Psychosocial consequences among women with false-positive results after mammography screening in Norway.

BACKGROUND: Mammography screening may cause psychosocial harm for women experiencing a false-positive screening result. Previous studies suggest long-term consequences. The aim of the present study was to assess psychosocial consequences of false-positive findings on screening mammography within a six month follow-up. METHODS: A prospective matched cohort survey study using the questionnaire 'Consequences of Screening for Breast Cancer' (COS-BC), which was translated from Danish to Norwegian. Psychometric analyses investigated the measurement properties of the Norwegian version. Two screening clinics in Norway distributed the survey to 299 women with an abnormal mammogram and 541 women with a normal screen. Women received the questionnaire when receiving the screening result, and one and six months after screening. RESULTS: At six months, statistically significant differences appeared in two scales: existential values and breast examination. At six-month follow-up, women with false-positive results showed no statistically significant differences from women diagnosed with breast cancer in three outcomes: sense of dejection, anxiety, and keeping my mind off things. CONCLUSION: Our results indicate that the psychosocial consequences from having false-positive screening mammography results diminish after six months. The results support previous research describing breast-specific outcomes. However, our results indicate that Norwegian women are less frightened than other Scandinavian mammography screening participants.

Mortality in persons with undetected and diagnosed hypertension, type 2 diabetes, and hypothyroidism, compared with persons without corresponding disease - a prospective cohort study; The HUNT Study, Norway.

BACKGROUND: Suggested strategies in reducing the impact of non-communicable diseases (NCD) are early diagnosing and screening. We have limited proof of benefit of population screening for NCD. Increased mortality in persons with diagnosed NCD has been shown for decades. However, mortality in undetected NCD has barely been studied. This paper explores whether all-cause mortality differed between persons with diagnosed hypothyroidism, type 2 diabetes (T2DM), and hypertension, compared with persons with undetected-, and with persons without the corresponding disease. METHODS: A prospective cohort study of the general population in Nord-Trøndelag, Norway. Persons ≥20 years at baseline 1995-97 were followed until death or June 15, 2016. Cox proportional hazards models were used to compute age and multiple adjusted hazard ratios (HR) with 95% confidence intervals (CI) for the association between disease status and all-cause mortality. The number of participants in the hypothyroidism study was 31,960, in the T2DM study 37,957, and in the hypertension study 63,371. RESULTS: Mortality was increased in persons with diagnosed type 2 diabetes and hypertension, compared to persons without corresponding disease; HR 1.69 (95% CI 1.55-1.84) and HR 1.23 (95% CI 1.09-1.39), respectively. Among persons with undetected T2DM, the HR was 1.21 (95% CI 1.08-1.37), whilst among undetected hypothyroidism and hypertension, mortality was not increased compared with persons without the diseases. Further, the association with mortality was stronger in persons with long duration of T2DM (HR 1.96 (95% CI 1.57-2.44)) and hypertension (HR 1.32 (95% CI 1.17-1.49)), compared with persons with short duration (HR 1.29 (1.09-1.53) and HR 1.16 (1.03-1-30) respectively). CONCLUSIONS: Mortality was increased in persons with diagnosed T2DM and hypertension, and in undetected T2DM, compared with persons without the diseases. The strength of the association with mortality in undetected T2DM was however lower compared with persons with diagnosed T2DM, and mortality was not increased in persons with undetected hypothyroidism and hypertension, compared with persons without the diseases. Thus, future research needs to test more thoroughly if early diagnosing of these diseases, such as general population screening, is beneficial for health.

Diagnostic labelling influences self-rated health. A prospective cohort study: the HUNT Study, Norway.

BACKGROUND: Studies have shown an independent association between poor self-rated health (SRH) and increased mortality. Few studies, however, have investigated any possible impact on SRH of diagnostic labelling. OBJECTIVE: To test whether SRH differed in persons with known and unknown hypothyroidism, diabetes mellitus (DM) or hypertension, opposed to persons without these conditions, after 11-year follow-up. METHODS: Prospective population-based cohort study in North-Trøndelag County, Norway, HUNT2 (1995-97) to HUNT3 (2006-08). All inhabitants aged 20 years and older were invited. The response rate was 69.5% in HUNT2 and 54.1% in HUNT3. In total, 34144 persons aged 20-70 years were included in the study population. The outcome was poor SRH. RESULTS: Persons with known disease had an increased odds ratio (OR) to report poor SRH at follow-up; figures ranging from 1.11 (0.68-1.79) to 2.52 (1.46-4.34) (men with hypothyroidism kept out owing to too few numbers). However, in persons not reporting, but having laboratory results indicating these diseases (unknown disease), no corresponding associations with SRH were found. Contrary, the OR for poor SRH in women with unknown hypothyroidism and unknown hypertension was 0.64 (0.38-1.06) and 0.89 (0.79-1.01), respectively. CONCLUSIONS: Awareness opposed to ignorance of hypothyroidism, DM and hypertension seemed to be associated with poor perceived health, suggesting that diagnostic labelling could have a negative effect on SRH. This relationship needs to be tested more thoroughly in future research but should be kept in mind regarding the benefits of early diagnosing of diseases.

Women's Experiences With Mammography Screening Through 6 Years of Participation--A Longitudinal Qualitative Study.

In this article we explore women's experiences with 6 years of mammography screening. Regular and repeated mammography screening is promoted as an important tool for disease prevention among women worldwide. The purpose of the present study was to explore how continued participation in screening influences how women perceive screening and breast cancer. We carried out focus groups with 24 screening participants in 2003 and 2009. Our analysis highlights that while women were excited about the examination in 2003, it was perceived as routine in 2009. Waiting for the results became easier over the years, while stress related to receiving the results letter did not diminish. Knowledge of risk factors for breast cancer did not change. Personal risk assessment remained low, though high incidence of cancer among acquaintances suggested high risk for breast cancer among women in general. Analysis of participant experiences suggests that continuous participation in screening has led surveillance medicine to become a part of ordinary life.

Cohort profile: Norwegian Epidemiologic Osteoporosis Studies (NOREPOS).

AIMS: This paper describes the history, purpose, data collection and contributions in the research collaboration Norwegian Osteoporosis Epidemiologic Studies (NOREPOS). METHODS: NOREPOS encompasses almost 85,000 bone mineral density measurements within Cohort of Norway and data on almost 140,000 hip fractures in Norway 1994-2008. Included are anthropometric measurements, blood pressure, lipids and glucose, and 50 standard questions on sociodemographic factors, diseases and risk factors. Blood samples/DNA are stored. The main research question posed in NOREPOS is why hip fracture rates in Norway are the highest in the world. Data on hip fractures 2009-2013 will be added in 2014. RESULTS: Main findings include: Every hour a Norwegian suffers a hip fracture; hip fracture incidence rates declined after 1999; only 16% of patients used anti-osteoporosis drugs 1 year after hip fracture; 25% of patients died within 1 year after the fracture; 12% suffered a new hip fracture within 10 years; rural dwellers had lower hip and forearm fracture incidence than city dwellers; magnesium in tap water may be protective whereas bacterial contamination, cadmium and lead may be harmful to bone health; low serum vitamin D and E levels were associated with higher hip fracture risk; vitamin A was not associated with fracture risk; and abdominal obesity increased the risk of hip fracture when BMI was accounted for. CONCLUSIONS: NOREPOS encompasses a unique source of information for aetiological research, genetic studies as well as for biomarkers of osteoporosis and fractures. Because of the increasing number of elderly people in Europe, hip fractures will continue to pose an international public health and health care challenge.

A prospective population-based cohort study of lactation and cardiovascular disease mortality: the HUNT study.

BACKGROUND: Recent studies suggest that lactation has long-term effects on risk for cardiovascular disease in women, but the effects on cardiovascular mortality are less well known. METHOD: In a Norwegian population-based prospective cohort study, we studied the association of lifetime duration of lactation with cardiovascular mortality in 21,889 women aged 30 to 85 years who attended the second Nord-Trøndelag Health Survey (HUNT2) in 1995-1997. The cohort was followed for mortality through 2010 by a linkage with the Cause of Death Registry. Adjusted hazard ratios (HR) for death from all causes and cardiovascular disease were calculated using Cox regression. RESULTS: During follow-up, 1,246 women died from cardiovascular disease. Parous women younger than 65 years who had never lactated had a higher cardiovascular mortality than the reference group of women who had lactated 24 months or more (HR 2.77, 95% confidence interval [CI]: 1.28, 5.99). There was some evidence of a U-shaped association, where women who reported lactating 7-12 months had a HR of 0.55 (95% CI: 0.27, 1.09). No clear associations were observed among women 65 years or older. CONCLUSIONS: Excess cardiovascular mortality rates were observed among parous women younger than 65 years who had never lactated. These findings support the hypothesis that lactation may have long-term influences on maternal cardiovascular health.

Maternal recall of breastfeeding duration twenty years after delivery.

BACKGROUND: Studies on the health benefits from breastfeeding often rely on maternal recall of breastfeeding. Although short-term maternal recall has been found to be quite accurate, less is known about long-term accuracy. The objective of this study was to assess the accuracy of long-term maternal recall of breastfeeding duration. METHODS: In a prospective study of pregnancy and birth outcome, detailed information on breastfeeding during the child's first year of life was collected from a cohort of Norwegian women who gave birth in 1986-88. Among 374 of the participants, data on breastfeeding initiation and duration were compared to recalled data obtained from mailed questionnaires some 20 years later. Intraclass correlation coefficient (ICC), Bland-Altman plot, and Kappa statistics were used to assess the agreement between the two sources of data. Logistic regression was used to assess predictors of misreporting breastfeeding duration by more than one month. RESULTS: Recorded and recalled breastfeeding duration were strongly correlated (ICC=0.82, p < 0.001). Nearly two thirds of women recalled their breastfeeding to within one month. Recall data showed a modest median overestimation of about 2 weeks. There were no apparent systematic discrepancies between the two sources of information, but recall error was predicted by the age when infants were introduced to another kind of milk. Across categories of breastfeeding, the overall weighted Kappa statistic showed an almost perfect agreement (κ = 0.85, 95% confidence interval [CI] 0.82 - 0.88). CONCLUSION: Breastfeeding duration was recalled quite accurately 20 years after mothers gave birth in a population where breastfeeding is common and its duration long.

Hip fractures in Norway 1999-2008: time trends in total incidence and second hip fracture rates: a NOREPOS study.

Declining incidences of hip fractures are reported from western countries. Norway has among the highest rates in the world. The aim of this study was to investigate trends in total hip fracture rates in Norway between 1999 and 2008 and risk of second hip fractures. All hospitalizations given a hip fracture diagnosis code (International Classification of Diseases (ICD) 9 or ICD 10) (cervical, trochanteric or subtrochanteric) in Norwegian hospitals were retrieved with accompanying surgical procedure codes and additional diagnoses. A total of 93,123 hip fractures were identified between 1999 and 2008 in persons ≥50 years. Annual incidences of hip fractures were calculated and tested for trends. Rates of first and second hip fractures (2006-2008) were compared. The age-standardized total incidence of hip fracture decreased by 13.4 % (95 % confidence interval (CI): 11.0-15.6) in women and 4.8 % (95 % CI: 0.7, 8.7) in men. Age-adjusted rates of second hip fractures did not change in the observation period. In those with a prior hip fracture, the age-standardized risk of a subsequent hip fracture was 2.5-fold (95 % CI: 2.5, 2.6) in women, and 4.6-fold (95 % CI: 4.5, 4.7) in men. Total hip fracture rates declined in both genders during 1999-2008, whereas rates of second hip fractures did not change.

Increased circulating hepatocyte growth factor (HGF): a marker of epithelial ovarian cancer and an indicator of poor prognosis.

OBJECTIVE: Hepatocyte growth factor (HGF) has been described to be increased in different cancers. In the present study we wanted to investigate whether HGF in serum can distinguish between benign and malignant ovarian tumors, and whether serum HGF levels can predict the outcome in patients with ovarian carcinomas. METHODS: We included 123 consecutive patients appointed for laparotomy due to a pelvic mass. Preoperative levels of serum cancer antigen 125 (CA 125), HGF and HGF activator (HGFA) were quantified with immunological methods. We performed immunohistochemical analyses of HGFα, HGFß and the receptor c-Met. Five-year survival of patients with advanced disease (stage III and stage IV) was analyzed with the Kaplan-Meier method. RESULTS: Sixty patients had ovarian carcinomas, 23 borderline tumors, and 40 benign ovarian tumors. Patients with ovarian carcinomas had significantly higher preoperative HGF and CA 125 serum levels than patients with benign ovarian tumors, and borderline tumors. Patients with borderline tumors had significantly higher CA 125 values than benign cases. A combination of CA 125 and HGF increased the specificity in predicting carcinoma. We observed abundant HGFα, HGFß and c-Met expressions in all ovarian tumors. Patients with advanced disease and preoperative serum HGF values ≥2SD above reference value had a shorter disease-free survival than patients with advanced disease and serum HGF <2SD above reference value. CONCLUSIONS: HGF in serum is an indicator of ovarian carcinoma in women with a pelvic mass, and of a poor prognosis in advanced ovarian cancer.

Experiences of recall after mammography screening--a qualitative study.

Women participating in biannual mammography screening for 20 years have a cumulative risk of 20% of being recalled. We conducted a prospective qualitative interview study with eight nonsymptomatic women recalled after mammography screening. These women expressed mixed emotions over being recalled. Information about recall rates and breast cancer risk was seen as alarming, and cancer risk estimates were seen by some as high. The short time between recall and examination was reassuring, but it was also perceived as an indication of malignancy. Despite distress from examinations, most of the women continued to want medical examinations to detect cancer early.

Risk of hip and forearm fracture in subjects with type 2 diabetes mellitus and latent autoimmune diabetes of adults. The HUNT Study, Norway.

Type 1 and type 2 diabetes mellitus incur an increased risk of fracture, with a generally higher risk among individuals with type 1 diabetes. The fracture risk among individuals with latent autoimmune diabetes of adulthood (LADA) is not known. The present cohort study aimed to estimate the risk of hip and forearm fracture among individuals with LADA, alongside type 1 and type 2 diabetes, using data from the second survey of the Trøndelag Health Study (HUNT2) in 1995-97. All inhabitants aged 20 years or older (N = 92,936) were invited to attend, of whom 65,234 (70%) participated. A total of 1972 (3%) reported to have diabetes; 1399 were found to have type 2 diabetes, 144 to have LADA, and 138 to have type 1 diabetes. All participants were followed prospectively with respect to hip- and forearm fractures by linkage to the local fracture registry. During a median follow-up of 16.2 years, 2695 persons with hip fractures and 3533 persons with forearm fractures were identified. There was an increased risk of hip fracture in women with type 2 diabetes (HR = 1.51, 95% CI 1.24-1.85) and LADA (HR = 2.15, 95% CI 1.25-3.72), whereas women with type 1 diabetes did not have a significantly increased risk (HR = 2.13, 95% CI 0.89-5.14). Among men, only LADA was associated with an increased risk of hip fracture (HR = 2.69, 95% CI 1.34-5.41). There was no statistically significant association between any of the diabetes types and forearm fracture. In women with type 2 diabetes, the highest risks of hip fracture were observed among those with highest HbA1c level at baseline, longest time since diagnosis, and most visual and movement impairment. We found that individuals with LADA had an increased risk of hip fracture similar to that previously reported for individuals with type 1 diabetes, and no increased risk of forearm fracture.

MEPE loss-of-function variant associates with decreased bone mineral density and increased fracture risk.

A major challenge in genetic association studies is that most associated variants fall in the non-coding part of the human genome. We searched for variants associated with bone mineral density (BMD) after enriching the discovery cohort for loss-of-function (LoF) mutations by sequencing a subset of the Nord-Trøndelag Health Study, followed by imputation in the remaining sample (N = 19,705), and identified ten known BMD loci. However, one previously unreported variant, LoF mutation in MEPE, p.(Lys70IlefsTer26, minor allele frequency [MAF] = 0.8%), was associated with decreased ultradistal forearm BMD (P-value = 2.1 × 10-18), and increased osteoporosis (P-value = 4.2 × 10-5) and fracture risk (P-value = 1.6 × 10-5). The MEPE LoF association with BMD and fractures was further evaluated in 279,435 UK (MAF = 0.05%, heel bone estimated BMD P-value = 1.2 × 10-16, any fracture P-value = 0.05) and 375,984 Icelandic samples (MAF = 0.03%, arm BMD P-value = 0.12, forearm fracture P-value = 0.005). Screening for the MEPE LoF mutations before adulthood could potentially prevent osteoporosis and fractures due to the lifelong effect on BMD observed in the study. A key implication for precision medicine is that high-impact functional variants missing from the publicly available cosmopolitan panels could be clinically more relevant than polygenic risk scores.

The ERAP2 gene is associated with preeclampsia in Australian and Norwegian populations.

Preeclampsia is a heritable pregnancy disorder that presents new onset hypertension and proteinuria. We have previously reported genetic linkage to preeclampsia on chromosomes 2q, 5q and 13q in an Australian/New Zealand (Aust/NZ) familial cohort. This current study centered on identifying the susceptibility gene(s) at the 5q locus. We first prioritized candidate genes using a bioinformatic tool designed for this purpose. We then selected a panel of known SNPs within ten prioritized genes and genotyped them in an extended set of the Aust/NZ families and in a very large, independent Norwegian case/control cohort (1,139 cases, 2,269 controls). In the Aust/NZ cohort we identified evidence of a genetic association for the endoplasmic reticulum aminopeptidase 1 (ERAP1) gene (rs3734016, P (uncorr) = 0.009) and for the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene (rs2549782, P (uncorr) = 0.004). In the Norwegian cohort we identified evidence of a genetic association for ERAP1 (rs34750, P (uncorr) = 0.011) and for ERAP2 (rs17408150, P (uncorr) = 0.009). The ERAP2 SNPs in both cohorts remained statistically significant (rs2549782, P (corr) = 0.018; rs17408150, P (corr) = 0.039) after corrections at an experiment-wide level. The ERAP1 and ERAP2 genes encode enzymes that are reported to play a role in blood pressure regulation and essential hypertension in addition to innate immune and inflammatory responses. Perturbations within vascular, immunological and inflammatory pathways constitute important physiological mechanisms in preeclampsia pathogenesis. We herein report a novel preeclampsia risk locus, ERAP2, in a region of known genetic linkage to this pregnancy-specific disorder.

Urban-Rural Differences in Hip Fracture Mortality: A Nationwide NOREPOS Study.

Higher hip fracture incidence in urban than in rural areas has been demonstrated, but urban-rural differences in posthip fracture mortality have been less investigated, and the results are disparate. Hence, the aims of the present register-based cohort study were to examine possible urban-rural differences in short- and long-term mortality in Norwegian hip fracture patients and their potential associations with sociodemographic variables, and to investigate possible urban-rural differences in excess mortality in hip fracture patients compared with the general population. Data were provided from the NOREPOS hip fracture database, the 2001 Population and Housing Census, and the National Registry. The urbanization degree in each municipality was determined by the proportion of inhabitants living in densely populated areas (rural: <1/3, semirural: 1/3 to 2/3, and urban: >2/3). Age-adjusted mortality rates and standardized mortality ratios were calculated for hip fracture patients living in rural, semirural, and urban municipalities. A flexible parametric model was used to estimate age-adjusted average and time-varying HRs by category of urbanization with the rural category as reference. Among 96,693 hip fracture patients, urban residents had higher mortality than their rural-dwelling counterparts. The HR of mortality in urban compared with rural areas peaked during the first 1 to 2 years postfracture with a maximum HR of 1.20 (95% CI, 1.10 to 1.30) in men and 1.15 (95% CI, 1.08 to 1.21) in women. The differences were significant during approximately 5 years after fracture. Adjusting for sociodemographic variables did not substantially change the results. However, absolute 30-day mortality was not significantly different between urban and rural residents, suggesting that health-care quality immediately postfracture does not vary by urbanization. The novel findings of a higher long-term mortality in urban hip fracture patients might reflect disparities in health status or lifestyle, differences in posthip fracture health care or rehabilitation, or a combination of several factors. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Childhood cod liver oil consumption and bone mineral density in a population-based cohort of peri- and postmenopausal women: the Nord-Trondelag Health Study.

Use of cod liver oil, which is rich in vitamins A and D, is traditionally recommended during the fall and winter months as a protective measure against vitamin D deficiency in several countries. It is not known whether childhood cod liver oil intake is related to variations in bone mineral density (BMD) or fractures in adult life. In 2001, a total of 3,052 Norway women aged 50-70 years had forearm BMD measured in a substudy of the population-based Nord-Trøndelag Health Study. Women reporting no childhood cod liver oil intake had statistically significantly higher BMD than those with any ingestion of cod liver oil. The odds ratio for low BMD (>1 standard deviation below age-specific mean) in women reporting cod liver oil intake throughout the year as compared with women with no intake was 2.3 (95% confidence interval: 1.4, 3.9), adjusted for body mass index, smoking, menopausal status, estrogen use, and current milk consumption. There were indications of a negative dose-response effect of childhood cod liver oil intake on bone. Although the vitamin A content of commercial cod liver oil was recently reduced by 75% in Norway, the past high concentration remains a possible explanation for the observed negative association between childhood cod liver oil intake and forearm BMD.

Genetic association of preeclampsia to the inflammatory response gene SEPS1.

OBJECTIVE: The objective of the study was to test for a genetic association between the G-105A promoter polymorphism of the inflammatory mediator Selenoprotein S (SEPS1) and preeclampsia. STUDY DESIGN: A retrospective study in a large Norwegian case-control cohort compared maternal genotype and allele frequencies of the SEPS1 g.-105G>A polymorphism genotyped by SNPlex assay in preeclamptic (n = 1139) and control (n = 2269) women. Statistical significance was determined by chi2 and multivariate regression analyses. RESULTS: Women with preeclampsia were 1.34 times more likely to have the GA or AA genotype (P = .0039; 95% confidence interval [CI] 1.09 to 1.64) and 1.22 times more likely to carry the A allele (P = .023; odds ratio, 1.22; 95% CI, 1.02 to 1.46). CONCLUSION: The A allele of the SEPS1-105G>A polymorphism is a significant risk factor for preeclampsia in this population.

Brittle bones, pain and fractures--lay constructions of osteoporosis among Norwegian women attending the Nord-Trøndelag Health Study (HUNT).

Osteoporosis has been labelled the disease of the 21st century. Over the past couple of centuries there have been various notions of this disease in medicine. In the present medical discourse, the emphasis is on prevention rather than treatment, making osteoporosis into a major risk factor for bone fractures. In Norway, osteoporosis is a particularly prevalent condition, leading to bone mass measurements being included in several large health surveys. In a follow-up study of the second round of the Nord-Trøndelag Health Study (HUNT), women aged 55-75 years were invited to participate in focus groups to talk about their experiences in relation to their bone density measurements. Findings from these focus groups show that osteoporosis is perceived as a disease characterized by brittle bones, pain and fractures. The physical appearance of a hunchbacked old woman is a dominant way of portraying the disease. It is mainly perceived as prevalent among women, but evidence that men can get it is provided through the example of a famous male athlete who became osteoporotic. Causal explanations for the disease are dominated by culturally shaped anecdotal evidence wherein medical knowledge has been included. Limits to lay constructions of osteoporosis based on such evidence are discussed. Talking about osteoporosis across generations the women applied different explanations for the condition over time. In doing so, they also showed that they have adopted the morality of the new public health where the individual has control over her health through self-governance. Whereas this was no option for their grandmothers, their grandchildren's generation was seen as one failing to meet their obligations to become healthy citizens. The lay construction of osteoporosis can thus be seen as one that has developed from a situation where osteoporotic persons were perceived as victims of harsh circumstances to one of individual responsibility.

Effect of inhaled corticosteroids on forearm bone mineral density: the HUNT study, Norway.

PURPOSE: To study the effect of inhaled corticosteroid (ICS) on bone mineral density (BMD) in an observational longitudinal study. METHODS: In 1995-97, as part of the Nord-Trøndelag Health Study, Norway, 10,941 subjects aged 20 yr or more, either reporting asthma diagnosis/asthma-related symptoms or randomly selected, were interviewed, underwent spirometry and had their forearm BMD assessed. Among these, 4705 persons were invited to follow-up interview and bone densitometry in 2001; a total of 2848 subjects were eligible for analyses. RESULTS: Use of corticosteroids for respiratory diseases was reported by 1262 subjects, and 528 subjects had used ICS at both baseline and follow-up. The yearly loss of adjusted forearm distal BMD was higher in those reporting use of ICS at both baseline and follow-up compared to subjects without respiratory symptoms. In women the figures were 3.14 versus 2.26 mg/cm2, whilst in men they were 3.76 versus 1.92 mg/cm2 (both p<0.01). No significant association was found between loss of BMD and neither daily dose nor duration of ICS use. Reduced lung function (forced expiratory flow in 1s) was an independent risk factor for increased bone loss in both sexes. CONCLUSIONS: ICS users had greater bone loss at the forearm compared to ICS naive persons, but no significant dose-response effect between ICS and BMD was found. Residual confounding by disease severity cannot be ruled out, but even in case of an ICS causal effect, this should have minor clinical significance in most patients using low to moderate doses of ICS.

Ovulation Prevalence in Women with Spontaneous Normal-Length Menstrual Cycles - A Population-Based Cohort from HUNT3, Norway.

BACKGROUND: Ovulatory menstrual cycles are essential for women's fertility and needed to prevent bone loss. There is a medical/cultural expectation that clinically normal menstrual cycles are inevitably ovulatory. Currently within the general population it is unknown the proportion of regular, normal-length menstrual cycles that are ovulatory. Thus, the objective of this study was to determine the population point prevalence of ovulation in premenopausal, normally menstruating women. The null hypothesis was that such cycles are ovulatory. METHODS: This is a single-cycle, cross-sectional, population-based study-a sub-study of the HUNT3 health study in the semi-rural county (Nord Trøndelag) in mid-Norway. Participants included >3,700 spontaneously (no hormonal contraception) menstruating women, primarily Caucasian, ages 20-49.9 from that county. Participation rate was 51.9%. All reported the date previous flow started. A single, random serum progesterone level was considered ovulatory if ≥9.54 nmol/L on cycle days 14 to -3 days before usual cycle length (CL). RESULTS: Ovulation was assessed in 3,168 women mean age 41.7 (interquartile range, [IQR] 36.8 to 45.5), cycle length 28 days (d) (IQR 28 to 28) and body mass index (BMI) 26.3 kg/m2 (95% CI 26.1 to 26.4). Parity was 95.6%, 30% smoked, 61.3% exercised regularly and 18% were obese. 1,545 women with a serum progesterone level on cycle days 14 to -3 were presumed to be in the luteal phase. Of these, 63.3% of women had an ovulatory cycle (n = 978) and 37% (n = 567) were anovulatory. Women with/ without ovulation did not differ in age, BMI, cycle day, menarche age, cigarette use, physical activity, % obesity or self-reported health. There were minimal differences in parity (96.7% vs. 94.5%, P = 0.04) and major differences in progesterone level (24.5 vs. 3.8 nmol/L, P = 0.001). CONCLUSION: Anovulation in a random population occurs in over a third of clinically normal menstrual cycles.