On Oral Contraceptives Research Articles

SAT347 Surprising Turn Of Events In A Patient With Weight Gain: Simultaneous Diagnosis Of Macroprolactinoma And Polycystic Ovary Syndrome

Abstract Disclosure: A.N. Keskinkilic: None. D. Sistla: None. Background: The differential diagnoses of excess weight gain are broad and endocrinopathies constitute a small proportion of these etiologies. A pattern of associated symptoms, classical exam findings and hormonal testing can signal some endocrine causes. However, diagnosis can still be challenging due to overlapping clinical and biochemical features and concurrent presentations of endocrine disorders. Here, we present a diagnostically challenging rare case of a young female with weight gain who had simultaneous diagnosis of macroprolactinoma and PCOS. Clinical Case: A 34-year-old healthy female presented with one year of weight gain despite lifestyle changes. She also reported headaches, acne, hirsutism, stretch marks, excessive sweating, and had 10 years of amenorrhea while on oral contraceptives (OCs). Labs revealed mildly low free T4 of 0.72 ng/dl (n: 0.70-1.48 ng/dl) and significantly elevated prolactin (PRL) of 259.8 ng/ml (n: 1.2-29.9 ng/ml); normal FSH, LH, GH, IGF, TSH, ACTH, 1 mg dexamethasone suppression test, and 24-hour urinary cortisol. HbA1c, lipid panel, plasma metanephrine and androgen levels were normal. MRI pituitary revealed a 2.1 x 1.9 x 1.5 cm macroadenoma with mild compression to the optic chiasm. A low dose levothyroxine and cabergoline 0.25 mg twice weekly was started with dose increment to 0.5 mg twice weekly. At 6-month follow-up, PRL decreased to 30 ng/ml. Repeat MRI showed a decrease in size of the pituitary adenoma (1.5 x 1.4 x 1.3 cm). However, she could not tolerate cabergoline due to persistent headaches and depression. Hence, she elected to undergo transsphenoidal pituitary resection. Tumor pathology showed sparsely granulated lactotroph adenoma. Post op PRL level normalized, and MRI showed radiological cure of the adenoma. Headaches improved but amenorrhea persisted despite discontinuation of OCs for 6 months. Progesterone challenge tests resulted in withdrawal bleed suggesting anovulation. Repeat work-up ruled out nonclassical CAH, Cushing’s, and androgen-secreting tumors. However, subsequent pelvic ultrasound confirmed polycystic ovarian morphology, suggesting PCOS. The patient preferred to avoid OCs and could not tolerate metformin. She elected progesterone IUD placement for endometrial protection in combination with lifestyle changes with notable improvement in her symptoms. Conclusion: PCOS is a diagnosis of exclusion. Thorough evaluation of symptoms like weight gain, amenorrhea, clinical hyperandrogenism is recommended to rule out serious pathology like prolactinoma. Dual diagnosis of PCOS and macroprolactinoma is rare and should be suspected if menstrual abnormalities persist even after treatment of hyperprolactinemia. Presentation: Saturday, June 17, 2023

EE246 Cost-Effectiveness of OC/Lep Intervention for Treatment of Dysmenorrhea and Endometriosis in Japan

Self-care with over-the-counter (OTC) by non-steroidal anti-inflammatory drugs (NSAIDs), Chinese Medicines and whatever, is widely used for pelvic pain relief in dysmenorrhea patients in Japan; however, guideline-recommended intervention consists based on Oral Contraceptives (OC) and low-dose estrogen and progestin hormonal combinations (LEP). This study aims to assess the cost-effectiveness of OC/LEP for the prevention of disease progression and/or ovarian cancer, compared to no use, in Japan.

Novel Bruton's tyrosine kinase inhibitor remibrutinib: Assessment of drug-drug interaction potential as a perpetrator of cytochrome P450 enzymes and drug transporters and the impact of covalent binding on possible drug interactions

Pharmacokinetic drug-drug interactions (DDIs) are investigated to ensure safety for patients receiving concomitant medications. Here, we present a strategy to characterise the DDI potential of remibrutinib, as an inhibitor of drug-metabolising enzymes and drug transporters, and as an inducer. Initial in vitro studies were performed, followed by a biomarker-based assessment of induction in a first in human study, concluded by a clinical study to verify initial results. Remibrutinib is a covalent inhibitor of Bruton's Tyrosine kinase (BTKi) carrying a reactive acrylamide moiety (warhead), thus the potential contribution of covalent binding (off-target) to observed interactions was investigated as this could lead to prolonged and more potent drug interactions. DDI assessment was focused on the putative inhibition of key metabolic enzymes (Cytochrome P450, CYP), drug transporters and a potential effect on oral contraceptives (OC) by induction of enzymes that are involved in their clearance (CYP3A4). The impact of covalent binding was assessed by synthesising an identical reference molecule but with an inactivated warhead. An interaction potential of limited clinical relevance was revealed for remibrutinib for CYP enzymes and drug transporters. The reactive warhead of remibrutinib had no impact on CYP enzyme and transporter inhibition, including time-dependent inhibition of CYP3A4, but may increase the induction potential of remibrutinib. Observed inhibition of metabolic enzymes indicated that remibrutinib is a weak inhibitor of CYP3A4 and CYP2C9 and is not a clinically relevant inhibitor of uptake and efflux transporters, except for intestinal P-glycoprotein and breast cancer resistance protein inhibition. OC may be safely administered and are effective when given with pharmacologically relevant doses of remibrutinib.

Estradiol effects on spatial memory in women

To examine the role of estradiol in hippocampal-dependent spatial memory in women, 86 female undergraduates were tested in a virtual Morris water task (VMWT), a virtual radial arm maze (VRAM), and a mental rotation task (MRT) within a single daily session. The VMWT and RAM were also administered 24 h later to examine the effects of estradiol on memory consolidation. Women on oral contraceptives (OCs) or those who were naturally cycling and exhibited low estradiol (LE) or high estradiol (HE), as determined by salivary assays, were included. At the start of day two, the HE group showed superior spatial reference memory on the VMWT relative to the LE group, as evidenced by significantly shorter distances navigating to the hidden platform. The LE group also had the poorest probe trial performance at the start of day two compared to both other groups. There were no group differences in performance on the RAM or MRT. These results provide support for estradiol’s role in the consolidation of spatial reference memory in women, and emphasize the differential sensitivities of various virtual memory tasks in assessing spatial memory function in women.

Abstract B26: The natural history of ovarian high-grade serous carcinoma from time effects of ovulation inhibition and progesterone clearance of p53-defective lesions

Abstract High-grade serous carcinoma (HGSC) is the most common and devastating type of ovarian cancer; its etiology, mechanism of malignant transformation, and origin remain controversial. Recent studies have identified secretory cells at the fimbria of the fallopian tube as the cell of origin of HGSC, initiating TP53 mutation, evolving to tubal precursor lesions, including “p53 signature” and serous tubal intraepithelial carcinoma (STIC), and metastasizing to the ovary as clinically evident ovarian cancer. The etiologic mechanisms associated with the known epidemiologic risk factors, i.e., ovulation and retrograde menstruation, have also been unveiled. Mutagens and transforming growth factors, such as reactive oxygen species and IGF axis proteins, as well as the apoptosis-rescuing protein hemoglobin are abundantly present in the ovulatory follicular fluid and peritoneum fluid, which bathes the fimbrial epithelium, and induces malignant transformation after repeated exposure. Meanwhile, in accordance with the proposed therapeutic effect of progesterone from studies on oral contraceptive (OC) use or term pregnancy, our recent study indicated that the p53-null tubal epithelial cells are selectively cleared by progesterone depending on its progesterone receptor (PR). In this report, by analyzing different time-effects of OC use or pregnancy in the prevention of ovarian cancer and by aligning them with the carcinogenic and therapeutic clearance concepts of ovulation and P4, as well as the fact of progressive loss of PR during tubal transformation, we deduced the natural history of ovarian HGSC. The natural history begins at the first ovulation and spans more than 30 years, taking 10 years from the normal tubal epithelium to the “p53 signature” status, another 15 years to PR(-) STIC, and a final 5+ years to HGSC. The estimated natural history may help understand the pathogenesis of HGSC and defines the window for early detection and chemoprevention. Citation Format: Tang-Yuan Chu, Na-Yi Yuan Wu, Jing Wang. The natural history of ovarian high-grade serous carcinoma from time effects of ovulation inhibition and progesterone clearance of p53-defective lesions [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B26.

Adherence to multiple medications in the TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) cohort: effect of additional medications on adherence to primary diabetes medication.

Background Non-adherence to diabetes medication leads to poor outcomes and increased healthcare costs. Multiple factors affecting adherence in adults with type 2 diabetes (T2D) have been identified, but pediatric data is sparse. We aimed to determine whether initiation of additional oral medications or insulin affects adherence to primary study medication (PSM) in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study. Methods Six hundred and ninety-nine youth (aged 10-17 years) with recent-onset T2D were randomized in the TODAY study. Participants were categorized as adherent (≥80% taken by pill count) or non-adherent (<80%), and adherence was compared between those on additional medications or not. Subgroup analyses to assess influence of race/ethnicity, gender, medication type, or depression were performed. Results At 36 months, 46.3% of participants were taking additional oral medications and 31.9% were on insulin. There was no difference in study medication adherence with additional oral medications (55.1%, 67.1%, and 56.7% at month 36 in those prescribed 0, 1, or 2+ additional medications; p = 0.16). Girls on oral contraceptives (OC) had higher adherence (65.2% vs. 55.8% at month 36; p = 0.0054). Participants on insulin had lower adherence (39.7% vs. 59.3% at 36 months; p < 0.0001). There was decreased adherence in participants with baseline depression (p = 0.008). Conclusions Additional oral medications did not influence adherence to diabetes medications in TODAY. Addition of insulin led to reduced adherence. In subgroup analyses, OC use was associated with higher adherence in girls, while baseline depression was associated with lower adherence overall. Further studies examining potentially modifiable risk factors of adherence in pediatric T2D are needed.

1511 Epiploic Appendagitis After Rigorous Exercise in a Woman: An Easily Misdiagnosed Cause of Acute Abdomen

INTRODUCTION: Acute abdominal pain can be a surgical emergency. However, benign etiologies, such as epiploic appendagitis (EA), can present with similar symptoms. We report a case of an otherwise healthy woman, on oral contraceptives (OCP), presenting with severe abdominal pain related to epiploic appendagitis. Timely recognition of this condition is important to avoid misdiagnosis and unnecessary surgical interventions. CASE DESCRIPTION/METHODS: A 44-year-old woman with a past medical history of ovarian cyst and BMI 25 presented to the Emergency Department with a three-day history of sharp left lower quadrant (LLQ) pain. Patient reported that she started a vigorous aerobic exercise regimen 6 weeks before. Only medication was norgestimate-ethinyl estradiol for contraception. Vital signs normal. Physical exam showed tender LLQ without rebound tenderness or rigidity. Initial testing including complete blood count, basic metabolic panel, pregnancy test, urinalysis, and vaginitis panel were unremarkable. Given worsening pain, CT scan of abdomen and pelvis with contrast was obtained showing an encapsulated oval, pericolonic fatty nodule adjacent to the sigmoid colon, with surrounding fat stranding consistent with EA. Patient was discharged home with conservative pain management. Her OCP was discontinued. She had no symptom recurrence within a 3-year period. DISCUSSION: EA is an uncommon cause of acute abdominal pain that mimics serious medical or surgical emergencies such as acute diverticulitis, appendicitis, or, gynecological emergencies such as ruptured ectopic pregnancy. It is, generally, a self-limited ischemic infarction involving the epiploic appendices, which are normal outpouching fat of the lower colon and rectum. EA can be divided into primary versus secondary. The primary form is caused by either torsion or spontaneous venous thrombosis of an epiploic appendage central draining vein. It commonly occurs in men aged 20–50. Risk factors include obesity, hernia, and rigorous exercise. Secondary form is related to inflammation of adjacent organs. Although our patient does not match the typical profile for EA, rigorous exercise and probably OCP usage, a risk factor for thromboembolic phenomena, may have triggered this episode. Diagnosis of EA is by imaging via ultrasound or CT scan, and complete resolution typically occurs within two weeks with conservative management. Prompt identification of EA is essential in patients at risk, to avoid unnecessary surgical procedures.

SAT-443 Osilodrostat Has No Clinically Relevant Effect on the Pharmacokinetic (PK) Profile of a Monophasic Oral Contraceptive in Healthy Females Receiving Cortisol Replacement Therapy

Background: Osilodrostat, a potent oral 11β-hydroxylase inhibitor, is in Phase 3 development for endogenous Cushing’s syndrome (CS). As CS occurs mostly in females of childbearing age, it is important to determine the effect of osilodrostat on oral contraceptives (OCs). We report the effect of multiple osilodrostat doses on the PK profile of a single OC dose in healthy females on cortisol replacement. Methods: This Phase 1, single-center, open-label, three-period, drug-drug interaction study enrolled healthy, non-smoking females aged 18-50 y with regular menstrual cycles. A single OC dose, containing ethinyl estradiol (EES) 30 μg and levonorgestrel (LVG) 150 μg, was given on day (D) 1 of treatment period 1 (TP1; D1-7). In TP2 (D8-19), osilodrostat 30 mg twice daily was given with hydrocortisone 20 mg daily; a second OC dose was given on D15. Hydrocortisone was tapered/discontinued during TP3 (D20-28). Primary variable: AUClast (area under curve from time 0 to last measurable concentration) and Cmax (peak plasma concentration) of EES and LVG, calculated from a 120h OC PK profile on D1 and D15. Secondary endpoints: osilodrostat PK; safety/tolerability of OC and osilodrostat co-administration. Results: 24 subjects were enrolled (mean ± SD age, 37 ± 7 years; Caucasian, 96%). EES and LVG AUClast were similar when OC was given with osilodrostat (n=19) vs alone (n=24) [geometric mean: EES, 541 vs 537 pg∙h/mL; LVG, 44900 vs 42300 pg∙h/mL]. Insignificant decreases in Cmax were seen for OC with osilodrostat vs alone (geometric mean: EES, 51.6 vs 59.8 pg/mL; LVG, 3360 vs 3800 pg/mL). Apparent total clearance, t½ (half-life) and tmax (time to Cmax) were similar with and without osilodrostat for EES and LVG, except for a small increase in t½ of LVG with osilodrostat (26.4 vs 22.9 h). For osilodrostat PK (n=19), geometric means for AUCτ (AUC to end of dosing period at steady state) and Cmax, and median tmax, were 1620 ng∙h/mL, 299 ng/mL, and 1.0 h, respectively. Most (92%) subjects received both OC doses; 83% completed osilodrostat treatment. At the end of TP3 (2 days after last hydrocortisone dose), 79% of subjects had ACTH-stimulated serum cortisol below the protocol-defined threshold, although all had normal unstimulated levels at study end; these results may be related to high osilodrostat doses, hydrocortisone supplementation, timing of first stimulation test after last hydrocortisone dose or another factor. Other common AEs: nausea (46%), headache and nasopharyngitis (both 38%). Four (17%) subjects discontinued due to: palpitations, n=1; throat tightness, n=1; asthenia and exhaustion, n=1; positive pregnancy test, n=1 (not confirmed by ultrasound). Conclusion: Concomitant treatment of osilodrostat (highest dose used in Phase 3 trials) with a single OC dose did not result in clinically relevant changes in OC PK parameters, suggesting that OC can be given with osilodrostat and provide adequate contraception.

Substrate oxidation in female adults during endurance exercise throughout menstrual cycle phases: IronFEMME pilot study

The main aim of the study was to investigate the effect of menstrual cycle phases on substrate oxidation during steady state intensity exercise in adult females with regular menstrual cycle and on oral contraceptive (OC). Twenty-four healthy endurance and strength trained females, with regular menstrual cycle phases (n= 15; Age 35.6±4.2; height 163.9±5.9 cm; body mass 58.1±5.2 kg; VO2peak 50.3±3.6 ml·min-1·kg-1) or on oral contraceptives (n=9; Age 30.4±4.5; height 163.9±9.0 cm; body mass 58.1±6.7 kg; VO2peak 52.4±4.2 ml·min-1·kg-1) participated in the study. All participants performed a graded maximal exercise test to determine their peak oxygen consumption (VO2peak). Participants then exercised at the speed corresponding to 75% of VO2peak for 40 minutes on a treadmill in each menstrual cycle phase: regular menstrual cycle group (early follicular phase, mid-follicular phase and luteal phase) and OC group (hormonal phase and non-hormonal phase). There were no differences in the respiratory exchange ratio of each phase, in regular menstrual cycle phase group (mean±SEM): early-follicular phase 0.89±0.01, mid-follicular phase 0.87±0.01 and luteal phase 0.88±0.01 (p>0.05). There were also no differences in respiratory exchange ratio for the participants using oral contraceptive: hormonal phase 0.89±0.01 and non-hormonal phase 0.91±0.01 (p>0.05). However, we found that OC may influence fat oxidation (p=0.018) during the hormonal phase. Our preliminary results suggest that menstrual cycle and oral contraceptive do not influence substrate oxidation in females with regular menstrual cycle phases. Regarding the few disparities, more research is needed to understand how sexual hormones influence substrate oxidation in female.

Exposure Opportunity: The Advantages of Including Men in Analyses of Female-Related Risk Factors.

Intuitively, researchers do not include subjects who do not have the opportunity to be exposed, such as men in studies on oral contraceptives (OCs). We aimed to explore in which situations it is nevertheless beneficial to do so. We considered the effect of including men in case-control analyses of 8 different hypothetical data sets on the effect of OC use and venous thrombosis. In all scenarios, OC use was the exposure of interest, sex the factor that determined exposure opportunity, and air travel another risk factor. In some of these scenarios, sex and air travel were included as confounders or effect modifiers. Logistic regression was used to estimate odds ratios. Standard errors of the estimated log odds ratios, including and excluding men, were compared. We also studied the effect of including men using data from 1999-2004 from a case-control study on risk factors for venous thrombosis, conducted in the Netherlands. In all hypothetical examples, and in the real-data study, addition of men to the analysis yielded the same odds ratios when correctly adjusting for confounding. Moreover, use of additional subjects often led to more precise estimates. We suggest that subjects who do not have the opportunity to be exposed should not routinely be excluded from epidemiologic studies.

Spontaneous Renal Infarction in a Middle Aged Female on Oral Contraceptives (OCs)

Spontaneous Renal Infarction in a Middle Aged Female on Oral Contraceptives (OCs)

Changes in Neuromuscular Performance throughout the Menstrual Cycle in Physically Active Females

PURPOSE: The purpose of this study was to determine the change in neuromuscular performance throughout the menstrual cycle in college-aged females and the effect of hormonal contraception on these changes. METHODS: Fifty physically active college females (25 on oral contraceptives (OC)) were recruited to participate in three visits throughout one menstrual cycle. Visits coincided with the follicular (Fp), ovulatory (Op), and the luteal (Lp) phases. Blood was drawn at each visit to determine circulating concentrations of estradiol (E2), progesterone (P4), and relaxin (R2). Grip strength, knee joint laxity, q-angle, and isokinetic quadriceps strength at 60°/sec, 180°/sec, and 300°/sec were measured. Data were analyzed using linear mixed effect models taking into account repeated measures. RESULTS: Grip strength was lower during Fp (30.1 ± 0.7 kg/m2) than during Op (31.5 ± 0.7 kg/m2, p=0.003) and Lp (32.6 ± 0.7 kg/m2, p<0.001). Isokinetic peak torque (IPT) at 60°/sec was lower during Fp (112 ± 3 ft-lbs) than during the Op (116 ± 3 ft-lbs, p=0.009). IPT at 180°/sec was lower during the Fp (73 ± 2.0 ft-lbs) than the Op (79 ± 2 ft-lbs, p<0.001) and Lp (82 ± 2 ft-lbs, p<0.001). Results were similar for the 300°/sec isokinetic testing with lower peak torque during Fp (58 ± 2 ft-lbs) than the Op (63 ± 2 ft-lbs, p<0.001) or Lp (63 ± 2 ft-lbs, p<0.001). No differences were observed among any of the visits for knee joint laxity, or quadriceps angle. The OC-by-phase interaction was not significant for any of the outcomes or R2 concentration, but was significant for E2 and P4 with the concentrations of E2 and P4 being lower during the ovulatory and luteal phases in the OC group. Inclusion of E2, P4 or R2 in statistical models did not affect any of the outcomes for either group. CONCLUSION: Results indicate that muscular performance is diminished during follicular phase (menstruation) and the lack of significant OC-by-phase interaction indicates that this effect is not related to OC use, E2 concentrations, or P4 concentrations. Based on these data we postulate that female athletes may be at a greater risk of injury due to decreased strength during Fp than other phases of their cycle; future studies should focus on attenuating the strength decrease observed during menstruation.

Inappropropriate Use of Inferior Vena Cava Filters May Cause Harm

Background: Technical improvements of inferior vena cava filters (IVCF) have led to a markedly increased use of this modality over the last two decades.While these devices may provide significant short-term protection from pulmonary embolism (PE) in patients for whom anticoagulation is contraindicated or ineffective, the risk-benefit ratio is unknown in a variety of indications not recommended by current guidelines. Serious long-term complications include an increased risk of deep vein thrombosis (DVT), IVCF malposition, fracture, migration and embolism.Methods: In this paper, we describe a case demonstrating multiple complications of IVCF placement. In addition, we attempted to review all available literature to identify data on the risk-benefit ratio of conventional versus liberal use of IVCF.Results: (i) Case Description: A 38-year-old woman with a history of recurrent VTE presented with severe abdominal pain. Her initial left popliteal vein thrombosis and PE had occurred in 2000 after a few months on oral contraceptives (OC). She was treated with warfarin for a year. A recurrent unprovoked episode of left iliofemoral DVT was diagnosed four years later, at which time she was off OC. Indefinite warfarin treatment was started, given her young age and recurrent VTE. She became pregnant two years later and was switched to enoxaparin until two months after delivery. However, she did not restart warfarin and experienced no complications until three years later, when a prophylactic temporary IVC filter was placed prior to partial hysterectomy for menorrhagia. The surgery was performed without complications, but six months later she developed a recurrent untriggered right femoral DVT and began to experience sharp pains and an abrupt change in her bowel habits. At presentation, a CT scan (below) determined that her IVC filter had migrated out of position with its wires protruding into her aorta and spine and perforating her duodenum. Major abdominal and vascular surgery was performed to remove the filter. A thrombophilia panel returned with normal results. The patient was started on rivaroxaban indefinitely with no further issues.(ii) Literature review: A PubMed search of all English language clinical trials with the key word "IVC filter" resulted in a total of 46 papers, 6 of which did not focus on outcomes of cava filters leaving 40 papers for review. These 40 papers were individually studied. We could identify no papers directly comparing standard versus liberal indications. Complication rates varied widely among the reviewed case series.Conclusion: While temporary IVC filters are an effective method of preventing PE when anticoagulation therapy is contraindicated or ineffective, there is no data in current medical literature comparing outcomes of standard versus liberal indications of IVCF use. Such studies are urgently needed to support or refute current medical practices in the United States and other developed countries. Furthermore, retrievable filters should be retrieved as soon as clinically feasible to avoid long-term complications, such as illustrated by our case.Axial contrast-enhanced CT showing migrated anterior arm of IVC filter protruding into the duodenum.Sagittal CT image showing posterior arm extending to the adjacent psoas muscle. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Abstract A52: Oral contraceptive use and risk of colorectal polyps in a colonoscopy based study in western Washington state

Abstract Background: Most colorectal cancers arise from polyp precursor lesions, including advanced adenomas and a subset of serrated polyps, termed sessile serrated polyps. Growing literature on oral contraceptives (OC) use and risk of colorectal cancer suggests an inverse association. However, very little is known about the role of OC in the development of colorectal polyps. We investigated the relationship between OC use and the risk of subsets of colorectal polyps in a colonoscopy based study in western Washington State. Methods: Study participants were 20-79 year-old women enrollees at Group Health, an integrated health care system in Seattle, Washington who underwent a colonscopy for any indication from 1998-2007. Study eligible participants completed a structured interview to collect risk factor information, including reproductive history and exogenous hormone use. OC use was categorized according to ever use, recency of use, and duration of use. Participants were diagnosed as having adenomas (n=298), serrated polyps (n=336), both types of polyps (n= 105) or as polyp-free controls (n=615) on the basis of a standardized pathology review. Multivariable polytomous logistic regression was used to compare case groups with polyp-free controls and other case groups; odds ratios (OR) and 95% confidence intervals were estimated adjusted for age, race, educational status, body mass index, smoking, alcohol intake, anti-inflammatory drug use, use of postmenopausal hormones, parity and age at first birth. Results: Ever use of OC was not associated with risk for adenomas (adjusted OR 0.82, 95% CI 0.57-1.20) or serrated polyps (adjusted OR 0.93, 95% CI 0.64-1.36) while the risk for synchronous presence of both types of polyps was elevated (adjusted OR 1.43, 95% CI 0.77-2.67) (p=0.39 for the three polyp subtypes). Strength of association did not vary significantly between adenomas and serrated polyps for duration of use (p=0.43) and time since last use (p=0.75). Additionally, the associations did not differ significantly by age, lesion severity (advanced vs. nonadvanced for adenomas, sessile serrated vs. hyperplastic for serrated polyps), or location (right vs left) for either adenomas or serrated polyps. Conclusions: We observed no strong evidence that adenomas or serrated polyps were associated with ever use of OC pills. Although the majority of studies suggest a reversible effect of exogenous postmenopausal hormones on colorectal neoplasia, we did not find any association between time since last use of OC pills and development of either types of polyps. Further larger studies are needed to better understand the mechanistic processes through which oral contraceptives may be associated with the development of adenomas and serrated polyps. Citation Format: Sheetal Hardikar, Andrea N. Burnett-Hartman, Polly A. Newcomb. Oral contraceptive use and risk of colorectal polyps in a colonoscopy based study in western Washington state. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A52.

Abstract B31: Oral contraceptive use in relation to breast cancer subtypes in African American women: Results from the AMBER Consortium

Abstract Introduction. Evidence on oral contraceptive (OC) use in relation to breast cancer subtypes is sparse and the findings are inconsistent. We investigated duration and recency of OC use in relation to molecular subtypes of breast cancer in a pooled analysis of data from African American women. Methods. The African American Breast Cancer Epidemiology and Risk (AMBER) Consortium is a collaborative research project which pools data, samples, and tumor tissue from several studies. The present analysis was based on data from the Black Women's Health Study, the Carolina Breast Cancer Study, and the Women's Circle of Health Study. Pathology reports and/or cancer registry data were abstracted to classify cancers by molecular subtype. Exposures of interest were duration and recency of OC use. Never use was defined as never having used OCs or use that lasted less than 1 year. Duration was categorized as &amp;lt;5 years, 5-9 years, and ≥10 years; recency was categorized as &amp;lt;5 years ago, 5-9 years ago, and ≥10 years ago. Multivariable analyses controlled for age, study, time period, geographic area, age of menarche, parity, age at first birth, lifetime duration of breastfeeding, history of breast cancer in a first-degree female relative, menopausal status, age at menopause, female hormone use, body mass index (BMI), educational attainment, alcohol consumption, and cigarette smoking. Polytomous unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) in pooled data and in each study separately. The likelihood ratio test was conducted to examine potential interaction. Between-study heterogeneity was assessed by performing meta-analyses with a random-effects model. Results. The study population included 14,106 African American women, of whom 1,839 had estrogen receptor-positive (ER+) breast cancer, 1,037 had estrogen receptor-negative (ER-) breast cancer, 495 had triple negative breast cancer (ER-, progesterone receptor-negative, and HER2 receptor-negative), and 10,061 were controls. ORs for ≥10 years duration of OC use were elevated for both ER+ and ER- breast cancer (ER+, OR=1.30, 95% CI 1.11-1.52; ER-, OR=1.59, 95% CI 1.31-1.94). OC use within the past 5 years was also associated with risk of both ER+ (1.57, 95% CI 1.27-1.94) and ER- (1.72, 95% CI 1.33-2.22) breast cancer. ORs for TN breast cancer were similar to those for ER- breast cancer. Results were consistent across age groups, including for early-onset breast cancer (diagnosed before age 40). The only evidence of multiplicative interaction was for OC use with BMI and the interaction was statistically significant for ER- breast cancer (p&amp;lt;0.01). For both ER+ and ER- breast cancer, OC use was not associated with risk among women with BMI &amp;lt;25. For ER- breast cancer, OC use was associated with increased risk among both overweight and obese women, whereas for ER+ breast cancer, the association was present only among obese women. Results from a meta-analysis of study-specific results were similar to results from the pooled data, with a p-value &amp;gt;0.05 indicating no statistically significant heterogeneity. Conclusion. Our results suggest that oral contraceptive use, particularly long duration and recent use, is associated with an increased risk of both ER+ and ER- breast cancer, and that obesity may modify the association. Potential mechanisms for this interaction will be discussed. Citation Format: Traci N. Bethea, Lynn Rosenberg, Chi-Chen Hong, Melissa A. Troester, Kathryn A. Lunetta, Elisa V. Bandera, Pepper Schedin, Virginia F. Borges, Andrew F. Olshan, Christine B. Ambrosone, Julie R. Palmer. Oral contraceptive use in relation to breast cancer subtypes in African American women: Results from the AMBER Consortium. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B31. doi:10.1158/1538-7755.DISP13-B31

Poster 324 Cerebral Venous Sinus Thrombosis (CVST) in a 49-year-old Woman on Oral Contraceptives (OCP)

Poster 324 Cerebral Venous Sinus Thrombosis (CVST) in a 49-year-old Woman on Oral Contraceptives (OCP)

Effect of hormonal contraceptives on lipid profile and the risk indices for cardiovascular disease in a Ghanaian community.

BackgroundHormonal contraceptives (HCs) have been shown to alter lipid profile among various population groups with different patterns of dyslipidemia and cardiovascular (CV) risk. The study aimed at determining the lipid profile pattern and CV risk in a Ghanaian cohort.MethodsPurposive random sampling was done. Forty-seven and 19 cases were on oral contraceptives (OCs) and injectable contraceptives (ICs), respectively; five were on subdermal implant. Twenty-four non-users served as controls. Biodemographic and lipid profiles were determined. Total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), and very-low-density lipid lipoprotein cholesterol (VLDLC), were determined. Castelli index I and II were calculated.ResultsThe mean age difference between the HC and control groups was insignificant. However, diastolic blood pressure (BP) differences were significant (P=0.006). The body mass index (BMI) of the OC and IC groups were significantly different from the control group (P=0.003 and P=0.008, respectively). TC levels for the control and case groups were 3.35±0.62 mmol/L and 4.07±0.91 mmol/L, respectively (P=0.002). LDLC levels for the control and case groups were 1.74±0.57 mmol/L and 2.38±0.84 mmol/L, respectively (P=0.003). Castelli index I (TC/HDLC) and II (LDLC/HDLC) were significantly different between the control and OC groups (P=0.026 and P=0.014, respectively). Spearman’s rho correlation showed significant influence of HC use on TG (P=0.026), TC (P=0.000), LDLC (P=0.004), and VLDLC (P=0.026) over time.ConclusionHC use is associated with significant increases in BMI, diastolic BP, TC, LDLC, and Castelli index I and II. These changes carry a potential risk in the development of CV disease.

Who needs selection bias?

Present day low participation rates in certain parts of research is concerning. It is not unusual that half (or even more) of those invited to participate in a research project decline the invitation. Many think this will always lead to selection bias regardless of the type of study in question. That is fortunately not the case. Selection bias is a reason for concern in studies that aim to obtain a representative sample concerning risk factors or outcomes. Those who decline participation will often have a higher risk profile (lower social status, smokers etc) and more chronic disorders. Selection bias of the most serious type is related to the specific hypothesis when the hypothesis is known to participants. Being asked to participate in a study on oral contraceptives (OC) and breast cancer, for example, may be more appealing to women with breast cancer who have used OC. Selection is therefore often of concern in case–control studies. Non-response and selection bias is of less concern in follow-up studies where the outcome is not known at the time of recruitment. The reason for limited interest in “representativeness” is that scientific inference addresses a potential cause–effect relation in general, not in a specific population. Whether an established cause–effect relation is present in a specific population with a given effect estimate is a matter of effect measure modification and the distribution of component causes in that population at that given time period. Non-response in a follow-up study is expected to affect the structure of the population and influence the confounder distribution, often by producing less confounding because those with health problems and extreme lifestyle factors are more likely to decline participation. Since these factors may act as confounders, selection may change effect sizes without bias but just because effect sizes are population-specific. One should, however, be aware of a selection bias that would not be present with complete case ascertainment as illustrated in figure 1. Without selection (S), C 3 would not cause bias, but S (conditioned upon) will link C 3 to E, and establish the backdoor E-C 3 -D that can be closed by adjusting for C 3 . In a like manner, C 1 and C 2 have confounding potential because conditioning on S will produce the backdoor paths C 1 -C 3 -D and C 1 -C 2 -D. Adjustments for C 2 and C 3 will be needed. This will happen even in situations where S is not directly linked to D (because D has not occurred at the time of recruitment). Direct selection bias relating S to both E and D is only expected if D can be predicted by study participants (eg, by using the family history of disease occurrence). Selection in a cohort will not in itself lead to selection bias but will often produce a different confounder structure and therefore call for a different strategy when deciding on which confounders to include and how to treat them in the analysis.

Exogenous and Endogenous Hormones in Relation to Glioma in Women: A Meta-analysis of 11 Case-Control Studies

Background and ObjectivePrevious investigations of glioma risk in women have focused on oral contraceptive (OC), hormone replacement therapy (HRT), and reproductive factors. However, the results of published studies were inconclusive and inconsistent. Thus, a meta-analysis based on published case-control studies was performed to assess the role of exogenous and endogenous hormones factors in glioma risk.MethodsThe PubMed and EMBASE databases were searched without any restrictions on language or publication year. Reference lists from retrieved articles were also reviewed. We included case-control studies reporting relative risks (RRs) with corresponding 95% confidence intervals (CIs) (or data to calculate them) between oral contraceptive (OC) and hormone replacement therapy (HRT) use, reproductive factors and glioma. Random-effects models were used to calculate the summary risk estimates.ResultsFinally, 11 eligible studies with 4860 cases and 14,740 controls were identified. A lower risk of glioma was observed among women who were ever users of exogenous hormones (OC RR = 0.707, 95% CI = 0.604–0.828; HRT: RR = 0.683, 95% CI = 0.577–0.808) compared with never users. An increased glioma risk was associated with older age at menarche (RR = 1.401, 95% CI = 1.052–1.865). No association was observed for menopause status, parous status, age at menopause, or age at first birth and glioma risk.ConclusionThe results of our study support the hypothesis female sex hormones play a role in the development of glioma in women. Additional studies are warranted to validate the conclusion from this meta-analysis and clarity the underlying mechanisms.

Influence of Depressed Mood and Psychological Stress Symptoms on Perceived Oral Contraceptive Side Effects and Discontinuation in Young Minority Women

Background We examined the influence of depressed mood and psychological stress on oral contraceptive (OC) side effects and discontinuation.