Cycle In Healthy Women Research Articles

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.

Effects of concurrent vaginal miconazole treatment on the absorption and exposure of Nestorone® (segesterone acetate) and ethinyl estradiol delivered from a contraceptive vaginal ring: a randomized, crossover drug–drug interaction study

ObjectivesTo evaluate the effects of concurrent administration of three vaginal miconazole nitrate formulations on the absorption and exposure of Nestorone® (segesterone acetate) and ethinyl estradiol from a novel contraceptive vaginal ring (NES/EE CVR). Study designThis was an open-label, randomized, crossover, drug–drug interaction study conducted over three menstrual cycles in healthy women with regular menses. We compared systemic exposure to NES and EE by determining area under the curve (AUC8–21d) with CVR only and CVR with each miconazole treatment. Three different miconazole formulations (single-dose suppository, multiple-dose suppository or multiple-dose cream) were administered in a single dose on day 8 or multiple doses on days 8–10 after CVR insertion. We evaluated safety and tolerability of the CVR in the presence of antimycotic comedication. ResultsForty-five participants were randomized, and 29 completed participation. Systemic exposure to NES and EE released from the CVR increased with single or multiple doses of miconazole suppositories but not with multiple-dose cream. The maximum EE geometric mean ratio (GMR) for AUC8–21d was 1.67 (1.51–1.86) for single-dose and 1.42 (1.21–1.66) for multiple-dose suppositories. By contrast, systemic exposure to NES and EE was comparable with and without miconazole cream (all GMRs and confidence intervals within 0.80 to 1.25). Adverse events (AEs) were similar with CVR only and with all miconazole treatment groups. There were no serious treatment-related AEs. ConclusionsMiconazole vaginal suppositories were associated with increased systemic levels of NES and EE, while systemic exposure with miconazole vaginal cream was comparable to no miconazole exposure. ImplicationsCoadministration of miconazole suppositories with the investigational NES/EE CVR led to higher systemic exposure of both hormones, while coadministration with miconazole cream did not affect hormone levels. Women utilizing the NES/EE CVR may be advised to use an oral formulation or miconazole cream rather than suppository to treat vaginal candidiasis.

Transvaginal Echographic Diagnosis of Chronic Cervicitis

Objective: To study the echographic semiotics of cervicitis in women of reproductive age in a transvaginal way. Materials and methods: The study included 166 women aged 19-35 years with chronic cervicitis. The diagnosis was established on the basis of clinico-laboratory, colposcopic and cytological studies. In 71 (42.8%) cases, the age of women varied between 19-25, in 95 (57.2%) - 26-35 years. The diagnosis was established on the basis of clinico-laboratory, colposcopic and cytological studies. The comparative group (СG) consisted of 50 healthy women who had a childbirth and abortion in an anamnesis, with normal vaginal microbiocenosis and without pathological changes in the cervix. In 18 (36%) cases their age varied within the limits of 19-25, in 32 (64%) - 26- 35 years respectively. Results: The increased echogenicity of endocervix was not observed in 4-6 days of the cycle in healthy women and in 94 (56.6 ± 3.8%) cases of chronic cervicitis were observed. The heterogeneity of the endocervical echostructure in healthy women was recorded in 2 (4.0 ± 2.8%), and in cases of healthy women in 153 (92.2 ± 2.1%) cases, respectively (p <0.001). Hyperechoic inclusions in endocervix were observed in 112 cases (67.5 ± 3.6%) of chronic cervicitis, and in 4 (8.0 ± 3.8%) cases of healthy women (p <0.001). Cysts of endocervix in healthy women were noted in 67 (40.4 ± 3.8%) cases, and in healthy women - in 3 (6.0 ± 3.4%) cases, respectively (p <0.001). Among women with chronic cervicitis, small cystic cavities in the outer throat area were detected in 92 (55.4 ± 3.9%) cases, colposcopically in 71 (42.8 ± 3.8%) in cases (p <0, 05) Conclusions: In the early proliferative phase of the cycle, a combination of structural heterogeneity, increased echogenicity, the presence of an irregular shape of small cystic cavities and hyperechoic inclusions, moderate or increased vascularization are reliable signs of chronic endocervicitis. Chronic cervicitis in the majority of cases is accompanied with pseudo-erosion. Transvaginal echographically, pseudo-erosion is diagnosed better than erosion. In the diagnosis of erosion, transvaginal echography is inferior to colposcopy, but better reveals deepseated changes. Transvaginal echography can better characterize the changes within the endocervix, which is not available endoscopy

Aberrant Endometrial DNA Methylome and Associated Gene Expression in Women with Endometriosis.

Endometriosis is an estrogen-dependent, progesterone-resistant disorder largely derived from retrograde transplantation of menstrual tissue/cells into the pelvis, eliciting an inflammatory response, pelvic pain, and infertility. Eutopic endometrium (within the uterus), giving rise to pelvic disease, displays cycle-dependent transcriptomic, proteomic, and signaling abnormalities, and although its DNA methylation profiles dynamically change across the cycle in healthy women, studies in endometriosis are limited. Herein, we investigated the DNA methylome and associated gene expression in three phases of the cycle in eutopic endometrium of women with severe endometriosis versus controls, matched for ethnicity, medications, smoking, and no recent contraceptive steroid use. Genome-wide DNA methylation and gene expression were coassessed in each sample. Cycle phase was determined by histology, serum hormone levels, and unsupervised principal component and hierarchical cluster analyses of microarray data. Altered endometrial DNA methylation in endometriosis was most prominent in the midsecretory phase (peak progesterone), with disruption of the normal pattern of cycle-dependent DNA methylation changes, including a bias toward methylation of CpG islands, suggesting wide-range abnormalities of the chromatin remodeling machinery in endometriosis. DNA methylation changes were associated with altered gene expression relevant to endometrial function/dysfunction, including cell proliferation, inflammation/immune response, angiogenesis, and steroid hormone response. The data provide insight into epigenetic reprogramming and steroid hormone actions in endometrium contributing to the pathogenesis and pathophysiology of endometriosis.

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.

Are Women Sensitive to the Acute Anxiolytic Effect of Diazepam?

Objective: Several studies have shown the influence of ovarian hormones on the GABAergic system. As women are naturally exposed to monthly fluctuation of these hormones, it is possible that their response to benzodiazepines also change over the ovarian cycle. Bearing this in mind, this study aimed to evaluate the possible influence of the ovarian cycle of healthy women on the acute effect of diazepam. Methods: Forty subjectively healthy women were selected and randomly allocated to two different groups, according to their ovarian cycle phase, follicular (6 to 10 days from the first day of the cycle) or luteal (5 to 10 days after detection of urinary LH peak). Both groups completed the Video-Monitored Stroop Color-Word Test (VMSCWT), an experimental model of anxiety, under the influence of diazepam (10 mg) or placebo. Psychological parameters (State-Trait Anxiety Inventory, Self-evaluation of Tension Level, Visual Analogue Mood Scale) and physiological parameters (heart rate and gastrocnemius electromyogram activity) were evaluated throughout the test. All the data obtained were analyzed using analysis of variance (ANOVA) followed by Tukey’s test for post hoc comparisons, both at the 5% significance level. Results: The results showed that, in the follicular phase, women did not respond to the anxiolytic action of diazepam, although a sedative effect was observed; while in the luteal phase, there was no response to either sedative or anxiolytic actions. As a control for the experimental conditions, a group of 18 men was also administered to the VMSCWT. The results confirmed that both the anxiogenic test and the administered drug were working as expected, since diazepam managed to prevent the anxiety induced by the test. Conclusion: Therefore, the present findings indicate that the ovarian cycle can alter the effects of the acute administration of diazepam, which can vary from no effect to sedation, without going through anxiolysis.

Interaction of menstrual cycle phase and sexual activity predicts mucosal and systemic humoral immunity in healthy women

Several studies have documented shifts in humoral immune parameters (e.g., immunoglobulins) across the menstrual cycle in healthy women. It is thought that these shifts may reflect dynamic balancing between reproduction and pathogen defense, as certain aspects of humoral immunity may disrupt conception and may be temporarily downregulated at ovulation. If so, one could expect maximal cycle-related shifts of humoral immunity in individuals invested in reproduction – that is, women who are currently sexually active – and less pronounced shifts in women who are not reproductively active (i.e., abstinent). We investigated the interaction of sexual activity, menstrual cycle phase, and humoral immunity in a sample of 32 healthy premenopausal women (15 sexually active, 17 abstinent). Participants provided saliva samples during their menses, follicular phase, ovulation (as indicated by urine test for LH surge), and luteal phase, from which IgA was assayed. Participants also provided blood samples at menses and ovulation, from which IgG was assayed. Sexually active participants provided records of their frequency of sexual activity as well as condom use. At ovulation, sexually active women had higher IgG than abstinent women (d=0.77), with women reporting regular condom use showing larger effects (d=0.63) than women reporting no condom use (d=0.11). Frequency of sexual activity predicted changes in IgA (Cohen's f2=0.25), with women reporting high frequency of sexual activity showing a decrease in IgA at ovulation, while women reporting low frequency or no sexual activity showing an increase in IgA at ovulation. Taken together, these findings support the hypothesis that shifts in humoral immunity across the menstrual cycle are associated with reproductive effort, and could contribute to the mechanisms by which women's physiology navigates tradeoffs between reproduction and immunity.

Heart rate variability across the menstrual cycle in young women taking oral contraceptives.

Previous studies have shown that resting heart rate variability (HRV) is modified by different phases of the menstrual cycle in nonusers of oral contraceptive pills (OCP); however, the effect of OCP on autonomic control of the heart remains unclear. The purpose of this study was to investigate HRV during the low hormone (LH-not taking OCP) and during the high hormone (HH-active OCP use) phases of the menstrual cycle in young women. Seventeen healthy women (19-31 years) taking OCP for at least 6 consecutive months were enrolled in this study. Plasma estradiol and progesterone were verified at each visit. HRV was assessed by using one-lead electrocardiography in time and frequency domains, in which participants rested in the supine position for a 20-min period with a breathing rate of 15 cycles/min. In addition, resting heart rate, and systolic and diastolic blood pressure were obtained. Both plasma estradiol (LH: 19.8 ± 4.2 pg/mL vs. HH: 12.4 ± 1.5 pg/mL; p > .05) and progesterone (LH: 0.247 ± 0.58 ng/mL vs. HH: 0.371 ± 0.08 ng/mL; p > .05) (mean ± SE) levels were similar in both phases. No significant difference was obtained for any component of HRV, heart rate, or blood pressure between the LH and HH phases (p > .05). These results provide preliminary evidence that use of OCP does not affect HRV during the menstrual cycle in healthy women.

Differences in the Molecular Species of CA125 Across the Phases of the Menstrual Cycle.

CA125, a tumor-associated antigen, is primarily used to monitor epithelial ovarian cancer. There is evidence that different species of CA125 exist; however, it is not known if any of these species are present in healthy women during the menstrual cycle and if they are associated with serum concentrations of CA125. The purpose of this study was to determine if the molecular species of CA125 differ across the three phases of the menstrual cycle in healthy women. Healthy, Caucasian women between the ages of 18 and 39 were enrolled using strict criteria to exclude factors known to contribute to CA125 fluctuations. Menstrual cycle regularity was determined using calendars maintained by participants for 3 months. After cycle regularity was established, blood was drawn at three time points for Western blot analysis. Western blot analysis yielded 17 distinct profiles (i.e., patterns of species) of CA125, with 80% of the sample exhibiting 5 common profiles. No differences in demographic characteristics and serum CA125 values were found among the various CA125 profiles. Different molecular species of CA125 exist in healthy women with regular menstrual cycles. These data provide evidence that CA125 is not a homogeneous molecular species. Future research should evaluate the molecular composition and the clinical importance of these species.

Change of anti-Mullerian-hormone levels during follicular phase in PCOS patients

Anti-Mullerian-hormone (AMH) does not seem to fluctuate significantly during the menstrual cycle in healthy women. However, little is known about cycle fluctuations of AMH levels in patients with polycystic ovarian syndrome (PCOS). The purpose of this study was to examine AMH fluctuations during the follicular phase in PCOS patients receiving antiestrogens or recombinant follicle-stimulating hormone (FSH). About 40 PCOS patients diagnosed according to Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group 2003 and 19 controls were prospectively enrolled. PCOS patients received either antiestrogens or recombinant FSH for monoovulation induction and controls received antiestrogens. AMH levels were determined (1) between the 2nd and the 5th day of follicular phase and (2) when a single large dominant follicle ≥18 mm had appeared. Our study shows that AMH levels do not change during follicular development in controls as well as in PCOS patients with AMH levels < 5 ng/ml, irrespective of antiestrogen or FSH therapy. However, in PCOS patients with AMH levels ≥5 ng/ml, AMH declines significantly during follicular development (p < 0.01). We conclude that AMH levels should be determined in the early follicular phase in PCOS patients without the influence of antiestrogens or exogenous FSH, because these interventions may lower AMH values in patients with high levels.

Effects of anodal TDCS stimulation of left parietal cortex on visual spatial attention tasks in men and women across menstrual cycle

Sex hormonal variations have been shown to affect functional cerebral asymmetries in cognitive domains, contributing to sex-related differences in functional cerebral organization.The aim of this study was to investigate spatial attention by means of a bisection line test and computer-supported attention task during the menstrual cycle in healthy women compared to men, in basal condition and under Transcranial Direct Current Stimulation (TDCS) of the left parietal cortex. Women were studied during the menses, follicular and luteal phases, ascertained by transvaginal ultrasounds. In basal conditions, women showed a clear deviation toward the right in the bisection line test during the menstrual phase, similarly to men. The midpoint recognition in the computer-supported attention task was not influenced by the menstrual cycle for women, while men showed a significant increase in errors toward the left side. The anodal activation of the left parietal cortex did not affect the line bisection task, while in men it reduced the total amount of errors in midpoint recognition observed in the computer supported attention task. The hand-use effect demonstrated by the bisection-line test could be influenced by estrogen fluctuations, while the right hemisphere prevalence in spatial attention appears to be gender-related and scarcely influenced by the menstrual cycle. The left parietal cortex seems to exert a scarce effect on hand-use effect, while its activation is able to revert sex related right hemisphere supremacy.

The effects of kisspeptin administration on the menstrual cycle in healthy women

BackgroundKisspeptin (encoded by the KISS1 gene) is a crucial regulator of normal reproductive function. In human beings, KISS1 deletion results in a failure to go through puberty whereas activating mutations result in central precocious puberty. Administration of kisspeptin induces ovulation in rodents and sheep, but whether exogenous kisspeptin can alter the menstrual cycle in healthy women is not known. This study aimed to determine the effects of kisspeptin administration on the menstrual cycle in healthy women. MethodsA prospective, single-blinded, one-way crossover study at Imperial College, London, was performed. Five healthy female volunteers aged 24–37 years were recruited through adverts in the local press. They each received twice-daily subcutaneous injections of kisspeptin-54 or saline for 7 days during days 7 to 14 of their menstrual cycle. All women underwent serial assessments of basal reproductive hormones, ultrasound measurements, and luteinising hormone (LH) pulsatility, as well assessment of acute sensitivity to gonadotrophin-releasing hormone (GnRH) and kisspeptin injection. Because of the intensive protocol, women attended for assessments every 2–3 days throughout the cycle, rather than daily, to minimise stress and enhance compliance. Ethics approval was granted by the Hammersmith and Queen Charlotte's and Chelsea Hospitals Research Ethics Committee (registration number 05/Q0406/142). FindingsKisspeptin-54 treatment shortened the menstrual cycle (mean length of menstrual cycle: saline 28·6 days [SE 3·1] vs kisspeptin 26·8 [3·1], p=0·0043), advanced the onset of highest recorded serum LH (mean menstrual day of highest recorded LH 15·2 [SE 2·9] vs 13·0 [4·1], p=0·0372), and advanced the onset of the luteal phase of the menstrual cycle (mean menstrual day of progesterone increase 18·0 [SE 2·1] vs 15·8 [2·0], p=0·0402). On menstrual day 15, the largest ovarian follicle had a significantly higher diameter after kisspeptin-54 than after saline (mean diameter of largest follicle saline 10·0 mm [SE 4·4] vs kisspeptin 15·5 mm [2·2], p=0·04). LH pulsatility was maintained during kisspeptin-54 treatment. Sensitivity to exogenous kisspeptin-54 and exogenous GnRH was maintained during twice-daily kisspeptin-54 administration. InterpretationWe have shown, for the first time to our knowledge using biochemical and radiological data, that exogenous kisspeptin-54 advances the menstrual cycle in healthy women. These data have important therapeutic implications for the use of kisspeptin in the treatment of women with reproductive disorders. Even though participants attended every 2–3 days rather than daily, statistical significance in key parameters was still achieved, confirming the strength of the data. In addition, use of both biochemical and radiological data allowed detailed analysis of the underlying physiological processes. FundingWellcome Trust, National Institute for Health Research, UK Medical Research Council.

Pulse rate and Spo2 in different phases of menstrual cycle in healthy women of Kerala

Background and Objectives: The studies on relationship between different phases of menstrual cycle and pulse rate and Sp02 changes in healthy women of Kerala are inadequate. So, this preliminary study was plan to report the same. Material and Methods: The present study was performed in twenty healthy women of Kerala, age ranging from 20-40 (mean age 27+/- 61054). Spo2 and pulse rate were recorded with pulse - oximeter in different phases of menstrual cycle and analysis of data was done by spss 20.0. Results: Variations of pulse rate and Spo2 in different phases of menstrual cycle are not statistically significant at p &gt; 0.05. Conclusion: it was observed that there was slight increase in pulse rate in ovulatory phase and slight increase in Sp02 in secretory phase, though it is not statistically significant. It may be due to small sample size. Hence this study certainly merits continuing the work with more investigations in the field. Janaki Medical College Journal of Medical Sciences (2013) Vol. 1 (2): 65-69 DOI: http://dx.doi.org/10.3126/jmcjms.v1i2.9271

Plasma levels of stromal cell-derived factor-1 (CXCL12) and circulating endothelial progenitor cells in women with idiopathic heavy menstrual bleeding

Do plasma levels of stromal cell-derived factor-1 (CXCL12, sometimes termed SDF-1) and the numbers of circulating endothelial progenitor cells (EPCs), EPC colony-forming units (EPC-CFU) and mature endothelial cells (ECs) differ between women with idiopathic heavy menstrual bleeding of endometrial origin (HMB-E) and controls and are they related to plasma levels of other angiogenic growth factors? Angiogenesis is altered in women with HMB-E, characterized by a reduction in mean plasma levels of CXCL12, a low number of EPCs-CFUs and a high level of circulating ECs. Plasma levels of CXCL12 are significantly higher during the proliferative than the secretory phase of the menstrual cycle in healthy women and exhibit a negative correlation with blood EPC-CFUs. A prospective cohort study in a university hospital setting. Between 2008 and 2009 10 HMB-E patients were recruited from Karolinska University Hospital. Ten healthy women were also included in the analysis. Ten healthy control women and 10 HMB-E patients, all with regular menstrual cycles, provided 4 blood samples during a single menstrual cycle: 2 in the proliferative phase, 1 at ovulation and 1 in the secretory phase. We assessed plasma levels of CXCL12, vascular endothelial growth factor A(165) (VEGFA), basic fibroblast growth factor (bFGF) and granulocyte and granulocyte-macrophage colony-stimulating factors by ELISA. We counted circulating EPC-CFUs by culture, and ECs and EPCs by flow cytometry and immunostaining for cell surface markers. Plasma levels of CXCL12 were significantly lower in HMB-E patients compared with control women (P < 0.0001), with a significant decrease (P = 0.013) between the proliferative phase and ovulation. VEGFA showed a trend towards the same decreasing pattern as CXCL12, although not statistically significant (P = 0.086), whereas systemic VEGFA levels in control women remained unchanged across the different phases of the menstrual cycle (P = 0.473). HMB-E patients had a lower number of EPC-CFUs compared with control women (P = 0.014), with a positive correlation between the level of CXCL12 and EPC-CFUs (r = 0.428; P = 0.047). Whilst the level of circulating endothelial cells in HMB-E patients was higher than in control women, this did not reach statistical significance. In contrast, the levels of the hematopoietic/EPC marker CD34 were significantly lower in HMB-E patients than control women (P < 0.020). Small sample, unknown source of CXCL12, unknown balance between influx and efflux of EPCs from bone marrow and to the endometrium. Our results indicate that CXCL12 may play an important role in physiological angiogenesis in the endometrium, and that low and dysregulated levels of CXCL12 in women with HMB-E could affect vessel quality, integrity and repair. Financial support was provided through the regional agreement on medical training and clinical research (ALF) between the Stockholm County Council and Karolinska Institutet (number 20110258). This study was also supported by grants from the Swedish Labor Market Insurance. The authors have no conflict of interest to declare.

Association of pain catastrophizing with pain processing across the menstrual cycle in healthy women

Association of pain catastrophizing with pain processing across the menstrual cycle in healthy women

Premenstrual Dysphoric Disorder and the Brain

Premenstrual Dysphoric Disorder and the Brain

Comparing Pain Sensitivity and the Nociceptive Flexion Reflex Threshold Across the Mid-follicular and Late-luteal Menstrual Phases in Healthy Women

Understanding the relationship between the menstrual cycle and pain can contribute significantly to our knowledge of pain processing in women. Many early studies suggested that pain sensitivity was enhanced during the luteal phase of the menstrual cycle relative to the follicular phase; however, these studies were often limited by small sample sizes, lack of ovulation verification, focus on a single pain modality, inadequate assessment of menstrual cycle regularity, and low-powered statistical methods. The current study was designed to address these limitations and examine the difference in pain processing between the mid-follicular (days 5 to 8) and late-luteal (days 1 to 6 preceding menses) phases. Forty-one healthy, regularly cycling women attended testing sessions that measured pain sensitivity from mechanical pain threshold, electrocutaneous pain threshold/tolerance, and ischemia pain threshold/tolerance, as well as McGill Pain Questionnaire qsensory and affective ratings of electric and ischemic stimuli. Electrocutaneous stimulation was also used to assess nociceptive flexion reflex threshold, a physiological measure of spinal nociception. When analyses were limited to data collected only in the targeted menstrual phases (N=30), results indicated no menstrual phase effect on any pain outcome (all P's>0.05), with the exception of lower electrocutaneous pain thresholds during the late-luteal phase. No outcomes differed by menstrual phase in the full sample (N=41). This indicates nociceptive responding varies little between the mid-follicular and late-luteal phases. The present study suggests that experimental pain processing does not significantly differ between the mid-follicular and late-luteal phases of the menstrual cycle in healthy women. This implies hormonal variation across these 2 phases (ie, progesterone) has a minimal effect on subjective and physiological responses to pain.