Follicular Phase Research Articles

7299 An Eucaloric High-Fat Diet Suppresses Urinary Estrogen and Progesterone Metabolites, Mimicking Reprometabolic Syndrome in Normal Weight Women

Abstract Disclosure: K. Kuhn: None. A.P. Bradford: Consulting Fee; Self; Amazon. N.F. Santoro: Advisory Board Member; Self; Menogenix, Astellas, Que Oncology, Amazon. Consulting Fee; Self; Ansh. Introduction: Reprometabolic syndrome is associated with relative hypogonadotropic hypogonadism, reduced fecundability, and increased pregnancy loss in women with obesity. We employed a eucaloric, high-fat diet (HFD) to attempt to reproduce the decreased urinary estrogen and progesterone metabolites, characteristic of this phenotype, in healthy women of normal BMI. Materials and Methods: 18 women with normal BMI (18-24.9kg/m²), mean age 29.1±6.3, were recruited for a four-month study including a prescribed 30-day, eucaloric, high-fat, dietary intervention (48% calories from fat). Women collected daily morning urine for 4 menstrual cycles. Daily urinary estrone conjugate (E1c) and pregnanediol-3-glucuronide (Pdg) levels were measured by immunoassay before, during and after the HFD. Paired t tests were used to compare average urinary E1c and Pdg levels and area under the curve (AUC) to determine the impact of the HFD. Cycles were aligned by LH peak (day 0). Results: Participants were weight stable throughout the 4 month study period with no change in BMI (pre-diet BMI 21.46±1.95 kg/m2 and post-diet BMI 21.35±1.81 kg/m2). Average mid cycle E1c peak was significantly lower during (32.4 ng/mg creatinine) and after the HFD (26.5 ng/mg creatinine), compared to pre-diet levels (43.2 ng/mg creatinine; p< 0.001). Post-diet urinary Pdg (AUC) was also significantly lower than pre-diet (p< 0.01). Follicular (days -14 to 0) and luteal phase (days 2-14) E1c AUC was significantly decreased post HFD (p< 0.05). Follicular and luteal phase Pdg levels were also significantly decreased post HFD (p<0.001, both). No significant changes in menstrual cycle length were observed throughout the study. Conclusion: Consumption of a high-fat diet for one month was sufficient to induce a significant reduction in E1c and Pdg, characteristic of Reprometabolic Syndrome of obesity, in normal weight, eumenorrheic women. This finding provides important insights regarding the mechanisms underlying reproductive dysfunction in obesity and indicates that a dietary intervention may be an effective strategy to mitigate sub-optimal reproductive hormone levels in women with obesity-related subfertility. Presentation: 6/1/2024

Association of brown adipose tissue activity with circulating sex hormones and fibroblast growth factor 21 in the follicular and luteal phases in young women

BackgroundThermogenesis is influenced by fluctuations in sex hormones during the menstrual cycle in premenopausal women. The thermogenic activity and mass of brown adipose tissue (BAT) are regulated by endocrine factors, including sex hormones and fibroblast growth factor 21 (FGF21). However, the relationship between human BAT and these endocrine fluctuations within individuals remains to be elucidated. This study aimed to assess variations in BAT activity between the luteal and follicular phases and identify correlations with circulating levels of sex hormones and FGF21.MethodsHealthy young women were enrolled in an observational study. Measurement of BAT activity and blood analyses were performed in both the follicular and luteal phases. BAT activity was analyzed using thermography with 2-h cold exposure. Plasma 17β-estradiol, progesterone, and FGF21 levels were determined by enzyme-linked immunosorbent assay. A comparative analysis within individuals was conducted in 13 women to compare the follicular and luteal phases. Furthermore, sensitivity analysis was carried out in 21 women during the follicular phase only.ResultsPlasma 17β-estradiol and progesterone levels were significantly higher in the luteal phase, whereas plasma FGF21 level was significantly higher in the follicular phase. Comparison analysis found no significant differences in cold-induced BAT activity between the follicular and luteal phases in young women. Correlation analysis in both comparison and sensitivity analyses found that plasma 17β-estradiol and progesterone levels were not associated with BAT activity, whereas plasma FGF21 levels were significantly and positively correlated with BAT activity only in the follicular phase. In addition, plasma 17β-estradiol levels in the follicular phase were significantly and positively associated with plasma FGF21 levels in both the comparison and sensitivity analyses.ConclusionsThe thermogenic activity of BAT during cold exposure was comparable between the follicular and luteal phases in young women. Higher BAT activity was associated with elevated levels of plasma FGF21 only in the follicular phase, which is related to increased plasma 17β-estradiol levels.

Clinical characteristics and treatment during preconception and perinatal period of infertile women with non-classical 21-hydroxylase deficiency

ObjectiveA single-center observational study to determine the clinical characteristics and therapeutic dose adjustments in women of reproductive age with infertility and non-classical 21-hydroxylase deficiency (NC-21OHD).DesignA retrospective analysis of 20 women of reproductive age who were diagnosed with NC-21OHD during an infertility evaluation at Shengjing Hospital of China Medical University from January 2013 to May 2024 was performed. The clinical manifestations, auxiliary examinations, adjustment of glucocorticoid (GC) treatment during preconception and perinatal period, and pregnancy outcomes were analyzed.Results14 of 16 patients (87.5%) had inappropriately elevated progesterone levels during the follicular phase. The average levels of 17α-hydroxyprogesterone, testosterone, androstenedione, and dehydroepiandrosterone sulfate in the follicular phase were also significantly increased. All 20 infertile patients received GC treatment before preparing for pregnancy. During the follow-up, six of 20 patients had seven conceptions. three patients had spontaneous abortions in the first trimester and four patients delivered babies (4/20). Three patients had a GC dose that was maintained throughout pregnancy and one had an increase in the GC dose starting in the second trimester. Of the remaining 16 patients, seven are still trying to conceive and nine had discontinued treatment.ConclusionsAn abnormal increase in the follicular phase progesterone level is the most common serologic marker for NC-21OHD among infertile women. Ovulation can be restored after GC treatment, but the proportion of successful conceptions remains low. The dose of GCs in most pregnant women remained unchanged throughout pregnancy.

TLR-2 and TLR-4 mRNA expression in different grades of histopathological lesions of equine endometrium from follicular phase.

Increased synthesis and deposition of collagen(COL) in the extracellular matrix (ECM) of equine endometrium contributes to endometrosis. Toll-like receptors (TLRs) are transmembrane receptors involved in the innate immune response, recognized for their role in antigen recognition and previously associated with equine endometritis. The TLRs not only recognize pathogen-associated molecular patterns but also regulate inflammations, fibrosis and cancer. The aim of this study was to explore the relationship between TLR expression at different stages of Kenney and Doig's (K-D) grading and COL1 expression during the follicular phase of the oestrous cycle. Forty samples of endometrial tissues were collected post-mortem from mares on the follicular phase of the oestrous cycle (10 samples of each K-D category). Relative mRNA transcription of TLR-2, TLR-4 and COL1A2 genes was assessed using qPCR, and COL1 protein expression by Western blot analysis. The COL1A2 transcription increased in category IIB when compared to categories I, IIA and III endometria (p < .01). The relative protein abundance of COL1 showed no significant differences between endometrial categories (p > .05). As for the TLRs mRNA transcription, TLR-2/-4 transcripts increased in IIA when compared to the other K-D endometria categories (p < .05). Our findings suggest that TLRs may be involved in the initiation of the endometrial inflammatory response. Additional studies are needed to explore TLRs' potential role as diagnostic markers for monitoring inflammation progression and fibrosis development, as well as their involvement in the mechanisms underlying fibrotic pathways.

Influence of menstrual cycle and oral contraceptive phases on strength performance, neuromuscular fatigue, and perceived exertion.

The primary aim of the study was to assess differences in strength performance, neuromuscular fatigue, and perceived exertion across phases of the menstrual cycle [MC; early follicular (eFP), late follicular (lFP), and mid-luteal phase (mLP)] and oral contraceptives [OCs; active pill phase (aPP) and nonactive pill phase (nPP)]. The secondary aim was to analyze the influence of fluctuating serum 17β-estradiol and progesterone concentrations on these parameters in naturally menstruating women. Thirty-four women (21 with a natural MC and 13 using OCs) completed three or two experimental sessions, respectively. Mean propulsive velocity (MPVmean) and total number of repetitions (REPtotal) were assessed during a power [3 × 8 at 60% 1RM (one-repetition maximum)] and hypertrophy squat loading (3 sets to failure at 70% 1RM), respectively. Changes in bench press and squat MPV at 60% 1RM in response to the loadings were used as surrogates for nonlocal and local fatigue, respectively. Total blood lactate accumulation (BLAA) and markers of perceived exertion were assessed in each session. No significant differences between any of the MC or OC phases were observed for MPVmean, REPtotal, nonlocal and local fatigue, and markers of perceived exertion (all P > 0.050). A higher intraindividual 17β-estradiol concentration was significantly associated with a lower MPVmean (P = 0.019). BLAA was significantly higher in the lFP than in the mLP (P = 0.019) and negatively associated with the intraindividual progesterone concentration (P = 0.005). Although 17β-estradiol may negatively influence the MPV, it appears that fluctuations of both sex hormones across the MC and OC phases are not prominent enough to induce significant or practically relevant changes in the assessed parameters.NEW & NOTEWORTHY Although a high intraindividual 17β-estradiol concentration was associated with a lower movement velocity, markers of strength performance and surrogates for nonlocal and local fatigue remained unaffected by MC and OC phases. Blood lactate accumulation was significantly reduced in the mLP. Furthermore, our findings suggest that the impact of the MC phases varies greatly among individuals. Individuals with high fluctuations in sex hormone concentrations may experience relevant changes in the assessed parameters.

Exposure of antral follicles to medroxyprogesterone acetate during stimulation does not cause molecular perturbations in gonadotropin-responsiveness and steroidogenic function of granulosa cells in progestin-primed cycles.

Does medroxyprogesterone acetate (MPA) exposure in progestin-primed ovarian stimulation (PPOS) cycles cause molecular perturbations in the steroidogenic function and gonadotropin responsiveness of the granulosa cells? PPOS cycles are identical to traditional GnRH antagonist cycles not only for clinical IVF characteristics but also for gonadotropin receptor expression, response to gonadotropins, and steroidogenic function at the molecular level. PPOS is increasingly used as an alternative to GnRH antagonists due to the inhibitory effect of progesterone on LH release by reducing GnRH pulsatility at the hypothalamic level. Although a growing body of evidence from clinical studies did not indicate significant differences between PPOS and antagonist protocols for IVF cycle characteristics and obstetrical outcomes, it is still unknown whether exposure of the antral follicle cohort to progesterone or its synthetic derivatives during ovarian stimulation causes any subtle molecular aberrations in terms of steroidogenesis and gonadotropin responsiveness. To address this issue, detailed comparative molecular analyses were conducted in the luteinized mural granulosa cells (GCs) obtained from normal responding IVF patients undergoing PPOS and antagonist cycles. A clinical translational research study was conducted with IVF patients. This study included 55 normal responding IVF patients who underwent ovarian stimulation with either PPOS using MPA (5 mg twice daily) or GnRH antagonist cetrorelix acetate. Recombinant forms of FSH and hCG were used for ovarian stimulation and ovulation triggering, respectively. Luteinized mural GCs obtained during the oocyte retrieval procedure were used for the experiments. Cell culture, quantitative real-time PCR, immunoblotting, confocal time-lapse live cell imaging, and hormone assays were used. Demographic and IVF cycle characteristics of the patients undergoing ovarian stimulation with PPOS and GnRH antagonist were similar, including ovarian response, mature oocyte yield, and fertilization rates. Molecular analyses revealed that the expression of the enzymes involved in sex-steroid synthesis (StAR, SCC, 3β-HSD, 17β-HSD, aromatase) and the uptake/storage/utilization of cholesterol (LDL receptor, Hormone-sensitive lipase, hydroxy-methyl glutaryl Co-enzyme-A reductase, and Sterol O-acyltransferase1) in the GCs of the PPOS cycles were comparable to those of the antagonist cycles. The expression of the receptors for gonadotropins, estrogen, and progesterone hormones was also similar. Basal and hCG-induced increases in 3β-HSD expression and progesterone production and basal and FSH-induced increases in aromatase expression and E2 output of the GCs from PPOS patients did not exhibit any meaningful differences when compared with GCs from antagonist cycles. Furthermore, basal and hCG-induced up-regulation in the LDL receptor expression and cholesterol uptake did not differ between the groups. Confocal imaging also revealed similar patterns of expression for the steroidogenic enzymes and their co-localization with mitochondria. Lastly, the expression of the other important genes regulating cumulus expansion, ovulation, and luteal function [Relaxin, ADAMTS-1, and epidermal growth factor (EGF)-like growth factor amphiregulin] in the GCs of the PPOS and antagonist cycles were similar. N/A. Caution should be exercised when interpreting our data which was derived from normally responding patients whose ovulation was triggered with hCG. It is unclear whether the molecular parameters assessed vary according to infertility etiologies, magnitude of ovarian response, mode of trigger, and any other underlying ovarian pathologies or systemic diseases. MPA was the progestin used for PPOS and whether these findings can be generalized to other progestins is unknown. This study provides reassuring molecular evidence that exposure of antral follicle cohorts to MPA during the follicular growth phase does not have any detrimental effects on steroidogenic, ovulatory, and luteal functions when compared with GnRH antagonist cycles. This study was funded by the School of Medicine, the Graduate School of Health Sciences of Koc University and Koç University Research Center for Translational Medicine (KUTTAM), and equally funded by the Republic of Turkey Ministry of Development Research Infrastructure Support Program. All authors declare no conflict of interest. N/A.

Macro-FSH is a rare cause of inappropriately high FSH concentrations.

Assessment of hormone concentrations can be subjected to laboratory pitfalls. Macro-hormones are hormone-autoantibody complexes which are cleared slowly from circulation and cause a false elevation in hormones' concentrations. Macro-prolactin and macro-thyroid-stimulating hormone (TSH) are most frequently encountered while macro-follicle-stimulating hormone (FSH) has been rarely reported. We describe the case of a 30-year-old woman who had a gynaecological consultation due to failure in achieving pregnancy after 8 months of unprotected intercourse. She had regular menses, did not complain of climacteric symptoms and her medical history was unremarkable. Antral follicle count and anti-mullerian hormone concentrations were normal, and regular ovulation was documented. Unexpectedly, high early follicular phase FSH concentrations were confirmed on two occasions (57 and 51 IU/L), raising the suspicion of primary ovarian insufficiency. After excluding Turner's syndrome and autoimmune oophoritis, a laboratory artifact was hypothesized. Following polyethylene glycol precipitation, FSH levels dropped from 41.1 IU/L to 6.54 IU/L (recovery 16%) and the presence of macro-FSH was concluded. Laboratory interference can lead to misdiagnosis and unnecessary treatments. A laboratory artifact should be suspected when inconsistency exists between clinical presentation and laboratory results. Only five other cases of macro-FSH have been reported to date. Although macro-hormones generally have low biological activity and do not require treatment, the role of anti-FSH antibodies has been hypothesized in primary ovarian insufficiency and in vitro fertilization failure. Hormone quantification is a cornerstone in the diagnostic workup of endocrine disorders, but it can be subjected to laboratory interferences which can lead to unnecessary investigations and inappropriate treatments. A laboratory artifact should be suspected when a discrepancy is observed between clinical presentation and laboratory results, when extremely unusual analyte concentrations are observed and when inconsistent results are obtained by different analytical methods. Macro-hormones are hormone-autoantibody complexes which are cleared slowly from circulation and cause a false elevation in hormone concentrations. Macro-prolactin and macro-TSH are most frequently encountered, while macro-FSH has been rarely reported. Macro-hormones can be detected by polyethylene glycol precipitation, gel filtration chromatography, or by using protein G or protein A columns. Although macro-hormones generally have low biological activity and do not require treatment, the role of anti-FSH antibodies has been hypothesized in primary ovarian insufficiency and in vitro fertilization failure.

Hormonal status of patients with infertility and post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a mental disorder that occurs after a psychologically or physically traumatic event, and characterized by three main clusters of posttraumatic symptoms, as well as chronic and significant disturbances in emotion regulation, identity, and relationships. PTSD is more common in women, which suggests a role for the regulation of female sex hormones in its development.The objective: to study the hormonal status of women with infertility and PTSD.Materials and methods. 112 women with infertility were examined, who were divided into groups depending on the PTSD criteria. The I group included 36 women with PTSD criteria, who were diagnosed with infertility before the onset of the traumatic factor, the II group – 31 patients with fertility disorders which were diagnosed on the background of PTSD, the III group – 45 women with infertility and without signs of PTSD, the control group consisted of 50 healthy women who applied for a routine preventive examination.In all patients, on the 3rd–5th day of the menstrual cycle, the concentrations of prolactin, estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone were determined in the blood serum, in the saliva – cortisol, on the 21st day of the cycle – in the blood serum progesterone.Results. It was established that in women with infertility that was developed after the traumatic factor, the prolactin content is significantly higher (59.5±18.9 ng/ml) than in other groups of patients with fertility disorders (36.9±12.3 ng/ml in I group, 34.3±17.9 ng/ml – in the III group) and in the group of healthy women (13.5±5.6 ng/ml). The concentration of estradiol in the I group was within the reference values for the follicular phase of the cycle, but significantly lower (23.4±3.6 pg/ml) than in women of the other groups (from 87.6±14.6 pg/ml in the III group to 103.5±27.8 pg/ml in the group of healthy women). The average concentration of progesterone in the I (3.4±2.7 pg/ml) and II (4.1±2.9 pg/ml) groups was within the reference values, but was probably lower than that of healthy women (23.6±4.9 pg/ml), as well as women with infertility without signs of PTSD (19.4±5.1 pg/ml).In this study the patients with infertility which has developed on the background of PTSD had LH values within the reference normal range (2.0±0.5 U/L), but several times lower than in women with other reasons of infertility (12.0±3.6 U/l – in women with infertility before the development of PTSD, 6.0±1.9 U/l – in women with infertility without PTSD criteria) and in healthy women (9.2±3.4 U/l).An increased level of testosterone beyond the reference values was found only in women of the II group (3.3±1.9 nmol/l), in the other groups the average testosterone concentration ranged from 1.3±0.6 nmol/l in healthy women to 1.5±0.9 nmol/l in the I group and 1.8±0.7 nmol/l in women with infertility without signs of PTSD. Patients with PTSD are characterized by an increased level of cortisol in saliva, which indicates a prolonged reaction of the body to the trauma (8.8±0.3 ng/ml – in the I group, 10.3±0.4 ng/ml – in the II group), in groups without PTSD the level of this hormone in saliva was almost twice as low (5.4±0.2 ng/ml – in the III group and 5.9±0.3 ng/ml – in healthy women).Conclusions. 1. The patients with PTSD and infertility are characterized by high concentrations of cortisol in saliva and a decreased progesterone level in blood serum.2. In patients who had fertility disorders before a stressful event, a decreased estrogen concentration and an increased luteinizing hormone level were found in blood serum, which indicates endocrine disorders as a cause of infertility.3. Prolactin and testosterone levels were found to be higher in the patients with infertility that was developed after a traumatic event than in other women with reproductive function disorders. Both factors are pathogenetically related to the pathological reaction to stress.

The impact of chronic stress on the hormonal state of women affected by hostilities and displaced women

During times of war, refugee women often have high levels of chronic stress due to factors such as war, displacement and uncertainty. The study focuses on examining the hormonal responses of female refugees experiencing chronic stress from war and displacement.The objective: to assess the impact of chronic stress caused by war and displacement on the hormonal balance of refugee women.Materials and methods. 60 women were examined, who were divided into groups: the 1st group included women who were affected by hostilities (20 persons), and the 2nd group included displaced women (20 individuals). In these 40 women the hormonal studies were conducted in the conditions of military aggression in Ukraine. The control group (3rd group) included healthy women who were examined in the pre-war period. All examined women were 20–25 years old with an average body weight of 55–60 kg. Concentrations of progesterone, estradiol, follicle-stimulating hormone (FSH) and luteinizing hormone, prolactin in the I and II phases of the menstrual cycle (MC), cortisol in the I phase of the MC were determined in blood serum using the enzyme immunoassay method. An analysis of the results of research on the role of the hypothalamic-pituitary-adrenal system in the regulation of the stress response was carried out.Results. In the examined women, various disorders of MC were observed, such as: menometrorrhagia, hypermenorrhea, acyclic uterine bleeding, oligomenorrhea, and amenorrhea. The most pronounced changes in menstrual function were observed in women who were affected by hostilities. Such significant disorders of MC in women of this group coincided with changes in indicators of gonadotropic hormones of the pituitary gland and sex hormones in the blood.A study of the psycho-emotional state of women who suffered from hostilities established that these women have a significant stressful effect of various risk factors on the body. Changes in the levels of cortisol, prolactin and other hormones were detected.Conclusions. Studies have shown that chronic stress affects the hormonal status of women affected by hostilities and of displaced women, including FSH, estradiol, and prolactin levels.A significant increase in the level of FSH in the follicular phase of the menstrual cycle and an increase in the level of estradiol in the luteal phase were determined, which may indicate a compensatory reaction of the body to stress. A significant increase in the level of prolactin was also found, which can cause disorders of menstrual function and affect the psycho-emotional state.

Morphophysiological Assessment of the Cervix during the Reproductive Cycle and Early Pregnancy in Does Using Computed Tomography and Oxytocin Receptor Immunohistochemistry.

This study aimed to elucidate the morphophysiology and oxytocin receptor (OXTR) expression in the cervix of doe goats during various reproductive stages to enhance reproductive management strategies. A total of 40 cervical samples were categorized into follicular (n = 15), luteal (n = 10), and early pregnancy (n = 15) stages. Utilizing advanced imaging based on functional and morphological markers, the study employed computed tomography (CT) scans, histochemical staining (Masson trichrome and alcian blue), immunohistochemistry, Western blotting, and quantitative PCR (qPCR) to assess structural changes in the cervix and in OXTR expression during the estrous cycle and early pregnancy. CT scans revealed consistent cervical folds and a significant reduction in cervical width during pregnancy, suggesting structural adaptations for gestational integrity. Histochemical analyses indicated a well-organized collagen network and presence of mucins, essential for cervical function and integrity. Immunohistochemistry and Western blotting demonstrated elevated OXTR protein levels during the follicular stage, which were markedly reduced during pregnancy, indicating a role in facilitating cervical relaxation and sperm transport during estrus and maintaining cervical closure during gestation. qPCR analysis showed stable OXTR mRNA levels during follicular and luteal stages with a slight, non-significant increase during pregnancy, pointing towards posttranscriptional regulatory mechanisms. In conclusion, this study demonstrates that cervical morphology and OXTR expression in doe goats undergo significant changes across reproductive stages, with elevated OXTR protein levels during the follicular phase and notable reductions in cervical width and OXTR protein levels during pregnancy, indicating structural and functional adaptations for both reproductive processes and gestational integrity.

Observations on the reproductive morphology of the female short-beaked echidna, Tachyglossus aculeatus.

Although monotremes diverged from the therian mammal lineage approximately 187 million years ago, they retain various plesiomorphic and/or reptilian-like anatomical and physiological characteristics. This study examined the morphology of juvenile and adult female reproductive tracts across various stages of the presumptive oestrous cycle, collected opportunistically from cadaver specimens submitted to wildlife hospitals during the breeding season. In adult females, ovaries had a convoluted cortex with follicles protruding from the ovarian surface. While protruding antral follicles were absent from the ovaries of juvenile echidnas, histological analysis identified early developing primordial and primary follicles embedded into the ovarian cortex. The infundibulum epithelial cells of the oviducts were secretory during the follicular phase but not at other stages, the ampulla region was secretory at all stages and is likely responsible for the mucoid layer deposited around the zona pellucida, and the isthmus region of the oviduct appeared to be responsible for initial deposition of the shell coat, as in marsupials. Female echidnas have two separate uteri, which never merge and enter separately into the urogenital sinus (UGS). This study confirmed that both uteri are functional and increase in glandular activity during the luteal phase. In the juvenile uteri, the endometrium was immature with minimal, small uterine glands. A muscular cervical region at the caudal extremity of each uterus, just before the cranial region of the UGS was defined by the absence of glandular tissue in all female echidnas, including the juveniles. There was no evidence of a definitive vaginal region. A clitoris was also detected that possessed a less developed but similar structural (homologous) anatomy to the male penis; urethral ducts while present did not appear to be patent.

Differential expression of HIV target cells CCR5 and α4β7 in tissue resident memory CD4 T cells in endocervix during the menstrual cycle of HIV seronegative women.

Ovarian hormones are known to modulate the immune system in the female genital tract (FGT). We sought to define the impact of the menstrual cycle on the mucosal HIV target cell levels, and tissue-resident CD4 T cells. Here, we characterized the distribution, phenotype, and function of CD4 T cells with special emphasis on HIV target cells (CCR5+ and α4β7+) as well as tissue-resident memory (TRM; CD69+ and CD103+) CD4 T cells in FGT of cycling women. Peripheral blood and Endocervical cells (EC-collected from cytobrush) were collected from 105 healthy women and performed multicolor flow cytometry to characterize the various subsets of CD4 T cells. Cervicovaginal lavage (CVL) were collected for cytokine analysis and plasma were collected for hormonal analysis. All parameters were compared between follicular and luteal phase of menstrual cycle. Our findings revealed no significant difference in the blood CD4 T cell subsets between the follicular and luteal phase. However, in EC, the proportion of several cell types was higher in the follicular phase compared to the luteal phase of menstrual cycle, including CCR5+α4β7-cells (p=0.01), CD69+CD103+ TRM (p=0.02), CCR5+CD69+CD103+ TRM (p=0.001) and FoxP3+ CD4 T cells (p=0.0005). In contrast, α4β7+ CCR5- cells were higher in the luteal phase (p=0.0004) compared to the follicular phase. In addition, we also found that hormonal levels (P4/E2 ratio) and cytokines (IL-5 and IL-6) were correlated with CCR5+ CD4 T cells subsets during the follicular phase of the menstrual cycle. Overall, these findings suggest the difference in the expression of CCR5 and α4β7 in TRM CD4 T cell subsets in endocervix of HIV seronegative women between the follicular and luteal phase. Increase in the CCR5+ expression on TRM subsets could increase susceptibility to HIV infection during follicular phase of the menstrual cycle.

Impact of the Menstrual Cycle on the Cardiovascular and Ventilatory Responses During Exercise in Normoxia and Hypoxia.

Citherlet, Tom, Antoine Raberin, Giorgio Manferdelli, Nicolas Bourdillon, and Grégoire P Millet. Impact of the menstrual cycle (MC) on the cardiovascular and ventilatory responses during exercise in normoxia and hypoxia. High Alt Med Biol. 00:00-00, 2024. Introduction: Ovarian hormones influence several physiological functions in women. This study investigated how the hormonal variations across the menstrual cycle (MC) impact cardiovascular and ventilatory responses during rest and moderate exercise in normobaric hypoxia. Methods: Thirteen eumenorrheic women were tested during the early follicular (Fol1), late follicular (Fol2), and mid-luteal (Lut3) phases with measurement of hormonal levels. Heart rate (HR) variability, blood pressure, and baroreflex sensitivity (BRS) were evaluated at rest in normoxia. Ventilation (VE), peripheral oxygen saturation, and HR were monitored at rest and during moderate-intensity cycling exercise in hypoxia (FiO2 = 14%). Results: Despite expected hormone level variations, no significant changes were observed across the MC in HR variability (root mean square of successive differences; 64 (95% confidence interval [47, 81]) at Fol1, 54 [42, 66] at Fol2, 60 [44, 77] ms at Lut3), blood pressure (mean blood pressure; 85 [79, 90]), 87 [81, 93]), 84 [77, 92] mmHg), BRS (26 [17, 36], 28 [20, 35], 23 [17, 29] ms/mmHg), VE (rest: 8.9 [7.9, 9.8], 9.5 [9.0, 9.9], 9.0 [8.1, 9.9]; exercise: 53 [41, 66], 51.1 [36.4, 65.7], 54.4 [34.0, 74.8] l/min), peripheral oxygen saturation (rest: 89.8 [87.4, 92.1], 91.9 [88.7, 95.0], 90.2 [87.8, 92.6]; exercise: 80.5 [77.4, 83.5], 84.4 [80.4, 88.3], 81.9 [78.3, 85.4] %) HR (rest: 69.7 [60.2, 79.1], 70.8 [63.2, 78.3], 70.5 [64.0, 77.0]; exercise: 148 [136, 160], 146 [132, 161], 146 [132, 160] bpm), and cycling efficiency (0.17 [0.16, 0.18], 0.17 [0.13, 0.21], 0.16 [0.15, 0.18] %) (all p > 0.05). Discussion: From a practical point of view, there is no strong evidence of any usefulness of monitoring hormonal variations and the MC phases for women exercising in hypoxia.

Influence of Menstrual Phase and Symptoms on Match Running in Professional Footballers.

This study examined the effects of menstrual cycle phases and symptoms on match running performance in football (soccer) players. Twenty-one nonhormonal contraceptive using football players from four professional teams were monitored for up to four menstrual cycles during a domestic league season. Menstrual phases, classified as early-follicular phase (EFP), mid-late follicular phase (MFP), and luteal phase (LP), were determined by self-reporting of menstruation and urinary hormone tests (luteinizing hormone and pregnanediol-3-glucuronide). On match day, players completed a menstrual symptom severity questionnaire. In repeated matches, players wore 10 Hz Global Positioning Satellite (GPS) devices to measure relative (/min) total distance, high-speed running distance, very high-speed distance, peak speed, acceleration count, and deceleration count. Linear mixed models were performed for each GPS measure to determine the relationship with phase or symptoms. Data for 7 and 10 players were included for menstrual phase and menstrual symptoms analyses, respectively. A significantly higher total distance was reported during MFP compared to EFP (Δ 5.1 m min-1; p = 0.04) and LP (Δ 5.8 m min-1; p = 0.007). Significantly greater high-speed running was reported during MFP compared to EFP (Δ 1.2 m min-1; p = 0.012) and LP (Δ 1.1 m min-1; p = 0.007). No significant effect of menstrual phase was found for any other GPS measures (p > 0.05). Accelerations declined with increasing symptom severity (p = 0.021, estimate = -0.01count.min-1). Menstrual symptom severity did not affect any other GPS measures (p > 0.05). In conclusion, greater total distance and high-speed running occurred during the MFP. Additionally, accelerations minimally decreased with increasing menstrual symptom severity. Large intra- and inter-variability existed, suggesting individualized monitoring and management of menstrual effects on performance would be beneficial.

Efficacy of combined exercise training during different menstrual phases in young students with primary dysmenorrhoea

AbstractObjectivesThe objective of the study was to compare the effectiveness of combined exercise training during different menstrual phases on pain, quality of life and menstrual symptoms.MethodsA total of 72 participants for the study were randomly assigned into three groups: Group 1 (N = 24), Group 2 (N = 24) and Group 3 (N = 24) which had undergone combined exercise training during the follicular, luteal and bleeding phases of their menstrual cycle, respectively. The treatment programme included combined exercise training involving deep breathing exercises, Kegel exercises, core strengthening exercises and stretching exercises. Exercises were repeated 5 times with hold duration of 15 s with total of 30–40 min session with 5–10 min of warm‐up and cooldown sessions. Demographic data and outcome measures (Visual Analogue Scale [VAS], Menstrual Symptom Questionnaire [MSQ], and Working ability, Location, Intensity, Days, Duration [WaLIDD]) were assessed at baseline and assessed again during the first menstrual cycle after the completion of the treatment programme. One‐way ANOVA was used for between‐group comparisons of the normally distributed data.ResultsWithin‐group comparison of the outcome variables except VAS in group 3 showed a statistically significant difference in all groups. Comparison of post‐intervention results of the outcome measures of all the groups revealed a statistically significant difference for the VAS, while there was no statistically significant difference for in between the comparison of the WaLIDD and MSQ scoring.ConclusionCombined exercise training is effective in reducing pain only when performed during follicular and luteal phases and significantly improve quality of life and menstrual symptoms in all phases of the menstrual cycle.

Evaluation of Changes in the Patency of the Nasal Cavity and Eustachian Tube Depending on the Phase of the Menstrual Cycle: A Pilot Study.

(1) Background: Estrogen and progesterone, hormones specific to females, undergo fluctuations during the menstrual cycle. The aim of this study was to assess subjective and objective changes in nasal cavity and Eustachian tube patency depending on the phase of the menstrual cycle in two groups of women: those in a follicular phase group and those in a luteal phase group. (2) Materials and Methods: The study group consisted of 25 healthy non-pregnant women aged 24 to 32. Based on the phase of the cycle confirmed in sonography, they were divided into follicular phase (FP) and luteal phase (LP) groups. The Eustachian tube and nasal cavity patency examination was carried out using a SNOT-22 Questionnaire, a rhinomanometer, and a tympanometer. (3) Results: We observed that the incidence of nasal obstruction in SNOT-22 was significantly dependent on the cycle phase (p = 0.012) and was lower in the FP compared to the LP. Similar relationships were noticed between the cycle phase and the rhinomanometry outcome, where the LP was associated with a lower flow. We also revealed that the incidence of ear blockage significantly depended on the cycle phase (p = 0.001) and was lower in the FP compared to the LP. Women whose nasal patency deteriorated during the LP also had more negative pressure values in tympanometry. We observed that patients with negative PEAK L and R levels had a lower flow in rhinomanometry. (4) Conclusions: The results highlight the menstrual cycle's substantial impact on both subjective and objective nasal and Eustachian tube patency measurements. The novel finding in this study is that women whose nasal patency deteriorated during the luteal phase also had more negative pressure values in tympanometry. These results suggest that the deterioration of hearing during the menstrual cycle could be a result of swelling of the nasal mucosa and tubes.

Characterizing within-person variance in, and menstrual cycle associations with, event-related potentials associated with positive and negative valence systems: The reward positivity and the error-related negativity

Event-related potentials (ERPs) are widely employed as measures of transdiagnostic cognitive processes that are thought to underlie various clinical disorders (Hajcak et al., 2019). Despite their prevalent use as individual difference measures, the effects of within-person processes, such as the human menstrual cycle, on a broad range of ERPs are poorly understood. The present study leveraged a within-subject design to characterize between- and within-person variance in ERPs as well as effects of the menstrual cycle in two frequently studied ERPs associated with positive and negative valence systems underlying psychopathology—the Reward Positivity (RewP) and the Error- Related Negativity (ERN). Seventy-one naturally-cycling participants completed repeated EEG and ecological momentary assessments of positive and negative affect in the menstrual cycle's early follicular, periovulatory, and mid-luteal phases. We examined the mean degree of change between cycle phases in both ERPs, the between-person variability in the degree of change in both ERPs, and whether an individual’s degree of cyclical change in these ERPs show coherence with their degree of cyclical change in positive and negative affect recorded across the cycle. Results revealed no significant changes in positive and negative affect across the cycle and rather small changes in ERP amplitudes. Significant random slopes in our model revealed larger individual differences in trajectories of change in ERP amplitudes and affect, in agreement with prior evidence of heterogeneity in dimensional hormone sensitivity. Additionally, state-variance in these ERPs correlated with positive and negative affect changes across the cycle, suggesting that cycle-mediated ERP changes may have relevance for affect and behavior. Finally, exploratory latent class growth mixture modeling revealed subgroups of individuals that display disparate patterns of change in ERPs that should be further investigated.

Performance of the MiniMed 780G system on mitigating menstrual cycle-dependent glycaemic variability.

To map the glycaemic variabilities and insulin requirements across different phases of the menstrual cycle and assess the efficacy and performance of the MiniMed 780G system on mitigating glycaemic variabilities during phases of the menstrual cycle. A pilot study recruiting 15 adolescent and young adult females with type 1 diabetes was conducted. Only females with regular spontaneous menstruation were enrolled in the current study. Phases of each menstrual cycle were determined as either follicular phase or luteal phase. The study analysed continuous glucose monitoring metrics during two study periods: the open loop period (OLP) and the advanced hybrid closed-loop (AHCL) period; each period lasted 3 consecutive months. During the OLP, the mean time in range (TIR) significantly decreased during the luteal phase compared with the follicular phase (65.13% ± 3.07% vs. 70.73% ± 2.05%) (P < .01). The mean time above range significantly increased from 21.07% ± 2.58% during the follicular phase to 24.87% ± 2.97% during the luteal phase (P < .01). After initiating the AHCL period, TIR was comparable during both phases of the menstrual cycle (P = .72), without increasing the time spent below 70 mg/dL (P > .05). Regarding insulin delivery during the AHCL period, the percentage of Auto basal and Auto correction delivered by the algorithm increased by 13.55% and 30.6%, respectively (P < .01), during the luteal phase. The fully automated adaptive algorithm of the MiniMed 780G system mitigated menstrual cycle-dependent glycaemic variability, successfully attaining the recommended glycaemic outcomes with a TIR greater than 70% throughout the entire menstrual cycle.

Comparison of repeatability of subjective appetite sensations in men and women at different menstrual cycle phase.

appetite can be measured through subjective sensations of appetite (SSA), which can be assessed by means of scales, the most relevant being the visual analog scales (VAS). to analyze the repeatability of VAS in men and women in follicular phase (FF) and luteal phase (LF) of the menstrual cycle Materials and methods: 34 men and women were included. VAS of subjective appetite sensations (SAS) were applied before and after standardized breakfast in two sessions. women LP showed intra-class correlation coefficient (ICC) values greater than 0.5, and most of VAS in women FP and men showed ICC values greater than 0.7. The ICC of hunger and desire to eat were different between men and women LP. Comparisons of these ICC´s showed that only hunger and desire to eat were different between men and women. repeatability of VAS was similar between men and women in different stages of menstrual cycle. This is the first study to assess repeatability of VAS in women in LP and to objectively compare the repeatability of VAS to evaluate SAS.

Pupil to limbus diameter ratio as an emerging autonomic function test and its correlation with anthropometric parameters in different phases of menstrual cycle

The menstrual cycle is a physiological change in normal females, indicating the proper functioning of both endocrine and reproductive health. The pupil to limbus diameter (PLD) ratio is defined as the ratio of pupil diameter measured at an axial plane to the limbus diameter measured at the same or a parallel axial plane. Alterations in estrogen and progesterone levels may influence cardiac autonomic functions. This study aimed to correlate the PLD ratio with anthropometric parameters, such as body mass index (BMI) and waist circumference (WC), during different phases of the menstrual cycle among medical students.Methods: A cross-sectional study was conducted among first- and second-year female MBBS students aged 17 to 22 years. Anthropometric parameters, including height, weight, BMI, and WC, were measured for all participants. Eye photographs were taken during the follicular and luteal phases of the menstrual cycle, and the diameters were measured manually using the two-box method. The PLD ratios for both eyes showed a significant positive correlation with BMI (right eye: r = 0.682, p &lt; 0.000; left eye: r = 0.430, p &lt; 0.000) and waist circumference (right eye: r = 0.456, p &lt; 0.000; left eye: r = 0.315, p &lt; 0.001). The PLD ratio can serve as a simple, non-invasive, and cost-effective autonomic function test.