Current Oral Contraceptives Research Articles

Investigating the influence of oral contraceptive pill use on multiple sclerosis risk using UK Biobank data

ObjectiveTo investigate the association between oral contraceptive (OC) pill use and the risk of developing Multiple Sclerosis (MS), attempting to address the limitations present in previous studies which produced conflicting results. DesignPopulation-based cohort study using data from the UK Biobank. SubjectsThe study included 181,058 women of white ethnicity born in England between 1937 and 1970, among which 1131 had an MS diagnosis. ExposureOC use, considering the self-reported age of initiation and discontinuation. The exposures of interest include: i) ever use, ii) current use, iii) duration of current use in years, and iv) age and year at initiation. Main Outcome MeasuresMS diagnosis (ICD-10: G35) was used as outcome of interest, and the associations with the exposures of interest were investigated using marginal structural models with a time-to-event approach. To adjust for confounding, we included in the models several variables including MS polygenic risk score (MS-PRS), education level, parity, smoking, fertility problems, obesity, and mononucleosis. We further aimed to evaluate the influence of parity using a mediation analysis. ResultsThe association of both ever and current OC use did not result in a statistically significant MS hazard increase (ever vs never users, HR=1.30 [95%CI:0.93,1.82, p=0.12]; current vs never users, HR=1.35 [95%CI:0.81,2.25, p=0.25]). However, we highlighted parity as an effect modifier for this association. In nulliparous women, ever and current use resulted in a significant two-fold and three-fold MS hazard increase (HR=2.08 [95%CI:1.04,4.17, p=0.04] and HR=3.15 [95%CI:1.43,6.92, p=0.004]). These associations were supported by significant MS hazard increases for a higher duration of current use and for an earlier age at initiation. We further highlighted genetic MS susceptibility as another effect modifier, as a stronger OC-MS hazard association was found in women with a low MS-PRS. ConclusionOur findings highlighted how the association between OC use and MS vary based on individual characteristics such as parity and genetic MS susceptibility. Importantly, current use in nulliparous women was found to be associated with a three-fold increase in MS hazard. We acknowledge the need for cautious causal interpretation and further research to validate these findings across diverse populations and OC types.

Abstract 3442: Factors modifying the association between hormonal contraception and risk of early-onset breast cancer

Abstract Breast cancer rates among women younger than 50 years-old have been steadily increasing since the mid-1990s. There is consistent evidence that use of combination estrogen and progesterone oral contraceptives (OCs)—including contemporary formulations with lower estrogen—increases breast cancer risk. It is unclear, however, if this risk varies by factors such as progestin type in the OC formulation, timing of OC use, histopathologic characteristics of the breast cancer, or individual patient characteristics. This study included premenopausal women aged <50 years and cancer-free when they enrolled in the U.S.-based American Cancer Society Cancer Prevention Study-3 cohort between 2006 and 2013 (n=101,838 women). At enrollment participants responded to a detailed life history questionnaire including questions about type, brand, duration, and recency of OC use. Incident breast cancers diagnosed between 2006-2018 were identified through cancer registry linkages (n=759). Participants were followed until the first of 1) breast cancer diagnosis, 2) age >50 years, or 3) December 31, 2018. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate associations between OC use and breast cancer risk. On average, participants were 39.3 years at baseline and were followed for 5.7 years (up to 12.3 years). Current versus never use of OCs for 10+ years was associated with a higher risk of breast cancer (10-<20 years: HR=1.46, 95% CI: 1.03-2.07; 20-<30 years: HR=1.66, 95% CI: 1.14-2.41; 30+ years HR= 2.51, 95% CI: 0.77-8.16). Cessation of OC use progressively attenuated the association down to the null 15 years after discontinuation of use (HR=1.04, 95% CI: 0.73-1.49). Associations with current OC use varied by generation of progestin in the formulation (first generation: HR=1.37, 95% CI: 0.93-2.02; second: HR=1.79, 95% CI: 1.20-2.67; third: HR=1.65, 95% CI: 1.13-2.42; fourth: HR= 0.91, 95% CI: 0.49-1.67). The strongest associations were observed for use of formulations with norgestrel: HR=2.82, 95% CI: 1.54-5.19; norgestimate: HR=1.80, 95% CI: 1.19-2.72; and levonorgestrel: HR=1.56, 95% CI: 1.00-2.43. The OC-breast cancer associations were primarily limited to localized, grade 1 or 2, and ER+ disease. Race, income, body mass index, physical activity, alcohol use, cigarette smoking, parity, and breastfeeding did not appear to modify the associations. There were also no clear differences in the associations based on age at first or last OC use or timing relative to pregnancy. Current, long-term OC use was associated with increased risk of early-onset breast cancer. These data suggest that risks may vary with progestin content, and future studies are needed to define formulations that minimize breast cancer risk while still maximizing protection against other female cancers. Citation Format: Lauren R. Teras, Emily L. Deubler, Mark E. Sherman, Clara Bodelon, Lauren E. McCullough, James M. Hodge, Sicha Chantaprasopsuk, Alpa V. Patel. Factors modifying the association between hormonal contraception and risk of early-onset breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3442.

Morphologic alterations of the fear circuitry: the role of sex hormones and oral contraceptives.

Endogenous sex hormones and oral contraceptives (OCs) have been shown to influence key regions implicated in fear processing. While OC use has been found to impact brain morphology, methodological challenges remain to be addressed, such as avoiding selection bias between OC users and non-users, as well as examining potential lasting effects of OC intake. We investigated the current and lasting effects of OC use, as well as the interplay between the current hormonal milieu and history of hormonal contraception use on structural correlates of the fear circuitry. We also examined the role of endogenous and exogenous sex hormones within this network. We recruited healthy adults aged 23-35 who identified as women currently using (n = 62) or having used (n = 37) solely combined OCs, women who never used any hormonal contraceptives (n = 40), or men (n = 41). Salivary endogenous sex hormones and current users' salivary ethinyl estradiol (EE) were assessed using liquid chromatography - tandem mass spectrometry. Using structural magnetic resonance imaging, we extracted surface-based gray matter volumes (GMVs) and cortical thickness (CT) for regions of interest of the fear circuitry. Exploratory whole-brain analyses were conducted with surface-based and voxel-based morphometry methods. Compared to men, all three groups of women exhibited a larger GMV of the dorsal anterior cingulate cortex, while only current users showed a thinner ventromedial prefrontal cortex. Irrespective of the menstrual cycle phase, never users exhibited a thicker right anterior insular cortex than past users. While associations with endogenous sex hormones remain unclear, we showed that EE dosage in current users had a greater influence on brain anatomy compared to salivary EE levels and progestin androgenicity, with lower doses being associated with smaller cortical GMVs. Our results highlight a sex difference for the dorsal anterior cingulate cortex GMV (a fear-promoting region), as well as a reduced CT of the ventromedial prefrontal cortex (a fear-inhibiting region) specific to current OC use. Precisely, this finding was driven by lower EE doses. These findings may represent structural vulnerabilities to anxiety and stress-related disorders. We showed little evidence of durable anatomical effects, suggesting that OC intake can (reversibly) affect fear-related brain morphology.

Duration of oral contraceptive use relates to cognitive performance and brain activation in current and past users.

Previous studies indicate effects of oral contraceptive (OC) use on spatial and verbal cognition. However, a better understanding of the OC effects is still needed, including the differential effects of androgenic or anti-androgenic OC use and whether the possible impact persists beyond the OC use. We aim to investigate the associations of OC use duration with spatial and verbal cognition, differentiating between androgenic and anti-androgenic OC. Using functional magnetic resonance imaging (MRI), we scanned a group of 94 past and current OC-users in a single session. We grouped current OC users (N=53) and past OC users with a natural cycle (N=41) into androgenic and anti-androgenic user. Effects of OC use duration were observed for current use and after discontinuation. Duration of OC use was reflected only in verbal fluency performance but not navigation: The longer the current OC use, the less words were produced in the verbal fluency task. During navigation, deactivation in the caudate and postcentral gyrus was duration-dependent in current androgenic OC users. Only during the verbal fluency task, duration of previous OC use affects several brain parameters, including activation of the left putamen and connectivity between right-hemispheric language areas (i.e., right inferior frontal gyrus and right angular gyrus). The results regarding performance and brain activation point towards stronger organizational effects of OCs on verbal rather than spatial processing. Irrespective of the task, a duration-dependent connectivity between the hippocampus and various occipital areas was observed. This could suggest a shift in strategy or processing style with long-term contraceptive use during navigation/verbal fluency. The current findings suggest a key role of the progestogenic component of OCs in both tasks. The influence of OC use on verbal fluency remains even after discontinuation which further points out the importance of future studies on OC effects and their reversibility.

Effects of oral contraceptives on spatial cognition depend on pharmacological properties and phase of the contraceptive cycle.

The central nervous system effects of oral contraceptives (OCs) are not well-documented. In a set of 3 studies, we investigated a specific cognitive function, mental rotation, in healthy women currently using OCs for contraceptive purposes (n = 201) and in medication-free controls not using OCs (n = 44). Mental rotation was measured using a well-standardized and extensively validated psychometric test, the Vandenberg Mental Rotations Test (MRT). In an initial study (Study 1), current OC users (n = 63) were tested during the active or inactive phases of the contraceptive cycle in a parallel-groups design. Studies 2 and 3 were based on an archival dataset (n = 201 current OC users) that consisted of data on the MRT collected in real-time over a 30-year period and compiled for purposes of the present work. The OCs were combined formulations containing ethinyl estradiol (10-35 ug/day) plus a synthetic progestin. All 4 families of synthetic progestins historically used in OCs were represented in the dataset. Cognitive performance was evaluated during either active OC use (‘active phase’) or during the washout week of the contraceptive cycle (‘inactive phase’) when OC steroids are not used. The results showed a significant phase-of-cycle (POC) effect. Accuracy on the MRT was mildly diminished during the active phase of OC use, while scores on verbal fluency and speeded motor tasks were modestly improved. The POC effect was most evident in women using OCs that contained first- or second-generation progestins (the estrane family of progestins or OCs containing levonorgestrel), but not in women using OCs containing recently developed progestins and lower doses of ethinyl estradiol. Using independently established ratings of the estrogenic, androgenic, and progestogenic intensities of the different OC formulations, each brand of OC was classified according to its distinct endocrine profile. Multiple regression revealed that the effects of OC use on the MRT could be predicted based on the estrogenic strength of the contraceptives used. Estrogenic potency, not androgenic or anti-androgenic effects of the OC pill, may underlie the effects of OC usage on spatial cognition.

Oral Contraceptive and Menopausal Hormone Therapy Use and Risk of Pituitary Adenoma: Cohort and Case-Control Analyses.

No prospective epidemiologic studies have examined associations between use of oral contraceptives (OCs) or menopausal hormone therapy (MHT) and risk of pituitary adenoma in women. Our aim was to determine the association between use of OC and MHT and risk of pituitary adenoma in two separate datasets. We evaluated the association of OC/MHT with risk of pituitary adenoma in the Nurses' Health Study and Nurses' Health Study II by computing multivariable-adjusted hazard ratios (MVHR) of pituitary adenoma by OC/MHT use using Cox proportional hazards models. Simultaneously, we carried out a matched case-control study using an institutional data repository to compute multivariable-adjusted odds ratios (MVOR) of pituitary adenoma by OC/MHT use. In the cohort analysis, during 6 668 019 person-years, 331 participants reported a diagnosis of pituitary adenoma. Compared to never-users, neither past (MVHR = 1.05; 95% CI, 0.80-1.36) nor current OC use (MVHR = 0.72; 95% CI, 0.40-1.32) was associated with risk. For MHT, compared to never-users, both past (MVHR = 2.00; 95% CI, 1.50-2.68) and current use (MVHR = 1.80; 95% CI, 1.27-2.55) were associated with pituitary adenoma risk, as was longer duration (MVHR = 2.06; 95% CI, 1.42-2.99 comparing more than 5 years of use to never, P trend = .002). Results were similar in lagged analyses, when stratified by body mass index, and among those with recent health care use. In the case-control analysis, we included 5469 cases. Risk of pituitary adenoma was increased with ever use of MHT (MVOR = 1.57; 95% CI, 1.35-1.83) and OC (MVOR = 1.27; 95% CI, 1.14-1.42) compared to never. Compared to never use, current and past MHT use and longer duration of MHT use were positively associated with higher risk of pituitary adenoma in 2 independent data sets. OC use was not associated with risk in the prospective cohort analysis and was associated with only mildly increased risk in the case-control analysis.

Abstract P620: Non-O Blood Group and Risk of Early-Onset Ischemic Stroke in Oral Contraceptive Users

Introduction: While oral contraceptive (OC) use is generally safe, women at higher risk for vascular disease are advised to use alternative forms of contraception. Smoking, a prothrombotic factor, is a contraindication for OC use in women over age 35. ABO blood group, specifically the non-O blood types, has also been associated with thrombosis risk. We therefore hypothesized that the effects of smoking and OC use on stroke risk would be accentuated in women with non-O blood groups. Methods: Using data from the Genetics of Early Onset Stroke Study, we used 3 polymorphisms within the ABO locus to classify blood group type in women under age 50, including 347 cases and 383 controls. Logistic regression was used to assess the stroke risk of current OC use, defined as use within 30 days, adjusted for other risk factors, and stratified by O and non-O blood group type. Results: Of the 347 women with early-onset stroke, 45% had African ancestry, 51% had European ancestry, and 4% had other ancestry. The median age was 42 years. After adjusting for race, age, hypertension, diabetes, migraines and aura, and smoking status, the odds ratio (OR) for stroke for smoking alone and OC use alone were 3.0 (95% CI 2.1-4.2) and 3.7 (95% CI 1.7-8.4), respectively in this population. Blood group (O vs non-O) did not appreciably alter the magnitude of these associations. However, the joint risk of smoking and OC use was substantially higher in women with blood group non-O (OR = 9.5, 95% CI 3.2-34.9) vs in women with blood group O (OR=4.9, 95% CI 0.4-110.2). Conclusions: Our findings are consistent with the possibility that non-O type blood group confers an increased risk of early onset stroke among OC users who smoke. Further studies are needed to confirm or refute this possibility and to determine whether non-O blood type should be considered in assessing the risk of OC use.

Abstract 5760: Trends in oral contraceptive and intrauterine device use among reproductive aged women in the US from 1999-2017

Abstract Importance: Since the 1960s, an increase in the use of oral contraceptives (OC) and other hormonal contraceptives has mirrored a decreased incidence of ovarian and endometrial cancers in the US. With improved access and increased contraceptive options over time, it is important to follow trends of use and consider how changing patterns can affect gynecologic cancer risks. Objective: To evaluate trends in OC use and intrauterine device (IUD) use among reproductive aged women in the US. Methods: Nationally representative data from the National Health and Nutrition Examination Survey (NHANES, N=19,216) and the National Survey for Family Growth (NSFG, N=26,262) were used to determine current OC and IUD use among reproductive aged women in the US. Women with prior hysterectomy, bilateral oophorectomy or that were post-menopausal were excluded due to ineligibility for standard OCs. Adjusted logistic regression and unadjusted Joinpoint models (to determine inflection points) were used to evaluated trends in contraceptive use between 1999-2017. We used questionnaire data from continuous NHANES and NSFG cycles from 1999/2000 to 2015/16 and 2006/08 to 2015/17, respectively. Within each survey, temporal trends in OC use were assessed overall and by race, age, gravidity, education and BMI. OC formulation/generation were determined from current prescriptions in NHANES. Trends in IUD use were evaluated in NSFG. Results: Since 1999, self-reported OC use overall decreased annually by 3% in NHANES [OR 0.97 (95%CI 0.96, 0.99) P=0.001] and 4% in NSFG [0.96 (0.94, 0.97) P<0.001]. Annual percent change estimates from unadjusted joinpoint regression also suggested consistent decreases over time. Proportion of OC use by generation of progestin across all cycles was stable with an average of 42.3% 3rd generation, 31.3% 1st, 17.0% 2nd, and 9.5% 4th (the latter was limited to cycles from 2003/04 to 2015/16). Decreases in OC use over time did not vary by categories of race, age, education or BMI. However, trends in OC use varied significantly by gravidity in NHANES (Phet=0.05). OC use for nulligravid women was stable over time, while reported OC use decreased 4% annually in gravid women [OR 0.96 (0.94-0.98) P<0.001]. IUD use increased by 14% each year [OR 1.14 (1.11, 1.17) P<0.001]; 76.5% of users reported hormonal IUD use in the 2015/17 cycle. The largest uptake of IUD use (32% increase per year [OR 1.32 (1.21, 1.43) P<0.001]) occurred among nulligravid women, which was historically, a contraindication for IUD use. Conclusions: IUD use is increasing at a rate faster than that of the decreasing rate of OC use. There is some suggestion that like OC use, IUD use also reduces ovarian and endometrial cancer risks, although associations with hormonal IUDs are less clear. As such, the changing landscape of contraceptive practices in the US may alter future trends in ovarian and endometrial cancers and thus requires further surveillance. Citation Format: Lauren A. King, Kara A. Michels, Barry I. Graubard, Britton Trabert. Trends in oral contraceptive and intrauterine device use among reproductive aged women in the US from 1999-2017 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5760.

Association between oral contraceptives and risk of hemorrhagic stroke: a meta-analysis of observational studies.

To estimate the risk of hemorrhagic stroke associated with current use of oral contraceptives (OCs), and to further depict how the risk was affected by study characteristics. We searched PubMed, Embase, and Cochrane Library for relevant articles published up to February 2017 that examined the association between OC use and risk of hemorrhagic stroke. Two investigators independently reviewed articles based on inclusion criteria. The Newcastle-Ottawa scale was employed to evaluate quality of studies. Random-effects meta-analysis model was used to generate summary risk estimates. Fifteen independent studies (5 cohort studies and 10 case-control studies) with 4271 hemorrhagic stroke cases were included in this meta-analysis. The overall summary odds ratio (OR) for hemorrhagic stroke (HS) in relation to current OC use was 1.39 [95% confidence interval (CI), 1.05-1.83]. Subgroup analyses on hemorrhagic stroke types showed that OC use was associated with subarachnoid hemorrhage (SAH) (OR 1.68; 95% CI 1.21-2.12), but not with intracerebral hemorrhage (ICH) (OR 0.92; 95% CI 0.33-2.54). The risk of hemorrhagic stroke was increased slightly among current OC users with high-dose estrogen (OR 1.60; 95% CI 1.12-2.27). The risk of hemorrhagic stroke was further increased in OC users with additional risk factors including current smoking, hypertension, and history of migraine. This meta-analysis of observational studies suggests that current use of OCs could contribute to a small increased risk of hemorrhagic stroke, and the increased risk is related to subarachnoid hemorrhage, but not intracerebral hemorrhage.

Current smoking is associated with a larger waist circumference and a more androgenic profile in young healthy women from high-risk breast cancer families

The purpose was to elucidate the interplay between current smoking, anthropometric measurements, and endogenous hormone levels in women ≤ 40 years. Questionnaires on lifestyle and reproductive factors were completed by 269 healthy women from high-risk breast cancer families between 1996 and 2006 in Sweden. Blood samples for analyses of plasma testosterone, estradiol, androstenedione, sex hormone-binding globulin, and body measurements were obtained 5–10 days before predicted onset of the next menstrual period. Women without smoking status, who were currently breastfeeding, or using hormonal contraception other than combined oral contraceptives (OCs) were excluded (n = 27). Current smokers (n = 57) had larger waist circumference (adjp = 0.004) and waist-to-hip ratio (WHR) (adjp = 0.007) than non-smokers (n = 185). In non-OC users, adjusted mean androstenedione levels were higher in current smokers compared with non-smokers (10.3 vs. 8.6 nmol/L; adjp = 0.0002). While in current OC users estradiol levels were higher in smokers compared with non-smokers (22.5 vs. 17.4 pg/mL; adjp = 0.012). In multivariable models, WHR was associated with both current smoking (adjp ≤ 0.016) and higher levels of androstenedione (adjp = 0.05) or bioavailable testosterone (adjp = 0.001). Among non-OC users, a more androgenic profile was observed in current smokers compared with non-smokers, but not in current OC users. Irrespective of OC use, current smoking was associated with increased waist circumference.

Abstract 4263: Smoking impacts endogenous estradiol and testosterone levels in young healthy women

Abstract Introduction The purpose of the study was to elucidate the association between smoking and estradiol (E2) and testosterone (T) levels in young healthy women from high-risk families. Cigarette smoke contains multiple carcinogens and is considered a risk factor for breast cancer. However, tobacco also contains aromatase inhibiting substances, but the impact on hormonal levels in young women at the age when breast cancer is initiated is unclear and needs further elucidation. Material and methods Between 1996 and 2002, 258 healthy women from high-risk breast cancer families in Sweden were enrolled in a study on the impact of lifestyle factors in women <=40 years. Blood samples and body measurements were obtained in the luteal phase (5-10 days before predicted onset of the next menstrual cycle) by a trained research nurse. Participants filled out questionnaires on lifestyle and reproductive factors. Ongoing breastfeeding, use of hormonal contraceptives other than combined E+P oral contraceptives (OCs), as well as missing data on onset of next menstrual cycle and smoking status led to exclusion of 28 women. Two hundred thirty women including 33 known BRCA1/2 mutation carriers were included in the analyses. Weight and hormonal levels were not normally distributed and were transformed using the natural logarithm to obtain better distribution. Since OCs influence endogenous hormones, the women were stratified by current OC use. Multivariable linear regression were used to obtain P-values, adjusted for age, nulliparity, menstrual cycle day, waist-to-hip ratio (WHR), and weight. Geometric means for current smokers and non-smokers were standardized at age 29 years, nulliparity, number of days until onset of next menstrual period (7 days), WHR 0.76, and LNweight (64 kgs). Results In all women, the median age was 29 years old, (IQR 24-35), and the median year of birth was 1969, the median weight was 64 kgs, and the median WHR was 0.76. In total, 47% were parous, and 42% had ever smoked, whereas 22% were current smokers, and 38% were current OC users (40% of the smokers and 37% of the non-smokers). In non OC users, E2 levels were similar in smokers and non-smokers (adjP=0.26), while standardized total T levels were higher in smokers (51.8 vs 45.1 ng/dL; adjP =0.067). In contrast, among current OC users, smokers had higher standardized E2 levels (22.7 vs 17.7 pg/mL; adjP =0.023) compared with non-smokers, while total T levels were similar in smokers and non-smokers (adjP=0.56). Conclusion In non-OC users, a more androgenic profile was observed in smokers compared with non-smokers. While in OC users endogenous E2 levels were higher in smokers compared with non-smokers, which suggests that cigarette smoke may reduce the efficacy of the pill. Differential impact of smoking on endogenous E2 and total T levels in current OC users and non-users was thus observed. Therefore, history of OC use needs to be incorporated in studies on associations between smoking and breast cancer risk. Citation Format: Carolina Ellberg, Håkan Olsson, Helena Jernstrom. Smoking impacts endogenous estradiol and testosterone levels in young healthy women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4263. doi:10.1158/1538-7445.AM2017-4263

Abstract 4291: Body constitution in young healthy women from breast cancer higher risk families in relation to smoking

Abstract Introduction: The purpose of this study was to investigate potential associations between body composition and current smoking in young healthy women from high-risk families. Cigarette smoke contains >7000 chemicals of which 69 are established carcinogens and smoke also acts as an aromatase inhibitor. Smoking is now recognized as a carcinogen for the breast and influences both risk and prognosis. However, the underlying mechanisms need to be better elucidated. One study showed that breast cancer patients who smoked were younger, had a lower body mass index (BMI), smaller breast volumes, but a higher waist-to-hip ratio (WHR) than non-smokers. However, smoking was also associated with a higher frequency of prior oral contraceptive (OC) use. Since breast cancer development starts long before the tumor is clinically detectable, we aimed to study the impact of cigarette smoke on anthropometric factors. Material and methods: Between 1996 and 2006, 269 healthy women were included in a study on the impact of lifestyle factors in women <=40 years from high-risk breast cancer families. Thirty-six participants who had missing breast measurements or who had undergone previous breast surgeries, who were currently breast-feeding or who were current users of hormonal contraceptives other than combined E+P OCs or had missing smoking status were excluded, leaving 233 women of which 35 were known BRCA1/2 mutation carriers. Height, weight, waist- and hip circumference, and total breast volume were measured in a standardized way by a research nurse 5-10 days before predicted onset of the next menstrual period. Weight, BMI, breast volume, and waist circumference, were not normally distributed and were transformed using the natural logarithm to obtain a better distribution. Multivariable linear regression was used to obtain P-values, adjusted for age, nulliparity, and current OC use. Means and geometric means for smokers and non-smokers were standardized at age 29 years, nulliparity, and non-current OC use. Results: The median age was 29 years (IQR 24-35) and the median year of birth was 1970. Forty-two percent had ever smoked, 23% were current smokers, 28% were current OC users, and 54% were nulliparous. Current smoking was not associated with height, weight, BMI breast volume, or hip circumference (all adjPs=>0.18). However, current smokers had significantly larger standardized waist circumference (78 vs 74 cm; adjP=0.02), and higher standardized WHR (0.79 vs 0.76; adjP=0.003) compared with non-smokers. Conclusion: Current smokers had significantly larger waist circumference and higher WHR, but similar BMI and breast volume compared with non-smokers, although most women had anthropometric measures within WHO’s recommended limits. The difference in fat distribution towards more abdominal fat, suggests that current smoking is associated with a more inflammatory and/or androgenic profile at the age when breast cancer is initiated. Citation Format: Carolina Ellberg, Håkan Olsson, Helena Jernström. Body constitution in young healthy women from breast cancer higher risk families in relation to smoking [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4291. doi:10.1158/1538-7445.AM2017-4291

Oral Contraceptive Use and Risk of Ulcerative Colitis Progression: A Nationwide Study

Oral contraceptive (OC) use has been consistently linked to increased risk of inflammatory bowel disease. Nonetheless, a specific role of OC in the natural history of ulcerative colitis (UC) is unknown. We identified 6,104 incident female UC cases aged 16-51 years at diagnosis from the Swedish National Patient Register starting in January of 2003. Information on current OC use was obtained from the Prescribed Drug Register starting in July of 2005. We followed cases through December of 2014 for primary outcome defined as first UC-related surgery, and the secondary outcomes defined by recipient of the first prescription of oral steroids or anti-tumor necrosis factor (anti-TNF) use. We used Cox proportional hazard modeling with time-varying covariates to estimate multivariable-adjusted hazard ratio (aHR) and 95% confidence interval (CI). Over 31,421 person-years of follow up, we observed 162 cases of UC-related surgery. Compared with nonusers, current and past use of OC were not significantly associated with risk of UC-related surgery (aHR=0.79; 95% CI, 0.52-1.18; and aHR=0.74, 95% CI, 0.46-1.18, respectively). The association did not appear to be modified by type of OC use (progestin-only vs. combination of progestin and estrogen), longer duration of use, or higher number of dispensed prescriptions (All Ptrend>0.28). Similarly, longer use or higher cumulative number of OC prescriptions were not associated with increased risk of receiving a steroid prescription (Ptrend=0.68 and 0.63, respectively). In exploratory analyses restricted to Stockholm county, current OC use was not associated with increased risk of receiving anti-TNF therapy (aHR=0.83, 95% CI, 0.59-1.18). In a large nationwide registry of UC patients, we found no association between OC use and UC progression. Our data offer reassurance regarding the safety of OC assessed by its effect on risk of surgery and steroid or anti-TNF use in women with established UC.

Association Between Long-term Oral Contraceptive Use and Risk of Crohn’s Disease Complications in a Nationwide Study

Use of exogenous hormones, in the form of oral contraceptives (OCs), has been linked consistently to risk of Crohn's disease (CD). Nonetheless, it is not clear how OCs might contribute to the progression of CD. We conducted a prospective study of female patients with CD (age, 16-51 y), identified from the inpatient and outpatient care components of the Swedish National Patient Register from January 2002 through December 2013. Information on current OC use was obtained from the Prescribed Drug Register starting in July of 2005 and updated until December of 2013. Primary outcomes were defined as first CD-relatedsurgery and first steroid prescription. We used Cox proportional hazard modeling with time-varying covariates to estimate multivariable-adjusted hazard ratios (MV-adjusted HRs). We identified 482 incident cases of surgery among 4036 patients with CD, with a median follow-up period of 58 months. Compared with nonusers, the MV-adjusted HRs for surgery were 1.14 (95% confidence interval [CI], 0.80-1.63) forpast users and 1.30 (95% CI, 0.89-1.92) for current users. The risk of surgery increased with longer duration of use (Ptrend= .036) and higher prescribed daily dose (Ptrend= .016). Specifically, for women with more than3years of OC use, theMV-adjusted HR for surgery was 1.68 (95% CI, 1.06-2.67). The association was confined to the combination type of OC. We estimated that for every 83 patients with CD receiving the combination type of oral contraceptives for at least 1 year, 1 extra surgery is required. The rate of steroid prescriptions did not appear to increase with past or current use of OCs, compared with patients whohave not taken OCs (all Pcomparisons > .20). In a nationwide analysis of patients in Sweden, long-term use of OCs, particularly the combination type, was associated with an increased risk of surgery among women with established CD. Clinicians carefully should evaluate and monitor contraceptive options among women with established CD.

Oral Contraceptives and Breast Cancer Risk Overall and by Molecular Subtype Among Young Women

Evidence suggests that recent oral contraceptive (OC) use is associated with a small increased breast cancer risk; yet risks associated with contemporary OC preparations and by molecular subtype are not well characterized. We conducted a population-based case-control study of invasive breast cancer among women ages 20 to 44 residing in the Seattle-Puget Sound area from 2004 to 2010 (985 cases and 882 controls). We collected information on contraceptive use and participant characteristics via an in-person interview. Multivariable-adjusted logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). Lifetime duration of OC use for ≥ 15 years was associated with an increased breast cancer risk (OR, 1.5; 95% CI, 1.1-2.2). Current OC use (within 1 year of reference date) for ≥ 5 years was associated with an increased risk (OR, 1.6; 95% CI, 1.1-2.5) and there were no statistically significant differences in risk by OC preparation. Risk magnitudes were generally greater among women ages 20 to 39, and for estrogen receptor-negative (ER(-)) and triple-negative breast cancer (current use for ≥ 5 years among ages 20-39: ER(-) OR, 3.5; 95% CI, 1.3-9.0; triple-negative OR, 3.7; 95% CI, 1.2-11.8), although differences between groups were not statistically significant. Long-term use of contemporary OCs and current use for ≥ 5 years was associated with an increased breast cancer risk among women ages 20 to 44. Risk may be greater among younger women and for ER(-) and triple-negative breast cancer, but these findings require confirmation. Continued surveillance and pooled analyses of OC use and breast cancer risk by molecular subtype are needed as OC preparations evolve.

Oral contraceptives, human papillomavirus and cervical cancer

Oncogenic human papillomavirus is the key determinant of cervical cancer, but other risk factors interact with it to define individual risk. Among these, there is oral contraceptive (OC) use. A quantitative review of the link between OCs and cervical cancer was performed. Long-term (>5 year) current or recent OC use has been related to an about two-fold excess risk of cervical cancer. Such an excess risk, however, levels off after stopping use, and approaches unity 10 or more years after stopping. The public health implications of OC use for cervical cancer are limited. In any case, such implications are greater in middle-income and low-income countries, as well as in central and eastern Europe and Latin America, where cervical cancer screening and control remain inadequate.

Current Hormonal Contraceptive Use Predicts Female Extra-Pair and Dyadic Sexual Behavior: Evidence Based on Czech National Survey Data

Data from 1155 Czech women (493 using oral contraception, 662 non-users), obtained from the Czech National Survey of Sexual Behavior, were used to investigate evolutionary-based hypotheses concerning the predictive value of current oral contraceptive (OC) use on extra-pair and dyadic (in-pair) sexual behavior of coupled women. Specifically, the aim was to determine whether current OC use was associated with lower extra-pair and higher in-pair sexual interest and behavior, because OC use suppresses cyclical shifts in mating psychology that occur in normally cycling women. Zero-inflated Poisson (ZIP) regression and negative binomial models were used to test associations between OC use and these sexual measures, controlling for other relevant predictors (e.g., age, parity, in-pair sexual satisfaction, relationship length). The overall incidence of having had an extra-pair partner or one-night stand in the previous year was not related to current OC use (the majority of the sample had not). However, among the women who had engaged in extra-pair sexual behavior, OC users had fewer one-night stands than non-users, and tended to have fewer partners, than non-users. OC users also had more frequent dyadic intercourse than non-users, potentially indicating higher commitment to their current relationship. These results suggest that suppression of fertility through OC use may alter important aspects of female sexual behavior, with potential implications for relationship functioning and stability.

제4기 국민건강영양조사 자료에 근거한 한국 여성의 경구피임약 복용과 치주질환의 관련성

본 연구는 우리나라 여성을 대상으로 경구피임약 복용과 치주질환의 관련성을 분석하여 피임약이 치주질환에 미치는 영향을 파악하고자 하였다. 연구자료는 제4기 국민건강영양조사 자료 중 2008년과 2009년 결과를 이용하였고, 19-50세 폐경 전 가임여성 1,101명을 대상자로 선정하였다. 인구사회경제적 요인과 구강보건행태, 피임약 복용기간 및 치주질환 상태를 파악하여 chi-square 검정과 logistic regression 분석을 통해 경구피임약 복용과 치주질환과의 관련성을 조사하였다. 그 결과, 인구사회경제적 요인 중 연령과 결혼여부, 흡연상태가 경구피임약 복용과 통계적인 유의성을 나타내었다. 현재 경구피임약 복용여부와 치은조직 상태는 연관성이 없는 것으로 확인되었다. 치주질환 유병율은 연령에 따라 증가하였지만, 피임약 복용기간과 흡연, 칫솔질과 치간관리를 포함한 구강보건형태와는 통계적으로 유의한 차이를 보이지 않았다. 마지막으로 logistic regression 분석 결과, 혼란변수 보정여부에 따라 큰 차이 없이 치주질환은 경구피임약 복용여부 및 복용기간과 관련성이 없는 것으로 확인되었다. This study aims to evaluate the influence of oral contraceptive(OC) on periodontal disease. Research data was used the results derived from the Fourth Korean National Health and Nutrition Examination Survey(KNHANES), and 1,101 Korean women, aged 19 to 50 years with non-pregnant and premenopausal, were selected. The chi-square test and logistic regression analysis were performed to identify the relationship between OC use and periodontal disease, according to factors of demographic and socioeconomic, oral health behavior, OC use period, and periodontal status. In the results, OC use was statistically related with age, marital status and smoking. No significant differences were found in between the gingival condition and current OC use. The prevalence of periodontal disease increased with age, but did not have significant correlations with period of OC usage, smoking and oral health behavior. Final analysis was indicated that OC use is not associated with periodontal disease, regardless of adjustment for confounding variables.

374 Night shift work and prolactin in nurses and midwives - preliminary results

ObjectivesNight shift work and exposure to light at night suppress synthesis of melatonin and disrupt circadian rhythm. The pattern of secretion of many hormones, including prolactin, is dependent on circadian...

THU0535 Significantly Better Patient-Reported Outcomes in Women with Early Inflammatory Arthritis Using Oral Contraceptives Compared to Never Users

BackgroundData on the effects of oral contraceptives (OC) on the course of inflammatory arthritis (IA) are controversial. While some observations suggested a beneficial effect on disease activity, others did not....