Current Oral Contraceptive Users Research Articles

Cost-effectiveness of the dual prevention pill for contraception and HIV pre-exposure prophylaxis.

Women in sub-Saharan Africa (SSA) experience the world's highest rates of both HIV infection and unintended pregnancy. The Dual Prevention Pill (DPP) is a novel multipurpose prevention technology (MPT) that co-formulates HIV pre-exposure prophylaxis (PrEP) and combined hormonal oral contraception into a single daily pill. As a dual indication product, the DPP may be preferred by women facing these overlapping health risks. However, most SSA countries face severe healthcare resource constraints. Research is needed to assess whether, in what populations, and in what use cases the DPP would be cost-effective. We augmented an agent-based SSA HIV model with maternal health parameters including unintended pregnancy, abortion, and maternal mortality. Based on a previous market analysis, we assumed a primary DPP user population of current oral contraceptive users ages 25-49, and alternative user populations in different risk groups (age 15-24, sex workers, HIV-serodiscordant couples) and baseline product use profiles (unmet need for contraception, oral PrEP use, condom use). In three geographies (western Kenya, Zimbabwe, South Africa), we estimated HIV infections averted, pregnancies averted, disability-adjusted life-years (DALYs) averted, and the incremental cost-effectiveness ratio (ICER) over a 30-year time horizon, assuming equivalent adherence to the DPP as to oral contraceptives, higher adherence, or lower adherence. The DPP is likely to be a cost-effective alternative to oral PrEP among users in need of contraception. Among women not already using PrEP, the DPP is likely to be cost-saving in sex workers and serodiscordant couples. The DPP is unlikely to be cost-effective in oral contraceptive users in the general population. Switching from oral contraception to the DPP could be net harmful in some settings and populations if it were to substantially reduces adherence to oral contraception. Results were robust to a range of time horizons or discount rates. The DPP has the potential to be cost-effective and cost-saving in populations at substantial HIV risk. Outcomes are sensitive to adherence, implying that effective counseling and decision-making tools for users considering the DPP will be essential. More research is needed to understand real-life adherence patterns and ensure health benefits achieved from contraception alone are not lost.

Weak associations between personality and contraceptive choice.

Prospective randomized controlled trials on hormonal contraceptive (HC) effects on the brain are rare due to a number of methodological challenges. Thus, much of the evidence on HC effects on the brain comes from cross-sectional studies comparing HC-users to non-users. In interpreting these findings, it is of importance to be aware of potential confounds associated with women's contraceptive choices. Previous studies have discussed age, education, social status, sexual orientation, relationship status, and tolerability of HC. Given the current trend toward a reduction in HC use and increased skepticism toward HC it seems relevant to also identify variables associated with women's attitudes toward HC and whether they may represent confounds for neuroscientific studies. In the present study, we investigated whether women's personality characteristics were associated with their choice to use or not use HC in the present, past and future and the type of HC chosen. 1,391 females aged 18-45 years participated in an online survey including the HEXACO-60 personality questionnaire, as well as two different measures of gender role, and provided information about their current and previous contraceptive status, as well as experiences with and attitudes toward contraceptive use. We compared (i) current, previous and never-users of HC, (ii) prospective users of HC to women who opposed future HC use, and (iii) current users of IUDs to current users of oral contraceptives. Results revealed that associations between personality and the decision to use or not use HC were negligible, while differences in personality were observed corresponding to contraceptive type. Current users of IUDs showed higher agreeableness and extraversion compared to current users of oral contraceptives. The results suggest that personality is more strongly associated to the choice of contraceptive type rather than the choice between hormonal and non-hormonal options.

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.

Duration, recency, and type of hormonal contraceptive use and antimüllerian hormone levels

To assess whether the duration, recency, or type of hormonal contraceptive used is associated with antimüllerian hormone (AMH) levels, given that the existing literature regarding the association between hormonal contraceptive use and AMH levels is inconsistent. Cross-sectional study. Baseline data from the Study of the Environment, Lifestyle and Fibroids Study, a 5-year longitudinal study of African American women. The patients were 1,643 African American women aged 23-35 years at the time of blood drawing (2010-2012). None. Serum AMH level was measured by an ultrasensitive enzyme-linked immunosorbent assay. Linear regression models were used to estimate percent differences in mean AMH levels and 95% confidence intervals (CIs) according to use of hormonal contraceptives, with adjustment for potential confounders. In multivariable-adjusted analyses, current users of hormonal contraceptives had 25.2% lower mean AMH levels than non-users of hormonal contraceptives (95% CI: -35.3%, -13.6%). There was little difference in AMH levels between former users and non-users of hormonal contraceptives (-4.4%; 95% CI: -16.3%, 9.0%). AMH levels were not appreciably associated with cumulative duration of use among former users or time since last use among non-current users. Current users of combined oral contraceptives (-24.0%; 95% CI: -36.6%, -8.9%), vaginal ring (-64.8%; 95% CI: -75.4%, -49.6%), and depot medroxyprogesterone acetate (-26.7%; 95% CI: -41.0%, -8.9%) had lower mean AMH levels than non-users. The present data suggest that AMH levels are significantly lower among current users of most forms of hormonal contraceptives, but that the suppressive effect of hormonal contraceptives on AMH levels is reversible.

Epidemiologic and biologic correlates of serum HE4 and CA125 in women from the National Health and Nutritional Survey (NHANES)

ObjectivesIn women with ovarian cancer, tumor features largely determine serum HE4 and CA125 levels, but non-tumor factors may also influence levels and be better understood by studying determinants in a well-characterized sample of women without cancer. MethodsSerum HE4 and CA125 were measured in 2302 women from the 2001–2002 cohort of the National Heath and Nutritional Survey (NHANES). Publicly-available data on this cohort included demographic/reproductive variables, blood counts, and measurements of C-reactive protein (CRP), total homocysteine (tHcy), cotinine, and creatinine which were examined as predictors of HE4 and CA125 using multivariate models and correlational analyses. ResultsHE4 increased non-linearly by age and current smokers had higher HE4. CA125 was lower in postmenopausal women and non-whites and trended downward with increasing BMI. Current-users of oral contraceptives (OCs) had lower HE4 and CA125; and a downward trend for CA125 was seen with increasing OC use. Pregnant women had higher CA125 and nursing women higher HE4. HE4 and CA125 were positively correlated with neutrophils, monocytes, and the neutrophil-to-lymphocyte ratio and inversely correlated with lymphocytes and the lymphocyte-to-monocyte ratio. CRP was positively correlated with both HE4 and CA125 in postmenopausal women. Strong positive correlations existed for HE4 with both tHcy and creatinine. ConclusionsSerum levels of HE4 and CA125 are influenced by several hormonal or environmental stimuli which affect non-cancerous tissues normally expressing HE4 or CA125. Cytokine co-expression in those tissues may, in turn, affect white cell counts and account for their correlation with HE4 or CA125 levels.

Impact of oral contraceptives and breastfeeding on disease activity in a sample of Egyptian rheumatoid arthritis patients

BackgroundWomen are more affected by rheumatoid arthritis (RA) than men and the incidence of RA in women increases around the age of menopause indicating that hormonal factors may have a role in disease pathogenesis and progression. Despite several studies on the role of sex hormones and oral contraceptives (OCs) in RA patients, the effect of combined oral contraceptives on RA disease activity is still controversial, and since few studies have been performed in Egypt on this issue so we aimed to study the effect of OCs, breastfeeding, and prolactin on disease activity and their relation to the titer of autoantibodies in female Egyptian RA patients.ResultsOne hundred twenty married female RA patients were classified into three groups based on the OCs use (n = 40 each); current, past and non-users and according to lactation into three groups; lactating using OCs (n = 22), lactating not using OCs (n = 30), and non-lactating (n = 68). Our patients were using combined estrogen-progestin oral contraceptives. Clinical manifestations, disease activity, and laboratory findings were determined. The clinical manifestations including arthritis, and morning stiffness were significantly reduced in current users in comparison to past and non-users. Mean DAS28 was reduced significantly (p < 0.05) in current and past users of OCs. Also, using OCs during lactation reduced the clinical manifestations significantly. Lactating women who were not using OCs had significantly high DAS28 and ESR (p < 0.05) in comparison to lactating using OCs and non-lactating. On the other hand, using OCs reduced serum prolactin significantly. Lactating women not using OCs had significantly high serum prolactin (p < 0.05) and (p < 0.001) in comparison to lactating using OCs and non-lactating respectively which was correlated with DAS28 score.ConclusionOral contraceptives may be considered in RA female patients not only as a suitable birth control method but also it has a controlling effect on disease activity even during lactation.MessageOral contraceptives ameliorate disease activity in RA patients

Ulipristal acetate compared to levonorgestrel emergency contraception among current oral contraceptive users: a cost-effectiveness analysis

ObjectiveTo estimate the cost-effectiveness of ulipristal acetate (UPA) and levonorgestrel (LNG) emergency contraception (EC) on pregnancy prevention among combined oral contraceptive (COC) pill users with an extended pill-free interval. We accounted for the potential interaction of COCs and obesity on EC efficacy. MethodsWe built a decision-analytic model using TreeAge software to evaluate the optimal oral EC strategy in a hypothetical cohort of 100,000 twenty-five-year-old women midcycle with a prolonged "missed" pill episode (8–14 days). We used a 5-year time horizon and 3% discount rate. From a healthcare perspective, we obtained probabilities, utilities and costs inflated to 2018 dollars from the literature. We set the threshold for cost-effectiveness at a standard $100,000 per quality-adjusted life-year. We included the following clinical outcomes: number of protected cycles, unintended pregnancies, abortions, deliveries and costs. ResultsWe found that UPA was the optimal method of oral EC, as it resulted in 720 fewer unintended pregnancies, 736 fewer abortions and 80 fewer deliveries at a total cost savings of $50,323 and 79 additional adjusted life-years. UPA continued to be the optimal strategy even in the case of obesity or COCs impacting UPA efficacy, in which a COC interaction would have to change efficacy of UPA by 160% before LNG was the dominant strategy. ConclusionOur models found that UPA was the dominant choice of oral EC among COC users with a prolonged "missed" pill episode, regardless of body mass index or an adverse interaction of COCs on UPA. ImplicationsUlipristal acetate is the dominant choice of oral emergency contraception among combined oral contraceptive users.

Use of oral contraceptives and risk of ulcerative colitis – A systematic review and meta-analysis

Numerous studies have investigated the link between oral contraceptives and risk of ulcerative colitis (UC), but the results have been controversial. We systematically reviewed all relevant published studies and evaluated the association between the use of oral contraceptives and the development of UC by meta-analysis. Databases including PubMed, EMbase, CNKI and WanFang data were thoroughly searched from inception to September 2018 to collect the studies on the correlation between oral contraceptives and the risk of UC. The studies were screened according to the inclusion and exclusion criteria by two researchers independently, and the data were extracted and the quality was evaluated. Meta-analysis was performed using Stata 13.0 software. There were 12 studies involving 303,340 participants that reported on the association between oral contraceptives and UC. The pooled odds ratio (OR) of UC in oral contraceptive users was 1.25 [95% confidence interval (CI) 1.04–1.51, p = 0.02]. The risk was significant in the current oral contraceptive users (OR 1.49, 95% CI 1.12–1.96, p = 0.005) whereas the past oral contraceptive use was not significantly associated with UC (OR 1.17, 95% CI 0.95–1.43, p = 0.141). This study provides evidence of an association between the use of oral contraceptives and the onset risk of UC. The study also shows that the risk for patients who stop using the oral contraceptives was decreased. These findings may be used as important reference for the use of oral contraceptives and the management of UC patients.

The relationship between anti-Müllerian hormone serum level and body mass index in a large cohort of infertile patients

To evaluate the relationship between serum Anti-Müllerian hormone (AMH) level and body mass index (BMI) in infertile patients. Medical records of patients with infertility evaluated between January 2013 and February 2018 in the Reproductive Medicine Department of a private hospital were reviewed. Patients with the following criteria were excluded from the study: polycystic ovary syndrome, primary ovarian insufficiency, AMH values > 10 ng/mL, current oral contraceptive users and previous ovarian surgery or endometriosis, and anovulation of other causes, except decreased ovarian reserve. A total of 2204 infertile patients were included (mean age 34.58 ± 4.3 years, mean BMI 22.35 ± 3.6 kg/m2, and mean serum AMH 2.44 ± 2.17 ng/ml). In the entire group of patients, serum AMH level was positively correlated with BMI after adjustment for age (beta = 0.059, p < 0.005). When the association between serum AMH level and BMI was analysed in subgroups of patients, after adjustment for age, we found a positive correlation between the two parameters in patients ≤ 35 years old (< 0.05), of normal weight (p < 0.05) and with normal ovarian reserve (p < 0.05). After adjustment for age, BMI ≥ 25 kg/m2 was significantly associated with higher AMH values in comparison to normal weight patients. In infertile patients, AMH is positively correlated with BMI, especially in patients younger than 35 years, of normal weight and with normal ovarian reserve. Moreover, the presence of mild excess adiposity seems to be associated with higher AMH values. Our data contradict the previous studies showing a negative impact of excess adiposity on AMH serum levels.

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 &amp;lt;=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 &amp;gt;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 &amp;lt;=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=&amp;gt;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

Demographic, lifestyle, and other factors in relation to antimüllerian hormone levels in mostly late premenopausal women

To identify reproductive, lifestyle, hormonal, and other correlates of circulating antimüllerian hormone (AMH) concentrations in mostly late premenopausal women. Cross-sectional study. Not applicable. A total of 671 premenopausal women not known to have cancer. None. Concentrations of AMH were measured in a single laboratory using the picoAMH ELISA. Multivariable-adjusted median (and interquartile range) AMH concentrations were calculated using quantile regression for several potential correlates. Older women had significantly lower AMH concentrations (≥40 [n = 444] vs. <35years [n = 64], multivariable-adjusted median 0.73ng/mL vs. 2.52ng/mL). Concentrations of AMH were also significantly lower among women with earlier age at menarche (<12 [n = 96] vs. ≥14years [n = 200]: 0.90ng/mL vs. 1.12ng/mL) and among current users of oral contraceptives (n = 27) compared with never or former users (n = 468) (0.36ng/mL vs. 1.15ng/mL). Race, body mass index, education, height, smoking status, parity, and menstrual cycle phase were not significantly associated with AMH concentrations. There were no significant associations between AMH concentrations and androgen or sex hormone-binding globulin concentrations or with factors related to blood collection (e.g., sample type, time, season, and year of blood collection). Among premenopausal women, lower AMH concentrations are associated with older age, a younger age at menarche, and currently using oral contraceptives, suggesting these factors are related to a lower number or decreased secretory activity of ovarian follicles.

Reproductive and Lifestyle Determinants of Anti-Müllerian Hormone in a Large Population-based Study

Anti-müllerian hormone (AMH) is an ovarian reserve marker that is increasingly applied in clinical practice as a prognostic and diagnostic tool. Despite increased use of AMH in clinical practice, large-scale studies addressing the influence of possible determinants on AMH levels are scarce. We aimed to address the role of reproductive and lifestyle determinants of AMH in a large population-based cohort of women. In this cross-sectional study, age-specific AMH percentiles were calculated using general linear modeling with CG-LMS (Cole and Green, Lambda, Mu, and Sigma model, an established method to calculate growth curves for children). Women from the general community participating in the Doetinchem Cohort study were assessed. Two thousand three hundred twenty premenopausal women were included. The effect of female reproductive and lifestyle factors on shifts in age-specific AMH percentiles was studied. In comparison to women with a regular menstrual cycle, current oral contraceptive (OC) users, women with menstrual cycle irregularity, and pregnant women had significantly lower age-specific AMH percentiles (for OC use, 11 percentiles lower; for cycle irregularity, 11 percentiles lower; and for pregnancy, 17 percentiles lower [P value for all <.0001]). Age at menarche and age at first childbirth were not associated with the age-specific AMH percentile. Higher parity was associated with 2 percentiles higher age-specific AMH (P = .02). Of the lifestyle factors investigated, current smoking was associated with 4 percentiles lower age-specific AMH percentiles (P = .02), irrespective of the smoking dose. Body mass index, waist circumference, alcohol consumption, physical exercise, and socioeconomic status were not significantly associated with age-specific AMH percentiles. This study demonstrates that several reproductive and lifestyle factors are associated with age-specific AMH levels. The lower AMH levels associated with OC use and smoking seem reversible, as effects were confined to current use of OC or cigarettes. It is important to give careful consideration to the effect of such determinants when interpreting AMH in a clinical setting and basing patient management on AMH.

Contraindications to progestin-only oral contraceptive pills among reproductive-aged women

BackgroundProgestin-only oral contraceptive pills (POPs) have fewer contraindications to use compared to combined pills. However, the overall prevalence of contraindications to POPs among reproductive-aged women has not been assessed. Study DesignWe collected information on contraindications to POPs in two studies: (1) the Self-Screening Study, a sample of 1267 reproductive-aged women in the general population in El Paso, TX, and (2) the Prospective Study of OC Users, a sample of current oral contraceptive (OC) users who obtained their pills in El Paso clinics (n=532) or over the counter (OTC) in Mexican pharmacies (n=514). In the Self-Screening Study, we also compared women's self-assessment of contraindications using a checklist to a clinician's evaluation. ResultsOnly 1.6% of women in the Self-Screening Study were identified as having at least one contraindication to POPs. The sensitivity of the checklist for identifying women with at least one contraindication was 75.0% [95% confidence interval (CI): 50.6%–90.4%], and the specificity was 99.4% (95% CI: 98.8%–99.7%). In total, 0.6% of women in the Prospective Study of OC Users reported having any contraindication to POPs. There were no significant differences between clinic and OTC users. ConclusionThe prevalence of contraindications to POPs was very low in these samples. POPs may be the best choice for the first OTC oral contraceptive in the United States.

Large Prospective Study of Ovarian Cancer Screening in High-Risk Women: CA125 Cut-Point Defined by Menopausal Status

Previous screening trials for early detection of ovarian cancer in postmenopausal women have used the standard CA125 cut-point of 35 U/mL, the 98th percentile in this population yielding a 2% false positive rate, whereas the same cut-point in trials of premenopausal women results in substantially higher false positive rates. We investigated demographic and clinical factors predicting CA125 distributions, including 98th percentiles, in a large population of high-risk women participating in two ovarian cancer screening studies with common eligibility criteria and screening protocols. Baseline CA125 values and clinical and demographic data from 3,692 women participating in screening studies conducted by the National Cancer Institute-sponsored Cancer Genetics Network and Gynecologic Oncology Group were combined for this preplanned analysis. Because of the large effect of menopausal status on CA125 levels, statistical analyses were conducted separately in pre- and postmenopausal subjects to determine the impact of other baseline factors on predicted CA125 cut-points on the basis of 98th percentile. The primary clinical factor affecting CA125 cut-points was menopausal status, with premenopausal women having a significantly higher cut-point of 50 U/mL, while in postmenopausal subjects the standard cut-point of 35 U/mL was recapitulated. In premenopausal women, current oral contraceptive (OC) users had a cut-point of 40 U/mL. To achieve a 2% false positive rate in ovarian cancer screening trials and in high-risk women choosing to be screened, the cut-point for initial CA125 testing should be personalized primarily for menopausal status (50 for premenopausal women, 40 for premenopausal on OC, and 35 for postmenopausal women).

Potential reduction in neural tube defects associated with use of Metafolin-fortified oral contraceptives in the United States

The objective of the study was to estimate the potential reduction of neural tube defects (NTDs) through the use of Metafolin-fortified oral contraceptives (OCs) in the United States. A population-based decision analytic model was developed to estimate the benefits of increased red blood cell (RBC) folate levels through the use of Metafolin-fortified OCs on NTD risk during pregnancy. We modeled women who began the year taking Metafolin-fortified or traditional OCs. Folate levels were derived from the National Health and Nutrition Examination Survey and clinical trial data. NTD risk was estimated by applying a published risk equation to respective RBC folate levels. The number of predicted NTD cases declined by 23.7% to 31.4%, depending on median baseline folate levels in women taking a fortified OC compared with taking a traditional OC. Metafolin-fortified OCs have the potential to reduce the number of folate-dependent NTDs among current and recent OC users.

Epidemiology of the contraceptive pill and venous thromboembolism

Current users of combined oral contraceptives have an increased risk of venous thromboembolism. The risk appears to be higher during the first year of use and disappears rapidly once oral contraception is stopped. There is a strong interaction between hereditary defects of coagulation, combined oral contraceptive use and venous thromboembolism. Nevertheless, the routine screening of women before they use combined oral contraception is not recommended. Venous thromboembolism seems to be higher in overweight users, and after air, and possibly other forms of, travel. Both the oestrogen and progestogen content of combined oral contraceptives have been implicated in differences in venous thrombotic risk between products. Even if real, the absolute difference in risk between products is small, because the background incidence of venous thromboembolism in young women is low. All currently available combined oral contraceptives are safe. Progestogen-only oral contraceptives are not associated with an increased risk of venous thromboembolism.