Menstrual Cycle In Premenopausal Women Research Articles

Sleep and menstrual irregularities: A systematic review

Sleep is crucial to human bodily function, pathological sleep patterns including extremes of sleep duration, poor sleep quality, and shift work are closely linked to menstrual irregularity. Our goal in this review is to evaluate the literature on the relationship between sleep patterns and irregular menstrual cycles in females and possibly to lay out the future research that needs to be done to better understand this issue in the Jordanian population. A literature search was performed using the PubMed, Scopus, and Google Scholar databases. Several studies stated that inadequate sleep had a negative effect on the menstrual cycle of premenopausal women. This review shines a light on the influence of sleep disturbance on the incidence of menstrual problems and emphasizes the importance of regular sleep on the health of premenopausal women.

Association between menstrual cycle phase and metabolites in healthy, regularly menstruating women in UK Biobank, and effect modification by inflammatory markers and risk factors for metabolic disease

BackgroundPreliminary evidence demonstrates some parameters of metabolic control, including glycaemic control, lipid control and insulin resistance, vary across the menstrual cycle. However, the literature is inconsistent, and the underlying mechanisms remain uncertain. This study aimed to investigate the association between the menstrual cycle phase and metabolites and to explore potential mediators and moderators of these associations.MethodsWe undertook a cross-sectional cohort study using UK Biobank. The outcome variables were glucose; triglyceride; triglyceride to glucose index (TyG index); total, HDL and LDL cholesterol; and total to HDL cholesterol ratio. Generalised additive models (GAM) were used to investigate non-linear associations between the menstrual cycle phase and outcome variables. Anthropometric, lifestyle, fitness and inflammatory markers were explored as potential mediators and moderators of the associations between the menstrual cycle phase and outcome variables.ResultsData from 8694 regularly menstruating women in UK Biobank were analysed. Non-linear associations were observed between the menstrual cycle phase and total (p < 0.001), HDL (p < 0.001), LDL (p = 0.012) and total to HDL cholesterol (p < 0.001), but not glucose (p = 0.072), triglyceride (p = 0.066) or TyG index (p = 0.100). Neither anthropometric, physical fitness, physical activity, nor inflammatory markers mediated the associations between the menstrual cycle phase and metabolites. Moderator analysis demonstrated a greater magnitude of variation for all metabolites across the menstrual cycle in the highest and lowest two quartiles of fat mass and physical activity, respectively.ConclusionsCholesterol profiles exhibit a non-linear relationship with the menstrual cycle phase. Physical activity, anthropometric and fitness variables moderate the associations between the menstrual cycle phase and metabolite concentration. These findings indicate the potential importance of physical activity and fat mass as modifiable risk factors of the intra-individual variation in metabolic control across the menstrual cycle in pre-menopausal women.

Effect of COVID-19 vaccinations on menstrual cycle and postmenopausal bleeding among health care workers: A cross-sectional study.

To determine the effect of coronavirus disease 2019 (COVID-19) vaccination and its association with sociodemographic factors on the menstrual cycle in premenopausal women and on postmenopausal bleeding. This is a retrospective cross-sectional study conducted between September 22, 2022, and November 30, 2022, via a questionnaire distributed to 359 health care workers (HCWs) at Lebanese American University Medical Center-Rizk Hospital and St John's Hospital. Inclusion criteria included female Lebanese HCWs who were vaccinated and aged 18 to 65 years. Change in cycle length was significantly associated with age (P = 0.025 after the first dose and P = 0.017 after the second dose), level of education (P = 0.013 after the first dose and P = 0.012 after the second dose), and fibroids (P = 0.006 after the second dose and P = 0.003 after the third dose). The change in cycle flow was significantly associated with age (P = 0.028), fibroids (P = 0.002 after the second dose and P = 0.002 after the third dose), bleeding disorders (P = 0.000), and chronic medications (P = 0.007). The change in symptoms was associated with polycystic ovary syndrome (P = 0.021), chronic medications (P = 0.019 after the second dose and P = 0.045 after the third dose), and fibroids (P = 0.000). COVID-19 vaccination can influence the menstrual cycle. Age, body mass index, level of education, underlying comorbidities, and use of chronic medications are significantly associated with changes in menstrual length, flow, and symptoms following vaccination.

Enhanced protection with ischemic preconditioning against endothelial ischemia-reperfusion injury during the luteal phase of the menstrual cycle in premenopausal women

PURPOSE: In premenopausal women, we have previously shown that the capacity of remote ischemic preconditioning (IPC) to protect against endothelial ischemia/reperfusion (I/R) injury is diminished during the early follicular phase of the menstrual cycle compared with the late follicular phase. The aim of this research was to extend our initial findings by determining how the luteal phase of the menstrual cycle influences remote IPC to alleviate endothelial I/R injury in a second sample of women. It was hypothesized that the capacity of remote IPC to alleviate endothelial I/R injury will be greater during the luteal phase of the menstrual cycle compared with the early follicular phase. METHODS: Eleven premenopausal eumenorrheic women (age 24±3 yr.) not taking any contraceptive medications were studied. Primary outcomes were the assessment of vascular endothelial function measured during the early follicular (after onset of menses; days 1-6) and at the peak luteal phase (days 21-24 after positive urine progesterone test). Endothelium-dependent vasodilation was assessed by the forearm blood flow (FBF) response to reactive hyperemia using venous occlusion plethysmography with and without endothelial I/R injury (20 min brachial artery ischemia, 15 min reperfusion) when preceded by remote IPC (3×5 min cycles of arm ischemia). RESULTS: Without endothelial I/R injury, peak FBF was similar (P=0.25) between the early follicular (26.6±5.0 ml/100 ml tissue/min) and luteal phases (25.1±3.9 ml/100 ml tissue/min). In contrast, there was a significant main effect (P&lt;0.001) of cycle phase on the capacity of IPC to protect against endothelial I/R injury. During the early follicular phase, peak FBF was significantly (P&lt;0.001) diminished 18% with endothelial I/R injury (from: 26.6±5.0 to 21.8±4.6 ml/100 ml tissue/min) despite remote IPC. As a result, total FBF during reactive hyperemia (area under the curve) was decreased ~25% (P=0.006) after (45.1±10.0) compared with before (59.8±14.1 ml/100 ml tissue) endothelial I/R injury. However, during the luteal phase endothelial I/R injury was prevented with remote IPC. Indeed, in the presence of endothelial I/R injury, peak FBF was well preserved (from: 25.1±3.9 to 27.2±5.7 ml/100 ml tissue/min; P=0.267). As a result, total FBF was similar (P=0.774) after (55.9±13.3) compared with before (51.7±13.8 ml/100 ml tissue) endothelial I/R injury. The level of endothelial protection from I/R injury with remote IPC during the luteal phase was similar (P=0.34) to the late follicular phase in our previous study. CONCLUSIONS: IPC-mediated vascular endothelial protection is robust during the luteal phase of the menstrual cycle but wanes in the early follicular phase. Greater circulating estrogens and perhaps progesterone during the luteal phase may contribute to the protective benefits of IPC in women, and sheds light about how cardioprotection may change with ovarian hormone deficiency with the menopause transition. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Similar inflammatory response and conduit artery vascular function between sexes following induced inflammation

What is the central question of this study? Are there sex differences in vascular function following induced inflammation when oestrogen is typically similar between sexes? What is the main finding and its importance? The present study suggests no sex differences in conduit artery vascular responses to acutely induced inflammation during the low-oestrogen phase of the menstrual cycle in premenopausal women. However, women exhibit lower microvascular function than men. Overall, the results underpin the role of oestrogen in previously observed sex differences and the importance of reporting the phase in the hormonal cycle when women are studied. Sex differences in cardiovascular disease incidence in premenopausal women and age-matched men have been attributed to the cardioprotective influence of oestrogen. However, limited knowledge exists regarding sex differences following acute inflammation when oestrogen concentrations are lower in women. We evaluated sex differences in vascular responses to induced inflammation when oestrogen concentrations are typically lower in women (early follicular phase or placebo phase of hormonal contraception). In 15 women and 14 men, interleukin-6 (IL-6) concentrations and vascular function [via brachial artery flow-mediated dilatation (FMD)] were assessed at baseline (BL) and 24 (24H) and 48hours (48H) after administration of influenza vaccine. After induction of inflammation, both sexes exhibited an increase in IL-6 concentrations at 24H [mean (SD) BL vs. 24H: women, 0.563 (0.50) vs. 1.141 (0.65) pg/ml; men, 0.385 (0.17) vs. 1.113 (0.69) pg/ml; P<0.05] that returned to near-baseline concentrations by 48H (BL vs. 48H, P>0.05). There were no sex differences in FMD, allometrically scaled FMD or IL-6 concentrations at any time point (P>0.05). Notably, women exhibited significantly lower microvascular function than men at every time point [P<0.05; reactive hyperaemic area under the curve (in arbitrary units): women, BL 35,512 (14,916), 24H 34,428 (14,292) and 48H 39,467 (13,936); men, BL 61,748 (27,324), 24H 75,028 (29,051) and 48H 59,532 (13,960)]. When oestrogen concentrations are typically lower in women, women exhibit a similar inflammatory response and conduit artery function, but lower microvascular response to reactive hyperaemia, in comparison to age-matched men.

Adjuvant Surgical Oophorectomy Efficacy According to Hormonally-Determined Menstrual Cycle Phase

Purpose: While there is now considered to be no significant outcome impact of the timing of breast surgery in the menstrual cycle of premenopausal women with breast cancer, the data with respect to adjuvant surgical oophorectomy in women with breast cancer have received limited exposition and attention. In a trial investigating the timing of surgical oophorectomy in women with metastatic disease, we observed a trend for poorer overall survival in women in women in prolonged follicular phases of the menstrual cycle, with low progesterone levels. Methods: The data from a previously reported adjuvant randomized clinical trial addressing the timing of surgical oophorectomy in the menstrual cycle have been examined in detail, presenting here new data from pre-planned secondary analyses. Multivariable Cox models were used.

THE EFFECT OF THE MENSTRUAL CYCLE ON RENIN, ALDOSTERONE AND ALDOSTERONE-TO-RENIN RATIO IN FORMERLY PREECLAMPTIC AND HEALTHY WOMEN

Abstract Objective: The aldosterone-to-renin ratio (ARR) is widely used as a screening test for primary aldosteronism (PA) in patients with hypertension. The purpose of the present original investigation is to identify the impact hormonal changes have on renin, aldosterone, and the ARR during the menstrual cycle of premenopausal women when measured in strict standardised conditions. Design and method: We analysed 59 women with a history of preeclampsia and 6 healthy parous controls. Blood values were determined during both follicular and luteal phases of the menstrual cycle (days 1 and 14 respectively). Plasma aldosterone, active plasma renin concentration (APRC) and the ARR were measured under standardised conditions. All measurements were taken in the supine position at 9am, all patients maintained a standardised sodium diet (100 mmol/day) for no less than two weeks. In those who were receiving antihypertensive medications (n = 2), all medications were discontinued at least 1 week prior to screening. Results: When performing the Friedman's Test and the Wilcoxon signed rank test in formerly preeclamptic women (n = 59), aldosterone and renin were both significantly elevated in the luteal phase (mean rank aldosterone 1.2 and 1.8 p0.000 Z-4.7, mean rank renin 1.23 and 1.77 p0.000 Z -4.5, respectively), however the ARR values did not significantly differ between phases (mean rank 1.53 and 1.47 p0.7 Z-0.14). When performing the Friendman's Test in the control group (n = 6), the difference in aldosterone, renin and the ARR between the follicular and luteal phase was not significant (p0.059 for all parameters). Wilcoxon signed test revealed a significant difference in aldosterone (Z-2.02 p0.04), but the difference in renin and the ARR remained insignificant (p0.06). Conclusions: In this study of premenopausal women we found that both renin and aldosterone are significantly affected by the menstrual cycle. However the resulting ARR was not statistically significantly altered. Our study indicates that it is not necessary to take the menstrual phase of patients into account when performing and interpreting the ARR as a screening test for PA in patients with a history of preeclampsia.

Comparative histological study of fallopian tube in pre and post-menopausal women in tertiary care center of Bihar: An observational and prospective study

Infertility an on-going reproductive problem and tubal pathologies are considered as leading causes. Ectopic pregnancy (tubal), salpingitis, genital tuberculosis are serious and very common fallopian tubal pathologies in women of reproductive age group which incidence have been increased in past few decades. Better understanding of fallopian tube anatomy, physiology, function and sperm epithelial interaction is a necessity and also nature of epidemiology and histological pattern is important. Observational and prospective study done on randomly selected 150 females either pre-menopause and post-menopause. Their fallopian tubes as specimen were collected with greatest care and precautions either from Obstetrics &amp; Gynaecology or Pathology Department of IGIMS, Patna. Samples were processed in Histology section of the Department of Anatomy, IGIMS, Patna. The slides were studied under the compound microscope. Data collected from this study was presented in tabular form. Statistical analysis was done using Microsoft Excel Software. Patients were mostly reproductive age group, 26-30 years (26%) and 31-35 years (20.6%) and most of them had completed their family and desired to have contraception mostly tubal ligation. 40 years and above age group patients had menopause and were mostly complaint of dysfunctional uterine bleeding. Samples received by hysterectomy with B/L Salpingo-oophorectomy (43.3%), B/L tube ligation with caesarean section (43.3%), U/L Salpingo-oophorectomy (7.3%), B/L tube ligation (6%). In most of these cases the fallopian tubes were normal. In pre-menopausal patients most of the samples were obtained during pregnancy (63.02%) because caesarean section with or without tube ligation was very common. Followed to interval phase (21.70%) of menstrual cycle because it was the most preferred stage for any planned gynaecological surgery. 11 Premenopausal women while 6 post-menopausal women gave the history of I.U.C.D use during their reproductive years. Patients with past history of oral contraceptives and those with present history of its use in both young and old women.This study concluded that the histology of fallopian tube was normal and the results were consistent with previous similar studies. Histological examination of fallopian tube was normal despite of any past history of IUCD or OCP use or different phases or cyclical changes of menstrual cycle in pre-menopausal women.

Influence of Menstrual Cycle Timing on Screening Breast MRI Background Parenchymal Enhancement and Diagnostic Performance in Premenopausal Women.

To assess the influence of menstrual cycle timing on background parenchymal enhancement (BPE) and performance on screening breast magnetic resonance imaging (MRI) in premenopausal women at high risk for developing breast cancer. After Institutional Review Board approval, all screening breast MRIs performed from January 2007 through November 2010 in premenopausal women in whom day from last menstrual period was recorded were identified. Prospectively recorded BPE levels and Breast Imaging Reporting and Data System MRI assessments were extracted from our database. Subject outcomes were determined by using biopsy, imaging follow-up, and linkage with the regional tumor registry (minimum 12-month follow-up). Associations of BPE levels (minimal/mild versus moderate/marked) with menstrual cycle phase (follicular [day 0-15] versus luteal [day 16-35]) and week (1, 2, 3, or 4) were compared. Differences in MRI performance metrics, including abnormal interpretation rate (AIR), positive biopsy rate (PBR), cancer yield, sensitivity, and specificity, were compared between menstrual cycle phase and menstrual cycle week. Three-hundred twenty examinations in 244 premenopausal women met inclusion criteria with nine cancers diagnosed. BPE levels were not associated with menstrual cycle phase or week (P > 0.05). MRI performance metrics (ie, AIR, PBR, cancer yield, sensitivity, or specificity) did not differ significantly based on menstrual cycle phase or menstrual cycle week (P > 0.05). Obtaining screening breast MRI exams during specific phases or weeks of the menstrual cycle in premenopausal women does not reliably produce MRI examinations with lower BPE levels or improved performance.

Assessment of Vascular Function throughout the Menstrual Cycle

BACKGROUND: Fluctuating sex hormones throughout the menstrual cycle, particularly endogenous estrogen, have been documented to correspond with nitric oxide (NO) bioavailability and likely have a cardioprotective effect in premenopausal women. However, the corresponding temporal changes in vascular function are not entirely understood. METHODS: Passive leg movement (PLM) is a relatively novel technique assessing NO-mediated vascular function, with a higher degree of NO-dependence than the traditionally used flow-mediated dilation (FMD) technique that could provide additional insight. PURPOSE: To assess vascular function throughout the menstrual cycle in premenopausal women using PLM, in addition to FMD. RESULTS: Brachial artery FMD tended to be increased during the OV phase (8.8±1%) compared to the EF (7.8±1%) and ML (7.6±1%) phases. The femoral artery PLM AUC response during the ML phase was significantly lower than the EF response (leg blood flow AUC EF: 154±41 mL, OV: 79±24 mL, and ML: 44±15 mL). CONCLUSION: These findings support the importance of menstrual cycle when interpreting vascular function data as measured by FMD and PLM.

Sex Differences in Cardiac Arrhythmias: Clinical and Research Implications.

Sex differences have the potential to impact diagnostic and therapeutic interventions in a wide variety of medical conditions, and cardiac arrhythmias are no exception.1 Studies evaluating pathophysiology, disease course, and therapeutic options for cardiac arrhythmias have been performed predominantly in male patients. However, catheter and device-based therapies coupled with landmark clinical trials have contributed to an improved understanding of this important aspect. The objective of this review is to present the current state of knowledge on sex differences in cardiac arrhythmias with a focus on clinical management, while highlighting gaps in knowledge that would benefit from future investigation. ### Atrial Fibrillation and Atrial Flutter #### Disease Burden Atrial fibrillation (AF) and atrial flutter (AFL) are the most commonly encountered tachyarrhythmias in clinical practice, with significant implications for public health and healthcare costs. Stroke, hospitalization, and loss of productivity are the major consequences of AF.2 The incidence of AF (per 1000 person-years) is reported to be between 1.6 and 2.7 in women and between 3.8 and 4.7 in men.2 The age-adjusted incidence and prevalence of AF is lower in women compared with that in men, and accordingly, the lifetime risk of AF from the Framingham Heart Study at 40 years of age was higher in men (26.0% for men versus 23.0% for women).3 Another analysis from the Framingham Heart Study demonstrated no significant sex differences in the risk of developing AFL.4 The prevalence of AF continues to rise among both men and women. In a study investigating the global burden of disease from 1980 to 2010, there was not only an increase in overall burden, incidence, and prevalence of AF, but most importantly an increase in AF-associated mortality in both men and women (Figure 1).5 The age-adjusted mortality for women was consistently higher compared with that for men from 1990 to 2010 (Figure …

Effect of Menopause on Pulmonary Functions: An Analysis

ABSTRACT Background Sex hormones play an important role in women’s health. There is a close relationship between female sex hormones and lung function in postmenopausal women. Deterioration of lung function is observed more after menopause. Estrogen deficiency after menopause accelerates adverse effects of biological aging on lung mechanics in postmenopausal women. Our study uses spirometer to analyze and evaluate these effects of menopausal aging. Objective To study the effects of menopause on pulmonary function tests in women of perimenopausal age group. Materials and methods This study was carried out in the Department of Obstetrics and Gynecology in Indira Gandhi Government Medical College &amp; Hospital, Nagpur, India. A total of 50 women each in premenopausal and menopausal age group were included in our study. Venous blood was collected under aseptic precaution on 10 to 14 days and 18 to 23 days corresponding to follicular and luteal phase of menstrual cycle in premenopausal women and in postmenopausal women, and serum estrogen and progesterone levels were estimated by microparticle enzyme immunoassay. Pulmonary function of all subjects was measured with digital micro spirometer and data collected. Peak expiratory flow rate (PEFR), forced expiratory flow (FEF)25-75, forced expiratory volume in 1 second, and forced vital capacity were studied and correlated with symptoms. Data analysis was done using Student’s unpaired t-test and chi-square test. Results The mean percentage of predicted values of FEF25-75 and PEFR were lower in postmenopausal women compared with premenopausal women. Mean serum estrogen levels were significantly lower in postmenopausal women as compared with premenopausal women. Progesterone levels were lower in postmenopausal women and in proliferative phase of premenopausal women as compared with luteal phase of menstrual cycle. Conclusion As menopause sets in decreased hormonal levels leads to decreased lung capacity as evident by pulmonary function test. Decreased pulmonary function test can be attributed to lower levels of sex hormones estrogen and progesterone in postmenopausal women. How to cite this article Karia AK, Kedar KV, Munje RP. Effect of Menopause on Pulmonary Functions: An Analysis. J South Asian Feder Menopause Soc 2017;5(1):16-18.

Estrogen variation during the menstrual cycle does not influence left ventricular diastolic function and untwisting rate in premenopausal women

BackgroundAlthough a cardioprotective effect of estrogen has been suggested by experimental studies, clinical data on the influence of estrogen on left ventricular (LV) diastolic function are sparse. The LV untwisting rate obtained by 2D speckle tracking echocardiography (2D-STE) is correlated with the time constant of LV pressure decay (tau), and this correlation is independent of left atrial pressure. Therefore, we used conventional Doppler echocardiography and 2D-STE to investigate changes in LV diastolic function during a single menstrual cycle in premenopausal women. MethodsTwenty healthy premenopausal woman (mean age, 28.1±2.7 years) were enrolled. Clinical and echocardiographic data were obtained during the follicular phase (F-phase) and luteal phase (L-phase) of a single menstrual cycle. We compared the clinical and echocardiographic data, and estrogen levels between the two phases. ResultsThere were no significant differences in LV diastolic parameters derived from Doppler echocardiography (E/A, p=0.295; E/e′, p=0.449, DcT, p=0.178) or 2D-STE (peak untwisting rate, p=0.892; time-to-peak untwisting, p=0.951) between the two phases of the menstrual cycle. However, there was a significant decrease in estrogen levels between the F- and L-phases (177±119pg/ml vs. 35±12pg/ml, p<0.0001). ConclusionsLV diastolic function in healthy premenopausal women did not significantly change during the menstrual cycle. Estrogen does not appear to have a significant acute effect on LV diastolic function in premenopausal woman.

Investigation of the Roles of Cyclooxygenase-2 and Galectin-3 Expression in the Pathogenesis of Premenopausal Endometrial Polyps.

Background:The pathogenesis and etiology of endometrial polyps has not been elucidated. In this study, we aimed to examine the pathogenic mechanisms of endometrial polyp development using immunohistochemistry. We evaluated the expression of galectin-3 and cyclooxgenase-2 (COX-2) during the menstrual cycle in premenopausal women with endometrial polyps or normal endometrium.MethodsThirty-one patients with endometrial polyps and 50 healthy control patients were included in this study. The levels of expression of COX-2 and galectin-3 were studied by immunohistochemistry.Results:The percentage of COX-2–positive cells and the intensity of COX-2 staining in the endometrium did not vary during the menstrual cycle either in the control group or in patients with endometrial polyps. However, expression of galectin-3 was significantly lower in endometrial polyps and during the proliferative phase of the endometrium compared with the secretory phase.Conclusions:Our data suggests that the pathogenesis of endometrial polyps does not involve expression of COX-2 or galectin-3.

Estradiol Inhibits Th17 Cell Differentiation through Inhibition of RORγT Transcription by Recruiting the ERα/REA Complex to Estrogen Response Elements of the RORγT Promoter

The symptoms of vaginal candidiasis exacerbate in the second half of the menstrual cycle in premenopausal women when the serum estradiol level is elevated. Estradiol has been shown to inhibit Th17 differentiation and production of antifungal IL-17 cytokines. However, little is known about the mechanisms. In the present study, we used mouse splenocytes and found that estradiol inhibited Th17 differentiation through downregulation of Rorγt mRNA and protein expression. Estradiol activated estrogen receptor (ER)α to recruit repressor of estrogen receptor activity (REA) and form the ERα/REA complex. This complex bound to three estrogen response element (ERE) half-sites on the Rorγt promoter region to suppress Rorγt expression. Estradiol induced Rea mRNA and protein expression in mouse splenocytes. Using Rea small interfering RNA to knock down Rea expression enhanced Rorγt expression and Th17 differentiation. Alternatively, histone deacetylase 1 and 2 bound to the three ERE half-sites, independent of estradiol. Histone deacetylase inhibitor MS-275 dose- and time-dependently increased Rorγt expression and subsequently enhanced Th17 differentiation. In 15 healthy premenopausal women, high serum estradiol levels are correlated with low RORγT mRNA levels and high REA mRNA levels in the vaginal lavage. These results demonstrate that estradiol upregulates REA expression and recruits REA via ERα to the EREs on the RORγT promoter region, thus inhibiting RORγT expression and Th17 differentiation. This study suggests that the estradiol/ERα/REA axis may be a feasible target in the management of recurrent vaginal candidiasis.

Monthly haemostatic factor variability in women and men

Hormonal status influences haemostatic factors including fibrinogen, factor VII and plasminogen activator inhibitor (PAI-1), and concentrations differ among men, premenopausal and postmenopausal women. This study examines how phases of the menstrual cycle influence variability of fibrinogen, factor VII and PAI-1. We studied 103 subjects (39 premenopausal women, 18 postmenopausal women and 46 men) during three, randomized, 8-week energy- and nutrient-controlled experimental diets in the Dietary Effects on Lipids and Thrombogenic Activity (DELTA) Study. Fasting blood samples were collected weekly during the last 4 weeks of each diet period, and haemostatic factors were quantified. Two linear mixed-effects models were used for fibrinogen, factor VII and PAI-1: one to estimate and compare group-specific components of variance, and the other to estimate additional fixed effects representing cyclical functions of day of menstrual cycle in premenopausal women. Systematic cyclical variation with day of menstrual cycle was observed for fibrinogen (P < 0.0001), factor VII (P = 0.0012) and PAI-1 (P = 0.0024) in premenopausal women. However, the amplitude of cycling was small relative to the total magnitude of intra-individual variability. In addition, the intra-individual variance and corresponding coefficient of variation observed in premenopausal women did not differ from postmenopausal women and men. The variability in haemostatic factors in premenopausal women is no greater than for postmenopausal women or men. Consequently, premenopausal women can be included in studies investigating haemostatic factor responses without controlling for stage of menstrual cycle.

Failure to Consider the Menstrual Cycle Phase May Cause Misinterpretation of Clinical and Research Findings of Cardiometabolic Biomarkers in Premenopausal Women

Biomarker assessment plays a critical role in the study and prevention of disease. However, variation in biomarkers attributable to the menstrual cycle in premenopausal women may impair understanding the role of certain biomarkers in disease development and progression. Thus, in light of the recently increasing evidence of menstrual cycle variability in multiple cardiometabolic biomarkers, a reexamination of approaches for appropriately studying and diagnosing cardiovascular disease in premenopausal women is warranted. We reviewed studies (from 1934 through 2012) evaluating changes in cardiometabolic biomarkers across phases of the menstrual cycle, including markers of oxidative stress, lipids, insulin sensitivity, and systemic inflammation. Each was observed to vary significantly during the menstrual cycle. For example, nearly twice as many women had elevated cholesterol levels warranting therapy (≥200 mg/dL) during the follicular phase compared with the luteal phase (14.3% vs. 7.9%), with only 3% having consistently high levels during all phases of the cycle. Similarly, nearly twice as many women were classified as being at an elevated risk of cardiovascular disease (high sensitivity C-reactive protein >3 mg/L) during menses compared with other phases (12.3% vs. 7.4%). Menstrual cycle-associated variability in cardiometabolic biomarkers is an important source of variability that should be accounted for in both research and clinical settings.

Cardiac Symptoms Related to Paroxysmal Atrial Fibrillation Varied With Menstrual Cycle in a Premenopausal Woman

Atrial fibrillation, an arrhythmia observed more frequently in men than women, is induced by both sympathetic and parasympathetic autonomic nerve activations. The menstrual cycle in premenopausal women has been reported to modulate the autonomic nervous system: parasympathetic activity is dominant in the follicular phase and sympathetic activity is dominant in the luteal phase. However, the relationship between atrial fibrillation and the menstrual cycle has not yet been reported, because this arrhythmia is very rarely detected in premenopausal women. We experienced a 38 year-old woman with paroxysmal atrial fibrillation. Her menstrual cycle was 30.4 ± 0.5 days and the menstrual period was 3.9 ± 0.2 days for 22 cycles. Although she had taken flecainide 200 mg/day, bepridil 200 mg/day, and propranolol 20 mg/day, she sometimes experienced mild palpitations. QTc intervals measured at her visits to our clinic were 440 ± 3 msec in the follicular phase and 425 ± 2 msec in the luteal phase (P = 0.01). These changes in QTc intervals during the menstrual cycle are compatible with earlier reports. During the 22 menstrual cycles, she felt palpitations on 3.2 ± 0.7 days in the menstrual period, 6.4 ± 0.3 days in the follicular phase, and 4.1 ± 0.4 days in the luteal phase (P = 0.01). Afterward, the medication was changed from daily to periodic administration for one week beginning a couple of days before the expected menstrual time, and she did not feel symptomatic variation in her menstrual cycle. These data suggest that her symptoms related to atrial fibrillation might have been dependent on parasympathetic activity.

Apparent Diffusion Coefficients of Normal Uterus in Premenopausal Women With 3.0-T Magnetic Resonance Imaging

To investigate the apparent diffusion coefficients (ADCs) of the normal uterine zonal structures (myometrium, endometrium, and junctional zone) during different phases of the menstrual cycle among premenopausal women with different age groups. Magnetic resonance (MR) images of 67 healthy women were obtained during the midproliferative and midsecretory phases. They were further divided into 3 age groups: group A (age range, 20-29 years); group B (age range, 30-39 years), and group C (mean age, 44.62 years; age range, 40-49 years). All the women underwent 3.0-T MR scanning twice. The ADC values were compared among each uterine zonal structure and 3 age groups and were calculated between the midproliferative and midsecretory phase. The ADC values among each uterine zonal structures were significantly different from one another (P < 0.001). The ADC values for endometrium in women in their 30s were higher than those in their 20s and in their 30s during the midproliferative and midsecretory phases (P < 0.05), and the ADC values for endometrium in each age groups were lower during the midproliferative phase than those during the midsecretory phase (P < 0.05), but there were no statistical differences in the myometrium and the junctional zone between the 2 phases or among age groups (P > 0.05). These preliminary results suggested that the zone, age, and phase of the menstrual cycle in premenopausal women should be considered when interpreting the ADC values of uterine structures (especially for endometrium).

P5-01-09: Differences in Serum Estradiol and Prolactin Concentrations in Women Who Yield Nipple Aspiration Fluid and Those Who Do Not.

Abstract Introduction: Nipple aspiration fluid, NAF is an important biosample for breast cancer research, but its utility is limited by the fact that the fraction of NAF-yielders varies from 35% to 90% in various studies. NAF yielders (Y) and non-yielders (NY) are known to differ in demographic characteristics, but the systemic endocrine profiles of Y and NY populations have not been studied, and may affect the generalizability of findings in studies of NAF. Methods: A subset of participants from an ongoing case-control study was included (120 cases, 120 controls). Cases are women presenting to the Lynn Sage Breast Center with newly diagnosed unilateral breast cancer, and controls are women presenting to the Lynn Sage Mammography Center who do not have cancer. NAF collection was attempted on all consented subjects; those yielding ≥2 uL NAF were designated as Y and those yielding &amp;lt;2 uL NAF were NY (120 Ys, 120 NYs). Menopausal status, age, race, menstrual cycle phase, mammographic density, and serum hormone levels were also collected. Differences between Y and NY groups were tested using a t-test for age, χ2 for race, and Wilcoxon Sum Rank Test for serum hormone levels. Mammographic density was quantitated using digital or digitized images and the CUMULUS software. Linear regression was used to test the relationship between a logged serum hormone values and if a patient yielded adjusting for phase of menstrual cycle in premenopausal women. Results: Mean ages of Ys and NYs were not different 51.0 and 52.6, respectively (p=0.11). The distribution of Ys by race (Caucasian, African American, other), was not different (χ2 p=0.58). Median serum prolactin concentrations were higher in Ys than NYs for both pre- (7.0 and 2.5 ng/ml) and post-menopausal (5.6 and 2.4 ng/ml) women, respectively (both p&amp;lt;0.01). Median serum estradiol was lower in yielding premenopausal patients only (pre- 90.5 and 64.3 pg/ml p=0.02; post- p=0.59). Stratifying the premenopausal women further into cases and controls, the difference only held for cases and not for controls (p=0.02, p=.033). In the premenopausal patients the regression models suggested that these relationships for estradiol and prolactin remain even after adjusting for phase of the menstrual cycle. No differences in Ys versus NYs were found for progesterone, follicle stimulating hormone, or sex hormone binding globulin. Mammographic density was not different for Ys as compared to NYs for pre- (22% and 20%, p=0.83), but was marginally lower for post-menopausal Ys versus NYs (11% and 15% density; p=0.07). Following stratification of the postmenopausal women into cases and controls, the cases who yielded had significantly lower than NYs (11% and 19% density, p=0.03), but the control Ys and NYs were not different (10% and 11% density, p=0.65). Conclusion: Pre- and post-menopausal women who yield NAF display increased serum prolactin levels, whereas decreased estradiol levels were observed in premenopausal NAF Ys. These findings suggest that NAF yield has systemic endocrine determinants, with implications for biomarker research on NAF samples. Further characterization of Y and NY women is important, along with standardization of methods of NAF collection, since NAF yield varies widely between studies. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-01-09.