Duration Of Oral Contraceptive Use Research Articles

Oral contraceptive use and cancer: final report from the Oxford–Family Planning Association contraceptive study

BackgroundThis analysis provides the final results on cancer incidence in relation to oral contraceptive (OC) use from the Oxford–Family Planning Association (Oxford-FPA) contraceptive study, which closed at the end of 2010. An additional 6 years of observation have been added since our last report and there has been an increase in the numbers of cancers of over 50% at seven of the sites considered. Study DesignThe Oxford-FPA study includes 17032 women aged 25–39 years recruited from 1968 to 1974 at contraceptive clinics in England and Scotland. These women were using OCs, a diaphragm or an intrauterine device. Information about cancer incidence among them has been collected from recruitment until closure of the study. ResultsOC use was not related to nonreproductive cancer. Breast cancer findings (1087 cases) were entirely negative; the rate ratio (RR) comparing ever users of OCs with never users was 1.0 [95% confidence interval (CI): 0.9–1.1]. Only two cases of cervical cancer have been added since our last report (total: 61 cases); the RR comparing ever use with never use is now 3.4 (95% CI: 1.6–8.9). The risk of this disease increases sharply with duration of OC use and declines steadily with interval since last OC use. OC use protects against both uterine body cancer (124 cases) and ovarian cancer (143 cases). The RRs comparing ever use with never use were 0.5 (95% CI: 0.3–0.7) and 0.5 (95% CI: 0.4–0.7), respectively. Protection against both these cancers increased with duration of OC use and waned with interval since last use, but an effect was still present 28 or more years after discontinuation. ConclusionsIn our study, OC use had no effect on nonreproductive cancers or on breast cancer. The risk of cervical cancer was increased and that of uterine body cancer and ovarian cancer was decreased by OC use. All these effects increased with duration of use and declined with interval since last use. The beneficial effects of OC use on cancer outweighed the adverse effects. These findings should reassure older women who used OCs in the past.

Colorectal Cancer Risk Associated with Hormone Use Varies by Expression of Estrogen Receptor-β

The risk of colorectal cancer is reduced among users of oral contraceptives or menopausal hormone therapy, but associations with reproductive characteristics that are markers of a woman's endogenous hormone milieu have not been consistently observed. To help understand possible mechanisms through which exogenous and endogenous hormonal exposures are involved in colorectal cancer, we assessed the risk of these malignancies according to tumor expression of estrogen receptor-β (ESR2). In a population-based study of postmenopausal women (503 cases and 721 controls matched for sex and age), immunohistochemical expression of ESR2 was determined in 445 cases of incident colorectal cancer. Unconditional logistic regression was used in case-case analyses to assess heterogeneity between risk associations according to ESR2 status and in case-control analyses to estimate associations separately for ESR2-negative and ESR2-positive tumors. For ESR2-positive tumors but not ESR2-negative tumors, colorectal cancer risk significantly decreased with duration of oral contraceptive use [per five-year increments OR ESR2-positive, 0.87, 95% confidence interval (CI), 0.77-0.99; OR ESR2-negative, 1.02, 95% CI, 0.91-1.15; Pheterogeneity = 0.07] and with duration of menopausal hormone therapy use (per five-year increments OR ESR2-positive, 0.84, 95% CI, 0.74-0.95; OR ESR2-negative, 0.94, 95% CI 0.84-1.05; Pheterogeneity = 0.06). Significant heterogeneity according to ESR2 expression was found for the association with current use of menopausal hormone therapy (<0.5 years ago; Pheterogeneity = 0.023) but not for associations with reproductive factors. In conclusion, our results suggest that hormone use decreases risk for ESR2-positive but not ESR2-negative colorectal cancer.

664 THE INCREASE IN POOR LIFESTYLE FACTORS IS A RISK FOR HEPATOCELLULAR CARCINOMA IN PATIENTS WITH HEPATITIS C VIRUS INFECTION

more common and recently several prognostic molecular features have been described. The risk of bleeding of HCAs is around 18% and of malignant transformation 4%. Two-thirds of HCAs with malignant transformation are b-catenin-activated. We investigated whether liver adenomatosis has the same risk factors to develop complications. Methods: Study population of 36 patients, seen between 1990– 2012 (2 pts excluded with glycogen storage disease). Several liver biopsies or resection specimens were available in 21 pts. Baseline characteristics: female/male ratio = 35/1; age: 38 yrs (17–65); oral contraception (OC) 32/34; duration of OC use: 20 yrs (6–35); Diabetes: 8/36 (21%) and BMI >25: 17/31 (55%). Results: Median follow up is 63 month (4–170). Histology: HNF1a inactivated n=6 (29%), b catenin-activated n=3 (14%), inflammatory n =8 (38%) and mixed (19%): HNF1a + inflammatory (n =1), HNF1a + b catenin-activated (n =1), inflammatory + b catenin-activated (n =2). Complications: bleeding (excluding intratumoral): 3/36 (8%) and malignant transformation: 4/36 (11%). The median minimal size of the nodule with malignant transformation (HCC) was 9cm (8.4–9cm). All of them were b catenin-activated. Treatments and outcome: regression (after stop OC): 6/36 (17%) with complete regression in 1 pt; surgical resections (due to bleeding or suspicion of HCC): 19/36 (53%); LT (due to HCC): 2/36 (6%); none of the pts died. Conclusion: Our series confirms a strong female predilection and a link with the metabolic syndrome. Regression after stop OC was observed in 17% (with one complete regression). The risk of malignant transformation was 11% and was only seen in nodules >8cm. Different nodules can have different phenotype markers. Malignant transformation was only seen in b-catenin activated lesions. The management of liver adenomatosis needs to be adapted to the histological phenotype of the lesions.

Hormonal contraceptives, menstrual cycle and brain response to faces

Both behavioral and neuroimaging evidence support a female advantage in the perception of human faces. Here we explored the possibility that this relationship may be partially mediated by female sex hormones by investigating the relationship between the brain's response to faces and the use of oral contraceptives, as well as the phase of the menstrual cycle. First, functional magnetic resonance images were acquired in 20 young women [10 freely cycling and 10 taking oral contraception (OC)] during two phases of their cycle: mid-cycle and menstruation. We found stronger neural responses to faces in the right fusiform face area (FFA) in women taking oral contraceptives (vs freely cycling women) and during mid-cycle (vs menstruation) in both groups. Mean blood oxygenation level-dependent response in both left and right FFA increased as function of the duration of OC use. Next, this relationship between the use of OC and FFA response was replicated in an independent sample of 110 adolescent girls. Finally in a parallel behavioral study carried out in another sample of women, we found no evidence of differences in the pattern of eye movements while viewing faces between freely cycling women vs those taking oral contraceptives. The imaging findings might indicate enhanced processing of social cues in women taking OC and women during mid-cycle.

PS2-28: The Association of Body Composition Indices and Hormonal Contraceptive Use in Adolescent and Young Adult Women

Background/Aims Hormonal contraception is a popular contraceptive choice among sexually-active women. Yet its association with body composition in younger women is not well understood. We compared body composition measures by duration of Depo-Provera (DMPA) use and dose and duration of oral contraceptive (OC) use in adolescent and young adult women. Methods Study participants were Group Health Cooperative members. DMPA use (new prevalent or none) was collected in 170 adolescents aged 14-18 years and in 440 women aged 18-39 years. OC use was gathered in 301 adolescents aged 14-18 years and 305 women aged 19-30 years. Among OC users ethinyl estradiol (EE) dose (=30mcg vs. <30mcg) and months of use were also collected. For all participants weight BMI and truncal and total fat and lean mass were estimated using DEXA. Mean differences in baseline body composition by dose and duration of hormone contraception use were compared cross-sectionally using ANOVA. Results Adolescents who were prevalent DMPA users had higher baseline truncal and total fat mass compared to adolescent non-DMPA users. For example baseline mean (SE) total fat mass was 23.3 (1.2) kilograms for prevalent DMPA users but was 19.9 (0.9) kilograms for non-DMPA users (p<0.05). No mean differences in the body composition measures were observed between new DMPA vs. non- DMPA adolescent users or among young women regardless of DMPA use. With OC use baseline BMI and truncal and total fat mass differed by EE dose in young adult women. Baseline mean (SE) total fat mass in kilograms for women using =30mcg EE doses <30mcg EE doses and for non-OC users was 20.8 (0.9) 19.0 (0.9) and 22.2 (0.9) respectively (p=0.02). No differences were noted between EE dose and body composition indices in adolescents. For both adolescents and young women baseline body composition was not associated with duration of OC use. Conclusions Our results suggest that DMPA use is associated with fat mass in adolescents and that EE dose in OCs is associated with fat mass in young adult women. Analysis of follow-up data to determine if these relationships continue to be seen longitudinally is needed.

Effect of oral contraceptive use on lipid profile in Korean women aged 35–55 years

BackgroundAlthough oral contraceptives (OCs) are widely used, their effects on lipid profile need monitoring according to current usage in different populations. Study DesignA cross-sectional study was conducted using data from 1541 participants aged 35–55 years collected by the 2005–2009 Korea National Health and Nutrition Examination Surveys. OC use, demographic characteristics and dietary intake were obtained from the participants by questionnaire, and lipid levels were determined by analysis of blood samples. ResultsLonger duration of OC use was positively associated with increasing levels of high-density lipoprotein cholesterol (HDL-C) and decreasing levels of low-density lipoprotein cholesterol (LDL-C). After adjusting for demographic and dietary factors, the odds ratio (OR) of low HDL-C (<50 mg/dL) was significantly decreased in the longer-term (>12 months) OC users (OR=0.36, 95% confidence interval 0.24–0.52) compared with those who never used OCs. However, use of OCs was not associated with a risk of high total cholesterol (≥240 mg/dL), high LDL-C (≥130 mg/dL), high triglycerides (≥150 mg/dL) or high ratio of triglycerides to HDL-C (>3.8). ConclusionsThese data suggest that the use of OCs may reduce the risk of dyslipidemia, mainly due to the decreased risk of low HDL-C, in Korean women.

Abstract 4488: Inflammation-related biomarkers and risk of epithelial ovarian cancer

Abstract Introduction: Chronic inflammation caused by ovulation-related wound healing is theorized to cause ovarian carcinogenesis. We examined associations between three plasma biomarkers of inflammation, CRP, IL-6, and TNFαR-2, and risk of epithelial ovarian cancer in a nested case-control study of ovarian cancer cases and controls from the Nurses’ Health Study (NHS) and NHSII as well as in the Women's Health Study (WHS) cohort (CRP only). We further performed a meta-analysis with previously published studies of these biomarkers and ovarian cancer. Methods: Associations between quartiles of CRP, IL-6, and TNFαR-2 and risk of epithelial ovarian cancer were calculated using unconditional logistic regression (NHS/NHSII) or Cox proportional hazards regression (WHS); NHS/NHSII and WHS were combined using random effects meta-analysis. All analyses were adjusted for age, menopausal status/post-menopausal hormone use, duration of oral contraceptive use, tubal ligation, parity, and body mass index. The NHS/NHSII analyses were additionally adjusted for blood draw characteristics (fasting status, time of day and month of draw). Random effects meta-analysis was used to combine these results with previously published results. Results: In the NHS/NHSII (n=218 cases) and WHS (n=159 cases), a 59% increased ovarian cancer risk was observed in the 4th quartile of CRP compared to the 1st quartile (95% CI: 1.08-2.34). Further, CRP &amp;gt;10mg/L compared to &amp;lt;1 mg/L, was associated with a 2.21-fold increased ovarian cancer risk (95% CI: 1.29-3.80). In meta-analyses with previously published studies, the 3rd compared to the 1st tertile of CRP was associated with a 41% increased risk (95% CI: 1.14-1.74) (Table). There were no statistically significant associations between quartiles of IL-6 or TNFαR2 and ovarian cancer risk in the NHS/NHSII or in a meta-analysis with a previous publication. Conclusion: Our results suggest that higher levels of circulating CRP, but not IL-6 or TNFαR2, are associated with increased risk of ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4488. doi:1538-7445.AM2012-4488

Further evidence for lack of negative associations between hormonal contraception and mental health

BackgroundThere is limited and inconsistent information concerning the effects of hormonal contraception [oral contraceptives (OCs) and the levonorgestrel-releasing intrauterine system (LNG-IUS)] on mental health. The aim of this work was to further study the association(s) between the use of OCs and the LNG-IUS and psychopathology. Study designData concerning adult women who participated in the national FINRISK Study Surveys in Finland in 1997, 2002 and 2007 were analyzed. The associations between the current use, as well as the duration of use of OCs and the LNG-IUS vs. mood symptoms, psychological and physical symptoms and recent psychiatric diagnoses were tested. ResultsA negative association between the current use of OCs and Beck Depression Inventory-13 (BDI-13) score was found. Some other negative associations, all characterized by a small effect size, were detected between current use of OCs and the BDI items feelings of dissatisfaction, feelings of uselessness, irritability, lost interest in people and lost appetite. Additionally, only weak positive associations were found between the duration of OC use and irregular heart rate, insomnia and recent anhedonia. No noteworthy associations emerged between current use of the LNG-IUS, or its duration, and any of the inquired items. ConclusionThe use of hormonal contraception is not associated with negative influence on mental health. Current OC use seems to be associated with better mood, whereas the associations between duration of use of hormonal contraception and mental health effects are not clear.

Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case–control studies

SummaryBackgroundEndometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes of ovarian cancer.MethodsData from 13 ovarian cancer case–control studies, which were part of the Ovarian Cancer Association Consortium, were pooled and logistic regression analyses were undertaken to assess the association between self-reported endometriosis and risk of ovarian cancer. Analyses of invasive cases were done with respect to histological subtypes, grade, and stage, and analyses of borderline tumours by histological subtype. Age, ethnic origin, study site, parity, and duration of oral contraceptive use were included in all analytical models.Findings13 226 controls and 7911 women with invasive ovarian cancer were included in this analysis. 818 and 738, respectively, reported a history of endometriosis. 1907 women with borderline ovarian cancer were also included in the analysis, and 168 of these reported a history of endometriosis. Self-reported endometriosis was associated with a significantly increased risk of clear-cell (136 [20·2%] of 674 cases vs 818 [6·2%] of 13 226 controls, odds ratio 3·05, 95% CI 2·43–3·84, p<0·0001), low-grade serous (31 [9·2%] of 336 cases, 2·11, 1·39–3·20, p<0·0001), and endometrioid invasive ovarian cancers (169 [13·9%] of 1220 cases, 2·04, 1·67–2·48, p<0·0001). No association was noted between endometriosis and risk of mucinous (31 [6·0%] of 516 cases, 1·02, 0·69–1·50, p=0·93) or high-grade serous invasive ovarian cancer (261 [7·1%] of 3659 cases, 1·13, 0·97–1·32, p=0·13), or borderline tumours of either subtype (serous 103 [9·0%] of 1140 cases, 1·20, 0·95–1·52, p=0·12, and mucinous 65 [8·5%] of 767 cases, 1·12, 0·84–1·48, p=0·45).InterpretationClinicians should be aware of the increased risk of specific subtypes of ovarian cancer in women with endometriosis. Future efforts should focus on understanding the mechanisms that might lead to malignant transformation of endometriosis so as to help identify subsets of women at increased risk of ovarian cancer.FundingOvarian Cancer Research Fund, National Institutes of Health, California Cancer Research Program, California Department of Health Services, Lon V Smith Foundation, European Community's Seventh Framework Programme, German Federal Ministry of Education and Research of Germany, Programme of Clinical Biomedical Research, German Cancer Research Centre, Eve Appeal, Oak Foundation, UK National Institute of Health Research, National Health and Medical Research Council of Australia, US Army Medical Research and Materiel Command, Cancer Council Tasmania, Cancer Foundation of Western Australia, Mermaid 1, Danish Cancer Society, and Roswell Park Alliance Foundation.

Abstract A95: The impact of fertility drug use, infertility, and lifetime ovulation on ovarian cancer risk

Abstract Background: Ovarian cancer (OC) risk is associated with factors related to lifetime ovulation including hormone use, pregnancy, and breastfeeding. Factors increasing lifetime ovulation have been found to be positively associated with OC risk. Concern regarding the use of fertility drugs, the majority of which stimulate ovulation, and OC risk has increased over the past several decades as the rate of women seeking fertility treatment rapidly rises. The relationship between fertility drug use and OC is complex because the association may be attributable to several factors including: greater number of lifetime ovulatory cycles among nulliparous women, underlying causes of infertility, shared genetic susceptibility to ovarian cancer and infertility, or a correlate of infertility such as the use of fertility drugs. Controversy has surrounded fertility drug use as it relates to OC risk due to inconclusive results from previous studies, which were unable to account for these factors. Objective: The objective of this study was to evaluate the relationship between fertility drug use and OC risk, distinguish the effect of fertility drugs from underlying causes of infertility, and determine whether the relationship is modified by lifetime ovulation. Methods: The Hormones and Ovarian Cancer Prediction (HOPE) study includes 902 ovarian/peritoneal/fallopian tube cancer cases and 1,802 population-based controls recruited from Pennsylvania, Ohio, and New York and enrolled between 2003 and 2008. Trained interviewers collected detailed reproductive and medical histories through in-person interviews. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for fertility drug use and OC risk. Fertility drug use was classified as either never or ever using fertility drugs. The models were adjusted for age, race, education, site, family history of ovarian and breast cancers, duration of oral contraceptive use, duration of breastfeeding, hormone replacement therapy, tubal ligation, parity, and talc use. Lifetime ovulatory years were estimated by subtracting age of menarche from age of menopause and adjusting this by time spent pregnant, breastfeeding, or taking ovulation-suppressing contraceptives. Lifetime ovulation was classified as low, intermediate and high based on tertiles within age groups (&amp;lt;35, 35–55, and ≥55). Breslow-Day tests of homogeneity were used to assess the relationship between fertility drug use and OC risk with lifetime ovulation stratified by age as well as underlying causes of infertility. Results: Fertility drug use was not significantly associated with OC risk [OR=1.02, 95% CI: 0.70–1.47] when adjusting for known OC risk factors; the relationship remained non-significant when accounting for duration of use [OR=1.00, 95% CI: 0.98–1.01], and cause of infertility [p-heterogeneity=0.85]. Fertility drug use also remained non-significant after stratifying by lifetime ovulatory years for women &amp;lt;35 years old [p-heterogeneity=0.86], women 35–55 years old [p-heterogeneity=0.78], and women ≥55 years old [p-heterogeneity=0.52]. Lifetime ovulatory years were independently associated with OC risk among women &amp;lt;35 [OR=1.13, 95% CI: 1.04–1.23] and women 35–55 years old [OR=1.06, 95% CI: 1.04–1.08], but not for women ≥55 [OR=1.01, 95% CI: 0.99–1.02. Conclusion: These results provide further evidence that fertility drug use does not significantly contribute to overall OC risk when controlling for known risk factors and underlying cause of infertility. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A95.

Oral contraceptives and endometriosis: the past use of oral contraceptives for treating severe primary dysmenorrhea is associated with endometriosis, especially deep infiltrating endometriosis

The relationship between the use of oral contraception (OC) and endometriosis remains controversial. We therefore compared various characteristics of OC use and the surgical diagnosis of endometriosis histologically graded as superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA) or deep infiltrating endometriosis (DIE). This cross-sectional study included 566 patients without visible endometriosis at surgery as controls, and 410 patients with histologically proven endometriosis, categorized by their worst lesions as SUP n = 47, OMA n = 120 and DIE n = 243. Personal data, including on OC use, were prospectively collected during standardized interviews. Statistical analysis was performed using unconditional logistic regression. Past OC users had an increased incidence of endometriosis (adjusted odd ratios (OR) = 2.79, 95% confidence interval (CI) 1.74-5.12, P = 0.002) of any revised American Fertility Society stage. Women who had previously used OC for severe primary dysmenorrhea were even more frequently diagnosed with endometriosis (adjusted OR = 5.6, 95% CI 3.2-9.8), especially for DIE (adjusted OR = 16.2, 95% CI 7.8-35.3). Women who had previously used OC for other reasons also had an increased risk of endometriosis, but to a lesser extent (adjusted OR = 2.6, 95% CI 1.8-4.1). The age at which OC was initiated, duration of OC use and free interval from last OC use were not significantly different between control and endometriosis women, irrespective of histological grading. Current OC users did not show an increased prevalence of endometriosis (OR = 1.22, 95% CI 0.6-2.52). Our data indicate that a history of OC use for severe primary dysmenorrhea is associated with surgical diagnosis of endometriosis, especially DIE, later in life. However, this does not necessarily mean that use of OC increases the risk of developing endometriosis. Past use of OC for primary dysmenorrhea may serve as a marker for women with endometriosis and DIE.

The association between oral contraceptive use, bone mineral density and fractures in women aged 50–80 years

Background The associations between oral contraceptive (OC) use, bone mineral density (BMD) and the risk of fractures remain controversial. Study Design A cross-sectional study of 491 women aged 50–80 years was performed. We assessed OC use and fractures by questionnaire, and BMD and vertebral deformity by dual-energy x-ray absorptiometry. Results Ever use of OC was associated with significantly higher BMD at the total body (6%, p<.001) and spine (4%; p=.05) (but not hip) after adjustment for confounders. There was also a significant association between duration of OC use and total body and spine BMD. Use of OCs for 5–10 years was associated with reduced vertebral deformity (adjusted odds ratio 0.46, 95% confidence interval 0.22–0.94). Conclusions Oral contraceptive use and duration were associated with higher total body and spine BMD and a consistent reduction in vertebral deformities, although most associations did not reach significance.

Abstract P6-09-06: Oral Contraceptive Use and Overall Breast Disease Risk: Cross Sectional Retrospective Study

Abstract Background: Oral contraception (OC) is one of the most widely used means for birth control in the world. In several studies, OC has been associated with a slightly increased risk of breast cancer in current user, and with a decreased risk of benign disease. Little is known about atypical high risk lesions. Our goal was to investigate whether OC use was a risk factor or a protective factor for benign, high risk or malignant breast lesions. Material and methods : From 2001 to 2007, all non-palpable breast lesions referred to biopsy or cytology in Saint Louis hospital were prospectively registered. Demographic and clinical data including oral contraceptive pill use extent were reported. We defined benign lesions (fibroadenoma, blunt duct adenosis, fibrocystic changes, epithelial hyperplasia, others), high risk lesions (atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ and malignant lesions (ductal carcinoma in situ, invasive ductal or lobular carcinoma). The aim was to analyse the correlation between the duration of OC use and the occurrence of the breast disease classified by histology groups. Patients with previous history of benign breast disease or malignancy were excluded. Results: The analysis was performed on 1329 breast lesions. The breakdown of the lesions were as follows: 819 benign lesions (fibroadenoma n=155, blunt duct adenosis n=169, fibrocystic disease n=194, epithelial hyperplasia n=132, others n=170), 104 high risk lesions (atypical ductal hyperplasia n=54, atypical lobular hyperplasia n=29, lobular carcinoma in situ n=21), and 406 malignant lesions (ductal carcinoma in situ n=158, invasive ductal or lobular carcinoma n=248). The duration of oral contraception use was not significantly associated with the occurrence of benign, high risk or malignant breast disease. When focusing on benign lesion subtypes, no association was observed either. Older age was significantly correlated to the occurrence of atypia or carcinoma. Significant difference existed in the median age of apparition 55 y.o and 57 y.o respectively, versus 53 y.o for benign lesion (p&amp;lt; 0,0001), as well as menopausal status at diagnosis (57.7% and 68.3%, respectively, versus 53% for benign lesion) (p&amp;lt; 0,0001). Conclusion: In this cross sectional retrospective study, the duration of OC use was not associated with differential occurrence of benign, high risk and malignant breast lesion. Although a lack of statistical power may be invoked to explain the results, we are called to believe that the magnitude of an effect of OC use is small, if ever it exists. Results [Table 1] Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-09-06.

Abstract B100: Rotating night shift work and risk of ovarian cancer

Abstract Introduction: Night shift work has been associated with higher risks of breast, endometrial, colorectal, prostate cancer and non-Hodgkin's lymphoma. These associations may be driven by a diminished ability of the pineal gland to produce melatonin among those exposed to light at night. Melatonin likely has multiple anti-cancer mechanisms, including down-regulation of the reproductive axis and direct actions of melatonin on estrogen receptors — both of note for ovarian cancer. Moreover, melatonin exhibits a growth-inhibitory effect on ovarian cancer cell lines. Few epidemiological studies have evaluated an association between night shift work and ovarian cancer risk. Within the NHS and NHSII cohorts, we prospectively assessed the association of rotating night shift work with ovarian cancer risk. Methods: Total number of years of rotating night shift work (defined as at least 3 nights per month in addition to days and evenings during that month) was queried in 1988 for NHS and in 1989 for NHSII. Duration was updated in 1991, 1993, 2001, and 2005 for NHSII. We used Cox proportional hazards regression to model the incidence rate ratios (RR) and 95% confidence intervals (CI) of ovarian cancer for each shift work category (1-2 years, 3-5 years, 6-9 years, 10-14 years, 15-19 years, 20-29 years, and 30+ years), compared to those who never worked rotating shifts, adjusting for age in months, cohort, tubal ligation, duration of oral contraceptive use, parity, BMI, smoking status, menopausal status, family history of ovarian cancer, and duration of breastfeeding. In our analysis, we updated the values for these covariates when new data were available and otherwise carried forward the values from the previous cycle or the last cycle when each covariate was assessed. Results: There were 666 cases of ovarian cancer among 2,856,537 person-years of follow-up time. Overall, rotating shift work was not associated with ovarian cancer risk: 15-19 years vs. none: OR: 1.21; 95% CI: 0.78-1.86; 20-29 years vs. none: OR: 0.65; 95% CI: 0.35-1.19; 30+ years vs. none: OR: 0.79; 95% CI: 0.40-1.54. Estimates were unchanged when adjusted for menstrual irregularity. Conclusion: In this large prospective study, overall, there was no association between duration of rotating night shift work and risk of ovarian cancer. Additional analyses stratifying by hormonal receptor status. menopausal status and other potential effect modifiers are ongoing and may reveal subgroup associations. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B100.

Oral contraceptives, reproductive history and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition.

Background:Oral contraceptive use and reproductive factors may initiate long-term changes to the hormonal milieu and thereby, possibly influence colorectal cancer risk.Methods:We examined the association of hormonal and reproductive factors with risk of colorectal cancer among 337 802 women in the European Prospective Investigation into Cancer and Nutrition, of whom 1878 developed colorectal cancer.Results:After stratification for center and age, and adjustment for body mass index, smoking, diabetes mellitus, physical activity and alcohol consumption, ever use of oral contraceptives was marginally inversely associated with colorectal cancer risk (hazard ratio (HR), 0.92; 95% confidence interval (CI), 0.83–1.02), although this association was stronger among post-menopausal women (HR, 0.84; 95% CI: 0.74–0.95). Duration of oral contraceptive use and reproductive factors, including age at menarche, age at menopause, type of menopause, ever having an abortion, parity, age at first full-term pregnancy and breastfeeding, were not associated with colorectal cancer risk.Conclusion:Our findings provide limited support for a potential inverse association between oral contraceptives and colorectal cancer risk.

Risk factors for non-invasive lesions of the fallopian tube in BRCA mutation carriers

Objective To identify risk factors for the presence of a non-invasive lesion of the fallopian tube in women with a BRCA1 or BRCA2 mutation. Methods 173 BRCA mutation carriers underwent a prophylactic salpingo-oophorectomy at the University Health Network, Toronto between 2000 and 2008 and were evaluated for the presence of a non-invasive lesion of the fallopian tube. Patients were classified as having p53 overexpression (“p53-signature”), a tubal intra-epithelial carcinoma (TIC) or normal tubal epithelium. We obtained a risk factor questionnaire from all patients. We calculated odds ratios for several risk factors, comparing patients with a tubal abnormality to those with normal histology. Results Of the 173 patients, 43 (25%) were found to have a tubal lesion, including 23% of the BRCA1 mutation carriers and 27% of the BRCA2 mutation carriers. The prevalence of a non-invasive tubal lesion increased with age; an abnormality was present in 5% of women who had surgery before the age of 40 (1 of 12) and in 56% of women who underwent surgery at age 60 or above (6 of 13; p = 0.004). A non-invasive lesion of either type was found in 31.2% of women with a BMI > 25 kg/m 2) compared to 18.0% of patients with a BMI < 25 kg/m 2 at the time of surgery ( p = 0.05). The average duration of oral contraceptive use among women with normal tubes was 6.0 years, compared to an average duration of 4.0 years for women with a p53 signature ( p = 0.09) and was 2.7 years for women with a TIC ( p = 0.0003). Conclusion The prevalence of tubal p53 signature and TIC increases with age at salpingectomy and with BMI. Oral contraceptive use is associated with a decrease in the prevalence of TICs.

Reproductive risk factors and endometrial cancer: the European Prospective Investigation into Cancer and Nutrition

Endometrial cancer risk has been associated with reproductive factors (age at menarche, age at menopause, parity, age at first and last birth, time since last birth and use of oral contraceptives (OCs)]. However, these factors are closely interrelated and whether they act independently still requires clarification. We conducted a study to examine the association of menstrual and reproductive variables with the risk of endometrial cancer among the European Prospective Investigation into Cancer and Nutrition (EPIC). Among the 302,618 women eligible for the study, 1,017 incident endometrial cancer cases were identified. A reduction in endometrial cancer risk was observed in women with late menarche, early menopause, past OC use, high parity and a shorter time since last full-term pregnancy (FTP). No association was observed for duration of breast feeding after adjustment for number of FTP or for abortion (spontaneous or induced). After mutual adjustment, late age at menarche, early age at menopause and duration of OC use showed similar risk reductions of 7-8% per year of menstrual life, whereas the decreased risk associated with cumulative duration of FTPs was stronger (22% per year). In conclusion, our findings confirmed a reduction in risk of endometrial cancer with factors associated with a lower cumulative exposure to estrogen and/or higher exposure to progesterone, such as increasing number of FTPs and shorter menstrual lifespan and, therefore, support an important role of hormonal mechanisms in endometrial carcinogenesis.

Mortality among contraceptive pill users: cohort evidence from Royal College of General Practitioners’ Oral Contraception Study

Objective To see if the mortality risk among women who have used oral contraceptives differs from that of never users.Design Prospective cohort study started in 1968 with mortality data supplied...

Rate of Pregnancy After Using Drospirenone and Other Progestin-Containing Oral Contraceptives

To determine whether prior oral-contraceptive use has a negative effect on the ability of women to conceive in both the short-term and long-term. The European Active Surveillance Study on Oral Contraceptives (EURAS-OC) was a controlled, prospective, noninterventional cohort study of 59,510 users of oral contraceptives containing drospirenone or other progestins in clinical practice in seven European countries. In a planned secondary analysis, pregnancy outcomes were investigated in 2,064 participants in EURAS-OC who stopped oral-contraceptive use after study entry because of planned pregnancy. The influence of age, parity, progestin type, ethinylestradiol dose, duration of oral-contraceptive use, and smoking status on the rate of pregnancy was assessed. Overall, 21.1% (95% confidence interval [CI] 19.4-23.0%) of the past oral-contraceptive users were pregnant one cycle after oral-contraceptive cessation. This rate increased to 79.4% (95% CI 77.6-81.1%) at 1 year (13 cycles). Progestin type, ethinylestradiol dose, duration of oral-contraceptive use, and parity had no major influence on the rate of pregnancy after oral-contraceptive cessation. Up to age 35 years, age had only a minor influence on the rate of pregnancy. Rates of pregnancy were reduced in women older than 35 years and in current smokers. Previous oral-contraceptive use does not negatively affect initial and 1-year rates of pregnancy after oral-contraceptive cessation. A comparison of these data with data external to this study indicates that the negative effect of aging on fecundity is not amplified by oral-contraceptive use. II.

Oral contraceptives and postmenopausal hormones and risk of contralateral breast cancer among BRCA1 and BRCA2 mutation carriers and noncarriers: the WECARE Study

The potential effects of oral contraceptive (OC) and postmenopausal hormone (PMH) use are not well understood among BRCA1 or BRCA2 (BRCA1/2) deleterious mutation carriers with a history of breast cancer. We investigated the association between OC and PMH use and risk of contralateral breast cancer (CBC) in the WECARE (Women's Environment, Cancer, and Radiation Epidemiology) Study. The WECARE Study is a population-based case-control study of 705 women with asynchronous CBC and 1,398 women with unilateral breast cancer, including 181 BRCA1/2 mutation carriers. Risk-factor information was assessed by telephone interview. Mutation status was measured using denaturing high-performance liquid chromatography followed by direct sequencing in all participants. Outcomes, treatment, and tumor characteristics were abstracted from medical records. Ever use of OCs was not associated with risk among noncarriers (RR = 0.87; 95% CI = 0.66-1.15) or BRCA2 carriers (RR = 0.82; 95% CI = 0.21-3.13). BRCA1 carriers who used OCs had a nonsignificant greater risk than nonusers (RR = 2.38; 95% CI = 0.72-7.83). Total duration of OC use and at least 5 years of use before age 30 were associated with a nonsignificant increased risk among mutation carriers but not among noncarriers. Few women had ever used PMH and we found no significant associations between lifetime use and CBC risk among carriers and noncarriers. In conclusion, the association between OC/PMH use and risk of CBC does not differ significantly between carriers and noncarriers; however, because carriers have a higher baseline risk of second primaries, even a potential small increase in risk as a result of OC use may be clinically relevant.