Oral Contraceptive Users Research Articles

Abstract P620: Non-O Blood Group and Risk of Early-Onset Ischemic Stroke in Oral Contraceptive Users

Introduction: While oral contraceptive (OC) use is generally safe, women at higher risk for vascular disease are advised to use alternative forms of contraception. Smoking, a prothrombotic factor, is a contraindication for OC use in women over age 35. ABO blood group, specifically the non-O blood types, has also been associated with thrombosis risk. We therefore hypothesized that the effects of smoking and OC use on stroke risk would be accentuated in women with non-O blood groups. Methods: Using data from the Genetics of Early Onset Stroke Study, we used 3 polymorphisms within the ABO locus to classify blood group type in women under age 50, including 347 cases and 383 controls. Logistic regression was used to assess the stroke risk of current OC use, defined as use within 30 days, adjusted for other risk factors, and stratified by O and non-O blood group type. Results: Of the 347 women with early-onset stroke, 45% had African ancestry, 51% had European ancestry, and 4% had other ancestry. The median age was 42 years. After adjusting for race, age, hypertension, diabetes, migraines and aura, and smoking status, the odds ratio (OR) for stroke for smoking alone and OC use alone were 3.0 (95% CI 2.1-4.2) and 3.7 (95% CI 1.7-8.4), respectively in this population. Blood group (O vs non-O) did not appreciably alter the magnitude of these associations. However, the joint risk of smoking and OC use was substantially higher in women with blood group non-O (OR = 9.5, 95% CI 3.2-34.9) vs in women with blood group O (OR=4.9, 95% CI 0.4-110.2). Conclusions: Our findings are consistent with the possibility that non-O type blood group confers an increased risk of early onset stroke among OC users who smoke. Further studies are needed to confirm or refute this possibility and to determine whether non-O blood type should be considered in assessing the risk of OC use.

Androgenic morality? Associations of sex, oral contraceptive use and basal testosterone levels with moral decision making

Aside from cultural, psychological, or situational factors, differences in moral judgements might also be influenced by biological variables. Since previous studies have reported stronger utilitarian tendencies in men, the relationship between testosterone and moral judgments has gained interest. Utilitarian judgements focus on the consequences of an action in terms of a cost-benefit analysis while deontological judgements are based on rules that are independent of an action’s outcome or of situational features. We investigated decisions in moral dilemma situations in N = 157 young adults using a process dissociation approach to allow an independent estimate of underlying utilitarianism and deontology. Significant effects of sex (p = .009) and endocrine status (p = .011) on utilitarianism were found with the highest levels in men and the lowest in free cycling women while oral contraceptive users fell in between. Furthermore, there were correlations of salivary testosterone with utilitarianism in free cycling women (r = .303) and with deontology in men (r = -0.263) while no significant associations between testosterone and moral choices were found in oral contraceptive users. However, the duration of contraceptive use correlated negatively with deontology (r = -.316). The findings underscore the role of sex, endocrine status as well as testosterone in moral judgements but also point to specific associations depending on sex and oral contraceptive use.

Oxidative Stress Is Increased in Combined Oral Contraceptives Users and Is Positively Associated with High-Sensitivity C-Reactive Protein.

Information concerning the mechanisms underlying oxidative stress and low-grade inflammation in young healthy women predisposing eventually to future diseases is scarce. We investigated the relationship of oxidative stress and high-sensitivity C-reactive protein (hsCRP) in fertile-age women by oral combined contraceptive (OC) use. Caucasian Italian healthy non-obese women (n = 290; 100 OC-users; 190 non-OC-users; mean age 23.2 ± 4.7 years) were analyzed. Blood hydroperoxides, as oxidative stress biomarkers, were assessed by Free Oxygen Radical Test (FORT). Serum hsCRP was determined by an ultra-sensitive method (hsCRP). Markedly elevated oxidative stress (≥400 FORT Units) was found in 77.0% of OC-users and 1.6% of non-OC-users, odds ratio (OR) = 209, 95% CI = 60.9–715.4, p < 0.001. Elevated hsCRP levels ≥ 2.0 mg/L, considered risky for cardiovascular diseases (CVDs), were found in 41.0% of OC-users and 9.5% of non-OC-users, OR = 6.6, 95%CI 3.5–12.4, p < 0.001. Hydroperoxides were strongly positively correlated to hsCRP in all women (rs = 0.622, p < 0.001), in OC-users (rs = 0.442, p < 0.001), and in non-OC-users (rs = 0.426, p < 0.001). Women with hydroperoxides ≥ 400 FORT Units were eight times as likely to have hsCRP ≥ 2 mg/L. In non-OC-users only, hydroperoxides values were positively correlated with weight and body mass index, but negatively correlated with red meat, fish and chocolate consumption. Our research is the first finding a strong positive correlation of serum hydroperoxides with hsCRP, a marker of low-grade chronic inflammation, in young healthy women. Further research is needed to elucidate the potential role of these two biomarkers in OC-use associated side-effects, like thromboembolism and other CVDs.

Oral Contraceptives Do Not Affect Physiological Responses to Strength Exercise.

Umlauff, L, Weil, P, Zimmer, P, Hackney, AC, Bloch, W, and Schumann, M. Oral contraceptives do not affect physiological responses to strength exercise. J Strength Cond Res 35(4): 894-901, 2021-This study investigated the effect of oral contraceptive (OC) use on acute changes in steroid hormone concentrations and tryptophan (TRP) metabolites in response to strength exercise. Twenty-one women (age: 23 ± 3 years), 8 combined OC users (OC group) and 13 naturally cycling women (menstrual cycle [MC] group), participated. Testing was performed during the pill-free interval for the OC group and the follicular phase for the MC group. Subjects completed an intense strength exercise protocol (4 × 10 repetitions back squat). Blood samples were taken at baseline (T0), post-exercise (T1), and after 24 hours (T2) to determine serum concentrations of cortisol, estradiol, testosterone, TRP, and kynurenine (KYN). Statistical significance was defined as p ≤ 0.05. At T0, the OC group showed higher cortisol (OC: 493.7 ± 47.1 ng·mL-1, MC: 299.1 ± 62.7 ng·mL-1, p < 0.001) and blood lactate (OC: 1.81 ± 0.61 mmol·L-1, MC: 1.06 ± 0.30 mmol·L-1, p = 0.001) and lower estradiol (OC: 31.12 ± 4.24 pg·mL-1, MC: 38.34 ± 7.50 pg·mL-1, p = 0.023) and KYN (OC: 1.15 ± 0.23 µmol·L-1, MC: 1.75 ± 0.50 µmol·L-1, p = 0.005). No significant interactions (group × time, p > 0.05) were found for the hormones and TRP metabolites assessed. Oral contraceptive use did not affect the physiological response of steroid hormones and TRP metabolites to acute strength exercise during the low hormone phase of the contraceptive or MC in healthy young women, even when some baseline concentrations differed between groups. Consequently, these findings provide important implications for practitioners testing heterogeneous groups of female athletes.

Genetically Predicted C-Reactive Protein Associated With Postmenopausal Breast Cancer Risk: Interrelation With Estrogen and Cancer Molecular Subtypes Using Mendelian Randomization

BackgroundImmune-related etiologic pathways that influence breast cancer risk are incompletely understood and may be confounded by lifestyles or reverse causality. Using a Mendelian randomization (MR) approach, we investigated the potential causal relationship between genetically elevated C-reactive protein (CRP) concentrations and primary invasive breast cancer risk in postmenopausal women.MethodsWe used individual-level data obtained from 10,179 women, including 537 who developed breast cancer, from the Women’s Health Initiative Database for Genotypes and Phenotypes Study, which consists of five genome-wide association (GWA) studies. We examined 61 GWA single-nucleotide polymorphisms (SNPs) previously associated with CRP. We employed weighted/penalized weighted–medians and MR gene–environment interactions that allow instruments’ invalidity to some extent and attenuate the heterogeneous estimates of outlying SNPs.ResultsIn lifestyle-stratification analyses, genetically elevated CRP decreased risk for breast cancer in exogenous estrogen-only, estrogen + progestin, and past oral contraceptive (OC) users, but only among relatively short-term users (<5 years). Estrogen-only users for ≥5 years had more profound CRP-decreased breast cancer risk in dose–response fashion, whereas past OC users for ≥5 years had CRP-increased cancer risk. Also, genetically predicted CRP was strongly associated with increased risk for hormone-receptor positive or human epidermal growth factor receptor-2 negative breast cancer.ConclusionsOur findings may provide novel evidence on the immune-related molecular pathways linking to breast cancer risk and suggest potential clinical use of CRP to predict the specific cancer subtypes. Our findings suggest potential interventions targeting CRP–inflammatory markers to reduce breast cancer risk.

Abstract PO029: Oral contraceptive use and postmenopausal sex steroid hormone metabolism

Abstract OBJECTIVE: Oral contraceptive (OC) use is common in the United States and high-profile articles have renewed research interest in OC use and cancer risk. Several mechanisms have been proposed to explain how OC use influences postmenopausal cancer risk; one of the leading hypotheses is that OC use fundamentally alters feedback in the hypothalamic-pituitary-gonad axis, leading to long term changes in sex steroid hormone metabolism. However, women who use OCs are also unique with respect to factors that may affect both hormone metabolism and cancer risk. No studies have comprehensively commented on hormone levels in postmenopausal women who did and did not use OCs. DESIGN: We examined differences in circulating markers of sex steroid hormone metabolism associated with prior use of OCs among a subcohort of postmenopausal women from the Women’s Health Initiative Observational Study (983 women with at least one intact ovary and not currently using menopausal hormone therapy). MATERIALS AND METHODS: Using highly sensitive liquid chromatography–tandem mass spectrometry assays, we measured over 30 markers of estrogen and androgen metabolism in study serum samples. We used linear regression (adjusted and weighted) to estimate geometric mean hormone levels, which were then converted into relative percent differences. We controlled for potential confounders and stratified by: lifetime ovulatory cycles, body mass index, and parity (the focus of this abstract). RESULTS: Women with a history of OC use (n=346) had lower levels of estrogen metabolites than women who never used OCs (n=637), particularly when limiting this comparison among parous women (n=158 nulliparous women, n=825 parous women). In parous women, OC use was associated with reductions in total estrone (-18.5%, 95% confidence interval [CI] -31.1, -3.7%) and in estrogen metabolism overall: 2-hydroxylation metabolites were reduced by -18.5% (CI -28.2, -7.7%), 4-hydroxylation metabolites by -19.9% (CI -29.4, -9.1%), and 16-alpha-hydroxylation metabolites by -24.0% (CI -34.2, -12.2%). Hormone differences associated with OC use among nulliparous women were imprecise. When we made comparisons to nulliparous women who did not use OCs, women who both used OCs and were parous had lower testosterone (-21.2%, CI -33.1, -7.2%) and higher dihydrotestosterone relative to testosterone (its metabolic precursor; 16.5%, CI% -0.6, 36.6). However, aside from lower total estrone (-25.5%, CI -44.6, 0.2%), estrogen metabolism was not different between these groups. CONCLUSIONS: We saw evidence suggesting estrogen metabolism, as reflected in circulating markers, may be lower in postmenopausal women who previously used OCs. These effects were strongest among parous women, likely due to sufficient sample size, rather than any synergistic effect attributable to both using OCs and giving birth. These results support the idea that OC users have lower estrogen levels, but this should be evaluated in other age groups, as differences in hormone metabolism early in the lifecourse may lead women to use OCs. Citation Format: Kara A. Michels, Sally B. Coburn, Garnet Anderson, Louise A. Brinton, Chu Chen, Roni T. Falk, Margery L. Gass, Ashley M. Geczik, JoAnn E. Manson, Ruth M. Pfeiffer, Kerryn Reding, Gloria E. Sarto, Nicolas Wentzensen, Robert A. Wild, Xia Xu, Britton Trabert. Oral contraceptive use and postmenopausal sex steroid hormone metabolism [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr PO029.

Prior Oral Contraceptive Use and Longer Term Mortality Outcomes in Women with Suspected Ischemic Heart Disease.

Background: Previous Women's Ischemia Syndrome Evaluation (WISE) work demonstrated prior oral contraceptive (OC) use was associated with lower coronary artery disease (CAD) in women with suspected ischemia. The association of prior OC use with longer term all-cause and cardiovascular disease (CVD) mortality is unclear. Materials and Methods: WISE women undergoing coronary angiography for suspected ischemia (enrolled 1996-2001) with prior OC use history and 10-year follow-up data were analyzed. A blinded core laboratory assessed atherosclerotic CAD severity. Kaplan-Meier analyses evaluated prior OC use relative to all-cause and CVD mortality. Cox regression analyses adjusted for baseline differences. Mediation, interaction, and multicollinearity were analyzed. Results: Our 686 women had a mean age 62.5 ± 9.6 years, multiple cardiac risk factors, and 39% previously used OC. Prior OC users were younger, with less lipid-lowering medication use and lower atherosclerotic CAD severity scores (all p < 0.05). Prior OC use was associated with lower 10-year all-cause (p = 0.007) and CVD mortality (p = 0.019). After adjustment, this was no longer significant (p = 0.77 and p = 0.90, respectively). Atherosclerotic CAD severity score mediated one-third of the observed association. Prior OC use was associated with increased CVD mortality among women with very elevated menopausal systolic blood pressure (SBP). Conclusions: Unadjusted prior OC use was associated with lower longer-term all-cause and CVD mortality. One-third of this observed effect appears mediated by the atherosclerotic CAD severity score. Prior OC was adversely associated with CVD mortality in women with very elevated menopausal SBP. Additional investigation is needed to understand the potential benefits and harms of prior OC use. Clinical Trial Number: NCT00000554, or https://www.clinicaltrials.gov/ct2/show/NCT00000554.

Over-the-counter oral contraceptive use among women in Mexico: results from a national survey

AimIn Mexico, many pharmacies sell oral contraceptives (OCs) over the counter (OTC); however, little is known about the background characteristics of OTC pill users. The primary objective of this study...

The effects of short-term low energy availability, achieved through diet or exercise, on cognitive function in oral contraceptive users and eumenorrheic women

To date, no research has explored the effects of low energy availability (EA) on cognitive performance using dietary and exercise regimens relevant to athletes. Twenty female participants (10 eumenorrheic, 10 oral contraceptive [OC] users) completed three, 3-day conditions: 1) controlled-balanced EA without exercise (BAL; 45 kcal·kg·LBM-1·day-1), 2) diet-induced low EA without exercise (DIET; 15 kcal·kg·LBM-1·day-1) and 3) exercise-induced low EA (EX; 15 kcal·kg·LBM-1·day-1, including 30 kcal·kg·LBM-1·day-1 treadmill running at 70% V̇O2max). A cognitive test battery was completed before and after each 3-day condition. Mental rotation test accuracy improved in the BAL condition, but there was a decline in accuracy in the EX condition (BAL, +2.5%; EX, -1.4%; P = 0.042, d = 0.85). DIET (+1.3%) was not different to BAL or EX (P > 0.05). All other measures of cognitive performance were not affected by condition (P > 0.05) and OC use did not affect cognitive responses (P > 0.05). Accuracy in the mental rotation test was impaired when low EA was induced through increased exercise energy expenditure. All other aspects of cognition were unaffected by three days of low EA through diet or exercise. OC use did not mediate the effect of low EA on cognition. Novelty bullets • Cognitive function was not affected by 3 days diet-induced low energy availability (EA). • Only spatial awareness was impaired during 3 days exercise-induced low EA. • Reproductive hormones affected spatial awareness independent of EA.

Cardiorespiratory response to exercise in endurance-trained premenopausal and postmenopausal females.

To assess the influence of different hormonal profiles on the cardiorespiratory response to exercise in endurance-trained females. Forty-seven eumenorrheic females, 38 low-dose monophasic oral contraceptive (OC) users and 13 postmenopausal women, all of them endurance-trained, participated in this study. A DXA scan, blood sample tests and a maximal aerobic test were performed under similar low-sex hormone levels: early follicular phase for the eumenorrheic females; withdrawal phase for the OC group and at any time for postmenopausal women. Cardiorespiratory variables were measured at resting and throughout the maximal aerobic test (ventilatory threshold 1, 2 and peak values). Heart rate (HR) was continuously monitored with a 12-lead ECG. Blood pressure (BP) was measured with an auscultatory method and a calibrated mercury sphygmomanometer. Expired gases were measured breath-by-breath with the gas analyser Jaeger Oxycon Pro. One-way ANCOVA reported a lower peak HR in postmenopausal women (172.4 ± 11.7bpm) than in eumenorrheic females (180.9 ± 10.6bpm) (p = 0.024). In addition, postmenopausal women exhibited lower VO2 (39.1 ± 4.9ml/kg/min) compared to eumenorrheic females (45.1 ± 4.4ml/kg/min) in ventilatory threshold 2 (p = 0.009). Nonetheless, respiratory variables did not show differences between groups at peak values. Finally, no differences between OC users and eumenorrheic females' cardiorespiratory response were observed in endurance-trained females. Cardiorespiratory system is impaired in postmenopausal women due to physiological changes caused by age and sex hormones' decrement. Although these alterations appear not to be fully compensated by exercise, endurance training could effectively mitigate them. In addition, monophasic OC pills appear not to impact cardiorespiratory response to an incremental running test in endurance-trained females.

Methodological Approach of the Iron and Muscular Damage: Female Metabolism and Menstrual Cycle during Exercise Project (IronFEMME Study).

Background: The increase in exercise levels in the last few years among professional and recreational female athletes has led to an increased scientific interest about sports health and performance in the female athlete population. The purpose of the IronFEMME Study described in this protocol article is to determine the influence of different hormonal profiles on iron metabolism in response to endurance exercise, and the main markers of muscle damage in response to resistance exercise; both in eumenorrheic, oral contraceptive (OC) users and postmenopausal well-trained women. Methods: This project is an observational controlled randomized counterbalanced study. One hundered and four (104) active and healthy women were selected to participate in the IronFEMME Study, 57 of which were eumenorrheic, 31 OC users and 16 postmenopausal. The project consisted of two sections carried out at the same time: iron metabolism (study I) and muscle damage (study II). For the study I, the exercise protocol consisted of an interval running test (eight bouts of 3 min at 85% of the maximal aerobic speed), whereas the study II protocol was an eccentric-based resistance exercise protocol (10 sets of 10 repetitions of plate-loaded barbell parallel back squats at 60% of their one repetition maximum (1RM) with 2 min of recovery between sets). In both studies, eumenorrheic participants were evaluated at three specific moments of the menstrual cycle: early-follicular phase, late-follicular phase and mid-luteal phase; OC users performed the trial at two moments: withdrawal phase and active pill phase. Lastly, postmenopausal women were only tested once, since their hormonal status does not fluctuate. The three-step method was used to verify the menstrual cycle phase: calendar counting, blood test confirmation, and urine-based ovulation kits. Blood samples were obtained to measure sex hormones, iron metabolism parameters, and muscle damage related markers. Discussion: IronFEMME Study has been designed to increase the knowledge regarding the influence of sex hormones on some aspects of the exercise-related female physiology. Iron metabolism and exercise-induced muscle damage will be studied considering the different reproductive status present throughout well-trained females’ lifespan. Trial registrationThe study was registered at Clinicaltrials.gov NCT04458662 on 2 July 2020.

Effect of Pretreatment Oral Contraceptives on Fresh and Cumulative Live Birth In Vitro Fertilization Outcomes in Ovulatory Women

(Abstracted from Fertil Steril 2020;114:779–786) Oral contraceptives (OCs) consisting of estrogen and progesterone have extensively been used for cycle control and synchronization in the context of in vitro fertilization (IVF). Conflicting data exist among usage of OCs in women with dysmenorrhea.

Contraceptive discontinuities in the use of oral and injectable hormonal contraceptives, and male condoms

The study aimed to estimate the total contraceptive discontinuity rates in the use of oral and injectable hormonal contraceptives, and male condoms and dropout rates due to switches to more effective and less effective methods. Data on 2,051 women, users of primary healthcare services in three Brazilian state capitals, were collected using the contraceptive calendar. The results showed that 24.5% of users of oral hormonal contraceptives, 33.5% of users of injectables, and 39% of users of male condoms had discontinued the respective method after 12 months of use, independently of the reason, and that the rates varied little between the capitals but did depend on the method. The main reason for discontinuing use of the contraceptive method was the desire to become pregnant (20.8%). Conception while using the method was reported by 20% of the women, a proportion that reached 25.7% in users of male condoms. After 12 months with the method, the dropout rate for reasons related to the contraceptive method was 11.4% in users of injectables; 15.9% of users of male condoms switched to a more effective method; and 16.3% of users of injectables switched to a less effective method. Contraceptive discontinuity rates were high and varied according to the contraceptive method.

Does last contraceptive method used impact the return of normal fertility?

Yes, according to a prospective observational study of more than 17,000 women that evaluated fecundability after stopping contraception. The authors found hormonal intrauterine device (IUD) users had slightly increased fecundability compared with users of barrier methods. There was no difference in fecundability for users of copper IUDs, implant, oral contraception, patches, rings, or natural methods compared with barrier methods. Users of injectable contraceptives experienced the longest delay in return of normal fertility, about 5 to 8 menstrual cycles.

Pulmonary Venous Thrombosis and Cerebrovascular Accident in a Young Oral Contraceptive User Patient: A Case Report

Since there are millions of pill users around the world, the relationship between oral contraceptives, thrombotic events, and the cerebrovascular accident has been the focus of numerous studies. Most of the cases described in the literature are of deep venous thrombosis in the lower limbs and thromboembolism in the pulmonary artery. This article aims to report a rare case of pulmonary vein thrombosis, along with cerebrovascular accident in a young patient who uses oral contraceptives. We seek to elucidate this relationship between the use of different oral contraceptives and the risk of thrombus formation, in addition to providing a brief review of these pathological episodes in the body. In view of the scarce existence of studies with reports of pulmonary venous thrombosis, it is expected to provide information to the entire medical community.

Predictors of Discontinuation of Modern Spacing Contraceptives in India.

Data from National Family Health Survey (2015-2016) was analyzed to examine the contraceptive acceptance, discontinuation rates, and associated factors among reproductive age women in India over one year. Findings revealed that 11.7% accepted modern methods of which 68% were for spacing. Only 5% switched to other methods. Discontinuation rate was high among condom (56.8%) and oral contraceptive pill users (34.5%), among women aged less than 25 years, with parity less than 2, belonging to rural area, and having no education. Health concerns/side effects, husband's disapproval, or method failure were most common reasons cited for discontinuation. The data show high discontinuation rates among some subgroups of women and for certain methods. Hence, women need to be provided options to switch methods to meet changing contraceptive needs and health priorities. Continuum of care with follow-up and counselling can facilitate sustained contraceptive use to avert unintended pregnancies.

The Effect of the Oral Contraceptive Cycle Phase on Exercise-Induced Muscle Damage After Eccentric Exercise in Resistance-Trained Women.

Romero-Parra, N, Rael, B, Alfaro-Magallanes, VM, Janse de Jonge, X, Cupeiro, R, and Peinado, AB; On Behalf of the IronFEMME Study Group. The effect of the oral contraceptive cycle phase on exercise-induced muscle damage after eccentric exercise in resistance-trained women. J Strength Cond Res 35(2): 353-359, 2021-To evaluate the influence of the active pill phase versus withdrawal phase of a monophasic oral contraceptive (OC) cycle on exercise-induced muscle damage and inflammation after eccentric resistance exercise. Eighteen resistance-trained female OC users (age: 25.6 ± 4.2 years, height: 162.4 ± 5.0 cm, and body mass: 58.1 ± 5.7 kg) performed an eccentric squat-based exercise during the active pill phase and withdrawal phase of their OC cycle. Muscle soreness, counter movement jump (CMJ), and blood markers of muscle damage and inflammation were evaluated before and postexercise (0, 2, 24, and 48 hours). Creatine kinase (CK) values were higher in the withdrawal (181.8 ± 89.8 U·L-1) than in the active pill phase (144.0 ± 39.7 U·L-1) (p < 0.001). The highest CK concentrations and muscle soreness values were observed 24 hours postexercise (217.9 ± 117.5 U·L-1 and 44.7 ± 19.7, respectively) compared with baseline (115.3 ± 37.4 U·L-1 and 4.4 ± 9.2, respectively; p < 0.001). In addition, a decrease in CMJ immediately postexercise (20.23 ± 4.6 cm) was observed in comparison with baseline (24.2 ± 6.1 cm), which was not yet recovered 24 hours postexercise (21.9 ± 5.9 cm; p < 0.001). No other phase or time effects were observed. An eccentric squat-based exercise session elicits muscle damage but no inflammation response in resistance-trained women. Furthermore, the highest CK concentrations observed in the withdrawal phase suggest that this phase might be more vulnerable to muscle damage and, therefore, less adequate to administer high training loads. However, the lack of differences in other muscle damage variables between OC phases does not warrant any guidance on the active pill versus withdrawal phase.

The role of olfaction and sex-hormone status in empathy-related measures

Reports of a female advantage in empathy-related measures suggest a role for sex hormones, although the data are inconsistent. Studies also report similar sex differences in human olfactory perception. In rodents, olfaction is involved in detecting and integrating socially relevant information and is modulated by the brain actions of estrogens. We hypothesized that olfaction may untangle the mixed evidence on the relationship between sex hormones and empathy-related measures (cognitive and affective) in humans. To test this, we examined 60 healthy participants in three sex-hormone-status groups: free-cycling women tested in cycle phases with higher 17-β estradiol and progesterone, oral-contraceptive users (low estradiol and progesterone), and men. We assessed empathy-related measures, facial mimicry (from zygomaticus and corrugator muscle activity), and odor discrimination ability. In the empathy-related measures and facial mimicry, we did not find overall group effects or meaningful associations with salivary levels of estradiol, progesterone, or testosterone. Free-cycling women only outperformed men in the recognition of emotions from pictures of the eye region, but sex hormones were unrelated to emotion recognition performance. Oral contraceptive users showed higher scores in the affective empathy-related measure when viewing negative emotions, with no relation to hormone levels. Free-cycling women exhibited the strongest facial mimicry (viewing female, but not male protagonists), positively associated with progesterone. Finally, the groups differed in odor discrimination, with free-cycling women outperforming men. However, odor discrimination ability and empathy-related performance were not correlated. Our results support a role of sex hormones in odor perception and in empathy-related measures, to a certain extent. However, no common underlying mechanism was found.

Association of Oral Contraceptives use with Breast Cancer and Hormone Receptor Status in Iraqi Women

BACKGROUND: Worldwide, there is a significant concern regarding the association of breast cancer risk and oral contraceptives use. Differences in demographical and pathological breast cancer characteristics in Iraqi patients have been reported compared to other western countries; however, studies addressing the risk of breast cancer among oral contraceptive users in Iraq and subsequent correlation with hormonal receptor status are lacking.&#x0D; AIM: The aim of the study was to evaluate association of breast cancer risk and oral contraceptives use in patients visiting tertiary oncology center and to correlate hormone receptor status with history of oral contraception use in breast cancer patients.&#x0D; PATIENTS AND METHODS: Two hundred women with breast cancer were compared regarding patterns of oral contraceptives use with 300 age-matched healthy female controls by personal interview and questionnaire. Patient’s records were reviewed for hormone receptor status.&#x0D; RESULTS: A significantly higher proportion (49%) of women with breast cancer reported a positive history of combined oral contraceptives use as compared with (35.7%) healthy controls. Ever oral contraceptives users had a significantly increased risk of breast cancer (odds ratio [OR] = 1.73; 95%, confidence interval = 1.2–2.5, p = 0.003), with the highest risk was seen in early use before the age of 20 (OR = 6.62, p = 0.02); whereas increased duration of use did not significantly increase the risk of breast cancer. There was no significant association between estrogen and progesterone receptors expression profile in breast cancer patients and combined oral contraceptive use.&#x0D; CONCLUSION: In Iraqi women, the risk of breast cancer increases with oral contraceptives intake particularly when starts early before the age of 20 years. The hormonal receptor status of breast cancer patients is not significantly affected by combined oral contraceptives use.

Relationship Between Oral Contraceptives and the Risk of Gliomas and Meningiomas: A Dose-Response Meta-Analysis and Systematic Review

Glioma and meningioma are the most common primary brain tumors in adults. Epidemiologic studies of the relationship between female hormone exposure and exogenous hormone use and the risk of meningioma and glioma in females have yielded inconsistent results. Two investigators comprehensively searched 3 electronic databases, including PubMed, Embase, and Cochrane Library. A total of 11 case-control studies were enrolled for meta-analysis. Dose-response meta-analyses were conducted. Compared with the non-oral contraceptives (OCs) female users, the female OC users might have reduced risk of glioma (risk ratio [RR], 0.87; 95% confidence interval [CI], 0.77-0.97; I2= 42.6%). However, there was no obvious evidence of an association between OC use and the risk of meningioma in females (RR, 0.99; 95% CI, 0.87-1.13; I2= 42.7%). Using OCs for >10 years in females may significantly decrease the risk of glioma to 30% (RR, 0.7; 95% CI, 0.6-0.81; I2= 0%). The dose-response meta-analyses indicated that the risk of glioma in females significantly decreased when the duration of oral OC use was >7.5 years. OC use may not increase the risks of glioma and meningioma in females. Instead, the long-term use of OCs may significantly decrease the risk of glioma, and the benefits are even more pronounced when the time window is >7.5 years. Nonetheless, the pooled results in this study suggest that OC use may not increase the risk of meningioma. Therefore, our conclusion should be validated and supplemented in future larger studies.