Primary screening for increased fracture risk by the FRAX® questionnaire-uptake rates in relation to invitation method.

The aim of the study was to evaluate the feasibility and most efficient way of offering middle-aged Swedish women a primary fracture screening program via a questionnaire. Two out of five invited women returned the FRAX questionnaire and those contacted directly by mail were most prone to respond. PURPOSE: Osteoporosis and its associated fractures are increasing, and this study aims to explore ways to identify women at an increased risk of fracture using the FRAX® algorithm. METHODS: Three thousand middle-aged women were invited and presented a questionnaire distributed by three different methods-by mail, at routine mammography, or internet-based. RESULTS: In total, 1120 (37.3%) women responded to the questionnaire and agreed to participate. The response rates for the mail, mammography, and internet-based groups were 39.1%, 35.7%, and 25.2% respectively. Women in the mammography group weighed more, were slightly older than the other women, and also had a higher BMI than women from the mail and internet-based groups. No difference was observed between the groups regarding previous fracture, family history for fracture, current smoking, glucocorticoid use, and alcohol usage. The mammography group had a higher median (interquartile range) major osteoporotic FRAX® score (10.0% (7.8-17.0)) than the mail group (9.7% (7.1-15.0); p = 0.005) and the internet-based group (8.7% (6.7-14.0); p = 0.001). CONCLUSIONS: Two out of five early postmenopausal women returned the questionnaire and women contacted directly by mail were more prone to respond. Out of the participants, 26.6% had a 10-year fracture risk score ≥ 15% according to the FRAX® algorithm.

Associations between cadmium exposure and circulating levels of sex hormones in postmenopausal women.

Recent epidemiological as well as in vivo and in vitro studies collectively suggest that the metalloestrogen cadmium (Cd) could be a potential risk factor for hormone-related cancers in particularly breast cancer. Assessment of the association between Cd exposure and levels of endogenous sex hormones is of pivotal importance, as increased levels of such have been associated with a higher risk of breast cancer in postmenopausal women. The present study investigated the perceived relationship (multivariable-adjusted linear regression analyses) between Cd exposure [blood Cd (B-Cd) and urinary Cd (U-Cd)], and serum levels of androstenedione, testosterone, estradiol, and sex-hormone binding globulin (SHBG), in 438 postmenopausal Swedish women without hormone replacement therapy (HRT). A significant positive association between B-Cd (median 3.4 nmol/L) and serum testosterone levels, as well as a significant inverse association between B-Cd and serum estradiol levels and with the estradiol/testosterone ratio were encountered. However, U-Cd (median 0.69 nmol/mmol creatinine) was inversely associated with serum estradiol levels only. Our data may suggest that Cd interferes with the levels of testosterone and estradiol in postmenopausal women, which might have implications for breast cancer risk.

Low androstenedione/sex hormone binding globulin ratio increases fracture risk in postmenopausal women. The Women's Health in the Lund Area study.

The Women's Health in the Lund Area (WHILA) project (n=6917) is a cohort study that started in 1995 and includes a postal questionnaire, physical examination, bone density measurement and blood laboratory analyses. Fracture data have been added, and in this report fracture risk and its association with sex hormones was analysed in postmenopausal women without current hormone therapy (HT). A total of 409 women (median age 56.8 years) with 489 fractures were identified from the postmenopausal women without HT during a median follow-up time of 8.4 years. Lower serum levels of androstenedione (p<0.001), testosterone (p=0.008), androstenedione/sex hormone binding globulin (SHBG) ratio (p<0.001), testosterone/SHBG ratio (p=0.003) and higher levels of SHBG (p=0.005) were observed in women with fractures compared to no fracture. No difference in oestradiol levels was observed. Androstenedione and androstenedione/SHBG ratio were further divided into percentiles. Increased fracture risk was found in postmenopausal women with androstenedione in 5th percentile compared to 11-89th percentile HR 1.51 (95% CI 1.02-2.24). The androstenedione/SHBG ratio (11-89th percentile as reference) showed increased fracture risk in women with low ratio 5th percentile HR 1.75 (95% CI 1.20-2.54) and decreased fracture risk with high ratio 95th percentile HR 0.52 (95% CI 0.28-0.98). An increased fracture risk during follow-up was encountered in postmenopausal women with low serum androstenedione and androstenedione/SHBG ratio at baseline and a decreased fracture risk with high androstenedione/SHBG ratio. This study suggests that postmenopausal osteoporosis is influenced by lower levels of androgens.

Hormone therapy and coronary heart disease risk by vasomotor menopausal symptoms.

OBJECTIVES: We examined whether the association between hormone therapy (HT) use and coronary heart disease (CHD) risk differed between women with and without vasomotor symptoms (VMS). STUDY DESIGN: We used data from a Dutch (EPOS) and Swedish (WHILA) population-based sample of 8865 women, aged 46-64 years, and free of CHD, stroke, venous thrombosis/pulmonary embolism or cancer at baseline. Data on HT use, VMS and potential confounders were collected by questionnaires. MAIN OUTCOME MEASURES: CHD endpoints, obtained via registries. RESULTS: 252 CHD cases occurred during 10.3 years of follow-up. Neither for women with nor for women without flushing or (night) sweats ever HT use was associated with CHD risk, compared with never HT use. Among women with intense VMS, ever HT use borderline significantly decreased CHD risk compared with never HT use (HR 0.48 [95% CI 0.20-1.03]). Among women without intense VMS, ever HT use was associated with a borderline significant increased CHD risk (HR 1.28 [95% CI 0.96-1.70]; P for interaction=0.02). However, after multivariate adjustment, as compared to never HT use, ever HT use was not associated with risk of CHD among women with or without intense VMS. CONCLUSIONS: In both groups of women with and without VMS, HT use does not seem to be associated with the risk of CHD. Hence, our findings do not support the view that HT use increases the CHD risk among women with an indication, i.e. VMS, but this needs to be confirmed in specifically designed studies.

Retinol may counteract the negative effect of cadmium on bone.

Cadmium and high vitamin A intake are both proposed risk factors for low bone mineral density (BMD), but potential interactions have not been studied. Within the Women's Health in the Lund Area, a population-based study in southern Sweden, we measured retinol in serum among 606 women aged 54-64 y. Data on BMD were measured by DXA at the distal forearm. Parathyroid hormone (PTH), bone alkaline phosphatase (bALP), and osteocalcin in serum and deoxypyridinoline (DPD) and cadmium in urine were available. Associations were evaluated using multivariable-adjusted linear regression analysis. Serum retinol concentrations (median, 1.9; range, 0.97-4.3 µmol/L) were inversely associated with the bone formation markers bALP and osteocalcin (P ≤ 0.04) and with PTH (P = 0.07) and tended to be positively associated with BMD (P = 0.08) but not with the bone resorption marker DPD, indicating different effects on bone compared to urinary cadmium (median, 0.66; range, 0.12-3.6 nmol/mmol creatinine). Women with serum retinol less than the median and cadmium greater than the median had lower BMD than those with retinol greater than the median and cadmium less than the median (P = 0.016 among all women and P = 0.010 among never-smokers). Our findings suggest that adequate vitamin A status may counteract the adverse association between cadmium and BMD.

Serum estradiol does not differentiate stress, mixed and urge incontinent women around menopause. A report from the Women's Health in the Lund Area (WHILA) study.

OBJECTIVE: To outline serum estradiol levels in perimenopausal women with stress, mixed or urge incontinence. We believe the majority of urgency symptoms in perimenopausal women to be caused by a pelvic floor dysfunction and a hypermobility of the bladder neck. If this is the case, there would be no difference in estradiol levels between the groups. SETTING: University hospital. In the observational Women's Health in the Lund Area study, a subset of 400/2221 women reporting urinary incontinence completed a detailed questionnaire regarding lower urinary tract symptoms and had their serum steroid hormone levels measured. Statistical analyses were made by Chi-square test, nonparametrical tests, ANOVA, multi- and univariate logistic regression analysis. RESULTS: Stress incontinence was reported by 196, mixed incontinence by 153 and urge incontinence by 43 women; in 369, serumestradiol values were available. Serum estradiol did not differ significantly between stress incontinent (median 49.5 pmo/l, range 2.63-875.4), urge incontinent (median 31.6 pmol/l, range 2.63-460.7) or mixed incontinent women (median 35.5 pmol/l, range 2.63-787.9, p=0.62). Logistic regression analysis correcting for age, parity, hormonal status, smoking, hysterectomy and BMI also failed to show any difference in estradiol levels between the groups (p=0.41-0.58). CONCLUSION: No significant differences in serum estradiol levels between stress, mixed or urge incontinent perimenopausal women could be demonstrated.

Vasomotor symptoms, estradiol levels and cardiovascular risk profile in women.

OBJECTIVES: We investigated whether menopausal vasomotor symptoms (VMS) are related to an adverse cardiovascular risk profile. Furthermore, we examined the association between estradiol levels and VMS, and whether an association between VMS and cardiovascular risk factors can be explained by estradiol levels. STUDY DESIGN: We used data from a Swedish population-based sample of 5857 women, aged 50-64 years. Data on VMS and potential confounders were collected by questionnaires. MAIN OUTCOME MEASURES: Body mass index (BMI), waist hip ratio (WHR), glucose, blood pressure, lipid profile and estradiol levels were measured. RESULTS: Symptoms of flushing/sweats were reported by 55% and sweats by 31% of all women. Estradiol concentrations were significantly lower in women with VMS. After multivariate adjustment, women with symptoms of sweats had a statistically significantly higher BMI, waist hip ratio, total cholesterol level, LDL level, triglycerides level, glucose level, systolic and diastolic blood pressure. These patterns did not change after correction for estradiol. The associations between flushing/sweats combined and cardiovascular risk factors were less pronounced. CONCLUSIONS: Women with VMS have a less favorable cardiovascular risk profile. Although estradiol levels were significantly lower among women with VMS, the increased cardiovascular risk profile cannot be explained by circulating estradiol levels.

The women's health in the Lund area (WHILA) study--an overview.

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.

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.

OBJECTIVE: To outline possible associations between urinary incontinence (UI) and serum levels of steroid hormones in middle-aged women. DESIGN AND SETTING: Community-based observational study. SAMPLE: All women aged 50-59 living in the Lund area by December 1995 were invited to a screening procedure. Sixty-four percent (n = 6,917) attended the screening that included physical and laboratory examinations and questionnaires. METHODS: Serum levels of cortisol, testosterone, androstendione, SHBG (sex hormone-binding globulin), and estradiol were analyzed and the 2,221 (32%) women who reported urinary leakage causing a social or hygienic problem were compared to those who denied incontinence. MAIN OUTCOME MEASURE: Possible differences in serum levels of steroid hormones in continent and incontinent women. RESULTS: There were no significant differences between continent and incontinent women regarding serum levels of cortisol, testosterone, androstendione, or testosterone + androstendione combined. Serum estradiol adjusted for body mass index, parity, smoking, and hysterectomy was significantly higher in incontinent women (87.1 +/- 138.4 pmol/l vs. 78.0 +/- 118.5 pmol/l, p = 0.005), whereas the ratio estradiol/SHBG was not. These differences persisted when the group of women not on hormonal treatment was analyzed. CONCLUSIONS: UI in middle-aged women seems related to higher serum estradiol levels. This corroborates with studies showing a higher incidence and/or prevalence of UI in women on hormone therapy. No association between UI and serum levels of cortisol, testosterone, or androstendione was found.

Prevalence of symptoms in relation to androgen concentrations in women using estrogen plus progestogen and women using estrogen alone.

OBJECTIVE: Women using estrogen plus progestogen therapy sometimes report difficult to describe symptoms, eg, changes in libido, mood, and memory, that may be related to decreased androgens. To evaluate the prevalence of such symptoms and relate these symptoms to androgen levels in women using estrogen plus progestogen therapy, data from the Women's Health in the Lund Area Study were analyzed. DESIGN: A total of 2,816 women using estrogen plus progestogen therapy were asked to complete a questionnaire consisting of questions concerning sexual well-being and different aspects of quality of life. Serum concentrations of testosterone, androstendione, sex hormone-binding globulin, and estradiol were measured. RESULTS: A total of 2,048 questionnaires were eligible for evaluation. Almost 40% of the women reported decreased libido. Approximately 70% were satisfied with their current sex life. Eight percent reported that intercourse was unpleasant because of vaginal dryness. No evident associations were found between libido and serum hormone concentrations. The most positive effects of estrogen plus progestogen therapy concerning memory and urinary tract and vaginal complaints were found in women with the highest and/or moderate testosterone levels (P < 0.05). CONCLUSIONS: We found no strong association between symptoms related to sexual well-being or quality of life and androgen concentrations in this study. Estrogen plus progestogen therapy did not seem to affect symptoms that might be related to low levels of androgens in the group of climacteric women whom we studied.

Cadmium-induced bone effect is not mediated via low serum 1,25-dihydroxy vitamin D.

Cadmium is a widespread environmental pollutant, which is associated with increased risk of osteoporosis. It has been proposed that cadmium's toxic effect on bone is exerted via impaired activation of vitamin D, secondary to the kidney effects. To test this, we assessed the association of cadmium-induced bone and kidney effects with serum 1,25-dihydroxyvitamin D (1,25(OH)(2)D); measured by enzyme immunoassay. For the assessment, we selected 85 postmenopausal women, based on low (0.14-0.39 microg/L) or high (0.66-2.1 microg/L) urinary cadmium, within a cross-sectional population-based women's health survey in Southern Sweden. We also measured 25-hydroxy vitamin D, cadmium in blood, bone mineral density and several markers of bone remodeling and kidney effects. Although there were clear differences in both kidney and bone effect markers between women with low and high cadmium exposure, the 1,25(OH)(2)D concentrations were not significantly different (median, 111 pmol/L (5-95th percentile, 67-170 pmol/L) in low- and 125 pmol/L (66-200 pmol/L) in high-cadmium groups; p=0.08). Also, there was no association between 1,25(OH)(2)D and markers of bone or kidney effects. It is concluded that 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.

Vasomotor symptoms are associated with a lower bone mineral density.

OBJECTIVE: The severity of vasomotor symptoms has been hypothesized to be linked to a lower bone mineral density (BMD). We examined whether women with vasomotor symptoms are different from women without symptoms with regard to BMD. METHODS: We used data from a population-based sample of 5,600 women, aged 46 to 57 years and free from bone diseases, who participated in the first cross-sectional part of the Eindhoven Perimenopausal Osteoporosis Study between 1994 and 1995. Questionnaires at baseline were used to collect data on vasomotor symptoms and potential confounders. At baseline, BMD of the lumbar spine was measured using dual energy x-ray absorptiometry. Linear regression analysis was used to analyze the data. RESULTS: Flushing was reported by 39% of all women, and night sweats, by 38% of all women. The average BMD was 1.01 +/- 0.14 g/cm and decreased with increasing frequency of flushing (P for trend < 0.0001) and night sweats (P for trend = 0.03). After multivariate adjustments for age, body mass index, menopause status, smoking, education, exercise, and hormone use, women with the highest frequency of symptoms had a 0.022 g/cm (95% CI, -0.03 to -0.01) lower BMD compared with asymptomatic women. Women who reported having the highest frequency of night sweats had a 0.011 g/cm (95% CI, -0.02 to -0.001) lower BMD compared with women with no symptoms of night sweats. CONCLUSIONS: Our findings show that vasomotor symptoms are associated with reduced bone density. It could be hypothesized that women with vasomotor symptoms might be more susceptible to the beneficial effects of estrogens, possibly by neutralizing the effect of estrogen fluctuations. Further research is needed to extend these findings to other estrogen-sensitive end organs.

Blood pressure in middle-aged women: are androgens involved? A population-based study of Swedish women: the Women's Health in the Lund Area study.

OBJECTIVE: To assess the prevalence of hypertension and use of antihypertensive drug therapy in relation to menopausal status and to delineate perceived associations between androgens and blood pressure in perimenopausal women. METHODS: A population-based sample of women aged 50-59 (n = 6893). Women were divided into three groups according to their hormonal status: premenopausal, postmenopausal without hormone therapy, and postmenopausal with hormone therapy. RESULT: In the premenopausal, postmenopausal without hormone therapy, and postmenopausal with hormone therapy groups, the prevalence of high blood pressure (>/= 140 mmHg systolic or >/= 90 mmHg diastolic) was 43.9, 49.9 and 45.8%, respectively. In women with normal blood pressure, adjusting for age, body mass index and smoking, there were negative associations between serum testosterone and systolic blood pressure in the total sample (P < 0.01) and the postmenopausal without hormone therapy group (P < 0.05). In women using antihypertensive drug therapy with a blood pressure of at least 140/90 mmHg, positive associations were found between serum testosterone and systolic blood pressure in the total series (P < 0.05) and in the postmenopausal without hormone therapy group (P < 0.05). CONCLUSION: Abnormal blood pressure is common in middle-aged women regardless of hormonal status. Our findings suggest that testosterone could have a dual influence on blood pressure in perimenopausal women.

Low-dose continuous combinations of hormone therapy and biochemical surrogate markers for vascular tone and inflammation: transdermal versus oral application.

OBJECTIVE: To compare the effects of low-dose transdermal estradiol (E2)/norethisterone acetate (NETA) patches (Estalis 25/125) with low-dose oral E2/NETA (Activelle) on cardiovascular biochemical markers after 12 and 52 weeks of treatment in postmenopausal women with intact uteri. DESIGN: Participants were randomly assigned to receive either transdermal E2/NETA (delivering daily doses of 25 microg E2 and 125 microg NETA, applied every 3-4 d) or oral E2/NETA (1 mg E2 and 0.5 mg NETA, given daily) in this open-label study. The following markers or their stable metabolites in serum or urine were assessed: P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, matrix metalloproteinase-9, homocysteine, cyclic guanosine monophosphate, serotonin, prostacyclin, thromboxane, and urodilatin. RESULTS: Significant decreases were found for P-selectin, intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and homocysteine for both hormone therapy (HT) regimens compared with baseline. Matrix metalloproteinase-9 was increased only by oral HT. The urinary concentrations of cyclic guanosine monophosphate, the ratio of prostacyclin to thromboxane metabolite, and the serotonin metabolite were significantly increased for both HT application modes, although the oral treatment showed a significantly greater increase than the transdermal one with respect to baseline. Urodilatin excretion was increased only by the oral regimen. CONCLUSIONS: Low-dose transdermal and oral HTs using E2 and NETA elicit favorable effects on cardiovascular biochemical markers. For most markers the magnitude of changes found were similar with respect to baseline; however, in some cases oral HT led to a significantly greater change, whereas in other cases the transdermal formulations seemed to provide greater benefits. Whether these differences may be attributed to the different administration routes or to different pharmacokinetic properties remains an open question. Overall low-dose transdermal HT seems to provoke the same benefit on the cardiovascular system as oral HT, as suggested by the results on vascular markers.

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.

OBJECTIVE: To delineate the health profile in middle-aged women with cardiovascular disease (CVD). METHODS: The Women's Health in the Lund Area (WHILA) project covered all women born 1935-1945 (n = 10,766) living in the Lund area; 6917 (64.2%) women completed a generic questionnaire and underwent physical and laboratory assessments. Of the 6917 women, 6416 were postmenopausal women, of whom 104 had CVD. For each woman with CVD, two controls were selected and matched for age, smoking habits, body mass index (BMI), waist/hip ratio (WHR), low-density lipoprotein cholesterol (LDL-C), high-density liproprotein cholesterol (HDL-C), diastolic blood pressure and hormonal status. RESULTS: One hundred four women (1.6%) reported CVD. Forty-nine had a myocardial infarction (MI), 49 had a stroke, and 6 women had both events; 71.4% were postmenopausal, with never use of hormone therapy (HT) (PM0), and 28.6% were postmenopausal with ever use of HT (PMT). Compared with the control group, serum androstendione was lower (p = 0.004) in the case group, and menopausal estradiol (E(2)) values were less frequent (p = 0.037) in cases from the PM0 group. Among psychological and somatic symptoms, nervousness (p < 0.05), difficulty relaxing, crying easily, visual disturbance (p

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.

OBJECTIVE: To outline perceived associations between various sex hormones and risk markers for cardiovascular disease in middle-aged women, with an emphasis on features of the metabolic syndrome (MS). DESIGN: Cross-sectional analysis. SETTING: Women's Health in the Lund Area Study. PATIENT(S): Population-based cohort. INTERVENTION(S): A generic questionnaire, physical examinations, and laboratory assessments were completed by 6,917 women aged 50-59 years living in the Lund area of southern Sweden. Women at or above defined cutoff limits for the MS were considered positively screened. After exclusion of women using hormone therapy (HT), 2,038 women with (MS+) and 2,054 women without features of the MS (MS-) were included. The ELISA techniques were used for the determination of serum androstendione (A), E2, T, sex hormone-binding globulin (SHBG), cortisol, insulin, and leptin levels. Serum lipids and lipoproteins were determined by conventional methods. Multiple linear regression analyses were performed, controlling for age, body mass index (BMI), and smoking habits. MAIN OUTCOME MEASURE(S): Features of the MS, sex steroids, cardiovascular risk markers. RESULT(S): In the MS+ group, a positive association was seen between A and systolic blood pressure. Estradiol was negatively associated with total cholesterol and diastolic blood pressure. The SHBG was negatively associated with triglycerides, blood glucose, and diastolic blood pressure and positively with high-density lipoprotein (HDL). In the MS- group, there were positive associations between A, blood glucose, and systolic blood pressure. Testosterone was positively associated with HDL. Estradiol was negatively associated with total cholesterol and positively with systolic blood pressure. The SHBG was positively associated with HDL and negatively with triglycerides and diastolic blood pressure. There were positive associations between cortisol, low-density lipoprotein (LDL) cholesterol, blood glucose, and systolic blood pressure and a negative association with triglycerides in both MS+ and MS- groups. CONCLUSION(S): Androstendione, E2, and T levels were associated with cardiovascular risk factors in middle-aged women. Effects by sex steroids on cardiovascular risk markers seem to be different in women with or without features of the MS.

One-year endometrial safety evaluation of a continuous combined transdermal matrix patch delivering low-dose estradiol-norethisterone acetate in postmenopausal women.

OBJECTIVE: To evaluate the safety and endometrial protection of low-dose transdermal estradiol (E2)/norethisterone acetate (NETA) patches (Estalis 25/125) in terms of post-treatment incidence of endometrial hyperplasia/cancer after 1 year of treatment in postmenopausal women with intact uteri. METHODS: Patients were randomized to receive either transdermal E2/NETA (delivering daily doses of E2 25 microg and NETA 125 microg; applied every 3-4 days) or oral E2/NETA (E2 1mg and NETA 0.5 mg; given daily) in this open-label study. The primary variable was the incidence of endometrial hyperplasia/cancer based on endometrial biopsies; secondary variables included vaginal bleeding/spotting patterns, patch adhesion, safety and tolerability. RESULTS: Six hundred and seventy-seven patients were randomized (507 in the transdermal group and 169 in the oral group; one did not receive study drug) and >80% completed the study. There were no cases of endometrial hyperplasia or cancer in either group and the upper limit of the one-sided 95% confidence interval in the transdermal group was 0.85%. Over time, both treatments were associated with a decreasing frequency of spotting/bleeding days. The overall incidence of adverse events (AEs) was comparable in both groups, and the majority was mild-to-moderate in intensity. Breast tenderness was the most frequently reported AE (transdermal 19.9% versus oral 28.4%). AEs related to the gastrointestinal system were more frequent with oral E2/NETA, and episodes of spotting and bleeding were more frequent with transdermal E2/NETA. Local skin tolerability of the transdermal matrix system was good. CONCLUSIONS: Transdermal E2/NETA (25 and 125 microg) provided adequate endometrial protection in postmenopausal women when evaluated according to CPMP/CHMP criteria, achieved a high rate of amenorrhea, and was well tolerated.

Patient characteristics associated with quality of life in European women seeking treatment for urinary incontinence: results from PURE.

OBJECTIVE: To investigate the association between patient characteristics and disease-specific and generic quality of life (QOL) as well as the degree of bother in women seeking treatment for urinary incontinence (UI). METHODS: The Prospective Urinary Incontinence Research (PURE) was a 6-mo observational study with 1055 physicians from 15 European countries enrolling 9487 women. QOL was assessed at the enrolment visit using the urinary Incontinence Quality of Life questionnaire (I-QOL) and the generic EQ-5D. A single-item instrument was used to measure the degree of bother. UI severity was assessed using the Sandvik Index. UI was categorised into stress (SUI), mixed (MUI), and urge (UUI) urinary incontinence by a patient-administered instrument (Stress and Urge Incontinence Questionnaire [S/UIQ]). Multivariate linear (I-QOL, EQ-5D Visual Analogue Scale) and logistic (bother, EQ-5D health state index) regressions were performed. RESULTS: Mean total I-QOL scores were significantly and independently associated with UI severity, nocturia, age, UI subtype, number of selected concomitant medical conditions, length of suffering from UI before contacting a doctor, smoking status, ongoing use of UI medication, and country. After adjusting for all the covariates, the total I-QOL scores for SUI, MUI, and UUI were 62.7, 53.8 and 60.1, respectively. As with I-QOL, UI severity was also the most important predictor for bother. The number of concomitant medical conditions, together with UI severity, was the variable most strongly associated with EQ-5D. CONCLUSION: In addition to the UI subtypes, severity of UI should be given more importance in treatment algorithms and in treatment decision-making by both the patient and the physician.

Obese women and the relation between cardiovascular risk profile and hormone therapy, glucose tolerance, and psychosocial conditions.

OBJECTIVE: To evaluate the relation between cardiovascular disease (CVD) risk factors and hormone therapy, serum hormone levels, glucose tolerance, and psychosocial and psychological conditions in subjectively healthy obese female subjects. RESEARCH DESIGN AND METHODS: The study included 606 women, aged 50-64 years, with BMI 30-40 kg/m(2) and no history of cardiovascular or other severe diseases. One group with a CVD risk profile (n = 473) (i.e., cholesterol >7.0 mmol/l, HDL cholesterol <1.2 mmol/l, triglycerides >2.0 mmol/l, systolic or diastolic blood pressure >140/90 mmHg, or waist-to-hip ratio >0.85) was compared with women without such risk (n = 133). Steroid hormones, leptin, insulin, and oral glucose tolerance tests (OGTTs) were analyzed. A subgroup of women with baseline impaired glucose tolerance (IGT) completed a 2.5-year follow-up OGTT. RESULTS: Fewer obese postmenopausal women with CVD risk had ever used hormone therapy (odds ratio 0.24 [95% CI 0.07-0.75]), after multivariate adjustments. Furthermore, women with CVD risk had a higher testosterone index (1.07 [1.01-1.13]) and more had insulin resistance (1.04 [1.00-1.08]) and IGT (2.92 [1.50-5.69]), while OGTT was similar at follow-up. No differences were observed regarding family history or lifestyle, except that fewer women with CVD risk consumed fruits, boiled vegetables, or whole-grain cereals. More women with CVD risk lived alone (3.26 [1.28-8.31]) and had more mental problems (1.16 [1.05-1.28]). CONCLUSIONS: Previously healthy obese women with a CVD risk profile seemed to have a high risk of diabetes, as well as psychosocial or psychological problems. Hormone therapy was associated with reduced CVD risk. Obesity's growing burden on society makes it more important to further target individuals that are at greatest risk of future health hazards.

Colorectal cancer in middle-aged women in relation to hormonal status: a report from the Women's Health in the Lund Area (WHILA) study.

OBJECTIVE: To delineate a perceived association of estradiol versus estradiol plus norethisterone hormone therapy on the prevalence of colorectal cancer in postmenopausal women. METHODS: The Women's Health in the Lund Area (WHILA) project covers 10,766 women aged 50-60 years, living in the Lund area, Sweden. Out of this population, 6908 (64%) women completed questionnaires, underwent physical and laboratory assessments and had self-reported information regarding colorectal cancer. Four hundred and twenty-two (6%) were premenopausal (PM), 3600 (52%) were postmenopausal without hormone therapy (PM0), 2452 (36%) were postmenopausal with combined hormone therapy (PMT-HT) and 364 (5%) were postmenopausal with estrogen monotherapy (PMT-E). RESULTS: There were 21 cases of colorectal cancer (0.3%), one in the PM group, 16 in the PM0 group, two in the PMT-HT group and another two in the PMT-E group. Colorectal cancer prevalence was lower in the PMT-HT than in the PM0 group (odds ratio (OR) = 0.18, 95% confidence interval (CI) = 0.04-0.80). However, for the PMT-E group, the OR (95% CI) was 1.02 (0.86-1.20). There was a positive association between low physical activity (p = 0.04), low parity (p = 0.02) and risk of colorectal cancer. CONCLUSION: Combined hormone therapy seemed to be associated with a lower risk of colorectal cancer in postmenopausal women in contrast to estrogen monotherapy. Hence the progestin might have a protective role.