Symptoms in peri- and postmenopausal women in relation to testosterone concentrations: data from The Women's Health in the Lund Area (WHILA) study.

OBJECTIVES: The aim of this study was to investigate possible associations between androgen concentrations in perimenopausal women and symptoms that may be associated with low androgen concentrations in the blood. METHODS: All women born in the period 1935-1945 and living in a defined geographic area in Sweden (n = 10 766) were invited to a screening program that included physical and laboratory examinations and a questionnaire. Three groups were identified: premenopausal women, women on hormone replacement therapy (HRT) and postmenopausal women without HRT. Concentrations of testosterone, androstendione, sex hormone binding globulin and estradiol were measured. Waist-hip ratio, body mass index and free testosterone index (FTI) were calculated. RESULTS: A total of 6908 women participated. The women on HRT had lower testosterone and FTI and were less satisfied with mood and energy (p < 0.05). Women with hot flushes had higher testosterone and FTI and women reporting coldness had lower concentrations (p < 0.05). Sexual well-being was not correlated to testosterone or FTI (p > 0.05). CONCLUSIONS: Lower testosterone concentrations were associated with lower quality of life in perimenopausal women but not to sexual well-being. There must be factors other than decrements in sex hormones that contribute to the emergence of some perimenopausal symptoms.

Could androgens protect middle-aged women from cardiovascular events? A population-based study of Swedish women: The Women's Health in the Lund Area (WHILA) Study.

OBJECTIVE: The aim of this analysis was to delineate perceived associations between androgens and cardiovascular events in perimenopausal women. DESIGN: A cross-sectional, population-based study of 6440 perimenopausal women aged 50-59 years, living in Southern Sweden. In all, 461 (7.1%) women were premenopausal (PM), 3328 (51.7%) postmenopausal without hormone therapy (HT) (PM0) and 2651 (41.2%) postmenopausal with HT (PMT). For further comparisons, 104 women (1.6%) who reported cardiovascular disease (CVD) were studied in detail; 49 had had a myocardial infarction, 49 a stroke and six women both events. For each woman with CVD, two matched controls were selected (n=208). RESULTS: In the matched controlled series, androstenedione levels were lower (p<0.005) in cases. Cases with hormone therapy had also lower testosterone levels than matched controls (p=0.05). In the total cohort, by using multiple logistic regression analyses, testosterone was positively associated with low density lipoprotein cholesterol (p<0.001) and high density lipoprotein cholesterol (HDL-C) (p<0.001) in all women, but negatively associated with levels of triglycerides in both the PM0 (p<0.001) and PMT (p<0.001) groups. Androstenedione levels were positively associated with HDL-C (p<0.05) and negatively with triglycerides (p<0.05) in the PM group. CONCLUSION: Women with cardiovascular disease had lower serum androgen levels, particularly women using hormone replacement therapy, even when controlled for lipids and other potential risk factors.

Lund Stroke Register: hospitalization pattern and yield of different screening methods for first-ever stroke.

OBJECTIVES: To explore case ascertainment, hospitalization, characteristics of both hospitalized and non-hospitalized patients in a population-based group of stroke patients. MATERIALS AND METHODS: One-year screening in Lund-Orup district for first-ever strokes using multiple prospective and retrospective methods. RESULTS: A total of 456 patients with first-ever stroke (n = 412 prospective screening methods, n = 17 primary care, n = 12 hospital registers, n = 10 death register, n = 2 autopsy registers, n = 3 other). Hospitalization proportion within 14 days was 84%. Patients sent home from emergency unit (n = 36) were often males (75%), had low 28-day case-fatality (0%), and less severe strokes (median National Institute of Health Stroke Scale score 2 vs 4 for all). Patients managed solely within primary care (n = 18) were elderly (median age 89 vs 77 years for all), resided in nursing homes (86% vs 8% for all) and had high 28-day-case-fatality (61%). CONCLUSIONS: Hospitalization was lower than expected. Two main categories of patients were not hospitalized: elderly patients at nursing homes with high case-fatality and patients with mild stroke.

Cardiovascular risk factors in middle-aged women and the association with use of hormone therapy: results from a population-based study of Swedish women. The Women's Health in the Lund Area (WHILA) Study.

OBJECTIVE: Cardiovascular diseases in women are multifactorial. Women carry different risk factors compared to men and these specific risk factors need to be delineated, particularly in relation to the hormonal situation, and effects of diet and lifestyle. METHODS: Out of the total cohort of 10,766 women born 1935-1945 living in the Lund area of southern Sweden, 6917 women completed a generic questionnaire and underwent a physical and laboratory assessment. According to hormonal status, 492 women were premenopausal (PM), 3600 were postmenopausal without hormone therapy (HT) (PM0) and 2816 were postmenopausal with ever-use of HT (PMT). Major cardiovascular risk factors as well as level of education, diet, and degree of physical activity were assessed in relation to hormonal status. RESULTS: Compared to the PM0 group, the women in the PMT group had a higher level of education, more often worked full time, more often had sedentary work and lived a more regular life. They also had a lower rate of cigarette consumption, lower waist-to-hip ratio and lower body mass index than women in the PM0 group. The PMT group had lower levels of serum total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglycerides than the PM0 group and also had lower systolic and diastolic blood pressures, a lower prevalence of type II diabetes mellitus, of deep venous thrombosis and of coronary artery disease. Low-risk factors for cardiovascular disease and high level of education were still associated with HT, after adjustment by multiple logistic regression. Major risk factors for coronary heart disease were similar between the PM and the PMT groups. CONCLUSION: Use of HT is accompanied by a lower risk profile for cardiovascular disease and also by several factors indicating a healthier lifestyle.

Socio-demographic and psychosocial factors are associated with features of the metabolic syndrome. The Women's Health in the Lund Area (WHILA) study.

AIM: The aim was to analyse any associations between socio-demographic and psychosocial factors and different features of the metabolic syndrome in a geographically well-defined population of middle-aged women. METHODS: A population of 10 766 Caucasian women aged 50-59 years was investigated regarding biological and socio-demographic conditions, physical activity, dietary habits, aspects of quality of life, and subjective physical and mental symptoms. The screening instrument was used to discriminate subjects as positive or negative on one or more of a total of eight variables considered to be linked to the metabolic syndrome. The cut-off values for positive screening were non-fasting capillary blood glucose >/= 8.0 mmol/l and serum triglycerides >/= 2.3 mmo/l, BMI >/= 30 kg/m2, WHR >/= 0.90, blood pressure >/= 160 and/or 95 mmHg, a family history of diabetes, and pharmacological treatment for hypertension or hyperlipidaemia. RESULTS: Altogether 6805 women (63.2%) participated: 3535 with positive and 3270 with negative screening. Multiple logistic regression analyses showed that comprehensive (OR 1.62, 95% CI 1.41-1.87) and upper secondary (1.40, 1.24-1.57) school, low physical quality of life (1.41, 1.23-1.61) and high sum of subjective physical symptoms (1.06, 1.04-1.08) were positively associated with one or more features of the metabolic syndrome, while high leisure-time exercise and healthy diet (0.84, 0.71-0.99), and low (

A screening procedure detecting high-yield candidates for OGTT. The Women's Health in the Lund Area (WHILA) study: a population based study of middle-aged Swedish women.

The objective was to evaluate a screening procedure for detecting high-yield candidates for an OGTT, in a population of middle-aged Swedish women. A two-step screening procedure was performed in 6917 subjects. Women with a positive screening outcome, i.e. increased non-fasting capillary blood glucose, serum triglycerides, BMI, WHR, blood pressure or a family history of diabetes, pharmacological treatment of hypertension or hyperlipidaemia at the primary screening underwent a 75-g OGTT. A control group of women with negative screening outcome (n = 221) also underwent an OGTT. In 2923 women with positive screening outcome, 517 (17.7%) had NFG/IGT (normal fasting venous blood glucose <5.6 mmol/l and 2h-glucose 6.7-9.9 mmol/l), 109 (3.7%) IFG/IGT (fasting 5.6-6.0 and 2h 6.7-9.9 mmol/l) and 223 (7.6%) diabetes (fasting > or = 6.1 or 2h > or = 10.0 mmol/l). These figures were three, five and four times higher, respectively, than in the control group with negative screening outcome (p < 0.001 for all); no differences were found for IFG/NGT (fasting 5.6-6.0 and normal 2h < 6.7 mmol/l) (4.6% vs. 7.2%). For predicting impaired glucose metabolism (IFG/NGT, NFG/IGT, IFG/IGT, diabetes), the screening instrument showed an estimated sensitivity of 70%, specificity of 55%, positive predictive value of 34% and negative predictive value of 85%, based on findings in the control sample. The odds ratio for NFG/IGT increased with the numbers of risk factors from 2.8 to 7.7, for IFG/ IGT from 5.7 to 55.0 and for diabetes from 2.5 to 18.1. High B-glucose, WHR and BMI were the three most important factors associated with an increased risk for NFG/IGT, IFG/IGT and diabetes. In subjects with IFG/NGT, none of the screening variables was associated with an increased risk. In summary, the results show a population screening method focused on features of the metabolic syndrome that discloses high-yield candidates for OGTT. A high prevalence of unknown impaired glucose metabolism was found in middle-aged women with a positive screening profile.

Dyslipidaemia and impaired well-being in middle-aged women reporting low Sense of Coherence. The Women's Health in the Lund Area (WHLA) Study.

OBJECTIVE: A low Sense of Coherence (SOC) is a concept related to a feeling of ill health. Not much is known about possible relationships between SOC and biological factors. SETTING: Population-based study of middle-aged women. SUBJECTS AND METHODS: Four-hundred-and-fifty women participated as a subgroup of a larger study of cardiovascular risk factor screening. A self-administered questionnaire with 29 questions related to SOC was completed in addition to questions on social background factors and medical history. RESULTS: The mean score of SOC was 150.9 (SD 23.4). HDL cholesterol was lower (p < 0.05) and triglyceride levels higher (p < 0.05) in women with low SOC (1.5 and 2.1 mmol/L) compared to women with medium (1.8 and 1.4 mmol/L) or high SOC (1.7 and 1.5 mmol/L). In multiple regression analysis, a low HDL cholesterol level was still significantly associated with low SOC (p < 0.05) after adjustment for possible confounders. Women reporting low SOC were further characterised by a higher proportion of subjects with regular clinical visits for health care (49% vs 35% and 29%). CONCLUSIONS: Middle-aged women reporting low SOC showed lower HDL cholesterol and higher triglyceride levels, and reported more clinical visits and medical symptoms than women with higher SOC.

Effects of norethisterone acetate addition to estradiol in long term HRT.

OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerability of hormone replacement therapy (HRT) among postmenopausal women living in the Lund area of Southern Sweden and to analyze treatment effects in different types or routes of HRT administration, as well as to compare with unopposed estrogen therapy. METHOD: in an ongoing, large population-based, prospective cohort study, this interim analysis included 3900 women. Of them, 693 postmenopausal women were eligible in the present analyses as they continued to use one of the four commercial HRT products for at least 2-3 years, i.e. continuous oral estradiol (E(2)) 2 mg+norethisterone acetate (NETA) 1 mg (CON-O), sequential oral estradiol 2 mg + norethisterone acetate 1 mg (CYC-O), sequential transdermal estradiol 50 microg + norethisterone acetate 250 microg (CYC-TRANS) and estradiol monotherapy. These women completed one generic questionnaire and one specific 'hormonal' questionnaire, as well as a personal interview pertaining to socio-demographics, detailed status of HRT use, and therapeutic efficacy and untoward side-effects by HRT. RESULTS: comparing the three combined E(2)+NETA groups with E(2) monotherapy, the beneficial effects on sexual desire and emotional well-being were significantly less in the combined groups than in E(2) monotherapy group. There was no significant difference regarding the negative side-effects between the groups. No significant difference was found between CON-O and CYC-O groups either in positive effects or in negative side-effects. A higher prevalence of positive effects was found in CYC-TRANS group than that in CYC-O group, especially in amelioration of sleep and urinary symptoms. Higher odd ratios of negative effects by HRT, such as irregular bleeds, weight gain, food craving and skin disorders were also found in CYC-TRANS group. CONCLUSION: in long-term HRT administration, the addition of a progestogen in HRT could compromise the beneficial effects of estradiol, particularly, the effects on women's emotional well being and psychosexual functioning. Administration of NETA continuously and sequentially had similar therapeutic efficacy and tolerability. More marked positive effects, such as improving of sleep and urinary symptoms, as well as nuisance side-effects, i.e. irregular bleeds, weight gain, food craving and skin disorders were encountered by the women using sequential transdermal regimen

Important factors for use of hormone replacement therapy: a population-based study of Swedish women. The Women's Health in Lund Area (WHILA) Study.

OBJECTIVE: The aim of this study was to delineate the use of hormone replacement therapy (HRT) among women who were born between December 2, 1935, and December 1, 1945, and living in the Lund area of southern Sweden and to analyze factors that contribute to the acceptance and continuation of HRT. METHODS: All women received a generic questionnaire pertaining to demographic background, lifestyle, health behavior, and climacteric symptoms and underwent a personal interview. An interim analysis was carried out on 3,900 women. We mailed a hormone questionnaire to the women who were using HRT (n = 1,875). This hormone questionnaire covered, for example, menopausal status, complaints, and alterations in and efficacy of HRT use, as well as the reasons for discontinuing HRT use. RESULTS: A total of 1,415 (76%) women answered the hormone questionnaire. Forty-eight percent were HRT ever users, and 32% were current users. Mean duration of HRT use was 47 months. The most common incentives for HRT use were alleviation of menopausal symptoms (72%) and prevention of bone loss (50%) and/or cardiovascular disease (31%). Forty-seven percent of HRT users reported that they had changed regimens at least once. HRT users had higher education, full-time work, and a higher consumption of alcohol but less consumption of cigarettes. They reported higher frequencies of climacteric symptoms, past histories of premenstrual syndrome, use of oral contraceptives, and hysterectomy. They also had a higher consumption of healthcare resources. A total of 177 women withdrew from therapy. The most common reasons for discontinuation of HRT were weight gain, anxiety of cancer, bleeding, breast tenderness, and emotional problems. Compared with current users, past users had less positive as well as fewer negative effects of HRT. Several variables contributed to compliance, including education, full-time work, regular exercise, low frequency of persistent climacteric symptoms, and alteration of regimens. CONCLUSION: Education, working conditions, lifestyle, interest in prevention, and severity of the climacteric symptoms are determinants for both acceptance of and compliance with HRT.

Urogenital symptoms in women aged 50-59 years. Women's Health in Lund Area (WHILSA) Study Group.

Problems related to the urogenital tract are common in elderly women. Control of micturition is often impeded and questionnaire-based studies have reported a prevalence of poor control of micturition in about 30% of postmenopausal women. In an ongoing cohort comprising women born between 1935 and 1945, an interim analysis was performed in 1800 women based on an interview and questionnaire. The prevalence of urinary incontinence was found to be 33%, which is in accordance with previous reports. The main difference between the interview and the questionnaire was that the interview could take into account intensity as well as intermittence of symptoms. There were no differences between premenopausal women and postmenopausal women using or not using hormone replacement therapy. In agreement with earlier studies, we found poorer control of micturition in parous women. A higher percentage of incontinence was also found in women who had lost more than 5 kg in body weight during the preceding 5 years. In addition, women with a family history of diabetes were more prone to complaints of incontinence. Of the 155 women who had a family history of diabetes, 66 were incontinent (p < 0.01). It was also found that women who were incontinent were more often on regular surveillance for various diseases, using more medications regularly and had been hospitalized during the last 5 years more often than women who were continent. There were no differences in smoking habits. The present results imply that urinary incontinence in women is of a complicated origin and that the hormonal situation plays a minor role for this socially handicapping symptom.

Cardiovascular mortality and morbidity in seven counties in Sweden in relation to water hardness and geological settings. The project: myocardial infarction in mid-Sweden.

An east-west regional gradient in cardiovascular mortality was found within seven counties in mid-Sweden during the years 1969-1983. The mortality differences were of considerable magnitude for ischaemic heart disease (IHD) as well as for stroke. In previous reports, in which the distribution of risk factors among middle-aged men was presented, the moderate variation among the communities could not explain the mortality variation. Water hardness has previously been reported to be inversely related to cardiovascular mortality in several countries. In this paper, water samples from all 76 communities in seven counties were analysed in relation to mortality rates from IHD and stroke for men and women. Water hardness (Ca+Mg and other minor constituents), and the sulphate and bicarbonate concentrations of the drinking water were inversely related to IHD as well as stroke mortality. The water factors were also inversely related to non-fatal IHD even when account was taken of the age variation and the traditional risk factors as measured by a postal questionnaire. Variation of the water factors accounted for 41% of the variation in IHD mortality rate and 14% of the variation in stroke mortality rate over the 76 communities.

Traditional risk-factor profile fails to explain striking geographical differences in IHD mortality among middle-aged men. The project "myocardial infarction in mid-Sweden".

An east-west gradient in cardiovascular mortality has been reported from the region of mid-Sweden. Postal questionnaire studies found that the risk factor distributions among middle-aged men were similar in areas with striking differences in cardiovascular mortality. In this study, 120 randomly selected 50-year-old men in two high mortality communities in the west and 120 men from two low mortality communities in the east were invited to a health survey in which serum lipids and other risk factors were analysed. Total serum cholesterol, LDL-cholesterol, HDL-cholesterol, and triglyceride levels were similar. Among fatty acids, stearic acid was high and arachidonic acid was low in the high mortality area. The levels of other traditional risk factors were the same. After taking these differences into account, the mortality differences remain large.

Are geographical differences in cardiovascular mortality due to morbidity differences or to methodological differences? The project "myocardial infarction in Mid-Sweden".

Geographical variations in cardiovascular mortality have been reported from Mid-Sweden. IHD mortality for men aged 45-64 was 60% higher in the western part than in the east. Mortality from stroke for men aged 45-74 was 73% higher on the west. Similar differences were found for women. One possible explanation could be that there are no incidence differences but that the mortality differences are due to different survival rates or to differences certifying the cause of death. These two possible explanations were tested in this study. Data for all patients hospitalised during the 10-year period 1972-1981 for myocardial infarction or stroke in a high mortality area, the County of Värmland in the west, and a low mortality area, the County of Uppsala in the east, were collected. In addition, a substudy was performed where the basis for the death certificate diagnosis was studied. The western area generally had a higher case fatality rate than the eastern. However, a larger proportion of the deaths the eastern area, occurred outside hospital, so that the net effect would be that the differences found were not large enough to explain the mortality differences. The autopsy rate in the western part was lower than in the east but since a larger proportion of the deaths occurred in hospital the rank order for IHD and stroke mortality between east and west was the same whether all IHD or stroke deaths were counted or only those considered the most well documented.

Are regional variations in ischaemic heart disease related to differences in coronary risk factors? The project 'myocardial infarction in mid-Sweden'.

In a previous report, a large regional variation was reported in total mortality and mortality rate from ischaemic heart disease (IHD) in mid-Sweden. In this report, IHD prevalence and risk factor data are presented. A postal questionnaire was sent out to a random sample of men aged 45-64 years in each of 40 communities. 14,675 men (88%) responded. Based on a validity study, IHD cases were defined as those with a history of myocardial infarction and/or angina pectoris. Age, smoking habits, antihypertensive treatment, body mass index, food habits, stress and physical activity during leisure time were used as risk factors. IHD prevalence showed the same geographical variation as IHD mortality, with a low prevalence in the east and a high prevalence in the west. There was a moderate variation in risk factor levels over the 40 communities. When this variation was taken into account the geographical IHD variation was somewhat smaller but still substantial. Other factors may involve socio-economics, drinking water qualities, mineral soil content or other environmental factors. Which of these cause the largest IHD variation is at present unknown, but is subject to systematic examination in this project.

Identification of cases of myocardial infarction: hospital discharge data and mortality data compared to myocardial infarction community registers.

Identification of incident myocardial infarction (MI) cases in a defined population using hospital discharge data and mortality data in combination has been suggested. This method of case identification was compared to that of use of MI community registers set up in accordance with principles adopted in a World Health Organization collaborative programme. The comparison comprised data for four Swedish cities over a number of years. On average 81% of incident hospital-treated cases below 65 years of age identified through MI community registers were found by the retrospective use of the method based on hospital discharge data and mortality data. Of hospital-treated cases identified by the latter method, 83% were also found by the MI community registers. For cases fulfilling the diagnostic criteria employed by the MI community registers this proportion would be higher, probably 87%-92%. Several reasons for cases being missed by either method were suggested by the results. According to the findings of this study, the case identification of the method based on hospital discharge data and mortality data seems to be somewhat less efficient compared to use of MI community registers. This may be of importance in descriptive epidemiological studies, but is of less significance in analytical studies. The relative efficiency of the former method could be improved by a more reliable system for the recording of hospital discharges. If supplemented by a validation procedure, it could yield sufficiently accurate data for many epidemiological applications at a fairly low cost.

Geographical variation of mortality from cardiovascular diseases. The Project 'Myocardial Infarction in mid-Sweden'.

In this study, the geographical variation of the mortality rate in mid-Sweden was studied. Data on mortality from all causes and mortality from cardiovascular diseases, cerebrovascular diseases, ischaemic heart disease (IHD) and non-cardiovascular diseases for men and women 45-74 years of age living in 76 communities in mid-Sweden were obtained from the National Bureau of Statistics. After age standardization, the rates for mortality from all causes and cardiovascular mortality were substantially higher in the Westernmost communities compared with those in the East, whereas for non-cardiovascular mortality there were no systematic differences. The county with the higher rate for IHD had a 60% higher rate for men aged 45-64 years and a 53% higher rate for women aged 45-64 years than the county with the lowest rate. The corresponding excess mortality rates from stroke were 73% for men aged 45-74 and 46% for women aged 45-74 years. The cause of this variation is not known. It is not due to the confounding effect of different age distributions in the communities, differences in the registration of causes of death, or differences in case fatality rate.