The effects of different exercises on weight loss and hormonal changes in women with polycystic ovarian syndrome: a network meta-analysis study.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine illnesses. There is evidence that exercise training positively affects on improvement of the pathogenic factors in women with PCOS. On the other hand, some studies reported similar effects of aerobic and resistance exercises or no effect of exercises on the improvement of the pathogenic factors. The aim of the current study was to perform a network meta-analysis of RCTs to evaluate the efficacy of exercises on body mass index (BMI), hormone concentrations, and regular menstruation in women with PCOS. METHODS: The search was performed from databases of PubMed, Scopus, and Web of Science with the keywords of exercise, resistance exercise, aerobic exercise, endurance exercise, yoga, polycystic ovary syndrome, randomized controlled trial based on the CONSORT, BMI, sex hormone and regular menstruation from inception until April 15, 2022. Bayesian random-effects network meta-analyses were performed to calculate mean difference and 95% credible intervals. RESULTS: Out of 1140 studies, 19 were eligible for inclusion. The results showed that moderate-intensity aerobic exercise effectively reduces BMI compared to no intervention and Yoga. No other forms of exercise led to weight loss. Additionally, exercise had no impact on sex hormones and regular menstruation. It was concluded that moderate-intensity aerobic exercise is the most effective for reducing BMI in women with PCOS. CONCLUSIONS: Due to the limitations regarding the small sample size and lack of subgroup and sensitivity analysis, the results of this study demonstrated that moderate-intensity, aerobic exercise is the most effective exercise for reducing BMI, while the other exercises were ineffective. Moderate-intensity aerobic exercise is suggested to decrease the BMI in women with PCOS. SYSTEMATIC REVIEW REGISTRATION: This systematic review and network meta-analysis study was registered in PROSPERO (CRD42022324839).

Diagnostic Value of Menstrual Blood Lipidomics in Endometriosis: A Pilot Study.

Endometriosis is a prevalent chronic inflammatory disease characterized by a considerable delay between initial symptoms and diagnosis through surgery. The pressing need for a timely, non-invasive diagnostic solution underscores the focus of current research efforts. This study examines the diagnostic potential of the menstrual blood lipidome. The lipid profile of 39 samples (23 women with endometriosis and 16 patients in a control group) was acquired using reverse-phase high-performance liquid chromatography-mass spectrometry with LipidMatch processing and identification. Profiles were normalized based on total ion counts. Significant differences in lipids were determined using the Mann-Whitney test. Lipids for the diagnostic model, based on logistic regression, were selected using a combination of variance importance projection filters and Akaike information criteria. Levels of ceramides, sphingomyelins, cardiolipins, triacylglycerols, acyl- and alkenyl-phosphatidylethanolamines, and alkenyl-phosphatidylcholines increased, while acyl- and alkyl-phosphatidylcholines decreased in cases of endometriosis. Plasmenylphosphatidylethanolamine PE P-16:0/18:1 and cardiolipin CL 16:0_18:0_22:5_22:6 serve as marker lipids in the diagnostic model, exhibiting a sensitivity of 81% and specificity of 85%. The diagnostic approach based on dried spots of menstrual blood holds promise as an alternative to traditional non-invasive methods for endometriosis screening.

Gene expression of aromatase, SF-1, and HSD17B2 in menstrual blood as noninvasive diagnostic biomarkers for endometriosis.

OBJECTIVE: Endometriosis diagnostic delays are still encountered due to the lack of a reliable, noninvasive diagnostic test. Besides, menstrual blood is a relatively untapped field for diagnostics, yet it provides a readily accessible source for investigating common gynecological conditions. In the present study, we aim to evaluate the expression levels of menstrual blood aromatase, SF-1, and HSD17B2 from women with and without endometriosis and their diagnostic performance. METHODS: A total of 40 subjects participated in this study, including 20 patients from each endometriosis and non-endometriosis group. The endometriosis group comprised patients with proven endometriosis confirmed by pathological diagnosis and pelvic ultrasound examination, then requiring endometrial biopsy determined by the clinicians. The non-endometriosis group consisted of women who had primary and secondary infertility and underwent endometrial examination without any visible endometriosis lesion. The menstrual blood and eutopic endometrial tissue of enrolled subjects were collected, and the relative expression of the genes was performed by quantitative real-time polymerase chain reaction (qPCR). ROC curve was used to evaluate the diagnostic efficacy of aromatase, SF-1, and HSD17B2. RESULTS: We found significantly higher expressions of aromatase, SF-1, and HSD17B2 in the menstrual blood of the endometriosis group compared to non-endometriosis (P < 0.05). In contrast, examination of eutopic endometrial tissue of both groups only found significant in HSD17B2 (P < 0.05), while aromatase and SF-1 showed no statistically significant variance. The Area Under Curve (AUC) of aromatase, SF-1, and HSD17B2 in the menstrual blood was 0.977, 0.862, and 0.807, respectively. The optimal cutoff value was determined to be >1.63 (sensitivity = 95 % and specificity = 90 %) for aromatase, >1.71 (sensitivity = 90 % and specificity = 80 %) for SF-1, and >1.83 (sensitivity = 80 % and specificity = 75 %) for HSD17B2. CONCLUSION: Our study showed that aromatase, SF-1, and HSD17B2 in the menstrual blood solidly discriminate between endometriosis and non-endometriosis patients with high diagnostic accuracy. However, further confirmation in larger cohorts is required to validate the reliability of these biomarkers to endometriosis.

Menstrual Blood Stem Cells-Derived Exosomes as Promising Therapeutic Tools in Premature Ovarian Insufficiency Induced by Gonadotoxic Systemic Anticancer Treatment.

Gonadotoxicity resulting from systemic and locoregional cancer treatments significantly threatens women's reproductive health, often culminating in premature ovarian insufficiency. These therapies, particularly alkylating agents and ionizing radiation, induce DNA damage and apoptosis in ovarian follicles, leading to infertility, amenorrhea, and estrogen deficiency, which exacerbate risks of osteoporosis and cardiovascular diseases. Existing fertility preservation methods do not prevent immediate ovarian damage, underscoring the need for innovative protective strategies. Menstrual blood-derived stem cells (MenSC) and their extracellular vesicles (EV) present promising regenerative potential due to their therapeutic cargo delivery and pathway modulation capabilities. Preclinical studies demonstrate that MenSC-derived EV ameliorate premature ovarian insufficiency by inhibiting granulosa cell apoptosis, promoting angiogenesis, and activating pivotal pathways such as SMAD3/AKT/MDM2/P53. However, comprehensive research is imperative to ensure the safety, efficacy, and long-term effects of MenSC-derived EV in clinical practice. In this review, we update the current knowledge and research regarding the use of MenSC-derived EV as a novel therapeutic weapon for ovarian regeneration in the context of gonadotoxicity induced by systemic anticancer treatment.

Granulosa cell insight: unraveling the potential of menstrual blood-derived stem cells and their exosomes on mitochondrial mechanisms in polycystic ovary syndrome (PCOS).

BACKGROUND: Polycystic ovary syndrome (PCOS) presents a significant challenge in women's reproductive health, characterized by disrupted folliculogenesis and ovulatory dysfunction. Central to PCOS pathogenesis are granulosa cells, whose dysfunction contributes to aberrant steroid hormone production and oxidative stress. Mitochondrial dysfunction emerges as a key player, influencing cellular energetics, oxidative stress, and steroidogenesis. This study investigates the therapeutic potential of menstrual blood-derived stem cells (MenSCs) and their exosomes in mitigating mitochondrial dysfunction and oxidative stress in PCOS granulosa cells. METHODS: Using a rat model of PCOS induced by letrozole, granulosa cells were harvested and cultured. MenSCs and their exosomes were employed to assess their effects on mitochondrial biogenesis, oxidative stress, and estrogen production in PCOS granulosa cells. RESULTS: Results showed diminished mitochondrial biogenesis and increased oxidative stress in PCOS granulosa cells, alongside reduced estrogen production. Treatment with MenSCs and their exosomes demonstrated significant improvements in mitochondrial biogenesis, oxidative stress levels, and estrogen production in PCOS granulosa cells. Further analysis showed MenSCs' superior efficacy over exosomes, attributed to their sustained secretion of bioactive factors. Mechanistically, MenSCs and exosomes activated pathways related to mitochondrial biogenesis and antioxidative defense, highlighting their therapeutic potential for PCOS. CONCLUSIONS: This study offers insights into granulosa cells mitochondria's role in PCOS pathogenesis and proposes MenSCs and exosomes as a potential strategy for mitigating mitochondrial dysfunction and oxidative stress in PCOS. Further research is needed to understand underlying mechanisms and validate clinical efficacy, presenting promising avenues for addressing PCOS complexity.

Adverse Menstrual Events Reported After and Before (or Without) COVID-19 Vaccination: A Systematic Review and Meta-Analysis of Comparative Observational Studies.

BACKGROUND: Reports of adverse menstrual events emerged during the COVID-19 vaccination campaign in multiple countries. This raised the question whether these reports were caused by the vaccines. The aim of this systematic review was to evaluate comparative studies on this topic (registered at PROSPERO [CRD42022324973]). METHODS: We included observational studies such as cohort studies and surveys comparing the response to self-reported questionnaires between post- versus pre-vaccination data. PubMed and Cochrane Library searches were conducted on 1 September 2023. The primary outcome was the incidence of any prespecified adverse menstrual event, and the outcome measure was the risk ratio. The meta-analysis was conducted by using the Mantel-Haenszel method and the random effects model. We summarized the results on risk factors as well as key findings of the studies included. RESULTS: We retrieved 161 references from electronic databases and additional sources such as references lists. Of those, we considered 21 comparative observational studies. The meta-analysis of any adverse menstrual adverse event reported in 12 studies resulted in a pooled estimate (risk ratio 1.13; 95% CI, 0.96-1.31) that did not favor any group. The analysis was constrained by considerable clinical and statistical heterogeneity. Risk factors for self-reported menstrual changes included a history of COVID-19 infection, the concern about COVID-19 vaccines, smoking, previous cycle irregularities, depression, and stress, and other issues. CONCLUSIONS: The risk ratio did not favor any group and heterogeneity was prevalent among the studies. Most studies suggested that the reported changes were temporary, minor, and nonserious.

Hypothalamic-pituitary-ovarian axis suppression is common among women during US Army Basic Combat Training.

OBJECTIVE: Less than half of servicewomen report loss of menses during initial military training. However, self-reported menstrual status may not accurately reflect hypothalamic-pituitary-ovarian (HPO) axis suppression and may underestimate reproductive health consequences of military training. Our aim was to characterise HPO axis function during US Army Basic Combat Training (BCT) in non-hormonal contraceptive-using women and explore potential contributors to HPO axis suppression. METHODS: In this 10-week prospective observational study, we enrolled multi-ethnic women entering BCT. Trainees provided daily first-morning voided urine, and weekly blood samples during BCT. Urinary luteinising hormone, follicle stimulating hormone, and metabolites of estradiol and progesterone were measured by chemiluminescent assays (Siemens Centaur XP) to determine hormone patterns and luteal activity. We measured body composition, via dual-energy X-ray absorptiometry, at the beginning and end of BCT. RESULTS: Trainees (n=55) were young (mean (95% CI): 22 (22, 23) years) with average body mass index (23.9 (23.1, 24.7) kg/m2). Most trainees (78%) reported regular menstrual cycles before BCT. During BCT, 23 (42%) trainees reported regular menses. However, only seven trainees (12.5%) had menstrual cycles with evidence of luteal activity (ELA) (ie, presumed ovulation), all with shortened luteal phases. 41 trainees (75%) showed no ELA (NELA), and 7 (12.5%) were categorised as indeterminant. Overall, women gained body mass and lean mass, but lost fat mass during BCT. Changes in body mass and composition appear unrelated to luteal activity. CONCLUSIONS: Our findings reveal profound HPO axis suppression with NELA in the majority of women during BCT. This HPO axis suppression occurs among women who report normal menstrual cycles.

Assessing the impact of hormonal contraceptive use on menstrual health among women of reproductive age - a systematic review.

BACKGROUND: Contraceptive methods are well-established in their ability to prevent pregnancy and increase individual agency in childbearing. Evidence suggests that contraceptives can also be used to treat adverse conditions associated with menstruation, including abnormal and prolonged uterine bleeding, heavy menstrual bleeding, painful menstruation, endometriosis, uterine fibroids, and premenstrual dysphoric disorders.This review investigates the effects of contraceptive techniques such as contraceptive pills, and long-acting reversible contraceptives (e.g. intrauterine devices, implants) on menstrual morbidity. METHODS: Over ten databases with no geographical boundaries were searched from inception until October 2023. Study designs were one of the following types to be included: parallel or cluster randomised controlled trials, controlled clinical trials, controlled before and after studies, interrupted time series studies, cohort or longitudinal analyses, regression discontinuity designs, and case-control studies. Ten team members screened the papers in pairs with a Kappa score of more than 7, and Covidence was used. Conflicts were resolved by discussion, and the full papers were divided among the reviewers to extract the data from eligible studies. RESULTS: Hormonal contraceptives are considered a well-tolerated, non-invasive, and clinically effective treatment for abnormal and prolonged uterine bleeding, heavy menstrual bleeding, painful menstruation, endometriosis, uterine fibroids, and premenstrual dysphoric disorders. Our studies investigating quality of life or well-being in women with heavy menstrual bleeding, endometriosis, or uterine fibroids have found improvements in all dimensions assessed. CONCLUSIONS: Hormonal contraceptives significantly reduce pain, symptom severity, and abnormal bleeding patterns associated with women who suffer from heavy menstrual bleeding, endometriosis, and uterine fibroids.

Hormonal contraceptives significantly reduce pain, symptom severity, and abnormal bleeding patterns associated with women who suffer from heavy menstrual bleeding, endometriosis, and uterine fibroids. Findings can inform clinical practice and policy decisions to ensure that women have access to safe and effective contraceptive options that promote both reproductive and non-reproductive health.

No unfavorable effects on the menstruation recovery of early postoperative hypoprolactinemia after transsphenoidal surgery in patients with lactotroph pituitary neuroendocrine tumor.

OBJECTIVE: Transsphenoidal surgery for lactotroph pituitary neuroendocrine tumor (PitNET) lowers serum prolactin concentrations, occasionally below the normal range. However, the clinical significance of postoperative hypoprolactinemia is still unclear. In this study, we retrospectively reviewed the female patients with lactotroph PitNET who were treated with transsphenoidal surgery to elucidate the influence of postoperative hypoprolactinemia on regular menstruation restoration and endocrinological remission. RESULTS: The serum prolactin levels in all thirty three participating females had decreased following surgery. Serum prolactin levels in seven patients had decreased below the lower limit of normal ranges (hypoproactinemia group) and in the remaining twenty six patients, it was within the normal range (non-hypoproractinemia group). In hypoprolactinemia group, regular menstruation was restored in all patients with only lactotroph axis deficiency. Nine patients from the non-hypoprolactinemia group experienced re-elevation of serum prolactin concentration (27%). No patient in hypoprolactinemia group experienced the relapse of hyperprolactinemia. These data suggest that early postoperative hypoprolactinemia after transsphenoidal surgery for lactotroph PitNET is not only a good predictive factor for endocrinological remission but also no unfavorable effects on regular menstruation restoration.

Selection of reference miRNAs for RT-qPCR assays in endometriosis menstrual blood-derived mesenchymal stem cells.

Choosing appropriate reference genes or internal controls to normalize RT-qPCR data is mandatory for the interexperimental reproducibility of gene expression data obtained by RT-qPCR in most studies, including those on endometriosis. Particularly for miRNAs, the choice for reference genes is challenging because of their physicochemical and biological characteristics. Moreover, the retrograde menstruation theory, mesenchymal stem cells in menstrual blood (MenSCs), and changes in post-transcriptional regulatory processes through miRNAs have gained prominence in the scientific community as important players in endometriosis. Therefore, we originally explored the stability of 10 miRNAs expressions as internal control candidates in conditions involving the two-dimensional culture of MenSCs from healthy women and patients with endometriosis. Here, we applied multiple algorithms (geNorm, NormFinder, Bestkeeper, and delta Ct) to screen reference genes and assessed the comprehensive stability classification of miRNAs using RefFinder. Pairwise variation calculated using geNorm identified three miRNAs as a sufficient number of reference genes for accurate normalization. MiR-191-5p, miR-24-3p, and miR-103a-3p were the best combination for suitable gene expression normalization. This study will benefit similar research, but is also attractive for regenerative medicine and clinics that use MenSCs, miRNA expression, and RT-qPCR.

Transplantation of hyaluronic acid and menstrual blood-derived stem cells accelerated wound healing in a diabetic rat model.

Diabetic wounds require a multifactorial approach because several factors are involved in its occurrence. Herein we investigated whether transplantation of hyaluronic acid (HA) in combination with menstrual blood derived stem cells (MenSCs) could promote healing in diabetic rats. Thirty days after induction of diabetes, sixty animals were randomly planned into four equal groups: the untreated group, HA group, MenSC group, and HA+MenSC group. Sampling was done for histological, molecular, and tensiometrical assessments. Our results indicated that the wound contraction rate, volumes of new epidermis and dermis, collagen density, as well as tensiometrical parameter were considerably increased in the treatment groups compared to the untreated group and these changes were more obvious in the HA+MenSC ones. In addition, the expression levels of TGF-ß and VEGF genes were significantly upregulated in treatment groups in comparison with the untreated group and were greater in the HA+MenSC group. This is while expression levels of TNF-α and IL-1ß genes were more considerably downregulated in the HA+MenSC group than the other groups. We concluded that the combined use of HA and MenSCs has more effects on diabetic wound healing.

Human Menstrual Blood-Derived Stem Cells Protect against Tacrolimus-Induced Islet Dysfunction via Cystathionine ß-Synthase Mediated IL-6/STAT3 Inactivation.

Diabetes imposes a huge burden worldwide. Islet transplantation is an alternative therapy for diabetes. However, tacrolimus, a kind of immunosuppressant after organ transplantation, is closely related to post-transplant diabetes mellitus. Mesenchymal stem cells (MSCs) have attracted interest for their potential to alleviate diabetes. In vivo experiments revealed that human menstrual blood-derived stem cells (MenSCs) treatment improved tacrolimus-induced blood glucose, body weight, and glucose tolerance disorders in mice. RNA sequencing was used to analyze the potential therapeutic targets of MenSCs. In this study, we illustrated that cystathionine ß-synthase (CBS) contributed to tacrolimus -induced islet dysfunction. Using ß-cell lines (MIN6, ß-TC-6), we demonstrated that MenSCs ameliorated tacrolimus-induced islet dysfunction in vitro. Moreover, MenSC reduced the tacrolimus-induced elevation of CBS levels and significantly enhanced the viability, anti-apoptotic ability, glucose-stimulated insulin secretion (GSIS), and glycolytic flux of ß-cells. We further revealed that MenSCs exerted their therapeutic effects by inhibiting CBS expression to activate the IL6/JAK2/STAT3 pathway. In conclusion, we showed that MenSCs may be a potential strategy to improve tacrolimus-induced islet dysfunction.

Epithelial mesenchymal transition in human menstruation and implantation.

The endometrium during the sexual cycle undergoes detachment, tissue remodeling, and differentiation during the menstrual cycle. Localized and transient destruction and regeneration of endometrial tissue are also essential for pregnancy. It is possible to attribute many causes of failure in infertility treatment to the implantation stage. To improve the success rate of plateau fertility treatment, it is important to understand the regeneration mechanism of the endometrium, a unique regenerative tissue in the human body. In association with cell proliferation, tissue remodeling requires the relocation of proliferative cells, and the steady-state epithelial cells need to be motile for the relocation. Transient add-on motile activity in epithelial cells is mediated by epithelial to mesenchymal transition (EMT) and reversible mesenchymal to epithelial transition (MET). The destruction and regeneration of endometrial tissue over a period of days to weeks requires a system with a rapid and characteristic mechanism similar to that of wound healing. Here, I review the relationship between the well-known phenomenon of EMT in wound healing and endometrial tissue remodeling during the sexual cycle and pregnancy establishment, which are automatically triggered by menstruation and embryonal invasion.

Outcomes of Vaginal Repair and Vaginal Repair Combined With GnRHa Administration in the Treatment of Cesarean Section Scar Defects: A Randomized Clinical Trial.

STUDY OBJECTIVE: To prospectively investigate whether the application of vaginal repair (VR) of cesarean section scar defect (CSD) combined with a gonadotropin-releasing hormone agonist (GnRHa) achieve better clinical outcomes than VR alone. DESIGN: A randomized clinical trial. SETTING: University Hospital. PATIENTS: A total of 124 women with CSD were undergoing expectant management from December 2016 to September 2021. 61 were randomized to VR+ GnRHa and 63 to VR alone. INTERVENTION: Vaginal repair combined with GnRHa and vaginal repair alone. MEASURES AND MAIN RESULTS: The primary outcome was the duration of menstruation and thickness of the remaining muscular layer (TRM) at 6 months after surgery. Secondary outcomes included the length, width, and depth of the CSD; operation time; estimated blood loss; hospitalization time; and operative complications. Women were treated with either VR (n = 63) or VR + GnRHa (n = 61). Menstruation and TRM in patients pre vs post comparisons either with VR or VR + GnRHa are significantly improved (p <.05). Significant differences in menstruation duration and TRM occurred in patients treated with VR + GnRHa compared with those treated with VR (p <.05). Moreover, the rate of CSD after surgery in the VR group was significantly higher than that in the VR + GnRHa group (p = .033), and CSD patients in the VR + GnRHa group achieved better therapeutic effects than those in the VR group (p = .017). Patients who received VR + GnRHa had a shorter menstruation duration and a greater increment of TRM postoperatively than patients treated with VR alone (p = .021; p = .002, respectively). CONCLUSION: VR + GnRHa therapy has a greater potential to improve scar healing and reduce the number of menstruation days than VR alone for symptomatic women with CSD.

Energy availability modulates regional blood flow via estrogen-independent pathways in regularly menstruating young women.

PURPOSE: This study aimed to investigate the impact of short-term low energy availability (LEA) on vascular function in young, regularly menstruating women. METHODS: Participants were 19 women, aged 22.9 ± 4.2 years, with body mass index 18-30 kg·m2. They were divided into two groups and completed two conditions in a crossover design: a 3-day control condition (CON) with an energy availability of 45 kcals·kgFFM-1·day-1 and a 3-day LEA condition of 15 kcals·kgFFM-1 day-1. Assessments were conducted during the early follicular phase of the menstrual cycle. Outcome measures included forearm blood flow (FBF), heart rate, blood pressure, arterial stiffness, resting energy expenditure (REE), metabolic blood markers and body composition. RESULTS: Significant time-by-condition interactions were found for resting FBF (p = .004), REE (p = .042), triiodothyronine (p = .006), ß-hydroxybutyrate (p = .002) and body mass (p < .001). Resting FBF was 1.43 ± 1.01 and 1.31 ± 0.61 (arbitrary units) at pre and post, respectively, in LEA and 1.52 ± 0.7 and 1.76 ± 0.57 at pre and post in CON. The LEA condition led to a decrease in triiodothyronine (pre: 1.54 ± 0.28, post: 1.29 ± 0.27 ng ml-1), REE (pre: 1588 ± 165, post: 1487 ± 160 kcals day-1) and body mass (pre: 61.4 ± 7.5, post: 59.6 ± 7.3 kg). Changes in resting FBF were significantly correlated with changes in REE in the LEA condition (r = 0.53; p = 0.02). CONCLUSION: Short-term LEA modifies regional blood flow and this might contribute to the observed decreased in REE. Findings emphasize the need for careful management of energy availability in populations at risk of LEA.

Interleukin 6 at menstruation promotes the proliferation and self-renewal of endometrial mesenchymal stromal/stem cells through the WNT/ß-catenin signaling pathway.

Background: At menstruation, the functional layer of the human endometrium sheds off due to the trigger of the release of inflammatory factors, including interleukin 6 (IL-6), as a result of a sharp decline in progesterone levels, leading to tissue breakdown and bleeding. The endometrial mesenchymal stem-like cells (CD140b+CD146+ eMSC) located in the basalis are responsible for the cyclical regeneration of the endometrium after menstruation. Endometrial cells from the menstruation phase have been proven to secrete a higher amount of IL-6 and further enhance the self-renewal and clonogenic activity of eMSC. However, the IL-6-responsive mechanism remains unknown. Thus, we hypothesized that IL-6 secreted from niche cells during menstruation regulates the proliferation and self-renewal of eMSC through the WNT/ß-catenin signaling pathway. Methods: In this study, the content of IL-6 across the menstrual phases was first evaluated. Coexpression of stem cell markers (CD140b and CD146) with interleukin 6 receptor (IL-6R) was confirmed by immunofluorescent staining. In vitro functional assays were conducted to investigate the effect of IL-6 on the cell activities of eMSC, and the therapeutic role of these IL-6- and WNT5A-pretreated eMSC on the repair of injured endometrium was observed using an established mouse model. Results: The endometrial cells secrete a high amount of IL-6 under hypoxic conditions, which mimic the physiological microenvironment in the menstruation phase. Also, the expression of IL-6 receptors was confirmed in our eMSC, indicating their capacity to respond to IL-6 in the microenvironment. Exogenous IL-6 can significantly enhance the self-renewal, proliferation, and migrating capacity of eMSC. Activation of the WNT/ß-catenin signaling pathway was observed upon IL-6 treatment, while suppression of the WNT/ß-catenin signaling impaired the stimulatory role of IL-6 on eMSC activities. IL-6- and WNT5A-pretreated eMSC showed better performance during the regeneration of the injured mouse endometrium. Conclusion: We demonstrate that the high level of IL-6 produced by endometrial cells at menstruation can induce the stem cells in the human endometrium to proliferate and migrate through the activation of the WNT/ß-catenin pathway. Treatment of eMSC with IL-6 and WNT5A might enhance their therapeutic potential in the regeneration of injured endometrium.

Factors influencing menstrual regularity among female workers: a cross-sectional analysis study.

BACKGROUND: Regularity of menstrual cycles is an important indicator of women's health and fertility, and female workers are exposed to several factors, such as sleep disorders, stress, and shift work, that affect their menstrual regularity. This makes it necessary to comprehensively identify the determinants of menstrual regularity. Therefore, this study identified the factors affecting menstrual regularity among female workers from physiological, psychological, and situational dimensions based on the theory of unpleasant symptoms. METHODS: This was a secondary analysis of the 2010-2012 Korea National Health and Nutrition Examination Survey and utilized the data of 2418 female workers. Based on the theory of unpleasant symptoms, physiological factors included age, age at menarche, childbirth experience, body mass index, and sleep duration. Psychological factors included stress level, depressive mood, and suicidal ideation. Situational factors included education level, household income, consumption of alcohol, engagement in smoking, and work schedule. The χ²-test and hierarchical logistic regression analysis were performed, reflecting the complex sample design. RESULTS: Age at menarche, childbirth experience, and body mass index among physiological factors and education level and work schedule among situational factors were found to be related to menstrual regularity. A higher risk of menstrual irregularities was found among those who had given birth (versus those who had not), had a high age at menarche (versus those with a low age at menarche), were obese (versus those who had a normal body mass index), had elementary school-level or lesser educational achievements (versus those with college graduate-level or higher educational achievements), and who had a shift work schedule (versus those with a fixed schedule). CONCLUSIONS: Intervention is needed for female workers who have these risk factors, and special attention must be paid to female workers who have a shift work schedule. Additionally, since body mass index can be controlled, intervention concerning body mass index is necessary to reduce menstrual irregularity.

Correlation of sex hormone levels with orthodontic tooth movement in the maxilla: a prospective cohort study.

BACKGROUND: Sex hormones secreted during the menstrual cycle and the application of orthodontic forces to teeth can affect the metabolism of periodontal ligaments. This study aimed to determine whether there are any differences in orthodontic tooth displacement during the menstrual cycle and when using hormonal contraceptives and whether the amount of female sex hormones influences the efficiency of tooth displacement. METHODS: A total of 120 women aged between 20 and 30 years with Angle Class II requiring transpalatal arch (TPA) to derotate teeth 16 and 26 were included in this study. The participants were divided into two groups: group A, which included women with regular menstruation, and control group B, which included women taking monophasic combined oral contraceptives. Group A was divided into subgroups according to the moment of TPA activation: menstruation (A1), ovulation phase (A2), and luteal phase (A3) (examination I). On intraoral scans, measurement points were marked on the proximal mesial cusps of teeth 16 and 26, and the intermolar distance (M1) was determined. The change in the position of the measurement points 6 weeks after activation (examination II) made it possible to determine the derotating extent of teeth 16 (O16) and 26 (O26) and the widening of the intermolar distance (M2-M1). In examinations I and II, tooth mobility in the alveoli was assessed using Periotest based on the periotest values (PTV) PTV1 and PTV2, respectively. RESULTS: A significant difference in all parameters was observed among groups A1, A2, and A3 (P < 0.001). Group A3 showed the highest values of parameters O16, O26, and M2-M1, and group A2 showed the lowest values, which did not differ from the control group (P = 0.64). PTV2 and PTV1 were the highest in group A3 and the lowest in groups A1 and B. Intergroup differences were statistically significant (P < 0.001). CONCLUSIONS: With the quantification of changes in tooth mobility in the alveoli during the menstrual cycle in women undergoing orthodontic treatment, it was possible to determine that female sex hormones affect the effectiveness of orthodontic treatment, and the optimal moment for TPA activation is the luteal phase of the menstrual cycle.

The Essential Role of PGF2α/PTGFR in Molding Endometrial Breakdown and Vascular Dynamics, Regulated by HIF-1α in a Mouse Menstrual-like Model.

In women of childbearing age, extensive decidualization, shedding and remodeling of the endometrium during the menstrual cycle are fundamental for successful pregnancy. The role of prostaglandins (PGs) in menstruation has long been proposed in humans, and the rate-limiting enzyme cyclooxygenase was shown to play a key role in endometrial breakdown and shedding in a mouse menstrual-like model in our previous study. However, the specific types of PGs involved and their respective roles remain unclear. Therefore, our objective was to investigate the mechanism through which PGs regulate endometrial disintegration. In this study, the microscopy was observed by HE; the protein levels of prostaglandins E1 (PGE1), prostaglandins E2 (PGE2), prostaglandin F2α (PGF2α) and Prostaglandin I2 (PGI2) were detected by ELISA; the mRNA level of Pfgfr2, Vascular Endothelial Growth Factor(Vegf), Angiostatin and Hypoxia inducible factor-1α (Hif1α) were examined by real-time PCR; PTGFR Receptor (PTGFR), VEGF, Angiostatin and HIF-1α protein levels were investigated by western blotting; the locations of protein were observed by Immunohistochemistry; HIF-1α binding PTGFR promoter was detected by Chromatin Immunoprecipitation (ChIP) and real-time PCR. We found that the concentrations of PGE1, PGE2, and PGF2α all increased significantly during this process. Furthermore, Ptgfr mRNA increased soon after Progesterone (P4) withdrawal, and PTGFR protein levels increased significantly during abundant endometrial breakdown and shedding processes. PTGFR inhibitors AL8810 significantly suppressed endometrial breakdown and shedding, promoted Angiostatin expression, and reduced VEGF-A expressions and vascular permeability. And HIF-1α and PTGFR were mainly located in the luminal/gland epithelium, vascular endothelium, and pre-decidual zone. Interestingly, HIF-1α directly bound to Ptgfr promoter. Moreover, a HIF-1α inhibitor 2-methoxyestradiol (2ME) significantly reduced PTGFR expression and suppressed endometrial breakdown which was in accord with PTGFR inhibitor's effect. Similar changes occurred in human stromal cells relevant to menstruation in vitro. Our study provides evidence that PGF2α/PTGFR plays a vital role in endometrial breakdown via vascular changes that are regulated by HIF-1α during menstruation.

The effect of perceived stress on menstrual complaints in university students.

Studies have examined the effect of stress on dysmenorrhea and premenstrual syndrome. For this reason in this study, it was aimed to determine the impact of stress on menstrual symptoms (adverse effects, abdominal pain, and coping methods). This descriptive and correlational study was conducted with 351 university students in Turkey by sharing the link to the questionnaire on online social media platforms. It was determined that those whose income was equal to their expenses had lower menstrual symptoms, having a chronic disease and smoking increased menstrual symptoms (F = 3.19/p = .04; t = 2.33/p = .02; t = 3.96/p = .00). The study identified that there was a positive low-level correlation (r: 0.25, p < .01) between the Perceived Stress Scale-14 and the Menstruation Symptom Questionnaire, and the 6.5 percent change in menstrual symptoms was explained by perceived stress. In the study, it is thought that stress affects the experience of menstrual symptoms. Therefore, it is believed that by providing training on stress and effective coping methods by midwives and nurses, menstrual symptoms can be reduced, contributing to women's health. For future studies, it is recommended to examine the effects of stress coping methods training on stress and menstrual complaints.