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Background: Maternal hormonal contraception use has been associated with childhood leukemia risk. However, studies are few and often based on self-reported information., Methods: Using registry data from Denmark, Norway, and Sweden, we identified 3,183,316 children (born 1996-2018) and followed them from birth until leukemia diagnosis, censoring (death, emigration, other cancer, 20th birthday) or study closure (December 31st, 2017, 2018 or 2020). We estimated hazard ratios (HRs) and 95 % confidence intervals (CIs) for childhood leukemia (any, lymphoid and non-lymphoid) associated with maternal recent use (≤ 3 months before or during pregnancy) or previous use (before recent use) of hormonal contraception overall and by type, compared to no use., Results: During 29,455,528 person-years, 1701 children developed leukemia (no use: 518, previous use: 974, recent use: 209). Maternal recent use of hormonal contraception was associated with an increased leukemia risk in children (HR 1.22, 95 % CI 1.04-1.44; incidence rate per 1,000,000 person-years [IR] 65), compared to no use (IR 53). The association was strongest for non-lymphoid leukemia (HR 1.69, 95 % CI 1.20-2.37) and mainly driven by the oral combined products, both for any leukemia (HR 1.29, 95 % CI 1.05-1.59) and non-lymphoid leukemia (HR 1.75, 95 % CI 1.17-2.62). Additionally, non-lymphoid leukemia was associated with recent use of the non-oral progestin-only products (HR 2.10, 95 % CI 1.28-3.44)., Conclusions: Although the absolute risk was low, maternal hormonal contraception use up to or during pregnancy was associated with an increased childhood leukemia risk, particularly non-lymphoid leukemia, and mainly driven by oral combined and non-oral progestin-only products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Potential regional differences in cancer incidence and survival would demand targeted interventions to decrease cancer related death., Methods: This descriptive cohort study provides an overview of regional cancer incidence and relative survival (RS) in Denmark during 2007-2021. National cancer incidence and RS estimates were calculated similar to the official statistics for the Danish Cancer Registry. Specifically, we estimated age-standardized (World) cancer incidence rates (ASR), and RS in 3-year periods by sex, and the five regions of Denmark (i.e., Region of Northern Denmark, Central Denmark Region, Region of Southern Denmark, Region Zealand, and Capital Region)., Results: We identified 578,107 incident cancers in Denmark during 2007-2021, of which 124 123 were diagnosed in 2019-2021. Small fluctuations were seen in ASR for cancer overall in all five regions during 2007-2018, followed by decreasing trends in 2019-2021. Men exhibited higher ASRs than women. Consistent improvements in 1- and 5-year RS were seen during the study period in all regions. However, for patients diagnosed in 2019-2021, the 5-year RS levelled off. These patients experienced 1-year RS of 83 % among men and 84 % among women, and the 5-year RS was also similar between sexes (men: 67 %, women: 70 %, overall: 68 %). Region Zealand generally presented lower RS estimates for both sexes combined., Conclusion: Cancer survival improved between 2007 and 2021 in all Danish regions for both sexes. However, the improvements in cancer survival appeared to have levelled off in the most recent period, 2019-2021. For both sexes, the lowest survival was suggested for Region Zealand., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Given that the evidence regarding the link between antidepressant use and ovarian cancer risk is equivocal, we investigated this research question by conducting two nationwide nested case-control studies among the Danish and Swedish populations., Methods: Altogether, 14,121 women with epithelial ovarian cancer (30-84 years old) (Denmark: 8976 diagnosed 2000-2019, Sweden: 5145 diagnosed 2010-2018) were randomly age-matched with 564,840 female controls (359,040 from Denmark, and 205,800 from Sweden) using risk set sampling. We used conditional logistic regression to estimate odds ratios (OR) with 95 % confidence intervals (CI) and combined the estimates based on the fixed-effect assumption. We also investigated potential effect modification by well-established risk factors for ovarian cancer., Results: Antidepressant use was associated with an overall reduced risk of ovarian cancer (OR = 0.92, 95%CI: 0.88-0.96), and that reduction was more pronounced in postmenopausal women and long-term users. The effect was most pronounced for serous ovarian tumors (OR = 0.90, 95%CI: 0.86-0.95) but was also observed in other subtypes, although not statistically significant. Among different types of antidepressants, selective serotonin reuptake inhibitors in general and citalopram in particular exhibited a noteworthy reduction in ovarian cancer risk (OR = 0.89, 95%CI: 0.82-0.96). Additionally, use of oral contraceptives and hormone replacement therapy individually modified the association between antidepressant use and ovarian cancer risk., Conclusions: Use of an antidepressant was associated with a slight, but statistically significant, decrease in ovarian cancer risk. Given the morbidity and mortality associated with ovarian cancer, and increasing use of antidepressants, these findings may be of significance to cancer prevention and should be studied in more detail mechanistically., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Use of menopausal hormone therapy (MHT) prior to an epithelial ovarian cancer (EOC) diagnosis has been suggested to be associated with improved survival. In a recent nationwide cohort study, we found that prediagnostic long-term MHT use, especially estrogen therapy (ET), was associated with improved long-term survival in women with nonlocalized EOC. Our aim was to investigate the influence of prediagnostic MHT use on long-term survival among women with localized EOC in the same nationwide study. Our study cohort comprised all women aged 50 years or older with an EOC diagnosis in Denmark 2000-2014 (n = 2097) identified from the Extreme study. We collected information on usage of systemic ET and estrogen plus progestin therapy (EPT) from the Danish National Prescription Registry. By using pseudo-values, 5- and 10-year absolute and relative survival probabilities were estimated with 95% confidence intervals (CIs) while adjusting for histology, comorbidity, and income. Relative survival probabilities >1 indicate better survival. The 5-year absolute survival probabilities were 61% and 56%, respectively, among women who were nonusers and users of prediagnostic MHT, whereas these numbers were 46% and 41%, respectively, regarding 10-year survival. Use of MHT was not significantly associated with an improved 5- or 10-year survival in women with localized EOC (5-year relative survival probability = 0.95, 95% CI: 0.89-1.02; 10-year relative survival probability = 0.92, 95% CI: 0.84-1.02). Similar findings were seen for systemic ET or EPT use. Our findings do not suggest a positive benefit from prediagnostic MHT use on long-term survival of localized EOC., (© 2024 UICC.)

Background and Purpose: Stage at cancer diagnosis is an important predictor of cancer survival. TNM stage is constructed for anatomic solid cancer diagnoses from tumor size (T), nodal spread (N) and distant metastasis (M) and categorized in groups 0-I, II, II and IV. TNM stage is imperative in cancer diagnosis, management and control, and of high value in cancer surveillance, for example, monitoring of stage distributions. This study yields an overview of TNM availability and trends in stage distribution in the Nordic countries for future use in monitoring and epidemiologic studies., Material and Methods: TNM information was acquired from the cancer registries in Denmark, Norway, Sweden, and Iceland during 2004-2016 for 26 cancer sites in the three former countries and four in Iceland. We studied availability, comparability, and distribution of TNM stage in three periods: 2004-2008, 2009-2013, and 2014-2016, applying a previously validated algorithm of 'N0M0 for NXMX'. For cancers of colon, rectum, lung, breast, and kidney, we examined TNM stage-specific 1-year relative survival to evaluate the quality in registration of TNM between countries., Results: Denmark, Sweden, and Iceland exhibited available TNM stage proportions of 75-95% while proportions were lower in Norway. Proportions increased in Sweden over time but decreased in Denmark. One-year relative survival differed substantially more between TNM stages than between countries emphasizing that TNM stage is an important predictor for survival and that stage recording is performed similarly in the Nordic countries., Interpretation: Assessment and registration of TNM stage is an imperative tool in evaluations of trends in cancer survival between the Nordic countries.

Background: The survival in patients diagnosed with cutaneous malignant melanoma (CMM) has improved in the Nordic countries in the last decades. It is of interest to know if these improvements are observed in all ages and for both women and men., Methods: Patients diagnosed with CMM in the Nordic countries in 1990-2016 were identified in the NORDCAN database. Flexible parametric relative survival models were fitted, except for Iceland where a non-parametric Pohar-Perme approach was used. A range of survival metrics were estimated by sex, both age-standardised and age-specific., Results: The 5-year relative survival improved in all countries, in both women and men and across age. While the improvement was more pronounced in men, women still had a higher survival at the end of the study period. The survival was generally high, with age-standardised estimates of 5-year relative survival towards the end of the study period ranging from 85% in Icelandic men to 95% in Danish women. The age-standardised and reference-adjusted 5-year crude probability of death due to CMM ranged from 5% in Danish and Swedish women to 13% in Icelandic men., Conclusion: Although survival following CMM was relatively high in the Nordic countries in 1990, continued improvements in survival were observed throughout the study period in both women and men and across age., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could appear to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Use of estrogen-containing menopausal hormone therapy has been shown to influence the risk of central nervous system (CNS) tumors. However, it is unknown how the progestin-component affects the risk and whether continuous versus cyclic treatment regimens influence the risk differently., Methods and Findings: Nested case-control studies within a nationwide cohort of Danish women followed for 19 years from 2000 to 2018. The cohort comprised 789,901 women aged 50 to 60 years during follow-up, without prior CNS tumor diagnosis, cancer, or contraindication for treatment with menopausal hormone therapy. Information on cumulative exposure to female hormonal drugs was based on filled prescriptions. Statistical analysis included educational level, use of antihistamines, and use of anti-asthma drugs as covariates. During follow-up, 1,595 women were diagnosed with meningioma and 1,167 with glioma. The median (first-third quartile) follow-up time of individuals in the full cohort was 10.8 years (5.0 years to 17.5 years). Compared to never-use, exposure to estrogen-progestin or progestin-only were both associated with increased risk of meningioma, hazard ratio (HR) 1.21; (95% confidence interval (CI) [1.06, 1.37] p = 0.005) and HR 1.28; (95% CI [1.05, 1.54] p = 0.012), respectively. Corresponding HRs for glioma were HR 1.00; (95% CI [0.86, 1.16] p = 0.982) and HR 1.20; (95% CI [0.95, 1.51] p = 0.117). Continuous estrogen-progestin exhibited higher HR of meningioma 1.34; (95% CI [1.08, 1.66] p = 0.008) than cyclic treatment 1.13; (95% CI [0.94, 1.34] p = 0.185). Previous use of estrogen-progestin 5 to 10 years prior to diagnosis yielded the strongest association with meningioma, HR 1.26; (95% CI [1.01, 1.57] p = 0.044), whereas current/recent use of progestin-only yielded the highest HRs for both meningioma 1.64; (95% CI [0.90, 2.98] p = 0.104) and glioma 1.83; (95% CI [0.98, 3.41] p = 0.057). Being an observational study, residual confounding could occur., Conclusions: Use of continuous, but not cyclic estrogen-progestin was associated with increased meningioma risk. There was no evidence of increased glioma risk with estrogen-progestin use. Use of progestin-only was associated with increased risk of meningioma and potentially glioma. Further studies are warranted to evaluate our findings and investigate the influence of long-term progestin-only regimens on CNS tumor risk., Competing Interests: LSM reports receiving grants from Health Insurance ”Denmark”, The Danish Cancer Society’s Scientific Committee, and Novo Nordisk for research unrelated to the present study. LSM reports being Vice Chair of Danish Society for PharmacoEpidemiology (DSFE) and representative for Nordic PharmacoEpidemiological Network (NorPen). CTP reports receiving grants from Bayer and Novo Nordisk for research unrelated to the present study. NP, AM, and SF declare no competing interests., (Copyright: © 2023 Pourhadi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To assess the association between use of menopausal hormone therapy and development of dementia according to type of hormone treatment, duration of use, and age at usage., Design: Nationwide, nested case-control study., Setting: Denmark through national registries., Participants: 5589 incident cases of dementia and 55 890 age matched controls were identified between 2000 and 2018 from a population of all Danish women aged 50-60 years in 2000 with no history of dementia or contraindications for use of menopausal hormone therapy., Main Outcome Measures: Adjusted hazard ratios with 95% confidence intervals for all cause dementia defined by a first time diagnosis or first time use of dementia specific medication., Results: Compared with people who had never used treatment, people who had received oestrogen-progestogen therapy had an increased rate of all cause dementia (hazard ratio 1.24 (95% confidence interval 1.17 to 1.33)). Increasing durations of use yielded higher hazard ratios, ranging from 1.21 (1.09 to 1.35) for one year or less of use to 1.74 (1.45 to 2.10) for more than 12 years of use. Oestrogen-progestogen therapy was positively associated with development of dementia for both continuous (1.31 (1.18 to 1.46)) and cyclic (1.24 (1.13 to 1.35)) regimens. Associations persisted in women who received treatment at the age 55 years or younger (1.24 (1.11 to 1.40)). Findings persisted when restricted to late onset dementia (1.21 (1.12 to 1.30)) and Alzheimer's disease (1.22 (1.07 to 1.39))., Conclusions: Menopausal hormone therapy was positively associated with development of all cause dementia and Alzheimer's disease, even in women who received treatment at the age of 55 years or younger. The increased rate of dementia was similar between continuous and cyclic treatment. Further studies are warranted to determine whether these findings represent an actual effect of menopausal hormone therapy on dementia risk, or whether they reflect an underlying predisposition in women in need of these treatments., Competing Interests: Declarations of interest: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years. NP, EAH, and AM declare no competing interests. LSM reports receiving grants from health insurance “Danmark”, The Danish Cancer Society’s Scientific Committee, and Novo Nordisk for research unrelated to the present study. LSM reports being Vice Chair of Danish Society for PharmacoEpidemiology and representative for Nordic PharmacoEpidemiological Network. CT-P reports receiving grants from Bayer and Novo Nordisk for research unrelated to the present study., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: A recent overview of cancer survival trends 1990-2016 in the Nordic countries reported continued improvements in age-standardized breast cancer survival among women. The aim was to estimate age-specific survival trends over calendar time, including life-years lost, to evaluate if improvements have benefited patients across all ages in the Nordic countries., Methods: Data on breast cancers diagnosed 1990-2016 in Denmark, Finland, Iceland, Norway, and Sweden were obtained from the NORDCAN database. Age-standardized and age-specific relative survival (RS) was estimated using flexible parametric models, as was reference-adjusted crude probabilities of death and life-years lost., Results: Age-standardized period estimates of 5-year RS in women diagnosed with breast cancer ranged from 87% to 90% and 10-year RS from 74% to 85%. Ten-year RS increased with 15-18 percentage points from 1990 to 2016, except in Sweden (+9 percentage points) which had the highest survival in 1990. The largest improvements were observed in Denmark, where a previous survival disadvantage diminished. Most recent 5-year crude probabilities of cancer death ranged from 9% (Finland, Sweden) to 12% (Denmark, Iceland), and life-years lost from 3.3 years (Finland) to 4.6 years (Denmark). Although survival improvements were consistent across different ages, women aged ≥70 years had the lowest RS in all countries. Period estimates of 5-year RS were 94-95% in age 55 years and 84-89% in age 75 years, while 10-year RS were 88-91% in age 55 years and 69-84% in age 75 years. Women aged 40 years lost on average 11.0-13.8 years, while women lost 3.8-6.0 years if aged 55 and 1.9-3.5 years if aged 75 years., Conclusions: Survival for Nordic women with breast cancer improved from 1990 to 2016 in all age groups, albeit with larger country variation among older women where survival was also lower. Women over 70 years of age have not had the same survival improvement as women of younger age.

Background: Survival of patients with colon and rectal cancer has improved in all Nordic countries during the past decades. The aim of this study was to further assess survival trends in patients with colon and rectal cancer in the Nordic countries by age at diagnosis and to present additional survival measures., Methods: Data on colon and rectal cancer cases diagnosed in the Nordic countries between 1990 and 2016 were obtained from the NORDCAN database. Relative survival was estimated using flexible parametric models. Both age-standardized and age-specific measures for women and men were estimated from the models, as well as reference-adjusted crude probabilities of death and life-years lost., Results: The five-year age-standardized relative survival of colon and rectal cancer patients continued to improve for women and men in all Nordic countries, from around 50% in 1990 to about 70% at the end of the study period. In general, survival was similar across age and sex. The largest improvement was seen for Danish men and women with rectal cancer, from 41% to 69% and from 43% to 71%, respectively. The age-standardized and reference-adjusted five-year crude probability of death in colon cancer ranged from 30% to 36% across countries, and for rectal cancer from 20% to 33%. The average number of age-standardized and reference-adjusted life-years lost ranged between six and nine years., Conclusion: There were substantial improvements in colon and rectal cancer survival in all Nordic countries 1990-2016. Of special note is that the previously observed survival disadvantage in Denmark is no longer present., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The severity of the COVID-19 pandemic and subsequent mitigation strategies have varied across the Nordic countries. In a joint Nordic population-based effort, we compared patterns of new cancer cases and notifications between the Nordic countries during 2020. We used pathology notifications to cancer registries in Denmark, the Faroe Islands, Finland, Iceland, Norway and Sweden to determine monthly numbers of pathology notifications of malignant and in situ tumours from January to December 2020 compared to 2019 (2017-2019 for Iceland and the Faroe Islands). We compared new cancer cases per month based on unique individuals with pathology notifications. In April and May 2020, the numbers of new malignant cases declined in all Nordic countries, except the Faroe Islands, compared to previous year(s). The largest reduction was observed in Sweden (May: -31.2%, 95% CI -33.9, -28.3), followed by significant declines in Finland, Denmark and Norway, and a nonsignificant decline in Iceland. In Denmark, Norway, Sweden and Finland the reporting rates during the second half of 2020 rose to almost the same level as in 2019. However, in Sweden and Finland, the increase did not compensate for the spring decline (annual reduction -6.2% and -3.6%, respectively). Overall, similar patterns were observed for in situ tumours. The COVID-19 pandemic led to a decline in rates of new cancer cases in Sweden, Finland, Denmark and Norway, with the most pronounced reduction in Sweden. Possible explanations include the severity of the pandemic, temporary halting of screening activities and changes in healthcare seeking behaviour., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Importance: The incidence of central nervous system (CNS) tumors in children appears to be increasing, yet few risk factors are established. There is limited information regarding whether maternal hormonal contraception use increases this risk., Objective: To examine the association between maternal hormonal contraception use and CNS tumors in children (<20 years)., Design, Setting, and Participants: In this nationwide cohort study based on population-based registry data, 1 185 063 children born in Denmark between January 1, 1996, and December 31, 2014, were followed up for a diagnosis of a CNS tumor (final follow-up on December 31, 2018)., Exposures: Maternal hormonal contraception use was analyzed according to any use, regimen (combined/progestin only), and route of administration (oral/nonoral), categorized as recent use (≤3 months before start and during pregnancy), previous use (>3 months before start of pregnancy), and no use. For injections, implants, and intrauterine devices that are used for a different time period, the categorization was appropriately altered., Main Outcomes and Measures: Hazard ratio (HR) and incidence rate difference (IRD) of CNS tumors diagnosed at younger than 20 years., Results: After 15 335 990 person-years of follow-up (mean follow-up, 12.9 years), 725 children were diagnosed with a CNS tumor. The mean age at diagnosis was 7 years, and 342 (47.2%) of the diagnosed children were female. The adjusted incidence rate of CNS tumors per 100 000 person-years was 5.0 for children born to mothers with recent hormonal contraception use (n = 136 022), 4.5 for children born to mothers with previous use (n = 778 843), and 5.3 for children born to mothers with no use (n = 270 198). The corresponding HRs were 0.95 ([95% CI, 0.74-1.23]; 84 children with CNS tumors; IRD, -0.3 [95% CI, -1.6 to 1.0]) for recent use and 0.86 ([95% CI, 0.72-1.02]; 421 children with CNS tumors; IRD, -0.8 [95% CI, -1.7 to 0.0]) for previous use, compared with no use. No statistically significant associations were found for recent or previous use of oral combined, nonoral combined, oral progestin only, or nonoral products compared with no use of hormonal contraception., Conclusions and Relevance: Among Danish children, there was no statistically significant association between any maternal hormonal contraception use and CNS tumor risk.

Study Question: Is maternal use of hormonal contraception associated with the development of epilepsy in the offspring?, Summary Answer: We found that maternal use of hormonal contraception was associated with a slightly increased risk of epilepsy in the offspring., What Is Known Already: Foetal exposure to exogenous hormones has been associated with changes in brain development. However, little is known about maternal hormonal contraception use and development of epilepsy in the offspring., Study Design, Size, Duration: A nationwide cohort of all live born children born in Denmark between 1 January 1998 and 31 December 2014, was followed from day 29 after birth for epilepsy (first diagnosis of epilepsy or first redeemed prescription for anti-epileptic medication) to censoring (emigration, death) or 31 December 2015, whichever occurred first., Participants/materials, Setting, Methods: Diagnoses of epilepsy were obtained from the National Patient Registry. The Danish National Prescription Registry supplied information on redeemed prescriptions for hormonal contraception and anti-epileptic medication. Maternal hormonal contraception use was categorized as never use (reference group), previous use (prescriptions redeemed >3 months before pregnancy start) and recent use (prescriptions redeemed ≤3 months before or during pregnancy)., Main Results and the Role of Chance: The data show that 17 585 children developed epilepsy during a median follow-up of 9.2 years (9 732 635 person-years). The hazard ratio (HR) for epilepsy was 1.07 (95% CI 1.02-1.13) in children of mothers who had used any type of hormonal contraception recently, compared with children of mothers who had not used hormonal contraception. The HR was similar for recent use of oral combined products, while the HRs for recent or previous use of non-oral combined products were 1.32 (95% CI 0.98-1.77) and 1.16 (95% CI 1.02-1.32), respectively. For non-oral progestin-only products, the HRs were 1.19 (95% CI 1.04-1.38) and 1.53 (95% CI 1.31-1.80), respectively, for recent and previous use., Limitations, Reasons for Caution: There may be some misclassification of maternal hormonal contraception use, as some women may not have used the redeemed prescriptions or used them at a different point in time; potentially leading to an attenuation of the estimates. In addition, although we were able to account for known risk factors for epilepsy, unknown or residual confounding cannot be ruled out., Wider Implications of the Findings: Our findings are based on nationwide population-based data and can therefore be applied to other similar populations. However, as this is the first study in this field, further studies are needed to confirm our findings., Study Funding/competing Interest(s): No specific funding was obtained for this study, which was supported by internal funding at the Unit of Virus, Lifestyle and Genes. All authors report no conflicts of interest., Trial Registration Number: N/A., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Differences in cancer survival between the Nordic countries have previously been reported. The aim of this study was to examine whether these differences in outcome remain, based on updated information from five national cancer registers., Materials and Methods: The data used for the analysis was from the NORDCAN database focusing on nine common cancers diagnosed 1990-2016 in Denmark, Finland, Iceland, Norway and Sweden with maximum follow-up through 2017. Relative survival (RS) was estimated at 1 and 5 years using flexible parametric RS models, and percentage point differences between the earliest and latest years available were calculated., Results: A consistent improvement in both 1- and 5-year RS was found for most studied sites across all countries. Previously observed differences between the countries have been attenuated. The improvements were particularly pronounced in Denmark that now has cancer survival similar to the other Nordic countries., Conclusion: The reasons for the observed improvements in cancer survival are likely multifactorial, including earlier diagnosis, improved treatment options, implementation of national cancer plans, uniform national cancer care guidelines and standardized patient pathways. The previous survival disadvantage in Denmark is no longer present for most sites. Continuous monitoring of cancer survival is of importance to assess the impact of changes in policies and the effectiveness of health care systems.

Although maternal use of hormones has been suspected of increasing the risk for childhood attention-deficit/hyperactivity disorder (ADHD), no study has examined hormonal contraception use in this context. We examined the association between maternal hormonal contraception use before or during pregnancy and ADHD risk in children. This nationwide population-based cohort study included 1,056,846 children born in Denmark between 1998 and 2014. Prescriptions for hormonal contraceptives redeemed by the mother was categorized as: no use, previous use (> 3 months before pregnancy), and recent use (≤ 3 months before or during pregnancy). Children were followed for ADHD, from birth until 31 December 2015. Cox proportional hazard models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). During 9,819,565 person-years of follow-up (median: 9.2), ADHD was diagnosed or a prescription for ADHD medication redeemed for 23,380 children (2.2%). The adjusted HR for ADHD was higher in children of mothers who had previously (HR 1.23; 95% CI 1.18-1.28) or recently (HR 1.30; 95% CI 1.24-1.37) used hormonal contraception than in those of mothers with no use. The highest estimates were seen for use of non-oral progestin products with HRs of 1.90 (95% CI 1.59-2.26) for previous use, 2.23 (95% CI 1.96-2.54) for recent use, and 3.10 (95% CI 1.62-5.91) for use during pregnancy. Maternal use of hormonal contraception was associated with an increased risk for ADHD in the offspring; more pronounced for non-oral progestin-only than other products.

Objectives: To investigate the influence of RA or preclinical RA on the risk of spontaneous abortion (SA) while taking age and duration of RA into consideration., Methods: By linkage of data from Danish national registries, we established a nationwide cohort of pregnancies in Denmark from 1 January 1977 to 31 December 2014. We used multiple logistic regression to estimate; odds ratios (OR) for SA in women with RA or preclinical RA, compared with women without, and OR for SA by maternal age in women with RA or preclinical RA., Results: A total of 2 612 529 pregnancies were included. Women aged <35 years diagnosed with RA <5 years before pregnancy had an increased risk of SA (OR = 1.25 95% CI: 1.07, 1.48), compared with women without RA aged <35. Women at the same age diagnosed with RA ≥5 years before pregnancy had an OR of 1.14 (0.96-1.34), compared with women without. Among women with RA aged ≥35 years and women with preclinical RA at time of pregnancy, no increased risk of SA was found. The risk of SA increased by maternal age in both women with RA, preclinical RA and in women without., Conclusion: Among women aged <35 years, the risk of SA was higher in women with RA compared with women without. After the age of 35 years, the risk of SA was no different from that among women without RA, even though the risk of SA increased with increasing age., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Importance: The association between the use of hormonal contraceptive and pancreatic cancer among premenopausal women has until now been unclear. This is the first study to investigate the risk of pancreatic cancer in pre-menopausal women., Objective: To determine whether hormonal contraception increases the risk of developing pancreatic cancer in pre-menopausal women., Design: A nationwide prospective cohort study followed all women in Denmark in the age range of 15-49 years without previous cancer or venous thrombosis from 1995 to 2014. The Danish National Prescription Registry provided individually updated exposure information on use of hormonal contraception. The Danish Cancer Registry provided cancer diagnoses, and the Danish National Patient Register containing clinical diagnoses and surgical codes at discharge from public and private hospitals., Setting: Population-based cohort study., Participants: All women living in Denmark aged 15-49 years at January 1st, 1995, and those subsequently reaching age 15 years up to December 31st, 2014 were eligible for the study., Results: Among 1.9 million women who were followed on average for 11.4 years, 235 pancreatic cancers occurred. Compared to never users, ever users of any type of hormonal contraception had a relative risk (RR) of pancreatic cancer of 0.90 (95% confidence interval (CI) 0.68-1.19). No overall association between duration of hormonal contraceptive use and pancreatic cancer risk was found. Neither was long-term use of hormonal contraception associated with pancreas cancer, RR 0.83 (95% CI 0.47-1.50). The risk did not vary between users of combined and progestogen-only products. All models were adjusted for age, completed or ongoing education, polycystic ovary syndrome, endometriosis and among parous women; parity, age at first birth, smoking and body mass index., Conclusions and Relevance: Compared to never users the risk of pancreatic cancer is not significantly higher among current and recent users of contemporary hormonal contraception and does not vary between users of combined and progestogen-only products. In conclusion, our study suggests no risk of pancreatic cancer with use of any type of hormonal contraception., Competing Interests: The authors have declared that no competing interests exist.

Background: Maternal hormonal contraception has been suspected of being linked to an increased risk of childhood cancer. The aim of this study was to assess the association between maternal use of hormonal contraception and diagnosis of leukaemia in their children., Methods: In this cohort study, we followed a nationwide cohort of 1 185 157 liveborn children between 1996 and 2014 listed in the Danish Medical Birth Registry and identified those diagnosed with leukaemia in the Danish Cancer Registry. Redeemed prescriptions from the Danish National Prescription Registry provided information about maternal hormonal contraceptive use, categorised as: no use (never used contraception before birth; reference category), previous use (>3 months before start of pregnancy), and recent use (≤3 months before and during pregnancy). We also calculated risk estimates separately for maternal hormonal contraceptive use during pregnancy. The primary outcome of interest was a diagnosis of any leukaemia in the children. Secondary outcomes were diagnoses of lymphoid leukaemia and non-lymphoid leukaemia. We used Cox proportional hazards models to estimate hazard ratios (HRs) with 95% CIs for risk of leukaemia in children. The Data Protection Agency registration number for this study is 2017-41-5221., Findings: Between Jan 1, 1996, and Dec 31, 2014, the 1 185 157 liveborn children accumulated 11 114 290 person-years of follow-up (median 9·3 years, IQR 4·6-14·2), during which 606 children were diagnosed with leukaemia (465 with lymphoid leukaemia and 141 with non-lymphoid leukaemia). Children born to women with recent use of any type of hormonal contraception were at higher risk for any leukaemia than children of women who never used contraception (HR 1·46, 95% CI 1·09-1·96; p=0·011); and for exposure during pregancy the risk was 1·78 (0·95-3·31; p=0·070). No association was found between timing of use and risk for lymphoid leukaemia (HR 1·23, 95% CI 0·97-1·57, p=0·089, for previous use and 1·27, 0·90-1·80, p=0·167, for recent use); however, the HRs for non-lymphoid leukaemia were 2·17 (1·22-3·87; p=0·008) for recent use and 3·87 (1·48-10·15; p=0·006) for use during pregnancy. Hormonal contraception use close to or during pregnancy might have resulted in one additional case of leukaemia per about 50 000 exposed children, or 25 cases during the 9-year study period., Interpretation: Our findings suggest the maternal hormonal use affects non-lymphoid leukaemia development in children. Since almost no risk factors have been established for childhood leukaemia, these findings suggest an important direction for future research into its causes and prevention., Funding: The Danish Cancer Research Foundation, the Arvid Nilssons Foundation, the Gangsted Foundation, the Harboe Foundation, and the Johannes Clemmesens Foundation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: The purpose of this study was to assess the relative risk of suicide attempt and suicide in users of hormonal contraception., Method: The authors assessed associations between hormonal contraceptive use and suicide attempt and suicide in a nationwide prospective cohort study of all women in Denmark who had no psychiatric diagnoses, antidepressant use, or hormonal contraceptive use before age 15 and who turned 15 during the study period, which extended from 1996 through 2013. Nationwide registers provided individually updated information about use of hormonal contraception, suicide attempt, suicide, and potential confounding variables. Psychiatric diagnoses or antidepressant use during the study period were considered potential mediators between hormonal contraceptive use and risk of suicide attempt. Adjusted hazard ratios for suicide attempt and suicide were estimated for users of hormonal contraception as compared with those who never used hormonal contraception., Results: Among nearly half a million women followed on average for 8.3 years (3.9 million person-years) with a mean age of 21 years, 6,999 first suicide attempts and 71 suicides were identified. Compared with women who never used hormonal contraceptives, the relative risk among current and recent users was 1.97 (95% CI=1.85-2.10) for suicide attempt and 3.08 (95% CI=1.34-7.08) for suicide. Risk estimates for suicide attempt were 1.91 (95% CI=1.79-2.03) for oral combined products, 2.29 (95% CI=1.77-2.95) for oral progestin-only products, 2.58 (95% CI=2.06-3.22) for vaginal ring, and 3.28 (95% CI=2.08-5.16) for patch. The association between hormonal contraceptive use and a first suicide attempt peaked after 2 months of use., Conclusions: Use of hormonal contraception was positively associated with subsequent suicide attempt and suicide. Adolescent women experienced the highest relative risk.

Objective: Maternal rheumatoid arthritis (RA) has been associated with an increased risk of autism spectrum disorder (ASD) in the offspring. We assessed the potential influence of both maternal and paternal RA on the risk of ASD in offspring to disentangle the influence of genetic inheritance from other conditions potentially leading to fetal programming., Method: The nationwide cohort study included all children born alive from 1977 to 2008 in Denmark (N = 1,917,723). Cox regression models were used to calculate hazard rate ratios (HR) of ASD in offspring exposed to maternal or paternal RA, compared to unexposed children., Results: Maternal RA was associated with an approximately 30% increased risk of ASD in the offspring (HR = 1.31 and 95% CI = 1.06-1.63). Also, paternal RA seemed to increase the risk of ASD by approximately 30% (HR = 1.33, 95% CI = 0.97-1.82)., Conclusion: Our findings suggest maternal as well as paternal RA to be associated with an increased risk of ASD in the offspring, indicating that genetic factors associated with RA may also play a role in the etiology of ASD in children of parents with RA., (Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Antidepressants are widely prescribed among women to treat depression and anxiety disorders, but studies of their effects on gynecological cancer risk are sparse. We assessed associations between various antidepressants and risk of epithelial ovarian cancer. By using Danish nationwide registers, we identified all women (cases) aged 30-84 years with incident epithelial (serous, endometrioid, clear cell or mucinous) ovarian cancer during 2000-2011 (n = 4,103) and matched each case to 20 population controls (n = 58,706) by risk-set matching. Data on drug use (including tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants, and potential confounder drugs), medical and reproductive history and socioeconomic parameters, were obtained from nationwide registries. We used conditional logistic regression models to estimate adjusted odds ratios (ORs) and two-sided 95% confidence intervals (CIs) for epithelial ovarian cancer associated with antidepressive drug use. Compared with non-use, use of selective serotonin reuptake inhibitors was associated with a decreased risk of ovarian cancer (OR, 0.85; 95% CI, 0.74-0.96), whereas the associations for other antidepressants were close to unity [tricyclic and related antidepressants: OR, 0.99 (95% CI, 0.78-1.26); other antidepressants: OR, 1.05 (95% CI, 0.76-1.46)]. For individual types of SSRI, reduced ORs were observed for citalopram OR, 0.78 (95% CI, 0.66-0.93), paroxetine 0.79 (95% CI, 0.56-1.12) and sertraline 0.80 (95% CI, 0.60-1.08). Among postmenopausal women, the inverse association was restricted to users of menopausal hormone therapy. In conclusion, use of selective serotonin reuptake inhibitors was associated with a decreased risk of epithelial ovarian cancer; thereby implying potential chemopreventive properties of these drugs., (© 2017 UICC.)

The influence of hormone therapy (HT) on risk for endometrial cancer is still casting which type of HT the clinicians recommend. It is unrevealed if HT has a differential influence on Type I versus Type II endometrial tumors, and little is known about the influence of, e.g., different routes of administration and about the influence of tibolone. We followed all Danish women aged 50-79 years without previous cancer or hysterectomy (n = 914,595) during 1995-2009. From the National Prescription Register, we computed HT exposures as time-dependent covariates. Incident endometrial cancers (n = 6,202) were identified from the National Cancer Registry: 4,972 Type I tumors and 500 Type II tumors. Incidence rate ratios (RRs) and 95% confidence intervals (Cls) were estimated by Poisson regression. Compared with women never on HT, the RR of endometrial cancer was increased with conjugated estrogen: 4.27 (1.92-9.52), nonconjugated estrogen: 2.00 (1.87-2.13), long cycle combined therapy: 2.89 (2.27-3.67), cyclic combined therapy: 2.06 (1.88-2.27), tibolone 3.56 (2.94-4.32), transdermal estrogen: 2.77 (2.12-3.62) and vaginal estrogen: 1.96 (1.77-2.17), but not with continuous combined therapy: 1.02 (0.87-1.20). In contrast, the risk of Type II tumors appeared decreased with continuous combined therapy: 0.45 (0.20-1.01), and estrogen therapy implied a nonsignificantly altered risk of 1.43 (0.85-2.41). Our findings support that continuous combined therapy is risk free for Type I tumors, while all other hormone therapies increase risk. In contrast, Type II endometrial cancer was less convincingly associated with hormone use, and continuous combined therapy appeared to decrease the risk., (© 2015 UICC.)

Objective: To assess the changes in perinatal outcomes in children born from 37 weeks of gestation after implementation of a more proactive labour induction practice from 2009., Design: Register-based cohort study., Setting: Denmark, 2000-12., Population: Newborns from 37 weeks of gestation., Methods: Perinatal outcomes were estimated using a logistic regression analysis with adjustment for gestational age, maternal age, parity, plurality, smoking and body mass index., Main Outcome Measures: Perinatal outcomes., Results: A total of 770 926 infants were included. Labour induction from 37 weeks increased from 9.7% in 2000-02 to 22.5% in 2011-12. From 2003-05 to 2011-12, the risk of umbilical cord pH < 7.0 decreased by 23%; odds ratio (OR) 0.77 (95% confidence interval 0.67-0.89), and the adjusted OR of Apgar score < 7 at 5 minutes was unchanged. The risk of admission to neonatal intensive care units increased by 56%; OR 1.56 (1.47-1.66), whereas the risk of neonatal deaths decreased by 44%; OR 0.56 (0.45-0.70). The risk of cerebral palsy was from 2000-02 to 2009-10 reduced by 26%; OR 0.74 (0.60-0.90). The proportion of infants born with fetal weight ≥ 4500 g decreased by one-third; OR 0.68 (0.65-0.71). However, the risk of shoulder dystocia increased by 32%; OR 1.32 (1.21-1.44), whereas the risk of peripheral nerve injuries was reduced by 43%; OR 0.57 (0.45-0.73)., Conclusion: The results suggest an overall improvement in perinatal outcomes as a result of a more proactive post-term labour induction practice., (© 2015 Royal College of Obstetricians and Gynaecologists.)

Objective: To assess indicators of fetal growth and risk of preterm birth in children of parents with rheumatoid arthritis (RA)., Methods: Through linkage of Danish national registries, we identified all children born in Denmark between 1977 and 2008. We used general linear regression models to estimate mean differences in indicators of fetal growth among children with a parent with RA compared to unexposed children. Odds ratios (ORs) and 95% confidence intervals (95% CIs) of preterm birth were calculated using a logistic regression model., Results: Of the 1,917,723 children included, a total of 13,556 children were exposed to maternal RA or maternal preclinical RA. Children exposed to maternal RA (n = 2,101) had approximately similar length, head circumference, and abdominal circumference at birth compared with children of mothers without RA. Birth weight was 87 gm lower (mean difference -87.04 gm [95% CI -111.23, -62.84]) and placenta weight was 14 gm lower (-13.45 gm [95% CI -21.46, -5.43]) than those in children of mothers without RA. Rather similar results were found in children exposed to maternal preclinical RA (n = 11,455). Compared with unexposed children, a higher risk of preterm birth was found in children exposed to maternal RA (OR 1.48 [95% CI 1.20, 1.84]) and preclinical RA (OR 1.32 [95% CI 1.07, 1.64]). No associations were found with paternal RA., Conclusion: Children exposed to either maternal RA or maternal preclinical RA are more often born preterm. However, indicators of fetal growth measured at birth were only slightly lower than those in unexposed children., (Copyright © 2014 by the American College of Rheumatology.)

Objective: The risk of fetal death increases steeply after 42 gestational weeks. Since 2009, Denmark has had a more proactive policy including prevention of prolonged pregnancy, and early intervention in women with diabetes, preeclampsia, high body mass index and of a higher age group. The aim of this study was to describe the development in fetal deaths with this more proactive birth induction practice, and to identify and quantify contributing factors for this development., Design: National cohort study., Setting: Denmark., Participants: Delivering women in Denmark, 1 January 2000 to 31 December 2012., Outcome Measures: Stillbirths per 1000 women at risk (prospective risk of stillbirth) and per 1000 newborn from 37 and 40 gestational weeks, respectively, through the study period., Results: During the study period, 829,165 children were live born and 3770 (0.45%) stillborn. Induction of labour increased from 12.4% in year 2000 to 25.1% in 2012 (p<0.001), and the percentage of children born at or after 42 weeks decreased from 8.0% to 1.5% (p<0.001). Through the same period, the prospective risk of stillbirth after 37 weeks fell from 0.70 to 0.41/1000 ongoing pregnancies (p<0.001), and from 2.4 to 1.4/1000 newborn (p<0.001). The regression analysis confirmed the inverse association between year of birth and risk of stillbirth. The lowest risk was observed in the years 2011-2012 as compared with years 2000-2002 with a fully adjusted HR of 0.69 (95% CI 0.57 to 0.83). The general earlier induction, the focused earlier induction of women with body mass index >30, twins, and of women above 40 years and a halving of smoking pregnant women were all independent contributing factors for the decrease., Conclusions: A gradually more proactive and differential earlier labour induction practice is likely to have mainly been responsible for the substantial reduction in stillbirths in Denmark., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Postmenopausal hormone therapy use increases the risk of ovarian cancer. In the present study, the authors examined the risks of different histologic types of ovarian cancer associated with hormone therapy. Using Danish national registers, the authors identified 909,946 women who were followed from 1995-2005. The women were 50-79 years of age and had no prior hormone-sensitive cancers or bilateral oophorectomy. Hormone therapy prescription data were obtained from the National Register of Medicinal Product Statistics. The National Cancer and Pathology Register provided data on ovarian cancers, including information about tumor histology. The authors performed Poisson regression analyses that included hormone exposures and confounders as time-dependent covariates. In an average of 8.0 years of follow up, 2,681 cases of epithelial ovarian cancer were detected. Compared with never users, women taking unopposed oral estrogen therapy had increased risks of both serous tumors (incidence rate ratio (IRR) = 1.7, 95% confidence interval: 1.4, 2.2) and endometrioid tumors (IRR = 1.5, 95% confidence interval: 1.0, 2.4) but decreased risk of mucinous tumors (IRR = 0.3, 95% confidence interval: 0.1, 0.8). Similar increased risks of serous and endometrioid tumors were found with estrogen/progestin therapy, whereas no association was found with mucinous tumors. Consistent with results from recent cohort studies, the authors found that ovarian cancer risk varied according to tumor histology. The types of ovarian tumors should be given attention in future studies.

Purpose: Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk., Methods: A total of 909,875 Danish women 50-79 years old without previous hormone-sensitive cancers or bilateral oophorectomy were followed in this nationwide cohort study 1995-2005. The National Register of Medicinal Product Statistics provided exposure information on all women who redeemed prescriptions on hormone therapy. The National Cancer and Pathology Register provided data on borderline ovarian tumors. Information on confounding factors was available from other national registers. Poisson regression analyses provided risk estimates with hormone exposures as time-dependent covariates., Results: In an average of 8.0 years of follow-up, 703 incident ovarian borderline tumors were detected. Compared with never users, hormone use for more than 4 years increased the risk of borderline tumors: relative risk (RR) 1.40; 95% confidence interval (CI), 1.09-1.81. Combined estrogen and progestin therapy for more than 4 years increased the risk: RR 1.49 (1.10-2.01), with no difference between cyclic and continuous combined therapy (p = 0.83); RR 1.56 (1.08-2.25) and 1.45 (0.87-2.43), respectively. The RR with estrogen therapy did not differ significantly from RR with combined therapy (p = 0.58): RR 1.27 (0.82-1.98). Disregarding the type of hormone therapy, hormone use for 4 years or less did not increase the risk of borderline tumors., Conclusions: Combined hormone therapy for more than 4 years increases the risk of ovarian borderline tumors.

Context: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration., Objective: To assess risk of ovarian cancer in perimenopausal and postmenopausal women receiving different hormone therapies., Design and Setting: Nationwide prospective cohort study including all Danish women aged 50 through 79 years from 1995 through 2005 through individual linkage to Danish national registers. Redeemed prescription data from the National Register of Medicinal Product Statistics provided individually updated exposure information. The National Cancer Register and Pathology Register provided ovarian cancer incidence data. Information on confounding factors and effect modifiers was from other national registers. Poisson regression analyses with 5-year age bands included hormone exposures as time-dependent covariates., Participants: A total of 909,946 women without hormone-sensitive cancer or bilateral oophorectomy., Main Outcome Measure: Ovarian cancer., Results: In an average of 8.0 years of follow-up (7.3 million women-years), 3068 incident ovarian cancers, of which 2681 were epithelial cancers, were detected. Compared with women who never took hormone therapy, current users of hormones had incidence rate ratios for all ovarian cancers of 1.38 (95% confidence interval [CI], 1.26-1.51) and 1.44 (95% CI, 1.30-1.58) for epithelial ovarian cancer. The risk declined with years since last use: 0 to 2 years, 1.22 (95% CI, 1.02-1.46); more than 2 to 4 years, 0.98 (95% CI, 0.75-1.28); more than 4 to 6 years, 0.72 (95% CI, 0.50-1.05), and more than 6 years, 0.63 (95% CI, 0.41-0.96). For current users the risk of ovarian cancer did not differ significantly with different hormone therapies or duration of use. The incidence rates in current and never users of hormones were 0.52 and 0.40 per 1000 years, respectively, ie, an absolute risk increase of 0.12 (95% CI, 0.01-0.17) per 1000 years. This approximates 1 extra ovarian cancer for roughly 8300 women taking hormone therapy each year., Conclusion: Regardless of the duration of use, the formulation, estrogen dose, regimen, progestin type, and route of administration, hormone therapy was associated with an increased risk of ovarian cancer.

Background: Alcohol intake has been shown to be associated with an increased risk for breast cancer. In the analysis of longitudinal prospective cohort studies, however, the analysis of repeated measurements of alcohol intake might not be straightforward., Methods: In this analysis of the Copenhagen City Heart Study, in which alcohol intake was measured four times, 9318 Danish women with no previous diagnosis of cancer were followed for breast cancer for 27 years, from 1976 to 2002. During follow-up, breast cancer was diagnosed in 476 women., Results: The association between alcohol intake at first measurement (baseline alcohol intake) and breast cancer was positive and approximately linear. When alcohol intake was updated during follow-up, no association was observed between breast cancer and alcohol intake. It is suggested that this difference in results may be attributable to long latency time between alcohol intake and breast cancer occurrence, because a markedly increased risk was estimated on the basis of direct lagging of risk time., Conclusions: Our results support the hypothesis that baseline alcohol intake is more strongly associated with breast cancer risk than updated intake, and we suggest that this is due to the long latency between alcohol intake and breast cancer.

Background/objective: Moderate alcohol consumption has beneficial effects on survival. Sex differences, however, have been suggested implying less beneficial effect among women. We examined the impact of alcohol consumed on weekdays and at weekends, respectively, on risk of death among women., Subjects and Methods: At baseline in 1993, a total of 17 772 female members of the Danish Nurse Association completed questionnaires on alcohol intake and other lifestyle factors. The influence of alcohol intake on risk of death was analyzed using Cox proportional hazard model., Results: Alcohol intake of 1-3 drinks per week was associated with the lowest risk of death. Intake above six drinks per weekend (Friday through Sunday) increased risk of death from all causes by 3% for each additional drink consumed per weekend (corresponding to an increased risk by 9% per drink per weekend day). Consumption of one or more drinks per weekday (Monday, Tuesday, Wednesday or Thursday) increased risk by 4% for each additional drink consumed per day., Conclusions: The results indicated an increasing risk of death for intake above six drinks per weekend and of one or more drinks per weekday.

Background: It has been hypothesized that obesity and insulin resistance may play a role in the development of asthma and allergy. The aim of the study was to examine the association of obesity and insulin resistance with asthma and aeroallergen sensitization., Methods: Cross-sectional population-based study of 3609 Danish men and women aged 30-60 years. Aeroallergen sensitization was defined as positive levels of specific IgE against a panel of inhalant allergens. Asthma was defined as self-reported physician diagnosed asthma. Allergic asthma was defined as the presence of both asthma and aeroallergen sensitization. The homeostasis model assessment of insulin resistance was used to estimate the degree of insulin resistance. Body mass index, waist-to-hip ratio, and waist circumference were used as measures of obesity. Data were analyzed by multiple logistic regression analyses., Results: Obesity was associated with increased risk of aeroallergen sensitization as well as allergic and nonallergic asthma. Insulin resistance was asssociated with aeroallergen sensitization and allergic asthma, but not nonallergic asthma. The associations of obesity with aeroallegen sensitization and allergic asthma became nonsignificant after adjustment for insulin resistance, whereas the association of obesity with nonallergic asthma was unaffected. No sex-differences were observed., Conclusion: Obesity may be related to an increased risk of aeroallergen sensitization and allergic asthma through mechanisms also involved in the development of insulin resistance.

Background: The aim of this study was to analyse the impact of alcohol intake and drinking pattern on the risk of breast cancer., Methods: A total of 17 647 nurses were followed from 1993 until the end of 2001. At baseline participants completed a questionnaire on alcohol intake and other lifestyle-related factors. Data were analysed using Cox's proportional hazard model., Results: During follow-up 457 women were diagnosed with breast cancer. The relative risk of breast cancer was 2.30 [Confidence interval (CI): 1.56-3.39] for alcohol intake of 22-27 drinks per week, compared to 1-3 drinks per week. Among alcohol consumers, weekly alcohol intake increased the risk of breast cancer with 2% for each additional drink consumed. Weekend consumption increased the risk with 4% for each additional drink consumed friday through sunday. Binge drinking of 4-5 drinks the latest weekday increased risk with 55%, compared with consumption of one drink. A possible threshold in risk estimates was found for consumption above 27 drinks per week., Conclusions: For alcohol consumption above the intake most frequently reported, the risk of breast cancer is increased. The risk is minor for moderate levels but increases for each additional drink consumed during the week. Weekend consumption and binge drinking imply an additional increase in breast cancer risk.

The sensible drinking limits may be too high depending on sex, age, genetic variation and other factors. Recent research on the alcohol-related risk of breast cancer and the impact of drinking patterns on health calls for an update of the literature. We focus on studies of the effect of alcohol on morbidity and mortality and conclude that the maximum of 21 drinks per week for men and 14 for women may be maintained. We emphasize that episodic intake of alcohol increases the risk of death and that the beneficial effect of alcohol is reached at an intake of one drink per day. We also specify groups for whom the drinking limits are not valid.