Previous Use Of Oral Contraceptives Research Articles

7590 Bone Mineral Content In Women With Functional Hypothalamic Amenorrhea Compared To Eumenorrheic Controls And Recently Menopausal Women

Abstract Disclosure: N. Safwan: None. E.R. Uddenberg: None. M.D. Hurtado: None. M. Saadedine: None. S.S. Faubion: None. O. Obrutu: None. S.L. Berga: None. M.D. Pisarska: None. C. Bairey Merz: None. C.L. Shufelt: None. Background: Functional hypothalamic amenorrhea (FHA) accounts for 30% of secondary amenorrhea due to suppression of GnRH associated hypercortisolemia resulting in chronic hypoestrogenemia. FHA occurs as a result of varying combinations of psychosocial stress, excessive exercise, and/or disordered eating. FHA is associated with decreased bone mineralization; however, it is unknown how bone health compares to older, menopausal women who also experience bone loss. We compared dual-energy x-ray absorptiometry (DXA) bone health parameters among women with FHA, eumenorrheic controls, and recently menopausal women and evaluated if previous oral contraceptive (OC) use among FHA women has an impact on bone mineral density (BMD). Methods: This cross-sectional study included 20 women with FHA, 9 eumenorrheic controls, and 12 recently menopausal women who underwent hip and spine DXA. All participants were not on hormone therapy. FHA was defined as amenorrhea >3 consecutive months, estradiol <50 pg/ml, FSH <10 mIU/L, and LH <10 mIU/L, excluding other etiologies including PCOS, prolactinoma, thyroid dysfunction, and pregnancy. Eumenorrheic controls had self-reported monthly menses confirmed with day 22-24 progesterone >3 ng/ml. Recently menopausal women had natural menopause <3 years of final menstrual period, and FSH >30 mIU/L. DXA bone health parameters were measured using Lunar iDXA (GE) including BMD from the lumbar spine (L1-L4) and hip. Statistical analysis included nonparametric testing with pairwise Wilcoxon rank sum and Kruskal Wallis, reported as median [interquartile ranges]. Results: By design, the mean age of FHA was 28 ± 6 yr, 29 ± 3 yr for controls, and 54 ± 2 yr for recently menopausal women (p<0.0001). There were no differences in weight or BMI among the groups (p=0.27, p=0.30, respectively). BMD L1-L4 differed among the three groups with 1.10 g/cm2 [1.00, 1.24] for FHA, 1.18 [1.15, 1.29] for eumenorrheic controls, and 1.02 [0.96, 1.08] for menopausal women (p=0.002). Pairwise analysis revealed a significant difference in BMD L1-L4 between FHA and controls (p=0.04) and menopausal women and controls (p=0.009, age-adjusted). However, there was no difference in BMD L1-L4 between FHA and menopausal women (p=0.08, age-adjusted). In FHA women with previous OC use, BMD L1-L4 was not different from eumenorrheic controls (p=0.20), while BMD L1-L4 differed from that of recently menopausal women (p=0.004). These differences were not observed at the hip. Conclusion: Compared to eumenorrheic controls, lumbar spine BMD in young women with FHA (mean age 28 yr) was similar to recently menopausal women (mean age 54 yr) emphasizing the profound bone impact of FHA. Previous OC use seems to mitigate FHA bone mineralization changes. Future studies should investigate if bone health differs among women with FHA based on underlying cause and if previous OC use plays a role in maintaining bone health. Presentation: 6/3/2024

Effect of Oral Contraceptive Use in Relation to Fertile Years on the Risk of Endometriosis in Women with Primary Infertility: A Ten-Year Single-Centre Retrospective Analysis.

Background and Objectives: Oral contraceptives (OCs) are usually used to treat endometriosis; however, the evidence is inconsistent about whether OC use in the past, when given to asymptomatic women, is protective against the development of future disease. We aimed to assess the relationship between the use of OCs and the likelihood of discovering endometriosis, considering the length of time under OCs during their fertile age. Materials and Methods: This was a monocentric retrospective cohort study in a tertiary-care University Hospital (Department of Human Reproduction, Division of Gynaecology and Obstetrics, University Medical Centre Ljubljana, Slovenia) carried out from January 2012 to December 2022. Reproductive-aged women scheduled for laparoscopic surgery for primary infertility and subsequent histopathological diagnosis of endometriosis were compared to women without an endometriosis diagnosis. They were classified based on the ratio of years of OC use to fertile years in four subgroups: never, <25%, between 25 and 50%, and >50. Results: In total, 1923 women (390 with and 1533 without endometriosis) were included. Previous OC use was higher in those with endometriosis than controls (72.31% vs. 58.64%; p = 0.001). Overall, previous OC usage was not related to histopathological diagnosis of endometriosis (aOR 1.06 [95% CI 0.87-1.29]). Women who used OCs for less than 25% of their fertile age had reduced risk of rASRM stage III endometriosis (aOR 0.50 [95% CI 0.26-0.95]; p = 0.036) or superficial implants (aOR 0.88 [95% CI 0.58-0.95]; p = 0.040). No significant results were retrieved for other rASRM stages. Using OCs for <25%, between 25 and 50%, or >50% of fertile age did not increase the risk of developing superficial endometriosis, endometriomas, or DIE. Conclusions: When OCs are used at least once, histological diagnoses of endometriosis are not increased. A protective effect of OCs when used for less than 25% of fertile age on superficial implants may be present. Prospective research is needed to corroborate the findings due to constraints related to the study's limitations.

Higher levels of insulin-like growth factor-1 in cord blood associate with risk of asthma at age 3.

Experimental studies and epidemiological data in adults suggest that somatomedin-C (insulin-like growth factor-1, IGF-1) may play a role in asthma by modulating airway inflammation, bronchial hyperreactivity, and airway smooth muscle hyperplasia. However, its role in children with asthma is not well understood. We established a birth cohort with 339 Chilean pregnant mothers enrolled at the time of delivery from December 2014 to January 2016. We obtained cord blood at birth and followed the offspring every 6 months until 30 months of age, recording data on atopy, wheezing, and other respiratory illnesses. We measured IGF-1 in cord blood and determined the Asthma Predictive Index (API) at 30 months. The cohort was divided according to the API. Complete data were available for 307/339 (91%) dyads, including 44 preschoolers with API+ and 263 with API-. Demographic characteristics were similar between groups, but mothers of API+ children had a higher prevalence of obesity, previous use of oral contraceptives, and higher education than those of API- children. API+ children had higher birth weight and significantly higher IGF-1 in cord blood (37.4 ± 13.2 in API+ vs. 30.5 ± 13.0 ng/ml in API-, p = .01). In the multivariable analysis, IGF-1 in cord blood remained independently associated with a higher risk of asthma (adjusted OR for API+ per ng/ml higher IGF-1 = 1.03 [1.0-1.06], p = .015). Higher insulin-like growth factor-1 in cord blood is associated with asthma risk in the preschool years.

Population-based cohort study of oral contraceptive use and risk of depression.

Research on the effect of oral contraceptive (OC) use on the risk of depression shows inconsistent findings, especially in adult OC users. One possible reason for this inconsistency is the omission of women who discontinue OCs due to adverse mood effects, leading to healthy user bias. To address this issue, we aim to estimate the risk of depression that is associated with the initiation of OCs as well as the effect of OC use on lifetime risk of depression. This is a population-based cohort study based on data from 264,557 women from the UK Biobank. Incidence of depression was addressed via interviews, inpatient hospital or primary care data. The hazard ratio (HR) between OC use and incident depression was estimated by multivariable Cox regression with OC use as a time-varying exposure. To validate causality, we examined familial confounding in 7,354 sibling pairs. We observed that the first 2 years of OC use were associated with a higher rate of depression compared to never users (HR=1.71, 95% confidence interval [CI]: 1.55-1.88). Although the risk was not as pronounced beyond the first 2 years, ever OC use was still associated with an increased lifetime risk of depression (HR=1.05, 95% CI: 1.01-1.09). Previous OC use were associated with a higher rate of depression compared to never users, with adolescent OC users driving the increased hazard (HR=1.18, 95% CI: 1.12-1.25). No significant association were observed among adult OC users who had previously used OCs (HR=1.00, 95% CI: 0.95-1.04). Notably, the sibling analysis provided further evidence for a causal effect of OC use on the risk of depression. Our findings suggest that the use of OCs, particularly during the first 2 years, increases the risk of depression. Additionally, OC use during adolescence might increase the risk of depression later in life. Our results are consistent with a causal relationship between OC use and depression, as supported by the sibling analysis. This study highlights the importance of considering the healthy user bias as well as family-level confounding in studies of OC use and mental health outcomes. Physicians and patients should be aware of this potential risk when considering OCs, and individualized risk-benefit assessments should be conducted.

Influence of Sociodemographic and Anthropometric Factors on Gallbladder Volume in Pregnancy in a Tertiary Hospital in Nigeria.

Our study sought to determine the effect of age, parity, body mass index (BMI), and previous oral contraceptive use on gallbladder volume and ejection fraction in pregnancy to enable obstetricians to identify patients at risk of gallbladder disease in pregnancy. We conducted a prospective cross-sectional study involving 190 pregnant women who were evaluated within 32 and 40 weeks gestation at the Fetal Assessment Unit of the Department of Radiology, University of Ilorin Teaching Hospital, Nigeria. Patients were scanned with a commercially available Siemens Ultrasound scanner using a curvilinear probe and a transducer frequency of 3.5 MHz. The fasting gallbladder volume (FGBV) and 30 minutes postprandial gallbladder volume (PGBV) were calculated using the prolate ellipsoid method. Gallbladder ejection fraction was determined using FGBV and PGBV. Each patient's biodata, medical history, and somatometric parameters were documented. A total of 190 volunteers were included in the study. BMI showed statistically significant positive, though weak correlations with FGBV (r = 0.179, p =0.015) and PGBV (r = 0.216, p =0.003). Maternal age, parity, and previous oral contraceptive use did not show any statistically significant correlation with gallbladder parameters. BMI showed a statistically significant but weakly positive correlation with FGBV and PGBV in pregnancy. Our study demonstrated that gallbladder volume in pregnancy might be dependent on BMI. Thus, high BMI may predispose to large gallbladder volume, increasing the risk of biliary stasis and gallstone formation in pregnancy. This is relevant for early detection and prevention of gallbladder disease and follow-up, including expectant management of subjects that may develop gallbladder disease in pregnancy.

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.

Environmental variables and genome-environment interactions predicting IBD diagnosis in large UK cohort

A combination of genetic susceptibility and environmental exposure is thought to cause inflammatory bowel disease (IBD), but the non-genetic component remains poorly characterized. We therefore undertook a search for environmental variables and gene-environment interactions associated with future IBD diagnosis in a large UK cohort. Using self-report and electronic health records, we identified 1946 Crohn’s disease (CD) and 3715 ulcerative colitis (UC) patients after quality control in the UK Biobank. Based on prior literature and biological plausibility, we tested 38 candidate environmental variables for association with CD, UC, and overall IBD using Cox proportional hazard regressions. We also tested whether these variables interacted with polygenic risk in predicting disease, following up significant (FDR < 0.05) results with tests for SNP-environment associations. We performed robustness analyses on all significant results. As in previous reports, appendectomy protected against UC, smoking (both current and previous) elevated risk for CD, current smoking protected against UC, and previous smoking imparted a risk for UC. Childhood antibiotic use associated with IBD, as did sun exposure during the winter. Socioeconomic deprivation was conferred a risk for IBD, CD, and UC. We uncovered negative interactions between polygenic risk and previous oral contraceptive use for IBD and UC. Polygenic risk also interacted negatively with previous smoking in predicting UC. There were no individually significant SNP-environment interactions. Thus, for a limited set of environmental variables, there was strong evidence of association with IBD diagnosis in the UK Biobank, and interaction with polygenic risk was minimal.

Prevalence and Risk Factors Associated With Gestational Diabetes Mellitus Among Pregnant Women: A Cross-Sectional Study in Ghana.

Gestational diabetes mellitus (GDM) is a global public health issue that have serious consequences on mother and her child's health. However, limited data is available on the prevalence of GDM and its associated risk factors in Ghana. This study investigated the prevalence and associated risk factors of GDM among women attending selected antenatal clinics in Kumasi, Ghana. This cross-sectional study included 200 pregnant women who attended antenatal clinics from Three-selected health facilities in the Ashanti Region, Ghana. Women already diagnosed of GDM were identified through their medical records and were confirmed based on the criteria of the International Association of Diabetes and Pregnancy Study Groups (IADPSG), which uses a fasting blood glucose of ≥ 5.1 mmol/L. A well-structured questionnaire was used to collect data on socio-demographic, obstetric, clinical and lifestyle risk factors. Multivariate logistic regression models were used to determine the independent risk factors of GDM. The overall prevalence of GDM among study participants was 8.5%. GDM was prevalent among age 26 and 30 years (41.2%), married participants (94.1%) with basic education (41.2%) and being Akan by ethnicity (52.9%). Previous history of oral contraceptive use (aOR: 13.05; 95% CI: 1.43-119.23, p=0.023), previous history of preeclampsia (aOR: 19.30; 95% CI: 2.15-71.63; p=0.013) and intake of soda drinks (aOR: 10.05, 95% CI: 1.19-84.73, p=0.034) were found to be independent risk factors of GDM. The prevalence of GDM was found to be 8.5% and this was associated with the previous use of oral contraceptives, history of preeclampsia and intake of soda drinks. Public health education and dietary lifestyle modification may be required for pregnant women who are at risk of GDM.

Previous contraceptive treatment relates to grey matter volumes in the hippocampus and basal ganglia

Oral contraceptive (OC) effects on the brain have gained increasing interest, but are highly controversial. Previous studies suggest that OC users have larger hippocampi, parahippocampi, fusiform gyri and Cerebelli. Preliminary evidence from one of those studies even suggests an effect of previous contraceptive use on the hippocampi of women who are not current users of OCs. Furthermore, more recent studies postulate an involvement of previous OC treatment in later development of mood disorders. To address the question whether previous OC treatment affects women’s brain structure later in life, high resolution structural images were obtained from 131 naturally cycling women. Among them, 52 women had never used OC before, 52 had previously used one OC for a continuous time period and 27 had previously used multiple contraceptives. The groups did not differ in gray matter volumes. Since endogenous sex hormones modulate gray matter volumes of the hippocampus and basal ganglia along the menstrual cycle, we hypothesize effects of OC use on these areas. Specifically, we hypothesize that a longer duration of previous OC treatment is related to larger hippocampi and larger basal ganglia. Indeed we found the duration of previous OC use to be positively correlated to hippocampal and basal ganglia volumes bilaterally. For the hippocampus, but not for the basal ganglia, this association disappeared after controlling for the time since discontinuation. These results suggest that for the hippocampus, but not for the basal ganglia, effects of previous contraceptive treatment are reversed after a time period comparable to treatment duration. These data question the immediate reversibility of OC effects on brain structure. Accordingly, some changes in the brain due to long-term contraceptive use, while subtle, may be long-lasting.

Abstract P1-08-27: Advanced stage at diagnosis and worse clinicopathologic features in young woman with breast cancer. A sub-analysis of Brazilian population through the AMAZONA III study (GBECAM 0115)

Abstract BACKGROUND: Breast cancer (BC) in young women is uncommon and often more aggressive. There are disparities in terms of screening coverage, diagnostic features and access to optimal treatment among young BC patients worldwide. To better understand this scenario through real world data we performed a sub-analysis of AMAZONA III study. METHODS: The AMAZONA III study (GBECAM 0115) is a prospective registry that included 2950 women newly diagnosed with invasive BC in Brazil during the period of January 2016 to March 2018 within 22 sites. Of them, 2888 patients had valid data regarding age at diagnosis and complete baseline information. For the purpose of comparisons of epidemiologic and clinicopathologic features at the time of diagnosis of BC, patients were divided in two groups: women aged ≤40 years (Group 1) and &amp;gt;40 years (Group 2). Quantitative variables were expressed with mean, while categorical variables were described as their count and percentage and compared using the chi-square test. RESULTS: Of 2888 women, 486 (17%) were ≤40 years of age. No differences were found between ethnicity, performance status, body mass index, personal income, health insurance and family history of cancer between the two groups. Young women had higher educational level (p&amp;lt;0.001), were more involved into a labor activity (p&amp;lt;0.001) and were more frequently married (p&amp;lt;0.001). There were also significant differences regarding nulliparity (p&amp;lt;0.001) and previous use of oral contraceptives (p&amp;lt;0.001). Mode of detection of BC was symptomatic in 73.4% of young group versus 64.5% in older group and screen-detected was only 26.6% vs. 35.5% respectively (p&amp;lt;0.001). Table 1 describes clinicopathological characteristics of the two groups. Young women presented more frequently with stage III,T3/T4, Grade 3 tumors and HER-2 positive, Luminal B and triple negative subtypes. Women older than 40 years had more stage I, Luminal A and Grade 1/2 tumors. CONCLUSION: Brazilian women under the age of 40 have unfavorable clinicopathological features of BC at diagnosis with more aggressive subtypes and advanced stage compared with older women. No differences in socioeconomic and ethnical aspects were found but a higher percentage of young women had symptomatic detection of BC which could explain the later stage of disease at diagnosis. Young women were economically active and the majority married which highlights the socioeconomic impact of this disease in Brazil. Breast cancer features by age groups at diagnosis in Brazilian women.InformationGroup 1 (≤40 years)Group 2 (&amp;gt; 40 years)p-valueN: 2888486 (16.83%)2402 (83.17%) Stage at diagnosis p&amp;lt; 0.001I76 (19.2%)541 (27.8%) II156 (39.4%)816 (41.9%) III146 (36.8%)489 (25.1%) IV19 (4.6%)101 (5.2%) Tumor size p&amp;lt; 0.001T1114 (27.1%)749 (36.9%) T2141 (33.6%)764 (37.6%) T3101 (24.1%)282 (13.9%) T464 (15.2%)235 (11.6%) Tumor grade p &amp;lt; 0.001Grade 146 (10.7%)381 (17.9%) Grade 2198 (46.2%)1150 (52.0%) Grade 3185 (43.1%)641 (30.1%) Molecular Subtype p &amp;lt; 0.001Luminal A106 (30.6%)957 (51.3%) Luminal B - HER 2 negative55 (15.8%)212 (11.4%) Luminal B- HER 2 positive79 (22.8%)298 (16.0%) HER 2 positive27 (7.8%)135 (7.2%) Triple negative80 (23.0%)264 (14.1%) Citation Format: Franzoi MA, Rosa D, Barrios C, Bines J, Cronemberger E, Queiroz G, Cordeiro de Lima VC, Junior R, Couto J, Emerenciano K, Resende H, Crocamo S, Reinert T, Van Evyl B, Neron Y, Dybal V, Lazaretti N, Costamilan RdC, de Andrade D, Mathias C, Zerwes Vacaro G, Borges G, Silva K, Werutsky G, Morelle A, Sampaio Filho CA, Mano M, Zaffaroni F, Simon S, Liedke PE. Advanced stage at diagnosis and worse clinicopathologic features in young woman with breast cancer. A sub-analysis of Brazilian population through the AMAZONA III study (GBECAM 0115) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-27.

Acute intermittent porphyria - a case report

Introduction. Acute intermittent porphyria is a rare inherited metabolic disorder caused by a decreased level of porphobilinogen deaminase. Subsequent accumulation of by-products in neural elements causes a classic triad of abdominal pain, neurological dysfunction, and psychiatric disturbances. Case report. A 22-year-old female patient with convulsions, episodes of blindness and progressive development of quadriparesis, bulbar paralysis, and respiratory failure was admitted to our intensive care unit twelve days after undergoing colon resection at the local hospital. The diagnosis was confirmed by a high level of porphobilinogen in urine. Previous use of oral contraceptives, antidepressants, and thiopental as induction agents for general anesthesia could represent precipitating factors. The patient was treated conservatively with high carbohydrate intake and human hemin. Six months after admission, the patient was transferred to the Department of Physical Medicine and Rehabilitation. Conclusion. Early diagnosis of acute intermittent porphyria is the cornerstone for successful treatment. The next step includes adequate therapy followed by the prevention of attacks.

Infertility as a risk factor for breast cancer: Results from a hospital-based case-control study.

Breast cancer is the most common cancer in women worldwide and its prevalence is increasing. The aim of this study was to investigate the extent to which a history of infertility can present as risk factors for breast cancer. This was a hospital-based case-control study. In this study, 1177 women with breast cancer were participated for assessing the risk for this cancer. The control was 1204 women with self-reported free-cancer history who were matched in terms of age and residence. Using logistic regression, it was examined whether infertility is a risk factor of case-control status in addition to marriage age, menarche age, body mass index, number of pregnancies, family history of breast cancer, and previous oral contraceptive use. The data were considered significant at P ≤ 0.05. Infertility history was reported in 12.5% (n = 147) of the cases and 5.8% (n = 70) of the controls. Infertility history was a relevant risk for case-control study in addition to other risk factors (odds ratio: 2.43; 95% confidence interval, 3.34-1.77). This study found that infertility may be as the main risk factor for breast cancer in Iranian women, therefore, doing breast screening in women who have one or more risk factors, must receive more emphasis.

Cardiovascular disease in a nationwide population of Danish women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is associated with obesity and low grade inflammation and the risk for cardiovascular disease (CVD) could be increased in PCOS. National register-based study including women with PCOS and no previous diagnosis of CVD, hypertension, or dyslipidemia. PCOS Denmark (N = 18,112) included women with PCOS in the Danish National Patient Register. PCOS Odense University Hospital (OUH, N = 1165) was an embedded cohort including premenopausal women with PCOS and clinical and biochemical examination. Three age-matched controls were included per patient in PCOS Denmark (N = 52,769). The main study outcome was CVD events including hypertension and dyslipidemia defined according to nationwide in- and outpatient hospital contact diagnosis codes and/or inferred from filled medicine prescriptions. The age at inclusion was median (quartiles) 29 (23–35) years and follow up was 11.1 (6.9–16.0) years. The Hazard ratio (95% CI) for development of CVD in PCOS Denmark was 1.7 (1.7; 1.8) (P < 0.001) and the total event rate of CVD was 22.6 per 1000 patient years in PCOS Denmark vs. 13.2 per 1000 patient years in controls (P < 0.001). The median age at diagnosis of CVD was 35 (28–42) years in PCOS Denmark vs. 36 (30–43) years in controls (P < 0.001). Obesity, diabetes, and infertility, and previous use of oral contraceptives were associated with increased risk of development of CVD in PCOS Denmark (P < 0.001). Women in PCOS OUH resembled women in PCOS Denmark regarding risk of CVD. Age, BMI, blood pressure, lipid status, and glycemic status predicted development of CVD in PCOS OUH. The event rate of CVD including hypertension and dyslipidemia was higher in PCOS compared to controls. The risk of developing CVD must be considered even in young women with PCOS.

Cardiovascular disease in a nationwide population of Danish women with polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS) is associated with obesity and low grade inflammation and the risk for cardiovascular disease (CVD) could be increased in PCOS.MethodsNational register-based study including women with PCOS and no previous diagnosis of CVD, hypertension, or dyslipidemia. PCOS Denmark (N = 18,112) included women with PCOS in the Danish National Patient Register. PCOS Odense University Hospital (OUH, N = 1165) was an embedded cohort including premenopausal women with PCOS and clinical and biochemical examination. Three age-matched controls were included per patient in PCOS Denmark (N = 52,769). The main study outcome was CVD events including hypertension and dyslipidemia defined according to nationwide in- and outpatient hospital contact diagnosis codes and/or inferred from filled medicine prescriptions.ResultsThe age at inclusion was median (quartiles) 29 (23–35) years and follow up was 11.1 (6.9–16.0) years. The Hazard ratio (95% CI) for development of CVD in PCOS Denmark was 1.7 (1.7; 1.8) (P < 0.001) and the total event rate of CVD was 22.6 per 1000 patient years in PCOS Denmark vs. 13.2 per 1000 patient years in controls (P < 0.001). The median age at diagnosis of CVD was 35 (28–42) years in PCOS Denmark vs. 36 (30–43) years in controls (P < 0.001). Obesity, diabetes, and infertility, and previous use of oral contraceptives were associated with increased risk of development of CVD in PCOS Denmark (P < 0.001). Women in PCOS OUH resembled women in PCOS Denmark regarding risk of CVD. Age, BMI, blood pressure, lipid status, and glycemic status predicted development of CVD in PCOS OUH.ConclusionThe event rate of CVD including hypertension and dyslipidemia was higher in PCOS compared to controls. The risk of developing CVD must be considered even in young women with PCOS.

Progesterone Receptor (PGR) Gene Variants Associated with Breast Cancer and Associated Features: a Case-Control Study.

Insofar as altered estrogen receptor-progesterone receptor (PR) expression contribute to breast cancer pathogenesis, previous studies examined the association of genetic variation in PR gene (PGR) with breast cancer, but with mixed outcome. We evaluated the association between PGR variants, and breast cancer and associated features. A retrospective case-control study involving 183 female breast cancer patients, and 222 control women. PGR genotyping was done by real-time PCR. Minor allele frequencies of rs1042838, rs590688, and rs10895068 PGR gene polymorphisms were significantly higher in breast cancer patients compared to controls. Patients carrying rs1042838 G/T, rs590688 C/C, and rs10895068 G/A genotypes had higher risk of breast cancer, while carriage of rs3740753 G/G genotype was associated with marginal reduction in breast cancer risk. In addition, carriage of rs1042839, rs3740753, and rs10895068 minor allele was associated with Her2 status, while rs3740753 and rs10895068 were associated with effective hormone replacement therapy. Furthermore, carriage of rs10895068 minor allele in breast cancer women were also associated with age at first pregnancy, hormone receptor (RH) status, and previous use of oral contraceptives. PGR haploview analysis documented moderate-strong linkage disequilibrium (non-random association of alleles at different loci) between 7 of the 8 tested PGR SNPs, thus allowing construction of 7-locus PGR haplotypes. Two haplotypes, ATGCCGA and GTGCCGA, both containing rs590688, were positively associated with breast cancer, thus assigning a breast cancer-susceptible nature to these haplotypes. PGR rs1042838, rs590688, and rs10895068, and ATGCCGA and GTGCCGA haplotypes are related with increased breast cancer susceptibility in Tunisian women.

Use of Oral Contraceptives and Breast Cancer Survival

Introduction: Oral contraceptives (OC) have been shown to give a transient increased breast cancer risk. However, studies on breast cancer survival after OC use are sparse and conflicting.Aim: The aim of this study was to examine previous use of OC in relation to survival after breast cancer diagnosis.Methods: Data was collected from Malmo Diet and Cancer Study, with baseline examinations between 1991 and 1996. Out of 17035 women who completed all study parts, 765 women with incident breast cancer were included in this study. Kaplan Meier and Cox Proportional Hazards analyses, with 95% confidence intervals (CI), were used to study OC in relation to breast cancer-specific and overall survival. All analyses were stratified on age at diagnosis.Results: Women who had ever used OC were younger and more often had grade III tumors than those who had never used OC. Breast cancer-specific survival in women who ever had used OC was better when adjusting for BMI, socioeconomic status as well as tumor characteristics. However, when adjusting for age at diagnosis, the results did not remain significant (0.68, CI 95% 0.39- 1.18). Stratified analyses on age at diagnosis (40-55, 56-70 and ≥ 71) showed no statistically significant associations.Conclusion: In this study we could not demonstrate a significant effect of OC use on breast cancer survival. (Less)

Prior oral contraceptive use in ovarian cancer patients: assessing associations with overall and progression-free survival

BackgroundPrior studies have described a reduced risk of developing ovarian cancer with the use of oral contraceptives. In this context, we decided to examine if oral contraceptive use prior to a diagnosis of ovarian cancer is associated with better overall and progression-free survival.MethodsThis retrospective cohort study included ovarian cancer patients who were seen at the Mayo Clinic in Rochester, Minnesota from 2000 through 2013. Patients completed a risk factor questionnaire about previous oral contraceptive use, and clinical data were extracted from the electronic medical record.ResultsA total of 1398 ovarian cancer patients responded to questions on oral contraceptive use; 571 reported no prior use with all others having responded affirmatively to oral contraceptive use. Univariate analyses found that oral contraceptive use (for example, ever versus never) was associated with better overall survival (hazard ratio (HR) 0.73 (95 % confidence interval (CI): 0.62, 0.86); p = 0.0002) and better progression-free survival (HR 0.71 (95 % CI: 0.61, 0.83); p < 0.0001). In multivariate analyses, contraceptive use continued to yield a favorable, statistically significant association with progression-free survival, but such was not the case with overall survival.ConclusionsThis study suggests that previous oral contraceptive use is associated with improved progression-free survival in patients diagnosed with ovarian cancer.

Lifestyle and reproductive risk factors associated with anal cancer in women aged over 50 years.

Background:Anal cancer incidence increases with age and is higher in women than men. Risk factors in this group other than high-risk human papillomavirus infection are unclear.Methods:In all, 1.3 million women were recruited in 1996–2001 and followed for incident anal cancer. Cox regression models were used to calculate relative risks (RRs) for anal cancer by various potential risk factors.Results:Five hundred and seventeen incident anal cancers were registered over 13 years of follow-up. The largest RR was associated with a history of cervical intraepithelial neoplasia grade 3 (CIN 3; RR=4.03, 95% CI 2.59–6.28). Other factors associated with significantly increased risks in multivariate analyses were: ever smoking (RR=1.49, 1.24–1.80); previous use of oral contraceptives (RR=1.51, 1.24–1.83); nulliparity (RR=1.61, 1.24–2.07); tubal ligation (RR=1.39, 1.13–1.70) and not living with a partner (RR=1.82, 1.40–2.38). The association with smoking was significantly greater for squamous cell carcinoma than adenocarcinoma of the anus (RR 1.66 vs 0.89, P for heterogeneity=0.04).Conclusions:History of CIN 3, smoking, past oral contraceptive use, nulliparity, tubal ligation and not living with a partner are risk factors for anal cancer in women. There was a significant increase in risk associated with smoking for squamous cell anal cancers but not adenocarcinomas.

History of oral contraceptive use in breast cancer patients: impact on prognosis and endocrine treatment response.

The purpose was to study oral contraceptive (OC) use in relation to breast cancer events and endocrine treatment response in a prospective population-based cohort, because it is unclear whether history of OC use impacts on prognosis in breast cancer patients. Between 2002 and 2011, 994 primary breast cancer patients without preoperative treatment were enrolled in Lund, Sweden and followed until December 2012. History of OC use was obtained from preoperative questionnaires. Tumor characteristics, clinical data, and date of death were obtained from pathology reports, patient charts, and population registries. Among the 948 patients with invasive cancer and no metastasis detected on the post-operative screen, 74 % had ever used OCs. Patients were followed for up to nine years (median follow-up 3 years), and 100 breast cancer events were recorded. Ever OC use was not associated with prognosis, irrespective of duration. However, any OC use before age 20 was associated with a threefold increased risk for breast cancer events in patients <50 years but not in patients ≥50 years (P interaction = 0.009). In patients ≥50 years with estrogen receptor positive tumors, previous OC use at any age was associated with a significantly decreased risk of breast cancer events among patients who received aromatase inhibitors compared to patients who never used OCs (adjusted HR 0.37: 95 % CI 0.15-0.87). OC use was not associated with tamoxifen-response. If confirmed, history of OC use may yield valuable prognostic and treatment predictive information in addition to currently used criteria.

Oral contraceptive use and risk of vulvodynia: a population‐based longitudinal study

To assess whether the risk of vulvodynia is associated with previous use of oral contraceptives (OCs). Longitudinal population-based study. Four counties in south-east Michigan, USA. A population-based sample of women, aged 18 years and older, enrolled using random-digit dialling. Enrolled women completed surveys that included information on demographic characteristics, health status, current symptoms, past and present OC use, and a validated screen for vulvodynia. The temporal relationship between OC use and subsequent symptoms of vulvodynia was assessed using Cox regression, with OC exposure modelled as a time-varying covariate. Vulvodynia, as determined by validated screen. Women aged <50 years who provided data on OC use, completed all questions required for the vulvodynia screen, and had first sexual intercourse prior to the onset of vulvodynia symptoms were eligible (n = 906). Of these, 71.2% (n = 645) had used OCs. The vulvodynia screen was positive in 8.2% (n = 74) for current vulvodynia and in 20.8% (n = 188) for past vulvodynia. Although crude cross-tabulation suggested that women with current or past vulvodynia were less likely to have been exposed to OCs prior to the onset of pain (60.7%), compared with those without this disorder (69.3%), the Cox regression analysis identified no association between vulvodynia and previous OC use (HR 1.08, 95% CI 0.81-1.43, P = 0.60). This null finding persisted after controlling for ethnicity, marital status, educational level, duration of use, and age at first OC use. For women aged <50 years of age, OC use did not increase the risk of subsequent vulvodynia.