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The Women's Health in the Lund Area (WHILA) study invited all women (n = 10,766) living in the Lund area of Southern Sweden by 1995, who were born between 1935 and 1945. The health screening program included a postal validated questionnaire concerning medical history, drug treatment, family history of diabetes and hypertension, menopausal status, smoking and alcohol habits, education, household, and working status, physical activity, quality of life as well as subjective physical and mental symptoms.
The screening consisted of a routine physical examination with standardized blood pressure measurements, bone densitometry and an extended laboratory examination. A link with the mammography registry was established. Based on menopausal status, the population was divided in three subgroups; premenopausal (PM), postmenopausal with hormone replacement therapy (PMT), and postmenopausal without hormone replacement therapy (PM0). Menopause was defined as a bleed-free interval of at least 12 months.
Of 10,766 women, 6917 (64.2%) had complete data sets. A number of observational analyses were carried out based on the screening data at baseline, to be followed by long-term follow-up analyses based on national register linkages that are currently being started.
Several projects have described the health status and risk factor profiles of a variety of diseases in middle-aged men. In contrast, middle-aged women as a group have not been studied that well in Europe.
Diabetes is as a risk factor for cardiovascular disease substantially greater in women than in men, as compared to non-diabetic controls. Estrogen deficiency and changes in free testosterone and sex–hormone binding globulin (SHBG) may be involved, but the possible interactions with other risk factors have not been considered in detail.
Peri- and postmenopausal osteoporosis is mainly caused by a reduction in estrogen. Reduced risk of osteoporosis has been described in type 2 diabetic patients. However, the mechanisms of the individual factors are not yet fully understood, and to what extent the hormonal status influences bone density in persons with co-existing morbidity, e.g. diabetes.
Nearly one third of postmenopausal women complain of incontinence. This is often a hidden problem as women hesitate to seek medical attention. However improved methods for diagnosis as well as treatment render further characterization of this problem an ostensible way of reducing an important health problem in women.
Little is known whether psychological factors and socio-demographic conditions influence prevalence and severity of the disease burden in middle-aged women. One aspect of this is cognitive processes as a reflection of psychological factors, such as self-reported sense of coherence.
1.1 Main objectives of WHILA study
The general objective is to study the health profile in a population-based cohort of women aged 50–59 years in a geographically defined area, in relation to biomedical metabolic factors, bone density, quality of life, life style, social conditions and different subjective symptoms. The perceived significance of hormonal changes in relation to these factors is also documented.
The general hypothesis is that there are interrelations between biological metabolic processes and socio-demographic and psychosocial conditions, and that detection of risk factors at an early stage and intervention in high-risk individuals, can delay or prevent the development of subsequent cardiovascular disease, diabetes, osteoporosis and urinary incontinence.
1.2 Study population
The Women's Health in the Lund Area (WHILA) study invited all women (n = 10,766) living in the Lund Area of Southern Sweden by December 1, 1995, and who were born between December 2, 1935, and December 1, 1945, to a screening procedure which took place from December 1, 1995 till February 3, 2000. A population registry comprising all inhabitants identified the study population.
Informed consent was obtained from all participating subjects and the Ethics Committee at Lund University approved the study as well as the Data Registry Inspection in Stockholm.
Women were told to fill out the questionnaire at home and then bring it to the screening centre in conjunction with the health screen process.
Of the 10,766 women, 6917 (64.2%) finally had a complete data set.
Non-responders in the cohort were examined and characterized via data from official registries.
The health screening program included laboratory examinations and a basic questionnaire that was mailed along with the invitation, and collected in conjunction with the first examination (primary screening) (Fig. 1).
Fig. 1Screening procedure for women with positive profile and re-examination of women with IGT.
Women with features of the metabolic syndrome (positive screening) underwent a baseline OGTT 1–4 weeks later. Women with IGT were subsequently invited to a 2.5-year follow-up study. A random sample of subjects without any positive screening variables was also studied (Fig. 2).
The basic (generic) questionnaire included 104 questions concerning medical history, drug treatment, family history of diabetes and CVD (parents or siblings with events before the age of 60 years), perimenopausal status, smoking and alcohol habits, education, household, working status, physical activity, general dietary habits, physical-, social-, and mental well-being (quality of life) as well as subjective physical and mental symptoms.
This questionnaire was a composite of several pre-existing and validated questionnaires [
Does hormone therapy increase allergic reactions and upper gastrointestinal problems? Results from a population-based study of Swedish woman. The women's health in the Lund area (WHILA) Study.
To further validate this particular questionnaire it was mailed twice to 100 women around 55 with 2 months interval between mailings, and results were compared.
All women who passed the baseline OGTT answered a validated food questionnaire, which described in detail the consumption of fat, fibres, fruits/vegetables and sweets/carbohydrates [
]. Women who were re-examined in the longitudinal follow-up study completed once again the two questionnaires.
All women who answered yes to the question whether they had used hormone therapy received a special hormonal questionnaire comprising five sections with 39 additional questions on HRT use and factors of potential interest for HRT use such as HRT prescriptions, purpose of HRT use, stated reasons for discontinuation as well as perceived positive and negative effects by HRT. This questionnaire also contained queries on mood changes such as PMS postpartum depression and mood changes related to use of hormonal contraception during their reproductive period.
Those women who on the visual analogue scale of problems with urinary continence had marked 2 or higher on a bothersomeness scale from 0 to 10 were given a specific “incontinence questionnaire” with an additional 16 questions pertaining to this problem among which also nocturia was addressed. Numbers of voids per day and night were registered but it was also possible to address the question of different nocturnal episodes per night as well as different void volumes.
Nocturia was defined as at least 2 nocturnal void episodes at least 5 nights per week with a bother index of 2 or more on a visual analogue scale from 0 to 10.
Frequency and severity of nocturia could then be statistically assessed by regression analysis or chi square test and perceived contributing variables assessed.
After completing the specific urologic questionnaire at the screening centre, women were interviewed once more on their continence problems. In a subset of women (n = 400) the questionnaire was mailed again 2–4 months after the initial one. Of the 369 women returning this second identical questionnaire responses to questions were identical in 92.1% to the initial urologic questionnaire as it appeared after corrections made during the interview.
1500 women with self-reported incontinence causing a social and/or hygienic problem along with 1500 women without incontinence were selected by computerized randomisation from the original WHILA cohort to receive also the Bristol Female Lower Urinary Tract Symptoms questionnaire, BFLUTS [
A specially trained nurse–midwife collected the questionnaires at the time of the examinations and personally interviewed each and every woman, and potential problems were addressed. At the interview, 19% of the subjects made some corrections in their written answers due to shear mistakes or misunderstandings when filling out the forms. The questionnaires were completed before the laboratory results were presented.
2.2 Laboratory variables
Random blood glucose as well as non-fasting serum levels of triglycerides, total cholesterol, HDL cholesterol and LDL cholesterol were measured with a Cholestech LDX-instrument (Cholestech Corporation, Hayward, CA, USA) on capillary whole blood. Allowing non-fasting samples enabled us to perform the primary screening at any time during the day.
2.3 Health screening program
2.3.1 Primary screening
The physical examination at the primary screening included measurements of body weight, height, minimal waist and maximal hip circumference (WHR). Body mass index (BMI) was calculated as kg/m2. To create an estimate, named BMI-increase, of how many women who had increased their BMI ≥ 25% during the past 25 years, the actual BMI was compared with self-reported body weight and height at 25 years of age.
Blood pressure (mmHg) was recorded twice in the right arm, after 15 min and 20 min rest in the seated position, with a mercury sphygmomanometer and a cuff size adjusted to the arm-width. Korotkoff phase V was used to define the diastolic blood pressure. The average of the recordings, measured to the nearest 2 mmHg, was the blood pressure used for statistical calculations.
ECG was recorded as a standard procedure with 12 leads.
All measurements were carried out in the same laboratory and by the same examiners. The cut-off values and prevalence figures on the metabolic variables for a positive screening, regarded as features of the metabolic syndrome, are shown in Table 1.
Table 1Number and percentage of women with screening variables at or above cut-off levels used (alone or in combination).
In addition serum aliquots were stored in a biobank for future analyses of which estradiol, testosterone, SHBG, androstendione and cortisol are now completed. KRYPTOR-automated immunofluorescent hormonal assays of testosterone and estradiol were performed (B.R.A.H.M.S. Ag., Hennigsdorf, Germany). A testosterone-index was introduced and defined as testosterone/SHBG × 100 and an estradiol-index as estradiol/SHBG × 100. These indices were used to consider both free and protein bound steroids. Hormonal assays of serum androstenedione, SHBG, cortisol, fasting insulin and leptin were performed using ELISA technique (DRG GmbH, Marburg, Germany). Fasting insulin and leptin were randomly analysed in every third women. Insulin resistance was expressed through the homeostasis assessment model (HOMA-IR).
TSH was examined in women with metabolic syndrome and in women with low wrist bone density (osteopeni or osteoprosis).
2.3.2 Baseline diagnostic OGTT
Women with one or more of the totally eight factors for positive primary screening were defined to have features of the metabolic syndrome. A 75-g 2 h OGTT in the fasted state and a clinical examination were performed by a physician 1–4 weeks after the primary screening. Venous whole blood samples were collected and a HemoCue instrument (HemoCue AB, Ängelholm, Sweden) was used for glucose analyses. The coefficient of variation was 2.8%. The diagnoses of IFG, IGT and diabetes were set according to WHO 1998.
The validity of the OGTT used in the study was analysed by testing the intra-individual variation in 640 women passing two OGTT's with 14 days interval, with IGT or diabetes at the first measurement. The 95% limits of agreement of the random test–retest differences, expressed in percentage as 100 (2SDdif/median level of individual average score), were 17.9% for fasting glucose and 38.1% for 2-h glucose. If the diagnostic categories in the present study were compared between the first OGTT and a mean of the first and second OGTT, this showed that 16.1% of women with IGT on the first turned normal according to the mean of both OGTT.
A computerized randomly selected sample (10%) of women without any features of the metabolic syndrome (negative primary screening) was also offered a baseline OGTT.
2.3.3 Bone mineral density measurement
Wrist bone mineral density (BMD) was measured by DEXA using an Osteometer DTX 200; (Medi-Tech A/S, Rodovre, Denmark) one and the same technician performed all measurements. Phantoms were used for external as well as for internal quality control.
2.3.4 Alcohol and smoking habits
Alcohol intake was defined as the weekly consumption of wine, beer and spirits converted into gram alcohol and divided into four categories; no consumption, ≤83 g/week, 84–167 g/week, and ≥168 g/week. Twelve-g alcohol equalized 1 drink.
Smoking was categorized by the lifetime consumption of pack years. One pack year corresponded to a consumption of 20 cigarettes per day for 1 year. Subjects were divided into three categories; never smokers (<1 pack year), past smokers and current smokers (≥1 pack year for both). Past smokers were those who had stopped smoking ≥1 month prior to the study.
2.3.5 Leisure time exercise
The subjects reported the duration, frequency and intensity of the leisure time exercise activity performed per week during the last year, corresponding to; hardly any activity, <30 min/week, 30–60 min/week, >60–120 min/week and >120 min/week of jogging and equivalent activities.
2.3.6 Physical activity at work
Physical activity at work during the last year was categorized into low, moderate and high physical intensity at work. Low referred to sedentary (white collar) work, moderate to mostly walking but not lifting heavily, and high to work with high degree of walking and lifting. Those without work during the last year were asked to categorize their work at home.
2.3.7 Dietary habits
The estimation of dietary intake in general was based on four questions with three sublevels from unhealthy to healthy pattern regarding fat, fibres, fruits/vegetables and sweets/carbohydrates. Women with a healthy intake of fat had low total consumption of fat, especially animal fat, but relatively more of vegetable oil, low-fat milk and meat, often fish, but seldom sausages, bakeries and whip cream. Healthy intake of fibres meant high total consumption of fibres, often through fibre-rich bread and whole grain cereals. Healthy intake of fruits/vegetables meant high total, daily consumption of both fruits and vegetables. Healthy pattern regarding sweets meant hardly ever using extra sugar, eating sweets, cookies or other bakeries. All subjects answered the four basic questions on diet and 40% of these women also completed the validated detailed food questionnaire [
], which ensured that the basic questions discriminated between unhealthy and healthy diet. Women defined to have healthy dietary habits were those indicating a healthy pattern on at least three out of the four basic questions, and with none of the four questions indicating an unhealthy pattern.
2.3.8 Socio-demographic factors
Household definitions included women living single or living with a partner or children.
Education was categorized into three classes; comprehensive school (in total 9 years), upper secondary school (in total 12 years), and university degree, according to the highest level of education stated by the respondent.
Working status referred to the subjects relation to the labour market; full time, part time, and subjects being unemployed, long-term sick-listed or with disability pension.
Does hormone therapy increase allergic reactions and upper gastrointestinal problems? Results from a population-based study of Swedish woman. The women's health in the Lund area (WHILA) Study.
]. The instrument refers to the WHO definition of health, and divides a subject's perception of symptoms into physical-, social-, and mental well-being. Altogether 19 topics on quality of life were estimated on a 7-step score from ‘very bad’ [
The influence of hormonal status and features of the metabolic syndrome on bone density: A population based study of Swedish women aged 50–59 years. The Women's Health in the Lund Area (WHILA) Study.
]. Also, 19 physical and 10 mental symptoms were listed to be answered with a yes or no, whether the woman had been troubled by any of the symptoms during the last 3 months, or not. Social well-being included all the original GQoL-variables family, housing, work, economy, but also five additional variables; partner, leisure time, sexual satisfaction, appreciation at home and appreciation outside home. Physical well-being included the GQoL-variables health, fitness, memory, and appetite, but excluded hearing and vision and included one other variable, bodily perception. Mental well-being included the entire GQoL-variables mood, energy, endurance, self-esteem and sleep. The symptom assessment was as the original except that the symptom overweight was excluded. Physical symptoms included eye-problem, impaired hearing, headache, dizziness, coughing, breathlessness, chest pain, loss of weight, sweating, feeling cold, pain in the legs, back ache, joint pain, abdominal pain, constipation, diarrhoea, loss of appetite, nausea and difficulty in passing urine. Mental symptoms included restlessness, difficulty to relax, nervousness, impaired concentration, sleeping disturbance, irritability, exhaustion, general fatigue, depression and crying easily.
2.3.10 Exclusion criteria
Women with known diabetes mellitus, stroke or myocardial infarction within the preceding year, as well as women with a severe, usually malignant, concurrent disease, were excluded from follow-up. The rationale for excluding stroke and myocardial infarction in the following screening process was to avoid influence of subjects with potentially acute metabolically deteriorated profiles. Women with a previously unknown disease that required other examinations or treatments, were referred to health care centres or specialist clinics, but were not excluded from the analyses.
2.3.11 Follow-up study
Women with normal OGTT or isolated IFG were not further studied, but in case of obesity, high blood pressure or hyperlipidaemia they were given verbal and written preventive advices and recommended a later appointment with their family physician. All women with diabetes, and also those in the sub-sample without any features of the metabolic syndrome and who had IGT at the OGTT, were informed and given lifestyle advices, and referred to their physician at the primary health care centre.
2.3.12 Control group at follow-up – women with normal glucose tolerance
A random sample (10%) of women without features of the metabolic syndrome attended baseline OGTT and those who had NGT served as the control group at the follow-up study. They were not given any specific advice. The OGTT was repeated at follow-up but no information was given at baseline that they would be invited to a re-examination.
2.3.13 Lifestyle intervention group – women with impaired glucose tolerance
Among women with features of the metabolic syndrome, those who had IGT received initial lifestyle advices and were invited to the 2.5-year follow-up study ending with a new OGTT.
Individual advice was given for 1 h from a physician how to achieve a healthier lifestyle concerning physical exercise, dietary habits, and smoking and alcohol consumption. The subjects’ individual answers given in the questionnaire and the results of the physical examination formed the bases for the advice given.
Overall, the recommendations aimed at motivating an increase of leisure time exercise to at least 1 h or more of moderately intense activities like jogging, cycling or swimming per week. Furthermore, the dietary advices included verbal and written descriptions on reduced total intake of fat and a higher relative part of unsaturated fat, increased consumption of fibres, vegetables, and reduced intake of different components of sugar. Smoking women were advised to make a complete stop. A reduction in alcohol consumption was recommended, especially in women with high consumption. However, none was urged to become an abstainer.
The dietary prescription included: (a) fruits ≥3 times daily, (b) vegetables ≥ once daily, (c) minimum 25 g fibres daily, (d) 25–30 energy% fat, (e) a higher relative part of unsaturated fat, (f) maximum 10 energy% saturated fat, (g) minimum 1000 mg calcium contents in diet/daily. Physical activity recommendations were aiming to increasing energy consumption with 500–1000 kcal/week.
Women with urinary incontinence estimated at ≥2 on the 0–10 scale, were randomized into either one group given one time occasion of information, or to a group followed at repeated occasions at their nearby health centre. The latter group was given verbal, written and practical information on pelvic floor exercise, under surveillance of midwife and physiotherapist. A subgroup analysis is conducted in collaboration with the Department of Gynaecology and the Department of Urology. Final analyses of the results were performed after 2 years.
3. Main results of WHILA
Apart from reviews, WHILA has produced 50 original publications on various aspects of female midlife health .In general these data are cross-sectional. The specific original WHILA papers published to date are all listed below.
3.1 Participants vs non-participants
The postal residences were analysed between participants and non-participants. There were no differences in the rate of women living in the central city of Lund compared to those living in the suburbs. Among the latter group, 5 of totally 21 suburbs showed differences in the distribution between the participant and non-participants (p = 0.009 to <0.001), indicating a higher drop-out rate in areas known to have lower socio-economic status. In total, these five suburbs seized 2489 (24.0%) women of the invited population.
Of the non-participating group 408 (10.6%) women had moved from the area recently prior to the mail invitation was handed out, but had already been included as part of the study population.
More non-participants than participants died during the period 1995–1998 (2.6% vs 0.2%; p < 0.001), as well as during the following 2 years, 1999–2000 (1.5% vs 0.3%; p < 0.001). The main cause of death in 1995–1998 was cancer (non-participants: n = 64/99, participants: n = 10/12). In the non-participating group, 14 of 99 of the deaths were caused by cardiovascular diseases, in contrast to none in the participating group. The cause of death after 1998 is under current analysis.
More participants visited during 1998 their general practitioner one or more times (53% vs 44%; p < 0.001) as well as consultants at outpatient clinics (49% vs 43%; p < 0.001), while fewer visited a psychiatrist (2.8% vs 4.4%; p < 0.001) or psychotherapist/psychologist (1.7% vs 2.3%; p = 0.019).
Fewer participants than non-participants were hospitalized during 1998 (8.2% vs 9.8%; p = 0.005), both concerning somatic care (7.8% vs 8.9%; p = 0.049) and psychiatric care (0.4% vs 0.9%; p = 0.002), and among these women, the participants stayed for shorter periods (9.3 ± 28.1 days vs 17.4 ± 37.8 days; p < 0.001).
The distribution of all types of diagnoses according to the International Classification of Diagnoses (ICD) was analysed among participating and non-participating women hospitalized during 1998. This showed a difference in women diagnosed with breast or ovarian cancer (0.6% vs 1.2%, p = 0.006), but no difference was seen in total numbers of malignancies. Furthermore, there were differences in diagnoses concerning instable angina pectoris/myocardial infarction (0.5% vs 1.0%, p = 0.005), chronic obstructive pulmonary disease (COPD) (0.2% vs 0.6%, p = 0.026), gastrointestinal diseases (1.0% vs 1.4%, p = 0.044), and in severe alcohol dependence (0.1% vs 0.4%, p = 0.012), but no differences were seen for other types of psychiatric diagnoses.
Among the 6917 women, 7% were PM (mean age 52.7 years), 41% PMT (mean age 55.1 years) and 52% were PM0 (mean age 55.6 years).
As in all other data women using HRT tended to be leaner. As our women are perimenopausal and close to the menopause (either just before or just after) the numerical magnitude of differences in our study is often small.
The most common HRT preparation was a continuous combined oral regimen consisting of 2 mg estradiol+1 mg norethisterone acetate (Kliogest).
Almost 52% had positive primary screening variables, and passed also the baseline OGTT examination. 13.6% were obese (BMI ≥ 30) and 37% had increased in BMI ≥ 25% over the last 25 years. Among hypertensive women, 49% had a corresponding increase in BMI. Blood pressure was 160/95 mmHg or higher in 18.1% of the subjects.
Biolgical factors are more important than socio-demographic and psychosocial conditions in relation to hypertension in middle-aged women. The Women's Health in the Lund Area (WHILA) Study.
Hypertension was more common among those with features of the metabolic syndrome. Hypertension was also more common among women with low education and among those consuming >84 g alcohol per week (12 g alcohol = 1 glass of wine). Abnormal blood pressure is common in middle-aged women regardless of hormonal status. 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.
An unhealthy lifestyle was positively associated with metabolic risk factors, and smoking- and alcohol-consumption. The results indicate that leisure-time physical activity had a higher impact than diet. 16% were current regular smokers and another 19% past smokers.
Androgens seemed to influence blood pressure in a complicated way so that at low ranges increasing testosterone led to lower blood pressures whereas at high ranges further augmentation resulted in higher blood pressure suggesting that testosterone could have a dual influence on blood pressure in perimenopausal women.
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.
Combined hormone therapy in postmenopausal women with features of metabolic syndrome. Results from a population-based study of Swedish women: Women's Health in the Lund Area Study.
Do sex hormones influence features of the metabolic syndrome in middle-aged women? A population-based study of Swedish women: the Women's Health in the Lund Area (WHILA) Study.
Fertil Steril.2007; 88 (Epub 2007 Mar 26): 163-171
Could quality of life impact the prevalence of metabolic syndrome? Results from a population-based study of Swedish women: the Women's Health in the Lund Area Study.
Sociodemographic risk factors of metabolic syndrome in middle-aged women: results from a population-based study of Swedish women, The Women's Health in the Lund Area (WHILA) Study.
Features of the metabolic syndrome were found among 3593 women or 51% of the population, and 14% had impaired glucose tolerance (IGT) and 6.4% diabetes. The general conclusion of the study was that there was a high prevalence of risk markers for diabetes in this population of women, and that many cases of previously unknown IGT and diabetes were found. Biological factors interrelated with socio-demographic and psychosocial disparities, such as low level of education, living single and low subjective physical well-being. Low or moderate, but not high alcohol consumption seemed beneficial on the metabolic profile. The results on smoking were contradictory to previous reports concerning the effect on features of the metabolic syndrome. Smoking showed an independent decreased risk for hypertension and was not associated with the development of diabetes. Menopausal status showed no relation to occurrence of hypertension.
In the longitudinal study, a single baseline session of extensive lifestyle advice from a physician seemed enough to significantly reduce the risk for new cases of diabetes. Among these women with IGT at baseline 38% had normal glucose tolerance at follow-up, while 11.9% had developed diabetes. These results are similar to what has been found in other more costly intervention studies. According to the results, screening of women at high-risk for diabetes should be carried out. A model for this procedure has been presented, as well as a description on preventive measures that can be performed at primary health care settings.
The influence of hormonal status and features of the metabolic syndrome on bone density: A population based study of Swedish women aged 50–59 years. The Women's Health in the Lund Area (WHILA) Study.
The osteoporosis- and osteopenia-prevalence in this study was 7% and 43%, respectively. A positive correlation was found between bone density and impaired metabolic factors like high body weight, blood pressure and serum lipids. However, women who smoked had low bone density. Hormone replacement therapy seemed to delay the age-dependent bone loss.
The presence of climacteric symptoms was related to low bone mass.
Low bone mass was also related to high serum cadmium concentrations [
Urodynamic charaterisation of women with naïve urinary incontinence: a population based study in subjecively incontinent and healthy 53–63 years old women.
Prevalence of urinary incontinence in relation to self-reported depression, intake of serotonergic antidepressants, and hormone therapy in middle-aged women: a report from the Women's Health in the Lund Area Study.
The relation between urinary incontinence and steroid hormone levels in perimenopausal women. A report from the Women's Health in the Lund Area (WHILA) Study.
Urinary incontinence was reported among 32% of the participants at the baseline examination, but this figure was even higher when the latest internationally accepted definition from 2002 was applied. Women with low body weight and a positive family history of diabetes more often had incontinence problems, and the most common type was urgency incontinence. Involuntary urinary leakage more than once weekly was by the majority of subjects considered to reduce quality of life. Successful treatment according to urodynamic test results was shown with individually modified programs for pelvic floor exercise. Serum estradiol adjusted for body mass index, parity, smoking, and hysterectomy was significantly higher in incontinent women. No associations between UI and serum levels of cortisol, testosterone, or androstendione were found.
Urinary incontinence and self-reported depression seemed to be associated in middle-aged women. Use of serotonergic antidepressants or hormone therapy does not seem to be associated with a lower prevalence of urinary incontinence.
A prospective study of different types of hormone replacement therapy use and the risk of subsequent breast cancer: the women's health in the Lund area (WHILA) study (Sweden).
The WHILA study delivered one of the first reports indicating a higher risk of breast cancer in women using continuous combined HRT compared to sequential which in turn was higher than estrogen monotherapy which had virtually no increased risk [
A prospective study of different types of hormone replacement therapy use and the risk of subsequent breast cancer: the women's health in the Lund area (WHILA) study (Sweden).
The low levels of cadmium exposure present in the studied women, although high enough to be associated with lower bone mineral density and increased bone resorption, were not associated with lower serum concentrations of 1,25(OH)(2)D. Hence, decreased circulating levels of 1,25(OH)(2)D are unlikely to be the proposed link between cadmium-induced effects on kidney and bone. Tubular renal effects occurred at lower cadmium levels than previously demonstrated, and more important, glomerular effects were also observed. Although the effects were small, they may represent early signs of adverse effects, affecting large segments of the population. Subjects with diabetes seem to be at increased risk. Results from the present case–control study suggest that biomarkers for persistent organic pollutants exposure, 2,2′,4,4′,5,5′-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p′-DDE) including a follow-up design, confirms that p,p′-DDE exposure can be a risk factor for type 2 diabetes.
3.8 Sex hormones and climacteric and gynaecological problems [
Menopause-related symptoms: what are the background factors? A prospective population-based cohort study of Swedish women (The Women's Health in Lund Area Study).
Background factors influencing somatic and psychological symptoms in middle-age women with different hormonal status. A population-based study of Swedish women.
Long after surgery, several somatic and psychological symptoms were still more common in hysterectomized women. A low frequency of amenorrohic episodes and lower age at giving first birth, concomitant with a higher body weight already at age 25 may imply that women who end up hysterectomized have a specific health profile long before as well as long after surgery.
Severity and intensity of climacteric symptoms correlated with a history of PMS.
Effects of norethisterone acetate addition to estradiol in long term HRT. A population based study of Swedish women. The Women's Health in Lund Area (WHILA) Study.
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.
Does the hormonal situation modify lipid effects by lifestyle factors in middle-aged women? Results from a population-based study of Swedish women: the women's health in the Lund area study.
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.
Health hazards in middle-aged women with cardiovascular disease: a case–control study of Swedish women. the Women's Health in the Lund Area (WHILA) Study.
In accordance with the bulk of observational data, the 104 women with confirmed CVD events in WHILA used HRT to a lesser extent than healthy matched controls .CVD events were more common PMO women compared to PM even after matching for traditional risk factors including age, serum lipids and BMI. In PMO, women with sustained CVDs had lower serum estradiol but also lower serum androgens than healthy controls. The study revealed a higher prevalence of pathological ECG changes in postmenopausal women who had hypercholesterolemia than in normocholesterolemic women. Transdermal estradiol combined with MPA has a beneficial effect in reversing the process of atherosclerosis, as well as improving ECG patterns.
Alcohol was used by 75% of subjects but commonly in low to moderate levels. Non-drinkers had lower socio-demographic status, poorer health and more symptoms, especially physical symptoms. The presence of severe mental symptoms was strongly associated with severe physical symptoms. Few women with severe mental symptoms used psychotropic drugs. Middle-aged women with severe mental symptoms need to be identified and provided with appropriate psychopharmacological, hormonal, and/or psychosocial treatment.
3.11 Additional aspects of female midlife health [
Does hormone therapy increase allergic reactions and upper gastrointestinal problems? Results from a population-based study of Swedish woman. The women's health in the Lund area (WHILA) Study.
Nonhormonal drug use and its relation to androgens in perimenopausal women: a population-based study of Swedish women. The Women's Health in the Lund Area Study.
Hormone therapy in postmenopausal women seems to be associated with an increased usage of non-hormonal pharmacotherapy, rendering higher prevalence of such drugs in middle-aged women. Postmenopausal women with lower serum testosterone and a higher number of outpatient office visits, used medications for cardiovascular problems and depression more than other medications
Use of hormone replacement therapy seems to be related to a higher frequency of omeprazole and loratadine use, which implies that hormone replacement therapy, may be associated with more upper gastrointestinal symptoms as well as allergy [
Does hormone therapy increase allergic reactions and upper gastrointestinal problems? Results from a population-based study of Swedish woman. The women's health in the Lund area (WHILA) Study.
This study is unique by examining a large population-based cohort of women within a defined geographical area comprising both urban and rural residents of women from a broad perspective. A number of epidemiological data on middle-aged women's health and related risk factors are still missing. In this population both women in pre- and postmenopause, with and without hormone replacement therapy (HRT) were included. Hence the study set up allows comparisons of groups of women of the same chronological age but with different hormonal status which render results more reliable than using statistical approaches for age correction. The prevalence rates of diabetes, cardiovascular diseases and osteoporosis increases substantially in postmenopausal women. At the same time numerous symptoms and health complaints are set in, influencing quality of life. The study will evaluate this period in women's life and contribute with new understandings on the biological and socio-demographic and psychosocial conditions present during the menopausal transition.
5. Further study procedures
Further analyses are needed in order to better understand the underlying causes for the increasing numbers of people suffering from chronic disease such as diabetes. Previous reports from the WHILA study have indicated that not only biological but also social and psychosocial status is of importance for the risk of developing diabetes. Analyses of alcohol consumption and use of psychotropic drugs will continue, and also of data regarding work load and long-term sick leave.
Previous obstetrical journals among women with IGT or diabetes will be studied inclusive of offspring analyses.
Risk factor analyses will be carried out concerning interrelations between biomedical factors, drug treatment, social factors, lifestyle and the influence on bone tissue density and the risk for bone fractures.
6. Follow-up of total cohort
An initial follow-up of the initial responders (n = 6917) was carried out in 2009 which yielded an average follow-up time of 9 years. The follow-up used national registry data on morbidity and mortality, hospital admissions, drug use et cetera which will be analysed and compared with existing data.
In summary the WHILA study is a unique and immense compilation of demographic, anthropological and laboratory data from a large populations based cohort residing in a geographically defined area. It has and will in the future contribute to an increasing understanding of female health problems and provide intriguing suggestions for improvement of women's midlife health.
Provenance
Commissioned and externally peer reviewed.
Competing interests
None declared.
Contributors
All authors contributed equally to this manuscript.
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