Contemporary hormonal contraception and cervical cancer in women of reproductive age.

To determine cervical cancer risk associated with contemporary hormonal contraceptives, we conducted a cohort study of women aged 15 to 49 living in Denmark from 1995 to 2014, using routinely collected information about redeemed prescriptions, incident cancer and potential confounders. Poisson regression calculated adjusted cervical cancer risks among different contraceptive user groups by duration of use, time since last use, hormonal content and cancer histology. During >20 million person-years, 3643 incident cervical cancers occurred. Ever users of any hormonal contraceptives compared to never users had a relative risk (RR) of 1.19 (95% confidence interval [CI] 1.10-1.29). Increased risks were seen in current or recent users of any hormonal: RR 1.30 (95% CI 1.20-1.42) and combined: RR 1.40 (95% CI 1.28-1.53), but not progestin-only contraception: RR 0.91 (95% CI 0.78-1.07). Current or recent users of any hormonal contraception had an increased risk of both adenocarcinoma (RR 1.29, 95% CI 1.05-1.60) and squamous cancer (RR 1.31, 95% CI 1.19-1.44). The risk pattern among any hormonal and combined contraceptive users generally increased with longer duration of use and declined after stopping, possibly taking longer to disappear among prolonged users. Combined products containing different progestins had similar risks. Approximately one extra cervical cancer occurred for every 14 700 women using combined contraceptives for 1 year. Most women in our study were not vaccinated against human papillomavirus (HPV) infections. Our findings reinforce the urgent need for global interventions such as systematic screening, treatment of cervical intraepithelial neoplasia and HPV vaccination programmes to prevent cervical cancer, especially among users of combined contraceptives.

Statin use and risk of liver cancer: Evidence from two population-based studies.

Epidemiological studies of statin use and liver cancer risk have produced conflicting results. We examined the association between statin use and risk of primary liver cancer in two large independent study populations taking account of important covariates and main indications of statins such as high cholesterol and chronic liver disease. We performed a nested case-control study within the Scottish Primary Care Clinical Informatics Unit (PCCIU) database. Five controls were matched to cases with primary liver cancer and we used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with statin use. We also conducted a prospective cohort study within the UK Biobank using self-reported statin use and cancer-registry recorded primary liver cancer outcomes. Cox regression was used to calculate hazard ratios (HRs) and 95% CIs. In the PCCIU case-control analysis, 434 liver cancer cases were matched to 2,103 controls. In the UK Biobank cohort, 182 out of 475,768 participants developed incident liver cancer. Statin use was associated with 39% lower risk of liver cancer in the PCCIU (adjusted OR 0.61, 95% CI 0.43-0.87). When we examined specific subtypes of liver cancer in the UK Biobank, statin use was associated with lower risk of hepatocellular carcinoma (HCC; adjusted HR, 0.48; 95% CI, 0.24-0.94) but not intrahepatic bile duct carcinoma (IBDC; adjusted HR, 1.09; 95% CI, 0.45-2.64). In conclusion, we found a consistent inverse relationship between statin use and risk of primary liver cancer which was only seen for HCC but not IBDC.

Use of proton pump inhibitors and histamine-2 receptor antagonists and risk of gastric cancer in two population-based studies.

BACKGROUND: Studies have shown increased gastric cancer risk in users of proton pump inhibitors (PPI) and histamine-2 receptor antagonists, questioning the safety of gastric acid suppression. Therefore, we conducted a case-control study within the Scottish Primary Care Clinical Informatics Unit (PCCIU) database and a cohort study in the UK Biobank. METHODS: In PCCIU, five controls were matched to cases diagnosed in 1999-2011, and medications were determined from GP records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression. In the UK Biobank, medications were self-reported at cohort entry 2006-2010, and gastric cancer ascertained from cancer registries until 2014. Hazard ratios (HR) were calculated using Cox regression. RESULTS: PCCIU contained 1119 cases and 5394 controls. UK Biobank contained 250 cases in 471,779 participants. PPI users had a higher gastric cancer risk in PCCIU and UK Biobank when applying a 1-year lag (adjusted OR = 1.49, 95% CI 1.24, 1.80; adjusted HR = 1.28, 95% CI 0.86, 1.90, respectively), but these associations were attenuated when using a 2-year lag (adjusted OR = 1.13, 95% CI 0.91, 1.40; adjusted HR = 1.15, 95% CI 0.73, 1.82, respectively). CONCLUSIONS: Overall, we observed little consistent evidence of an increased risk of gastric cancer with PPI use.

Contemporary Hormonal Contraception and the Risk of Breast Cancer.

BACKGROUND: Little is known about whether contemporary hormonal contraception is associated with an increased risk of breast cancer. METHODS: We assessed associations between the use of hormonal contraception and the risk of invasive breast cancer in a nationwide prospective cohort study involving all women in Denmark between 15 and 49 years of age who had not had cancer or venous thromboembolism and who had not received treatment for infertility. Nationwide registries provided individually updated information about the use of hormonal contraception, breast-cancer diagnoses, and potential confounders. RESULTS: Among 1.8 million women who were followed on average for 10.9 years (a total of 19.6 million person-years), 11,517 cases of breast cancer occurred. As compared with women who had never used hormonal contraception, the relative risk of breast cancer among all current and recent users of hormonal contraception was 1.20 (95% confidence interval [CI], 1.14 to 1.26). This risk increased from 1.09 (95% CI, 0.96 to 1.23) with less than 1 year of use to 1.38 (95% CI, 1.26 to 1.51) with more than 10 years of use (P=0.002). After discontinuation of hormonal contraception, the risk of breast cancer was still higher among the women who had used hormonal contraceptives for 5 years or more than among women who had not used hormonal contraceptives. Risk estimates associated with current or recent use of various oral combination (estrogen-progestin) contraceptives varied between 1.0 and 1.6. Women who currently or recently used the progestin-only intrauterine system also had a higher risk of breast cancer than women who had never used hormonal contraceptives (relative risk, 1.21; 95% CI, 1.11 to 1.33). The overall absolute increase in breast cancers diagnosed among current and recent users of any hormonal contraceptive was 13 (95% CI, 10 to 16) per 100,000 person-years, or approximately 1 extra breast cancer for every 7690 women using hormonal contraception for 1 year. CONCLUSIONS: The risk of breast cancer was higher among women who currently or recently used contemporary hormonal contraceptives than among women who had never used hormonal contraceptives, and this risk increased with longer durations of use; however, absolute increases in risk were small. (Funded by the Novo Nordisk Foundation.).

The role of 5α-reductase inhibitors in gastro-oesophageal cancer risk: A nested case-control study.

PURPOSE: The strong male predominance of gastro-oesophageal cancer suggests that sex hormones play an important role. 5α-Reductase (5AR) inhibitors have antiandrogen effects and have been shown to decrease cancer cell proliferation and metastasis. We conducted the first epidemiologic investigation into the association between 5AR inhibitor use and gastro-oesophageal cancer risk. METHODS: We conducted a nested case-control study within the Scottish Primary Care Clinical Information Unit Research database. Male cases diagnosed with oesophageal or gastric cancer between 1999 and 2011 were matched to up to five male controls based on birth year, diagnosis year, and general practice. We used electronic prescribing records to ascertain medication use. We used conditional logistic regression to calculate odds ratios (ORs) for the association between 5AR inhibitor use and cancer risk, after adjusting for comorbidities and aspirin, statin, or proton pump inhibitor use. RESULTS: The study included 2003 gastro-oesophageal cancer cases and 9650 controls. There was some evidence of reduced gastro-oesophageal cancer risk among 5AR inhibitor users (adjusted OR = 0.75; 95% CI, 0.56-1.02), particularly for finasteride (adjusted OR = 0.68; 95% CI, 0.50-0.94). These decreases were more marked among those who received at least 3 years of 5AR inhibitors (adjusted OR = 0.54; 95% CI, 0.27-1.05; P value = .071) or finasteride (adjusted OR = 0.49; 95% CI, 0.24-0.99; P value = .046). CONCLUSIONS: We found evidence of reduced gastro-oesophageal cancer risk among users of 5AR inhibitors, particularly finasteride. However, larger epidemiological studies are required before randomised controlled trials are considered.

Clinical features in primary care electronic records before diagnosis of ankylosing spondylitis: a nested case-control study.

BACKGROUND: Ankylosing spondylitis (AS) often has a long period from first symptom presentation to diagnosis. We examined the occurrence of symptoms, prescriptions and diagnostic tests in primary care electronic records over time prior to a diagnosis of AS. METHODS: Nested case-control study using anonymised primary care electronic health records from Scotland. Cases were 74 adults with a first diagnosis of AS between 2000 and 2010. Controls were matched for age, sex and GP practice: (a) 296 randomly selected adults (b) 169 adults whose records contained codes indicating spinal conditions or symptoms. We extracted clinical features (symptoms, AS-related disorders, prescriptions and diagnostic tests). Conditional logistic regression was used to examine the association between clinical features (both individually and in combinations) and diagnosis of AS. We examined the associations between clinical features and diagnosis over time prior to diagnosis. RESULTS: Several new composite pointers were predictive of AS: including distinct episodes of axial pain separated by more than 6 months (OR 12.7, 95% CI 4.7 to 34.6); the occurrence of axial pain with and tendon symptoms within the same year (OR 21.7, 95% CI 2.6 to 181.5); and the co-occurrence (within 30 days) of axial pain and a prescription for nonsteroidal anti-inflammatory drug (OR 10.4, 95%CI 4.9 to 22.1). Coded episodes of axial pain increased steadily over the 3 years before diagnosis. In contrast, large joint symptoms and enthesopathy showed little or no time trend prior to diagnosis. CONCLUSIONS: We identified novel composite pointers to a diagnosis of AS in GP records. These may represent valuable targets for diagnostic support systems.

Medications that relax the lower oesophageal sphincter and risk of oesophageal cancer: An analysis of two independent population-based databases.

Excessive lower oesophageal sphincter relaxation increases gastro-oesophageal acid reflux, an oesophageal adenocarcinoma risk factor. Medications that relax this sphincter (benzodiazepines, calcium channel blockers, nitrates, ß2 agonists and xanthines) could promote cancer. These medications were investigated in two independent datasets. In the Scottish Primary Care Clinical Informatics Unit (PCCIU) database, a nested case-control study of oesophageal cancer was performed using GP prescription records. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for medication use and oesophageal cancer. In UK Biobank, a cohort study was conducted using self-reported medication use. Cox regression was used to calculate hazard ratios (HRs) and 95% CIs for medication use and oesophageal cancer, and by tumour subtype. Overall, 1,979 oesophageal cancer patients were matched to 9,543 controls in PCCIU, and 355 of 475,768 participants developed oesophageal cancer in UK Biobank. None of the medications investigated were significantly associated with oesophageal cancer risk apart from ß2 agonists, which were associated with increased oesophageal cancer risk in PCCIU (adjusted OR 1.38, 95% CI 1.12, 1.70) but not in UK Biobank (adjusted HR 1.21, 95% CI 0.70, 2.08). Medications that relax the lower oesophageal sphincter were not associated with oesophageal cancer, apart from ß2 agonists. This increased cancer risk in ß2 agonist users merits further investigation.

The effect of medications which cause inflammation of the gastro-oesophageal tract on cancer risk: a nested case-control study of routine Scottish data.

Bisphosphonate, tetracycline and spironolactone use has been shown to increase gastro-oesophageal inflammation, an accepted risk factor for cancer. However, evidence of the effect of these medications on gastro-oesophageal cancer risk are mixed or missing entirely. Therefore, we conducted a nested case-control study using the Primary Care Clinical Information Unit Research (PCCIUR) database from Scotland. Cases with oesophageal or gastric cancer between 1999 and 2011 were matched to up to five controls based on age, gender, year of diagnosis and general practice. Medication use was ascertained using electronic prescribing records. Conditional logistic regression was used to calculate odds ratios (ORs) for the association between medication use and cancer risk after adjustment for comorbidities and other medication use. A similar proportion of gastro-oesophageal cancer cases received bisphosphonates (3.9% vs. 3.5%), tetracycline (6.0% vs. 6.0%) and spironolactone (1.4% vs. 1.1%) compared with the controls. The adjusted ORs for the association between gastro-oesophageal cancer and bisphosphonates, tetracycline and spironolactone were 1.05 (95% CI: 0.85, 1.31), 0.99 (95% CI: 0.84, 1.17) and 1.04 (95% CI: 0.73, 1.49). Further analysis revealed bisphosphonates were associated with increased oesophageal cancer risk (1.34, 95% CI: 1.03, 1.74) but reduced gastric cancer risk (0.71, 95% CI: 0.49, 1.03), although there was no obvious dose-response relationship. Overall, there is little evidence that the use of bisphosphonate, tetracycline or spironolactone is associated with increased risk of gastro-oesophageal cancer. Our findings should reassure GPs and patients that these widely-used medications are safe with respect to gastro-oesophageal cancer risk.

Lifetime cancer risk and combined oral contraceptives: the Royal College of General Practitioners' Oral Contraception Study.

BACKGROUND: Oral contraceptives have been used by hundreds of millions of women around the world. Important questions remain regarding the very long-term cancer risks that are associated with oral contraception. Despite previous research, important questions remain about the safety of these contraceptives: (1) How long do endometrial, ovarian, and colorectal cancer benefits persist? (2) Does combined oral contraceptive use during the reproductive years produce new cancer risks later in life? (3) What is the overall balance of cancer among past users as they enter the later stages of their lives? OBJECTIVES: The purpose of this study was to examine the very long-term cancer risks or benefits associated with the use of combined oral contraceptives, including the estimated overall life-time balance. STUDY DESIGN: The 46,022 women who were recruited to the UK Royal College of General Practitioners' Oral Contraception Study in 1968 and 1969 were observed for up to 44 years. Directly standardized rates of specific and any cancer were calculated for "ever" and "never" users of combined oral contraceptives; data were standardized for age, parity, social class, and smoking. Attributable risk and preventive fraction percentages were calculated. Poisson regression that adjusted for the same variables was used to estimate incidence rate ratios between ever and never users and to examine effects by time since last oral contraceptive use. RESULTS: There were 4661 ever users with at least 1 cancer during 884,895 woman-years of observation and 2341 never users with at least 1 cancer during 388,505 woman-years of observation. Ever use of oral contraceptives was associated with reduced colorectal (incidence rate ratio, 0.81; 99% confidence interval, 0.66-0.99), endometrial (incidence rate ratio, 0.66; 99% confidence interval, 0.48-0.89), ovarian (incidence rate ratio, 0.67; 99% confidence interval, 0.50-0.89), and lymphatic and hematopoietic cancer (incidence rate ratio, 0.74; 99% confidence interval, 0.58-0.94). An increased risk of lung cancer was seen only among ever users who smoked at recruitment. An increased risk of breast and cervical cancer that was seen in current and recent users appeared to be lost within approximately 5 years of stopping oral contraception, with no evidence of either cancer recurring at increased risk in ever users with time. There was no evidence of new cancer risks appearing later in life among women who had used oral contraceptives. Thus, the overall balance of cancer risk among past users of oral contraceptives was neutral with the increased risks counterbalanced by the endometrial, ovarian, and colorectal cancer benefits that persist at least 30 years. CONCLUSION: Most women who choose to use oral contraceptives do not expose themselves to long-term cancer harms; instead, with some cancers, many women benefit from important reductions of risk that persist for many years after stopping.

Physical disease and resilient outcomes: a systematic review of resilience definitions and study methods.

BACKGROUND: Findings from physical disease resilience research may be used to develop approaches to reduce the burden of disease. However, there is no consensus on the definition and measurement of resilience in the context of physical disease. OBJECTIVE: The aim was to summarize the range of definitions of physical disease resilience and the approaches taken to study it in studies examining physical disease and its relationship to resilient outcomes. METHODS: Electronic databases were searched from inception to March 2013 for studies in which physical disease was assessed for its association with resilient outcomes. Article screening, data extraction, and quality assessment were carried out independently by 2 reviewers, with disagreements being resolved by a third reviewer. The results were combined using a narrative technique. RESULTS: Of 2280 articles, 12 met the inclusion criteria. Of these studies, 1 was of high quality, 9 were of moderate quality, and 2 were low quality. The common findings were that resilience involves maintaining healthy levels of functioning following adversity and that it is a dynamic process not a personality trait. Studies either assessed resilience based on observed outcomes or via resilience measurement scales. They either considered physical disease as an adversity leading to resilience or as a variable modifying the relationship between adversity and resilience. CONCLUSION: This work begins building consensus as to the approach to take when defining and measuring physical disease resilience. Resilience should be considered as a dynamic process that varies across the life-course and across different domains, therefore the choice of a resilience measure should reflect this.

Long-term survival benefits of thrombolysis: the Royal College of General Practitioners' myocardial infarction study.

OBJECTIVE: To investigate whether there is a long-term survival benefit from receipt of thrombolysis in routine care particularly pre-hospital thrombolysis, using 20 year mortality data from the RCGP myocardial infarction (MI) cohort study. METHODS: During 1991-92 the RCGP MI study assessed GP delivery of thrombolysis. Participants who received pre-hospital thrombolysis (n = 290), thrombolysis in hospital (n = 781) or no thrombolysis (n = 2021) were followed and mortality data collected to June 2012. The relationship between thrombolysis and survival time was analysed using Cox regression at 28 days, 1, 5, 10, 15 years post-AMI, and at end of follow-up (~20 years post-AMI). RESULTS: Compared to those who did not receive it, participants who received thrombolysis had a significant survival benefit at 28 days [adjusted hazard ratio (HR) 0.72, 95% confidence interval (CI): 0.58-0.90]; 1 year (adjusted HR 0.69, 95% CI: 0.57-0.83); 5 years (adjusted HR 0.76, 95% CI: 0.66-0.86); 10 years (adjusted HR 0.85, 95% CI: 0.77-0.95) and 15 years (adjusted HR 0.88, 95% CI: 0.80-0.96) post-AMI until end of follow-up (adjusted HR 0.92, 95% CI: 0.84-1.00). Pre versus in-hospital thrombolysis did not appear beneficial, although there was evidence among the pre-hospital group that short symptom onset-to-needle times conferred greater benefit. CONCLUSIONS: We found substantial long-term survival benefits associated with thrombolysis when used in routine care. Although primary percutaneous coronary intervention (pPCI) is now the choice treatment, thrombolysis remains an important option when pPCI cannot be delivered within 120 minutes of diagnosis.

Factors associated with age of onset and type of menopause in a cohort of UK women.

OBJECTIVE: We sought to describe the pattern of age at menopause and factors associated with type of menopause. STUDY DESIGN: This was a prospective cohort study of 5113 postmenopausal health survey respondents in the Royal College of General Practitioners' Oral Contraception Study. Logistic regression was used to evaluate associations between sociodemographics, lifestyle, and medical history and menopause type. RESULTS: Median age at natural menopause (n = 3650) was 49.0 years (interquartile range, 45.0-51.0), and at surgical menopause (n = 1463) was 42.4 years (38.0-46.4). Early natural menopause was associated with smoking, ever-use of oral contraception, sterilization, and history of endometriosis (all increased odds ratios) and ever-use of hormone replacement therapy (decreased). Surgical menopause was associated with manual social class, sterilization, and having a history of endometriosis, menorrhagia, or painful menstruation (all increased), and ever-use of hormone replacement therapy (decreased). CONCLUSION: Age at natural menopause was younger in this cohort than in other studies. More associations were found for surgical menopause than early natural menopause.

Lack of consensus between general practitioners and official guidelines on alcohol abstinence during pregnancy.

INTRODUCTION: Many pregnant women in Denmark have been advised that some alcohol intake is acceptable. In the 1999-2007-period, the Danish National Board of Health advised pregnant women that some alcohol intake was acceptable. From 2007, alcohol abstinence has been recommended. We aimed to describe the attitudes towards and knowledge about alcohol in pregnancy among general practitioners (GPs) in Denmark in 2000 and in 2009. MATERIAL AND METHODS: In 2000, we invited a representative sample of GPs in the catchment area of the Antenatal Care Centre in Aarhus to participate in the study. Participants were interviewed about their attitudes, beliefs, knowledge and information practice in relation to alcohol in pregnancy. Identical questions were sent to all GPs in the area in 2009. RESULTS: In 2000, most GPs (71%) considered that some alcohol intake in pregnancy was acceptable, mostly on a weekly level. There was considerable interperson variation in the participants' attitudes and recommendations to pregnant women. In 2009, significantly more GPs (51%) considered abstinence to be preferable, and significantly more GPs (53%) gave this advice to pregnant women than in 2000. Their knowledge about the official recommendations on alcohol was good. Older GPs were more likely to recommend abstinence. CONCLUSION: The attitudes towards and knowledge about drinking in pregnancy among GPs have changed along with the change in official policy. FUNDING: In 2000, data collection was funded by The Danish National Board of Health (J.no. 407-15-1999). TRIAL REGISTRATION: not relevant.

Is place or person more important in determining higher rural cancer mortality? A data-linkage study to compare individual versus area-based measures of deprivation.

Data from Northeast Scotland for 11,803 cancer patients (diagnosed 2007-13) were linked to UK Censuses to explore relationships between hospital travel-time, timely-treatment and one-year-mortality, adjusting for both area and individual-level socioeconomic status (SES). Adjusting for area-based SES, those living >60 minutes from hospital received timely-treatment more often than those living <15 minutes. Substituting individual-level SES changed little. Adjusting for area-based SES those living >60 minutes from hospital died within one year more often than those living <15 minutes. Again, substituting individual-level SES changed little. In Northeast Scotland distance to services, rather than individual SES, likely explains poorer rural cancer survival. BACKGROUND AND OBJECTIVE: The Northeast and Aberdeen Scottish Cancer and Residence (NASCAR) study found rural-dwellers are treated quicker but more likely to die within a year of a cancer diagnosis. A potential confounder of the relationship between geography and cancer mortality is socioeconomic status (SES). We linked the original NASCAR cohort to the UK Censuses of 2001 and 2011, at an individual level, to explore the relationship between travel time to key healthcare facilities, timely cancer treatment and one-year mortality adjusting for both area and individual-level markers of socioeconomic status. METHODS: A data linkage study of 11803 patients examined the association between travel times, timely treatment and one-year mortality with adjustment for area, and for individual-level, markers of socioeconomic status. RESULTS: Following adjustment for area-based SES measures those living more than 60 minutes from the cancer treatment centre were significantly more likely to be treated within 62 days of GP referral than those living within 15 minutes (Odds Ratio [OR]) 1.41; 95% (Confidence Interval [CI]) 1.23, 1.60]. Replacing area-based with individual-level SES measures from UK Censuses made little impact on the results [OR 1.39; 95% CI 1.22, 1.57].Following adjustment for area-based SES measures of socioeconomic status those living more than 60 minutes from the cancer treatment centre were significantly more likely to die within one year than those living closer by [OR 1.22; 95% CI 1.08, 1.38]. Again, replacing area-based with individual-level SES measures from UK Censuses made little impact on the result [OR 1.20; CI 1.06, 1.35]. CONCLUSIONS: Distribution of individual measures of socioeconomic status did not differ significantly between rural and urban cancer patients. The relationship between distance to service, timely treatment and one-year survival were the same adjusting for both area-based and individual SES. Overall, it seems that distance to services, rather than personal characteristics, influences poorer rural cancer survival.

Exploring the influence of rural residence on uptake of organized cancer screening - A systematic review of international literature.

Lower screening uptake could impact cancer survival in rural areas. This systematic review sought studies comparing rural/urban uptake of colorectal, cervical and breast cancer screening in high income countries. Relevant studies (n = 50) were identified systematically by searching Medline, EMBASE and CINAHL. Narrative synthesis found that screening uptake for all three cancers was generally lower in rural areas. In meta-analysis, colorectal cancer screening uptake (OR 0.66, 95 % CI = 0.50-0.87, I2 = 85 %) was significantly lower for rural dwellers than their urban counterparts. The meta-analysis found no relationship between uptake of breast cancer screening and rural versus urban residency (OR 0.93, 95 % CI = 0.80-1.09, I2 = 86 %). However, it is important to note the limitation of the significant statistical heterogeneity found which demonstrates the lack of consistency between the few studies eligible for inclusion in the meta-analyses. Cancer screening uptake is apparently lower for rural dwellers which may contribute to poorer survival. National screening programmes should consider geography in planning.

Reproductive Pattern of Parous Women and the Risk of Cancer in Later Life.

We assessed the risk of any and site-specific cancers in a case-control study of parous women living in northeast Scotland in relation to: total number of pregnancies, cumulative time pregnant, age at first delivery and interpregnancy interval. We analysed 6430 women with cancer and 6430 age-matched controls. After adjustment for confounders, women with increasing number of pregnancies had similar odds of cancer diagnosis as women with only one pregnancy. The adjusted odds of cancer diagnosis were no higher in women with cumulative pregnancy time 50-150 weeks compared to those pregnant ≤ 50 weeks. Compared with women who had their first delivery at or before 20 years of age, the adjusted odds ratio (AOR) among those aged 21-25 years was 0.81, 95% CI 0.74, 0.88; 26-30 years AOR 0.77, 95% CI 0.69, 0.86; >30 years AOR 0.63, 95% CI 0.55, 0.73. After adjustment, the odds of having any cancer were higher in women who had an inter-pregnancy interval >3 years compared to those with no subsequent pregnancy (AOR 1.17, 95% CI 1.05, 1.30). Older age at first pregnancy was associated with increased risk of breast and gastrointestinal cancer, and reduced risk of invasive cervical, carcinoma in situ of the cervix and respiratory cancer.

Menopause-related workload in general practice 1996-2005: a retrospective study in the UK.

BACKGROUND: Women with menopausal symptoms often consult with a health professional. Recently, hormone replacement therapy (HRT) prescribing has declined but the impact of this change on other aspects of general practice workload is unclear. OBJECTIVE: To investigate whether the menopause remains a workload issue. METHODS: A retrospective observational study of UK general practice (General Practice Research Database) using four random samples of 25000 women aged 45-64 years registered with a general practice during 1996, 1999, 2002 and 2005. We calculated the incidence and prevalence of menopause-related consultation; gynaecology referrals; prescriptions for HRT, clonidine and antidepressants during each year; examined patterns over time and investigated whether the types of preparations had changed. RESULTS: The prevalence and incidence of menopause-related consultation fell-from 18.1% of women aged 45-64 years consulting at least once in 1996 to 10.4% in 2005. Over time, the proportion of women consulting about the menopause who were not prescribed HRT or clonidine increased. The incidence and prevalence of HRT decreased, mainly between 2002 and 2005. The proportion of women prescribed oral HRT fell while the proportion prescribed cream or pessaries/suppositories increased, particularly among women without a hysterectomy. Referrals to gynaecology and the incidence and prevalence of clonidine prescribing increased but remained uncommon. Patterns of antidepressant prescribing did not appear menopause related. CONCLUSION: Although menopause-related workload has decreased over time, in 2005, over 10% of women aged 45-64 years consulted for a menopause-related matter. This suggests that the menopause remains an important part of UK general practice work.

Contemporary hormonal contraception and risk of endometrial cancer in women younger than age 50: A retrospective cohort study of Danish women.

OBJECTIVE: To examine the association between contemporary hormonal contraceptives and endometrial cancer risk in women younger than age 50. STUDY DESIGN: Cohort study of women living in Denmark aged 15-49 years through 1995-2014. National registries provided information about hormonal contraception use, incident endometrial cancer and confounders. Ever, current or recent, and former users of any hormonal contraception were compared with non-users, using Poisson regression to calculate incidence rate ratios (RR) with 95% confidence intervals. Duration, time since last use, tumor-specific and product-specific analyses, and population prevented fraction, were calculated. RESULTS: During 21.1 million person-years, 549 incident endometrial cancers occurred, with ever users of any hormonal contraception having a reduced premenopausal endometrial cancer risk compared with non-users; RR 0.60 (95% Confidence Interval 0.49 to 0.73). A lower risk of endometrial cancer was seen in all current or recent users of any hormonal contraception; 0.65 (0.52 to 0.83) and combined contraceptives; 0.57 (0.43 to 0.75), but not progestin-only contraceptives; levonorgestrel intrauterine system, LNG-IUS; 0.97 (0.66 to 1.42); other progestin-only contraceptives; 0.61 (0.27 to 1.37). Increased RRs were found for current use of any hormonal, combined contraceptives or LNG-IUS of ≤one year, probably because of protopathic bias. Longer durations of use were associated with significant reductions that became stronger with longer use. Former users of any hormonal contraception continued to benefit from a reduced risk of endometrial cancer >10 years after stopping. There was little evidence of differences in risk reduction by the type of progestin in combined oral contraceptives. Current or recent use of any hormonal contraception was associated with an approximate halving of risk of the most common tumor type I carcinoma, and an increased risk of the rarer sarcoma. Overall the estimated absolute reduced risk of endometrial cancer in ever users of hormonal contraceptives was 1.4 per 100,000 person-years, or approximately one less endometrial cancer for every 71,400 women of reproductive age who used hormonal contraception for one year. Use of hormonal contraception was estimated to prevent 25% of endometrial cancers in this population. CONCLUSIONS: Currently available combined hormonal contraceptives are still associated with enduring protection against endometrial cancer, particularly for type I carcinomas. IMPLICATIONS: We report substantive evidence of the association between different types of contemporary hormonal contraception and endometrial cancer risk in a national cohort of young Danish women. Currently available combined hormonal contraceptives are still associated with enduring protection against endometrial cancer, particularly for type I carcinomas.

Correction: Hormonal contraceptive use and risk of pancreatic cancer-A cohort study among premenopausal women.

[This corrects the article DOI: 10.1371/journal.pone.0206358.].