Monophasic Oral Contraceptives Research Articles

Drug-drug interactions of icenticaftor (QBW251) with a 5-probe cytochrome P450 cocktail and oral contraceptives.

A drug-drug interaction (DDI) study was conducted to evaluate the effect of icenticaftor (QBW251) on the pharmacokinetics (PK) of a 5-probe cytochrome P450 (CYP) substrate cocktail, guided by invitro studies in human hepatocytes and liver microsomes. Another DDI study investigated the effect of icenticaftor on the PK and pharmacodynamics (PD) of a monophasic oral contraceptive (OC) containing ethinyl estradiol (EE) and levonorgestrel (LVG) in premenopausal healthy female subjects. The static-mechanistic DDI assessment indicated that icenticaftor may moderately induce the metabolic clearance of co-medications metabolized by CYP3A4 (area under the concentration-time curve [AUC] ratio: 0.47) and potentially CYP2C; icenticaftor may also weakly inhibit the metabolic clearance of co-medications metabolized by CYP1A2 and CYP3A4 (AUC ratio: 1.35 and 1.86, respectively) and moderately inhibit CYP2B6 (AUC ratio: 2.11). In the CYP substrate cocktail DDI study, icenticaftor 300 mg twice daily (b.i.d.) moderately inhibited CYP1A2 (AUC ratio: 3.35) and CYP2C19 (AUC ratio: 2.70). As expected from the results of the invitro studies, weak induction was observed for CYP3A4 (AUC ratio: 0.51) and CYP2C8 (AUC ratio: 0.66). In the OC DDI study, co-administration of icenticaftor 450 mg b.i.d. with monophasic OC containing 30-μg EE and 150-μg LVG once daily reduced the plasma exposure of both components by approximately 50% and led to increased levels of follicle-stimulating hormone and luteinizing hormone. These results provide valuable guidance for the use of icenticaftor in patients taking concomitant medications that are substrates of CYP enzymes or patients using OCs.

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.

Effects of Hormonal Contraception and the Menstrual Cycle on Fatigability and Recovery From an Anaerobic Exercise Test.

Cabre, HE, Ladan, AN, Moore, SR, Joniak, KE, Blue, MNM, Pietrosimone, BG, Hackney, AC, and Smith-Ryan, AE. Effects of hormonal contraception and the menstrual cycle on fatigability and recovery from an anaerobic exercise test. J Strength Cond Res 38(7): 1256-1265, 2024-This study sought to evaluate the effects of oral contraceptive (OC) and hormonal intrauterine device (H-IUD) use, compared with a eumenorrheic (EUM) cycle, on fatigability and recovery between hormone the phases. Peak power (PP), average power (AP), fatigue index (FI), blood lactate, vessel diameter, and blood flow (BF) were measured from a repeated sprint cycle test (10 × 6 seconds) in 60, healthy, active women (mean ± SD ; age: 26.5 ± 7.0 years, BMI: 22.5 ± 3.7 kg·m -2 ) who used monophasic OC (≥6 months; n = 21), had a H-IUD (≥6 months; n = 20), or had regular naturally occurring menstrual cycle (≥3 months) or had a nonhormonal IUD (EUM; n = 19). Subjects were randomly assigned to begin in either the low-hormone phase (LHP) or high-hormone phase (HHP) and were tested once in each phase. Separate univariate analyses of covariances assessed the change from HHP to LHP between the groups, covaried for progesterone, with significance set at p ≤ 0.05. All groups demonstrated similar changes in PP, AP, FI, blood lactate, vessel diameter, and BF between the phases ( p > 0.05). Although not significant, AP was higher in LHP for OC (Δ -248.2 ± 1,301.4 W) and EUM (Δ -19.5 ± 977.7 W) and higher in HHP for H-IUD (Δ 369.3 ± 1,123.0 W). Oral contraceptive group exhibited a higher FI (Δ 2.0%) and reduced blood lactate clearance (Δ 2.5%) in HHP. In recreationally active women, hormonal contraception and hormone phases may minimally impact fatigue and recovery. Individual elite female athletes may benefit from understanding hormonal contraception type as performance and recovery may slightly vary across the cycle.

Effects of In-Exercise Carbohydrate Supplementation on Prolonged High-Intensity Exercise Performance in Oral Contraceptive Users.

To examine the impact of oral contraceptive (OC) phases on performance, physiological, and subjective responses to prolonged, intensive exercise when carbohydrate (CHO) stores are reduced. Ten well-trained female cyclists using monophasic OC completed 4 identical trials (>150min) under conditions of in-trial 60-g·h-1 CHO supplementation (CHO+) or placebo (CHO-) during the sugar- (SUG) and active-pill (ACT) phases of their OC cycle. Each trial comprised two 400-kcal time trials (TT) separated by 1hour of submaximal cycling at first ventilatory threshold. Change in completion time from TT1 to TT2 was minimized in CHO+ compared with CHO- (4.06 [2.55] vs 6.08 [5.33]min; P = .019, effect size = -0.36). An interaction effect of OC and CHO was observed for time to complete TT (P = .006), mean TT power (P = .002), mean TT heart rate (P = .002), and posttrial emotional balance (P = .020) and negative emotional state (P = .033). In ACT, mean TT power and heart rate were higher in CHO+ when compared with CHO-, resulting in faster TTs in CHO+ and improved posttrial emotional well-being. When CHO was not supplemented, TT power and heart rate were higher in SUG when compared with ACT, resulting in faster TTs in SUG and improved posttrial emotional balance. CHO depletion during ACT negatively influenced TT performance and emotional well-being when compared with SUG. Irrespective of OC pill phase, CHO supplementation should be prioritized to sustain performance and improve postexercise recovery-stress balance.

Midostaurin drug interaction profile: a comprehensive assessment of CYP3A, CYP2B6, and CYP2C8 drug substrates, and oral contraceptives in healthy participants.

Midostaurin, approved for treating FLT-3-mutated acute myeloid leukemia and advanced systemic mastocytosis, is metabolized by cytochrome P450 (CYP) 3A4 to two major metabolites, and may inhibit and/or induce CYP3A, CYP2B6, and CYP2C8. Two studies investigated the impact of midostaurin on CYP substrate drugs and oral contraceptives in healthy participants. Using sentinel dosing for participants' safety, the effects of midostaurin at steady state following 25-day (Study 1) or 24-day (Study 2) dosing with 50mg twice daily were evaluated on CYP substrates, midazolam (CYP3A4), bupropion (CYP2B6), and pioglitazone (CYP2C8) in Study 1; and monophasic oral contraceptives (containing ethinylestradiol [EES] and levonorgestrel [LVG]) in Study 2. In Study 1, midostaurin resulted in a 10% increase in midazolam peak plasma concentrations (Cmax), and 3-4% decrease in total exposures (AUC). Bupropion showed a 55% decrease in Cmax and 48-49% decrease in AUCs. Pioglitazone showed a 10% decrease in Cmax and 6% decrease in AUC. In Study 2, midostaurin resulted in a 26% increase in Cmax and 7-10% increase in AUC of EES; and a 19% increase in Cmax and 29-42% increase in AUC of LVG. Midostaurin 50mg twice daily for 28days ensured that steady-state concentrations of midostaurin and the active metabolites were achieved by the time of CYP substrate drugs or oral contraceptive dosing. No safety concerns were reported. Midostaurin neither inhibits nor induces CYP3A4 and CYP2C8, and weakly induces CYP2B6. Midostaurin at steady state has no clinically relevant PK interaction on hormonal contraceptives. All treatments were well tolerated.

Influence of menstrual cycle phase and oral contraceptive phase on exercise performance in endurance-trained females.

Limited data exists on the influence of menstrual cycle (MC) phase and oral contraceptive (OC) phase on physical performance in endurance-trained females due to poor control regarding MC verification and differentiation. We aimed to evaluate exercise performance and the respiratory response to exercise in three distinct phases of the MC and OC cycle in endurance-trained females. Using a prospective cohort study design, we recruited trained females (Vo<inf>2max</inf> 52±4 mL O<inf>2</inf>/min/kg) who were either not using oral contraceptives (NOC) or using monophasic OCs. NOC were tested in the early and late follicular phase (FP) and the mid-luteal phase (LP). OC-users were tested in the withdrawal phase (WP) and two times in the active OC phase (OCP). The test battery included DXA scans, blood sampling, a submaximal bike test, a maximal isometric knee-extensor strength test, 4 and 20-second bike sprints, and a 6 min time trial on a bike. MC phases were verified by the use of ovulation kits and circulating sex hormone levels. After the exclusion of four NOCs due to inadequate sex hormone levels, 11 NOC and 13 OC users were included in the final analysis. 6 min time trial performance, sprint performance, and most submaximal exercise intensity variables did not differ between MC phases and OC cycle phases. However, in NOC, ventilation (L/min) during exercise at 30% of aerobic peak power was 7.6% lower in the late FP compared to the LP (P<0.05). In OC users, muscle strength was 3.9% higher in the early OCP compared to WP (P<0.05), whereas body mass was higher in the late OCP compared to WP (P<0.05). Collectively, our study suggests that MC phase and OCP influence exercise performance to a limited extent in endurance-trained females.

Mental rotation, episodic memory, and executive control: Possible effects of biological sex and oral contraceptive use

Oral contraceptives (OCs) are one of the most common forms of hormonal birth control. A small literature suggests that OC use may affect visuospatial ability, episodic memory, and executive control. However, previous studies have been criticized for small sample sizes and the use of different, single cognitive tests. We investigated the degree to which biological sex and OC use might affect individual mental rotation, episodic memory, and executive control in a large sample of healthy, young adults (N = 155, including 52 OC users, 53 naturally cycling females, and 50 males) tested individually over videoconference. To measure cognition, we used a set of neuropsychological tasks inspired by Glisky and colleagues’ two-factor episodic memory and executive control battery, from which two composite scores (based on principal component analysis) were derived for each participant. Our pre-registered analysis revealed a clear female advantage in episodic memory, independent of OC use. In an exploratory analysis, gist memory was elevated in OC users. Interestingly, we found no significant sex-related differences nor effects of OC use on mental rotation or executive control. Duration of OC use was also not related to any of our cognitive measures. These results suggest that the use of combined, monophasic OCs does not lead to many significant changes in cognition in young adults, although young females overall may have better episodic memory than young males. Additional studies, including longitudinal designs and looking in more detail at the menstrual cycle and OC use history, will further clarify the effects of different types of OCs and their duration of use on different aspects of cognition.

The pharmacotherapeutic management of premenstrual dysphoric disorder

ABSTRACT Introduction Premenstrual dysphoric disorder (PMDD) is a prevalent psychiatric condition associated with substantial mental distress, impaired psychosocial functioning, high rates of co-morbid psychiatric conditions, and elevated risk of suicide. Areas covered We provide an update on epidemiology, pathophysiology, clinical presentation, and diagnosis of PMDD, with a focus on the pharmacological management of this condition. Expert opinion Given the high rates of false positives from retrospective assessments, prospective daily symptom monitoring for a minimal of two symptomatic menstrual cycles is critical to accurately confirm (or rule out) the diagnosis of PMDD. Serotonin-based antidepressants are well-established first-line treatments of PMDD. Second-line treatment includes the use of combined, monophasic oral contraceptives. In mild to moderate cases, independent meta-analyses have shown efficacy of Chasteberry extract (Vitex agnus cactus). Preliminary results with compounds blocking the synthesis of allopregnanolone are promising.

Oral contraceptive androgenicity affects symmetry processing speed in a visuospatial working memory task

Every day millions of women worldwide take oral contraceptives (OCs). Findings of their impact on cognition are inconclusive. It is suggested that OC generation may act as a potential modulating factor driving the inconsistencies among existing studies. The current study investigated whether the androgenic activity of monophasic OCs affects working memory (WM). We compared women using androgenic second generation OCs (OC2) and anti-androgenic fourth generation OCs (OC4) in addition to naturally cycling women (NC). Participants performed a visuospatial and verbal WM task. In the visuospatial WM task, participants decided whether an abstract pattern was symmetrical or not, while simultaneously maintaining a sequence of spatial positions of a square appearing in a matrix. In the verbal WM task, participants solved simple arithmetic equations while simultaneously maintaining a sequence of letters. Our results showed that NC women and OC users (OC2+4) did not differ on central measures in either WM task. However, when the OC generation was considered, OC2 users were significantly faster in the symmetry decision subtask of the visuospatial WM task compared to OC4 and NC women. This effect was thereby independent of the ethinylestradiol level in OC users. No differences between groups were found in the various measures of the verbal WM task. Our findings add further evidence that OCs androgenicity impacts selective visuospatial processes.

P562 A Phase 1 Study Evaluating the Effect of Coadministration of Etrasimod on the Pharmacokinetics and Pharmacodynamics of a Monophasic Oral Contraceptive in Healthy Female Volunteers

Abstract Background Etrasimod (ETR) is a once-daily (QD), oral, selective sphingosine 1-phosphate receptor modulator in clinical development for immune-mediated inflammatory disorders including inflammatory bowel disease (IBD) and atopic dermatitis. At diagnosis, ~50% of patients with IBD are &amp;lt;35 years old. Oral contraceptives (OC) are the most common birth control among women in the US. It’s important to ensure an IBD therapy does not impact the pharmacokinetic (PK)/pharmacodynamic (PD) performance of the OC. This study evaluated the effect of coadministration of ETR on the PK/PD performance of a monophasic OC. Methods This open-label Phase 1 study enrolled 21 premenopausal healthy female adults (18–40 years). On Days 1–21 of Period 1 (Days 1–28), participants received OC containing 30mcg ethinylestradiol (EE) and 50mcg levonorgestrel (LVG). On Day 23, participants initiated ETR 2mg QD such that steady-state concentrations were achieved by Day 28 and thereafter. On Days 29–49 of Period 2 (Days 29–50), the OC was coadministered with ETR 2mg QD. Samples for measuring the pharmacologically active components of the OC (EE and LVG) were collected over 24 hours on Days 21 and 49. Log-transformed primary PK parameters were calculated and compared using analysis of variance with treatment as fixed effect and participant as random effect. PD markers (follicle-stimulating hormone [FSH], luteinizing hormone [LH], estradiol, progesterone) were measured at baseline (Days 1 and 29) and throughout Periods 1 and 2. Largest ovarian follicle size measured by transvaginal ultrasound (TVUS), sex hormone–binding globulin (SHBG) levels, and Hoogland score were measured on Days 1 (before OC dosing), 11, 29 (before OC+ETR dosing), and 39. Safety and tolerability were also evaluated. Results Only minor-to-mild increases in EE and LVG Cmax,ss and AUCtau,ss exposure measures were observed when the OC was coadministered with ETR vs when the OC was administered alone (Table). These changes were not considered clinically relevant. Markers of ovarian activity (FSH, LH, estradiol, progesterone, SHBG, TVUS/Hoogland score) demonstrated no clinically relevant impact of coadministration of ETR on the PD performance of the OC. All treatments were generally well tolerated. Most treatment-emergent adverse events (AEs) were mild or moderate; 2 participants had severe AEs. No abnormalities in laboratory parameters, vital signs, or 12-lead electrocardiogram assessments were noted. Conclusion The PK/PD performance of the monophasic OC was not altered to a clinically relevant extent; thus contraceptive efficacy was maintained during coadministration with ETR. ETR and the monophasic OC, administered alone or in combination, were generally well tolerated.

Influence of oral contraceptive phase on cardiorespiratory response to exercise in endurance-trained athletes

Objective The aim of the study was to analyse the cardiorespiratory response to exercise during an oral contraceptive (OC) cycle in endurance-trained women. Methods Sixteen low-dose monophasic OC pill (OCP) users performed an interval-running protocol. The protocol consisted of eight 3 min bouts at 85% of participants’ maximal aerobic speed (vV̇ o 2peak) with a 90s recovery at 30% vV̇ o 2peak in two OC phases: a withdrawal phase (WP) and an active pill phase (APP). The non-parametric Wilcoxon test was applied to analyse differences (p < 0.05) in performance variables between OC cycle phases. Results Throughout the high-intensity intervals, higher ventilation (WP 80.90 ± 11.49 L/min, APP 83.10 ± 13.33 L/min; p < 0.001) and relative perceived exertion (WP 14.51 ± 2.58, APP 15.11 ± 3.11; p = 0.001) during the APP were found, whereas carbon dioxide production (WP 2040.92 ± 262.93 mL/min, APP 2010.25 ± 305.68 mL/min; p = 0.003) was higher in the WP. During the active recovery intervals, ventilation (WP 65.78 ± 9.90 L/min, APP 67.88 ± 12.66 L/min; p < 0.001) was higher in the APP, while heart rate (WP 159.93 ± 10.26 bpm, APP 159.74 ± 12.83 bpm; p = 0.029) was higher in the WP. Conclusion An increase in ventilation occurs during the APP, which is accompanied by higher perceived exertion. Therefore, coaches and athletes should be aware of these variations, especially perceived exertion, in regard to women’s training programmes, in order to improve their performance, wellness and adherence to physical activity.

The acute effect of the menstrual cycle and oral contraceptive cycle on measures of body composition.

This study aimed to investigate the effect of fluctuating female hormones during the menstrual cycle (MC) and oral contraceptive (OC) cycle on different measures of body composition. Twenty-two women with a natural MC and thirty women currently taking combined monophasic OC were assessed over three phases of the menstrual or oral contraceptive cycle. Body weight, skinfolds, bioelectric impedance analysis (BIA), ultrasound, dual-energy X-ray absorptiometry (DXA), and peripheral quantitative computed tomography (pQCT) measurements were performed to assess body composition. Urine specific gravity (USG) was measured as an indication of hydration, and serum oestradiol and progesterone were measured to confirm cycle phases. Five participants with a natural MC were excluded based on the hormone analysis. For the remaining participants, no significant changes over the MC and OC cycle were found for body weight, USG, skinfolds, BIA, ultrasound and pQCT measures. However, DXA body fat percentage and fat mass were lower in the late follicular phase compared to the mid-luteal phase of the MC, while for the OC cycle, DXA body fat percentage was higher and lean mass lower in the early hormone phase compared with the late hormone phase. Our findings suggest that assessment of body fat percentage through BIA and skinfolds may be performed without considering the MC or OC cycle. Body adiposity assessment via DXA, however, may be affected by female hormone fluctuations and therefore, it may be advisable to perform repeat testing using DXA during the same phase of the MC or OC cycle.

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.

Effect of administration of monophasic oral contraceptive on the body composition and aerobic and anaerobic capacities of female athletes.

To examine the effects of administration of monophasic oral contraceptive (OC) on the body composition and aerobic and anaerobic capacities of female athletes. Ten female athletes (23.0 ± 4.1 years old) participated in this study. All the subjects were examined during the menstrual cycle (early follicular [EF], middle luteal [ML]) and OC cycle (inactive OC, and active OC phases). After the menstrual cycle measurements, all the subjects began taking OC. The athletes tested using a body composition, circumferences, the lactate curve test, the maximal oxygen consumption test, and the Wingate test during all phases. Waist circumference was lower during the OC cycle than menstrual cycle (P < 0.05), and the other circumferences of parts were not different during the menstrual or OC cycles. However, there were no differences in body composition before and after taking OC. The phase of the menstrual or OC cycle did not affect maximal oxygen consumption, heart rate max or power output at a blood lactate concentration of 2 and 4 mmol/L between the menstrual and OC cycle phases. Although, the peak blood lactate level after the Wingate test was higher during the OC cycle (inactive OC phase, 13.0 ± 2.4 mmol/L; active OC phase, 12.4 ± 3.0 mmol/L) than during the menstrual cycle (EF phase, 11.9 ± 2.1 mmol/L; ML phase, 11.4 ± 2.1 mmol/L; P < 0.05), the peak and average power in the Wingate test did not change during the menstrual and OC cycle phases. Administration of monophasic OC did not affect the body composition or aerobic and anaerobic capacities of female athletes.

Cardiorespiratory Variables During A Maximal Running Test In Well-trained Females With Different Hormonal Profiles

Differences in estrogen and progesterone levels along a natural menstrual cycle and an oral contraceptive (OC) cycle may influence female´s performance. Previous literature reported lower strength, maximal oxygen consumption (VO2 max) and systolic volume in OC users. According to postmenopausal women, their low and stable levels of sex hormones may affect them in a different way than in young women. PURPOSE: To elucidate the effect of different hormonal profiles on maximal VO2, heart rate (HR) and ventilation (VE) in well-trained females. METHODS: Thirty-three eumenorrheic females (30.1±6.2 years, 59.3±8.4 kg, and 164.1±6.3 cm), twenty-three monophasic OC users (24.8±4.3 years, 58.6±5.8 kg, and 163.3±5.1 cm) and thirteen postmenopausal women (51.0±3.7 years, 54.9±4.1 kg, and 161.5±5.4 cm) participated in the study. A maximal graded test with a computerized treadmill was performed. Expired gases were measured breath-by-breath with the gas analyser Jaeger Oxygen Pro. HR was continuously monitored with a 12-lead ECG. Participants began with a warm-up of 3 minutes at 6 km/h. Then, the speed was set at 8 km/h, increasing 0.2 km/h every 12 seconds until exhaustion. RESULTS: One way ANOVA reported lower values in post-menopausal females compared to the other two groups (eumenorrheic and OC users) for all variables measured: VO2 max (2924.2±389.7 ml/min for the eumenorrheic; 2808.8±366.7 ml/min for the OC; and 2455.15±281.04 ml/min for the postmenopausal; p=0.001), maximal HR (184.2±10.3; 189.9±8.4; and 172.1±12.9 bpm respectively; p<0.001) and maximal VE (111.8±17.5; 114.7±15.1; and 96.4±10.4 l/min, respectively; p=0.003). Nonetheless, no significant differences in VO2max, HR and VE were found between eumenorrheic females and OC users. CONCLUSION: The drastic decrease of sex hormones in postmenopausal females, along with other hormonal and physiological changes caused by the age, may explain the drop in VO2 max, HR and VE in this population. In terms of young women, despite literature reported lower values in OC users, the lack of difference observed in this study may be due to the lower concentrations of sex hormones that OC pills have nowadays, or because of the fact that all were well-trained participants. Funding: DEP2016-75387-P (Spanish National Plan 2013-2016)

Changes in premenstrual symptoms in women starting or discontinuing use of oral contraceptives

It is not clear whether oral contraceptive (OC) treatment affects premenstrual symptoms in women. The aim of the present study was to evaluate changes in premenstrual symptoms (PMS) in women starting to use or discontinuing the use of OCs. Twenty-four healthy women with no previous diagnosis of premenstrual dysphoric disorder were included in this study with a prospective crossover design. Nineteen women completed daily ratings of somatic and mood symptoms during two hormonally different cycles, during a normal menstrual cycle and while using OCs. The menstrual cycle phases were hormonally verified and the low-dose, monophasic OCs were used in a 21/7 regimen. The onset of OC use significantly decreased premenstrual somatic symptoms, but it did not affect mood symptoms. In the women who discontinued OC use, no significant changes in neither somatic nor mood symptoms appeared in the premenstrual phase.

To Evaluate the Difference of the Efficacy of Short or Long-Term Cyclic Low-Dose Monophasic Oral Contraceptive (OC) Hormonal Therapy in the Recurrence of Endometrioma after Surgery

To Evaluate the Difference of the Efficacy of Short or Long-Term Cyclic Low-Dose Monophasic Oral Contraceptive (OC) Hormonal Therapy in the Recurrence of Endometrioma after Surgery

Sleep Deprivation Related Changes of Plasma Oxytocin in Males and Female Contraceptive Users Depend on Sex and Correlate Differentially With Anxiety and Pain Hypersensitivity.

Disturbed sleep is known to substantially aggravate both the pain condition and the affective state of pain patients. The neurobiological mechanisms underlying these adverse effects are unknown. Oxytocin (OT), being largely involved in social and emotional behavior, is considered to also play a modulatory role in nociception. We hypothesized a pathophysiological role of OT for the hyperalgesic and anxiogenic effects of sleep loss. An established human model of one night of total sleep deprivation (TSD) was used to test this hypothesis. Twenty young healthy students (n = 10 male and n = 10 female) were investigated in a balanced cross-over design, contrasting TSD with a night of habitual sleep (HS). All females took monophasic oral contraceptives (OC) and were investigated during their ‘pill-free’ phase. Plasma OT concentrations were correlated with (1) pain thresholds, (2) descending pain inhibition, and (3) state-anxiety scores. Compared to the HS condition, the plasma OT concentration was significantly increased in sleep deprived females (p = 0.02) but not males (p = 0.69). TSD resulted in pain hypersensitivity to noxious cold (p = 0.05), noxious heat (p = 0.023), and pricking stimuli (p = 0.013) and significantly increased state-anxiety (p = 0.021). While, independent of sex, lower heat pain thresholds correlated with higher plasma OT (p = 0.036), no such associations were found for cold/mechanical pain. In sleep-deprived females, higher plasma OT showed a mild (but insignificant) association with lower pain inhibition (p = 0.093). We found a positive correlation between anxiety-scores and OT (p = 0.021), which was enhanced when respecting “sex” (p = 0.008) and “sleep” (p = 0.001) in a hierarchical regression analysis. Altogether, our study revealed a complex and partially sex-dependent correlation between plasma OT and TSD-induced changes of experimental pain and anxiety. The minor role of OT for TSD-induced changes of evoked pain, and its major involvement in anxiety, argues against a specific role of OT for linking the adverse effects of TSD on pain sensitivity and anxiety with each other. Future investigations are needed in order to dissect out the effect of OC on the sex-dependent effects of TSD observed in our study.

Oral contraceptives augment the exercise pressor reflex during isometric handgrip exercise.

We sought to determine whether oral contraception alters the gender‐related differences observed in the exercise pressor reflex during isometric handgrip exercise. Fifteen men, fifteen normally menstruating women (WomenNM), and fifteen women taking monophasic oral contraceptives (WomenOC) completed two trials of a 3‐min isometric handgrip exercise protocol performed at 30% of their maximal voluntary contraction: (1) where arterial occlusion was applied to the previously exercising arm during a 3‐min recovery period (Occlusion trial); (2) where no arterial occlusion was applied during recovery (Control trial). Handgrip exercise elicited greater increases in mean arterial pressure (MAP) in MEN compared to both female groups (P < 0.05), and in WomenOC compared to WomenNM in both trials (P = 0.01, P = 0.03). After 3 min of recovery, sBP was 12% (P = 0.01) and 9% (P = 0.02) higher in the Occlusion trial when compared to the Control trial for MEN and WomenOC. Conversely, arterial occlusion in recovery from handgrip did not sustain elevated sBP in the Occlusion trial, and sBP returned to recovery levels not different to the Control trial, in WomenNM (P = 0.41). These data indicate that gender‐related differences in the metaboreflex during isometric handgrip exercise exist between men and normally menstruating women, but are blunted when men are compared to women taking oral contraceptives. We conclude that the suppression of 17β‐estradiol and/or progestogen in women via the administration of oral contraceptives attenuates sex‐related differences in the metaboreflex during isometric handgrip exercise.

Ovarian Lipid Metabolism Modulates Circulating Lipids in Premenopausal Women

The premenopausal circulating lipid profile may be linked to the hormonal profile and ovarian lipid metabolism. Assess how estradiol, progesterone, and ovarian lipid metabolism contributes to the premenopausal lipid profile; and evaluate the acute effects of a common hormonal oral contraceptive (OC) on circulating lipids. Experimental crossover with repeated measures. Academic hospitals. Eight healthy, regularly menstruating women. Participants underwent periodic serum sampling during a normal menstrual cycle; a standard 21-day, monophasic combined hormonal OC cycle (30 µg of ethinyl estradiol and 150 µg of levonorgestrel per day); menopause simulated by leuprolide acetate (22.5-mg depot); and an artificial menstrual cycle achieved via transdermal estradiol (50 to 300 µg/d) and vaginal micronized progesterone (100 to 300 mg/d). Primary outcomes included evaluation of total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, triglycerides, and the total cholesterol to HDL cholesterol ratio. To estimate the effect of estradiol, progesterone, and ovarian lipid metabolism, all specimens except those from the OC cycle were analyzed. Subgroup analysis was conducted on the follicular and luteal phases. In a separate analysis, the effect of the OC was evaluated relative to the normal menstrual cycle. Estradiol was significantly associated with increased levels of HDL cholesterol throughout the menstrual cycle and in the follicular phase. Ovarian effects were associated with reduced lipid levels, especially during the luteal phase. The OC was associated with an increased total cholesterol to HDL cholesterol ratio and triglycerides. Previously unappreciated factors including ovarian lipid metabolism may contribute to the premenopausal lipid profile.