Peripheral Vascular Ageing in Pulmonary Arterial Hypertension as Assessed by Common Carotid Artery Intima Thickness and Intima/Media Thickness Ratio: An Investigation Using Non-Invasive High-Resolution Ultrasound.

BACKGROUND: Pulmonary arterial hypertension (PAH; World Heath Organization [WHO] Group 1) is associated with increased pulmonary arterial pressure and resistance, with pulmonary vascular remodelling. The vascular anatomy of the systemic arteries has been less well studied. METHOD: Nineteen (19) patients with PAH, confirmed by right heart catheterisation (RHC), 14 patients with left ventricular heart failure with reduced ejection fraction (LVrEF), and 30 healthy subjects were enrolled. Common carotid artery (CCA) intima thickness, intima/media (I/M) thickness ratio, and intima-media thickness (IMT) were assessed using non-invasive ultrasound (22 MHz centre frequency). RESULTS: The CCA intima thickness was correlated with several RHC variables (all p<0.05). The intima was 56% thicker (+0.05 mm; 95% CI 0.03, 0.06; p<0.0001) and the I/M thickness ratio was 128% greater (+0.21; 95% CI 0.13, 0.28; p<0.0001) in patients with PAH than healthy subjects. These values were also significantly higher than in patients with LVrEF. In ROC curve analysis, the c-values for CCA intima thickness (0.92) and I/M ratio (0.87), but not for IMT, correctly indicated which individuals belonged to the PAH or healthy control groups. The CCA IMT showed no corresponding significant group differences or associations and was of no use according to receiver operating curve analysis. CONCLUSIONS: Patients with PAH displayed signs of peripheral vascular remodelling, challenging the common opinion that vascular changes in PAH are restricted to the lung vasculature. Correlations with cardiopulmonary variables from RHC support peripheral vascular coupling and the association with vascular ageing. Results from this pilot study warrant further confirmation.

Rapid eye movement sleep apnea and carotid intima thickness in men and women: a SHE-MUSTACHE cohort study.

Rapid eye movement (REM) obstructive sleep apnea might be particularly harmful to the cardiovascular system. We aimed to investigate the association between sleep apnea during REM sleep and signs of atherosclerotic disease in the form of carotid intima thickness in a community-based sample of men and women and possible sex differences in this association. The association between sleep apnea during REM sleep and intima thickness was analysed cross-sectionally in women from the community-based "Sleep and Health in Women" (SHE) study (n = 253) and age- and body mass index (BMI)-matched men from the "Men in Uppsala; a Study of sleep, Apnea and Cardiometabolic Health" (MUSTACHE) study (n = 338). Confounders adjusted for were age, BMI, gender, alcohol, and smoking. All participants underwent a full-night polysomnography, high-resolution ultrasonography of the common carotid artery, anthropometric measurements, blood pressure measurements, and answered questionnaires. There was an association between sleep apnea during REM sleep and thicker carotid intima that remained after adjustment for confounding (adjusted ß = 0.008, p = 0.032). The intima was increased by 9.9% in the group with severe sleep apnea during REM sleep, and this association between severe sleep apnea during REM sleep and increased intima thickness remained after adjustment for confounders (adjusted ß = 0.043, p = 0.021). More women than men had severe sleep apnea during REM sleep; moreover, in sex-stratified analyses, the association between sleep apnea during REM sleep and intima thickness was found in women but not in men. We conclude that severe REM sleep apnea is independently associated with signs of atherosclerosis. When stratified by sex, the association is seen in women but not in men.

Health-related quality of life in young women starting hormonal contraception: a pilot study.

OBJECTIVES: Our purpose was to study whether there is a difference in self-rated health-related quality of life (HRQOL) and changes in HRQOL perception after 3 months of hormonal contraceptive use in adolescents. Seasonal variations in symptoms of depression were also studied. METHODS: A test group (T1) (n = 193) and a selected control group (n = 238) of women aged 14-20 years who were visiting a young person's clinic completed the 36-item short-form health survey (SF-36) and answered additional questions on menstrual history and pattern, need for menstrual pain relief medication, and other regular medication. The test group was reassessed after 3 months of hormonal contraception (T2). Seasonal variations in reported SF-36 scores were studied for the whole group. RESULTS: The selected control group and test group at T1 were similar with regard to age at menarche and menstrual pattern. The duration of bleeding and use of painkillers were significantly reduced and the impact on everyday life was significantly improved after 3 months of hormonal contraception (p = .000, two-tailed). No changes in HRQOL or symptoms of possible depression were found after 3 months of hormonal contraception. The highest prevalence odds ratio for possible depression (SF-36 mental health scale score ≤48), adjusted for group, season and age, for spring vs winter, was 2.15 (95% confidence interval 0.95, 4.85). CONCLUSIONS: After 3 months of hormonal contraception both the number of days of menstrual bleeding and the use of medication to relieve menstrual pain were reduced, but there were no significant changes in self-rated HRQOL perception. Seasonal effects on HRQOL were reported.

Artery wall layer dimensions during normal pregnancy: a longitudinal study using noninvasive high-frequency ultrasound.

The vascular effects of normal pregnancy were investigated by estimating the intima and media thicknesses of the common carotid artery separately using 22-MHz ultrasound (Collagenoson, Meudt, Germany) in 57 healthy women with normal pregnancies and pregnancy outcomes, in all three trimesters and at 1 yr postpartum. A thick intima, thin media, and high intima-to-media (I/M) ratio are signs of a less healthy artery wall. Mean artery wall layer dimensions remained fairly constant during pregnancy, but the intima thickness and I/M thickness ratio appeared to improve (decrease) postpartum (P < 0.001 for both). The cardiovascular risk parameters of age, body mass index, and blood pressure in the first trimester were associated with higher I/M ratios, especially in the second trimester, whereas higher serum estradiol levels were significantly associated with a lower I/M ratio. Changes from the first to second trimesters in I/M ratio, taking into account differential changes in intima and media thickness, were significantly (P < 0.05-0.001) associated with all risk parameters tested except age, which was associated with increased intima thickness (P = 0.02). Associations with third trimester values and changes from first to third trimesters were similar but less apparent. Thus, fairly constant mean artery wall layer dimensions during pregnancy appeared to improve postpartum. However, higher age, body mass index, or blood pressure and lower serum estradiol levels in the first trimester appeared to negatively affect the artery wall, strongly suggesting that pregnancy has negative vascular effects in some women. A less likely explanation involves possible adaptation to physiological changes during and after pregnancy.

Self-reported health in adolescent girls varies according to the season and its relation to medication and hormonal contraception--a descriptive study.

OBJECTIVES: To study seasonal variations in self-rated health and depressive symptoms in adolescent girls and possible differences in reported health with regard to use of medications. METHOD: The SF-36 questionnaire was completed by 1250 girls with a mean age of 17 years, who visited a health centre in the course of one year. From January to July inclusive, depressive symptoms in 453 of the participants were also assessed using MADRS-S. Age and regular medication data were recorded. RESULTS: Significantly better mental health and less depressive symptoms were reported during the summer, than in winter months. Seasonality was more related to the SF-36 mental, than physical health subscales. Respondents treated with hormonal contraceptives (HCs) only and those not taking any medication scored better on several SF-36 subscales, than girls on antidepressives and other medications. Respondents taking HCs tended to report better physical health and less depressive symptoms on MADRS-S than those taking no medication. CONCLUSIONS: Adolescent girls showed seasonal variations in self-reported health and depressive symptoms, with more symptoms during winter months. HC users tended to report better physical health and less depressive symptoms than those on no medication. The high prevalence of suspected depression during the winter months deserves attention.

Protein and steroid profiles in follicular fluid after ovarian hyperstimulation as potential biomarkers of IVF outcome.

Controlled ovarian hyperstimulation is performed to assist with generation of multiple mature oocytes for use in in vitro fertilization (IVF). The goal of our study was to evaluate differences in protein and steroid profiles in ovarian follicular fluid (hFF) samples obtained during oocyte retrieval from women undergoing IVF treatment and to identify physiological pathways associated with the proteins. The hFF samples were depleted of abundant proteins, fractionated by ultrafiltration, digested, and analyzed by nano-LC-QTOF. Concentrations of 15 endogenous steroids were determined in the samples using LC-MS/MS methods. The total number of proteins identified in the samples was 75, of which 4, 7, and 2 were unique to the samples from women with viable pregnancy, miscarriage, and no pregnancy, respectively. Identified proteins were associated with the acute response signaling, coagulation system, intrinsic and extrinsic prothrombin activation, complement system, neuroprotective role of THOP1, FXR/RXR activation, role of tissue factor, and growth hormone pathways. A greater number of proteins associated with biosynthesis was found in hFF samples corresponding to the oocytes resulting in pregnancy. The abundance of seven proteins was found to be associated with steroidogenesis. The obtained data will contribute to better understanding of the pathogenesis and development of noninvasive markers for assessment of oocytes viability.

Risk factors for cardiovascular disease are increased in young adults treated with stem cell transplantation during childhood.

We measured risk factors for CVD in 18 patients at a median of 18.2 yr after SCT and in sex and age-matched controls. Three patients (17%), but none of the controls, met the criteria for the MetS (p = 0.25). In the patients, we found higher levels of triglycerides (0.94 vs. 0.62 mm, p = 0.019), total cholesterol (5.1 vs. 4.0 mm, p = 0.017), LDL (3.4 vs. 2.6 mm, p = 0.019), apolipoprotein B (1.04 vs. 0.74 g/L, p = 0.004), apolipoprotein B/A1 ratio (0.7 vs. 0.5, p = 0.026), and lower levels of adiponectin (4.9 vs. 7.5 mg/L, p = 0.008) than in the controls. The patients had a lower GHmax (9 vs. 20.7 mU/L, p = 0.002). GHmax was significantly correlated inversely with triglycerides (r = -0.64, p = 0.008), total cholesterol (r = -0.61, p = 0.011), apolipoprotein B (r = -0.60, p = 0.014), and apolipoprotein B/A1 ratio (r = -0.66, p = 0.005). We recorded a significantly thicker carotid intima layer among the patients than among matched controls (0.15 vs. 0.13 mm, p = 0.034). The level of adiponectin correlated inversely with carotid intima thickness (r = -0.55, p = 0.023). After SCT in childhood, long-term survivors may be at risk of developing premature CVD.

Obesity in adolescents associated with vascular aging - a study using ultra-high-resolution ultrasound.

Background: Obesity in adolescents is increasing worldwide and associated with an elevated cardiovascular risk later in life. In a group-comparative study, we investigated the association between adiposity in adolescents and signs of vascular aging and inflammation. Methods: Thirty-nine adolescents (10-18 years old), 19 with obesity and 20 with normal weight, were enrolled. The intima thickness and intima/media thickness ratio (I/M) were assessed using high-resolution ultrasound in the common carotid artery (center frequency 22 MHz) and the distal radial artery (RA; 50 MHz). Increased intima and high I/M are signs of vascular aging. Body characteristics, high-sensitivity C-reactive protein (hs-CRP), plasma lipids, and glycemic parameters were measured. Results: Adolescents with obesity, compared to normal-weight peers, had elevated plasma lipid, insulin c-peptide, and hs-CRP levels, the latter increasing exponentially with increasing adiposity. Obese adolescents had a thicker RA intima layer [0.005 mm; 95% confidence intervals (0.000, 0.009); P = 0.043] and a higher RA I/M [0.10; (0.040, 0.147); P < 0.0007]. Group differences for the RA I/M remained significant after adjustment for age, sex, fasting plasma insulin, and body mass index, both separately and together (P = 0.032). The RA I/M was correlated with hs-CRP, and both were correlated with the analyzed cardiovascular risk factors. Receiver operating curve c-values for RA I/M (0.86) and hs-CRP (0.90) strongly indicated correct placement in the obese or non-obese group. Conclusions: Adolescents with obesity had significantly more extensive vascular aging in the muscular RA, than normal-weight peers. The findings support an inflammatory link between obesity and vascular aging in adolescents.

Could SF-36 be used as a screening instrument for depression in a Swedish youth population?

OBJECTIVE: Depression among youth is a condition associated with serious long-term morbidity and suicide. The aim of this study was to investigate whether a HRQoL instrument, the short form 36 version 1.0 (SF-36), could be used to screen for depression in a clinical Youth Centre (YC). A second purpose was to describe self-reported health and depression. SETTING: A clinical YC at a University hospital. DESIGN: A sample of 660 youths, 14-20 years old was assessed with SF-36 and Montgomery Åsberg Depression Rating Scale, self-screening version (MADRS-S). Answers to all the questions in both instruments were given by 79% (519/660; 453 women and 66 men). Mean age in the sample was 17.5±1.6 years. RESULTS: Strong correlations were found between all the SF-36 subscales and the depression ratio scale MADRS-S. Receiver operating characteristic (ROC) curve analysis confirmed that the SF-36 subscales mental health (MH) and vitality (VT) could correctly predict depression on the individual level with Area Under the ROC Curve values 0.87 and 0.84 in ROC curves. Individuals scoring 48 or lower on MH and 40 or lower on VT should be followed up with a clinical interview concerning possible depressive disorder. Mild to moderate depression was common (35.5%), especially among women (37.5%). Men scored higher than women on all SF-36 subscales except for physical functioning. CONCLUSIONS: The SF-36 can be used to screen for suspect depression in a youth population followed by interview. This gives an opportunity to detect and treat emerging depressive symptoms early.

Low- and Fully N-Glycosylated Gonadotropins Circulating in Women With Polycystic Ovary Syndrome.

CONTEXT: A preponderance of basic luteinizing hormone (LH) molecules having elevated bioactivity was detected in the circulation of women with polycystic ovary syndrome (PCOS). Subsequent studies have shown that LH and follicle-stimulating hormone (FSH) both circulate as glycoforms differing in number of glycans: low-N-glycosylated glycoforms, LHdi and FSHtri, with high in vitro bioactivity, and fully glycosylated glycoforms, LHtri and FSHtetra, with high in vivo bioactivity. OBJECTIVE: This work aims to characterize the glycosylation patterns on circulating gonadotropin glycoforms in women with PCOS. METHODS: Serum samples, collected from 8 women with PCOS were included. The concentration, sulfonation, and sialylation of each glycoform were determined and compared with values of serum samples from healthy women: 22 women at follicular phase, 16 at midcycle, and 15 after menopause. RESULTS: All the women with PCOS had higher LHdi serum levels compared with those in the follicular-phase group. Median LHdi and median LHtri levels were significantly elevated in PCOS women. The percentage of LHdi was increased from 37 to 49 and that of FSHtri was decreased from 41 to 33. The LHdi, LHtri, and FSHtetra glycoforms were more sialylated and both LH glycoforms less sulfonated in women with PCOS. CONCLUSION: All women with PCOS had increased serum levels of LHdi, compared with those in the follicular phase. The percentage of LHdi was increased and that of FSHtri decreased in women with PCOS. The increased LHdi leads to maintenance of the abnormal early follicular development of the polycystic ovary, and the decreased FSHtri contributes to the arrested follicle growth.

Dimethylarginines correlate to common carotid artery wall layer dimensions and cardiovascular risk factors in pregnant women with/without preeclampsia: A group comparative study.

OBJECTIVES: Asymmetric- and symmetric dimethylarginines (ADMA, SDMA) are elevated in cardiovascular disease (CVD). Preeclampsia is a pregnancy-specific syndrome and is an independent risk factor for subsequent CVD. Aims were to investigate whether ADMA, SDMA levels and l-arginine/ADMA and l-arginine/SDMA ratios during pregnancy and their changes from pregnancy to postpartum are associated to arterial wall layer dimensions and cardiovascular risk factors in women with and without preeclampsia. STUDY DESIGN: Dimethylarginines were analyzed by LC-MS, and the common-carotid-artery (CCA) intima and media thicknesses were estimated using 22-MHz non-invasive ultrasonography in women with preeclampsia (cases = 48) and normal pregnancies (controls = 58) in similar gestational age, with reassessment one-year postpartum. A thick intima, thin media and high intima/media ratio (I/M) indicates a less healthy arterial wall. RESULTS: The median age of cases and controls was 30 years. During pregnancy, women with preeclampsia had higher plasma ADMA, SDMA and lower l-arginine/ADMA and l-arginine/SDMA (all p < 0.01) than women with normal pregnancies. Further, ADMA, SDMA, l-arginine/ADMA and l-arginine/SDMA correlated to intima thickness (rs = 0.33/0.33/-0.33/-0.35 and p < 0.01), I/M (rs = 0.26/0.28/-0.22/-0.26 and p < 0.05) and mean arterial pressure (MAP) (rs = 0.43/0.42/-0.39/-0.40 and p < 0.0001). Changes in ADMA, SDMA and l-arginine/SDMA from pregnancy to postpartum correlated to changes in intima thickness (rs = 0.22/0.32/-0.21 and p < 0.05/<0.01/<0.05), I/M (rs = 0.22/0.31/0.08 and p < 0.05/<0.01/=0.43) and MAP (rs = 0.31/0.53/-0.25 and p < 0.01/<0.001/<0.05). No correlations were found for conventional CCA intima-media-thickness. CONCLUSIONS: Dimethylarginines were associated to signs of adverse effects on arterial wall layer dimensions and cardiovascular risk factors in women with and without preeclampsia, during pregnancy and to their changes from pregnancy up to one-year postpartum.

Concentrations of nine endogenous steroid hormones in 70-year-old men and women.

OBJECTIVES: Circulating concentrations of endogenous steroids have systemic implications on health in elderly. However, population-based age- and ethnicity-specific data are scarce. The aim was to report sex-specific plasma concentrations of endogenous sex and adrenal steroids in elderly Swedish Caucasians, to examine the impact of BMI and to present concentrations in apparently healthy subjects. METHODS: A population-based observational study of 70-year olds, including 684 community-dwelling men and women enrolled in the PIVUS study, Sweden. Median plasma concentrations were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for pregnenolone, 17-hydroxypregnenolone, 17-hydroxy-progesterone, 11-deoxycortisol, DHEA, androstenedione, testosterone, estrone and estradiol. RESULTS: Plasma concentrations were significantly higher in men (n = 452) than in women (n = 232) for estradiol: median 61.3 pmol/L (95% CI, 11.4, 142.7) vs 18.4 (4.0, 127.3), for estrone: 92.8 (33.3, 206) vs 71.6 (17.8, 209) pmol/L, and for testosterone 13.8 (5.7, 28.0) vs 0.7 (0.2, 2.0) nmol/L. Higher concentrations of estrone and estradiol were observed in obese than non-obese women. Compared to non-obese men, obese men had lower concentrations of testosterone and its precursors: 17-hydroxypregnenolone, 17-hydroxyprogesterone, androstenedione and DHEA. The subgroup of apparently healthy individuals had median values > 20% lower for estrone and estradiol in women but slightly higher for testosterone in both sexes. CONCLUSIONS: Concentrations of estradiol, estrone and testosterone were higher in 70-year-old men than in women. BMI associated positively to estradiol and estrone in women and negatively to testosterone in men. Apparently healthy women had lower median concentrations of estradiol and estrone and men had higher median testosterone compared to all individuals.

The expression of syndecan-1, syndecan-4 and decorin in healthy human breast tissue during the menstrual cycle.

BACKGROUND: In order to unravel the interactions between the epithelium and the extra cellular matrix (ECM) in breast tissue progressing to cancer, it is necessary to understand the relevant interactions in healthy tissue under normal physiologic settings. Proteoglycans in the ECM play an important role in the signaling between the different tissue compartments. The proteoglycan decorin is abundant in the breast stroma. Decreased expression in breast cancer tissue is a sign of a poor tumor prognosis. The heparane sulphate proteoglycans syndecan-1 and syndecan-4 promote the integration of cellular adhesion and proliferation. The aim of this study was to investigate the gene expression and location of decorin, syndecan-1 and syndecan-4 in the healthy breast during the menstrual cycle. METHODS: Tissue from healthy women undergoing breast reduction plastic surgery was examined using immunohistochemistry (n = 38) and Real-Time RT-PCR (n = 20). Both parous and nulliparous women were eligible and the mean age of the women was 34(+/- 10 years) with regular menstrual cycles (28 +/- 7 days). None of the women had used hormonal treatment the last three months. The women were randomized to needle biopsy two months before the operation in the follicular or luteal menstrual phase and for another biopsy at the operation in the opposite phase. Serum samples were obtained to characterize the menstrual phase. The Wilcoxon signed rank test and Mann Whitney test were used for statistical analyses. RESULTS: By real time-RT-PCR the gene signal for all three proteoglycans; decorin (p = 0.02) and syndecan-1 (p = 0.03) and syndecan-4 (p = 0.02) was significantly lower among parous women in the luteal phase than in the follicular phase. Immunohistochemistry confirmed the identification of the proteins but no significant difference between menstrual phases was observed. Serum samples verified the menstrual phase. CONCLUSIONS: Our study shows, for the first time in the healthy breast, a significantly lower expression of the genes for the three proteoglycans, decorin, syndecan-1 and syndecan-4 in the luteal phase during the menstrual cycle. These changes were registered under normal physiologic conditions. Since ECM molecules appear to be involved in tumor progression, these findings in the normal breast could constitute a base for further studies in women receiving hormonal therapy or those with breast cancer.

Preclinical atherosclerosis in adolescents with psychotic or bipolar disorders investigated with carotid high-frequency ultrasound.

OBJECTIVE: Early-onset psychosis (EOP) and bipolar disorder (EOBP) (at <18 years of age), are associated with an increased future risk of cardiovascular disease (CVD) and premature death. Yet it is unknown whether the arteries show visible signs of atherosclerosis in EOP and EOBP. This study investigated whether having EOP or EOBP was associated with detectable signs of preclinical atherosclerosis. METHOD: By using 22 MHz high-frequency ultrasound, different layers of the arterial wall of the left common carotid artery (LCCA) were assessed in 77 individuals with EOP (n = 25), EOBP (n = 22), and in age-matched healthy controls (n = 30). Conventional CVD confounders were included in the analyses. RESULTS: Adolescents with EOP and EOBP, compared to controls, had a significantly thicker LCCA intima thickness (0.132 vs. 0.095 mm, p < .001) and intima/media ratio (0.24 vs. 0.17 p < .001). There was a nonsignificant intima difference between EOP and EOBP. Conventional CVD risk factors did not explain the association between EOP/EOBP and intima thickness. In the group of EOP/EOBP, there was a significant correlation between the dose of current antipsychotic medication and intima thickness; however, the correlation was attenuated to a nonsignificant level when adjusted for global function. CONCLUSIONS: Adolescents with EOP or EOBP had an increased LCCA intima thickness, interpreted as a sign of preclinical atherosclerosis. Global function of the disorders was the strongest determinant of intima thickness. The findings, if replicated, might have implications for long-term treatment of EOP and EOBP in order to reduce a future risk of CVD.

Steroid profiles in ovarian follicular fluid from regularly menstruating women and women after ovarian stimulation.

BACKGROUND: Information on the concentrations of steroids in ovarian follicular fluid (FF) from regularly menstruating (RM) women has been limited because of the absence of methods for the simultaneous quantification of multiple steroids in small volumes of FF. We studied steroid profiles in FF during the early follicular phase of the menstrual cycle and after ovarian stimulation for in vitro fertilization (IVF), and compared concentrations with published values obtained by immunoassay (IA). METHODS: We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure 13 steroids in 40-microL aliquots of FF samples from 21 RM women and from 5 women after ovarian stimulation for IVF. Relationships between concentrations of steroids and their ratios (representations of the enzyme activities) were evaluated within and between subgroups. RESULTS: The concentrations of testosterone (Te), androstenedione (A4), and estradiol (E2) measured by LC-MS/MS were lower than those previously reported in studies with IAs. In RM women, androgens were the most abundant class of steroids, with A4 being the major constituent. The concentrations of 17-hydroxyprogesterone (17OHP), total androgens, and estrogens were 200- to 1000-fold greater in FF than in serum. Compared with RM women, FF samples from women undergoing ovarian stimulation had significantly higher concentrations of E2 (P = 0.021), pregnenolone (P = 0.0022), 17OHP (P = 0.0007), and cortisol (F) (P = 0.0016), and significantly higher ratios of F to cortisone (P = 0.0006), E2 to estrone (P = 0.0008), and E2 to Te (P = 0.0013). CONCLUSIONS: The data provide the first MS-based concentration values for 13 steroids in ovarian FF from RM women, from estrogen- and androgen-dominant follicles, and from women after ovarian stimulation for IVF.

Tibolone low dose (1.25 mg/d) therapy and postural balance in elderly women.

UNLABELLED: Most hip fractures occur in subjects without osteoporosis and are associated with a fall. Conventional menopausal hormone therapy (HT) improves postural balance, which might explain the rapid reduction in hip fracture risk. It is unclear whether tibolone improves postural balance, which might determine its effects on peripheral fracture risk. OBJECTIVE: To study the short-term effects of low-dose tibolone therapy on postural balance in elderly women. METHODS: Eighty healthy women (70 evaluable), aged 60 years or more, were recruited through advertising in the local media. They were randomly allocated to receive either tibolone (1.25 mg/d) or placebo for 6 months. Postural balance was assessed as sway velocity, using a force platform. RESULT(S): Baseline characteristics, including serum estradiol values and postural balance, were similar in the two study groups. On average, the overall dosing compliance was very high, over 97% in both groups. After 6 months, sway velocity had decreased (improved) by 7.6% (-0.97 cm/s; P=0.16 vs. baseline) in the tibolone arm and by 2.5% (-0.30 cm/s; P=0.59 vs. baseline) in the placebo group. The difference 0.67 cm/s was not statistically significant (95% CI -2.44, 1.10; P=0.45). Adjustments for age, serum estradiol level and variable value at baseline, revealed similar results. CONCLUSIONS: Short-term treatment with tibolone (1.25 mg/d), compared to placebo, did not significantly affect postural balance function in elderly women.

Health-related self-assessed quality of life in young people at a Youth Centre in Sweden.

OBJECTIVE: To study the self-reported health of young people visiting a Youth Centre (YC) at a University hospital, describe possible gender differences and to compare the results with those in previous Swedish reports on similar age groups using the same instrument. DESIGN: All young people who visited a YC at a particular, randomly chosen time, were verbally asked to fill out a questionnaire, Short Form 36. The interviews were conducted during a 12-month period to lessen the impact of seasonal variations. SETTING: A YC at the department for obstetrics and gynaecology, Uppsala University hospital. PARTICIPANTS: A total of 1495 young people aged 14-25 years who visited the YC. RESULTS: The study population (n = 1495). Response rate was 96%. This population reported lower overall scores compared with the normative Swedish population from 1992. Further, females scored significantly lower than males on all subscales (p < 0.001), except for 'Physical Functioning'. The lowest scores were reported for the subscales Vitality, Role Emotional and Mental Health. CONCLUSION: This study describes physical functioning and mental health among young people visiting a YC. The results indicate a worsening of the perceived physical and MH in young individuals, especially in young women. Further studies are needed to monitor changes in MH and quality of life over time in this group and assess the effects of interventions. This study enhances the importance of a holistic approach towards health and health promotion comprising both physical and mental health issues.

Sub-clinical atherosclerosis in the common carotid artery in women with/without previous pre-eclampsia: A seven-year follow-up.

BACKGROUND AND AIMS: Pre-eclampsia is associated with increased risk of cardiovascular disease and premature death. However, conventional common carotid artery intima-media thickness (CCA-IMT) measurement does not reflect this. In contrast, measurement of the individual CCA intima and media thicknesses clearly indicates increased vascular risk both at diagnosis and about one year after pre-eclampsia. This study examined whether individual CCA wall layers, risk factors for cardiovascular disease, and markers of endothelial dysfunction had normalized or remained unfavorable seven years after pre-eclampsia. METHODS: The individual CCA intima and media thicknesses were measured using 22 MHz ultrasound. Conventional cardiovascular risk factors were recorded. A thick intima, thin media and high intima/media thickness ratio (I/M) are signs of sub-clinical atherosclerosis. RESULTS: The median age of women with previous pre-eclampsia (cases = 23) or normal pregnancies (controls = 35) was 39/37 years. At follow-up (median about seven years), the intima remained thicker and the I/M was higher in cases than in controls [all p < 0.0001; p < 0.001 after adjustment for time to follow-up, body mass index (BMI), and mean arterial pressure (MAP)], whereas the CCA-IMT was illogically thinner. Further, BMI, MAP, hip circumference, abdominal height, serum endostatin and apolipoprotein B levels were higher in cases (all p < 0.05). Intima and I/M measurements were correlated with age, MAP, endostatin and apolipoprotein B, whereas no logical correlations were found for CCA-IMT. CONCLUSIONS: The arteries in cases but not controls were still adversely affected after seven years. Measuring intima thickness and I/M appears preferable to measuring CCA-IMT for demonstrating vascular risk after pre-eclampsia.

Effects of pre- and postmenopausal use of exogenous hormones on receptor content in normal human breast tissue: a randomized study.

OBJECTIVE: To examine the effects of exposure to endogenous and exogenous hormones on estrogen receptor-alpha (ERalpha) and progesterone receptor (PR) levels in normal human breast tissue. METHODS: In a randomized study of women scheduled for mammary reduction plasty (n = 81), ERalpha and PR content in breast parenchyma was analyzed in premenopausal (n = 49) and postmenopausal (n = 16) women. Premenopausal women were randomized to surgery in the follicular or luteal phase of the menstrual cycle or after oral contraceptive treatment for 2 months. Postmenopausal women were randomized to sequential or estrogen-only therapy for 2 months prior to surgery. RESULTS: ERalpha content was higher in parous than in nulliparous (p = 0.009) premenopausal women and displayed a positive association with age (r(s) = 0.51, p = 0.0002). Compared with premenopausal women in the follicular phase, postmenopausal women had higher ERalpha content (p = 0.040) whereas premenopausal women on oral contraception had lower ERalpha (p = 0.048) and PR (p = 0.007) content. Smokers had lower PR content than non-smokers (p = 0.02). CONCLUSION: In the present study ERalpha content was higher in parous than in non-parous women and associated with premenopausal age. Short-term oral contraceptives yielded lower ERalpha and PR contents. Postmenopausal estrogen/progestogen combined therapy yielded lower PR content than estrogen-only therapy.

Obstructive sleep apnea during rapid eye movement sleep is associated with early signs of atherosclerosis in women.

Study Objectives: Although obstructive sleep apnea (OSA) is associated with overall cardiovascular disease and mortality, the association with atherosclerotic cardiovascular disease is less clear, especially in women. Recently, it has been suggested that OSA during rapid eye movement (REM) sleep, associated with long apneas and deep desaturations, could have severe cardiometabolic consequences. The aim of this study was to investigate whether OSA during REM sleep is associated with early signs of atherosclerosis in a population-based sample of women. Methods: In the community-based "Sleep and Health in Women" (SHE) cohort study, 400 women underwent polysomnography, anthropometric measurements, blood sampling, blood pressure measurement, and answered questionnaires. Ten years later, 201 of the original participants, free of known atherosclerotic disease at baseline and without continuous positive airway pressure treatment for OSA, underwent a high-frequency ultrasound of the common carotid artery to assess the individual thickness of the layers of the artery wall. Results: Severe OSA during REM sleep (REM apnea-hypopnea index [AHI] ≥ 30) was associated with a thicker intima. This association was still significant after adjustment for age, body mass index, alcohol, and smoking, as well as for further adjustment for systolic blood pressure, low-density lipoprotein, C-reactive protein, and diabetes (ß-coefficient, 0.008; p-value, 0.022). The association between a REM AHI of ≥30 and intima thickness was also seen in women with no or mild OSA and normal non-REM AHI. Conclusions: In this study of a community-based sample of women, severe OSA during REM sleep was independently associated with early signs of atherosclerosis.