Oral Contraceptive Users Research Articles

Hormonal Contraceptive Use and Physical Performance, Body Composition, and Musculoskeletal Injuries during Military Training.

Purpose: To investigate associations between hormonal contraceptive use and physical performance, body composition, and musculoskeletal injuries in basic military training.Methods: Female British Army recruits (n = 450) were grouped as non-users (n = 182), combined oral contraceptive users (COCP; n = 184), or progestin-only users (POC; n = 144). Physical performance (2.4 km run, lift strength, leg power), body composition, iron and vitamin D status, and bone metabolism were measured at the start (week 1) and end (week 13) of training. Lower body musculoskeletal injuries were recorded from medical records.Results: Training decreased 2.4 km run time (-3.7%) and fat mass (-9.6%), and increased lift strength (4.5%), leg power (1.5%), lean mass (5.4%), and whole-body (0.9%), arms (1.8%), and legs (1.4%) aBMD (p ≤ 0.015); the training response was not different between groups (p ≥ 0.173). Lift strength was lower in COCP users than non-users (p = 0.044). Whole-body, trunk, and legs aBMD were lower in POC users than non-users and/or COCP users (p ≤ 0.041). There were no associations between hormonal contraceptive use and musculoskeletal or bone stress injury (p ≥ 0.429). Training did not change ferritin (p = 0.968), but decreased haemoglobin and total 25(OH)D, and increased PTH, βCTX, and PINP (p ≤ 0.005); the training response was not different between groups (p ≥ 0.368). Total 25(OH)D was higher, and βCTX and PINP were lower, in COCP users than non-users and POC users; PTH was lower in COCP users than non-users, and; βCTX and PINP were higher in POC users than non-users (p ≤ 0.017).Conclusions: Hormonal contraceptive use was not associated with performance or injury outcomes in military training.

Current oral contraceptive use affects explicit and implicit measures of depression in women.

Some data suggest that increased depressive symptoms may occur in women using combined oral contraceptives (OCs). However, this idea is controversial and the existing evidence is conflicting. The present study compared negative affect in 53 healthy women (M age = 19.9 years) during intervals of active daily OC hormone intake and during the washout week of the contraceptive cycle when no exogenous estrogens or progestins are used. A prospective counterbalanced repeated-measures study design was employed. Depressive affect was evaluated using standard psychometric tests of explicit (self-perceived) and implicit negative affect. Implicit measures are considered less subject to bias related to social expectations, self-awareness, or willingness to disclose. Other than their usual OCs, participants were medication-free and had been using OCs for a median of 12 mo. We found that measures of implicit affect (e.g., Affect Misattribution Procedure, Emotional Stroop Test) displayed a more depressive-like pattern of performance during active hormone intake, particularly among a subgroup of OC users who reported experiencing high levels of depressive affect more generally. In contrast, participants' self-perceptions suggested that they perceived their negative symptoms to be greater during the 'off' phase of the OC cycle, when OC steroids are withdrawn and menses occurs. The present findings reinforce the possibility of depressive mood effects associated with OC usage, and highlight the utility of including implicit measures, but also illustrate the complexity of mood assessment in OC users.

A comparative study of hormonal contraceptive use and vitamin D levels at Gondar Town 2023.

Vitamin D deficiency is an emerging public health problem globally, with devastating health consequences. Some studies suggest that exogenous sex hormones, found in hormonal contraceptives, may enhance vitamin D levels. However, the reasons for this association are not fully understood, as women using hormonal contraception may have different lifestyle habits affecting their vitamin D status. Therefore, this study seeks to explore the relationship between hormonal contraceptive use and vitamin D levels. A Facility based comparative cross-sectional study was conducted in Gondar town from February to April 2023, involving a total of 162 women using three types of hormonal contraceptives (Norplant, DMPA, and COC) and 162 age and BMI-matched non-users as controls in a 1:1 ratio. Participants were selected using systematic random sampling. A semi-structured questionnaire was used to collected data regarding the socio-demographic, economic, obstetric, lifestyle, and clinical information. 5 milliliters of blood samples were collected from each participant for Laboratory analysis of serum vitamin D, calcium, and alkaline phosphates using a Beckman Coulter chemistry analyzer. Independent t-tests, ANOVA with post hoc Bonferroni test was used to compare statistics between the two groups, and logistic regression models to identify factors associated with Vitamin D deficiency. The mean serum Vitamin D levels of Norplant, DMPA, and COC users were 24.08 (± 5.17), 24.83 (± 5.52), and 31.90 (± 6.94) respectively; whereas control group has mean Vitamin D level of 22.00 (± 7.97). On the current study the prevalence of Vitamin D deficiency (< 20 ng/ml) among hormonal contraceptive users was found to be 21.6% (35/162), whereas 48.14% (78/162) of non-user controls had vitamin D deficiency. The odds of having Vitamin D deficiency was higher among participants who attained higher education, who never eat fish and have never been used vitamin D Supplements. However, the use of combined oral contraceptives (COC) shown to reduce the odd of having vitamin D deficiency by 90%. Similarly, individuals with normal and hypercalcemia state shown to have lower odd of having Vitamin D deficiency. Users of combined oral contraceptives (COC) had significantly higher mean serum Vitamin D levels compared to users of Norplant and DMPA, as well as non-users. The prevalence of Vitamin D deficiency was lower among COC users compared to non-users, highlighting a potential protective effect of COC use against Vitamin D deficiency.

Assessing the awareness and knowledge of the adverse ocular side effects associated with oral contraceptives among women between the ages of 16 and 40 in Benin-city, Edo state, Nigeria

PurposeOral contraceptives are routinely used by women, because they are effective birth control methods, but few women are aware of their adverse ocular side effects. This study was carried out to determine the level of awareness and knowledge of the adverse ocular side effects associated with oral contraceptive use among women in Benin-City, Edo State, Nigeria. MethodThis was a cross-sectional study conducted over an eight-month period from February 2023 to September 2023, including 402 women (n = 402). The study employed both self-administered online and printed questionnaires. ResultsThe mean age of the participants was 27.76 ± 7.03. A total of 196 had tertiary education, 131 had secondary education and 75 had no educational background. Two-hundred thirty-seven participants were users of oral contraceptives, while 165 had never used them. Of the participants that were users of oral contraceptives, 44 had previously experienced visual problems as a side. The study results reveal that 289 participants (71.9%) were not aware of the potential adverse effects of oral contraceptives, while only 82 participants (20.4%) were aware. ConclusionThe results of this study show that there is poor awareness of the side effects of oral contraceptives, more specifically, the adverse effects on the eyes. It is recommended that more public health awareness campaigns be initiated, with the goal of accurately educating women about the ocular pathologic risks associated with oral contraceptives. Furthermore, healthcare workers should effectively communicate the risks associated with oral contraceptives to their patients. This can help women looking for contraception options make informed decisions about using oral contraceptives.

Unravelling the Causal Relationship between Endometriosis and the Risk for Developing Venous Thromboembolism: A Pooled Analysis.

To investigate the effect of endometriosis on venous thromboembolism (VTE) in oral contraceptive (OC) users. Pooled analysis on a harmonized dataset compromising international patient-centric cohort studies: INAS-VIPOS, INAS-SCORE, and INAS-FOCUS. Eleven European countries, the United States, and Canada. Individuals being newly prescribed an OC with or without an endometriosis and no VTE history. Detailed information was captured using self-administered questionnaires at baseline and every 6 to 12 months thereafter. Self-reported VTEs were medically validated and reviewed by an independent adjudication committee. Incidence rates (IRs) were calculated per 10,000 woman-years. The association of endometriosis on VTE was determined in a time-to-event analysis, calculating crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) using stabilized inverse probability of treatment weighting (IPTW). A total of 22,072 women had an endometriosis diagnosis, and 91,056 women did not. Women with endometriosis contributed 78,751 woman-years during which 41 VTE events occurred (IR: 5.2/10,000, 95% CI: 3.7-7.1) compared to 127 VTEs during 310,501 woman-years in women without endometriosis (IR: 4.1/10,000, 95% CI: 3.4-4.9). The hazard ratio of VTE in women with endometriosis was 1.79 (95% CI: 1.24-2.57) using stabilized IPTW controlling for age, body mass index, smoking, education, age at menarche, and family history of VTE. Subgroup and sensitivity analyses showed similar results. These results highlight the importance of considering endometriosis as a potential factor contributing to VTE in women using OC; however, further research on the relationship between endometriosis and VTE is warranted.

Clinico-epidemiological profile & outcome of patients presenting with cerebral venous thrombosis to emergency department

ObjectivesTo better understand the clinical and radiological characteristics of Cerebral Venous Thrombosis (CVT), we conducted a study focusing on the assessment of neurological outcomes and factors associated with poor prognosis in patients with CVT. MethodsThis prospective, observational study took place over two years (July 2020 to June 2022) in a tertiary care teaching hospital in South India, encompassing adults aged 18 years and over. Key data points included demographic information, symptomatology, physical and neurological examinations, neuroimaging findings, hospital interventions, and neurological outcomes at discharge and at a six-week telephonic follow-up. ResultsA total of 140 patients with CVT, median age 34 years, were studied. 61.4 % were males. The most common symptoms and signs were headaches (70.7 %) and papilledema (60.7 %). Hemorrhagic infarct was the most prevalent finding on the non-contrast computed tomography (NCCT) of the brain, involving 39.4 % of patients. The most commonly affected sinus was the superior sagittal sinus. Risk factors most often observed were alcoholism (45 %), smoking (21.4 %), anemia (27.1 %), oral contraceptive pill usage (12.1 %), and hypertension (12.1 %). Deep vein thrombosis or pulmonary embolism was present in 5 % of the patients. The mean hospital stay was 13.9 days, with 6.4 % of patients requiring endotracheal intubation at presentation and 22.9 % during their stay. The observed in-hospital mortality rate was 17.9 %, increasing to 22.4 % at the six-week follow-up. Morbidity (mRS 3–5) was 24.3 % at discharge, decreasing to 8.2 % at six-week follow-up. Favorable outcomes were reported in 57.9 % of cases at discharge, rising to 69.4 % at six weeks. ConclusionsOur study underscores the importance of recognizing cardinal symptoms and diverse risk factors of CVT, including alcoholism and anemia. Majority of CVT occurrences were observed in males aged 18–29. Critical determinants of heightened morbidity and mortality were identified, including lower GCS scores and the necessity for advanced interventions. Notably, majority of patients presented favorable neurological outcomes at six-week follow-up.

Emotion and birth control: Emotion regulation ERPs differ based on menstrual cycle phase and hormonal contraceptive use

While hormonal contraceptives (HCs) like oral contraceptive pills (OCs) and intrauterine devices (IUDs) can reportedly influence mood, the evidence is mixed, and the mechanisms remain unclear. Emotion reactivity and regulation processes may be hormone-sensitive and underlie these mood changes. This study sought to investigate the role of the menstrual cycle and HC use in emotion regulation using ERP measures during an emotion regulation paradigm. Participants with a natural cycle (NC) were measured in the mid-follicular and mid-luteal phase (within-subject design, n = 26), and compared with OC (n = 36) and IUD (n = 25) users. The centroparietal late positive potential (LPP) reflected negative emotion reactivity and its modulation by cognitive reappraisal served as a marker for emotion regulation processing. NC participants had a lower LPP amplitude in the mid-luteal compared to the mid-follicular phase. Reactivity to negative emotional stimuli decreased over time in the mid-luteal phase, whereas the HC groups showed sustained LPP activation. Reappraisal led only to significant LPP changes in the mid-follicular phase, and not in the mid-luteal phase or HC groups. Our results showed a specific left frontal activity (FR-LPP) in the contrast that reflected emotion regulation processing. This activity was highest in the mid-follicular phase, and was significantly different from the OC users but not from the IUD group. Higher self-reported PMS symptoms were associated with stronger effects on the reduced mid-luteal LPP activity and with lower FR-LPP amplitude in the mid-follicular phase. No effect of OC phase (active pill use versus pill pause) was found. These findings add insights into the neurophysiological underpinnings of hormone-related mood changes and demonstrate the importance of considering hormonal status and PMS symptoms in emotion research.

Effects of Hormonal Contraception and the Menstrual Cycle on Maximal Strength and Power Performance.

To evaluate the effects of oral contraceptive (OC) and hormonal intrauterine device (H-IUD) use, compared to an eumenorrheic (EUM) cycle, on maximal strength and power between hormone phases. One repetition max (1RM) leg press and bench press, peak force (PF) from knee extension and upright row isometric dynamometry, and power from vertical jump height (VJH) and reactive strength index (RSI; cm/s) were measured in 60 healthy, active women (mean ± standard deviation [SD]; Age: 26.5 ± 7.0 yrs, BMI: 22.5 ± 3.7 kg/m2) who were monophasic OC users for ≥6 months (n = 21), had a H-IUD for ≥6 months (n = 20), or had regularly naturally occurring menstrual cycle for ≥3 months or were using a non-hormonal IUD (EUM; n = 19). Participants were randomly assigned to begin in the follicular phase/placebo pill (low hormone phase; LHP) or in the luteal phase/active pill (high hormone phase; HHP) and were tested once in each phase. Estimates of total lean mass (LM), leg LM, and arm LM were measured via dual energy x-ray absorptiometry. Separate univariate ANCOVAs were used to assess the change from HHP to LHP between groups, with LM and progesterone as covariates. Leg press 1RM was significantly different across phases between groups (p = 0.027), with higher leg press 1RM in the HHP for the OC group (mean difference[∆HHP-LHP] ± standard error: ∆7.4 ± 15.9 kg; p = 0.043) compared to the H-IUD group (∆-8.9 ± 23.8 kg; p = 0.043). All groups demonstrated similar bench press 1RM, PF, VJH, and RSI between phases (p > 0.05). Lower body strength was greater in the HHP for OC users (5.6% increase) suggesting lower body maximal strength outcomes may be influenced by hormonal contraception type.

Increased Serum Levels of Inflammatory Markers and Promoter Hypermethylation of BRCA1 and BRCA2 in Oral Contraceptive Users

Background: Oral contraceptives (OCs) are widely used to prevent pregnancy, particularly among reproductive-age women. Although undesired physiological consequences, such as increased susceptibility to cancer, have been suggested, the exact molecular mechanism is not well elucidated. Thereby, the current study aimed to assess the effects of OCs on the inflammatory markers and BRCA1 and BRCA2 gene-specific DNA methylation in the serum of OCs-exposed women. Methods: The current cross-sectional study involved 70 adult women, 35 of whom had used oral contraceptive pills (OCP, 0.03 mg ethinyl estradiol, and 0.15 mg levonorgestrel) to prevent pregnancy, and 35 of whom had used condoms. The promoter methylation status of the two mentioned tumor suppressor genes was assessed by methylation-specific PCR. Moreover, serum levels of IL-1, IL-6, and TNF-α were evaluated using the ELISA method. Results: The findings revealed a significant difference in cytokines between groups (p &lt;0.001). However, no significant differences were revealed regarding TNF-α between the two groups. Additionally, the frequency of promoter hypermethylation of BRCA1 and BRCA2 in OCP users was significantly higher (p &lt;0.05). Conclusion: The current findings suggested that OCP usage could increase serum levels of inflammatory markers and promote the hypermethylation of two suppressor genes. Hence, further studies are encouraged to reveal the association between OCP usage and cancer through hypermethylation of BRCA1 and BRCA2 and induction of inflammation.

Sexual function, quality of life, anxiety, and depression in women of reproductive age using hormonal, nonhormonal, and no contraceptive methods.

Hormonal contraceptive use has been related to adverse effects, including impacts on sexual function and sexual satisfaction, although the difference in the effects on sexual function with the use of hormonal vs nonhormonal contraceptive methods remains controversial. In this study we sought to compare the prevalence of dyspareunia, sexual function, sexual satisfaction, quality of life, anxiety, and depression between women using hormonal, nonhormonal, or no contraceptive methods and to compare these outcomes between the most frequently used contraceptive methods. This cross-sectional study included sexually active women of reproductive age who were stratified into 3 groups: women using hormonal, nonhormonal, or no contraceptive methods. Based on the use of questionnaires administered to the study participants, we compared sexual function in the 3 groups and more specifically among users of oral contraceptives, copper and hormonal intrauterine devices, and barrier methods. Participants completed 4 questionnaires to assess sexual function (Female Sexual Function Index), sexual satisfaction (Sexual Quotient-Feminine Version), quality of life (12-item Medical Outcomes Short Form Health Survey), and anxiety and depression (Hospital Anxiety and Depression Scale). This study included 315 women classified into 3 groups on the basis of contraceptive use: 161 in the hormonal contraceptives group (median [interquartile range] age, 24 [23-28] years), 97 in the nonhormonal contraceptives group (age 26 [23-30] years), and 57 in the no contraceptive methods group (age 28 [24-35] years). Dyspareunia prevalence showed no difference between the groups. In the quality of life domain, compared with women in the nonhormonal contraceptive group, women in the hormonal contraceptive group were younger and had lower sexual function satisfaction, reduced arousal, and heightened pain (P< .05), as well as higher anxiety and depression levels (P= .03, for both), increased pain (P= .01), and poorer overall health (P= .01). No difference was found between these groups in other quality of life domains. Regarding contraceptive methods, women using copper intrauterine devices had better sexual function, including higher rates of arousal and lower anxiety, than women using oral contraceptives (P< .05). The results of this study highlight worse sexual function and sexual satisfaction and higher levels of anxiety and depression in women using hormonal contraceptive methods than in women using nonhormonal methods. The findings of this study strengthen the evidence of differences in sexual function between women using oral contraceptives and those using copper intrauterine devices. Sexual function was also compared among users of oral contraceptives, copper and hormonal intrauterine devices, and barrier methods. However, less frequently used contraceptive methods, such as hormonal injections and vaginal rings, could not be compared in this sample. Women using hormonal contraceptive methods were younger, had lower sexual function and satisfaction, and experienced higher anxiety and depression levels than women using nonhormonal contraceptive methods.

Influence of Menstrual Cycle and Oral Contraceptive Phases on Bone (re)modelling Markers in Response to Interval Running

To explore how sex hormone fluctuations may affect bone metabolism, this study aimed to examine P1NP and β-CTX-1 concentrations across the menstrual and oral contraceptive (OC) cycle phases in response to running. 17β-oestradiol, progesterone, P1NP and β-CTX-1 were analysed pre- and post-exercise in eight eumenorrheic females in the early-follicular, late-follicular, and mid-luteal phases, while 8 OC users were evaluated during the withdrawal and active pill-taking phases. The running protocol consisted of 8 × 3min treadmill runs at 85% of maximal aerobic speed. 17β-oestradiol concentrations (pg·ml−1) were lower in early-follicular (47.22 ± 39.75) compared to late-follicular (304.95 ± 235.85;p = < 0.001) and mid-luteal phase (165.56 ± 80.6;p = 0.003) and higher in withdrawal (46.51 ± 44.09) compared to active pill-taking phase (10.88 ± 11.24;p < 0.001). Progesterone (ng·ml−1) was higher in mid-luteal (13.214 ± 4.926) compared to early-follicular (0.521 ± 0.365; p < 0.001) and late-follicular phase (1.677 ± 2.586;p < 0.001). In eumenorrheic females, P1NP concentrations (ng·ml−1) were higher in late-follicular (69.97 ± 17.84) compared to early-follicular (60.96 ± 16.64;p = 0.006;) and mid-luteal phase (59.122 ± 11.77;p = 0.002). β-CTX-1 concentrations (ng·ml−1) were lower in mid-luteal (0.376 ± 0.098) compared to late-follicular (0.496 ± 0.166; p = 0.001) and early-follicular phase (0.452 ± 0.148; p = 0.039). OC users showed higher post-exercise P1NP concentrations in withdrawal phase (61.75 ± 8.32) compared to post-exercise in active pill-taking phase (45.45 ± 6;p < 0.001). Comparing hormonal profiles, post-exercise P1NP concentrations were higher in early-follicular (66.91 ± 16.26;p < 0.001), late-follicular (80.66 ± 16.35;p < 0.001) and mid-luteal phases (64.57 ± 9.68;p = 0.002) to active pill-taking phase. These findings underscore the importance of studying exercising females with different ovarian hormone profiles, as changes in sex hormone concentrations affect bone metabolism in response to running, showing a higher post-exercise P1NP concentrations in all menstrual cycle phases compared with active pill-taking phase of the OC cycle.

Influence of endogenous and exogenous hormones on the cardiovascular response to lower extremity exercise and group III/IV activation in young females.

Oral contraceptive (OC) use can increase resting blood pressure (BP) in females as well as contribute to greater activation of group III/IV afferents during upper body exercise. It is unknown, however, whether an exaggerated BP response occurs during lower limb exercise in OC users. We sought to elucidate the group III/IV afferent activity-mediated BP and heart rate responses while performing lower extremity tasks during early and late follicular phases in young, healthy females. Females not taking OCs (NOC: n = 8; age: 25 ± 4 yr) and those taking OCs (OC: n = 10; age: 23 ± 2 yr) completed a continuous knee extension/flexion passive stretch (mechanoreflex) and cycling exercise with subsystolic cuff occlusion (exercise pressor reflex), which was followed by a 2-min postexercise circulatory occlusion (PECO) (metaboreflex). Data collection occurred on two occasions: once during the early follicular phase (days 1-4) and once during the late follicular phase (days 10-14) of their menstrual cycle (NOC) or during the placebo and active pill phases (OC). Resting mean arterial BP and heart rate were not different between phases in NOC and OC participants (P > 0.05). Hemodynamic responses to metaboreflex, mechanoreflex, and collective exercise pressor reflex activation were not different between phases in both groups (P > 0.05). In conclusion, although OCs are known to increase BP at rest, our findings indicate that neither endogenous nor exogenous (OC) sex hormones modulate BP during large, lower limb muscle exercise with or without group III/IV afferent activation in young, healthy females.NEW & NOTEWORTHY Sex differences in the cardiovascular response to exercise have been demonstrated and may be dependent on sex hormone levels. Furthermore, oral contraceptives (OCs) have been shown to exaggerate the blood pressure response to upper extremity exercise. The results of this study indicate that neither endogenous nor exogenous (OC) sex hormones modulate BP during lower extremity dynamic exercise or with group III/IV afferent activation in young, healthy females.

Prunes May Blunt Adverse Effects of Oral Contraceptives on Bone Health in Young Adult Women: A Randomized Clinical Trial

BackgroundOral contraceptives (OCs) may promote bone loss, thereby leading to suboptimal bone health later in life. Research is needed to determine whether dietary interventions can blunt OC-related bone loss; prune consumption, shown to be effective in improving bone density in previous studies, could provide a safe and inexpensive solution. ObjectivesThe purpose of this study was to determine whether 12 mo of consuming 50 g of prunes daily would prevent bone loss or increase bone accrual in young (18–25 y) OC users. MethodsNinety women were randomly assigned to a control group not using OCs (non-OC), an OC group not consuming prunes (OC), and an OC group consuming 50 g prunes daily (OC+P) for 12 mo. Bone mineral density (BMD) was measured at baseline and after 12 mo via dual-energy X-ray absorptiometry (at all sites) and peripheral quantitative computed tomography (at tibia). Blood samples were collected at baseline and after 6 and 12 mo to assess biomarkers. ResultsThere were no significant differences between groups for dietary intake, physical activity, serum tartrate-resistant acid phosphatase-5b, or bone alkaline phosphatase concentrations. Baseline serum C-reactive protein and vitamin D concentrations were higher (P < 0.001) for OC and OC+P groups than those in the non-OC group. Serum parathyroid hormone was higher for non-OC group than OC group at both baseline (P = 0.049) and final (P = 0.032). BMD measured by dual-energy X-ray absorptiometry at all sites did not change among groups. Ultradistal radius BMD increased over time (P < 0.05) within non-OC and OC+P groups. Trabecular density of the distal tibia as measured by peripheral quantitative computed tomography decreased from baseline to 12 mo within the OC group only (P = 0.016). ConclusionsOC use tended to promote minor negative effects on bone and consuming prunes tended to provide a potential protective effect on trabecular density of the distal tibia and ultradistal radius.This trial was registered at www.clinicaltrials.gov as NCT04785131.

Influence of Oral Contraceptives on Lipid Profile and Trajectories in Healthy Adolescents—Data From the EVA-Tyrol Study

PurposeOral contraception is one of the most popular contraceptive methods both in adults and adolescents. However, the effects of oral contraception on lipids in adolescents are not well studied. MethodsLipid profiles were measured and contraceptive use was assessed in 14- to 19-year-old female participants of the prospective population-based Early Vascular Ageing-Tyrol Study between 2015 and 2018, twice on average 22 months apart. ResultsFor this analysis, data from 828 young women with a median age of 17.0 years were available. Of them, 317 (38%) used oral contraceptives (OCs). OC users had a slightly higher systolic and diastolic blood pressure and larger changes over time and were more likely to use cigarettes than nonusers. Total cholesterol (179.6 vs. 162.4 mg/dL), low-density lipoprotein-cholesterol (106.4 vs. 94.6 mg/dL), and triglycerides (104.0 vs. 67.0 mg/dL) were significantly higher in OC users after multivariable adjustment in linear regression models. No difference in high-density lipoprotein-cholesterol between the two groups was found. In 558 females, follow-up data were available. Those who initiated OC use had on average 15.4 mg/dL higher low-density lipoprotein-cholesterol and 36.2 mg/dL higher triglyceride level changes between baseline and follow-up than never users. Duration of OC use did not show a significant association with lipid levels and changes. DiscussionWe showed an independent association between OC use and blood lipids as well as lipid trajectories over time in a large cohort of healthy adolescents. These changes are especially relevant to consider in adolescents with other risk factors for dyslipidemia or other cardiovascular risk factors.

The influence of oral contraceptives on the exercise pressor reflex in the upper and lower body.

Previous research has demonstrated that oral contraceptive (OC) users have enhanced cardiorespiratory responses to arm metaboreflex activation (i.e., postexercise circulatory occlusion, PECO) and attenuated pressor responses to leg passive movement (PM) compared to non-OC users (NOC). We investigated the cardiorespiratory responses to arm or leg metaboreflexand mechanoreflex activation in 32 women (OC, n = 16; NOC, n = 16) performing four trials: 40% handgrip or 80% plantarflexion followed by PECO and arm or leg PM. OC and NOC increased mean arterial pressure (MAP) similarly during handgrip, plantarflexion and arm/leg PECO compared to baseline. Despite increased ventilation (VE) during exercise, none of the women exhibited higher VE during arm or leg PECO. OC and NOC similarly increased MAP and VE during arm or leg PM compared to baseline. Therefore, OC and NOC were similar across pressor and ventilatory responses to arm or leg metaboreflexand mechanoreflex activation. However, some differences due to OC may have been masked by disparities in muscle strength. Since women increase VE during exercise, we suggest that while women do not display a ventilatory response to metaboreflex activation (perhaps due to not reaching a theoretical metabolite threshold to stimulate VE), the mechanoreflex may drive VE during exercise in women.

Reduced threat avoidance but increased stress induced approach bias in women taking oral contraceptives

Recent research has increasingly acknowledged the impact of oral contraceptives on affective behavior and stress responses; however, the underlying mechanisms are still not well understood. Studies have previously shown that steroid hormones modulate automatic approach and avoidance behavior. Here, we thus investigated the effects of oral contraceptives on approach and avoidance behavior and whether these effects are modulated by stress. The study comprised 130 female participants, half of whom were using oral contraceptives, while the other half were not using any hormonal contraception (NC). The participants completed the Approach Avoidance Task (AAT), which measures automatic approach and avoidance behavior to socio-affective signals. The AAT was run once before and once after a stress manipulation using the Socially Evaluated Cold Pressor Test. OC users showed absent avoidance behavior to social threat signals and a stress-induced increase in approach behavior to positive social signals. The latter was found in particular in women taking androgenic acting OC, demonstrating that different OC preparations need to be taken into account in research on OC effects. However, OC and NC group did not differ in their cortisol stress response. Overall, the results suggest that OC usage impacts on approach and avoidance behavior to social signals, which might also contribute to the development of affective side effects.

Effects of the Menstrual Cycle and Hormonal Contraceptive Use on Metabolic Outcomes, Strength Performance, and Recovery: A Narrative Review.

The effects of female sex hormones on optimal performance have been increasingly recognized as an important consideration in exercise and sport science research. This narrative review explores the findings of studies evaluating the effects of menstrual cycle phase in eumenorrheic women and the use of hormonal contraception (oral contraceptives and hormonal intrauterine devices) on metabolism, muscular strength, and recovery in active females. Ovarian hormones are known to influence metabolism because estrogen is a master regulator of bioenergetics. Importantly, the menstrual cycle may impact protein synthesis, impacting skeletal muscle quality and strength. Studies investigating muscular strength in eumenorrheic women report equivocal findings between the follicular phase and luteal phase with no differences compared to oral contraceptive users. Studies examining recovery measures (using biomarkers, blood lactate, and blood flow) do not report clear or consistent effects of the impact of the menstrual cycle or hormonal contraception use on recovery. Overall, the current literature may be limited by the evaluation of only one menstrual cycle and the use of group means for statistical significance. Hence, to optimize training and performance in females, regardless of hormonal contraception use, there is a need for future research to quantify the intra-individual impact of the menstrual cycle phases and hormonal contraceptive use in active females.

Variables Affecting CA15.3 Tumor Antigen Expression and Antibodies against It in Female National Health and Nutritional Survey Participants.

Cancers of ductal origin often express glycoprotein mucin 1 (MUC1), also known as CA15.3, with higher levels leading to poor prognosis. Conversely, anti-MUC1 antibodies develop in some patients, leading to better prognosis. We sought to identify epidemiologic factors associated with CA15.3 antigen or antibody levels. Levels of CA15.3 antigen and anti-CA15.3 IgG antibodies were measured in archived sera from 2,302 mostly healthy women from the National Health and Nutritional Survey; and epidemiologic predictors of their levels were examined using multivariate and correlational analyses. Among racial groups, Black women had the highest levels of CA15.3 antigen and lowest levels of antibodies. Increasing body mass index and current smoking were associated with low anti-CA15.3 antibody levels. Low CA15.3 antigen levels were seen in oral contraceptive users and high levels in women who were pregnant or lactating at the time of blood collection, with the latter group also having high antibody levels. Past reproductive events associated with high antigen levels included the following: later age at menarche, having given birth, and history of endometriosis. Lower antigen levels were seen with increasing duration of OC use. Anti-CA15.3 antibody levels decreased with an increasing estimated number of ovulatory years. Key determinants of CA.15.3 antigen or antibody levels include the following: race, body mass index, smoking, later menarche, childbirth, number of ovulatory cycles, and endometriosis. This study supports the premise that known epidemiologic factors affecting risk for or survival after MUC1-expressing cancers may, at least partially, operate through their association with CA15.3 antigen or antibody levels.

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

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

Genome-wide investigation of exogenous female hormones, genetic variation, and venous thromboembolism risk

BackgroundIncreased risk of venous thromboembolism (VTE) is a life-threatening side effect for users of oral contraceptives (OCs) or hormone therapy (HT). ObjectivesTo investigate the potential for genetic predisposition to VTE in OC or HT users, we conducted a gene-by-environment case-only meta-analysis of genome-wide association studies (GWAS). MethodsUse or nonuse of OCs (7 studies) or HT (8 studies) at the time of the VTE event was determined by pharmacy records or self-report. A synergy index (SI) was modeled for each variant in each study and submultiplicative/supramultiplicative gene-by-environment interactions were estimated. The SI parameters were first meta-analyzed across OC and HT studies and subsequently meta-analyzed to obtain an overall estimate. The primary analysis was agnostic GWAS and interrogated all imputed genotypes using a P value threshold of <5.0 × 10−8; secondary analyses were candidate-based. ResultsThe VTE case-only OC meta-analysis included 2895 OC users and 6607 nonusers; the case-only HT meta-analysis included 2434 HT users and 12 793 nonusers. In primary GWAS meta-analyses, no variant reached genome-wide significance, but the smallest P value approached statistical significance: rs9386463 (P = 5.03 × 10−8). We tested associations for 138 candidate variants and identified 2 that exceeded statistical significance (0.05/138 = 3.62 × 10−4): F5 rs6025 (P = 1.87 × 10−5; SI, 1.29; previously observed) and F11 rs2036914 (P = 2.0 × 10−4; SI, 0.91; new observation). ConclusionThe candidate variant approach to identify submultiplictive/supramultiplicative associations between genetic variation and OC and HT use identified a new association with common genetic variation in F11, while the agnostic interrogations did not yield new discoveries.