Cycle In Healthy Women Research Articles

Plasma volume is associated with micronutrient mass but not concentration in healthy US women of reproductive age

BackgroundPlasma transports nutrients and composes more than half of the volume of blood. A few prior studies suggest that plasma volume fluctuations may impact certain micronutrient concentrations. We hypothesized a slight negative correlation between plasma volume and micronutrient biomarkers throughout the menstrual cycle in healthy women of reproductive age (n = 45). MethodsThe study involved three visits during one menstrual cycle where fasting blood samples were taken to measure biomarker concentrations for zinc, copper, magnesium, manganese, iron, ferritin, retinol, and hemoglobin. A bolus dose of indocyanine green (ICG; equivalent to 0.25 mg.kg-1 of body weight) was injected to measure plasma volume. The total circulating micronutrient biomarker mass was calculated using the plasma volume and biomarker concentration. We used Spearman's correlation and fractional polynomial regression techniques to assess the relationship between plasma volume and biomarker concentration and mass. ResultsPlasma volume ranged from 1210 to 3520 mL. During all three visits, the correlation between micronutrient biomarker concentrations and plasma volume ranged from -0.05 to 0.10 (all P > 0.05); However, there was a strong positive correlation between biomarker mass and plasma volume, ranging from 0.26 to 0.95 (all P < 0.05). Five of the eight biomarkers examined (zinc, copper, magnesium, retinol, and hemoglobin) showed a correlation coefficient > 0.70 (P < 0.001) between mass and plasma volume. ConclusionOur findings indicate that biomarker concentrations are maintained across a range of plasma volume, suggesting that plasma volume may not be necessary to interpret micronutrient status in healthy non-pregnant women of reproductive age.

The Cycle study: a prospective study on cholesterol levels during the menstrual cycle

Abstract Background Previous studies showed fluctuating lipid levels during the menstrual cycle in healthy women with normal cholesterol (nChol). Cycle-related variations in lipid levels in women with familial hypercholesterolemia (FH) have not been studied, while these might have important consequences for lipid management. Purpose To investigate menstrual cycle-related fluctuations in lipid levels in women with FH compared to those with nChol. Methods In the Netherlands and Norway, 20 women with clinical/genetic FH and 63 healthy women with nChol were included - details are presented in the figures. Participants had to have a regular cycle between 21-35 days, while pregnant women, and those using hormone-based contraceptives without hormone free interval (HFI) were excluded. Lipid levels were measured in the follicular (visit 1), ovulation (visit 2), and luteal (visit 3) phases. In women using oral contraceptives (OC) measurements were taken during day 12-14 of the pill period (visit 1) and during day 5-7 of the HFI (visit 2). Results Mean (sd) age of the included subjects was 33 (9) years, BMI 23.9 (4) kg/m2, and cycle duration 28 (2) days. These characteristics were similar in FH and nChol. Women with nChol showed slight, although statistically significant, cycle-related variations in cholesterol levels (mean maximum variation total Chol 0.53, LDL-Chol 0.39 and HDL-Chol 0.22 mmol/L; figure 1). FH women who did not receive statin therapy for various reasons showed largest mean variations (total Chol 0.80, LDL-Chol 0.59 and HDL-Chol 0.23 mmol/L), with the highest lipid levels during the ovulation phase. The women with OC had an increase in total- and LDL-cholesterol (groups combined: mean difference 0.55 and 0.51 mmol/L, respectively) between the two visits (n=9) (figure 2). Conclusions In women with untreated FH and normal cholesterol with a regular menstrual cycle, total- and HDL-cholesterol were highest at ovulation. These menstrual fluctuations were absent in women with FH who used statins. Women with OC showed an increase in total- and LDL-cholesterol from the contraceptive pill period to the HFI. Even though in most women the absolute variation in lipid levels during the menstrual cycle and OC are modest, the moment of measurement can be of clinical value in particular in women with untreated high lipid levels. In these women, it is recommended to measure lipid levels at a fixed time of the menstrual cycle.Figure 1Figure 2

Choroidal Morphology and Systemic Circulation Changes During the Menstrual Cycle in Healthy Japanese Women.

Changes in systemic circulatory dynamics and choroidal thickness are poorly understood. This study aimed to investigate the time course of changes in choroidal morphology during normal menstrual cycles in healthy women using enhanced depth imaging optical coherence tomography (EDI-OCT). This prospective study included 15 left eyes of 15 healthy Japanese women (mean age, 20.2 ± 0.8 years) with a normal menstrual cycle. Using EDI-OCT, the subfoveal choroidal thickness (SCT) was manually measured during the late follicular and mid-luteal phases. Intraocular pressure (IOP), systolic, diastolic, and mean blood pressure (SBP, DBP, and MBP), and heart rate (HR) were also evaluated during these phases. SBP, DBP, and MBP were significantly elevated in the mid-luteal phase. The average SCT was significantly decreased in the mid-luteal phase. In contrast, there were no significant changes in IOP or HR. These findings indicate that choroidal thickness decreases during the mid-luteal phase in healthy Japanese women with normal menstrual cycles depending on systemic circulatory dynamics. However, since the difference in the SCT values between the late follicular and the mid-luteal phase is not large (7 μm), the menstrual cycle may have little influence on the interpretation of choroidal thickness data in clinical practice.

OR09-05 GPBAR1- Understanding Its Function In The Secretory Endometrium

Abstract Disclosure: M. Saad-Naguib: None. P. Timmins: None. L. George: None. C. Samuels: None. N. Douglas: None. A.V. Babwah: None. Every successful pregnancy relies on implantation of an embryo into a receptive uterine endometrium. While implantation failure accounts for 50% of pregnancy failures, it remains the least understood aspect of pregnancy. In the mid-secretory (MS) phase of the menstrual cycle, under the influence of progesterone and cAMP, fibroblasts decidualize, a critical requirement for implantation. Decidualization involves the differentiation of stromal fibroblasts into secretory epithelioid cells that contribute to the formation of the decidua, the support of the pregnancy prior to placentation. A defective decidua can lead to implantation failure, but if implantation occurs, it could compromise placenta formation and function. Several studies have demonstrated the importance of G protein-coupled receptors (GPCRs) in mouse endometrial receptivity and decidualization. GPCRs are transmembrane signaling molecules that are ubiquitously expressed in the body and regulate almost every cellular and physiological process. They are major pharmaceutical targets, with 35% of all the drugs approved by the US FDA targeting GPCRs. To identify novel GPCR regulators of embryo implantation, we conducted bulk RNA sequencing of the human endometrium at the periovulatory (PO) and mid-secretory (MS) phase in natural menstrual cycles in healthy women of reproductive age and observed that genes encoding 11 GPCRs, not previously reported to regulate implantation, were differentially expressed between these two time points. Among these was the gene encoding the G protein-coupled bile acid receptor 1 (GPBAR1), and this was upregulated 4.6-fold in the MS vs PO phase. Single cell RNA sequence analysis showed that within the human endometrium, GPBAR1 mRNA expression is mostly and strongly localized to stromal fibroblasts. Upon activation by secondary bile acids, GPBAR1 couples to Gαs leading to an increase in intracellular cAMP levels. We hypothesize that in the MS endometrium, upon ligand binding, GPBAR1 produces cAMP and induces human endometrial stromal cell (HESC) decidualization. This hypothesis is being tested in vitro using primary HESCs. Interestingly, in the pregnant mouse, GPBAR1 mRNA is barely expressed at the implantation site on E7.5, and therefore unlikely plays a role in stromal cell decidualization in the mouse. Whether Gpbar1 is expressed in the pregnant mouse endometrium prior to implantation and plays a role in regulating endometrial receptivity is being investigated. Overall, our studies have uncovered a GPCR, that to our knowledge, has not been previously described in the human endometrium. Our data show that the expression of this GPCR is upregulated at the time of endometrial stromal cell decidualization, and therefore it might regulate decidualization and/or be required for decidual function in women. These possibilities are being examined. Presentation: Friday, June 16, 2023

Resting energy metabolism and sweet taste preference during the menstrual cycle in healthy women.

Differences in blood concentration of sex hormones in the follicular (FP) and luteal (LP) phases may influence energy metabolism in women. We compared fasting energy metabolism and sweet taste preference on a representative day of the FP and LP in twenty healthy women (25·3 (sd 5·1) years, BMI: 22·2 (sd 2·2) kg/m2) with regular self-reported menses and without the use of hormonal contraceptives. From the self-reported duration of the three prior menstrual cycles, the predicted FP and LP visits were scheduled for days 5-12 and 20-25 after menses, respectively. The order of the FP and LP visits was randomly assigned. On each visit, RMR and RQ by indirect calorimetry, sweet taste preference by the Monell two-series forced-choice tracking procedure, serum fibroblast growth factor 21 by a commercial ELISA (FGF21, a liver-derived protein with action in energy balance, fuel oxidation and sugar preference) and dietary food intake by a 24-h dietary recall were determined. Serum progesterone and oestradiol concentrations displayed the expected differences between phases. RMR was lower in the FP v. LP (5042 (sd 460) v. 5197 (sd 490) kJ/d, respectively; P = 0·04; Cohen effect size, d rm = 0·33), while RQ showed borderline significant higher values (0·84 (sd 0·05) v. 0·81 (sd 0·05), respectively; P = 0·07; d rm = 0·62). Also, in the FP v. LP, sweet taste preference was lower (12 (sd 8) v. 16 (sd 9) %; P = 0·04; d rm = 0·47) concomitant with higher serum FGF21 concentration (294 (sd 164) v. 197 (sd 104) pg/ml; P < 0·01; d rm = 0·66). The menstrual cycle is associated with changes in energy expenditure, sweet taste preference and oxidative fuel partitioning.

O-267 Uterine contractility in women with adenomyosis differs significantly from healthy control women - the waves study

Abstract Study question Description of uterine contractility characteristics in adenomyosis patients compared to healthy controls and according to degree of dysmenorrhoea measured by quantitative 2D transvaginal ultrasound (TVUS). Summary answer Women with adenomyosis show differences in uterine contraction patterns (frequency, amplitude, velocity, and contraction coordination) compared to healthy controls and depending on degree of dysmenorrhoea. What is known already The natural contraction pattern of the uterus changes throughout the menstrual cycle in response to cyclic changes in hormones. In abnormal uteri, such as adenomyotic uteri, this response may be different. Adenomyosis can cause dysmenorrhoea, menorrhagia, dyspareunia, and subfertility. These symptoms could be explained by different contraction patterns of the uterus, however, this has not yet been objectively quantified due to the absence of a suitable measurement tool. Recently, speckle-tracking and strain analysis of 2D TVUS was used to assess differences in contraction coordination, frequency, velocity, and direction, depending on the phase of the menstrual cycle in healthy women. Study design, size, duration This study is part of an ongoing multi-centre prospective observational cohort study investigating uterine contractility in TVUS recordings. Our study includes the TVUS recordings of 31 women with adenomyosis and 106 women with healthy uteri. Patients were included in 3 centres from 2017 to 2023 (Netherlands, Greece, Italy). Participants/materials, setting, methods 31 women with sonographic suspicion of adenomyosis and 106 women with healthy uteri with natural menstrual cycles were included. Uterine contraction frequency, amplitude, velocity, and coordination were assessed by applying a dedicated speckle tracking and strain analysis to 2-4-minute TVUS recordings in midsagittal section. Degree of dysmenorrhoea was measured according to visual analogue score (VAS). Women with suspicion of adenomyosis were compared to women with healthy uteri according to the phase of their menstrual cycle. Main results and the role of chance Age, BMI, parity and uterus volume were significantly higher in the women with adenomyosis compared to the healthy controls (p &amp;lt; 0.05). Uterine contractility differed between women with adenomyosis and healthy controls during the periovulatory phase, revealing lower frequency (1.50±0.25 vs. 1.75±0.35, p = 0.031), higher amplitude (0.076±0.039 vs. 0.046±0.018, p = 0.001), and lower velocity (0.64±0.18 vs. 0.84±0.22, p = 0.020) of uterine contractions in the group with adenomyosis patients. In the late luteal phase, women with adenomyosis showed higher amplitude (0.050±0.02 vs. 0.035±0.01, p = 0.039) and lower velocity (0.51±0.11 vs. 0.72±0.16, p = 0.032) than the healthy controls. During menstruation, women with adenomyosis showed a trend towards higher contraction amplitude (0.044± 0.01 vs. 0.037±0.01, p = 0.051) compared to healthy controls. During the menstrual, periovulatory and late luteal phase, women with adenomyosis showed reduced contraction coordination (p = 0.047, p = 0.015 and p = 0.011, respectively) compared to healthy controls. Increased dysmenorrhoea (VAS score) in overall adenomyosis patients was associated with lower contraction velocity (p = 0.043) and a tendency towards lower frequency (p = 0.160) and higher amplitude (p = 0.154). Limitations, reasons for caution No sub-analysis was done to assess effects of additional adenomyosis characteristics (i.e. adenomyosis severity, adenomyosis type, adenomyosis location). Women with extensive adenomyosis were not included due to impossibility to perform analysis of ultrasound images. Women with adenomyosis were older, had higher BMI and larger uterus volumes than healthy controls. Wider implications of the findings Uterine contractility differs between patients with adenomyosis versus healthy women throughout the menstrual cycle. More dysmenorrhoea in adenomyosis patients was also associated with a different contractility pattern. This suggests an aetiological mechanism for the clinical presentation of adenomyosis (i.e. dysmenorrhoea and subfertility) and presents potential therapeutic markers. Trial registration number NL52466.100.15

0111 Wearable-based Measures of Sleep Across the Menstrual Cycle in Healthy Women in the Reproductive Stage and Early Menopause

Abstract Introduction Sleep is an essential part of women’s health and well-being. Hormonal fluctuations that occur across the menstrual cycle or when approaching menopause might affect sleep quality. Most studies rely on self-reported data, or laboratory measures in small samples, to examine changes in sleep across the menstrual cycle. Here, we investigated sleep quality, as measured continuously with a wearable device, across the menstrual cycle in different reproductive stages (reproductive, menopausal transition). Methods 56 women participated, with 31 in the reproductive stage (age: 24.65 +/- 6.09 years) and 25 in the early menopausal transition (47.36 +/- 2.78 years). Participants were healthy, without sleep disorders, and free of premenstrual and mood complaints, as well as not using hormonal contraceptives. Sleep was tracked with the Oura ring across an entire menstrual cycle – confirmed as ovulatory using ovulation tests. Participants also completed a sleep diary each morning, rating sleep quality and how refreshed they felt. Measures were averaged for four phases: menses, ovulation, mid-luteal, late-luteal. Participants were assessed for mood symptoms (DASS-21) once during each of these phases. Results Objective measures of sleep quality (Total Sleep Time, Efficiency, and Wake After Sleep Onset) did not change across the menstrual cycle in either group or differ between groups. Similarly, self-reported sleep and mood symptoms remained stable across the menstrual cycle, although women in the menopausal transition reported poorer sleep quality and felt less refreshed than reproductive stage women, overall. Physiological measures (Temperature, Heart Rate, and Heart Rate Variability) during sleep reflected the well-known fluctuations across the menstrual cycle (e.g., increased temperature in the luteal phase vs. menses) in both groups of women. Conclusion Objective, wearable-derived measures indicate sleep quality remains stable across the menstrual cycle during reproductive and early-menopausal transition stages, at least in healthy women without mood or premenstrual complaints. While women in the menopausal transition reported a poorer sleep quality, there was no difference in objective sleep continuity measures between groups. Future studies are needed to better understand sleep across the reproductive lifespan, considering cycle-related (e.g., premenstrual syndrome) and other factors that could make some women sensitive to menstrual cycle effects on sleep. Support (if any) NIH, RF1AG061355 (BAKER/MEDNICK)

Circulating dihydrotestosterone, testosterone, and free testosterone levels and dihydrotestosterone-to-testosterone ratios in healthy women across the menstrual cycle

To characterize the circulating androgen levels across the menstrual cycle in healthy women using highly sensitive and accurate methods and report sex differences in the relative levels of dihydrotestosterone (DHT) to testosterone (T) levels. Prospective cohort study. Research clinic, academic teaching hospital. Twenty-one healthy premenopausal women, aged 19-40 years, with regular menstrual cycles. Not applicable. Serum total T and DHT levels measured using liquid chromatography-tandem mass spectrometry, free T levels measured using a standardized equilibrium dialysis method coupled with measurement of the T levels in the dialysate using liquid chromatography-tandem mass spectrometry, and comparison of the DHT-to-T ratio between healthy women and age-matched healthy men. The serum total and free T levels increased across the follicular phase and peaked at midcycle (total T, 43.6 ± 16.2 ng/dL; free T, 15.6 ± 11.9 pg/mL) and gradually declined in the luteal phase. The DHT level did not significantly change across the menstrual cycle. The DHT-to-T ratios were 1:4 and 1:13 in women and men, respectively. In healthy premenopausal women, the total and free T levels varied significantly across the menstrual cycle, whereas the DHT levels did not change; the peak total and free T levels in the midcycle period were higher than previously reported, underscoring the importance of establishing menstrual phase-specific reference ranges to avoid misdiagnosis of hyperandrogenism. Women have significantly higher DHT levels relative to total T than men; the significance of this sex difference in the DHT-to-T ratio needs further investigation.

Cardiovascular Function in Different Phases of the Menstrual Cycle in Healthy Women of Reproductive Age.

Background: Sex hormones influence the cardiovascular (CV) function in women. However, it is uncertain whether their physiological variation related to the regular menstrual cycle affects the CV system. We studied changes in the hemodynamic profile and body’s water content and their relation to sex hormone concentration in healthy women during the menstrual cycle. Material and methods: Forty-five adult women were examined during the early follicular, late follicular, and mid-luteal phases of the same menstrual cycle. The hemodynamic profile was estimated non-invasively by cardiac impedance while water content was estimated by total body impedance. Results were compared with repeated measures ANOVA with post-test, if applicable. Results: There were no significant changes in most hemodynamic and water content parameters between the menstrual cycle phases in healthy women. Left ventricular ejection time differed significantly among phases of the menstrual cycle, with shorter values in the mid-luteal phase (308.4 vs. 313.52 ms, p < 0.05) compared to the late follicular phase. However, the clinical relevance of such small differences is negligible. Conclusions: Changes in sex hormones during the physiological menstrual cycle appear to have no considerable effect on healthy women’s hemodynamic function and water accumulation.

P-305 Uterine contractile function across the menstrual cycle in healthy women: an exploration of objective reference values of sub-endometrial motion using speckle tracking

Abstract Study question To explore the characteristics of normal uterine contractile function across the menstrual cycle in healthy women using a novel quantitative ultrasound method. Summary answer We confirm reproducible differences in uterine contractility across the menstrual cycle; highest activity seen in the periovulatory phase, and lowest in the late luteal phase. What is known already Uterine peristalsis is the rhythmic, wave-like motion of the subendometrial layer of the uterus. Various subjective methods using visual interpretation suggest that uterine peristalsis features are different in the various stages of the menstrual cycle, and they are thought to be important for fertility. However, no method has been developed which can assess all uterine contraction features simultaneously. Recently, a new automated quantitative method to measure uterine contractility was validated in IVF patients to analyse uterine peristalsis on transvaginal ultrasound recordings with speckle-tracking. With this method a new contraction feature – coordination – can be assessed alongside frequency, direction, amplitude. Study design, size, duration Multi-centre observational prospective cohort study carried out in the outpatient gynaecology department of the Catharina Hospital in Eindhoven, the Netherlands, the University of Naples, Federico II, Naples, Italy and Embryolab Fertility centre in Thessaloniki, Greece. Patients were included from September 2020 up to January 2022. Primary outcomes were the contraction frequency (contractions/minute), amplitude, direction (Cervix-to-fundus, Fundus-to-cervix), and coordination. Participants/materials, setting, methods 63 women were included from the gynaecological department of participating centres. Women were included if they were ≥18 years of age, premenopausal and had a normal, natural menstrual cycle. A normal cycle was defined as: regular (duration ± 28 days), no dysmenorrhea, no menometrorrhagia. Transvaginal ultrasounds were performed during the menstrual phase (M), late follicular (periovulatory) phase (LF), early luteal phase (EL, ovulation + 3 days) and/or late luteal phase (LL, ovulation + 7 days). Main results and the role of chance Uterine contractility features were extracted from the gathered ultrasound recordings using a quantitative dedicated speckle tracking algorithm previously developed by our group. Each patient underwent a four-minute ultrasound of the uterus in mid-sagittal section. Patients had a mean age of 32 years, cycle duration of 27.8, and BMI of 23.0. The majority of women was nulliparous. The majority of uterine contraction features differed significantly between menstrual cycle phases. Contraction frequency was highest in the LF phase and lowest in the M and LL phases (1.55 vs. 1.28/min, p = 0.001). A trend was found for contractions during the periovulatory and early luteal phases contractions to travel mainly from cervix-to-fundus direction, whilst the menstrual phase showed contractions mainly from the fundus to cervix (p &amp;gt; 0.05). No significant difference between phases was found for contraction amplitude. Contraction coordination (simultaneous contraction of the anterior and posterior walls in the same direction) was highest in the periovulatory phase (p = 0.002). Our results are in line with with previous published studies using subjective visual inspection. Limitations, reasons for caution This is the first study investigating contraction coordination as a specific feature of uterine peristalsis. Not all patients were available for multiple ultrasounds during the same cycle, thereby a within-subjects comparison of the uterine contractions was not possible. Wider implications of the findings We explored further implementation of a quantitative method of uterine peristalsis measurement. Our investigation of a novel contraction characteristic - coordination - opens up possibilities for research and a potential etiological/treatment target. Further research using this method and suggested reference values will provide insight into contraction characteristics in abnormal uteri. Trial registration number NCT02310802

P-325 Endometriosis has no negative effect on embryo quality and morphokinetics. A retrospective case control study

Abstract Study question Does endometriosis affect embryo quality assessed by a time-lapse morphokinetic model analysis? Summary answer Endometriosis does not seem to have a negative effect on embryo morphokinetics and embryo quality assessed by a time-lapse in-house model. What is known already Endometriosis is strongly associated with infertility. Clinical studies suggest lower implantation and pregnancy rates in women with endometriosis. Embryos of women with endometriosis exhibit a higher incidence of developmental delay and arrested development than those derived from women without the disease. Poor oocyte and embryo quality have been suggested as a possible cause. It has been found that time-lapse systems which capture images of embryos at frequent time intervals allow continuous assessment of their quality. Developing an in-house model for embryo selection based on embryos with known implantation data (KID) enables detecting the highest quality embryos selected for transfer. Study design, size, duration A retrospective case control study between July 2013 and December 2020 which evaluated embryos from 58 ICSI cycles of women with endometriosis and 487 ICIS cycles of healthy women treated for male factor infertility. Morphokinetic parameters and rate of high-quality embryos were compared. High-quality was considered as: time to pronucleus fading (tPNf)&amp;lt;24.08, T2&amp;lt;26.6, S2&amp;lt;0.9, and t8&amp;lt;56 hours following insemination for cleavage embryos, and t2&amp;lt;26.6, S2&amp;lt;0.9, t8&amp;lt;56 and time to start blastulation (tSB)&amp;lt;96.6 hours for blastocysts. Participants/materials, setting, methods At a single infertility unit, women with endometriosis were compared to healthy women with male factor infertility as the control group. The main outcome was embryo kinetics which included: time to polar body extrusion (tPB2), time to pronucleus fading (tPNf), cleavage timings (t2-t8), synchrony of the second and third cycles (S2 and S3), duration of the second cycle (CC2) time to start blastulation (tSB). These parameters were set based on an in-house morphokinetic model. Main results and the role of chance We compared 154 embryos derived from 58 ICSI cycles of women with endometriosis to 1,387 embryos derived from 487 ICSI control cycles of couples with male factor as a single cause of infertility.There was a wider use of agonist protocol (48.3% vs 15.7%,p&amp;lt;0.001) and a higher rate of nuliparity (81% vs 61.5%, p = 0.003) in women with endometriosis compared to the control group. Demographic and treatment parameters were comparable including: maternal age, BMI, Gravidity, number of cycles, gonadotropins dosage, basal serum FSH, basal serum LH, estradiol and progesterone level at the day of ovum pick-up, number of oocytes aspirated, number of mature oocytes. There was no difference in tPB2, tPNf, t2-t8, S2 and S3, CC2, tSB between the groups. The rate of top quality embryos was comparable for both groups; for day 3 p = 0.25 and for day 5 p = 0.72. Pregnancy rate for the study and control group was 38.8% and 45%, respectively, p = 0.36. Limitations, reasons for caution One limitation is the retrospective methodology. Endometriosis severity was not taken into account which might be a confounding factor. The strengths are a single center study with embryos cultured under the same standardized laboratory conditions. However, a larger scale study might be needed. Wider implications of the findings Time lapse in-house model is an additive informative tool for embryo quality. Opposed to what was thought so far, the use of our time-lapsed system demonstrated that embryos of women with endometriosis had similar quality to healthy women. This can be used to reassure women with endometriosis before IVF treatment. Trial registration number not applicable

0317 Interaction of Sleep and Emotion Across the Menstrual Cycle

Abstract Introduction Women experience increased risk for sleep and affective disorders compared to men, attributed in part to monthly oscillations in sex hormones. Emotional functioning worsens during the perimenstrual phase. There is increasing evidence that sleep continuity also decreases during this phase. Thus, this study examined the interactive effects of sleep and menstrual phase on emotion across two menstrual cycles in healthy women. Methods Participants (N=51, 43% Caucasian) aged 18-35 (m=23.67) completed actigraphy and daily sleep/emotion diaries over two menstrual cycles (m days=51.29). Cycles were identified via date of menses and urinary ovulation detection, and coded into four phases: perimenstrual, mid-follicular, periovulatory, and mid-luteal. The perimenstrual phase was defined the 3 days prior to and the 3 days following menses onset. Variables included diary and actigraphic total wake time (TWT), daily ratings of positive (happy, calm, enthusiastic) and negative (angry, afraid, sad) affect using a 9-point scale. Relationships between phase, sleep, and emotion were estimated using multistep hierarchical linear modeling. Pandemic-related stress and daily US and region-specific COVID-19 case counts were included as covariates in adjusted models. Results Mean menstrual cycle length was 28.61±2.69 days. Menstrual phase was first entered into models as predictors for sleep and emotion variables independently. The perimenstrual phase positively predicted anger (p&amp;lt;.001) but no other emotions. Additionally, the perimenstrual phase predicted higher rates of TWT, such that diary-reported TWT was 8-16 minutes longer during the perimenstrual (m=67.54, SE=3.37) compared to other phases (p&amp;lt;.001). Actigraphic TWT was also increased by 4-7 minutes (m=61.54, SE=3.37) in the perimenstrual phase (p&amp;lt;.001). A second model included the interaction term, TWT*phase to the original model. Positive emotions were .05-.10 points lower (p’s=.006-.02) when TWT was greater in the perimenstrual phase. Conclusion Menstruating women experienced greater rates of anger and sleep disruption during the perimenstrual phase compared to other phases. When poor sleep occurred during the perimenstrual phase, however, women reported reduced positive emotions. Sleep disruptions, particularly occurring during the perimenstrual phase, may be an important intervention target for women at risk for affective disorders. Future studies should be mindful to assess menstrual phases when assessing sleep and circadian rhythm. Support (If Any)

Menstrual Cycle-Associated Changes in Micronutrient Biomarkers Concentration: A Prospective Cohort Study

Objective: To evaluate variations in micronutrient biomarker concentrations and deficiencies across the menstrual cycle in a cohort of healthy women. Methods: This prospective cohort study was conducted among healthy women of reproductive age living in the State College area, Pennsylvania, (n = 45). Data collection occurred at the early follicular phase, the late follicular phase, and the midluteal phase. Fasting blood samples were collected to measure micronutrient biomarkers. Results: At the early follicular phase, the mean ± SD concentrations for zinc, copper, magnesium, and retinol were 81.8 ± 16.2 µg/dL, 80.1 ± 12.8 µg/dL, 17.9 ± 1.4 mg/L, and 39.4 ± 9.3 µg/dL, respectively. The geometric mean (95% CI) for manganese, iron and ferritin concentrations were 1.51 [1.21, 1.87] µg/L, 106.7 [90.8, 125.4] µg/dL, and 26.4 [20.5, 34.0] µg/L, respectively. Mean concentrations of zinc and magnesium declined by 6.6% (p = 0.009) and 4.6% (p < 0.001) from the early follicular phase to the midluteal phase, respectively. Other biomarkers remained relatively constant across the cycle. At the early follicular phase, the prevalence of low serum concentrations for zinc, copper, magnesium, manganese, iron, and ferritin was 22%, 7%, 29%, 13%, 14%, and 28%, respectively. Also, in early follicular phase, 36% had anemia, and 13% specifically had iron deficiency anemia. The prevalence of magnesium deficiency was significantly higher at the midluteal phase vs. the early follicular phase (p = 0.025). Conclusions: Our study suggests that while many micronutrient concentrations are relatively constant across the menstrual cycle in healthy women, zinc and magnesium decline, and the prevalence of magnesium deficiency increases. Supplemental data for this article is available online at

Assessment of the Levels of Peripheral Lymphocytes Subpopulation in Healthy Women of Childbearing Age: a Prospective Cohort Study.

To evaluate changes in the levels of the peripheral lymphocyte subpopulation (PBLS) during the menstrual cycle in healthy women of childbearing age (HWOBA), for establishing a normal reference range. Flow cytometric analysis was performed for the assessment of the levels of PBLS during one menstrual cycle in HWOBA. Moreover, ovulation was monitored. The multivariable logistic regression models were used to evaluate the effects of age and body mass index (BMI) on PBLS. The levels of PBLS including CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD16+CD56+ lymphocytes and ratio of Th1/Th2 cells, were relatively stable during the menstrual cycle. However, each increment in age (year) was proportional to a decrease (14%) in the level of CD8+ T cells and an increase (10%) in the level of CD19+ B cells (p < 0.05). Increased BMI was inversely proportional to the level of CD16+CD56+ natural killer (NK) cells. Thus, the normal reference intervals for PBLS in HWOBA were established. The levels of PBLS can be used for daily monitoring of immune status in HWOBA. Notably, age and BMI may affect PBLS level. The normal reference ranges for PBLS levels can provide a basis for the research and treatment of recurrent pregnancy loss.

Subjective sleep quality and characteristics across the menstrual cycle in women with and without Generalized Anxiety Disorder

ObjectivePast studies have found that various psychiatric symptoms fluctuate over the menstrual cycle. Sleep disturbance is a transdiagnostic feature of psychiatric conditions and is associated with several symptoms that exhibit menstrual fluctuations. Although some evidence indicates that subjective sleep quality changes over the menstrual cycle in healthy women, no studies have investigated whether sleep fluctuates over the menstrual cycle in psychiatric populations, other than premenstrual dysphoric disorder. MethodsThe present study used a mixed between- within-groups design to compare self-reported sleep characteristics (sleep onset latency, number and duration of night-time awakenings, and total sleep time), sleep quality, insomnia symptoms, and daytime sleepiness in women with (n = 31) and without (n = 32) generalized anxiety disorder (GAD) at two time points within a single menstrual cycle – the early-follicular (low ovarian hormones) and mid-luteal (high ovarian hormones) phases. ResultsWomen with GAD reported lower sleep quality, more insomnia symptoms, and more daytime sleepiness (ηp2 = 0.13–0.14), but comparable sleep characteristics, compared to women without GAD. In both groups, sleep variables remained stable over the menstrual phases examined. Within-person changes in estradiol and progesterone between the two menstrual phases were mostly not associated with within-person changes in sleep variables, except that larger increases in estradiol were associated with a reduction in the number of night-time awakenings from the early-follicular to mid-luteal phases (β = −0.26). ConclusionThese findings indicate that subjective sleep disturbance, unlike other psychiatric symptoms, may not be modulated by the menstrual cycle and ovarian hormones during the phases examined in this study.

Effects of Menstrual Different Phases on Liver-Kidney Functions in Healthy Women

Background: The menstrual cycle is a critical rhythm of life regulated by interactive levels of estradiol, progesterone, luteinizing hormones, and follicular stimulation, during this cycle several metabolic parameters fluctuate in conjunction with sex hormones, therefore, this work was performed to investigate whether the menstrual cycle in healthy women affects the liver and kidney function. Materials and Methods: The study was conducted in the Faculty of Education for girls during the period October 2018–January 2019. It involved the participation of thirty healthy women with age between 18 and 26 years. All participants were non-smokers with no use of contraceptives or hormones. In addition, they confidently mentioned that they had had regular menstrual cycles (between 24 and 32 days). Results: Our findings showed that the liver enzymes (ALT, AST and ALP) levels were higher in the luteal phase than their levels in the follicular phase (P≤ 0.05). However, there were no significant differences in the level of blood urea and serum creatinine between the two phases. Conclusion: It can be concluded that the measurement of liver function test can be affected by the phases of menstrual cycle. It is important to take that into consideration when assessing the liver enzymes. It may also be of interest the potential beneficial effect endogenic E2 on liver enzymes.

Changes in pulp sensitivity across the menstrual cycle in healthy women and women with temporomandibular disorders.

Menstrual cycle may contribute to experimental pain measures in healthy women and women with chronic pain. The present study aimed to investigate variation in pulp sensitivity across the menstrual cycle in healthy women and women with temporomandibular disorders (TMD) and to explore the effect of TMD pain and psychosocial variables on the pulp response. This longitudinal study involved 47 regularly menstruating women aged 20-45, 24 healthy and 23 with diagnosed painful TMD. The electric and cold stimuli were performed by electric pulp tester and refrigerant spray, respectively, on mandibular lateral incisors, in five menstrual phases (menstrual, follicular, periovulatory, luteal and premenstrual). Research Diagnostic Criteria for TMD were used to assess TMD, chronic pain, depression and somatisation. Regression analysis was performed to investigate the effect of the predictor variables on the pulp sensitivity. Significant phase-related differences were observed for pain intensity to cold stimuli. Higher pain sensitivity was reported in menstrual in comparison with luteal phase (P=.019) among healthy women, and in menstrual in comparison with follicular (P=.033), periovulatory (P=.003) and luteal (P=.007) phases in TMD women. No significant differences were recorded for electric stimuli. Regression analysis identified depression as the determinant of cold and electric response in menstrual phase, regardless of age and presence of TMD. Menstrual phase in healthy and TMD women with regular menstrual cycle is characterised with higher pulp sensitivity to cold stimuli. Depressive symptoms independently influence pulp response in this phase.

Counterpoint: Investigators should not control for menstrual cycle phase when performing studies of vascular control that include women.

Observed sex differences in the epidemiology of cardiovascular disease incidence and the efficacy of clinical intervention strategies, coupled with recent mandates from the National Institutes of Health (NIH), and its international counterparts to consider sex as a biological variable in all preclinical and clinical work (15), have led to increased enrollment of women in human physiology studies of vascular function with the goal of improving external validity and clinical applicability of the findings. However, standard practice in these studies is to test women during the early follicular phase (~days 1-5) of the menstrual cycle, during which estrogen and progesterone concentrations are lowest, and either exclude or limit testing of women who use hormonal contraceptives to the placebo phase. This approach seeks to control for, or limit, differences in circulating hormone concentrations between men and women and is based on the dogmatic theory that cyclic changes in estrogen and progesterone concentrations lead to greater variability in study outcomes and uninterpretable datasets. Contrary to this common approach, we propose that limiting testing of women to this single phase 1) decreases external validity of the findings, 2) obfuscates potential physiological differences contributable to differences in sex hormone concentrations between men and women, and 3) is, in many instances, contradicted by literature that demonstrates limited or no variability in vascular measurements across the menstrual cycle.

Sağlıklı Kadınlarda Menstrüel Siklus Boyunca Gövde Kas Enduransı, Esneklik ve Uyku Probleminin İncelenmesi

Sağlıklı Kadınlarda Menstrüel Siklus Boyunca Gövde Kas Enduransı, Esneklik ve Uyku Probleminin İncelenmesi

The ovarian cycle may influence the exhaled volatile organic compound profile analyzed by an electronic nose

Introduction. We aimed to investigate whether the sex hormone profile during the ovarian cycle in healthy women could affect the volatile organic compound (VOC) profile analyzed by an electronic nose (e-nose). Methods. We enrolled 21 healthy, never-smoking, regularly menstruating women who were not taking any medications. A series of exhaled breath measurements were performed on all subjects at predefined intervals (days 1–6, 7–12, 13–19, 20–25 and 26–31; day 1 was the first day of menstruation) during their ovarian cycle and analyzed by an e-nose (Cyranose 320). Results. By principal component analysis, significant modifications of the exhaled VOC profile were observed over the cycle for principal component 1 (PC1; p = 0.001). In particular, the PC1 value was significantly higher during the premenstrual period and during menstruation compared with the first third of estrogen phase, mid-cycle and the first third of progestational phase (for all parameters p < 0.05 and p < 0.01, respectively). Subsequent linear discriminant analysis confirmed the above findings. Conclusions. The ovarian cycle may alter the exhaled VOC pattern and this should be taken into account during serial measurements of these markers in the female population.