Population-Based Characterization of Menstrual Migraine and Proposed Diagnostic Criteria.

Importance: There is a need for better recognition and more extensive research into menstrual migraine (MM) in the general population, and a revision of the diagnostic criteria for MM is warranted to move the field forward. Increased understanding of MM is crucial for improving clinical care, diagnosis, and therapy for MM. Objectives: To assess the clinical characteristics of MM, including severity and treatment response, and to propose new diagnostic criteria for pure MM and menstrually related migraine. Design, Setting, and Participants: This is a case-control study of Danish individuals with migraine. All individuals completed a 105-item validated diagnostic migraine questionnaire, sent via the Danish electronic mailing system (e-Boks) between May and August 2020, allowing diagnosis of pure MM and menstrually related migraine by the International Classification of Headache Disorders, Third Edition (ICHD-3). Data analysis was performed from September 2021 to November 2022. Exposure: Diagnosis of migraine. Main Outcomes and Measures: Clinical characteristics of women with MM and women with nonmenstrual migraine (non-MM) were compared using the ICHD-3 diagnostic criteria. A simulation of the risk of randomly misclassifying MM was based on number of migraine attacks during 3 menstrual cycles (3 × 28 days), and simulation analyses were performed using 100 000 permutations of random migraine attacks in migraine patients. Results: A total of 12 618 individuals, including 9184 women, with migraine participated in the study. Among the women with migraine, the prevalence of MM was 16.6% (1532 women), and the prevalence of non-MM was 45.9% (4216 women). The mean (SD) age was 38.7 (8.7) years for women with MM and 37.0 (9.2) years for women with non-MM. Of the 1532 women with MM, 410 (26.8%) fulfilled ICHD-3 diagnostic criteria for pure MM, 1037 (67.7%) fulfilled ICHD-3 diagnostic criteria for menstrually related migraine, and 152 (9.9%) fulfilled proposed diagnostic criteria for rare pure MM. MM was associated with a higher frequency of migraine-accompanying symptoms (odds ratio [OR], 1.98; 95% CI, 1.71-2.29), more frequent (OR, 7.21; 95% CI, 5.77-9.03) and more severe (OR, 1.17; 95% CI, 1.13-1.21) migraine attacks, lower frequency of nonmigraine headache (OR, 0.31; 95% CI, 0.18-0.49), an overall greater response to treatment with triptans (OR, 1.66; 95% CI, 1.24-2.24), better improvement of migraine attacks during late pregnancy (OR, 5.10; 95% CI, 2.17-14.00), and faster reappearance of migraine attacks post partum (OR, 3.19; 95% CI, 2.40-4.25). Hormonal contraceptive-related MM was associated with a higher prevalence of migraine without aura than migraine related to spontaneous menstruation (OR, 1.82; 95% CI, 1.62-2.06). Otherwise, no differences between hormonal and spontaneous MM were observed. The risk of random diagnostic misclassification of ICHD-3 menstrually related migraine in women with high frequency episodic migraine was 43%. This risk was reduced to 3% when applying the proposed criteria for menstrually related migraine. Conclusions and Relevance: In this case-control study, MM in the general population had clinical characteristics that were quantitively different from those of non-MM. Detailed descriptive data and suggested improved diagnostic criteria for pure MM and menstrually related migraine were provided.

Cycling matters: Sex hormone regulation of vascular potassium channels.

Sex hormones and the reproductive cycle (estrus in rodents and menstrual in humans) have a known impact on arterial function. In spite of this, sex hormones and the estrus/menstrual cycle are often neglected experimental factors in vascular basic preclinical scientific research. Recent research by our own laboratory indicates that cyclical changes in serum concentrations of sex -hormones across the rat estrus cycle, primary estradiol, have significant consequences for the subcellular trafficking and function of KV. Vascular potassium channels, including KV, are essential components of vascular reactivity. Our study represents a small part of a growing field of literature aimed at determining the role of sex hormones in regulating arterial ion channel function. This review covers key findings describing the current understanding of sex hormone regulation of vascular potassium channels, with a focus on KV channels. Further, we highlight areas of research where the estrus cycle should be considered in future studies to determine the consequences of physiological oscillations in concentrations of sex hormones on vascular potassium channel function.

Emotion-induced brain activation across the menstrual cycle in individuals with premenstrual dysphoric disorder and associations to serum levels of progesterone-derived neurosteroids.

Premenstrual dysphoric disorder (PMDD) is a debilitating disorder characterized by severe mood symptoms in the luteal phase of the menstrual cycle. PMDD symptoms are hypothesized to be linked to an altered sensitivity to normal luteal phase levels of allopregnanolone (ALLO), a GABAA-modulating progesterone metabolite. Moreover, the endogenous 3ß-epimer of ALLO, isoallopregnanolone (ISO), has been shown to alleviate PMDD symptoms through its selective and dose-dependent antagonism of the ALLO effect. There is preliminary evidence showing altered recruitment of brain regions during emotion processing in PMDD, but whether this is associated to serum levels of ALLO, ISO or their relative concentration is unknown. In the present study, subjects with PMDD and asymptomatic controls underwent functional magnetic resonance imaging (fMRI) in the mid-follicular and the late-luteal phase of the menstrual cycle. Brain responses to emotional stimuli were investigated and related to serum levels of ovarian steroids, the neurosteroids ALLO, ISO, and their ratio ISO/ALLO. Participants with PMDD exhibited greater activity in brain regions which are part of emotion-processing networks during the late-luteal phase of the menstrual cycle. Furthermore, activity in key regions of emotion processing networks - the parahippocampal gyrus and amygdala - was differentially associated to the ratio of ISO/ALLO levels in PMDD subjects and controls. Specifically, a positive relationship between ISO/ALLO levels and brain activity was found in PMDD subjects, while the opposite was observed in controls. In conclusion, individuals with PMDD show altered emotion-induced brain responses in the late-luteal phase of the menstrual cycle which may be related to an abnormal response to physiological levels of GABAA-active neurosteroids.

Attention, response inhibition, impulsivity, and decision-making within luteal phase in women with premenstrual dysphoric disorder.

Cognitive impairment is a key feature of depressive disorder. Various forms of cognitive function have yet to be investigated in women with premenstrual dysphoric disorder (PMDD) during early luteal (EL) and late luteal (LL) phases. Therefore, we evaluated response inhibition and attention in PMDD in these two phases. We also examined the associations between cognitive functions, impulsivity, decision-making style, and irritability. There is a total of 63 female participants with PMDD and 53 controls, as determined through psychiatric diagnostic interviewing and a weekly symptoms checklist. The participants completed a Go/No-go task, Dickman's impulsivity inventory, Preference for Intuition and Deliberation scale, and the Buss-Durkee Hostility Inventory: Chinese Version-Short Form at the EL and LL phases. The women with PMDD had poorer attention in the Go trials at the LL phase and poorer response inhibition in the No-go trials at the EL and LL phases. Repeated measures analysis of variance revealed an LL exacerbation of deficit in attention among PMDD group. In addition, impulsivity negatively correlated with response inhibition at the LL phase. Preference for deliberation correlated with attention at the LL phase. Women with PMDD experienced LL declined attention and impaired response inhibition across the luteal phase. Response inhibition is linked to impulsivity. The deficit in attention links preference for deliberation among women with PMDD. These results reveal the different courses in different domains of cognitive impairment in PMDD. Further studies are required to elucidate the mechanism underlying cognitive dysfunction in PMDD.

Characterization of Self-reported Improvements in Knowledge and Health Among Users of Flo Period Tracking App: Cross-sectional Survey.

BACKGROUND: Research shows that poor knowledge and awareness of menstrual and pregnancy health among women are associated with adverse reproductive health and pregnancy outcomes. Menstrual cycle- and pregnancy-tracking mobile apps are promising tools for improving women's awareness of and attitudes toward their reproductive health; however, there is little information about subscribers' perceptions of app functionality and its impact on their knowledge and health. OBJECTIVE: This study aimed to explore knowledge and health improvements related to menstrual cycle and pregnancy, as well as improvements in general health among Flo app users. We also investigated what components of the Flo app were associated with the abovementioned improvements and evaluated whether those improvements differed based on education level, country of residence (low- and middle-income vs high-income countries), free or premium subscription to the app, short- or long-term use of the app, and frequency of use. METHODS: Flo subscribers who had been using the app for no less than 30 days, completed a web-based survey. A total of 2212 complete survey responses were collected. The survey included demographic questions and questions about motivations guiding the use of the Flo app and which components of the app improved their knowledge and health, as well as to what extent. RESULTS: Most study participants reported improvements in menstrual cycle (1292/1452, 88.98%) and pregnancy (698/824, 84.7%) knowledge from Flo app use. Participants with higher levels of education and those from high-income countries reported using the app predominantly for getting pregnant (χ21=4.2, P=.04; χ21=52.3, P<.001, respectively) and pregnancy tracking (χ21=19.3, P<.001; χ21=20.9, P=.001, respectively). Participants with less education reported using the app to avoid pregnancy (χ21=4.2; P=.04) and to learn more about their body (χ21=10.8; P=.001) and sexual health (χ21=6.3; P=.01), while participants from low- and middle-income countries intended to mainly learn more about their sexual health (χ21=18.2; P<.001). Importantly, the intended use of the app across education levels and country income levels matched areas in which they had gained knowledge and achieved their health goals upon use of the Flo app. Period, fertile days, and ovulation predictions as well as symptom tracking were consistently the top 3 components in the app that helped users with their cycle knowledge and general health. Reading articles or watching videos helped with users' education regarding their pregnancy. Finally, the strongest improvements in knowledge and health were observed in premium, frequent, and long-term users. CONCLUSIONS: This study suggests that menstrual health apps, such as Flo, could present revolutionary tools to promote consumer health education and empowerment on a global scale.

Double stimulation for the management of poor-prognosis patients: where are we going?

PURPOSE OF REVIEW: The technical improvements in IVF allowed the implementation of nonconventional ovarian stimulation protocols for some specific patients. Where time is crucial, such as with oncologic patients, poor-prognosis patients, patients with low ovarian reserve, and those with advanced maternal age, access to IVF treatment is even more critical. Some of these protocols might start in the late follicular phase, luteal phase, or involve both stimulations within the same ovarian cycle. RECENT FINDINGS: Until now, published evidence showed that oocytes retrieved from unconventional protocol seem to be developmentally, genetically, and reproductively competent. Second stimulation in the same ovarian cycle after the conventional approach may represent a sound alternative to oocyte accumulation. This can be proposed in progress after careful counselling focused on the patients' chances of finding at least one euploid embryo on account of their age and of the number of blastocysts obtained after the conventional approach. SUMMARY: The adoption of these new strategies, known as double stimulation protocol, can be conceived as a real full-personalization of ovarian stimulation. Multicentre prospective RCTs are urgently needed to evaluate the efficacy, efficiency, and costs of double stimulation versus two consecutive conventional approaches with standard or mild stimulation and in a different IVF setting.

Sexual attraction to visual sexual stimuli in association with steroid hormones across menstrual cycles and fertility treatment.

BACKGROUND: Steroid hormones (i.e., estradiol, progesterone, and testosterone) are considered to play a crucial role in the regulation of women's sexual desire and sexual attraction to sexual stimuli throughout the menstrual cycle. However, the literature is inconsistent, and methodologically sound studies on the relationship between steroid hormones and women's sexual attraction are rare. METHODS: This prospective longitudinal multisite study examined estradiol, progesterone, and testosterone serum levels in association with sexual attraction to visual sexual stimuli in naturally cycling women and in women undergoing fertility treatment (in vitro fertilization, IVF). Across ovarian stimulation of fertility treatment, estradiol reaches supraphysiological levels, while other ovarian hormones remain nearly stable. Ovarian stimulation hence offers a unique quasi-experimental model to study concentration-dependent effects of estradiol. Hormonal parameters and sexual attraction to visual sexual stimuli assessed with computerized visual analogue scales were collected at four time points per cycle, i.e., during the menstrual, preovulatory, mid-luteal, and premenstrual phases, across two consecutive menstrual cycles (n = 88 and n = 68 for the first and second cycle, respectively). Women undergoing fertility treatment (n = 44) were assessed twice, at the beginning and at the end of ovarian stimulation. Sexually explicit photographs served as visual sexual stimuli. RESULTS: In naturally cycling women, sexual attraction to visual sexual stimuli did not vary consistently across two consecutive menstrual cycles. While in the first menstrual cycle sexual attraction to male bodies, couples kissing, and at intercourse varied significantly with a peak in the preovulatory phase, (all p ≤ 0.001), there was no significant variability across the second cycle. Univariable and multivariable models evaluating repeated cross-sectional relationships and intraindividual change scores revealed no consistent associations between estradiol, progesterone, and testosterone and sexual attraction to visual sexual stimuli throughout both menstrual cycles. Also, no significant association with any hormone was found when the data from both menstrual cycles were combined. In women undergoing ovarian stimulation of IVF, sexual attraction to visual sexual stimuli did not vary over time and was not associated with estradiol levels despite intraindividual changes in estradiol levels from 122.0 to 11,746.0 pmol/l with a mean (SD) of 3553.9 (2472.4) pmol/l. CONCLUSIONS: These results imply that neither physiological levels of estradiol, progesterone, and testosterone in naturally cycling women nor supraphysiological levels of estradiol due to ovarian stimulation exert any relevant effect on women's sexual attraction to visual sexual stimuli.

Vestibular Disorders and Hormonal Dysregulations: State of the Art and Clinical Perspectives.

The interaction between endocrine and vestibular systems remains poorly documented so far, despite numerous observations in humans and animals revealing direct links between the two systems. For example, dizziness or vestibular instabilities often accompany the menstrual cycle and are highly associated with the pre-menopause period, while sex hormones, together with their specific receptors, are expressed at key places of the vestibular sensory network. Similarly, other hormones may be associated with vestibular disorders either as causal/inductive factors or as correlates of the pathology. This review was carried out according to the PRISMA method, covering the last two decades and using the MEDLINE and COCHRANE databases in order to identify studies associating the terms vestibular system and/or vestibular pathologies and hormones. Our literature search identified 646 articles, 67 of which referred directly to vestibular dysfunction associated with hormonal variations. While we noted specific hormonal profiles depending on the pathology considered, very few clinical studies attempted to establish a direct link between the expression of the vestibular syndrome and the level of circulating hormones. This review also proposes different approaches to shed new light on the link between hormones and vestibular disorders, and to improve both the diagnosis and the therapeutic management of dizzy patients.

Knee Laxity in the Menstrual Cycle after Anterior Cruciate Ligament Reconstruction: A Case Series.

The aim of this study was to compare anterior knee laxity (AKL), genu recurvatum (GR), and muscle stiffness between reconstructed and contralateral sides in females who underwent anterior cruciate ligament (ACL) reconstruction during early follicular and ovulatory phases. AKL was measured as an anterior displacement of the tibia using a KS measure. GR was measured as the range of motion of knee hyperextension using a hyperextension apparatus. Muscle stiffness was measured for semitendinosus (ST) and biceps femoris long head (BF) using a MyotonPRO. The study investigated eighteen knees in nine females (Age, 20.4 ± 1.5 years; BMI, 21.5 ± 1.5) with normal menstrual cycles at least 1 year after reconstruction using hamstring autograft. E2 (Estradiol) concentration did not differ between the two phases, but AKL on the reconstructed side was lower during the ovulatory phase (8.3 [5.9-9.3] mm) than during the early follicular phase (9.4 [7.3-9.7] mm) (p = 0.044, r = 0.756), whereas there was no significant difference between the two phases on the contralateral side. AKL side-to-side difference, GR, and muscle stiffness (ST and BF) on both sides did not differ in either phase. These results indicate that AKL may behave differently on the reconstructed and contralateral sides during the menstrual cycle.

Reduced model for female endocrine dynamics: Validation and functional variations.

A normally functioning menstrual cycle requires significant crosstalk between hormones originating in ovarian and brain tissues. Reproductive hormone dysregulation may cause abnormal function and sometimes infertility. The inherent complexity in this endocrine system is a challenge to identifying mechanisms of cycle disruption, particularly given the large number of unknown parameters in existing mathematical models. We develop a new endocrine model to limit model complexity and use simulated distributions of unknown parameters for model analysis. By employing a comprehensive model evaluation, we identify a collection of mechanisms that differentiate normal and abnormal phenotypes. We also discover an intermediate phenotype-displaying relatively normal hormone levels and cycle dynamics-that is grouped statistically with the irregular phenotype. Results provide insight into how clinical symptoms associated with ovulatory disruption may not be detected through hormone measurements alone.

The Effect of Menstrual-Cycle Phase on Immune Responses to a 5-km Cycling Time Trial: An Exploratory Study.

PURPOSE: Exercise has transient effects on the immune system that could influence infection risk and tissue recovery after exercise. Little is known about how the menstrual cycle interacts with the immune responses to acute exercise. This exploratory study sought to evaluate the effect of menstrual-cycle phase on peripheral blood mononuclear cell counts before and immediately after a bout of intense aerobic exercise. METHODS: Seven naturally menstruating women (age: 27 [3] y) completed three 5-km cycling time trials coinciding with the early-follicular, late-follicular, and mid-luteal stage, confirmed by hormonal measurement. Venous blood samples were taken and examined for the presence of immune cell types using flow cytometry. RESULTS: Reductions in circulating CCR7+CD45RA+ naïve CD4+ T cells, CD4+CD25+ regulatory T cells, and CD56+CD57+ natural killer cells observed during the early-follicular phase were attenuated when exercise was performed during the late-follicular phase. Similarly, reductions in circulating CD56+CD57+ natural killer cells and CD14+TLR4+ monocytes following exercise in the early-follicular phase were abolished when exercise was performed in the midluteal phase. CONCLUSIONS: These preliminary findings indicate that the effect of acute high-intensity exercise on immune-cell mobilization and activation varies across the menstrual cycle, potentially impacting the anti-inflammatory effects of regulatory T cells and the cell-mediated effects of both natural killer CD57+ cells and monocytes expressing TLR4.

Oral contraceptive use and menstrual cycle influence acute cerebrovascular response to standing.

PURPOSE: To determine if the menstrual cycle and oral contraceptives (OC) influence responses to acute orthostatic stress and if these factors are clinically relevant to the diagnosis of initial orthostatic hypotension (iOH). METHODS: Young, healthy women were recruited, including OC users (n = 12) and non-users (NOC; n = 9). Women were tested during the low hormone (LH; placebo pills; days 2-5 natural cycle) and high hormone (HH; active dose; days 18-24 natural cycle) menstrual phases. Changes in mean arterial pressure, cardiac output, heart rate, the 30:15 heart rate ratio and cerebrovascular resistance indices within 30 s of standing were examined. RESULTS: There were no effects of OC or menstrual cycle on hemodynamic responses during standing (all p>0.05). In the LH phase, OC users had a greater fall in mean middle cerebral artery blood velocity (MCAV) compared to NOC (p<0.05). However, this was reversed in the HH phase, where OC users had a reduced fall in mean MCAV (p<0.05). Interestingly, 8 women (OC and NOC) had drops in systolic/diastolic blood pressure meeting the criteria for iOH, and 7 of those 8 women displayed this drop in a single phase of the menstrual cycle. CONCLUSION: Our results indicate that chronic versus acute OC use (i.e., long-term use observed via LH phase versus short-term use observed via HH phase) have opposing effects on cerebral blood velocity during standing. Further, our results highlight that multiple assessments across the cycle may be necessary to accurately diagnose iOH, as most women met the diagnostic criteria during a single menstrual phase.

Menstrual cycle phases, sex hormones and hand preference modulate nerve conduction velocity in healthy subjects.

The aim of the present study was to investigate the relationship between hand preference and electrophysiological parameters in women menstrual cycle phases and men. Our study was conducted on 25 healthy, naturally cycling females and 30 healthy males between the ages of 18 and 25 who participated voluntarily. The female participants completed three test sessions (early follicular phase, the late follicular phase, and the luteal phase). We measured sex hormone concentrations in blood samples collected. Nerve conduction velocity was calculated using electromyography by stimulating the median nerves of the left and right hands of both the male and female participants. The median nerve conduction velocities of the dominant hands of both the males and females were higher than those of the non-dominant hands. The median nerve conduction velocity during the follicular phase of both the right-handed and left-handed females was higher than in the right-handed and left-handed males, while the latency was shorter. When we evaluated the nerve conduction velocities of the participants, we observed the effects of sexual dimorphism and lateralization. The findings suggested that nerve conduction velocity was found to be affected during the phases of the menstrual cycle in healthy female volunteers.

Altered visual cortex excitability in premenstrual dysphoric disorder: Evidence from magnetoencephalographic gamma oscillations and perceptual suppression.

Premenstrual dysphoric disorder (PMDD) is a psychiatric condition characterized by extreme mood shifts during the luteal phase of the menstrual cycle (MC) due to abnormal sensitivity to neurosteroids and unbalanced neural excitation/inhibition (E/I) ratio. We hypothesized that in women with PMDD in the luteal phase, these factors would alter the frequency of magnetoencephalographic visual gamma oscillations, affect modulation of their power by excitatory drive, and decrease perceptual spatial suppression. Women with PMDD and control women were examined twice-during the follicular and luteal phases of their MC. We recorded visual gamma response (GR) while modulating the excitatory drive by increasing the drift rate of the high-contrast grating (static, 'slow', 'medium', and 'fast'). Contrary to our expectations, GR frequency was not affected in women with PMDD in either phase of the MC. GR power suppression, which is normally associated with a switch from the 'optimal' for GR slow drift rate to the medium drift rate, was reduced in women with PMDD and was the only GR parameter that distinguished them from control participants specifically in the luteal phase and predicted severity of their premenstrual symptoms. Over and above the atypical luteal GR suppression, in both phases of the MC women with PMDD had abnormally strong GR facilitation caused by a switch from the 'suboptimal' static to the 'optimal' slow drift rate. Perceptual spatial suppression did not differ between the groups but decreased from the follicular to the luteal phase only in PMDD women. The atypical modulation of GR power suggests that neuronal excitability in the visual cortex is constitutively elevated in PMDD and that this E/I imbalance is further exacerbated during the luteal phase. However, the unaltered GR frequency does not support the hypothesis of inhibitory neuron dysfunction in PMDD.

Endometrial microstimulation effects on endometrial receptivity assessed by transvaginal color Doppler sonography.

OBJECTIVE: This study investigated the effect of endometrial microstimulation (EM) on endometrial receptivity using transvaginal color Doppler sonography (TVCDS). METHOD: Women of childbearing age who were preparing to conceive (n = 90) were randomly divided into the EM group (n = 30), who were examined by EM on days 3-5 of the menstrual cycle, and the control group (n = 60). TVCDS was conducted during the implantation window phase, and endometrial thickness, endometrial pattern, endometrial movement, blood flow type, and uterine and spiral arterial hemodynamic parameter measurements were made. The groups were compared to identify differences. RESULTS: Endometrial thickness (0.97 ± 0.18 cm and 0.95 ± 0.17 cm), endometrial movement (type 1: 46.7% and 51.7%; type 2: 30.0% and 28.3%; type 3: 6.7% and 5.0%; type 5: 16.7% and 15.0%), and hemodynamic parameters of the uterine (pulsatility index [PI]: 2.46 ± 0.50 and 2.41 ± 0.48; resistance index [RI]: 0.85 ± 0.05 and 0.84 ± 0.05) and spiral (PI: 1.11 ± 0.32 and 1.19 ± 0.33; RI: 0.48 ± 0.11 and 0.51 ± 0.08) arteries did not differ significantly between groups (P > 0.05). However, the endometrial pattern (a trilaminar pattern: 80.0% and 58.3%; P = 0.041) and blood flow type (type I: 16.7% and 43.3%; type II: 63.3% and 40.0%; type III 20.0% and 16.7%; P = 0.038) differed significantly between groups. CONCLUSION: Endometrial microstimulation did not alter endometrial pathological staging, endometrial thickness, or movement, nor did it affect uterine and spiral arterial blood flow parameters. However, it may be able to abrade abnormal endometrial tissue, optimizing the endometrial pattern. Endometrial microstimulation may support local spiral artery regeneration and increase endometrial blood supply in new cycles.

Ovarian hormones in relation to naturally cycling women's conception risk: Empirical evidence and implications for behavioral endocrinology.

A substantial body of literature has examined how women's psychology and behavior vary as a function of conception risk across the ovarian cycle. These effects are widely believed to be outcomes of hormonal regulation, in particular effects of estrogens (E) and progesterone (P). Increasingly, researchers have sought to test predictions about how psychological processes or behavior vary as a function of conception risk by examining associations with estrogen (e.g., estradiol) and progesterone levels. Yet issues regarding how best to assess these associations arise. Should hormone levels be log-transformed? Do hormone ratios best capture their joint effects? How important are hormone interactions? How should outliers be treated? Across two large datasets, we examined hormonal predictors of conception risk, estimated from day of a luteinizing hormone (LH) surge. Log-transformed E and P levels predicted conception risk better than raw E and P levels did. The raw E/P ratio was a relatively poor predictor, whereas the log-transformed ratio (ln[E/P]) was a relatively good predictor. E × P interactions were detected but weak. Outliers were frequent, especially in distributions of raw hormone levels. Hormone measures predicted two psychological outcomes in these datasets-sexual desire and preferences for strength and muscularity-in parallel to how strongly they predicted conception risk. These results give rise to several recommendations regarding treatment of hormone measures and their use in analyses.

Menstrual cycle affects iron homeostasis and hepcidin following interval running exercise in endurance-trained women.

PURPOSE: Menstrual cycle phase affects resting hepcidin levels, but such effects on the hepcidin response to exercise are still unclear. Thus, we investigated the hepcidin response to running during three different menstrual cycle phases. METHODS: Twenty-one endurance-trained eumenorrheic women performed three identical interval running protocols during the early-follicular phase (EFP), late-follicular phase (LFP), and mid-luteal phase (MLP). The protocol consisted of 8 × 3 min bouts at 85% of the maximal aerobic speed, with 90-s recovery. Blood samples were collected pre-exercise and at 0 h, 3 h and 24 h post-exercise. RESULTS: Data presented as mean ± SD. Ferritin were lower in the EFP than the LFP (34.82 ± 16.44 vs 40.90 ± 23.91 ng/ml, p = 0.003), while iron and transferrin saturation were lower during the EFP (58.04 ± 19.70 µg/dl, 14.71 ± 5.47%) compared to the LFP (88.67 ± 36.38 µg/dl, 22.22 ± 9.54%; p < 0.001) and the MLP (80.20 ± 42.05 µg/dl, 19.87 ± 10.37%; p = 0.024 and p = 0.045, respectively). Hepcidin was not affected by menstrual cycle (p = 0.052) or menstrual cycle*time interaction (p = 0.075). However, when comparing hepcidin at 3 h post-exercise, a moderate and meaningful effect size showed that hepcidin was higher in the LFP compared to the EFP (3.01 ± 4.16 vs 1.26 ± 1.25 nMol/l; d = 0.57, CI = 0.07-1.08). No effect of time on hepcidin during the EFP was found either (p = 0.426). CONCLUSION: The decrease in iron, ferritin and TSAT levels during the EFP may mislead the determination of iron status in eumenorrheic athletes. However, although the hepcidin response to exercise appears to be reduced in the EFP, it shows no clear differences between the phases of the menstrual cycle (clinicaltrials.gov: NCT04458662).

Muscle Performance during the Menstrual Cycle Correlates with Psychological Well-Being, but Not Fluctuations in Sex Hormones.

PURPOSE: We aimed to study variations in strength and power performance during the menstrual cycle (MC) in eumenorrheic young women and during the pill cycle in oral contraceptives (OC) users. METHODS: Forty healthy, normal-weight women between 18 and 35 yr (n = 30 eumenorrheic women; n = 10 OC users) completed this prospective cohort study. Seven to nine times during the MC/pill-cycle, the participants completed a physical performance test series, a questionnaire about psychological well-being, blood sampling, and determination of body mass. The physical tests included isometric handgrip strength, elbow flexor strength, countermovement jump (CMJ) height, and a 10-s Wingate bike test. RESULTS: No direct correlation was observed between the variations in sex hormones and physical performance parameters. However, positive correlations were observed between physical performance outcomes and self-reported motivation, perception of own physical performance level, pleasure level, and arousal level. CMJ was 6% lower in the late luteal phase (LL) compared with the midluteal phase (ML) (P = 0.04). Wingate peak power was 3% lower in early follicular (EF) compared with the ML (P = 0.04). Furthermore, Wingate average power was 2%-5% lower in LL compared with all other MC phases. In line with these observations, physical pain was higher in EF and LL, and the pleasure level was lower in EF compared with the other MC phases. In OC users, we observed no variation in performance and self-reported parameters between the placebo-pill phase and the OC-pill phase. CONCLUSIONS: Impairments in CMJ and Wingate performance were observed at the end and start of MC compared with other MC phases, which were associated with lower psychological well-being, but not the sex hormone fluctuations.