Long-term Use Of Oral Contraceptives Research Articles

Joint modeling of gene-environment correlations and interactions using polygenic risk scores in case-control studies.

Polygenic risk scores (PRSs) are rapidly emerging as a way to measure disease risk by aggregating multiple genetic variants. Understanding the interplay of the PRS with environmental factors is critical for interpreting and applying PRSs in a wide variety of settings. We develop an efficient method for simultaneously modeling gene-environment correlations and interactions using the PRS in case-control studies. We use a logistic-normal regression modeling framework to specify the disease risk and PRS distribution in the underlying population and propose joint inference across the 2 models using the retrospective likelihood of the case-control data. Extensive simulation studies demonstrate the flexibility of the method in trading-off bias and efficiency for the estimation of various model parameters compared with standard logistic regression or a case-only analysis for gene-environment interactions, or a control-only analysis, for gene-environment correlations. Finally, using simulated case-control data sets within the UK Biobank study, we demonstrate the power of our method for its ability to recover results from the full prospective cohort for the detection of an interaction between long-term oral contraceptive use and the PRS on the risk of breast cancer. This method is computationally efficient and implemented in a user-friendly R package.

New advances in the treatment of thin endometrium.

Thin endometrium (TE) is defined as a mid-luteal endometrial thickness ≤7mm. TE can affect endometrial tolerance, leading to lower embryo implantation rates and clinical pregnancy rates, and is also associated with impaired outcomes from assisted reproductive treatment. Herein, we systematically review TE causes, mechanisms, and treatments. TE pathogenesis has multiple causes, with the endometrium becoming thinner with age under hormonal influence. In addition, uterine cavity factors are important, as the inflammatory environment may affect expressions of certain genes thereby inhibiting endometrial stromal cell proliferation and promoting apoptosis. Long-term oral contraceptive use or the use of ovulation-promoting drugs are also definite factors contributing to endometrial thinning. Other patients have primary factors, for which the clinical etiology remains unknown. The main therapeutic strategies available for TE are pharmacological (including hormonal and vasoactive drugs), regenerative medicine, intrauterine infusion of growth factor-granulocyte colony-stimulating factor, autologous platelet-rich plasma, and complementary alternative therapies (including traditional Chinese herbal medicine and acupuncture). However, the associated mechanisms of action are currently unclear. Clinical scholars have proposed various approaches to improve treatment outcomes in patients with TE, and are exploring the principles of efficacy, offering potentials for novel treatments. It is hoped that this will improve TE tolerance, increase embryo implantation rates, and help more couples with infertility with effective treatments.

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

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

An empirical evaluation of approximate and exact regression-based causal mediation approaches for a binary outcome and a continuous or a binary mediator for case-control study designs

BackgroundIn the causal mediation analysis framework, several parametric regression-based approaches have been introduced in past years for decomposing the total effect of an exposure on a binary outcome into a direct effect and an indirect effect through a target mediator. In this context, a well-known strategy involves specifying a logistic model for the outcome and invoking the rare outcome assumption (ROA) to simplify estimation. Recently, exact estimators for natural direct and indirect effects have been introduced to circumvent the challenges prompted by the ROA. As for the approximate approaches relying on the ROA, these exact approaches cannot be used as is on case-control data where the sampling mechanism depends on the outcome.MethodsConsidering a continuous or a binary mediator, we empirically compare the approximate and exact approaches using simulated data under various case-control scenarios. An illustration of these approaches on case-control data is provided, where the natural mediation effects of long-term use of oral contraceptives on ovarian cancer, with lifetime number of ovulatory cycles as the mediator, are estimated.ResultsIn the simulations, we found few differences between the performances of the approximate and exact approaches when the outcome was rare, both marginally and conditionally on variables. However, the performance of the approximate approaches degraded as the prevalence of the outcome increased in at least one stratum of variables. Differences in behavior were also observed among the approximate approaches. In the data analysis, all studied approaches were in agreement with respect to the natural direct and indirect effects estimates.ConclusionsIn the case where a violation of the ROA applies or is expected, approximate mediation approaches should be avoided or used with caution, and exact estimators favored.

Knowledge, Attitude, and Prevalence Towards Cervical Cancer Screening Among Women in a Nigerian Urban Municipality

BACKGROUND: Cervical cancer is a significant global health concern, particularly in less developed regions, ranking as the fourth most common cancer among women. Nigeria faces its crisis, with approximately 15,000 women diagnosed annually, resulting in a two-thirds fatality rate. An alarming 40 million Nigerian women remain at risk, underscoring the urgency of improved screening and disease surveillance, compounded by the absence of a national cancer policy and limited awareness. Cervical cancer can be reduced by more than 90% through regular screening. It is caused by sexually transmitted HPV and risk factors include multiple sexual partners, smoking, long-term oral contraceptive use, and immunosuppression. AIM: The study aimed to ascertain the knowledge, attitude, and practices toward cervical cancer screening and the factors that influence the practice of screening among women of the reproductive age group in Calabar Municipality. METHODS: Using a cross-sectional study design, 414 women were enrolled from two public hospitals, four private hospitals, and a non-governmental women’s center through a meticulous multi-stage sampling technique, employing semi-structured questionnaires. Socio-demographic variables were collected, and a 31-item questionnaire was used to assess the level of knowledge, attitudes, and practices toward cervical cancer. Data were analyzed using IBM SPSS version 26; p-values less than 0.05 were considered significant. RESULTS: The mean ages of respondents were 28.01 ± ((8.8357), 293 were single, while 107 were married. 69.67% had received at least tertiary education. 51.9% were employed, and the rest were unemployed. All 414 respondents were familiar with cervical cancer, but 65.7% lacked adequate knowledge of screening. Approximately 60% were aware of screening tests, with health workers as their primary information source. Most women displayed a favorable attitude toward screening; 97.3% expressed willingness if the procedure was explained and accessible, 96.4% if it was free and safe, and 97.6% supported screening for women under 30 years. Unfortunately, only 8% had undergone screening, with Pap smears as the commonest screening method for 84.8% of those who had received screening. Out of 381 respondents who had never been screened, 101 did not think they were at risk, 89 did not know where to get screened, 75 believed their religion protected them, and 37 found it expensive. In bivariate analysis, age, marital status, employment status, and knowledge of screening significantly correlated with good practice (p<0.05). CONCLUSION: The underutilization of screening services in an urban setting is concerning, signaling the potential for cancer care disparities in rural areas. Urgent interventions are needed to foster more favorable attitudes and practices, particularly in developing countries like Nigeria, where cervical cancer remains a leading women's health concern. With Nigeria's limited healthcare financing and fragile health system, cervical cancer screening promotion is crucial. Community-based strategies should be utilized to promote screening, and medical outreaches organized to eliminate healthcare barriers. The government should increase funding for the health sector and provide more screening centers while empowering healthcare providers.

Hormonal contraception and cervical cancer: does the correlation exist?

The article presents a systematic analysis of scientifi c publications concerning the eff ect of combined hormonal contraceptives on the risk of the development of cervical cancer. The following databases were used for literary search: PubMed, Cochrane, Google Scholar, elibrary.ru. Key words and their combinations were: “cervical cancer”, “cervical intraepithelial neoplasia”, “human papillomavirus”, “contraception”, “combined oral contraceptives”, “hormonal contraceptives”. 147 scientifi c publications have been analyzed, and 10 of them have been selected with the use of I/E criteria. Based on the analyzed literature, a conclusion was made. Long-term use of combined oral contraceptives against the background of persistence of the human papillomavirus increases the risk of developing cervical cancer.

Effect of contraceptive hormonal therapy on mammographic breast density: A longitudinal cohort study

PurposeEvaluate the longitudinal relationship between mammographic density and hormonal contraceptive use in late reproductive-aged women. MethodsPatients aged 35–50 years old who underwent 5 or more screening mammograms within a 7.5-year period between 2004 and 2019 in a single urban tertiary care center were randomly selected. Patients were categorized into four cohorts based on hormonal contraceptive exposure during a 2-year lead-in period and a 7.5-year study period: 1) never exposed, 2) always exposed, 3) interval hormonal contraceptive start, and 4) interval hormonal contraceptive stop. The primary outcome was difference in BI-RADS breast density category between initial and final mammograms. ResultsOf the 708 patients included, long-term use of combined oral contraceptives or a levonorgestrel intrauterine device were not associated with an increase in breast density category over the 7.5-year study period, compared to those with no hormonal contraceptive exposure. Initiation of combined oral contraceptives was associated with an increase in breast density category (β = 0.31, P = 0.045); however, no difference in initial density category was noted between those exposed and those never exposed to combined oral contraceptives during the 2-year lead-in period, and discontinuation was not associated with a decrease in breast density category when compared to those with continuous exposure. Conclusion(s)Long-term use of combined oral contraceptives or a levonorgestrel intrauterine device was not associated with an increase in BI-RADS breast density category. Initiation of a combined oral contraceptive was associated with an increase in breast density category, although this may be a transient effect.

Correlation between Oral Contraceptive Use and the Incidence of Cervical Cancer

Cervical cancer is a malignant tumor that develops in the cervix and is the second most common type of cancer experienced by women in the world. Causes of cervical cancer include HPV infection, use of oral contraceptives, age of marriage, parity and exposure to cigarette smoke. This study aims to determine the correlation between oral contraceptive use and the incidence of cervical cancer. This literature study research involved secondary data derived from the Google Scholar, Research Gate and Science Direct databases. The keywords applied in the study were oral contraceptives, birth control pills AND cervical cancer. The journals involved were searched for similarities, dissimilarities and compared to one another. As mentioned in 11 journals, long-term use of oral contraceptives of ≥5 years could increase the risk of cervical cancer. Furthermore, three journals stated the grade of cervical precancerous lesions of CIN 2/3 as the risk factor of cervical cancer, and two journals stated the grade of cervical cancer of stage 2/2+ as the risk factor of cervical cancer. Based on the chi-square test results, 4 journals presented a significance value (p-value) of <0.05, which indicated a correlation between oral contraceptives and the incidence of cervical cancer. 9 other journals found the highest OR value = 9.11 and the lowest OR = 1.50 which meant that women who used Oral contraceptives were 9 times more at risk of developing cervical cancer. Oral contraceptive use was associated with cervical cancer based on the duration of use of more than 5 years and led to a risk of causing CIN 2/3 among women. There were other factors that could affect the incidence of cervical cancer, namely age of marriage, parity and exposure to cigarette smoke.

The potent contraceptive gestodene exerts insulinotropic effects through its a-ring reduced metabolites with intrinsic estrogen-like activity in pancreatic β-cells.

The contraceptive gestodene is a potent synthetic progestin used in several low-dose contraceptive formulations. Clinical studies reported a relationship between long-term use of combined oral contraceptives containing gestodene (GDN) and profound alterations in glucose metabolism in women. The observation that contraceptive synthetic progestins exert hormone-like effects other than their progestational activities, prompted us to investigate whether GDN may induce estrogen-like effects, even though GDN does not interact with estrogen receptors. The aim of this study was to investigate whether GDN affect pancreatic β-cell activity, directly or through its conversion to other bioactive metabolites. The effects of GDN and its two derivatives 3β,5α-tetrahydro-GDN and 3α,5α-tetrahydro-GDN on insulin 2 (Ins II) and glucokinase (Gk) expression and glucose-stimulated insulin secretion were determined in pancreatic islets from female rats. Gestodene did exert significant effects on islet β-cells activity. The most striking finding was that 3β,5α-tetrahydro-GDN and 3α,5α-tetrahydro-GDN had greater stimulatory effects on Ins II and Gk expression than that observed with GDN, consistent with their effects on glucose-stimulated insulin secretion. The effects on gene expression induced by GDN-derivatives were abolished by ICI 182,780 and MPP. In addition, the presence of inhibitors of androgen and progestin-metabolizing enzymes eliminated gene expression induced by GDN. These results indicated that GDN is metabolized to A-ring reduced metabolites with estrogen-like activities and through this mechanism, GDN may affect β-cell activity. Altogether, the data suggest that 19-nortestosterone-derived contraceptives such as GDN, possess insulinotropic effects through their conversion into metabolites with intrinsic estrogen-like activity in pancreatic β-cells.

Steady-state estradiol triggers a unique innate immune response to allergen resulting in increased airway resistance

RationaleAsthma is a chronic airway condition that occurs more often in women than men during reproductive years. Population studies have collectively shown that long-term use of oral contraceptives decreased the onset of asthma in women of reproductive age. In the current study, we hypothesized that steady-state levels of estrogen would reduce airway inflammation and airway hyperresponsiveness to methacholine challenge.MethodsOvariectomized BALB/c mice (Ovx) were implanted with subcutaneous hormone pellets (estrogen, OVX-E2) that deliver consistent levels of estrogen [68 ± 2 pg/mL], or placebo pellets (OVX-Placebo), followed by ovalbumin sensitization and challenge. In conjunction with methacholine challenge, immune phenotyping was performed to correlate inflammatory proteins and immune populations with better or worse pulmonary outcomes measured by invasive pulmonary mechanics techniques.ResultsHistologic analysis showed an increase in total cell infiltration and mucus staining around the airways leading to an increased inflammatory score in ovarectomized (OVX) animals with steady-state estrogen pellets (OVX-E2-OVA) as compared to other groups including female-sham operated (F-INTACT-OVA) and OVX implanted with a placebo pellet (OVX-Pl-OVA). Airway resistance (Rrs) and lung elastance (Ers) were increased in OVX-E2-OVA in comparison to F-INTACT-OVA following aerosolized intratracheal methacholine challenges. Immune phenotyping revealed that steady-state estrogen reduced CD3+ T cells, CD19+ B cells, ILC2 and eosinophils in the BAL across all experiments. While these commonly described allergic cells were reduced in the BAL, or airways, we found no changes in neutrophils, CD3+ T cells or CD19+ B cells in the remaining lung tissue. Similarly, inflammatory cytokines (IL-5 and IL-13) were also decreased in OVX-E2-OVA-treated animals in comparison to Female-INTACT-OVA mice in the BAL, but in the lung tissue IL-5, IL-13 and IL-33 were comparable in OVX-E2-OVA and F-INTACT OVA mice. ILC2 were sorted from the lungs and stimulated with exogenous IL-33. These ILC2 had reduced cytokine and chemokine expression when they were isolated from OVX-E2-OVA animals, indicating that steady-state estrogen suppresses IL-33-mediated activation of ILC2.ConclusionsTherapeutically targeting estrogen receptors may have a limiting effect on eosinophils, ILC2 and potentially other immune populations that may improve asthma symptoms in those females that experience perimenstrual worsening of asthma, with the caveat, that long-term use of estrogens or hormone receptor modulators may be detrimental to the lung microenvironment over time.

Association of Chlamydia trachomatis infection with cervical atypia in adolescent women with short-term or long-term use of oral contraceptives: a longitudinal study in HPV vaccinated women

ObjectiveWe assessed the relationship between Chlamydia trachomatis infection, duration of oral contraceptive (OC) use and cervical atypia among young adult Finnish women.DesignA longitudinal study.Setting and participantsWomen who were included in...

Association between Oral Contraceptive Use and the High-Sensitivity C-Reactive Protein Level in Premenopausal Korean Women.

Although oral contraceptives (OCs) are widely used, few national epidemiological studies have evaluated the association between OC use and serum high-sensitivity C-reactive protein (hs-CRP) levels in Korean women. This population-based cross-sectional study was conducted with data from the 2015–2018 National Health and Nutrition Examination Survey. In the sample of 5332 premenopausal women aged ≥19 years, hs-CRP concentrations were 1.087 mg/L among OC users and 0.953 mg/L among OC non-users. After adjustment for confounders, OC users had an increased likelihood of having risky (>1.0 mg/L) hs-CRP levels (adjusted odds ratio (aOR) = 1.58; 95% confidence interval (CI), 1.25–1.98) compared with OC non-users. In addition, the aOR for high-risk (>3.0 mg/L) hs-CRP levels in OC users compared with non-users was 1.51 (95% CI, 1.06–2.16). These findings demonstrate that OC use alters the concentration of hs-CRP, a biomarker of chronic low-grade inflammation, and suggest that long-term OC use is a risk factor in the pathogenesis of inflammatory diseases, including cardiovascular diseases.

Prediction, assessment, and management of suboptimal GnRH agonist trigger: a systematic review.

This systematic review aimed to identify baseline patient demographic and controlled ovarian stimulation characteristics associated with a suboptimal response to GnRHa triggering, and available options for prevention and management of suboptimal response. PubMed, Google Scholar, Medline, and the Cochrane Library were searched for keywords related to GnRHa triggering, and peer-reviewed articles from January 2000 to September 2021 included. Thirty-seven studies were included in the review. A suboptimal response to GnRHa triggering was more likely following long-term or recent oral contraceptive use and with a low or high body mass index. Low basal serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol serum levels were correlated with suboptimal oocyte yield, as was a low serum LH level on the day of triggering. A prolonged stimulation period and increased gonadotropin requirements were correlated with suboptimal response to triggering. Post-trigger LH < 15 IU/L best correlated with an increased risk for empty follicle syndrome and a lower oocyte retrieval rate. Retriggering with hCG may be considered in patients with suboptimal response according to post-trigger LH, as in cases of failed aspiration. Pre-treatment assessment of patient characteristics, with pre- and post-triggering assessment of clinical and endocrine cycle characteristics, may identify cases at risk for suboptimal response to GnRHa triggering and optimize its utilization.

Association between past oral contraceptive use and the prevalence of hypertension in postmenopausal women: the fifth (2010\u20132012) Korea National Health and Nutrition Examination Survey (KNHANES V)

BackgroundThere is little evidence as to whether the use of oral contraceptives(OC) during the fertile years affects the development of postmenopausal hypertension. This study aimed to evaluate the association between past use of OC and development of hypertension in postmenopausal women.MethodsThis was a cross-sectional study conducted using data from the Fifth Korea National Health and Nutrition Examination Survey of postmenopausal women. Subjects were classified into three groups based on past OC use duration: nonusers, short-term users(0–30 months), and long-term users(≥ 30 months). We evaluated the development of hypertension in women after menopause. A multivariable logistic regression model was used to identify the association between the use of OC during the fertile years and the prevalence of hypertension after menopause following adjustment for potential confounding factors.ResultsOf the 3,386 postmenopausal women, 2,713 were nonusers of OC, 489 were short-term users, and 184 were long-term users. Women who had used OC for 30 months or more had a significantly greater prevalence of hypertension after menopause than those who had never taken OC. The association between taking OC for 30 months or more during the fertile years and the prevalence of hypertension after menopause was significant following adjustment for potential confounding factors (adjusted OR:1.75; 95%CI:1.12–2.74).ConclusionThis study identified an association between past OC use and an increased prevalence of hypertension in postmenopausal women. Our results suggest that long-term use of OC during the fertile years can be an important risk factor for subsequent hypertension after menopause.

ADOLESCENT KNOWLEDGE LEVEL ABOUT CERVIC CANCER PREVENTION

Cervical cancer is the most common cancer among women. Cervical cancer attacks the female reproductive organs and uterus. Every year thousands of women die from cervical cancer. Poor living habits can also cause outbreaks of cervical cancer, such as smoking, lack of nutrition, long-term use of oral contraceptives, sexual activity that is often among adolescents. The level of knowledge of young women about cervical cancer prevention in the MayjendSutoyo College Foundation Senior High School Medan. World Health Organization (WHO) states, currently cervical cancer is ranked among the various types of cancer that causes death in women in the world. Cervical cancer can be prevented by doing primary prevention and secondary prevention. This type of research is a descriptive study conducted. The population in this study were female students at the MayjendSutoyo College Foundation in Medan. A sample of 39 people were taken in total sampling. Data obtained using a questionnaire. The conclusion of the study is the level of knowledge of young women in the MayjendSutoyo Medan Foundation High School in the prevention of cervical cancer is still in the sufficient category.

The relationship between hormonal contraception and cervical dysplasia/cancer controlling for human papillomavirus infection: A systematic review

ObjectiveStudies on the effect of long-term use of combined oral contraceptives (COCs) on cervical dysplasia and/or cancer risk have been inconsistent. Less is known about the effects of other forms of hormonal contraception (HC). We examine whether HC use increases the risk of incident cervical intraepithelial neoplasia (CIN) 2, 3 and/or cancer after accounting for preexisting human papillomavirus (HPV) infection. Study DesignSystematic review of prospective studies on HC use as risk factor for cervical dysplasia with HPV infection documented prior to outcome assessment including PubMed and EMBASE records between January 2000 and February 2020 (Prospero #CRD42019130725). ResultsAmong nine eligible studies, seven described recency and type of HC use and therefore comprise the primary analysis; two studies limit comparisons to ever versus never use and are summarized separately. All seven studies explored the relationship between oral contraceptive (OC) use and cervical dysplasia/cancer incidence: two found increased risk (adjusted odds ratio, aOR = 1.5–2.7), one found no association but decreased risk when restricted to women with persistent HPV (adjusted hazard ratio = 0.5), and four found no association. None of the seven studies differentiated between COC and progestin-only pills (POPs) by use recency or duration. The only study that included injectable progestin-only contraception (DMPA) found increased CIN3 incidence among current versus never users (aOR = 1.6). The one study that included Norplant found no association. Two studies included intrauterine device (IUD) use, but did not differentiate between hormonal and copper IUDs, and found no association. ConclusionWe found no consistent evidence that OC use is associated with increased risk for cervical dysplasia/cancer after controlling for HPV infection. There were too few studies of progestin-only injectables, implants or IUDs to assess their effect on cervical dysplasia/cancer risk. ImplicationsUse of single self-reported HC measures and insufficient distinction by hormonal constituent cloud our understanding of whether some HCs increase risk for cervical cancer. Methodologically rigorous studies with distinct HCs measured as time-varying exposures are needed to inform cervical cancer prevention efforts and improve our understanding of cervical cancer etiology.

Time-Dependent Effects of Oral Contraceptive Use on Breast, Ovarian, and Endometrial Cancers.

Oral contraceptive use has been suggested to influence the risk of breast, ovarian, and endometrial cancer. The purpose of this study is to clarify the time-dependent effects between long-term oral contraceptive use and cancer risk. We performed an observational study in 256,661 women from UK Biobank, born between 1939 and 1970. Information on cancer diagnoses were collected from self-reported data and from national registers until March 2019. Cumulative risk of cancer over the timespan of the study, as measured by the OR, and instantaneous risk, as measured by the HR, were assessed using Logistic and Cox regression analyses, respectively. The odds were lower among ever users, compared with never users, for ovarian cancer [OR = 0.72; 95% confidence interval (CI), 0.65-0.81] and endometrial cancer (OR = 0.68; 95% CI, 0.62-0.75), an association that was stronger with longer use (P < 0.001). Increased odds were seen for breast cancer in women when limiting the follow-up to 55 years of age (OR = 1.10; 95% CI, 1.03-1.17), but not for the full timespan. We only found a higher HR for breast cancer in former users immediately (≤2 years) after discontinued oral contraceptive use (HR = 1.55; 95% CI, 1.06-2.28), whereas the protective association for ovarian and endometrial cancer remained significant up to 35 years after last use of oral contraceptives. Given the body of evidence presented in our study, we argue that oral contraceptives can dramatically reduce women's risk of ovarian and endometrial cancer, whereas their effect on lifetime risk of breast cancer is limited. SIGNIFICANCE: These results enable women and physicians to make more informed decisions considering oral contraceptive use, thus constituting an important step toward personalized medicine.

Efeitos Colaterais a longo prazo associados ao uso de Anticoncepcionais Hormonais Orais

Oral hormonal contraceptives are effective contraceptive methods that prevent unwanted pregnancies from occurring. They are classified according to a hormonal composition as combinations and mini pills and not different from the other drugs, these also have associated effects. Thus, the objective of this research was to outline the effects related to the continuous and long-term use of oral hormonal contraceptives. This is an Integrative Review carried out based on articles published between the years 2015 and 2021, in the databases MEDLINE, BDENF, LILACS and Google Scholar. Among the results found, it was shown that oral contraceptive hormones can cause greater damage to health, such as thrombosis, increased blood pressure, cardiovascular problems, neoplasms, especially with long-term use. It is concluded that it is necessary that health professionals, especially pharmacists, and visual women on alert, regarding the effects triggered by the prolonged use of the oral hormonal method and the aggravations of these when associated with modifiable and non-modifiable risk predispositions. Relevant to women's health.

Effects of Exogenous Hormones and Reproductive Factors on Female Melanoma: A Meta-Analysis.

Epidemiological findings on the effects of hormones on melanoma risk have been inconsistent. We therefore conducted a meta-analysis to examine the relationship between exogenous hormonal and reproductive factors and the risk of melanoma in women. We performed a search of PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI) database through April 2020 for relevant studies. Based on heterogeneity, we performed the meta-analysis of the risk estimates using either fixed effect or random effect models. We identified 38 studies that met the analytical criteria, involving 3,571,910 participants. The results showed that long-term use of oral contraceptives (OC) may increase the risk of melanoma in women (≥5 years [pooled RR=1.18; 95% CI: 1.07–1.31; I2=0%] and ≥10 years [pooled RR=1.25; 95% CI: 1.06–1.48; I2=0%]). Women who first used OC 15–19 years previously were more likely to develop melanoma (pooled RR=1.52; 95% CI: 1.03–2.24; I2=0%), while the years since the last use and the age at first use were not associated with the development of melanoma in women. Hormone replacement therapy (HRT) increased the incidence of melanoma in women (pooled RR=1.12, 95% CI: 1.02–1.24; I2=50%) and was especially associated with an increased risk of superficial spreading melanoma (SSM) (pooled RR=1.26; 95% CI: 1.17–1.37; I2=0%), and estrogen and estradiol may be the main active agents that contribute to the increased risk of melanoma, but these results may be due to a combination of sun exposure factors. With regard to reproductive factors, decreased parity and being aged ≥20 years at first birth may be associated with an increased risk of melanoma in females, while menopausal status and age at menarche are not associated with the incidence of melanoma in females. Further large-scale prospective studies are necessary to reveal new pathophysiological mechanisms and new therapeutic targets for cutaneous melanoma.

S2733 A Curious Case of a Bleed Without a Cause

INTRODUCTION: Spontaneous subcapsular hematoma of the liver is usually associated with pregnancy, coagulopathy or liver lesion. We report a rare case of spontaneous subcapsular liver hematoma without any of the above risk factors. CASE DESCRIPTION/METHODS: A 59-year-old lady with a history of hypertension presented with sudden-onset in the right upper abdomen, right chest, shoulder and neck pain. She was otherwise hemodynamically stable other than being mildly hypertensive. Work-up for cardiac ischemia was negative. She was noted to have a low hemoglobin of 10.4 g/dl (prior baseline was 13.7 g/dL) and she had mild hepatocellular injury (ALT 32 IU/L, AST 31 IU/L). She underwent CT scan to rule out pulmonary embolism which incidentally revealed a large subcapsular liver hematoma. MRI abdomen confirmed a large lenticular shaped subscapular collection along the right lobe of the liver measuring approximately 12 × 4 × 16 cm. There was no focal hepatic lesion to explain the cause of bleeding. She did not recall any preceding trauma and there was no obvious trauma on exam. She was not taking any blood thinners. She admitted to inadvertently using oral contraceptives (OCP) for over 30 years for purely birth control purposes. The patient was admitted for observation and remained clinically stable over the next few days. At her 1-month follow-up, an office ultrasound showed that the size of the hematoma had decreased when compared to her prior ultrasound during her hospitalization (thickness from intercostal view decreased from 42 mm to 35 mm). At her 1-year follow-up, an MRI abdomen was repeated that showed a minimal residual hematoma and no discrete underlying lesion. DISCUSSION: Spontaneous subcapsular hematoma of the liver represents an accumulation of blood between the capsule of Glisson and the liver parenchyma, and is frequently located around the right lobe. If it ruptures into the peritoneum, it can be potentially fatal. Our case is unique in that none of the usual risk factors such as pregnancy, trauma, blood thinner use or underlying liver lesion were present. To our knowledge, there are very few similar case reports that describe spontaneous subcapsular hepatic hematoma. OCP use is generally associated with the development of hepatic adenoma, which can in turn cause spontaneous subcapsular hematoma. Theoretically, long-term OCP use in a post-menopausal hypertensive lady (such as in our case) may mimic the pathophysiology of pregnancy and independently lead to spontaneous subcapsular bleeding.Figure 1.: MRI showing large hepatic subcapsular hematoma and no focal lesion.Figure 2.: MRI showing nearly resolved hepatic subcapsular hematoma.