Current Hormonal Contraceptive Use Research Articles

Abstract PS10-01: Hormonal Contraception and Breast Cancer Risk for Carriers of Germline Pathogenic Variants in BRCA1 and BRCA2

Abstract BACKGROUND: Current use of hormonal contraception is associated with a 20-30% relative increase in the risk of breast cancer (BC) for women in the general population compared with never using. Longer duration of use is associated with higher risk, and the risk remains elevated above that of never users for at least 5 years after cessation. Most published data are for various formulations of the combined oral contraceptive pill, but associations are similar for progestogen-only contraceptives, including intrauterine devices. For women in the general population who use hormonal contraceptives in their 20s and 30s, when baseline BC risk for most women is low, these increased relative risks translate into only small increases in absolute risk. It is unclear whether use of hormonal contraceptives increases BC risk for women carrying a germline BRCA1 or BRCA2 pathogenic variant (PV). These women are at markedly higher risk of early-onset BC, so even slightly increased relative risks could translate to important increases in their absolute risk of BC. This study assessed the association between use of any hormonal contraception and BC risk for BRCA1 and BRCA2 PV carriers using individual participant data from four prospective cohorts. METHODS: Data from females born after 1920 with a PV in BRCA1 or BRCA2 and no history of cancer or bilateral mastectomy at cohort entry were analyzed. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for BC (invasive disease or ductal carcinoma in situ) associated with use of hormonal contraceptives for at least 1 year, with age as the timescale, entry at cohort enrolment, and censoring at the earlier of bilateral mastectomy, death, diagnosis of another cancer or last follow-up. Analyses were adjusted for study, birth cohort, first-degree family history of BC, parity, premenopausal bilateral oophorectomy and menopausal status. Current use of hormonal contraceptives was defined as use within the previous year, to account for cessation of use due to BC symptoms or clinical investigation. RESULTS: Of 3,882 BRCA1 and 1,509 BRCA2 PV carriers, 53% and 71%, respectively had ever used hormonal contraceptives (for at least one year). The median cumulative duration of hormonal contraceptive use was 4.8 and 5.7 years, respectively. Overall, 488 BRCA1 and 191 BRCA2 PV carriers developed incident BC during a median of 5.9 and 5.6 years of follow-up, respectively. For BRCA1 PV carriers, use of hormonal contraceptives for at least 1 year was associated with increased BC risk (HR [95% CI]: 1.29 [1.04-1.60] p=0.019). BC risk increased with longer cumulative duration of hormonal contraceptive use (HR [95% CI]: 1.13 [0.88-1.45] p=0.35, 1.48 [1.11-1.96] p=0.007 and 1.56 [1.13-2.17] p=0.007 for 1-5, 6-10 and >10 years of use, respectively), with an estimated proportional increase in risk of 3% (1%-5%, p=0.002) for each additional year of use. For BRCA2 PV carriers, there was no evidence that current or past use, or cumulative duration of use, were associated with increased risk of BC, but confidence intervals on the HRs were wide. CONCLUSION: Hormonal contraceptive use is associated with an increased risk of BC for women carrying PVs in BRCA1 and risk increases with cumulative duration of use. Hormonal contraceptives are an important healthcare option for women; they provide excellent contraceptive efficacy and reduce risks of ovarian and endometrial cancer. Decisions about use of hormonal contraceptives in women at increased risk for BC due to BRCA1 PVs need to carefully weigh the risks and benefits; while shorter-term use may result in only small increases, prolonged cumulative use may result in larger increases in absolute BC risk that may not be acceptable to some women. Citation Format: Kelly-Anne Phillips, Joanne Kotsopoulos, Susan Domchek, James Chamberlain, Julie Bassett, Amber Aeilts, Irene Andrulis, Saundra Buys, Wanda Cui, Mary Daly, Andrea Eisen, William Foulkes, Michael Friedlander, Jacek Gronwald, John Hopper, Esther John, Beth Karlan, Raymond Kim, Jan Lubiński, Kelly Metcalfe, Katherine Nathanson, Christian F. Singer, Heather Symecko, Nadine Tung, Steven Narod, Mary Beth Terry, Roger Milne. Hormonal Contraception and Breast Cancer Risk for Carriers of Germline Pathogenic Variants in BRCA1 and BRCA2 [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS10-01.

Hormonal contraceptive use and women’s well-being: links with body image, eating behavior, and sleep

ABSTRACT The goal of the current study was to examine associations between hormonal contraceptive use and indicators of well-being including body image, eating behavior, sleep and energy level. Drawing on a health protection framework, we expected that individuals who use hormonal contraceptives would be more attuned to health and report more positive health attitudes and behaviors on these dimensions. Undergraduate college women (N = 270; M = 19.39 years, SD = 2.43, range 18–39 years) from diverse racial/ethnic and sexual orientation groups completed a survey online. Measures included hormonal contraception use, body image, weight control behavior, breakfast consumption, sleep behavior, and daytime energy level. Nearly 1/3 (30.9%) of the sample reported current hormonal contraceptive use, with most users reporting use of birth control pills (74.7%). Women who used hormonal contraceptives reported significantly higher appearance orientation and body surveillance, lower average energy, more frequent night awakenings, and more naps. Longer duration of hormonal contraceptive use was significantly related to higher body surveillance, and engaging in more unhealthy weight control behavior. Hormonal contraceptive use is not related to indicators of greater well-being. Rather, hormonal contraceptive use is related to greater attention to appearance, lower daytime energy, and some indicators of poorer sleep quality. Clinicians who prescribe hormonal contraceptives should attend to body image, sleep and energy concerns among users.

Use of systemic hormonal contraception and depression: a nested case-control study

IntroductionDepression is twice as common in women as in men, especially in the young age group. Multiple factors may contribute to this gender difference. Growing attention is being focused on the role of sex hormones, including those of hormonal contraception (HC). Some recent studies have indicated a higher risk of depression among women using HC, although the results are inconclusive.ObjectivesThe aim of this study is to examine the associations between the use of hormonal contraception and the risk of depression in childbearing age women.MethodsThe original cohorts for the study included all women aged 15-49 years with at least one redeemed prescriptions for HC in Finland in 2017 (n=294,356), and a 1:1 age-matched cohort of non-users. After exclusion of prevalent cases (n=35,102), all incident cases of depression (as recorded in the Care Register of Health Care and Register of Primary Health Care Visits) in 2018-2019 were identified (n=23,480), and a 4:1 age-matched control group (n=93,920) was selected from the above cohorts. Current use of HC in the 180 days before the event was compared in cases and controls, and associations with risk of depression were tested via conditional multivariate logistic regression models.ResultsDuring the follow-up, 23,480 incident cases of depression were identified. Current use (in the 180 days before the event) of HC (OR 0.82, 95% CI 0.79-0.85), in particular of estradiol- or ethinylestradiol-containing combined HC was associated with a lower risk of depression (OR 0.83, 95% CI 0.76–0.89; OR 0.74, 95% CI 0.71–0.78, respectively) compared to non-use of HC. The results remained significant (OR 0.87, 95% CI 0.81-0.95; and OR 0.77, 95% CI 0.73-0.81, respectively) after controlling for covariates (marital and socioeconomic status, education level, chronic diseases). Use of progestin-only contraception was not associated with altered risk of depression.ConclusionsUse of HC in childbearing age women is not associated with increased risk of depression. Rather, the use of estradiol- or ethinylestradiol-containing HC is associated with a lower risk of depression.Disclosure of InterestNone Declared

Use of hormonal contraception and attempted suicide: a nested case-control study

IntroductionIn Finland more than 40% of fertile aged women used some type of hormonal contraception (HC) in the period 2010-2013. A proportion of women using HC complains of side effects, including mood symptoms. The relationship between the use of HC and the risk of attempted suicide (AS) is still a matter of debate.ObjectivesTo assess the association of the use of HC with the risk of AS during 2017-2019.MethodsData were retrieved from the Prescription Centre, Care Register of Health Care, Register of Primary Health Care Visits and Statistics Finland. A total of 587 823 women, aged 15-49 years, using and not using HC in 2017 were analysed in the initial incidence study. All incident AS cases during 2018-2019, and their 4:1 age-matched controls (1 174 346 person-years) were analysed in a nested case-control setting via conditional logistic regression models.ResultsAltogether 818 AS cases occurred during the follow-up (incidence rate: 0.70/1000 person-years, 95% CI 0.65–0.75), with an IRR of HC vs. no-HC use of 0.73 (0.63–0.83). Current use (in the 180 days before the event) of estradiol- or ethinylestradiol-containing HC was associated with a lower risk of AS (0.53, 0.33–0.87; 0.49, 0.37–0.64, respectively) compared to non-use of HC. After controlling for covariates (marital and socioeconomic status, education level, use of psychotropic medications), only current use of HC containing ethinylestradiol remained significant (0.39, 0.23–0.65).ConclusionsA lower risk of AS is associated with the use of HC, and specifically of ethinylestradiol-containing HC.DisclosureNo significant relationships.

Prevalence of hormonal contraceptive use and reported side effects of the menstrual cycle and hormonal contraceptive use in powerlifting and rugby

ABSTRACT OBJECTIVES The prevalence of hormonal contraceptive (HC) use and the associated symptomology of use or non-use are under-studied in athletic populations, and in particular, in strength and collision sports. This study aimed to investigate the prevalence of hormonal contraceptive use and reported side effects of the menstrual cycle and hormonal contraceptive use in powerlifters and rugby players. METHODS Competitive female powerlifters and rugby players (aged ≥18 y), representing a strength and a collision sport respectively, completed an anonymous online questionnaire for the purpose of assessing self-reported prevalence of HC use, and symptoms of the menstrual cycle and HC use. Athletes were categorized by sport (powerlifters, n=149; rugby players, n=135) in order to conduct a stratified analysis. For open-ended questions, a content analysis was conducted to categorize responses, and frequency analyses were performed. RESULTS Current HC use was reported by 51.1% of athletes, with similar prevalence for the two sports (powerlifting, 48.3% vs. rugby, 54.1%, P=0.34). Side effects of the menstrual cycle were reported in 83.5% of non-HC users, with the most common being unspecified cramping (42.4%), headache/migraine (24.5%), and fatigue (24.5%). Side effects were reported in 40.0% of HC users, with the most common being mood changes (17.9%), stomach pain (8.3%) and headaches/migraines (6.9%). CONCLUSION A large proportion of HC users and non-users in this study experience negative side effects of HC use and the menstrual cycle, respectively. The symptoms experienced by both groups are wide-ranging, with a high degree of variation between individuals. The negative side-effects experienced by HC users and non-users may have an influence on athletic performance, and this requires future investigation.

Anti-Müllerian hormone levels among contraceptive users: evidence from a cross-sectional cohort of 27,125 individuals

Anti-Müllerian hormone has become the clinical biomarker-based standard to assess ovarian reserve. As anti-Müllerian hormone testing becomes more common, more individuals are seeking to interpret the values obtained while using contraceptives. To appropriately counsel women, a better understanding of anti-Müllerian hormone levels in women using different contraceptives is needed. To study the association between different forms of contraceptives and anti-Müllerian levels in women of reproductive age. This is a cross-sectional study including 27,125 US-based women aged 20 to 46 years, accessing reproductive hormone results through Modern Fertility and who provided informed consent to participate in the research. Anti-Müllerian hormone levels were collected through dried blood spot card (95.9%) or venipuncture (4.1%), and previous work has shown high correlation between hormone levels collected by these 2 methods. Multiple linear regressions were run to compare anti-Müllerian hormone levels in women using contraceptives with women not on any contraceptive, controlling for age, age of menarche, body mass index, smoking, sample collection method, cycle day, and self-reported polycystic ovary syndrome diagnosis. We also analyzed whether duration of contraceptive use predicted anti-Müllerian hormone levels in users of the hormonal intrauterine device and combined oral contraceptive pill, given the size of these contraceptive groups. Mean anti-Müllerian hormone levels were statistically significantly lower in women using the combined oral contraceptive pill (23.68% lower; coefficient, 0.76; 95% confidence interval, 0.72-0.81; P<.001), vaginal ring (22.07% lower; coefficient, 0.78; 95% confidence interval, 0.71-0.86; P<.001), hormonal intrauterine device (6.73% lower; coefficient, 0.93; 95% confidence interval, 0.88-0.99; P=.014), implant (23.44% lower; coefficient, 0.77; 95% confidence interval, 0.69-0.85; P<.001), or progestin-only pill (14.80% lower; coefficient, 0.85; 95% confidence interval, 0.76-0.96; P=.007) than women not on any contraceptive when controlling for covariates. Anti-Müllerian hormone levels were not significantly different when comparing women not using any contraceptives to those using the copper intrauterine device (1.57% lower; coefficient, 0.98; 95% confidence interval, 0.92-1.05, P=.600). Associations between contraceptive use and anti-Müllerian hormone levels did not differ based on self-reported polycystic ovary syndrome diagnosis. Duration of hormonal intrauterine device use, but not of combined oral contraceptive pill use, was slightly positively associated with anti-Müllerian hormone levels, although this small magnitude effect is likely not clinically meaningful (coefficient, 1.002; 95% confidence interval, 1.0005-1.003; P=.007). Current hormonal contraceptive use is associated with a lower mean anti-Müllerian hormone level than that of women who are not on contraceptives, with variability in the percent difference across contraceptive methods. These data provide guidance for clinicians on how to interpret anti-Müllerian hormone levels assessed while on contraceptives and may facilitate more patients to continue contraceptive use while being evaluated for their ovarian reserve.

An audit of hormonal contraceptive use in Women’s Super League soccer players; implications on symptomology

ABSTRACT Purpose To audit hormonal contraceptive use and associated symptomology in elite women’s soccer in England. Methods Seventy-five elite women’s soccer players from the Women’s Super League (WSL) completed a questionnaire to assess: hormonal contraceptive (HC) use or non-use, reasons for initiation and discontinuation and the symptoms experienced by HC and non-HC users. Results Twenty-eight per cent reported current HC use, with 43% having used HCs previously. Combined HCs accounted for 62% of total usage, with progestin-only HCs making up the remainder. Eighty-six per cent pre-empted negative symptoms before commencing HCs, with 38% experiencing adverse symptoms. Negative symptoms were most common in progestin-only HC users (63%). Eighty-six per cent reported benefits associated with HC usage include pain management and the ability to predict or control their cycles. Six non-HC users reported amenorrhea, with one medically diagnosed. Negative MC-related symptoms were reported by 74%, with 4% unable to train due to these symptoms. Unfavorable symptoms typically occurred during the first days of menstruation (59%). Conclusion Most WSL players do not currently use HCs (72%). Most HC users reported benefits of HC usage, whilst most non-HC users reported negative symptoms especially around menstruation. Practitioners should track players' MCs to help minimise discomfort and maximise performance.

Risky sexual behaviour and contraceptive use among young women in the Czech Republic.

This study aimed to obtain sexual and reproductive behaviour data of late adolescent women in the Czech Republic and to analyse the relationships between sexual behaviour and social, demographic, and behavioural factors. Data were obtained using the Computer-Assisted Web Interviewing method from 25 April to 2 May 2018 from a representative group of sexually active women aged 18-24 years. Results were statistically evaluated using sign schema on adjusted residuals. A total of 525 women participated (median age of coitarche - 16 years, condom use with/without hormonal contraception - 65%, unprotected sex - 9.3% in the sexual debut). Anamnestic artificial abortion and sexually transmitted disease (STD) rates were 5.3% and 3.8%, respectively. Early coitarche, number of sexual partners, history of abortion, and STDs were positively correlated with current hormonal contraceptive use; the number of sexual partners and use of hormonal contraception were negatively correlated. Hormonal contraceptive users were more likely vaccinated against human papilloma virus (HPV) in comparison with women without any contraception. There was no correlation between risky sexual behaviour, contraceptive use, and socio-demographic factors. Women with early coitarche and a high cumulative number of sexual partners have more unwanted pregnancies and STDs; moreover, those with regular coital activity without contraception are less frequently vaccinated against HPV.

Evaluation of Vascular Endothelial Function in Young and Middle-Aged Women with Respect to a History of Pregnancy, Pregnancy-Related Complications, Classical Cardiovascular Risk Factors, and Epigenetics.

The aim of the study was to examine the effect of previous pregnancies and classical cardiovascular risk factors on vascular endothelial function in a group of 264 young and middle-aged women 3 to 11 years postpartum. We examined microvascular functions by peripheral arterial tonometry and EndoPAT 2000 device with respect to a history of gestational hypertension, preeclampsia, fetal growth restriction, the severity of the disease with regard to the degree of clinical signs and delivery date. Besides, we compared Reactive Hyperemia Index (RHI) values and the prevalence of vascular endothelial dysfunction among the groups of women with normal and abnormal values of BMI, waist circumference, systolic and diastolic blood pressures, heart rate, total serum cholesterol levels, serum high-density lipoprotein cholesterol levels, serum low-density lipoprotein cholesterol levels, serum triglycerides levels, serum lipoprotein A levels, serum C-reactive protein levels, serum uric acid levels, and plasma homocysteine levels. Furthermore, we determined the effect of total number of pregnancies and total parity per woman, infertility and blood pressure treatment, presence of trombophilic gene mutations, current smoking of cigarettes, and current hormonal contraceptive use on the vascular endothelial function. We also examined the association between the vascular endothelial function and postpartum whole peripheral blood expression of microRNAs involved in pathogenesis of cardiovascular/cerebrovascular diseases (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-92a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-210-3p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p). A proportion of overweight women (17.94% and 20.59%) and women with central obesity (18.64% and 21.19%) had significantly lower RHI values at 10.0% false positive rate (FPR) both before and after adjustment of the data for the age of patients. At 10.0% FPR, a proportion of women with vascular endothelial dysfunction (RHI ≤ 1.67) was identified to have up-regulated expression profile of miR-1-3p (11.76%), miR-23a-3p (17.65%), and miR-499a-5p (18.82%) in whole peripheral blood. RHI values also negatively correlated with expression of miR-1-3p, miR-23a-3p, and miR-499a-5p in whole peripheral blood. Otherwise, no significant impact of other studied factors on vascular endothelial function was found. We suppose that screening of these particular microRNAs associated with vascular endothelial dysfunction may help to stratify a highly risky group of young and middle-aged women that would benefit from early implementation of primary prevention strategies. Nevertheless, it is obvious, that vascular endothelial dysfunction is just one out of multiple cardiovascular risk factors which has only a partial impact on abnormal expression of cardiovascular and cerebrovascular disease associated microRNAs in whole peripheral blood of young and middle-aged women.

Human papillomavirus infection and cervical dysplasia in HIV-positive women: potential role of the vaginal microbiota.

To assess the associations between microbiological markers of vaginal dysbiosis and incident/cleared/type-swap/persistent high-risk human papillomavirus (hrHPV) infection; and incident/cured/cleared/persistent high-grade cervical intraepithelial neoplasia (CIN2+) while controlling for persistent hrHPV infection. Two nested case-control studies (N = 304 and 236) within a prospective cohort of HIV-positive women in Johannesburg, South Africa. Participants were examined for hrHPV type (INNO-LiPA), cervical dysplasia (histology), and vaginal microbiota (VMB) composition (V3-V4 Illumina HiSeq 2x300 bp) at baseline and endline, a median of 16 months later. Women with incident hrHPV compared to those who remained hrHPV-negative were less likely to have an optimal Lactobacillus crispatus or jensenii-dominated VMB type at end-line [relative risk ratio (RRR) 0.125, P = 0.019], but not at baseline. Having different hrHPV types at both visits was associated with multiple anaerobic dysbiosis markers at baseline (e.g. increased bacterial vaginosis-associated anaerobes relative abundance: RRR 3.246, P = 0.026). Compared to women without CIN2+, but with hrHPV at both visits, women with incident CIN2+ had increased Simpson diversity (RRR 7.352, P = 0.028) and nonsignificant trends in other anaerobic dysbiosis markers at end-line but not baseline. These associations persisted after controlling for age, hormonal contraception, and CD4 cell count. Current hormonal contraceptive use (predominantly progestin-only injectables) was associated with increased CIN2+ risk over-and-above persistent hrHPV infection and independent of VMB composition. hrHPV infection (and/or increased sexual risk-taking) may cause anaerobic vaginal dysbiosis, but a bidirectional relationship is also possible. In this population, dysbiosis did not increase CIN2+ risk, but CIN2+ increased dysbiosis risk. The CIN2+ risk associated with progestin-only injectable use requires further evaluation.

A pilot study for exploring blood spot anti-mullerian hormone for population-based adolescent reproductive health research.

Studies of Anti-Müllerian Hormone (AMH) rely upon serum measures and clinical samples of older reproductive-aged women intended/attempting pregnancy, with known fertility issues or medical morbidities. We explored the utility of minimally invasive AMH as a measure of fecundability in population-based reproductive health research. We analyzed baseline data from 191 participants in a pilot, longitudinal cohort study, the Young Women's Stress Study. Using an integrated biosocial design, we collected interviewer-administered surveys on demographic, psychosocial, health, and method feasibility/acceptability information and finger-stick capillary dried blood spots (DBS). We used descriptive and bivariate statistics (correlation, T-tests, ANOVA) to estimate method feasibility/acceptability and unadjusted AMH mean concentrations overall and across sociodemographic, reproductive, and health covariates. AMH concentrations ranged from 1.02 to 22.23 ng/mL, with a mean of 5.66 ng/mL. AMH concentrations were associated with current hormonal contraceptive use, menstrual cycle frequency, and irregular menstrual patterns, but not with other known correlates. Most participants stated the DBS method was comfortable (81%) and would be likely to provide it again (88%). While these pilot data suggest AMH fell within normal range and our DBS methods were acceptable/feasible, the broader question of its usefulness for population reproductive health research remains unanswered. Larger, longitudinal studies are needed to validate AMH against time-to-pregnancy and gold standard measures in young healthy samples and across different sociodemographic groups. Public health and social scientists should consider the resource costs of AMH, ethical issues, and risks of (over)interpretation, with a reproductive justice and human rights frame in mind.

A high resolution LC–MS targeted method for the concomitant analysis of 11 contraceptive progestins and 4 steroids

In the context of hormonal contraception and hormone replacement therapy (HRT), many women are exposed to exogenous hormones. Current use of hormonal contraception with combined ethinyl estradiol and different progestins bestows a breast cancer relative risk (RR) of 1.2- while combined HRT has a RR of 2. Although these exposures present an important public health issue, little is known about the effects of individual progestins on the breast and other tissues. Increasing availability of large scale biobanks, high throughput analyses and data management tools enable ever expanding, sophisticated population studies. In order to address the impact of distinct progestins on various health indicators, it is desirable to accurately quantify progestins in clinical samples.Here we have developed and validated a high resolution liquid chromatography mass spectrometry (LC–MS) targeted method for the simultaneous quantification of 11 synthetic progestins widely used in oral contraceptives, gestodene, levonorgestrel, etonogestrel, chlormadinone acetate, cyproterone acetate, drospirenone, desacetyl norgestimate, medroxyprogesterone acetate, norethindrone, dienogest, nomegestrol acetate, and 4 endogenous steroid hormones, progesterone, testosterone, androstenedione, and cortisol in blood samples. This highly specific quantitative analysis with high resolution Orbitrap technology detects and quantifies 15 compounds using their internal standard counterparts in a single 12 min LC–MS run. Sensitivity is attained by the use of the instrument in targeted selected ion monitoring mode. Lower limit of quantitation ranges from 2.4 pg/ml for drospirenone to 78.1 pg/ml for chlormadinone acetate. The method provides comprehensive progestin panel measurements with as little as 50 μl of murine or human plasma.

Abstract P265: History of Hypertensive Disorders of Pregnancy and Early Manifestation of Vasomotor Symptoms 8-10 Years Post Delivery

Introduction: Women with hypertensive disorders of pregnancy (HDP) have excess cardiovascular disease (CVD) risk in the years following delivery compared with women with uncomplicated pregnancies, with black women having excess burden of both HDP and CVD. After pregnancy yet prior to the menopause transition, nearly 30% of women in their late reproductive years report having vasomotor symptoms (VMS) including night sweats and hot flashes. VMS, particularly, early-onset VMS, have also been associated with increases in blood pressure and subclinical CVD. However, it is unknown if underlying vascular dysfunction in women with a history of HDP may increase the risk of VMS and contribute to racial differences in symptom manifestation. Hypothesis: Women with a history of HDP will have an increased risk of VMS as compared with women without a history of HDP. Methods: Women with a singleton live birth at Magee-Womens Hospital (Pittsburgh, PA) during 2008-2009 were enrolled 8-10 years post-delivery (median age=37.5; interquartile range=8.0) in our ongoing prospective cohort study assessing maternal cardiometabolic and microvascular disease (n=312). Using log-binomial logistic regression, we estimated the risk of VMS associated with history of HDP, adjusting for race, body mass index, current smoking, age, and education. Additional adjustment was made for current hormonal contraceptive use. Women with single or double oophorectomy (n=7) were excluded in a sensitivity analysis. Given the excess burden of HDP and CVD, as well as early-onset VMS in black women, we also assessed effect measure modification by maternal race. Results: Thirty percent of women with a history of HDP reported having vasomotor symptoms compared with 18% of women without a history of HDP. This excess risk of VMS persisted after accounting for covariates (adjusted risk ratio (aRR) 1.61, 95% confidence interval (CI) 1.06, 2.47). Excess risk of VMS persisted in women with a history of HDP after excluding those with a single or double oophorectomy (aRR 1.60, 95% CI 1.03, 2.47). Additional adjustment for hormonal contraceptive use resulted in a non-statistically significant increased risk of VMS (aRR 1.59, 95% CI 0.98, 2.59). Race did not modify the association between history of HDP and VMS (P value for interaction = 0.79). Conclusions: History of HDP was associated with excess risk of VMS in young women prior to menopause transition. There may be common underlying vascular changes that contribute to HDP and VMS that may also place women at future risk for CVD. How these reproductive factors may converge and be related to excess cardiometabolic risk warrants additional study.

Intrauterine, Infant, and Childhood Factors and Ovarian Reserve in Young African American Women

Background: Ovarian toxic exposures during early development may contribute to reduced ovarian reserve in adulthood. Materials and Methods: We explored a range of intrauterine, infant, and childhood factors in relation to a biomarker of ovarian reserve, anti-Müllerian hormone (AMH) concentrations, in adulthood. We conducted a cross-sectional exploratory study of 1600 African American women 23-35 years of age residing in the Detroit, Michigan metropolitan area, who had serum AMH measurements (Ansh Labs PicoAMH enzyme-linked immunosorbent assay) and no previous polycystic ovarian syndrome diagnosis. Information on 32 intrauterine, infant, and childhood factors was ascertained by self-administered questionnaires, with 87% of participants receiving assistance from mothers. The percent differences in AMH concentrations in relation to early-life factors and 95% confidence intervals (CIs) were estimated using multivariable linear regression, adjusting for age, current hormonal contraceptive use, and body mass index. Results: Of the early-life factors evaluated in this study, two maternal pregnancy factors were associated with lower AMH concentrations in adult participants. Participants whose mothers lived or worked on a farm (vs. neither lived nor worked on a farm) when pregnant with the participant had 42% lower AMH concentrations (95% CI = -62 to -9). Among participants whose mothers lived in Michigan when pregnant with the participant (n = 1238), maternal residence in Detroit for at least a month was associated with 22% lower AMH concentrations (95% CI = -34 to -8) in the participant. Conclusions: Further research is merited to replicate our findings and identify the aspects of maternal farm exposure and Detroit residence that may be associated with lower AMH concentrations.

Symptoms of premenstrual syndrome in female migraineurs with and without menstrual migraine

BackgroundMenstrual migraine (MM) and premenstrual syndrome (PMS) are two conditions linked to specific phases of the menstrual cycle. The exact pathophysiological mechanisms are not fully understood, but both conditions are hypothesized to be triggered by female sex hormones. Co-occurrence of MM and PMS is controversial. The objective of this population-based study was to compare self-assessed symptoms of PMS in female migraineurs with and without MM. A total of 237 women from the general population who self-reported migraine in at least50% of their menstruations in a screening questionnaire were invited to a clinical interview and diagnosed by a neurologist according to the International Classification of Headache Disorders II (ICHD II), including the appendix criteria for MM. All women were asked to complete a self-administered form containing 11 questions about PMS-symptoms adapted from the Diagnostic and Statistical Manual of Mental Disorders. The number of PMS symptoms was compared among migraineurs with and without MM. In addition, each participant completed the Headache Impact test (HIT-6) and Migraine Disability Assessment Score (MIDAS).FindingsA total of 193 women returned a complete PMS questionnaire, of which 67 women were excluded from the analyses due to current use of hormonal contraception (n = 61) or because they did not fulfil the ICHD-criteria for migraine (n = 6). Among the remaining 126 migraineurs, 78 had MM and 48 non-menstrually related migraine. PMS symptoms were equally frequent in migraineurs with and without MM (5.4 vs. 5.9, p = 0.84). Women with MM reported more migraine days/month, longer lasting migraine attacks and higher HIT-6 scores than those without MM, but MIDAS scores were similar.ConclusionWe did not find any difference in number of self-reported PMS-symptoms between migraineurs with and without MM.

Serum AMH levels in healthy women from BRCA1/2 mutated families: are they reduced?

Do BRCA1/2 mutation carriers have a compromised ovarian reserve compared to proven non-carriers, based on serum anti-Müllerian hormone (AMH) levels? BRCA1/2 mutation carriers do not show a lower serum AMH level in comparison to proven non-carriers, after adjustment for potential confounders. It has been suggested that the BRCA genes play a role in the process of ovarian reserve depletion, although previous studies have shown inconsistent results regarding the association between serum AMH levels and BRCA mutation status. Hence, it is yet unclear whether BRCA1/2 mutation carriers may indeed be at risk of a reduced reproductive lifespan. STUDY DESIGN, SIZE,DURATION: A multicenter, cross-sectional study was performed between January 2012 and February 2015 in 255 women. We needed to include 120 BRCA1/2 mutation carriers and 120 proven non-carriers to demonstrate a difference in AMH levels of 0.40 µg/l (SD±0.12 µg/l, two-sided alpha-error 0.05, power 80%). Healthy women aged 18-45 years who were referred to the Clinical Genetics Department and applied for predictive BRCA1/2 testing because of a familial BRCA1/2 mutation were asked to participate. A cross-sectional assessment was performed by measuring serum AMH levels and filling out a questionnaire. Multivariate linear regression analyses adjusted for age, current smoking and current hormonal contraceptive use were performed on log-transformed serum AMH levels. Out of 823 potentially eligible women, 421 (51.2%) were willing to participate, and of those, 166 (39%) did not meet our inclusion criteria. Two hundred and fifty-five women were available for analyses; 124 BRCA1/2 mutation carriers and 131 proven non-carriers. The median [range] AMH level in carriers was 1.90 µg/l [0.11-19.00] compared to 1.80 µg/l [0.11-10.00] in non-carriers (P=0.34). Adjusted linear regression analysis revealed no reduction in AMH level in the carriers (relative change=0.98 (95%CI, 0.77-1.22); P=0.76). Participants were relatively young. Power was insufficient to analyze BRCA1 and BRCA2 mutation carriers separately. AMH levels may have been influenced by the use of hormonal contraceptives, though similar proportions of carriers and non-carriers were current users and adjustments were made to correct for potential confounding in our analysis. Limitations of the current analysis and limitations of the existing literature argue for prospective, well-controlled follow-up studies with recurrent AMH measurements to determine whether carriers might be at risk for low ovarian reserve and to definitively guide care. This study was partially financially supported by a personal grant for Inge A.P. Derks-Smeets, kindly provided by the Dutch Cancer Society (Grant Number UM 2011-5249). Theodora C. van Tilborg, Inge A.P. Derks-Smeets, Anna M.E. Bos, Jan C. Oosterwijk, Christine E. de Die-Smulders, Lizet E. van der Kolk, Wendy A.G. van Zelst-Stams, Maria E. Velthuizen, Marinus J.C. Eijkemans and Margreet G.E.M. Ausems have nothing to disclose. Ron J. van Golde has received unrestricted research grants from Ferring and Merck Serono, outside the submitted work. Annemieke Hoek received an unrestricted educational grant from Ferring pharmaceutical BV, The Netherlands and a speaker's fee for post graduate education from MSD pharmaceutical company, outside the submitted work. Joop S.E. Laven has received unrestricted research grants from Ferring, Merck Serono, Merck Sharpe & Dome, Organon, and Schering Plough, outside the submitted work. Frank J.M. Broekmans is a member of the external advisory board for Merck Serono (The Netherlands), outside the submitted work. NTR no. 4324.

Novel correlates between antimüllerian hormone and menstrual cycle characteristics in African-American women (23–35 years-old)

To characterize normative antimüllerian hormone (AMH) levels and ascertain which factors are associated with AMH inalarge cohort of reproductive-age women. Cross-sectional study. Not applicable. A total of 1,654 African-American women (AAW) ages 23-34 at recruitment. Not applicable. Serum AMH measured using an ultrasensitive ELISA. The median AMH was 3.18ng/mL, and there was a significant, but nonlinear, relationship between age and AMH, with levels peaking at age 25. As AMH was not normally distributed, log transformation was performed and used for all analyses. In a multivariable age-adjusted model, body mass index, current use of hormonal contraception, and history of a thyroid condition were inversely associated with AMH, while history of abnormal menstrual bleeding and menstrual cycles longer than 35days were positively associated with AMH. While age is correlated with AMH, it accounts for only a portion of the variation seen. This study adds valuable information to the existing literature on normative AMH levels in young reproductive-age women. While our findings fill a critical data gap for ovarian reserve in AAW, the insights gained will be of benefit for all women.

Incident Detection of High-Risk Human Papillomavirus Infections in a Cohort of High-Risk Women Aged 25-65 Years.

The risk of incident high-risk human papillomavirus (HR-HPV) infection associated with recent sexual behaviors is undefined in mid-adult women (defined as women aged 25-65 years). Triannually, 420 female online daters aged 25-65 years submitted vaginal specimens for HPV testing and completed health and sexual behavior questionnaires. The cumulative incidence of and risk factors for incident HR-HPV detection were estimated by Kaplan-Meier and Cox proportional hazards methods. The 12-month cumulative incidence of HR-HPV detection was 25.4% (95% confidence interval [CI], 21.3%-30.1%). Current hormonal contraceptive use was positively associated with incident HR-HPV detection. Lifetime number of male sex partners was also positively associated but only among women not recently sexually active with male partners. In analysis that adjusted for hormonal contraceptive use and marital status, women reporting multiple male partners or male partners who were new, casual, or had ≥1 concurrent partnership had a hazard of incident HR-HPV detection that was 2.81 times (95% CI, 1.38-5.69 times) that for women who reported no male sex partners in the past 6 months. Thus, among women with multiple male partners or male partners who were new, casual, or had ≥1 concurrent partnership, approximately 64% of incident HR-HPV infections were attributable to one of those partners. Among high-risk mid-adult women with recent new male partners, multiple male partners, or male partners who were casual or had ≥1 concurrent partnership, about two thirds of incident HR-HPV detections are likely new acquisitions, whereas about one third of cases are likely redetections of prior infections.

Oral contraceptive exposure in newly pregnant women not linked to birth defects

University of California, San Francisco School of Pharmacy, told Pharmacy Today. “If a woman mistakenly continued using oral contraceptives during the early part of pregnancy, it didn’t increase the risk of birth defects.” Using Danish health registries, the researchers studied four exposure groups and found that prevalence of major birth defects—about 25 per 1,000 births—was consistent across each group. Nearly 70% of the mothers stopped using oral contraceptives more than 3 months before pregnancy; 21% never used oral contraceptives; 8% used oral contraceptives until 0 to 3 months

Prevalence of and risk factors for bacterial vaginosis among women of reproductive age attending cervical screening in southeastern Brazil.

To determine the prevalence of and risk factors for bacterial vaginosis. A cross-sectional study of women aged 14-54 years attending 18 primary healthcare units in Botucatu, Brazil, for cervical screening was undertaken between September 1, 2012, and January 31, 2013. Data on sociodemographics, sexual behavior, and medical history were obtained by interview. Vaginal swabs were taken to classify the vaginal flora according to the Nugent scoring system. Candida sp. hyphae and infection by Trichomonas vaginalis were also evaluated by microscopy and culture, respectively. Stepwise logistic regression analysis was performed to identify risk factors independently associated with bacterial vaginosis. Among 1519 women included in analyses, 457 (30.1%) had bacterial vaginosis. Variables independently associated with bacterial vaginosis were a single marital status (OR 1.4; 95%CI 1.1-1.8), partner infidelity (OR 1.5; 95%CI 1.2-1.9), abnormal discharge in the previous year (OR 1.5; 95%CI 1.2-2.0), and concurrent trichomoniasis (OR 4.1; 95%CI 1.5-11.5). Current use of hormonal contraception (OR 0.7; 95%CI 0.5-0.9), luteal phase of menstrual cycle (OR 0.8; 95%CI 0.6-0.9), higher income (OR 0.8; 95%CI 0.6-0.9), and vaginal candidiasis (OR 0.5; 95%CI 0.3-0.9) all had protective effects. The prevalence of bacterial vaginosis in the study population is high. The epidemiological data provide evidence of the sexual transmissibility of bacterial vaginosis.