fracture (RR, 2.3; CI, 1.0-5.2). Weight gain of 10% or more beginning at age 50 years provided borderline protection against the risk of hip fracture (RR, 0.7; CI, 0.4-1.0). The RRs for weight gain of 10% or more were protective only among women in the middle and high tertiles of body mass index at age 50 years and were not significant (middle tertile RR, 0.8; CI, 0.3-1.8; high tertile RR, 0.6; CI, 0.2-1.9). CONCLUSIONS: Weight history is an important determinant of the risk of hip fracture. Weight loss beginning at age 50 years increases the risk of hip fracture in older white women, especially among those who are thin at age 50 years; weight gain of 10% or more decreases the risk of hip fracture. Physicians should include weight history in their assessment of postmenopausal older women for risk of hip fracture.     

Prospective study of calcium channel blocker use, cardiovascular disease, and total mortality among hypertensive women: the Nurses' Health Study

BACKGROUND: In several observational studies, patients prescribed calcium channel blockers had higher risks of cardiovascular diseases and mortality than those prescribed other antihypertensive medications. We explored these associations in the Nurses' Health Study. METHODS AND RESULTS: A total of 14 617 women who reported hypertension and regular use of diuretics, beta-blockers, calcium channel blockers, ACE inhibitors, or a combination in 1988 were included in the analyses. Cardiovascular events and deaths were ascertained through May 1, 1994. We documented 234 cases of myocardial infarction. Calcium channel blocker monodrug users had an age-adjusted relative risk (RR) of myocardial infarction of 2.36 (95% CI, 1.43 to 3.91) compared with those prescribed thiazide diuretics. Women prescribed calcium channel blockers had a higher prevalence of ischemic heart disease. After adjustment for these and other coronary risk factors, the RR was 1.64 (95% CI, 0.97 to 2.77). Comparing the use of any calcium channel blocker (monodrug and multidrug users) with that of any other antihypertensive agent, the adjusted RR was 1.42 (95% CI, 1.01 to 2.01). An association between calcium channel blocker use and myocardial infarction was apparent among women who had ever smoked cigarettes (covariate-adjusted RR, 1.81; 95% CI, 1.20 to 2.72) but not among never-smokers (RR, 0.94; 95% CI, 0.48 to 1.84). CONCLUSIONS: In analyses adjusted only for age, we found a significant elevation in RR of total myocardial infarction among women who used calcium channel blockers compared with those who did not. After adjustment for comorbidity and other covariates, the RR was reduced. Whether the remaining observed elevated risk is real, or a result of residual confounding by indication, or chance, or a combination of the above cannot be evaluated with certainty on the basis of these observational data.     

Chondroitin 4-sulphate exhibits inhibitory effect during Cu2+-mediated LDL oxidation

OBJECTIVE: To determine whether the rate of cardiovascular disease is different among parous women with a general practitioner reported history of toxaemia of pregnancy than among those not reported to have experienced toxaemia, or among nulliparous women. DESIGN: Prospective cohort study. SETTING: 1400 general practitioners throughout the United Kingdom. SUBJECTS: Women who had never used oral contraceptives who were recruited to the Royal College of General Practitioners' oral contraception study (original cohort about 23000). MAIN OUTCOME MEASURES: Age, social class, and smoking standardised incidence rates for hypertensive disease, acute myocardial infarction, other acute ischaemic heart disease, other chronic ischaemic heart disease, angina pectoris, total ischaemic heart disease, total cerebrovascular disease, and total venous thromboembolic disease in the three groups. RESULTS: Compared with parous women with no history of toxaemia, those who had experienced toxaemia had a significantly increased risk of hypertensive disease (relative risk (RR) 2.35), acute myocardial infarction (RR 2.24), chronic ischaemic heart disease (RR 1.74), angina pectoris (RR 1.53), all ischaemic heart disease (RR 1.65), and venous thromboembolism (RR 1.62). The rates for all cerebrovascular disease and peripheral vascular disease were also increased but not significantly. Nulliparous women were more likely to develop hypertension or all cerebrovascular disease later in life than parous women without a history of toxaemia. CONCLUSIONS: A history of toxaemia of pregnancy increases the risk of several distinct cardiovascular conditions later in life. Although causality cannot be inferred (other characteristics of the women may account for both an increased risk of toxaemia and a risk of subsequent vascular disease), the findings merit further research because of their potential importance.     

High free fatty acid concentration: an independent risk factor for hypertension in the Paris Prospective Study

BACKGROUND: An inconsistent relationship has been reported between insulin and hypertension incidence. Free fatty acids are related to insulin-resistance and may have a direct effect on hypertension. We examined the effect of free fatty acids on hypertension incidence, taking into account other abnormalities of the insulin-resistance syndrome. METHODS: In all, 2968 non-hypertensive and non-diabetic Caucasian men were followed for 3 years. Hypertension incidence was defined as systolic blood pressure (SBP) > or =160 mmHg or diastolic blood pressure (DBP) > or =95 mmHg or drug treatment for hypertension. RESULTS: Free fatty acid elevation was a highly significant risk factor for hypertension when controlled for age, family history of hypertension, alcohol consumption, body mass index, iliac circumference and weight change. Further controlling for SBP, heart rate and fasting insulin and glucose did not decrease its predictive power (hazard rate ratio [RR] = 1.58, 95% confidence interval [CI]: 1.30-1.91 comparing the 90th to the 10th percentiles at fasting; RR = 1.54, 95% CI: 1.33-1.79 at 2 h). In a forward stepwise model controlled for age, family history of hypertension, alcohol consumption and SBP, the selected variables explaining the occurrence of hypertension were, in order, weight change, 2-h free fatty acids, iliac circumference and fasting free fatty acids, whereas body mass index, heart rate, insulin, glucose and other lipids did not enter into the model. CONCLUSIONS: Free fatty acids elevation, when controlled for all known risk factors and other abnormalities of the insulin-resistance syndrome, is a risk factor for hypertension. These results highlight the possible benefits of treatment using free fatty acid oxidation inhibitors.     

Epidemiology of genital prolapse: observations from the Oxford Family Planning Association Study

OBJECTIVE: To explore the epidemiology of uterovaginal and post-hysterectomy prolapse. DESIGN: Cohort study. SETTING: Seventeen large family planning clinics in England and Scotland. POPULATION: 17,032 women who attended family planning clinics between 1968 and 1974, aged between 25 and 39 years at study entry. METHODS: Annual follow up by interview, postal or telephone questionnaire until July 1994. Further details on all hospital admissions were obtained from the hospital discharge summaries. All women were flagged at time of recruitment in the NHS central registers. MAIN OUTCOME MEASURE: In-patient admission with diagnosis of prolapse (ICD codes 8th Revision 623.0-623-9). RESULTS: The incidence of hospital admission with prolapse is 2.04 per 1000 person-years of risk. Age, parity, calendar period and weight were significantly associated with risk of an inpatient admission with prolapse after adjustment for principal confounding factors. Significant trends were observed with regard to smoking status and obesity (Quetelet Index) at entry to the study and risk of prolapse. Social class, oral contraceptive use and height were not significantly associated with risk of prolapse. The incidence of prolapse which required surgical correction following hysterectomy was 3.6 per 1000 person-years of risk. The cumulative risk rises from 1% three years after a hysterectomy to 5% 15 years after hysterectomy. The risk of prolapse following hysterectomy is 5.5 times higher (95% CI 3.1-9.7) in women whose initial hysterectomy was for genital prolapse as opposed to other reasons. CONCLUSION: Among the potential risk factors that were investigated, parity shows much the strongest relation to prolapse.     

Risk factors for falls of hospitalized stroke patients

BACKGROUND AND PURPOSE: Patients with stroke are at a high risk for falling. We assessed the fall incidence and risk factors for patients hospitalized as the result of an acute stroke. METHODS: We studied a cohort of 720 stroke patients from 23 hospitals in The Netherlands. The data were abstracted from the medical and nursing records. RESULTS: We studied 346 women and 374 men with a median age of 75 years; 77% of the patients had had a cerebral infarct, 17% had had a hemorrhage, and 6% had had an undefined stroke. We recorded 104 patients (14%) who fell at least once; there were a total of 173 falls. The incidence of falls was 8.9/1000 patients per day. The daily incidence was 6.2/1000 patients for first falls and 17.9/1000 patients for second falls. Heart disease (relative risk [RR], 1.6; 95% confidence interval [CI], 1.0 to 2.4), mental decline (RR, 1.6; 95% CI, 1.0 to 2.4), and urinary incontinence (RR, 2.3; 95% CI, 1.3 to 4.1) were incremental risk factors for first falls, whereas the use of major psychotropic drugs lowered the fall risk (RR, 0.5; 95% CI, 0.3 to 0.8). The fall RR for patients with one previous fall was 2.2 (95% CI, 1.5 to 3.2), adjusted for the other risk factors. Most falls occurred during the day. Approximately 25% of the falls caused slight-to-severe injury, whereas three falls (2%) led to hip fractures. CONCLUSIONS: Stroke patients have at risk of falling. The identification of patients at risk may be a first step toward the implementation of fall-prevention measures for these patients.     

Survival and incidence of myocardial infarction in men with ambulatory ECG-detected frequent and complex ventricular arrhythmias. 10 year follow-up of the 'Men born 1914' study in Malm?, Sweden

AIM: To assess to what extent do frequent or complex ventricular arrhythmias, detected during 24 h ambulatory electrocardiographic recording (ECG), influence prognosis with regard to survival and incidence of ischaemic heart disease. METHODS AND RESULTS: The study subjects were the 456 randomly selected men born in 1914, the population-based cohort study of 1982-83, in Malm?, Sweden. The main outcome measures were total mortality and incidence of cardiac event (myocardial infarction and death from ischaemic heart disease). Frequent or complex ventricular arrhythmias (Lown classes 2-5) were detected in 49% of the men with (n = 77), and in 35% of those without, a history of myocardial infarction or angina pectoris at baseline, P = 0.019. Independent of clinically evident coronary artery disease at baseline, and after adjustment for traditional atherosclerotic risk factors and use of digitalis or beta-blocker therapy, frequent or complex ventricular arrhythmias were associated with an increased mortality from ischaemic heart disease (relative risk (RR), 2.1; 95% confidence interval (CI), 1.2-3.9) and an increased cardiac event rate (RR, 1.6; 95% CI, 1.0-2.5)). Men free from both ischaemic-type ST depression and frequent or complex ventricular arrhythmias (used as the control group) had the lowest ischaemic heart disease death rate, 5.9 per 1000 person-years. The combination of ST depression and frequent or complex ventricular arrhythmias was associated with an ischaemic heart disease death rate of 20.9 per 1000 person-years. The cardiac event rate in these two groups was 15.6 and 76.1 per 1000 person-years, respectively (adjusted RR, 2.3; CI, 1.1-4.6). CONCLUSIONS: In elderly men without a history of myocardial infarction and angina pectoris, frequent or complex ventricular arrhythmias during ambulatory ECG recording is associated with an increased incidence of myocardial infarction and mortality. Men who, during ambulatory ECG recording, also demonstrate ST-segment depression have an even less favourable prognosis.     

No increased risk of malignancies and mortality in cyclosporin A-treated patients with rheumatoid arthritis

OBJECTIVE: To evaluate the cyclosporin A (CSA)-attributed risk of developing malignancies in general and malignant lymphoproliferative diseases (LPDs) and skin cancers in particular, as well as the CSA-attributed incidence of mortality in patients with rheumatoid arthritis (RA). METHODS: In a retrospective, controlled cohort study, the incidence of malignancies and mortality was evaluated in 208 CSA-treated patients with RA compared with 415 matched control patients with RA between 1984 and 1995. Patients were followed up for a median of 5.0 years (range 1.4-12.0). RESULTS: Forty-eight cases of malignancy (8 in the CSA group and 40 in the control group; relative risk [RR] 0.40, 95% confidence interval [95% CI] 0.19-0.84) were identified, of which 8 were malignant LPDs (2 CSA versus 6 control; RR 0.67, 95% CI 0.14-3.27) and 14 were skin cancers (2 CSA versus 12 control; RR 0.33, 95% CI 0.08-1.47). Seventy-three patients died (16 CSA versus 57 control; RR 0.56, 95% CI 0.33-0.95) due primarily to cardiovascular diseases (4 CSA versus 22 control; RR 0.36, 95% CI 0.13-1.04) or a malignancy (3 CSA versus 8 control; RR 0.67, 95% CI 0.18-2.43). Proportional hazards regression analysis with correction for potential confounding factors did not significantly change the results. CONCLUSION: The study findings suggest that CSA treatment in RA patients does not increase the risk of malignancies in general or the risk of malignant LPDs or skin cancers in particular. Moreover, the incidence of mortality in CSA-treated RA patients was comparable to that in matched control RA patients.     

Association of malignant brain tumors and cancers of other sites

PURPOSE: We conducted an exploratory study of brain tumors that occurred as a second primary malignancy to identify potential risk factors for brain tumors. METHODS: Using data from the Surveillance, Epidemiology, and End Results (SEER) Program, we calculated the sex-specific standardized incidence ratio (SIR), adjusted to age and time period, as an estimate of the relative risk (RR) of developing a second primary brain tumor following other cancers. RESULTS: We found an elevated RR of brain tumors after bladder cancer in both men (RR, 1.7; 95% confidence interval [CI], 1.2 to 2.3) and women (RR, 1.7; 95% CI, 0.8 to 3.2); this effect was present for both astrocytoma and glioblastoma multiforme. Elevated RRs of brain tumors were also found after sarcoma (RR, 4.4; 95% CI, 1.8 to 9.0) and leukemia (RR, 2.9; 95% CI, 1.6 to 4.8) in men, and after colorectal cancer (RR, 1.8; 95% CI, 1.3 to 2.4) and endometrial cancer (RR, 1.4; 95% CI, 1.0 to 1.9) in women. The highest RR observed in this study was for CNS lymphoma following any first primary malignancy in men (RR, 7.9; 95% CI, 5.5 to 11.0). CONCLUSION: The associations of brain tumors with bladder, colorectal, and endometrial cancers in women, and an increased occurrence of CNS lymphoma as a second malignancy in men, are new findings that have not been described previously.     

Decaffeinated coffee and acute myocardial infarction. A case-control study in Italian women

The relationship between consumption of decaffeinated coffee and acute myocardial infarction was analyzed in a case-control study conducted in Italy between 1983 and 1992. Case patients were 433 women with acute myocardial infarction, aged 24 to 69 years (median age, 52 years), and control subjects included 869 women in hospital for a wide spectrum of acute conditions, other than cardiovascular, neoplastic, digestive, and hormone-related diseases or conditions associated with long-term modification of diet. Regular use of decaffeinated coffee was reported by 11% of the case patients and 7% of the control subjects. Compared with women who did not drink decaffeinated coffee, the relative risk (RR) was 1.3 (95% confidence interval (CI), 0.8 to 2.2) for one cup/d and 2.1 (95% CI, 1.1 to 3.9) for 2 or more cups (chi 2(1) for trend = 5.62, P = 0.02). The estimates were somewhat higher after allowance for education, marital status, body mass index, and smoking status (RR for > or = 2 cups of decaffeinated coffee per day, 2.5; 95% CI, 1.2 to 4.9), and somewhat lower after further allowance for diabetes, hypertension, and hyperlipidemia (RR, 1.7; 95% CI, 0.8 to 3.6). There was no association between duration of use of decaffeinated coffee and infarction risk. The relationship between decaffeinated coffee and infarction was consistent across strata of age, education, smoking, and history of hyperlipidemia. Thus, a relationship of marginal significance was observed in this study between decaffeinated coffee and myocardial infarction, of similar magnitude to that described for caffeinated coffee. This indicates that (i) caffeine is unlikely to be a relevant factor in any potential coffee-myocardial infarction relationship, and (ii) shifting from caffeinated to decaffeinated coffee is unjustified in order to reduce any possible coffee-related infarction risk.     

Cardiovascular morbidity in patients with obstructive sleep apnea in relation to the severity of respiratory disorder

BASIC PROBLEM AND OBJECTIVE: Untreated patients with obstructive sleep apnoea (OSA) have an increased risk of death from cardiovascular (cv) disease. This study was undertaken to determine the disease spectrum in patients with sonographically proven OSA (apnoea-hypopnoea index > or = 5), with special reference to cv risk factors and accompanying diseases in relation to the severity of their respiratory abnormalities. The study's aim was to clarify what risk factors and accompanying diseases were associated with different degrees of OSA. PATIENTS AND METHODS: A systematic recording of cv risk factors and accompanying diseases as well as their association to the severity of nocturnal respiratory disorders was made for 175 patients (165 men, 10 women, mean age 54 +/- 10.2 years) with sonographically proven OSA (mean apnoea-hypopnoea index 37 +/- 24.4). RESULTS: The body mass index (BMI) was significantly related to the severity of the respiratory disorder (apnoea-hypopnoea index, AHI, P < 0.05, odds ratio [OR]: 1.95; 95% confidence interval [CI]: 1.15-3.31). In a multivariate analysis, nocturnal breathing pause (P < 0.05; OR: 3.8; 95% CI: 1.3-11.1), left ventricular hypertrophy (P < 0.01; OR: 3.9; 95% CI: 1.5-10.3) and diabetes mellitus (P < 0.05; OR: 4.2, 95% CI: 1.2-14.7) were independently associated with a high-grade breathing disorder (AHI > or = 20). The incidence of left ventricular hypertrophy rose with an increasing severity of nocturnal OSA. CONCLUSION: These data indicate that in patients with high-grade OSA (AHI > or = 20) there is a further grouping together of cardiovascular risk factors, namely increasing body weight, diabetes mellitus, arterial hypertension and left ventricular hypertrophy; they explain the increased mortality rate among these patients from vascular complications.     

Women's health in midlife: the influence of the menopause, social factors and health in earlier life

OBJECTIVE: To describe the health symptoms of a large representative sample of British women at age 47 years, and to examine the influence of the menopause allowing for social factors and health in earlier adult life. DESIGN: A national prospective birth cohort study. Information on health problems, menstrual cycle, use of hormone replacement therapy and life stress at 47 years was collected using a postal questionnaire. Information on health, smoking behaviour and educational attainment earlier in life had been collected at previous home visits. SETTING: England, Scotland and Wales. POPULATION: A general population sample of 1498 women, 84% of those sent a questionnaire. MAIN OUTCOME MEASURE: Twenty self-reported health symptoms over the previous 12 months. RESULTS: Women who had experienced an early natural menopause had a strongly raised risk of vasomotor symptoms (hot flushes or night sweats), sexual difficulties (vaginal dryness or difficulties with intercourse) and trouble sleeping. However, there was little or no excess risk of other somatic or psychological symptoms. In contrast, all types of symptoms were more common among women who had had a hysterectomy or were users of hormone replacement therapy. Women with the least education, stressful lives, or a previous history of poor physical and psychological health at age 36 also reported more symptoms at 47 years compared with other women, but adjustment for these factors in a logistic regression model did not affect the relations between symptoms and current menopausal status. For vasomotor symptoms, postmenopausal women had an adjusted odds ratio of 4.7 (95% CI 2.6-8.5) and perimenopausal women had an adjusted odds ratio of 2.6 (95% CI 1.9-3.5) compared with premenopausal women. Corresponding adjusted odds ratios for sexual difficulties were 3.9 (95% CI 2.1-7.1) and 2.2 (95% CI 1.4-3.2), and for trouble sleeping were 3.4 (95% CI 1.9-6.2) and 1.5 (95% CI 1.1-2.0). CONCLUSIONS: Specific symptoms were clearly associated with the natural menopause. More general health concerns were common among women in middle life, particularly among those with stressful lives, or those who had had a hysterectomy or started taking hormone replacement therapy before they were postmenopausal. Appropriate advice and support needs to be easily accessible.     

Risk factors for contralateral breast cancer in Chennai (Madras), India

BACKGROUND: This is the first cohort study conducted in India to identify risk factors for contralateral breast cancer (CBC) among patients with first primary breast cancer. METHODS: Patients with first primary breast cancer diagnosed in 1960-1989 at the Cancer Institute (WIA) in Chennai, India, were followed-up until 31 December 1994. The risk of CBC was assessed among unilateral breast cancer (UBC) patients who survived for >12 months following the diagnosis of breast cancer and did not develop a second cancer (n = 2665) and among those who developed a CBC > or =12 months after the diagnosis of breast cancer (n = 39). RESULTS: The age-adjusted incidence of CBC among women with UBC was seven times the incidence (per single breast) in the general population. Among women with UBC the relative risk (RR) was 4.5 (95% CI: 1.1-19.6) comparing those with and without a history of breast cancer in the mother, and 2.8 (95% CI: 1.2-6.7) comparing age at first birth 21-25 versus earlier. The RR was 0.3 (95% CI: 0.1-0.6) comparing those with and without hormone therapy for their UBC. Radiotherapy for the UBC had no significant effect on the incidence of CBC. CONCLUSION: Positive family history of breast cancer and later age at first childbirth emerged as stronger risk factors for CBC than UBC. Hormone therapy reduces the risk of CBC.     

A rivalry of foulness: official and unofficial investigations of the London cholera epidemic of 1854

OBJECTIVE: To describe and explain sex differences in antihypertensive drug use. DESIGN AND METHODS: From 1987 to 1995, two cross-sectional population-based surveys of cardiovascular disease risk factors in The Netherlands were carried out among 56026 men and women aged 20-59 years. Polytomous logistic regression modelling was used to adjust for potential confounders of the association between sex and use of different antihypertensive drugs. RESULTS: The response rate was 40% for men and 46% for women. Of these respondents, 40% (1041) of the hypertensive men and 59% (1403) of the hypertensive women were being treated pharmacologically; 57% (595) of the treated men and 54% (760) of the treated women were on monotherapy for hypertension with a diuretic (men 14.8%, women 37.2%), a beta-blocker (men 59.0%, women 45.3%), a calcium antagonist (men 8.6%, women 5.0%) or an angiotensin converting enzyme inhibitor (men 17.7%, women 12.5%). Among those on monotherapy for hypertension, women were less likely than men to be using a beta-blocker [prevalence odds ratio (POR), female/male=0.34; 95% confidence interval (CI) 0.24-0.47], a calcium antagonist (POR=0.27, 95% CI 0.15-0.48) or an angiotensin converting enzyme inhibitor (POR=0.34, 95% CI 0.22-0.52) than a diuretic. These sex differences persisted after adjustment for all factors that could have influenced the choice of these antihypertensive drugs (indications and contra-indications for the four antihypertensive drug classes). The sex differences in antihypertensive drug use were smaller among hypertensives with a history of cardiovascular disease (adjusted PORs, female/male, for beta-blockers, calcium antagonists and ACE inhibitors, respectively, compared to diuretics were 0.80 with 95% CI 0.20-3.24, 0.40 with 95% CI 0.10-0.48 and 0.64 with 95% CI 0.12-3.39) than among those without such a history. CONCLUSIONS: The different patterns of antihypertensive drug use among hypertensive men and women seem irrational, and cannot be explained by factors known to influence antihypertensive drug choice. Among hypertensives with a history of cardiovascular disease, the sex differences were smaller than among those without such a history. Further research is required to explain the sex differences in the choice of antihypertensive drug by prescribers, and to investigate the consequences of these differences for long-term patient outcomes.     

Stroke and use of low-dose oral contraceptives in young women: a pooled analysis of two US studies

BACKGROUND AND PURPOSE: The available data on low-dose oral contraceptive pill (OCP) use and stroke risk in US women are limited by small numbers. We sought more precise estimates by conducting a pooled analysis of data from 2 US population-based case-control studies. METHODS: We analyzed interview data from 175 ischemic stroke cases, 198 hemorrhagic stroke cases, and 1191 control subjects 18 to 44 years of age. RESULTS: For ischemic stroke, the pooled odds ratio (pOR) adjusted for stroke risk factors for current use of low-dose OCPs compared with women who had never used OCP (never users) was 0.66 (95% confidence interval [CI], 0.29 to 1.47) and compared with women not currently using OCPs (nonusers) the pOR was 1.09 (95% CI, 0.54 to 2.21). For hemorrhagic stroke, the pOR for current use of low-dose OCPs compared with never users was 0.95 (95% CI, 0.46 to 1.93) and compared with nonusers the pOR was 1.11 (95% CI, 0.61 to 2.01). The pORs for current low-dose OCP use and either stroke type were not elevated among women who were >/=35 years, cigarette smokers, obese, or not receiving medical therapy for hypertension. pORs for current low-dose OCP use were 2.08 (95% CI, 1. 19 to 3.65) for ischemic stroke and 2.15 (95% CI, 0.85 to 5.45) for hemorrhagic stroke among women reporting a history of migraine but were not elevated among women without such a history. Past OCP use (irrespective of formulation) was inversely related to ischemic stroke but unrelated to hemorrhagic stroke. CONCLUSIONS: Women who use low-dose OCPs are, in the aggregate, not at increased risk of stroke. Studies are needed to clarify the risk of stroke among users who may be susceptible on the basis of age, smoking, obesity, hypertension, or migraine history.     

Ion channels, cell volume, and apoptotic cell death

BACKGROUND: Condylomata acuminata is one of the most common sexually transmitted diseases (STDs) diagnosed in the United States, yet relatively little research has been conducted on the determinants of this disease in well-defined populations. GOAL: To determine the exposures that predispose a woman to the development of condylomata acuminata or genital warts. STUDY DESIGN: A population-based case-control study was conducted among enrollees of Group Health Cooperative of Puget Sound. Patients (94 women with incident and 55 women with recurrent condyloma) were diagnosed between April 1, 1987 and September 30, 1991. Control subjects were 133 women without a history of genital warts. An in-person interview was conducted to collect information on subject characteristics, exposures, and on all episodes of genital warts. RESULTS: Women with five or more partners within the 5 years before reference date were over seven times more likely to have incident condyloma (relative risk [RR], 7.5; 95% confidence interval [CI], 3.1-18.1) and over 12 times more likely to have recurrent condyloma (RR, 12.8; 95% CI, 4.2-38.9) compared with women with only one sexual partner during this time period. An increased risk of incident condyloma was also associated with a history of any STD (RR, 2.6; 95% CI, 1.1-5.8), a history of oral herpes (RR, 2.2; 95% CI, 1.1-4.4), and a history of allergies (RR, 2.0 95% CI, 1.0-3.8). Our data did not support a strong association between risk of condyloma and smoking or recent use of oral contraceptives. CONCLUSION: Our results suggest that risk of condyloma is primarily related to sexual behavior. We did not observe a strong association between risk of condyloma and many of the exposures considered to be potential cofactors for anogenital cancers associated with other types of human papillomaviruses.     

Impact of major cardiovascular disease risk factors, particularly in combination, on 22-year mortality in women and men

BACKGROUND: The appropriateness of current cardiovascular disease (CVD) risk factor guidelines in women continues to be debated. OBJECTIVE: To present new data on the appropriateness of current CVD risk factor guidelines, for women and men, from long-term follow-up of a large population sample. METHODS: Cardiovascular disease risk factor status according to current clinical guidelines and long-term impact on mortality were determined in 8686 women and 10503 men aged 40 to 64 years at baseline from the Chicago Heart Association Detection Project in Industry; average follow-up was 22 years. RESULTS: At baseline, only 6.6% of women and 4.8% of men had desirable levels for all 3 major risk factors (cholesterol level, <5.20 mmol/L [<200 mg/dL]; systolic and diastolic blood pressure, <120 and <80 mm Hg, respectively; and nonsmoking). With control for age, race, and other risk factors, each major risk factor considered separately was associated with increased risk of death for women and men. In analyses of combinations of major risk factors, risk increased with number of risk factors. Relative risks (RRs) associated with any 2 or all 3 risk factors were similar: for coronary heart disease mortality in women, RR= 5.72 (95% confidence interval [CI], 2.35-13.93), and in men, RR = 5.51 (95% CI, 3.10-9.77); for CVD mortality in women, RR = 4.54 (95% CI, 2.33-8.84), and in men, RR = 4.12 (95% CI, 2.56-6.37); and for all-cause mortality in women, RR = 2.34 (95% CI, 1.73-3.15), and in men, RR = 3.20 (95% CI, 2.47-4.14). Absolute excess risks were high in women and men with any 2 or all 3 major risk factors. CONCLUSIONS: Combinations of major CVD risk factors place women and men at high relative, absolute, and absolute excess risk of coronary heart disease, CVD, and all-cause mortality. These findings support the value of (1) measurement of major CVD risk factors, especially in combination, for assessing long-term mortality risk and (2) current advice to match treatment intensity to the level of CVD risk in both women and men.