Menstrual Cycle In Healthy Women Research Articles

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

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

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.

Mapping changes in women's visual functions during the menstrual cycle: narrative review.

This article systematically updates the literature on changes in visual functions during the phases of the normal menstrual cycle in women. To update Guttridge's 1994 review of visual structures and functions associated with the menstrual cycle and broaden the search through psychophysical, neuroimaging and neurobehavioral measurements covering 1994-2020. Narrative review conducted in a neurosciences and behavior laboratory in Brazil. The PubMed, Cochrane Clinical Answers and Google Scholar databases were searched. After screening and applying the eligibility criteria, 32 articles were examined. Through this analysis, the following information was extracted: (1) geographical distribution of the study; (2) sample size (according to age and phase of the menstrual cycle); (3) type of measurements according to psychophysical, neuroimaging and neurobehavioral instruments; (4) vision testing model; (5) visual subcategory evaluated; (6) categories of processed visual stimuli; and (7) main findings. The menstrual phases give rise to significant changes in visual functions, including in relation to orientation and spatial attention, visual campimetry and visual sensitivity. These relate specifically to the follicular and luteal phases. These findings theoretically expand the effects of menstrual cycles on visual functions found by Guttridge (1994). Despite some inconsistencies in the studies analyzed, it was found that visual processing during the follicular and luteal phases of the normal menstrual cycle of healthy women can explain physiological, cognitive, behavioral and social modulations.

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

Endometrial vascular development in heavy menstrual bleeding: altered spatio-temporal expression of endothelial cell markers and extracellular matrix components.

Are there any phenotypic and structural/architectural changes in the vessels of endometrium and superficial myometrium during the normal menstrual cycle in healthy women and those with heavy menstrual bleeding (HMB)? Spatial and temporal differences in protein levels of endothelial cell (EC) markers and components of the extracellular matrix (ECM) were detected across the menstrual cycle in healthy women and these are altered in HMB. HMB affects 30% of women of reproductive age with ~50% of cases being idiopathic. We have previously shown that the differentiation status of endometrial vascular smooth muscle cells (VSMCs) is altered in women with HMB, suggesting altered vessel maturation compared to controls. Endometrial arteriogenesis requires the co-ordinated maturation not only of the VSMCs but also the underlying ECs and surrounding ECM. We hypothesized that there are spatial and temporal patterns of protein expression of EC markers and vascular ECM components in the endometrium across the menstrual cycle, which are altered in women with HMB. Biopsies containing endometrium and superficial myometrium were taken from hysterectomy specimens from both healthy control women without endometrial pathology and women with subjective HMB in the proliferative (PP), early secretory (ESP), mid secretory (MSP) and late secretory (LSP) phases (N = 5 for each cycle phase and subject group). Samples were fixed in formalin and embedded in paraffin wax. Serial sections (3μm thick) were immunostained for EC markers (factor VIII related antigen (F8RA), CD34, CD31 and ulex europaeus-agglutinin I (UEA-1) lectin), structural ECM markers (osteopontin, laminin, fibronectin and collagen IV) and for Ki67 to assess proliferation. Immunoreactivity of vessels in superficial myometrium, endometrial stratum basalis, stratum functionalis and luminal region was scored using either a modified Quickscore or by counting the number of positive vessels. In control samples, all four EC markers showed a dynamic expression pattern according to the menstrual cycle phase, in both endometrial and myometrial vessels. EC protein marker expression was altered in women with HMB compared with controls, especially in the secretory phase in the endometrial luminal region and stratum functionalis. For example, in the LSP expression of UEA-1 and CD31 in the luminal region decreased in HMB (mean quickscore: 1 and 5, respectively) compared with controls (3.2 and 7.4, respectively) (both P = 0.008), while expression of F8RA and CD34 increased in HMB (1.4 and 8, respectively) compared with controls (0 and 5.8, respectively) (both P = 0.008). There was also a distinct pattern of expression of the vascular structural ECM protein components osteopontin, laminin, fibronectin and collagen IV in the superficial myometrium, stratum functionalis and stratum basalis during the menstrual cycle, which was altered in HMB. In particular, compared with controls, osteopontin expression in HMB was higher in stratum functionalis in the LSP (7.2 and 11.2, respectively P = 0.008), while collagen IV expression was reduced in stratum basalis in the MSP (4.6 and 2.8, respectively P = 0.002) and in stratum functionalis in the ESP (7 and 3.2, respectively P = 0.008). The protein expression of vascular EC markers and ECM components was assessed using a semi-quantitative approach in both straight and spiral arterioles. In our hospital, HMB is determined by subjective criteria and levels of blood loss were not assessed. Variation in the protein expression pattern between the four EC markers highlights the importance of choice of EC marker for investigation of endometrial vessels. Differences in expression of the different EC markers may reflect developmental stage dependent expression of EC markers in endometrial vessels, and their altered expression in HMB may reflect dysregulated vascular development. This hypothesis is supported by altered expression of ECM proteins within endometrial vessel walls, as well as our previous data showing a dysregulation in VSMC contractile protein expression in the endometrium of women with HMB. Taken together, these data support the suggestion that HMB symptoms are associated with weaker vascular structures, particularly in the LSP of the menstrual cycle, which may lead to increased and extended blood flow during menstruation. This study was funded by Wellbeing of Women (RG1342) and Newcastle University. There are no competing interests to declare. Not applicable.

The Menstrual Cycle Influences Emotion but Has Limited Effect on Cognitive Function.

From a psychological perspective, the menstrual cycle has been a research topic for more than 50 years. The most recent menstrual cycle research has been driven by an increased interest in sex differences in neuroscience, and the urge to understand sex disparities in prevalence, clinical presentation, and treatment response in psychiatric or neurologic disorders. Indeed, the menstrual cycle is an excellent model of ovarian steroid influence on emotion, behavior, and cognition. This review summarizes the emotion-related and cognitive findings of methodologically sound menstrual cycle studies. In particular, the review is devoted to the sex hormone-induced emotional disturbances in women with premenstrual dysphoric disorder, a subgroup of women responding with enhanced sensitivity to the normal fluctuations in endogenous hormone levels during the menstrual cycle. In addition, emotion processing and cognitive findings across the menstrual cycle in healthy women are also discussed. The overall conclusion is that that menstrual cycle differences in sexually dimorphic cognitive tasks are small and difficult to replicate. Emotion-related changes are more consistently found and are better associated with progesterone and the luteal phase, than with estradiol.

Cytomorphometric changes of oral mucosa during normal hormonal turnovers in healthy young menstruating women

Oral mucous membrane is an excellent indicator of the constitutional state of a patient. The oral mucosa is under tropic influence of various hormones and thus reflects the systemic status of an individual. Very few cytomorphometric studies are done to evaluate the role of sex hormones on oral mucosa. This study was done to determine the morphometric changes in a cell and nuclear diameter of exfoliated cells from the oral mucosa during the course of normal menstrual cycle in healthy women. The purpose of this study was to determine whether oral smears reflect hormonal state of menstrual cycle. In this study consisting of 40 study subjects and 20 control subjects, smears were collected from buccal mucosa twice per week for a period of three months. Morphometric analysis of the cell and nuclear diameter was done and results were statistically analysed. Cell diameter showed significant changes during various phases of the menstrual cycle of healthy young women. In Comparison of both study and control groups, no significant changes were seen in cell and nuclear diameter of the exfoliated cells. The present study showed changes in cell diameter of the study group which could be related to the role of female sex hormones.

Joint Model of Iron and Hepcidin During the Menstrual Cycle in Healthy Women.

Hepcidin regulates serum iron levels, and its dosage is used in differential diagnostic of iron-related pathologies. We used the data collected in the HEPMEN (named after HEPcidin during MENses) study to investigate the joint dynamics of serum hepcidin and iron during the menstrual cycle in healthy women. Ninety menstruating women were recruited after a screening visit. Six fasting blood samples for determination of iron-status variables were taken in the morning throughout the cycle, starting on the second day of the period. Non-linear mixed effect models were used to describe the evolution of iron and hepcidin. Demographic and medical covariates were tested for their effect on model parameters. Parameter estimation was performed using the SAEM algorithm implemented in the Monolix software. A general pattern was observed for both hepcidin and iron, consisting of an initial decrease during menstruation, followed by a rebound and stabilising during the second half of the cycle. We developed a joint model including a menstruation-induced decrease of both molecules at the beginning of the menses and a rebound effect after menses. Iron stimulated the release of hepcidin. Several covariates, including contraception, amount of blood loss and ferritin, were found to influence the parameters. The joint model of iron and hepcidin was able to describe the fluctuations induced by blood loss from menstruation in healthy non-menopausal women and the subsequent regulation. The HEPMEN study showed fluctuations of iron-status variables during the menstrual cycle, which should be considered when using hepcidin measurements for diagnostic purposes in women of child-bearing potential.

Sağlıklı Kadınlarda Menstrüel Siklus Esnasında Mukosiliyer Klerens Süresi

Amaç: Nazal mukosiliyer klerens, nazal solunum epitelinin en önemli savunma mekanizmasıdır. Hormonal değişikliklerin nazal mukoza aktivitesini etkilediği varsayılmaktadır. Bu çalışmada sağlıklı kadınlarda menstrüel siklusun mukosiliyer klerens süresi üzerine etkisi araştırılmıştır. Gereç ve Yöntemler: Çalışma grubunu, yaşları 20-40 yıl arasında 25 sağlıklı kadın oluşturdu. Katılımcılar ayrıntılı anamnez, kulak-burun-boğaz muayenesi ve nazal endoskopi sonrasında nazal mukosiliyer klerens süresi, midsiklus ve menstrüasyon esnasında sakarin testi ile değerlendirildi. Bulgular: Çalışmaya katılan kadınların yaş ortalaması (±standart sapma) 34,7±4,6 yıl idi. Midsiklusta mukosiliyer klerens süresi ortalama 11,7±2,8 (aralık:7-16 dk) iken, menstrüasyon esnasında bu değer istatistiksel olarak daha uzun, 16,3±2,4 (aralık:12-22 dk) olarak saptandı (p=0,0001). Sonuç: Bu çalışmada, kadınların menstrüasyon esnasında nazal mukosiliyer klerens süresinin uzadığı saptanmıştır. Menstrüasyon esnasında hastaların sıklıkla şikâyetçi olduğu nazal tıkanıklık hissi nazal mukosiliyer klerens süresinin uzamasına bağlı olabilir. Objective: Nasal mucociliary activity is the most important defence mechanism of the respiratory tract. Variations in steroid hormones in women have been reported to be one of the various factors effecting the activity of nasal mucosa. Our aim was to investigate the effect of menstrual cycle on nasal mucociliary clearance time. Material and Methods: A total of 25 healthy women (age, 20-40 years-old) consisted of the study group. After evaluation of detailedhistory, ear-nose and throat and nasal endoscopic examinations, nasal mucociliary clearance time of these women were evaluated by saccharin test during midcycle and menstruation. Results: Mean age (±standard deviation) of the women was 34.7±4.6 years-old. Mean mucociliary clearance time at midcycle and during menstruation was 11.7±2.8 (range: 7-16) and 16.3± 2.4 (range: 12-22) minute, respectively (p=0.0001). Conclusion: In the present study, the mucociliary clearance time during menstruation was found to be prolonged in women. Nasal congestion in menstruating women may be due to prolonged nasal mucociliary clearance time.