Midfollicular Phase Research Articles

Effect of the menstrual cycle on knee joint position sense and dynamic balance

The objective of this study was to examine how the menstrual cycle affects knee joint position sense (JPS) and dynamic balance. Forty-five physically active women (age 20.87 ± 0.54 years) participated in this study. Pain was measured with a Visual Analogue Scale (VAS). Knee JPS was measured using the passive-active repositioning method using a digital inclinometer. The modified Star Excursion Balance Test was used to assess dynamic balance (SEBT). The VAS scores were higher in the menses phase compared to the mid-luteal phase (p < 0.001) and mid-follicular phase (p = 0.002). No significant differences were found between phases of the menstrual cycle for JPS in 30° (p > 0.05) and 60° of knee flexion (p > 0.05). There were significant differences in the anterior (p = 0.028), posteromedial (p < 0.001), and posterolateral (p < 0.001) directions of the modified SEBT. The values of the anterior direction in a mid-follicular phase were higher than the menses phase (p = 0.017). Mid-luteal phase values in the posteromedial direction were greater than mid-follicular phase (p = 0.008) and menses phase (p < 0.001). The values of the posterolateral direction in the mid-luteal phase (p < 0.001) and mid-follicular phase (p = 0.009) were higher than in the menses phase. In conclusion, the knee JPS did not change during the menstrual cycle in physically active women. However, the dynamic balance performance was at the lowest level in the menses phase. The risk of injury should be considered during menstruation, especially in activities that require dynamic balance skills in physically active women.

Repeated Sprint Variations According to Circadian Rhythm at Different Menstrual Cycle Phases.

This study assessed the repeated sprint performance in relation to circadian rhythm during different menstrual cycle phases (MCP). Twelve volunteer eumenorrheic women team sport athletes performed 5×6-s cycling sprints in morning (9 am to 10 am) and evening (6 pm to 7 pm) sessions during the mid-follicular (FP, 6th-10th d) and luteal phases (LP, 19th-24th d). Body weight, oral body temperature, resting heart rate and lactate levels together with estradiol, progesterone and cortisol levels were determined before tests. Relative peak and mean power and performance decrements were determined as performance variables and maximum heart rate, lactate and ratings of perceived exertion were determined as physiological variables. Evening body temperatures were significantly higher. Cortisol levels were higher in the morning and in the FP. Resting lactate levels did not vary with MCP or time of day, but a significant MCP x time of day interaction was observed. Body weight showed no change according to time of day and MCP. There was no significant effect of MCP and time of day on performance and physiological variables, in contrast, maximum lactate values were notably higher in the evening. In conclusion, MCP and time of day need not be considered during repeated sprint exercises of eumenorrheic women athletes.

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

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

O-302 Feasibility and efficacy of a flexible and simplified ovarian stimulation protocol for oocyte donors, combining random-start corifollitropin alpha and progestin primed ovarian stimulation protocol (PPOS)

Abstract Study question Is the total number of retrieved oocytes in donors equivalent, according to the onset phase of stimulation with corifollitropin alpha in a random-start PPOS protocol? Summary answer The total number of retrieved and mature oocytes were not different after starting stimulation in the early, mid or late follicular or luteal phases. What is known already Recent studies have shown the ability to obtain oocytes of equivalent quality after follicular or luteal phase ovarian stimulation and have also demonstrated the efficacy and safety of the PPOS protocol in oocytes donors. In order to provide a more friendly, simplified and flexible ovarian stimulation protocol reducing the burden for donors, we studied the impact on oocyte yield of combining a random start corifollitropin alpha stimulation with the concomitant prevention of premature LH surge by progestin administration. Study design, size, duration This multicenter open-labelled RCT was performed in 4 oocytes donation centers from July 2020 to September 2023 to assess the equivalence in terms of number of retrieved oocytes of a delayed onset of corifollitropin alpha stimulation with concomitant administration of desogestrel in Mid Follicular Phase (MFP/D4-D7 of the natural cycle), Late Follicular Phase (LFP/D8-D11), Ovulatory Phase (OP/D12-D15) or Luteal Phase (LP/D16-D30) compared to the standard start in Early Follicular Phase (EFP/D1-D3). Participants/materials, setting, methods From 110 randomized oocyte donors,102 reached triggering of ovulation with triptoreline acetate and OPU : EFP n = 22, MFP n = 20, LFP n = 19, OP n = 18 and LP n = 23. The sample size was calculated to show an equivalence between groups in total number of retrieved oocytes. Secondary endpoints were the number of mature oocytes, premature LH surge and Ovarian Hyperstimulation Syndrome rates. Differences were tested using a ANOVA test or a Pearson’s Chi2 test, as appropriate. Main results and the role of chance Donors were 33 [29.2-35.0] years old [95% Confidence interval] with a mean BMI of 23.4 [21.1-26.3] kg/m2. The mean number (SD) of retrieved oocytes was 14.2 (9.1). In intention to treat analysis, there was no significant difference between the 5 groups, regarding the total number of retrieved oocytes. The mean numbers of retrieved oocytes from the 5 groups were 12.5 (7.7), 13.2 (8.0), 15.7(9.8), 17.8 (11.4), and 12.8(8.3), respectively in the EPF group, the MPF group, the LPF group, the OP group and the FP group, with no significant differences between the groups (p = 0.30). The mean (SD) number of mature oocytes was 11.8 (7.6) with no significant differences between the 5 groups. Only one premature LH surge was reported in the MFP group (0.98%). Four minor to moderate OHSS were reported (3.9%). Limitations, reasons for caution The main limitation of our study is the small sample size responsible for a lack of power. But to our knowledge, this is the first RCT to compare the number of oocytes retrieved, according to the onset phase of ovarian stimulation in a random-start PPOS protocol, for oocyte donors. Wider implications of the findings The proportion of ovarian stimulation cycles with freeze-all is constantly increasing worldwide. Therefore simplified, ultra-flexible ovarian stimulation protocols could be proposed to maintain the spread of the workload along the working days without programming, with fewer injections and reduced burden for patients, with the same efficacy. Trial registration number NCT03895099

O-009 Comparison of the flexible Progestin-Primed Ovarian Stimulation with the GnRH antagonist protocol in predicted suboptimal responders: a freeze-all randomized controlled trial

Abstract Study question Is the Flexible Progestin-Primed Ovarian Stimulation (fPPOS) non-inferior to GnRH antagonist regarding fertility outcomes in women with a suboptimal response scheduled for freeze-all cycles? Summary answer In predicted suboptimal responders, who do not contemplate a fresh embryo transfer, the ongoing pregnancy outcomes of fPPOS was comparable to that of GnRH-antagonist protocol. What is known already Recent retrospective cohort studies involving donor cycles have demonstrated that Medroxyprogesterone Acetate (MPA) can be effectively and flexibly employed during the mid-follicular phase of the PPOS protocol. This approach prevents premature ovulation without compromising oocyte yields. Given its lesser degree of pituitary suppression, the fPPOS protocol may be particularly relevant for women predicted to have a suboptimal response (defined as AFC &amp;lt; 10) where accumulation of more oocytes could enhance cumulative success rates. Study design, size, duration This is a open-label RCT, performed in a single IVF centre Between July 2019 and June 2023. A total of 484 women scheduled for freeze-all strategy were randomly assigned to fPPOS or GnRH-antagonist protocol. The primary outcome was live birth per woman starting stimulation following18 months of randomization. In this abstract, we present fertility outcomes following the initial frozen embryo transfer (FET) and ongoing pregnancy rates per women within a period of 6 months. Participants/materials, setting, methods Women (AFC&amp;lt;10) referred for IVF/ICSI and did not intend to undergo a fresh transfer, were recruited for this study. MPA (10 mg/day) and Cetrotide (0.25 mg/day) were initiated either when the leading follicle reached 14 mm or on the sixth day of stimulation, whichever occurred first. Due to the COVID-19 pandemic, 22 women withdrew from the study at the stimulation commencement, resulting in 462 women included in the analysis. Data underwent intention-to-treat and per-protocol analyses. Main results and the role of chance No significant difference was observed between the two groups in terms of serum endocrine profiles and stimulation parameters, including the consumption of gonadotropins. Within the 6-month period, 79.5% of women in the fPPOS group and 84.02% in the GnRH antagonist group had undergone at least one cycle of FET (P = 0.234).The ongoing pregnancy rates per women were 48.20% (107/222) in the fPPOS group versus 52.92% (127/240) in the GnRH-anta group (RR: 0.91, 95%CI, 0.76 to 1.09, P = 0.311). There are 62 women who are ongoing pregnancy but do not reached live birth during the follow-up period. Regarding the outcomes of the initial FET cycle, there was no difference in the ongoing pregnancy rate between the two groups (49.01% vs 48.37%, RR: 1.03, 95% CI, 0.81 to 1.26, P = 0.908). Other outcomes including biochemical pregnancy rate (62.25% vs 63.59%), clinical pregnancy rate (60.26% vs 57.61%), and miscarriage rate per pregnancy (16.48% vs 15.09%), also exhibited no significant differences. The number of oocytes retrieved, two-pronuclear oocytes, viable and high-quality embryos, as well as the total number of embryos cryopreserved were also similar between groups. There was one case of premature ovulation in the fPPOS group and none in the GnRH-ant group. Limitations, reasons for caution Due to the distinct administration routes of the medications, blinding was not feasible in this open-label trial, which may affect the assessment of outcomes. All participants were recruited in a single center from one country, limiting the generalizability. In this abstract, we only report on the ongoing pregnancy outcomes. Wider implications of the findings This is the first freeze-all RCT comparing the long-term outcomes of fPPOS and GnRH antagonist in autologous ovarian stimulation cycles. Eliminating the variability of fresh and frozen transfers, the fPPOS seems an efficacious alternative for women with predicted suboptimal response, when a GnRH antagonist would have been the preferred regimen. Trial registration number ChiCTR2000030356

Dampened circadian amplitude of EEG power in women after menopause.

Postmenopausal women are at high risk of developing sleep-wake disturbances. We previously reported dampened circadian rhythms of melatonin, alertness and sleep in postmenopausal compared with young women. The present study aims to further explore electroencephalography power spectral changes in the sleep of postmenopausal women. Eight healthy postmenopausal women were compared with 12 healthy, naturally ovulating, young women in their mid-follicular phase. Participants followed a regular 8-hr sleep schedule for ≥ 2 weeks prior to laboratory entry. The laboratory visit included an 8-hr baseline sleep period followed by an ultradian sleep-wake cycle procedure, consisting of alternating 1-hr wake periods and nap opportunities. Electroencephalography power spectral analysis was performed on non-rapid eye movement sleep obtained over a 48-hr period. The baseline nocturnal sleep of postmenopausal women comprised lower power within delta and sigma, and higher power within alpha bands compared with that of younger women. During nighttime naps of the ultradian sleep-wake cycle procedure, lower power within delta and sigma, and higher power within beta bands were observed in postmenopausal women. During the ultradian sleep-wake cycle procedure, postmenopausal women presented lower power of delta, theta and sigma (14-15 Hz), undetectable rhythms of delta and theta, and a dampened or undetectable rhythm of sigma (12-15 Hz) power compared with younger women. Our results support the hypothesis of a dampened circadian variation of sleep microstructure in healthy-sleeping postmenopausal women. Circadian changes with aging are potential mechanisms for increased susceptibility to develop sleep disturbances; however, further research is needed to clarify their clinical implications and contribution to insomnia.

Changes in the Objective Measures of Sleep in Association with Menses Among Female Athletes with Poor Subjective Sleep Quality: Female Athletes with Poor Subjective Sleep Quality Have More Sleep Arousals During Menses.

Female athletes with menstrual abnormalities have poor sleep quality. However, whether female athletes with poor sleep quality based on subjective assessment have distinctive changes in objective measures of sleep in association with menses remains unclear. This study aimed to compare changes in objective sleep measurements during and following menses between collegiate female athletes with and without poor subjective sleep quality. Female collegiate athletes (age range/mean ± standard deviation: 18-22/ 22.2±1.1) with regular menstrual cycles were recruited. The participants underwent home electroencephalogram monitoring during the first and second nights after the onset of menses and one night between the seventh and 10th nights after menses onset (mid-follicular phase). The Pittsburgh Sleep Quality Index (PSQI) was used to assess the subjective sleep quality. Interactions between the presence of poor subjective sleep quality (ie, PSQI ≥6) and changes in objective measures of sleep in association with menses were analyzed. Data of 45 athletes, including 13 with poor subjective sleep quality, showed that changes in arousal index in athletes with poor subjective sleep quality were distinctive from those in athletes without poor subjective sleep quality (p = 0.036 for interaction). In athletes with poor subjective sleep quality, the arousal index was significantly increased in menses (p for analysis of variance, 0.015), especially on the first night after the onset of menses compared with during the mid-follicular phase (p = 0.016). Collegiate female athletes with regular menstrual cycles are likely to have poor subjective sleep quality in association with more frequent arousal during the first night after the onset of menses than during the mid-follicular phase.

Cortical morphology variations during the menstrual cycle in individuals with and without premenstrual dysphoric disorder

BackgroundPremenstrual dysphoric disorder (PMDD) is hypothesized to stem from maladaptive neural sensitivity to ovarian steroid hormone fluctuations. Recently, we found thinner cortices in individuals with PMDD, compared to healthy controls, during the symptomatic phase. Here, we aimed at investigating whether such differences illustrate state-like characteristics specific to the symptomatic phase, or trait-like features defining PMDD. MethodsPatients and controls were scanned using structural magnetic resonance imaging during the mid-follicular and late-luteal phase of the menstrual cycle. Group-by-phase interaction effects on cortical architecture metrics (cortical thickness, gyrification index, cortical complexity, and sulcal depth) were assessed using surface-based morphometry. ResultsIndependently of menstrual cycle phase, a main effect of diagnostic group on surface metrics was found, primarily illustrating thinner cortices (0.3 < Cohen's d > 1.1) and lower gyrification indices (0.4 < Cohen's d > 1.0) in patients compared to controls. Furthermore, menstrual cycle-specific effects were detected across all participants, depicting a decrease in cortical thickness (0.4 < Cohen's d > 1.7) and region-dependent changes in cortical folding metrics (0.4 < Cohen's d > 2.2) from the mid-follicular to the late luteal phase. LimitationsSmall effects (d = 0.3) require a larger sample size to be accurately characterized. ConclusionsThese findings provide initial evidence of trait-like cortical characteristics of the brain of individuals with premenstrual dysphoric disorder, together with indications of menstrual cycle-related variations in cortical architecture in patients and controls. Further investigations exploring whether these differences constitute stable vulnerability markers or develop over the years may help understand PMDD etiology.

Impact of an Advanced Hybrid Closed-Loop System on Glycemic Control Throughout the Menstrual Cycle in Women with Type 1 Diabetes Prone to Hypoglycemia.

This study aimed to evaluate the impact of advanced hybrid closed loop (AHCL) on glycemic control throughout the menstrual cycle (MC) in women with type 1 diabetes. We included 39 pairs of spontaneous MCs from 13 participants, before and after switching from sensor-augmented pump to AHCL. Baseline time below range <70 mg/dL (TBR <70) was significantly higher during the midfollicular phase than during late luteal phase (5.7% ± 5.0% vs. 4.1% ± 3.0%), but similar time in range 70-180 mg/dL (TIR) was observed throughout the MC. After switching to AHCL, a reduction in TBR <70 and an increase in TIR were observed in all phases. Phase-dependent changes in insulin infusion were detected and pre-existing differences in TBR <70 were eradicated (3.5% ± 3.2% vs. 3.0% ± 3.0%). However, TIR became significantly higher during the early follicular phase than during the late luteal phase (79.1% ± 9.3% vs. 74.5% ± 10.0%). In conclusion, AHCL improved glycemic control throughout the MC, but performance differed according to phase.

Higher Depressive Symptoms in Irregular Menstrual Cycles: Converging Evidence from Cross-Sectional and Prospective Assessments

Background: Menstrual cycle regularity is an important marker of reproductive health and associated with physiological and psychological illnesses, as well as experiencing stress. We hypothesized that individuals with irregular menstrual cycles report higher depressive symptom severity, after controlling for stress occurrence. Methods: The hypothesis was examined through two measurement approaches: a cross-sectional and a prospective, longitudinal study. In the cross-sectional study, participants (n = 394) reported depressive symptoms and their overall menstrual cycle regularity. In the longitudinal study, participants (n = 77) completed questionnaires on depressive symptoms and stress during the mid-follicular and periovulatory phase of one menstrual cycle. Depressive symptoms were compared between participants with regular and irregular cycles through a Welch t test and an ANCOVA. Results: Participants with irregular menstrual cycles reported more depressive symptoms in the cross-sectional analysis. Similarly, in the longitudinal analysis, the group with a current irregular menstrual cycle reported more depressive symptoms after controlling for stress occurrence. When including only complete data sets without multiple imputation (n = 52), the direction of the effects remained but did not reach statistical significance. Conclusions: The results indicate an association between depressive symptoms and menstrual cycle irregularity. Limitations were that although we investigated the menstrual cycle prospectively, it would have been more precise to include two or more cycles and daily sex hormone measurements. Further limitations were the suboptimal statistical power and the data collection during the COVID pandemic. We give recommendations on how to incorporate the association of depressive symptoms and cycle irregularity in future study designs on women’s mental health.

The degree of risk factor and accumulation effect for large niche in individuals after cesarean section

BackgroundThe risk factors associated with niche on the cesarean scar have been reported, however, the degree of these factors associated with large niche and the accumulation effects of these risk factors on the development of large niche are unclear.MethodsLarge niche was evaluated by transvaginal sonography during mid-follicular phase. Logistic regression model was used to assess 32 risk factors by univariate analysis. Then, a scoring model based on the screened risk factors was generated. The performance of this model was evaluated by area under curve (AUC). Finally, the scoring model was applied in 123 women to assess the external validation.Result(s)In the training cohort study, 163 women were diagnosed with large niche. The final scoring model involves eight risk factors with the rating scores including age at delivery (30–34 years: 1 point; ≥ 35 years: 4.5 points), retroflexed uterus (8.5 points), meconium-stained amniotic fluid (4.5 points), twice CSs (4.0 points), postpartum endometritis (4.5 points), premature rupture of membranes (2.5 points), intrahepatic cholestasis of pregnancy (mild to moderate: 3 points; severe: 6.5 points), and cervical dilatation (1-3 cm: 2.0 points; 4-10 cm: 4.5 points). The accumulation effect with a cut-off value of 8.0 in the scoring was associated with the large niche after CS.Conclusion(s)This is the first scoring model to objectively quantify the risk of a large niche after CS. Optimal risk factors control by avoiding high score factors and multiple factors accumulation may eliminate the risk of large niche development.

Validity of SenseWear Armband in assessing the energy expenditure at different exercise intensities during menstrual cycle

Objective: The purpose of this study was to determine the validity of the SenseWear Armband (SWA) in assessing the energy expenditure at different exercise intensities during midfollicular and luteal phases of the menstrual cycle. Material and Methods: Twenty volunteer women athletes (age: 20.6±1.6 yrs, height: 168.3±7.3 cm; menstrual cycle: 28.8±2.1 days) with regular menstrual cycle participated in the study. Participants performed treadmill running exercise for 10 min at 35% and 75% of their VO2max in their midfollicular (days 7-9) and luteal phases (days 21-23). Phases of the menstrual cycle were confirmed by hormone analysis. Energy expenditure during the running exercise was assessed simultaneously by the indirect calorimetric method, and the SWA. Multi-way ANOVA was used for the effect of method (2) x phase (2) x intensity (2) on energy expenditure. In addition, the Pearson correlation coefficient was determined between the variables. Results: Estradiol and progesterone levels measured in the midfollicular phase were significantly higher than in luteal phase (p&lt;0.05). Energy expenditure at 75% intensity was significantly higher than energy expenditure at 35% intensity (p&lt;0.05). No significant method (p&gt;0.05) and phase (p&gt;0.05) effect was found in energy expenditure. There was no significant method x phase, phase x intensity, and method x phase x intensity interaction (p&gt;0.05), however method x intensity interaction was significant (p&lt;0.05). At the midfollicular phase the correlations between energy levels from indirect calorimetric and SWA methods were not significant (for 35%, r=0.382; for 75%, r=0.147; p&gt;0.05). In contrast, significant correlation was found between energy levels from the indirect calorimetric, and the SWA methods at the luteal phase (for 35%, r=0.495; for 75%, r=0.748; p&lt;0.05). Conclusions: The results of the present study indicated that energy expenditures at different menstrual phases were similar and that SWA was a valid method in assessing energy expenditure at different exercise intensities during the menstrual cycle.

FRI424 Allopregnanolone Levels Are Elevated in the Follicular Phase and Predict Premenstrual Depression and Anxiety Symptom Severity in Women with Menstrually Related Mood Disorder

Abstract Disclosure: A. Kimball: None. J. Bourassa: None. M. Chicote: None. A.V. Gerweck: None. L.E. Dichtel: Other; Self; Dr. Dichtel is a Mass General Brigham (MGB) Innovation Fellow hosted by Third Rock Ventures. Financial interests were reviewed and are managed by MGH and MGB in accordance with their COI policies. K.K. Miller: None. Menstrually related mood disorder (MRMD), which includes premenstrual dysphoric disorder (PMDD) and subthreshold PMDD, is marked by severe psychiatric impairment in the late luteal phase of the menstrual cycle, but little is known about the mechanisms responsible. Allopregnanolone is a neuroactive metabolite of progesterone and a potent GABAA receptor allosteric activator with antidepressant and anxiolytic properties. We have shown that allopregnanolone levels increase, while the allopregnanolone/progesterone ratio decreases, from the follicular to luteal phase in healthy women. We hypothesized that allopregnanolone levels would decrease in association with the increase in depression severity experienced in the late luteal phase by women with MRMD. We studied 23 women with regular menses [MRMD (n=9) and healthy controls with no premenstrual symptoms or psychiatric history (HC) (n=14)] in the mid-follicular (cycle day 6-10), mid-luteal (5-9 days after LH surge), and late luteal (9-13 days after LH surge) phases. No subjects took gonadal steroids or psychotropic medications. The Daily Record of Severity of Problems was used to diagnosed PMDD (≥5 symptoms) and subthreshold PMDD (1-4 symptoms). Depression and anxiety symptom severity were assessed using the Quick Inventory of Depressive Symptomatology and Generalized Anxiety Disorder 7-item Scale, respectively. Fasting plasma hormone levels were measured by GC/MS. Data are presented as median(95% CI). Normal ranges were calculated as the 95% CI of HC. Median age [30(28,33) years] and BMI [23.8(22.9,29.0) kg/m2] were similar between groups. Depression severity was greater in MRMD vs HC [7(3,13) vs 2(1,4), p=0.005) in the late luteal phase only, as expected. In the follicular phase, the median allopregnanolone level was higher in MRMD vs HC [86(40,148) vs 29(24,73) pg/mL, p=0.05] and frankly elevated in 6 of 9 (67%) MRMD women. The median allopregnanolone/progesterone ratio in the follicular phase was higher in MRMD vs HC [0.8(0.4,2.2) vs 0.4 (0.3,0.8), p=0.03] and elevated in 4 of 9 (44%) MRMD women. There were no differences in neuroactive steroid levels between groups during the luteal phase. Higher allopregnanolone levels in the follicular phase were associated with greater depression severity in the mid-luteal (r=0.51, p=0.01) and late luteal (r=0.54, p=0.007) phase and greater anxiety severity in the late luteal phase (r=0.41, p=0.05). Conclusion: Contrary to our hypothesis, we found that levels of neuroactive steroids, which have antidepressant effects, were higher in the follicular phase in women with MRMD – who experience depression in the late luteal phase – compared with HC. This suggests that increased conversion of progesterone to allopregnanolone in the follicular phase, resulting in elevated allopregnanolone levels, may be a compensatory response to premenstrual depression and anxiety in some women with MRMD. Presentation Date: Friday, June 16, 2023

Women in their mid-follicular phase outcompete hormonal contraceptive users, an effect partially explained by relatively greater progesterone and cortisol reactivity to competition

Early evidence suggests that hormonal contraceptive (HC) use alters psychological functioning and competitive behavior. Yet, there is limited data on endocrine models for explaining how HC use affects these outcomes. In this pre-registered and open-data study, we test if HC users and naturally cycling (NC) females in their low (mid-follicular) and high (mid-luteal) progesterone phase differ in competitive persistence and whether progesterone and cortisol reactivity mediate of this effect. HC users (N = 73) in the active hormone-exposure phase and NC participants in the mid-follicular (N = 69) or mid-luteal (N = 72) phase completed two behavioral measures of competitive persistence, holding up a weight for time followed by attempting to solve an unsolvable anagram. Participants also completed measures of handgrip strength and self-reported competitiveness as well as gave saliva samples before and after the tasks for hormone assay. Results showed that NC-follicular group had greater competitive persistence in the weight-holding task compared to both NC-luteal (d = 0.38) and HC use (d = 0.43) groups independent of physical strength and self-reported competitiveness covariates. Although anagram task performance showed similar trends for group differences, analyses for this task were inconclusive. Baseline progesterone did not mediate the effect of cycle phase group on competitive persistence. HC users showed relatively blunted cortisol and progesterone reactivity, and this effect partially mediated the difference in competitive persistence between HC users and the NC-follicular group. In sum, results suggest that HC use could downregulate competitive behavior at least partly by dampening cortisol-progesterone reactivity. These findings offer a new endocrine model for understanding HC use and cycle phase effects on motivational and energetic outcomes required for optimal performance in competitive contexts.

Cyclical exacerbation of suicidal ideation in female outpatients: Prospective evidence from daily ratings in a transdiagnostic sample.

Suicide is a leading cause of death among females of reproductive age. The menstrual cycle is a plausible yet understudied trigger for acute suicide risk. Cross-sectional studies have demonstrated a greater frequency of suicide attempts and deaths in the weeks before and after the onset of menses compared to other cycle phases. Here, using prospective daily ratings, we examine the relationship between the cycle and suicidal ideation (SI) and related symptoms known to show a cyclical change in some patients (depression, hopelessness, guilt, rejection sensitivity, interpersonal conflict, anxiety, mood swings, and anger/irritability). Thirty-eight naturally cycling outpatients recruited for past-month SI reported SI severity and other symptoms across an average of 40 days. Participants were excluded for hormone use, pregnancy, irregular cycles, serious medical illness, and body mass index > 29.9 or < 18. Intraclass correlations ranged from .29 to .46, highlighting that most symptom variance lies within-person. Cyclical worsening of symptoms was evaluated using phase contrasts in multilevel models. Most symptoms, including SI, were significantly worse in the perimenstrual phase than in all other phases. Additionally, anger/irritability was higher in the midluteal than in the midfollicular phase, and several symptoms of depression were higher in the midfollicular than in the periovulatory phase. Otherwise, symptoms did not significantly differ between the midluteal, midfollicular, and periovulatory phases. Cycle phase predictors accounted for 25% of the within-person variance in SI. Females with SI may be at risk for perimenstrual worsening of SI and related symptoms. These findings highlight the importance of assessing the cycle phase for improved prediction of suicide risk. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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.

0737 Age, menstrual phase, and circadian preference impact sleep in menstruating individuals

Abstract Introduction An eveningness chronotype is generally associated with reduced sleep continuity and quality, as well as social jetlag. Changes in hormones and menstrual phase similarly impact sleep, although research on the chronobiological effects of these changes are equivocal. This study aimed to examine the role of menstrual cycle in daily self-report and actigraphy-assessed sleep in two consecutive menstrual cycles. Methods Participants (n=51; 43% Caucasian), 18-35 years (23.67±4.68) completed actigraphy and daily sleep diaries over two menstrual cycles (m days=51.29). Four menstrual phases were identified via dates of menstrual bleeding and urinary ovulation testing: perimenstrual (±3 days of bleeding), mid-follicular, periovulatory, and mid-luteal. Relationships between menstrual phase and sleep parameters were estimated using multistep hierarchical linear modeling. Subjective and objective measures yielded the following sleep variables: Total Wake Time (TWTsub and TWTobj), Sleep Efficiency (SEsub and SEobj), and mid-sleep point (MSP). Participants completed the Morning-Eveningness Questionnaire (MEQ) at baseline. Results Mean cycle length was 28.61 days±2.69. Age was significantly associated with TWTobj (r=-.32, p &amp;lt;.001); SEobj (r=.34, p &amp;lt;.001), and MSP (r=-.42, p &amp;lt;.001) such that older participants had shorter TWT, higher SE, and earlier MSP. TWTobj was 4-7 minutes lower during the mid-follicular (61.54±3.37) and mid-luteal phases (63.11±3.29) compared to the perimenstrual phase (67.54±3.37; p &amp;lt;.001). SEobj was higher in the mid-luteal phase (82.50±0.79) vs. the perimenstrual phase (80.71±0.82, p =.006). Perimenstrual women reported 8-16 minutes longer awake (TWTsub=52.23±5.01, p &amp;lt;.001) and had 1-3% reduction in SEsub (89.70±0.10, p &amp;lt;.001). MEQ negatively predicted TWTobj (p=.004) and SEobj (p=.003), but did not vary across menstrual phase. In morning-type individuals, TST was significantly higher in the periovulatory (b =1.81, p=.01) and mid-luteal phases (b=2.03, p&amp;lt;.001) compared to the perimenstrual phase. Conclusion With increasing age, women experienced reduced time awake, higher sleep efficiency, and earlier sleep timing. Eveningness predicted greater total wake time and lower sleep efficiency. With menstrual phase considered, disturbed sleep was highest in the perimenstrual phase and women reporting a stronger preference for eveningness reported shorter TST during the perimenstrual phase. These findings highlight the importance of considering the menstrual cycle in the sleep health of menstruating individuals. Support (if any)

Toward an optimal contraception dosing strategy.

Anovulation refers to a menstrual cycle characterized by the absence of ovulation. Exogenous hormones such as synthetic progesterone and estrogen have been used to attain this state to achieve contraception. However, large doses are associated with adverse effects such as increased risk for thrombosis and myocardial infarction. This study utilizes optimal control theory on a modified menstrual cycle model to determine the minimum total exogenous estrogen/progesterone dose, and timing of administration to induce anovulation. The mathematical model correctly predicts the mean daily levels of pituitary hormones LH and FSH, and ovarian hormones E2, P4, and Inh throughout a normal menstrual cycle and reflects the reduction in these hormone levels caused by exogenous estrogen and/or progesterone. Results show that it is possible to reduce the total dose by 92% in estrogen monotherapy, 43% in progesterone monotherapy, and that it is most effective to deliver the estrogen contraceptive in the mid follicular phase. Finally, we show that by combining estrogen and progesterone the dose can be lowered even more. These results may give clinicians insights into optimal formulations and schedule of therapy that can suppress ovulation.

Aberrant Intrinsic Brain Network Functional Connectivity During a Face-Matching Task in Women Diagnosed With Premenstrual Dysphoric Disorder

BackgroundPremenstrual dysphoric disorder (PMDD) is characterized by affective, cognitive, and physical symptoms, suggesting alterations at the brain network level. Women with PMDD demonstrate aberrant discrimination of facial emotions during the luteal phase of the menstrual cycle and altered reactivity to emotional stimuli. However, previous studies assessing emotional task-related brain reactivity using region-of-interest or whole-brain analysis have reported conflicting findings. Therefore, we utilized both region-of-interest task-reactivity and seed-voxel functional connectivity (FC) approaches to test for differences in the default mode network, salience network, and central executive network between women with PMDD and control participants during an emotional-processing task that yields an optimal setup for investigating brain network changes in PMDD. MethodsTwenty-four women with PMDD and 27 control participants were classified according to the Daily Record of Severity of Problems. Participants underwent functional magnetic resonance imaging scans while completing the emotional face-matching task during the midfollicular and late-luteal phases of their menstrual cycle. ResultsNo significant between-group differences in brain reactivity were found using region-of-interest analysis. In the FC analysis, a main effect of diagnosis was found showing decreased default mode network connectivity, increased salience network connectivity, and decreased central executive network connectivity in women with PMDD compared with control participants. A significant interaction between menstrual cycle phase and diagnosis was found in the central executive network for right posterior parietal cortex and left inferior lateral occipital cortex connectivity. A post hoc analysis revealed stronger FC during the midfollicular than the late-luteal phase of PMDD. ConclusionsAberrant FC in the 3 brain networks involved in PMDD may indicate vulnerability to experience affective and cognitive symptoms of the disorder.

Premature progesterone elevation during the early and mid-follicular phases in fresh in vitro fertilization (IVF) cycles is associated with lower live birth, clinical pregnancy, and implantation rates.

Evaluate follicular phase progesterone elevation (≥ 1.5ng/mL) prior to trigger during IVF stimulation and its effects on live birth rate (LBR), clinical pregnancy rate (CPR), and implantation rate (IR) in fresh IVF cycles. This was a retrospective cohort study within an academic clinic. A total of 6961 fresh IVF and IVF/ICSI cycles from October 1, 2015 to June 30, 2021 were included and grouped by progesterone (PR) prior to trigger: PR < 1.5ng/mL (low PR group) and PR ≥ 1.5ng/mL (high PR group). Main outcome measures included LBR, CPR, and IR. Among all cycle starts, 1568 (22.5%) were in the high PR group and 5393 (77.5%) were in the low PR group. Of the cycles which proceeded to an embryo transfer, 416 (11.1%) were in the high PR group and 3341 (88.9%) were in the low PR group. The high PR group had significantly lower IR (RR 0.75; 95% CI 0.64-0.88), CPR (aRR 0.74; 95% CI 0.64-0.87), and LBR (aRR 0.71; 95% CI 0.59-0.85) compared to the low PR group. When stratified by progesterone on the day of trigger (TPR), there was a clinically notable decrease in IR (16.8% vs 23.3%), CPR (28.1% vs 36.0%), and LBR (22.8% vs 28.9%) in the high PR group compared to the low PR group even when TPR < 1.5ng/mL. In fresh IVF cycles in which TPR < 1.5ng/mL, progesterone elevation ≥ 1.5ng/mL at any point in time prior to trigger negatively impacts IR, CPR, and LBR. This data supports testing of serum progesterone in the follicular phase prior to trigger, as these patients may benefit from a freeze-all approach.