Social Stress during the Estrus or Luteal Phase in Sheep.

In mammals, progesterone and estrogens affect the stress response. The study aimed to compare the physiological and behavioral responses to the social isolation of ewes during the estrus or luteal phase. Estrous and diestrous ewes (n = 10 and 8 respectively) were individually isolated in a novel place for 10 min. Ewes' behavior was recorded during the test. Cortisol, blood proteins and glucose concentrations, and the skin surface temperature were determined before and after the test. Cortisol increased immediately after the test ended (P = 0.02). Serum total protein (P = 0.02), globulin (P < 0.0001), and plasma glucose (P = 0.006) concentrations were greater in estrus than in the luteal phase. The abdominal skin surface temperature was greater during estrus than during the luteal phase (P = 0.02). Ewes in estrus spent more time standing up immobile than ewes in the luteal phase (P = 0.05). In conclusion, the physiological and behavioral responses changed according to the phase of the estrous cycle. These results highlight the need for future studies focusing on how reproductive status influences the stress response to different management practices in sheep.

Selective attention towards infants in nulliparous women across the menstrual cycle.

Research in women showed that testosterone is associated with decreased selective attention towards infant stimuli, which can be compensated for by oxytocin administration. In theory, caregiving behavior is thought to be mediated by oxytocin. Oxytocin binds to dopaminergic neurons and thus supposedly motivates aspects of caregiving through its influence on dopaminergic transmission. Most previous studies on caregiving behaviors were thereby performed in women under hormonal contraception to avoid hormonal fluctuations. However, recent studies repeatedly demonstrated decisive influences of the hormonal changes across the female menstrual cycle on dopamine-mediated behaviors, suggesting that estradiol acts as dopamine agonist in the follicular phase and progesterone as dopamine antagonist in the luteal phase. In the present study, we investigated selective attention towards infants as one central aspect of caregiving behavior over the natural menstrual cycle and in relation to interindividual differences of estradiol and progesterone. As expected, we found that women with higher estradiol in the follicular phase also showed higher selective attention towards infant faces among adult distractors, whereas the correlation disappeared in the luteal phase. In contrast, progesterone did not correlate with selective attention towards infants. The present findings collectively support the assumption that estradiol may act as dopamine agonist in the follicular phase, thereby supposedly promoting an important aspect of caretaking behavior.

Luteal Phase Defects and Progesterone Supplementation.

Importance: Luteal phase defects (LPDs), or an insufficiency of progesterone production during the luteal phase of the menstrual cycle, have been identified as a potential cause of recurrent pregnancy loss (RPL), but its exact contribution to RPL is not well-defined. In addition, the role of exogenous progesterone supplementation during pregnancy remains controversial. Objective: The goal of this review is to provide an updated, evidence-based summary of LPD, including prevalence and potential pathophysiologic mechanisms, and to explore the current controversies regarding progesterone supplementation for management and treatment of RPL. Evidence Acquisition: A literature review identified relevant research using a PubMed search, Cochrane summaries, review articles, textbook chapters, databases, and society guidelines. Results: Endogenous progesterone plays a crucial role in the first trimester of pregnancy, and therefore, insufficiency may contribute to RPL. However, the precise relationship between LPD and RPL remains unclear. Luteal phase defect is primarily a clinical diagnosis based on a luteal phase less than 10 days. Although there may be a possibility of incorporating a combined clinical and biochemical approach in defining LPD, the current lack of validated diagnostic criteria creates a challenge for its routine incorporation in the workup of infertility. Moreover, no treatment modality has demonstrated efficacy in improving fertility outcomes for LPD patients, including progesterone supplementation, whose inconsistent data do not sufficiently support its routine use, despite its minimal risk. It is imperative that women diagnosed with LPD should be worked up for other potential conditions that may contribute to a shortened luteal phase. Future work needs to focus on identifying a reproducible diagnostic test for LPD to guide treatment. Conclusions and Relevance: Currently, the perceived relationship between LPD and RPL is challenged by conflicting data. Therefore, patients with an abnormal luteal phase should undergo a thorough workup to address any other potential etiologies. Although supplemental progesterone is commonly utilized for treatment of LPD and RPL, inconsistent supporting data call for exogenous hormone therapy to be only used in a research setting or after a thorough discussion of its shortcomings.

Luteal phase support in assisted reproductive technology.

Infertility affects one in six couples, with in vitro fertilization (IVF) offering many the chance of conception. Compared to the solitary oocyte produced during the natural menstrual cycle, the supraphysiological ovarian stimulation needed to produce multiple oocytes during IVF results in a dysfunctional luteal phase that can be insufficient to support implantation and maintain pregnancy. Consequently, hormonal supplementation with luteal phase support, principally exogenous progesterone, is used to optimize pregnancy rates; however, luteal phase support remains largely 'black-box' with insufficient clarity regarding the optimal timing, dosing, route and duration of treatment. Herein, we review the evidence on luteal phase support and highlight remaining uncertainties and future research directions. Specifically, we outline the physiological luteal phase, which is regulated by progesterone from the corpus luteum, and evaluate how it is altered by the supraphysiological ovarian stimulation used during IVF. Additionally, we describe the effects of the hormonal triggers used to mature oocytes on the degree of luteal phase support required. We explain the histological transformation of the endometrium during the luteal phase and evaluate markers of endometrial receptivity that attempt to identify the 'window of implantation'. We also cover progesterone receptor signalling, circulating progesterone levels associated with implantation, and the pharmacokinetics of available progesterone formulations to inform the design of luteal phase support regimens.

Does the interplay of emotion-related personality traits and reproductive hormones predict individual variation in emotion recognition?

Person-related variation has been identified in many socio-cognitive domains, and there is evidence for links between certain personality traits and individual emotion recognition. Some studies, utilizing the menstrual cycle as a hormonal model, attempted to demonstrate that hormonal fluctuations could predict variations in emotion recognition, but with merely inconsistent findings. Remarkably, the interplay between hormone fluctuations and other person-related factors that could potentially influence emotion recognition remains understudied. In the current study, we examined if the interactions of emotion-related personality traits, namely openness, extraversion, and neuroticism, and the ovulatory cycle predict individual variation in facial emotion recognition in healthy naturally cycling women. We collected salivary ovarian hormones measures from N = 129 (n = 72 validated via LH test) women across their late follicular and mid-luteal phases of the ovulatory cycle. The results revealed a negative association between neuroticism scores and emotion recognition when progesterone levels (within-subject) were elevated. However, the results did not indicate a significant moderating influence of neuroticism, openness, and extraversion on emotion recognition across phases (late follicular vs. mid-luteal) of the menstrual cycle. Additionally, there was no significant interaction between openness or extraversion and ovarian hormone levels in predicting facial emotion recognition. The current study suggests future lines of research to compare these findings in a clinical setting, as both neuroticism and ovarian hormone dysregulation are associated with some psychiatric disorders such as premenstrual dysphoric disorder (PMDD).

The Influence of Menstrual-Cycle Phase on Measures of Recovery Status in Endurance Athletes: The Female Endurance Athlete Project.

PURPOSE: To investigate the influence of menstrual-cycle (MC) phase on measures of recovery status, that is, resting heart rate, perceived sleep quality, and physical and mental readiness to train, among female endurance athletes. METHODS: Daily data were recorded during 1 to 4 MCs (ie, duration ≥21 and ≤35 d, ovulatory, luteal phase ≥10 d) of 41 trained-to-elite-level female endurance athletes (mean [SD]: age 27 [8] y, weekly training: 9 [3] h). Resting heart rate was assessed daily using a standardized protocol, while perceived sleep quality and physical and mental readiness to train were assessed using a visual analog scale (1-10). Four MC phases (early follicular phase [EFP], late follicular phase, ovulatory phase, and midluteal phase [MLP]) were determined using the calendar-based counting method and urinary ovulation-prediction test. Data were analyzed using linear mixed-effects models. RESULTS: Resting heart rate was significantly higher in MLP (1.7 beats·min-1, P = .006) compared with EFP without significant differences between the other MC phases. Perceived sleep quality was impaired in MLP compared with late follicular phase (-0.3, P = .035). Physical readiness to train was lower both in ovulatory phase (-0.6, P = .015) and MLP (-0.5, P = .026) compared with EFP. Mental readiness to train did not show any significant differences between MC phases (P > .05). CONCLUSIONS: Although significant, the findings had negligible to small effect sizes, indicating that MC phase is likely not the main determinant of changes in measures of recovery status but, rather, one of the many possible stressors.

The Effect of Different Luteal Phase Support Applications on Clinical Pregnancy Outcomes in Frozen-Thawed Embryo Transfer.

Purpose: During the frozen-thawed embryo transfer (FET) method, controlled ovarian hyperstimulation is used. At the same time, progesterone support is given for luteal phase support. In this study, we investigated the effects of various luteal phase support agents administered orally, intramuscularly (IM), and vaginally during FET on pregnancy rates. Methods: The files of 166 patients between the ages of 21 and 44 in the Assisted Reproductive Techniques Center of Acibadem Mehmet Ali Aydinlar University Atakent Hospital were analyzed retrospectively between 2016 and 2022. The patients' FSH, LH, E2, P4, AMH, and TSH levels were measured. The GnRH antagonist protocol was initiated on the 2nd or 3rd day of menstruation. Three types of progesterone agents were used in females with PCOS. Three different methods were applied: 50 mg/ml of IM progesterone daily, 90 mg of progesterone gel 2∗1 vaginally, and dydrogesterone acetate tb. orally 3∗1. FET was performed on women who received 21 days of treatment by thawing 5th-day embryos. B-hCG was performed on the 12th day after the transfer, and evaluations were made. The study results were evaluated as follows: for the whole study group, for those <30 years of age, for those 30-35 years of age, and for those >35 years of age. Results: A total of 164 patients, 57 females using vaginal progesterone gel, 30 females using oral progesterone tablet, and 77 females using IM progesterone, who met the inclusion criteria, were included in the study. The pregnancy outcomes of IM progesterone application were statistically significantly higher in the entire study group and the >35 age group when compared to the vaginal progesterone gel application. It was found that the pregnancy outcomes of IM progesterone application increased statistically significantly in the <30 age group when compared to outcomes in the other groups, using vaginal progesterone gel and oral progesterone tb. Conclusions: We found that IM progesterone application was more effective than vaginal progesterone gel application for luteal phase support. Many randomized controlled, especially live birth rate studies, are required before results can more closely approximate those for the general population.

Influence of the starting day of luteal phase stimulation on double stimulation cycles.

Background: Double ovarian stimulation is one of the most used strategies in poor-prognosis patients. There is a high heterogeneity between the studies regarding the execution of this stimulation protocol. The aim of this study was to investigate whether the day on which luteal phase stimulation begins after the first oocyte retrieval affects ovarian response in DuoStim cycles. Methods: This observational and retrospective study included 541 DuoStim cycles between January 2018 and December 2021 in a private fertility clinic. Patients were assigned to 4 groups according to the timing of the onset of luteal phase stimulation after oocyte retrieval (0-2nd day, 3rd day, 4th day and 5th-6th day). The primary outcome was the number of oocytes retrieved in the luteal phase in each group. Results: No differences were found between groups in the number of oocytes collected (5.12 ± 3.56 vs. 5.39 ± 3.74 vs. 5.61 ± 3.94 vs. 5.89 ± 3.92; p=0,6), MII or number of follicles. An increase in the duration of stimulation was found when stimulation started on the 4th day (10.42 ± 2.31 vs. 10.68 ± 2.37 vs. 11.27 ± 2.40 vs. 10.65 ± 2.37 days, p=0,033). A lower number of fertilized oocytes was observed when stimulation began before the fourth day (3.36 ± 2.80 vs. 3.95 ± 2.53 vs. 4.03 ± 2.73 vs. 4.48 ± 3.11; p=0,036). The number of blastocysts was higher when the stimulation started 5-6 days after retrieval (1.82 ± 1.74 vs. 2.13 ± 1.61 vs. 2.33 ± 2.06 vs. 2.91 ± 2.39; p= 0,030). Discussion: The number of oocytes retrieved does not differ depending on the day that stimulation begins. However, oocytes competence in terms of fertilized oocytes and blastulation, appears to be lower when the second stimulation starts before the fourth day after oocyte retrieval.

GABA-ergic Modulators: New Therapeutic Approaches to Premenstrual Dysphoric Disorder.

Premenstrual dysphoric disorder (PMDD) is characterized by the predictable onset of mood and physical symptoms secondary to gonadal steroid fluctuation during the luteal phase of the menstrual cycle. Although menstrual-related affective dysfunction is responsible for considerable functional impairment and reduction in quality of life worldwide, currently approved treatments for PMDD are suboptimal in their effectiveness. Research over the past two decades has suggested that the interaction between allopregnanolone, a neurosteroid derivative of progesterone, and the gamma-aminobutyric acid (GABA) system represents an important relationship underlying symptom genesis in reproductive-related mood disorders, including PMDD. The objective of this narrative review is to discuss the plausible link between changes in GABAergic transmission secondary to the fluctuation of allopregnanolone during the luteal phase and mood impairment in susceptible individuals. As part of this discussion, we explore promising findings from early clinical trials of several compounds that stabilize allopregnanolone signaling during the luteal phase, including dutasteride, a 5-alpha reductase inhibitor; isoallopregnanolone, a GABA-A modulating steroid antagonist; and ulipristal acetate, a selective progesterone receptor modulator. We then reflect on the implications of these therapeutic advances, including how they may promote our knowledge of affective regulation more generally. We conclude that these and other studies of PMDD may yield critical insight into the etiopathogenesis of affective disorders, considering that (1) symptoms in PMDD have a predictable onset and offset, allowing for examination of affective state kinetics, and (2) GABAergic interventions in PMDD can be used to better understand the relationship between mood states, network regulation, and the balance between excitatory and inhibitory signaling in the brain.

Effect of stress on spatial working memory and EEG signal dynamics in the follicular and luteal phases of the menstrual cycle in young single girls.

AIM: Women undergo behavioral changes during the menstrual cycle. This study aimed to investigate the effect of estradiol (Es) on stress and effect of stress on spatial working memory (WM) and also to investigate electroencephalogram (EEG) signal's dynamics in the early and late follicular (EF and LF) and luteal (LU) phases of unmarried girls' menstrual cycle. METHODS: Stress was induced by presentation of a short (3 min) movie clip. Simultaneous with a memory test and stress induction, EEG, serum Es levels, and galvanic skin response (GSR) were assessed. RESULTS: Serum Es concentrations were decreased in LF, LU, and EF phases. The mean GSR score decreased after stress induction in all three phases, but it increased in the LF and LU phases versus the EF phase. Spatial WM diminished after stress induction in all three phases, but it increased in the LF phase versus the two phases before and after stress induction. Average power spectrum density in all frequency bands increased after stress induction in the frontal and prefrontal channels in the spatial WM test. CONCLUSION: The results showed that stress led to spatial WM dysfunction; however, Es improved spatial WM performance in the LF phase versus the other two phases.

Menstrual cycle influences on cue-induced smoking cravings and heart rate variability.

Women experience greater difficulties in quitting smoking than men, though the hormonal factors contributing to this sex difference remain to be clarified. The current study aimed to examine menstrual cycle effects on smoking cue-induced cravings as well as examine dynamic reproductive hormone change as a potential mediator underlying any cycle effects observed. Twenty-one women who smoke underwent two laboratory sessions - one in the mid-follicular phase and the other in the late luteal phase - involving an in-vivo smoking cue task, administered before and after exposure to a psychosocial laboratory stressor. Heart rate variability (HRV) and subjective smoking cravings were assessed in response to the cue task. The degree of change in the urinary metabolites of estradiol and progesterone from 2 days before to the day of each laboratory session was measured. Results revealed that both before and following exposure to psychosocial stress, highly nicotine-dependent women exhibited smaller cue-induced increases in HRV relative to the follicular phase. In contrast, less nicotine-dependent women exhibit an increase in HRV in both menstrual cycle phases. Results furthermore suggest that menstrual cycle effects seen in highly nicotine-dependent women are driven by the decline in estradiol and progesterone occurring in the late luteal phase. Though limited by a small sample size, this study suggests that withdrawal from reproductive hormones in the late luteal phase may alter highly nicotine-dependent women's physiological response to smoking cues, which may reflect greater difficulty resisting temptation. These findings may provide some insight regarding women's greater difficulty in maintaining abstinence after quitting smoking.

Retrospective study of influencing factors on the outcomes of luteal phase stimulation in patients with dual stimulation.

Background: Dual/double stimulation (DS) is an ovarian stimulation strategy that has emerged in recent years; it is characterized by two rounds of ovarian stimulation and oocyte retrieval in the same menstrual cycle. DS can greatly shorten the time required to obtain valid embryos in assisted reproduction. For fertility preservation, DS can speed up oocyte storage process. However, factors influencing luteal phase ovarian stimulation (LPS) outcomes in DS have not been elucidated. Methods: A total of 156 cycles from 78 cases were studied. Patients were grouped and analyzed according to their follicular phase ovarian stimulation (FPS) types. Female ages, ovarian stimulation protocols, number of oocytes retrieved, embryo quality were recorded. Comparisons of outcomes were conducted between different groups. Results: Our study found that LPS obtained similar outcomes to follicular phase stimulation (FPS), and that the choice of FPS protocol affected the efficiency of LPS, the antagonist protocol and progestin-primed ovarian stimulation (PPOS) protocol resulted in better embryo outcomes in LPS. In LPS of DS, sufficient stimulation duration was the guarantee of embryo quality (number of available embryos: ß = 0.145, 95% CI [0.078-0.211], P = 0.000; number of high-quality embryos: ß = 0.114, 95% CI [0.057-0.171], P = 0.000). Discussion: This study provided ideas for the precise use of DS. We suggest to further expand the sample size of DS in the future, conduct prospective controlled studies, unify the sample size of each subgroup, include the ovarian reserve of patients in the grouping basis, and exclude the influence of male factors. We hope that this study will help further refinement of DS so as to maximize patient benefits from it. Conclusion: When the DS strategy is considered in the follicular phase, the antagonist protocol and PPOS protocol are more recommended for better embryo outcomes in LPS. During LPS, adequate ovarian stimulation duration is the most important guarantee for LPS efficiency.

Comparison of pregnancy rates in antagonist cycles after luteal support with GnRH-agonist versus progesterone: prospective randomized study.

PURPOSE: To compare pregnancy rates in GnRH-antagonist cycles triggered with hCG after luteal phase support with intranasal GnRH-agonist as sole luteal phase support versus standard vaginal progesterone preparation. METHODS: Prospective randomized controlled study of patients who underwent antagonist-based IVF cycles triggered with hCG at university-affiliated tertiary medical center between 2020 and 2022. Patients meeting the inclusion criteria were randomly assigned to either intranasal GnRH-agonist or vaginal progesterone for luteal phase support. Pregnancy rates were the main outcome compared between the two study groups. RESULTS: A total of 150 patients underwent 164 cycles, 127 cycles of which were included in the study cohort. Of them, 64 (50.4%) and 63 (49.6%) cycles were treated with GnRH-agonist or progesterone, respectively, as sole luteal phase support. A significantly higher pregnancy rate was demonstrated in the GnRH-agonist group compared with the progesterone group. After adjustment of several potential confounders such as age, body mass index, past obstetric history, number of IVF cycles, oocyte retrieved and embryos transferred, GnRH-agonist was still associated with a higher pregnancy rate (odds ratio 3.4, 95% confidence interval 1.4-8.3). Ovarian hyperstimulation syndrome rates were similar between the groups. CONCLUSIONS: This prospective study suggests that nasal GnRH-agonist for luteal phase support is associated with higher pregnancy rates compared with standard progesterone support in an antagonist-based protocol triggered with hCG, while maintaining a similar safety profile. TRIAL REGISTRATION: Clinicaltrials.gov NCT05484193. Date of registration: August 02 2022. The trial was retrospectively registered.

[No improvement in live birth rate after luteal phase support by GnRH agonist]. / Absence d'amélioration du taux de naissance vivante après soutien de la phase lutéale par agoniste de la GnRH.

OBJECTIVES: To evaluate the impact of adding a GnRH agonist (GnRH-a) in luteal phase support (LPS) on live birth rates in IVF/ICSI in antagonist protocols. METHODS: In total, 341 IVF/ICSI attempts are analyzed in this retrospective study. Patients were divided into two groups: A f: LPS with progesterone alone (179 attempts) between March 2019 and May 2020; B: LPS with progesterone and an injection of triptorelin (GnRH-a) 0.1mg 6 days after oocyte retrieval (162 attempts) between June 2020 and June 2021. The primary outcome was live birth rate. The secondary outcomes were miscarriage rate, pregnancy rate and ovarian hyperstimulation syndrome rate. RESULTS: The baseline characteristic are identical between the two groups except the infertility duration (longer in the group B). There was no significant difference between the two groups in live birth rate (24.1% versus 21.2%), pregnancy rate (33.3% versus 28.1%), miscarriage rate (4.9% versus 3.4%) and no increase the SHSO rate. The multivariate regression analysis after adjustment for age, ovarian reserve and infertility duration did not reveal a significant difference in live birth rate between the two groups. CONCLUSION: In this study, the results showed no statistically significant association with the single injection of a GnRH-a in addition to progesterone on live birth rate in luteal phase support.

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.

Psychophysiological Responses to Self-Selected Exercise Intensity Over the Menstrual Cycle: A Randomized Crossover Phase Trial.

Purpose: This study investigated the psychophysiological responses during self-selected exercise intensity over the course of the menstrual cycle (MC). Methods: Seventeen healthy women with regular MCs completed three randomized treadmill bouts of 30 min of self-selected exercise intensity during menstruation, mid-follicular, and late luteal phases. Anxiety, menstrual distress (i.e., pain, behavior change, autonomic reaction, fluid retention, and negative affect) and profile of mood (i.e., tension, depression, and anger) were measured before exercise. Arousal, heart rate (HR), motivation, rating of perceived exertion and affective valence were measured before, during and after each exercise session. Results: Anger, anxiety, behavior change, pain, and negative affect were significantly greater (p < .05) during menstruation compared to the mid-follicular phase, whereas fluid retention, anger, behavior change, and autonomic reaction were greater (p < .05) during the late luteal phase compared with the mid-follicular phase. Participants felt more negative affective valence and less motivation to start exercise during menstruation compared with other MC phases. Average treadmill speed (5.8 ± 1.1 vs 6.0 ± 0.7 vs 5.9 ± 0.7 km/h-1, p = .36) and %HRmax (74.9 ± 3.2 vs 77.8 ± 5.4 vs 77.4 ± 7.1%, p = .40) did not differ between menstruation, mid-follicular, and late luteal phases. Also, noteworthy is that participants self-selected an intensity that exceeded the minimum levels recommended for health and cardiorespiratory fitness promotion (64-70% HRmax). Conclusions: Results of this study indicate that psychophysiological responses are negatively impacted mainly during menstruation and the late luteal phase of the MC. These findings may be helpful for professionals who work to promote the initiation and maintenance of exercise in women.

Understanding the female athlete: molecular mechanisms underpinning menstrual phase differences in exercise metabolism.

Research should equitably reflect responses in men and women. Including women in research, however, necessitates an understanding of the ovarian hormones and menstrual phase variations in both cellular and systems physiology. This review outlines recent advances in the multiplicity of ovarian hormone molecular signaling that elucidates the mechanisms for menstrual phase variability in exercise metabolism. The prominent endogenous estrogen, 17-ß-estradiol (E2), molecular structure is bioactive in stabilizing plasma membranes and quenching free radicals and both E2 and progesterone (P4) promote the expression of antioxidant enzymes attenuating exercise-induced muscle damage in the late follicular (LF) and mid-luteal (ML) phases. E2 and P4 bind nuclear hormone receptors and membrane-bound receptors to regulate gene expression directly or indirectly, which importantly includes cross-regulated expression of their own receptors. Activation of membrane-bound receptors also regulates kinases causing rapid cellular responses. Careful analysis of these signaling pathways explains menstrual phase-specific differences. Namely, E2-promoted plasma glucose uptake during exercise, via GLUT4 expression and kinases, is nullified by E2-dominant suppression of gluconeogenic gene expression in LF and ML phases, ameliorated by carbohydrate ingestion. E2 signaling maximizes fat oxidation capacity in LF and ML phases, pending low-moderate exercise intensities, restricted nutrient availability, and high E2:P4 ratios. P4 increases protein catabolism during the luteal phase by indeterminate mechanisms. Satellite cell function supported by E2-targeted gene expression is countered by P4, explaining greater muscle strengthening from follicular phase-based training. In totality, this integrative review provides causative effects, supported by meta-analyses for quantitative actuality, highlighting research opportunities and evidence-based relevance for female athletes.

Luteal phase support with progesterone does not improve pregnancy rates in patients undergoing ovarian stimulation with letrozole.

RESEARCH QUESTION: Does luteal phase support with vaginal progesterone improve clinical pregnancy rates in patients undergoing ovarian stimulation with letrozole? DESIGN: This was a retrospective cohort study of patients undergoing ovarian stimulation with letrozole paired with intrauterine insemination (IUI) or timed intercourse (TIC) from January 2018 to October 2021. The primary outcome of clinical pregnancy rate (CPR) was calculated for cycles with and without luteal phase progesterone support. Univariate logistic regressions were done to evaluate predictor variables for CPR. Clinically important covariates including age, body mass index, anti-Müllerian hormone concentration, diagnosis of ovulatory dysfunction and multifollicular development were included in a multivariate analysis evaluating the relationship between luteal progesterone use and odds of clinical pregnancy. Secondary outcomes including spontaneous abortion, biochemical pregnancy and ectopic pregnancy were calculated. Live birth rates were calculated for cycles in a secondary analysis. RESULTS: A total of 492 letrozole ovarian stimulation cycles in 273 patients were included. Of these cycles, 387 (78.7%) used vaginal progesterone for luteal support and 105 (21.3%) did not. The unadjusted CPR per cycle was 11.6% (45/387) with progesterone and 13.3% (14/105) without progesterone (P = 0.645). After adjusting for significant covariates including age, BMI, diagnosis of ovulatory dysfunction and multifollicular development, the odds for clinical pregnancy were not significantly improved in cycles with exogenous progesterone (odds ratio [OR] 1.15, 95% confidence interval [CI] 0.48-2.75, P = 0.762). A follow-up analysis demonstrated that live birth rate was 10.7% (41/384) with and 12.5% (13/104) without luteal progesterone, respectively (P = 0.599). CONCLUSIONS: Luteal support with vaginal progesterone does not significantly improve CPR in ovarian stimulation cycles using letrozole.

Dietary energy intake across the menstrual cycle: a narrative review.

Females are often underrepresented in the scientific literature, but awareness of the need for female-specific research is increasing. Review articles have been published on the effects of the menstrual cycle on aspects of exercise performance and physiology, yet to date no research has reviewed the effect of menstrual cycle phase on dietary energy intake. Fluctuations in endogenous sex hormones across the menstrual cycle influence a range of physiological processes, including those involved in nutritional status. Observational research typically quantifies female athletes' nutritional intakes at a single time point; however, this may provide inaccurate information if dietary intake fluctuates across the menstrual cycle. Similarly, this may have implications for interventional research, where dietary intake is often poorly controlled or monitored. This review aimed to synthesize the published literature on dietary energy intakes of naturally menstruating females in various phases of the menstrual cycle. The review critiques the relevant literature in light of recent publications on good practice for female research, explores the impact of the menstrual cycle on energy intake, identifies gaps within the evidence base, and informs future research. Overall, energy intake appears to be lower in the follicular phase compared with the luteal phase, with a particular decrease in the days leading up to and including ovulation. The magnitude of these fluctuations is not yet clearly quantifiable and most likely varies, both between individuals, and from cycle to cycle. This review notes the lack of high-quality research investigating the energy intakes of females across the menstrual cycle, and the very limited data available for female athletes and others who undertake large amounts of physical activity. It also highlights the need for researchers to take into consideration anovulatory cycles and the potential effects of premenstrual disorders on dietary intake.

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.