Oral Contraceptive Use Research Articles

Thrombosis in Young Women on Ocps Likely Is Caused By an Unmasking Effect of Estrogens on Underlying Thrombophilias

Background: Estrogen-containing oral contraceptives (OCPs) increase the risk for thrombosis 3-4 fold in otherwise healthy young women, although the absolute thrombosis rate in young OCP users is only 0.05% per year (Trenor CC, Pediatrics. 2011;127: 347). In our prospective cohort database 70% of lower extremity venous thromboembolism in adolescent girls were associated with OCP use, usually of recent onset (<6months). OCPs are associated with acquired resistance to activated protein C (APC), an important thrombin regulatory pathway, with an increase in fibrinolysis (Douxfils J, Contraception, 2020;102:396). A causative role for estrogens in thrombus formation in young women is not completely understood. Aims: This study evaluated thrombin generation, thrombin reduction by APC (activated protein C resistance, APCR), fibrinolysis and thrombophilia in healthy young males, healthy young females who were using or not using estrogen hormone therapy (i.e. oral contraceptive pills/OCPs) and young females with thrombosis who were using or not using OCPs at the time of thrombus presentation. The goal of this study was to measure the effects of OCPs on laboratory assays of coagulation and fibrinolysis to reveal potential mechanisms in increased thrombosis risk. Methods: This was an analysis of a consented, prospective cohort study (Thrombo-PICS). Healthy controls included men and women with no personal or family history of bleeding or clotting who were using or not using OCPs and on no other relevant medications. Study groups included females who presented with thrombosis with no OCP use, or OCP use for less than six months versus six or more months. All participants with a history of thrombosis were studied three or more months following the onset of thrombosis and no longer on OCPs. Laboratory assays performed included calibrated automated thrombography (CAT) with and without thrombomodulin (CAT TM) to determine thrombin generation (endogenous thrombin potential, ETP) and thrombin reduction with APC (% ETP reduction, APCR) respectively, and the euglobulin clot lysis time (ELT) to model fibrinolysis. Factors known to cause APCR and to be associated with thrombosis were also assayed, including factor V Leiden (FVL), the prothrombin gene mutation (PTM), protein C, protein S, lipoprotein(a), and the lupus anticoagulant (LA). Overall results were presented using descriptive statistics. Chi-Squared tests and paired t-tests were used to make paired comparisons. Parametric and non-parametric paired comparisons were used to evaluate group differences in ETP, % ETP reduction, ELT and presence thrombophilic traits relative to estrogen use and history of thrombosis. Results: Table 1 and Figure 1 display results. All groups of females with a history of thrombosis had decreased mean %ETP reduction compared to healthy females not on OCPs (p=0.02), with the lowest values occurring in females with thrombosis following less than six months of OCP use. There was also a lower prevalence of abnormal CAT TM values amongst healthy controls not on OCPs as compared to thrombosis patients not on OCPs (19 vs 51%, p=0.005).Healthy females on OCPs showed an increased ETP (p=0.002) and a marked reduction in ELT (p<0.001) as compared to all other groups. Females with a history of thrombosis, whether associated with OCPs or not, were similar to healthy females not using OCPs in regard to ETP and ELT. Furthermore, females who developed thrombosis on OCPs were more likely to have a thrombophilic trait than healthy controls on OCPs (48 vs 4%, p<0.001). Healthy men were found to have a greater %ETP reduction than healthy women (p=0.04), while having a lower ETP than healthy women (p=0.007). There were no differences in ELTs between healthy male and female controls (p=0.39). Discussion: OCPs were associated with increased thrombin generation, increased APCR and accelerated fibrinolysis in healthy female controls. The lower ELT in healthy controls using OCPs suggests that increased fibrinolysis may partially balance acquired APCR from estrogen use. We were unable to test fibrinolysis in females on OCPs prior to the onset of thrombosis. Females with thrombosis onset within six months of starting OCPs showed the highest prevalence of thrombophilic traits known to cause APCR. These data suggest that the APCR effect of OCPs potentially augments the prothrombotic effect of underlying thrombophilias in the promotion of clinical thrombosis.

Exploring the interactive effects of oral contraceptive use and dietary fat intake on blood pressure, cardiovascular reactivity, and glucose tolerance in normotensive women.

Objective: To understand how dietary fat consumption and the use of oral contraceptives interact to affect blood pressure, cardiovascular reactivity, and glucose tolerance in normotensive women. Study Design: Cross-section study. Setting: Hayatabad Medical Complex, Peshawar. Period: December 2022 to April 2023. Material & Methods: A total of 120 normotensive women aged between 18 and 35 years were recruited from local healthcare centers, clinics, and educational institutions. Demographic characteristics, oral contraceptive use, and dietary fat intake were assessed through self-reporting and validated food frequency questionnaires. Resting blood pressure measurements, cardiovascular reactivity during standardized stressors, and glucose tolerance through oral glucose tolerance tests were recorded. Results: The study found no significant associations between oral contraceptive use and blood pressure, cardiovascular reactivity, or glucose tolerance. Similarly, dietary fat intake did not significantly influence these health parameters. Conclusion: The results emphasize the importance of personalized healthcare recommendations for women using oral contraceptives, considering individual variations and other lifestyle factors. Further research with larger, longitudinal studies is warranted to elucidate the potential long-term effects of these interactions and promote cardiovascular health for women worldwide.

Association between endometriosis and risk of type 2 diabetes: Results from the prospective E3N cohort.

Several studies suggest an association between endometriosis and the risk of cardio-metabolic diseases. This study aimed to prospectively evaluate the association between history of endometriosis and incident type 2 diabetes. E3N is a prospective cohort of 98,995 French women aged 40-65years at inclusion. Multivariable Cox regression models were used to estimate hazard ratios and 95% confidence intervals for the association between endometriosis and incident type 2 diabetes. We evaluated effect modification by age, body mass index, infertility treatment, adherence to the Mediterranean diet, and menopausal status. Age at inclusion was 51±6years and there were 2672 incident cases of type 2 diabetes. A total of 4606 women reported surgically-confirmed endometriosis among 83,582 women with no history of diabetes at inclusion. Endometriosis was not associated with type 2 diabetes risk in a model adjusted for age, BMI, physical activity, smoking, education, age at menarche and oral contraceptive use (hazard ratio [HR]=1.09; 95% confidence interval [CI]=0.92-1.29), neither after further adjustment for family history of diabetes, hypertension and menopausal status (HR=0.97;95%CI=0.80-1.16). The relationship did not differ by age at inclusion, BMI, infertility treatment, diet or menopausal status (p>0.05). Surgically-confirmed endometriosis was not associated with the risk of type 2 diabetes in this large cohort, confirming that endometriosis is not a risk marker for type 2 diabetes.

Abstract 071: Oral Contraceptive Use and Development of Acute Ischemic Stroke: A Population‐Based Retrospective Cohort Study

Introduction Existing evidence remains conflicting regarding the association between oral hormonal contraceptive (OCP) use and the risk of acute ischemic stroke (AIS). Large‐scale analyses and observational data evaluating this clinical question in recent years are scarce, despite widespread use of hormonal contraception in adult females of child‐bearing age. Modern OCP formulations contain lower doses of estrogen, the putative causative agent for AIS in this population, and underscores the need to re‐evaluate the risk initially demonstrated in older formulations containing higher levels of estrogen. Methods Hospitalizations for female patients aged 15‐50 were identified in the National Inpatient Sample (NIS) registry from 2015‐2020, excluding admissions associated with pregnancy or the postpartum period. The study exposure was use of OCPs and the primary endpoint was AIS, identified by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD‐10‐CM) coding. Propensity score (PS) adjustment by inverse probability weighting (IPW) was used to mimic the effects of randomization by balancing baseline clinical characteristics associated with stroke between OCP and non‐OCP users to reduce measured confounding. In addition to age and race/ethnicity, a battery of more than forty confounding covariates representing established risk factors for AIS in the general and young population were identified (cardiovascular disease, lifestyle risk factors, congenital abnormalities, vasculopathies, hypercoagulable states, migraine with aura, among others) and balanced between OCP and non‐OCP users. Sensitivity testing was performed by evaluating stroke incidence in a sub‐group of patients without any risk factors present and by assessing a negative control (head trauma), with which an association of OCP use would not be expected. The effect size of the association between OCPs and AIS was presented as an adjusted odds ratio (aOR) with 95% confidence interval (CI), with statistical significance evaluated at p < 0.001. Results PS adjustment by IPW to balance all available AIS risk factors between OCP users and non‐users yielded 23,253,209 hospitalizations, 11,654,398 (50.1%) of which were associated with OCP use. The incidence of AIS was significantly greater in OCP users compared to non‐OCP users (2.8% vs. 0.4%; aOR 7.50, 95% CI 7.43 to 7.58; p < 0.001). Sub‐group analysis of hospitalizations without any stroke risk factors also demonstrated a significant association of OCP use with the development of AIS (1.3% vs. 0.1%; aOR 14.84, 95% CI 13.16 to 16.72; p < 0.001) following adjustment for age and race/ethnicity. In negative control analysis, OCP use was not associated with admissions associated with head trauma (1.4% vs. 1.4%; OR 1.03, 95% CI 0.95 to 1.10; p = 0.485). Conclusion Retrospective observational data from the United States in recent years suggests an association between OCP use and AIS, independent of well‐established risk factors for stroke and despite widespread adoption of lower estrogen formulations.

Breast cancer risk factors based on reproductive and nonreproductive profiling of Pakistani women: A hospital based case control study.

Breast cancer (BC) is a global public health problem attributed to varying risk factors. The designing of a targeted screening program focused on at-risk women can be cost-effective in reducing its burden. A hospital based case control study was conducted on 138 cases of breast cancer and 169 healthy controls to investigate the reproductive and non-reproductive risk factors for breast cancer in Pakistani women. The odds ratios (ORs) and 95% confidence intervals (CIs) were computed with unconditional logistic regression. Almost all i.e. 97.83% of cases were married (OR=5.03),70.29% were illiterate (OR=1.88), 73.19% were aged >35 years (OR=0.632) and 81.16% belonged to the poor class(OR=1.81). Early age at menarche (OR, 2.55; 95% CI 1.50-4.31, P=0.0001), hormone replacement therapy (OR=2.057, 95% CI 1.283-3.295, P= 0.002) early pregnancy (OR,2.23, 95% CI 1.29-3.88, P=0.004), history of miscarriage (OR, 2.11, 95% CI 1.32-3.39,P=0.002) & oral contraceptive use (OR, 2.76, 95% CI 1.54-4.92, P= 0.006) were significantly associated with BC. The study highlights the dire need for effective public health programs for high-risk women to address this highly fatal disease.

Assessment of community pharmacists’ knowledge and counselling practices on oral contraceptives use

The consequences of unwanted pregnancy are a public health concern and the knowledge of pharmacists on contraceptives is important being the most accessed healthcare provider. The study assessed the knowledge of community pharmacists in Ibadan, Oyo State, Nigeria on oral contraceptives and counselling practices during dispensing of the same. 110 community pharmacists were assessed using self-administered questionnaires. Data collected include socio-demographics, knowledge, and current counselling practices of participants on contraceptives. Data was entered into IBM-SPSS version 23 and analyzed using descriptive and inferential statistics. Chi-square was used to determine the association between socio-demographic characteristics, knowledge and counselling practices of participants. 130 questionnaires were distributed and 110 were retrieved giving a response rate of 84.6%. There were more males (64, 58.2%) than females and the mean age of participants was 32.72±9.00 years. The majority (92, 83.6%) had only their first degree. Participants’ knowledge of oral contraceptives was found to be high with 80 (72.7%) having good knowledge while 27 (24.5%) had good counselling practices. There was no significant association between socio-demographics and knowledge of contraceptives. Higher educational qualification had no positive influence on their counselling practices with significant number of participants with Bachelor of Pharmacy qualifications having better counseling practices (p=0.03). The knowledge of participants on the use of oral contraceptives also significantly influenced their counselling practice (p=0.03). Community pharmacists need further training on how to counsel patients on use of oral contraceptives in other to reduce unplanned pregnancy, and consequently prevent uncontrolled population growth.

Thirty-day mortality rates among young adult stroke patients and their characteristics at Kiruddu and Mulago hospitals in Uganda: A prospective observational cohort study.

Stroke outcomes among young adults in Uganda are unclear. This study therefore determined the clinical characteristics and 30-day outcome among young adults with an acute stroke. In a prospective observational cohort study, 61 young adults with confirmed stroke were followed up for 30 days. Socio-demographic and clinical characteristics were collected using a study questionnaire. Kaplan-Meier curves, and modified Poisson regression were performed for factors associated with the 30-day mortality outcome. A third of the screened stroke survivors, (61/195) were young adults aged between 18 and 50 years. About two-thirds were male. More than half were diagnosed with ischaemic strokes while 42.6% had a haemorrhagic stroke. Nearly half (29/61) were known hypertensives, 43% (26/61) had a history of alcohol consumption with 95% classified as dependent on CAGE assessment. Ten percent had a prior smoking history while 29% of the female gender had a prior history of oral contraception use. Twenty-three percent (14/61) of the young stroke patients died within 30 days of stroke onset (95% CI: 0.01, 0. 901). A history of smoking (adjusted prevalence ratio: aPR;5. 094, 95% CI: 3.712, 6. 990) and stroke severity National Institutes of Health Stroke score (NIHSS) >16; Prevalence ratio (PR) -3. 301, 95%CI: 1. 395, 7. 808) and not drinking alcohol (aPR (adjusted prevalence ratio) -7. 247, 95% CI: 4. 491, 11.696) were associated with 30- day mortality. A third of all stroke survivors were young adults. About 23. 3% died within 30 days of stroke onset. Stroke severity and a history of smoking were associated with mortality. Identifying high risk patients and early outpatient follow up may help reduce the 30-day mortality in our settings.

Predictors of cervical tumour size for outpatients with cervical cancer at the University of Gondar referral hospital: a retrospective study design

BackgroundCervical cancer is one of the most serious threats to women's lives. Modelling the change in tumour size over time for outpatients with cervical cancer was the study's main goal.MethodsA hospital conducted a retrospective cohort study with outpatients who had cervical cancer. The information about the tumour size was taken from the patient's chart and all patient data records between May 20, 2017, and May 20, 2021. The data cover 322 cervical cancer outpatients' basic demographic and medical information. When analysing longitudinal data, the linear mixed effect model and the connection between tumour sizes in outpatients were taken into consideration. A linear mixed model, a random intercept model, and a slope model were used to fit the data.ResultA sample of 322 cervical cancer outpatients was examined, and 148 (or 46% of the outpatients) tested positive for HIV. The linear mixed model with a first-order autoregressive covariance structure revealed that a change in time of one month led to a 0.009 cm2 reduction in tumour size. For every kilogramme more in weight, the tumour size change in cervical cancer patients decreased considerably by 0.0098 cm2. The tumour size change in the cervical cancer patient who was HIV-positive was 0.4360 cm squared greater than that in the HIV-negative outpatients.ConclusionAs a consequence, there was a significant association between the longitudinal change in tumour size and the predictor variables visit time, therapy, patient weight, cancer stage, HIV, oral contraceptive use, history of abortion, and smoking status.

Venous thromboembolism among physically active young adult females

BackgroundYoung adult females are at risk of venous thromboembolism (VTE) due to various acquired and transient factors. In recent years, a growing number of females have engaged in strenuous physical activity, but its role as a risk factor for VTE is uncertain. ObjectivesTo determine the incidence of VTE in young adult females engaged in strenuous physical activity. MethodsA large national cohort of female individuals enlisted in the Israeli Defense Forces between 2012 and 2019 was analyzed. The study group consisted of participants undergoing strenuous physical training during their military service, while the control group maintained regular activity levels. We compared the incidence of VTE between the groups and adjusted for potential risk factors using a multivariate Cox analysis. ResultsThe cohort included 160,718 female individuals aged 18 to 21years, of whom 11,745 engaged in strenuous physical activity and 148,973 served as controls. During a mean follow-up of 1.7 years, VTE occurred in 5 individuals (0.04%) in the strenuous activity group and 47 individuals (0.03%) in the control group. The incidence per 10,000 person-years was 2.41 (95% CI, 0.78-5.62) for the strenuous activity group and 1.82 (95% CI, 1.34-2.42) for the controls. Strenuous activity did not increase the risk for VTE in univariate or multivariate regression, with a hazard ratio (HR) of 1.27 (95% CI, 0.49-4.22). Use of oral contraceptives was the only significant risk factor, demonstrating dose effect; HR 1.95 (95% CI, 1.06-3.57) for low dose and HR 3.62 (95% CI, 1.40-9.37) for medium estrogen dose contraceptives. ConclusionStrenuous physical activity did not increase the risk for VTE among a large cohort of young adult female individuals.

Influence of Surgical Technique on Post-Operative Complications in the Extraction of the Lower Third Molar: A Retrospective Study.

The surgical extraction of the impacted third molar is frequently associated with several complications. The purpose of this study is to assess how two different surgical protocols affect post-operative complications during the extraction of the lower impacted third molars. In order to compare and evaluate two different techniques (triangular flap vs. envelope flap), and the relative post-extraction complications, two groups of 150 patients each underwent to surgical impacted third molar extraction and 60 days of follow-up. The complication rate in the two groups was 14.00% in group A and 17.33% in group B. There was a strong association between smoking (OR: 2.8) and the use of oral contraceptives (OR: 1.75) with complications. The age- and sex-related incidence of complications in hard tissue healing has great variability in the literature; the analysis performed on our data did not show a statistically significant association between them. Even though related to a higher incidence of transient changes in sensitivity, it was found that the envelope flap saw a lower percentage of complications. There is still no clarity on which is the best protocol for the extraction of the lower impacted third molar, and the choice often depends on the surgeon's experience.

Menstrual cycle hormones and oral contraceptives: a multimethod systems physiology-based review of their impact on key aspects of female physiology.

Hormonal changes around ovulation divide the menstrual cycle (MC) into the follicular and luteal phases. In addition, oral contraceptives (OCs) have active (higher hormone) and placebo phases. Although there are some MC-based effects on various physiological outcomes, we found these differences relatively subtle and difficult to attribute to specific hormones, as estrogen and progesterone fluctuate rather than operating in a complete on/off pattern as observed in cellular or preclinical models often used to substantiate human data. A broad review reveals that the differences between the follicular and luteal phases and between OC active and placebo phases are not associated with marked differences in exercise performance and appear unlikely to influence muscular hypertrophy in response to resistance exercise training. A systematic review and meta-analysis of substrate oxidation between MC phases revealed no difference between phases in the relative carbohydrate and fat oxidation at rest and during acute aerobic exercise. Vascular differences between MC phases are also relatively small or nonexistent. Although OCs can vary in composition and androgenicity, we acknowledge that much more work remains to be done in this area; however, based on what little evidence is currently available, we do not find compelling support for the notion that OC use significantly influences exercise performance, substrate oxidation, or hypertrophy. It is important to note that the study of females requires better methodological control in many areas. Previous studies lacking such rigor have contributed to premature or incorrect conclusions regarding the effects of the MC and systemic hormones on outcomes. While we acknowledge that the evidence in certain research areas is limited, the consensus view is that the impact of the MC and OC use on various aspects of physiology is small or nonexistent.

Association of oral contraceptive pill use and depression among US women

BackgroundThe link between oral contraceptive pill (OCP) and depression is still unclear. This work analyses the prevalence and correlates of major depression in US women using OCP. MethodsThis study used the National Health and Nutrition Examination Survey (NHANES) 2005–2012 data to provide the prevalence and correlates of major depression in women using OCP. Major depression was defined as a score of ≥10 using the Patient Health Questionnaire-9 (PHQ-9). ResultsA total of 6239 women aged 18–55 years were included in the present analysis. Current OCP users had a lower prevalence of major depression (4.6 %; 95 % CI, 3.2 to 6.6) compared to former users of OCP (11.4 %; 95 % CI, 10.1 to 12.9) and never users of OCP (10 %; 95 % CI, 8.3 to 12.1). Current users of OCP were significantly less likely to report major depression compared to former users of OCP (OR 0.59; 95CI%, 0.39 to 0.90) after adjusting for potential confounders. The prevalence of major depression was higher in women who were: black or Hispanic, widowed/divorced/separated, those with a low and middle income, current smokers, current users of antidepressants, and with history of cancer and thyroid problems. LimitationsThis is a cross-sectional study. ConclusionThe prevalence of major depression among women using OCP may be lower than in former users of OCP, however, the burden of depression remains high. Further research with longitudinal follow-up for depression in women using OCP is needed to understand real world effect of the OCP on depression.

Exogenous hormone therapy and non-melanoma skin cancer (keratinocyte carcinoma) risk in women: a systematic review and meta-analysis

Previous studies reported inconsistent results regarding the association between keratinocyte carcinoma (KC) and exogenous hormone therapy. This study aimed to investigate the association between the use of exogenous sex hormones and the risk of KC among women. The databases of PubMed, Ovid Medline, Cochrane, and Web of Science were searched until May 2023. A total of 5293 patients with KC and 106,424 controls were included for analysis. The meta-analysis indicated that oral contraceptives (OC) and hormonal replacement therapy (HRT) use were associated with an increased risk of squamous cell carcinoma (SCC) (OR/RR = 1.25, 95% CI 1.10 to 1.43, I2 = 41.6%, p = 0.080). Subgroup analysis showed that OC use increased the risk of SCC (OR/RR = 1.37, 95% CI 1.15 to 1.63), whereas no significant association was shown between HRT use and risk of SCC (OR/RR = 1.13, 95% CI 0.93 to 1.37). Additionally, OC and HRT use were linked to an increased risk of basal cell carcinoma (BCC) (OR/RR = 1.16, 95% CI 1.09 to 1.25, I2 = 30.1%, p = 0.188). Further subgroup analysis suggested both OC and HRT use were associated with an increased risk of BCC (OC: OR/RR = 1.13, 95% CI 1.01 to 1.25; HRT: OR/RR = 1.19, 95% CI 1.09 to 1.30). In conclusion, our findings support the hypothesis that the risk of KC among women may be affected by the use of exogenous hormones.

Incessant ovulation: a review of its importance in predicting cancer risk.

Estrous cycles are recurring changes in therian mammals induced by estrogen, progesterone, and other hormones culminating in endometrial proliferation, ovulation, and implantation if fertilization occurred. In women, the estrous cycle is the menstrual cycle; but, unlike most mammals, the end of an infertile cycle is marked by endometrial sloughing and the start of another without an anestrous phase. Women stop cycling at menopause, while in most mammals, cycles continue until death. Epidemiologic studies identified menarche, menopause, births, lactation, and oral contraceptive (OC) use as key risk factors for ovarian, breast, and endometrial cancers. A composite variable was created to estimate the number of cycles not interrupted by events that stop ovulation. Captured by the phrase "incessant ovulation", repetitive cycles were first postulated to affect ovarian cancer risk and later extended to breast and endometrial cancers. These associations could be explained by cumulative effects of repetitive tissue changes within reproductive organs, immune consequences of repetitive ovulation through the glycoprotein mucin 1, and residual effects of past ovulations that enhance ovarian production of testosterone. The latter two pathways could affect the risk for cancers in other organs not considered "reproductive".

SAT299 Comparison Of Plasma Cortisol-, Salivary Cortisol- And Salivary Cortisone-response To The Short Synacthen Test In Women Using Oral Contraceptives

Abstract Disclosure: N. Bäcklund: None. S. Lundstedt: None. T. Olsson: None. P.M. Dahlqvist: None. G. Brattsand: None. Introduction: The short Synacthen test (SST) is a cornerstone in the diagnosis of adrenal insufficiency (AI). However, cortisol levels in serum or plasma may be misleadingly elevated by estrogen containing oral contraceptives (OCs), due to increased levels of cortisol binding protein (CBG). This may falsely declare a woman with AI to be cortisol sufficient. Salivary cortisol and cortisone closely correlate with the unbound fraction of plasma cortisol and is thus less likely to be influenced by variations in CBG levels. Our hypothesis was that the salivary cortisol and cortisone response to SST would be similar in women with and without OC use. Materials and methods: A standard intravenous 250 µg SST was performed in 87 women without known diseases or medications affecting the cortisol axis, 41 using OCs containing ethinylestradiol and 46 controls. Plasma cortisol was analyzed by Roche Elecsys Cortisol II assay and salivary cortisol and cortisone by LC-MS/MS in samples collected at baseline (time 0), and 30 and 60 minutes after Synacthen injection. The effect of OCs upon plasma cortisol, salivary cortisol and salivary cortisone was assessed by a two-way ANOVA with sampling time after SST as repeated measure. Results: There was an overall effect of OCs on plasma cortisol, but not on salivary cortisol or cortisone. Plasma cortisol levels were considerably higher in the OC group vs. controls at all time points; +150% at 0 minutes; +90% at 30 minutes; and +86% at 60 minutes. There was a significant interaction between OC use and sample time point for both salivary cortisol and cortisone. Mean salivary cortisol in women using OCs was 37% higher vs. controls at 0 minutes but was instead lower in the OCs group at 30 and 60 minutes after SST (-13% and -11%, respectively). Similarly, mean salivary cortisone was also slightly higher in the OC group than controls at baseline (+13%) and somewhat lower at 30 and 60 minutes (-6% and -7%). Conclusion: Plasma cortisol levels during an SST were significantly elevated in women using OCs containing estrogen whereas OC effects upon salivary cortisol and cortisone levels were modest, especially for salivary cortisone. Analysis of salivary cortisone is a promising alternative to plasma cortisol for diagnosis of AI in women using OCs. Presentation: Saturday, June 17, 2023

SAT383 Case Study: Impact of Weight Reduction and Oral Contraceptive Pills on Hyperandrogenism

Abstract Disclosure: A. Syeda: None. T.L. Anderson: None. D. Millar: None. P. Madhavan: None. Introduction: Polycystic ovarian syndrome (PCOS) is a commonly encountered cause of hyperandrogenism which could interfere with fertility. Typical therapeutic options for hyperandrogenism including hormonal contraceptives and anti-androgen medication are contraindicated when planning pregnancy. This case highlights the profound impact of weightloss and oral contraception use to treat severe hyperandrogenism in select cases. Case: A 31-year-old female presented for initial evaluation of hyperandrogenism noted during evaluation for infertility. Laboratory investigations revealed a free testosterone level of 172 ng/dL (n:9-55 ng/dl), SHBG of 17 nmol/L (25-122 nmol/L), DHEAS of 306 ug/dL (n:99-340 ug/dL), TSH of 1.79 uIU/mL (n:0.35-4.96 uIU/mL), ACTH of 12.1 (n:7.2-63.3 pg/mL), cortisol of 9.6 ug/dL (7-23 ug/dL), prolactin of 7.85 ng/mL (3.34-26.72 ng/mL). The patient reported hirsutism, increasing body hair, darkening of skin and significant weight gain over the past 4 years. Menstrual cycles have been reported as being irregular since menarche. Vital signs were stable with a blood pressure of 112/84 mm Hg. Physical examination was remarkable for generalized obesity, hirsutism, and acanthosis nigricans, no abnormal abdominal striae were appreciated. Considering significant elevation in testosterone levels despite low SHBG, an MRI of abdomen and pelvis was obtained which demonstrated ovarian cysts with no concern for ovarian malignancy. CT of the abdomen without contrast was negative for adrenal mass. The overall clinical picture was suggestive of a diagnosis of PCOS. As the patient was planning pregnancy, oral contraceptive agents and spironolactone were deferred initially. The patient was encouraged to lose weight with lifestyle modifications and was started on up titrating dose of Metformin as tolerated. The patient complied with the recommendations and over the course of two years her weight decreased from 171 lbs. to 158 lbs. In the interim, she was placed on oral contraceptive pills for 2 months to undergo hysteroscopy. Subsequently, the testosterone levels normalized to 17 ng/dL. Conclusion: Although previous research has demonstrated the significance of weight loss, for reducing symptoms in patients with PCOS, this role has not been well elucidated in cases of severe hyperandrogenism without a neoplastic cause. The mechanism of interaction between weight loss, oral contraceptive pills and decreased androgens is based on the reduction in insulin resistance which causes a decrease in theca cell androgen synthesis and an increased SHBG. Additionally, a decrease in adiposity reduces the conversion of Δ4-androstenedione to testosterone. Notably, in this case there is potentially a causal relationship between the patient's weight loss of 13 pounds (7.6% of her body weight), OCP use and her return to normal testosterone levels. Presentation Date: Saturday, June 17, 2023

Cardiovascular responses to combined mechanoreflex and metaboreflex activation in healthy adults: effects of sex and low- versus high-hormone phases in females.

Females generally have smaller blood pressure (BP) responses to isolated muscle mechanoreflex and metaboreflex activation compared with males, which may explain sex differences in BP responses to voluntary exercise. The mechanoreflex may be sensitized during exercise, but whether mechanoreflex-metaboreflex interactions differ by sex or variations in sex hormones remains unknown. Thirty-one young healthy subjects (females, n = 16) performed unilateral passive cycling (mechanoreflex), active cycling (40% peak Watts), postexercise circulatory occlusion (PECO; metaboreflex), and passive cycling combined with PECO (combined mechanoreflex and metaboreflex activation). Beat-to-beat BP, heart rate, inactive leg vascular conductance, and active leg muscle oxygenation were measured. Ten females underwent exploratory testing during low- and high-hormone phases of their self-reported menstrual cycle or oral contraceptive use. Systolic BP and heart rate responses did not differ between sexes during active cycling [Δ30 ± 9 vs. 29 ± 11 mmHg (males vs. females), P = 0.9; Δ33 ± 8 vs. 35 ± 6 beats/min, P = 0.4] or passive cycling with PECO (Δ26 ± 11 vs. 21 ± 10 mmHg, P = 0.3; Δ14 ± 7 vs. 18 ± 15 beats/min, P = 0.3). Passive cycling with PECO revealed additive, not synergistic, effects for systolic BP [males: Δ23 ± 14 vs. 26 ± 11 mmHg (sum of isolated passive cycling and PECO vs. combined activation); females: Δ26 ± 11 vs. 21 ± 12 mmHg, interaction P = 0.05]. Results were consistent in subset analyses with sex differences in active cycling BP (P > 0.1) and exploratory analyses of hormone phase (P > 0.4). Despite a lack of statistical equivalence, no differences in cardiovascular responses were found during combined mechanoreflex-metaboreflex activation between sexes or hormone levels. These results provide preliminary data regarding the involvement of muscle mechanoreflex-metaboreflex interactions in mediating sex differences in voluntary exercise BP responses.NEW & NOTEWORTHY The muscle mechanoreflex may be sensitized by metabolites during exercise. We show that cardiovascular responses to combined mechanoreflex (passive cycling) and metaboreflex (postexercise circulatory occlusion) activation are primarily additive and do not differ between males and females, or across variations in sex hormones in females. Our findings provide new insight into the contributions of muscle mechanoreflex-metaboreflex interactions as a cause for prior reports that females have smaller blood pressure responses to voluntary exercise.

Dietary advanced glycation end products are associated with an increased risk of breast cancer in Iranian adults

BackgroundDietary advanced glycation end products (AGEs) can play an important role in increasing inflammatory factors and oxidative stress as risk factors for cancers. In the present study, we aimed to assess the relationship between dietary AGEs and the risk of breast cancer (BC) in Iranian adult women.MethodsThis hospital-based case-control study includes 401 participants aged ≥ 30 years old. The cases group consisted of 134 women diagnosed with histologically confirmed BC. The control group included 267 women enrolled randomly from patients admitted to the same hospitals. Dietary intake information was determined using a validated food frequency questionnaire, and dietary AGEs intake was computed for all participants. Logistic regression models, adjusted for potential confounders, were used to determine the odds ratios (OR) and 95% confidence interval (CI) of BC across tertiles of dietary AGEs.ResultsThe mean ± SD age and body mass index of the study population were 47.92 ± 10.33 years and 29.43 ± 5.51 kg/m2, respectively. The median (interquartile) of dietary AGEs in all individuals was 9251(7450, 11,818) kU/day. After adjusting for age, first pregnancy age, and energy intake, participants in the highest tertile of dietary AGEs intakes had higher odds of BC compared to those in the lowest tertile of dietary AGEs (OR:2.29;95%CI:1.19–4.39, Ptrend:0.012). Additionally, in the multivariable model, after adjusting for age, age at first pregnancy, energy, menopausal status, family history of cancer, anti-inflammatory drug use, Vitamin D supplementation, physical activity, body mass index, number of childbirths, and history of abortion, breastfeeding, and oral contraceptive pills use, the odds of BC were increased across tertiles of dietary AGEs intake (OR: 2.33; 95%CI: 1.18–4.60, Ptrend: 0.017).ConclusionThe present findings suggest that a diet with high AGEs is associated with a higher likelihood of BC in adult women.

An Endocrine Perspective on Lynch Syndrome

"Background: A germline mutation of the MisMatch Repairgene that causes a malfunctioning DNA system is the defining feature of the hereditary illness known as Lynch syndrome. This review will discuss the endocrine aspects of LS and highlight current advancements in the area. Methods: We searched the available literature of the last 10 years for terms such as endocrine tumors and LS. Our goal is to provide a summary of the most recent information available on the endocrine perspective in Lynch syndrome. Results: The hormonal chemoprevention methods cited are the use of combined oral contraceptives, the use of progestogen-releasing intrauterine devices, and the use of progesterone-only drugs. In addition, after surgical exclusion of the uterus and ovaries, a method frequently adopted for LS patients, it is necessary to start hormonal menopausal therapy, taking into account certain age-specific features. In addition, numerous LS-associated endocrine tumor types have been described. Conclusions: Many hormonal variants are available that are useful in the chemoprevention involved in the treatment of LS. Menopausal hormone therapy is imperative for LS patients who need it. Clinicians need to be aware of the possible association of certain types of aggressive endocrine cancers associated with LS."

Effects of oral contraceptives and menopausal hormone therapy on the risk of rheumatoid arthritis: a prospective cohort study.

Oral contraceptives (OC) and menopausal hormone therapy (MHT) contain exogenous sex hormones and are used by millions of women around the world. However, their effect on the development of rheumatoid arthritis (RA) is still debated and the current literature suggests that they may exert opposite effects on the risk of RA. The present study aimed to estimate the effects of exogenous hormones on the development of RA, both during the reproductive lifespan and later in life. The association between OC and RA, as well as between MHT and late-onset RA (LORA), was investigated using time-dependent Cox regression modelling in white British women from the UK Biobank (n = 236 602 and n = 102 466, respectively) and replicated in women from all ethnic groups. OC use was associated with a decreased risk of RA in ever-users [hazard ratio (HR) = 0.89; 95% CI = 0.82-0.96], as well as in current (HR = 0.81; 0.73-0.91) and former users (HR = 0.92; 0.84 -1.00), compared with never-users. In contrast, MHT use was associated with an increased risk of LORA in ever-users (HR = 1.16; 1.06-1.26) as well as in former users (HR = 1.13; 1.03-1.24) compared with never-users. OC use appears to protect against RA, while MHT may increase the risk of LORA. This study provides new insights into the possible inverse effect of exposure to different exogenous sex hormones on the risk of RA.