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).

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.

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.

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.

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.

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.

COVID-19 and abnormal uterine bleeding: potential associations and mechanisms.

The impact of COVID-19 on menstruation has received a high level of public and media interest. Despite this, uncertainty exists about the advice that women and people who menstruate should receive in relation to the expected impact of SARS-CoV-2 infection, long COVID or COVID-19 vaccination on menstruation. Furthermore, the mechanisms leading to these reported menstrual changes are poorly understood. This review evaluates the published literature on COVID-19 and its impact on menstrual bleeding, discussing the strengths and limitations of these studies. We present evidence consistent with SARS-CoV-2 infection and long COVID having an association with changes in menstrual bleeding parameters and that the impact of COVID vaccination on menstruation appears less significant. An overview of menstrual physiology and known causes of abnormal uterine bleeding (AUB) is provided before discussing potential mechanisms which may underpin the menstrual disturbance reported with COVID-19, highlighting areas for future scientific study. Finally, consideration is given to the effect that menstruation may have on COVID-19, including the impact of the ovarian sex hormones on acute COVID-19 severity and susceptibility and reported variation in long COVID symptoms across the menstrual cycle. Understanding the current evidence and addressing gaps in our knowledge in this area are essential to inform public health policy, direct the treatment of menstrual disturbance and facilitate development of new therapies, which may reduce the severity of COVID-19 and improve quality of life for those experiencing long COVID.

An investigation of endometrial vascularity in normally menstruating women and those in other physiological states using 3D ultrasound imaging.

OBJECTIVES: This study aimed to determine the normal vasculature indices of the endometrium and to correlate them with those in various physiological states. METHODS: Women undergoing ultrasound at the Feto-Maternal Center, Qatar in 2020-2021 as part of their gynecologic evaluation were enrolled into the study. They were divided into those with normal menses and no additional pathology, those following spontaneous miscarriage, postpartum and menopausal. Three-dimensional (3D) evaluation of the endometrial vasculature was done and the parameters quantified included vascularization index (VI), flow index (FI), vascularization flow index (VFI), endometrial thickness, endometrial volume and uterine volume. JASP, an open-source statistical analysis software, was used for analysis and an independent t-test to compare the vascularity indices. A multivariate regression analysis was also done to look at the factors affecting the endometrial vascular indices within the luteal phase. RESULTS: A total of 461 women were studied: 122 in the follicular phase, 199 in the luteal phase, 90 after a spontaneous miscarriage, 29 postpartum, and 16 menopausal. The vascularity indices were highest after miscarriage and lowest postnatally. There were no significant effects of age, gravida, para, or abortions on VI and VFI. However, there was a significant positive effect of age on FI (P = 0.019) There was a significant increase in endometrial volume and thickness in the luteal phase as compared to follicular phase (P < 0.01), but there was no difference in the vascularity indices. The uterine and endometrial volume in the postnatal group were nearly double that of the luteal group (P value <0.01 and 0.014, respectively). There was a significant decrease in flow index in the postnatal group compared to the luteal group (P < 0.01), suggesting low flow intensity in the postnatal group. CONCLUSIONS: Endometrial vascular indices measured using 3D Doppler can be used to determine normal vascular indices and vary with physiological states such as after miscarriages, postnatally and in the menopausal states.

Association between the occurrence of adenomyosis and the clinical outcomes of vaginal repair of cesarean section scar defects: an observational study.

BACKGROUND: To examine the correlation between the occurrence of adenomyosis and the outcome of vaginal repair of cesarean section scar defects (CSDs). METHODS: A total of 278 women with CSD were enrolled in this retrospective observational cohort study at the Shanghai First Maternity & Infant Hospital between January 2013 and August 2017. Patients were divided into two groups according to preoperative magnetic resonance imaging (MRI) findings: the adenomyosis group and the non-adenomyosis group. They all underwent vaginal excision and suturing of CSDs and were required to undergo examinations 3 and 6 months after surgery. Preoperative and postoperative clinical information was collected. Optimal healing was defined as a duration of menstruation of no more than 7 days and a thickness of the residual myometrium (TRM) of no less than 5.8 mm after vaginal repair. RESULTS: Before vaginal repair, for patients in the adenomyosis group, the mean duration of menstruation was longer and TRM was significantly thinner than those in patients in the non-adenomyosis group (p < 0.05). The TRM and duration of menstruation 3 and 6 months after surgery were significantly improved in both groups (p < 0.05). There were more patients with optimal healing in the non-adenomyosis group than in the adenomyosis group (44.7% vs. 30.0%; p < 0.05). Furthermore, 59.3% (32/54) of the women tried to conceive after vaginal repair. The pregnancy rates of women with and without adenomyosis were 66.7% (8/12) and 61.9% (26/42), respectively. The duration of menstruation decreased significantly from 13.4 ± 3.3 days before vaginal repair to 7.6 ± 2.3 days after vaginal repair in 25 patients (p < 0.001). The TRM increased significantly from 2.3 ± 0.8 mm before vaginal repair to 7.6 ± 2.9 mm after vaginal repair (p < 0.001). CONCLUSIONS: Vaginal repair reduced postmenstrual spotting and may have improved fertility in patients with CSDs. Patients with adenomyosis are more likely to have suboptimal menstruation and suboptimal healing of CSDs. Adenomyosis might be an adverse factor in the repair of uterine incisions.

Association Between Menstrual Patterns and Adverse Pregnancy Outcomes in Patients With Polycystic Ovary Syndrome.

Objective: To investigate the results of in vitro fertilization among polycystic ovary syndrome (PCOS) patients using the long-acting long protocol regarding the relationship between menstrual patterns and adverse pregnancy outcomes. Design: Retrospective cohort study. Setting: University-affiliated reproductive medical center. Background: The menstrual patterns of patients with PCOS is considered related to metabolism; however, no study has analyzed the outcome of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) in patients with PCOS who have different menstrual patterns. This study aimed to observe the outcomes of IVF/ICSI in patients with PCOS with different menstrual patterns who used the long-acting long protocol. Methods: This was a retrospective analysis in the first cycle of IVF/ICSI at the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2019. In total, 1834 patients with PCOS were classified into the regular menstruation group (n=214), the oligomenorrhea group (n=1402), and the amenorrhea group (n=218). Results: PCOS patients who used the long-acting long protocol of IVF/ICSI had similar clinical pregnancy rates and live birth rates despite having different menstrual patterns. The overall incidence of adverse pregnancy outcomes, including abortion, spontaneous preterm birth (sPTB), gestational diabetes(GDM), hypertensive disorder inpregnancy (HDP), and premature rupture of membranes(PROM, was significantly higher in the amenorrhea group than in the regular menstrual and oligomenorrhea groups (25.88% vs. 30.41% vs. 43.69%; P = 0.013). Additionally, the rates of GDM (2.35% vs. 6.10% vs. 13.79%; P=0.015) and macrosomia (5.26% vs. 10.94% vs. 18.39%; P=0.026) in the amenorrhea group were significantly higher than those in the other two groups. Correction for confounding factors showed that menstrual patterns are related to the occurrence of adverse pregnancy outcomes. Amenorrhea is an independent risk factor for adverse pregnancy outcome (OR [odds ratio]: 2.039, 95% CI [confidence interval]: 1.087-3.822), GDM (OR: 5.023, 95% CI: 1.083-23.289), and macrosomia (OR: 4.918, 95% CI: 1.516-15.954). Conclusions: IVF/ICSI can achieve similar pregnancy and live birth rates in PCOS patients with different menstrual patterns. However, the overall incidence of adverse pregnancy outcomes in PCOS patients with amenorrhea is higher than that in patients with regular menstruation or oligomenorrhea.

The Vaginal Microbiome of Nonhuman Primates Can Be Only Transiently Altered to Become Lactobacillus Dominant without Reducing Inflammation.

The vaginal microbiome composition in humans is categorized based upon the degree to which one of four species of Lactobacillus is dominant (Lactobacillus crispatus, community state type I [CST I], Lactobacillus gasseri, CST II, Lactobacillus iners, CST III, and Lactobacillus jensenii, CST V). Women with a vaginal microbiome not dominated by one of the four Lactobacillus species tend to have a more diverse microbiome, CST IV. CSTs I, II, III, and V are common in North America and Europe and are associated with lower incidences of some pathogens, such as human immunodeficiency virus (HIV), human papillomavirus (HPV), and Gardnerella vaginalis. As a result, therapeutic interventions to change the composition of the vaginal microbiomes are under development. However, Homo sapiens is the only mammalian species which has high frequencies of Lactobacillus-dominated vaginal microbiomes. Here, we treated female nonhuman primates (NHPs) with regimens of metronidazole and high levels of L. crispatus to determine how well these animals could be colonized with L. crispatus, how this influenced the immunological milieu, and how Lactobacillus treatment influenced or was influenced by the endogenous vaginal microbiome. We find that NHPs can transiently be colonized with L. crispatus, that beta diversity and not the number of doses of L. crispatus or pretreatment with metronidazole predicts subsequent L. crispatus colonization, that L. crispatus does not alter the local immunological milieu, and that the vaginal microbiome composition was resilient, normalizing by 4 weeks after our manipulations. Overall, this study suggests these animals are not amenable to long-term L. crispatus colonization. IMPORTANCE NHPs have proven to be invaluable animal models for the study of many human infectious diseases. The use of NHPs to study the effect of the microbiome on disease transmission and susceptibility is limited due to differences between the native microbiomes of humans and NHPs. In particular, Lactobacillus dominance of the vaginal microbiome is unique to humans and remains an important risk factor in reproductive health. By assessing the extent to which NHPs can be colonized with exogenously applied L. crispatus to resemble a human vaginal microbiome and examining the effects on the vaginal microenvironment, we highlight the utility of NHPs in analysis of vaginal microbiome manipulations in the context of human disease.

Analysis on clinical association of uterine scar diverticulum with subsequent infertility in patients underwent cesarean section.

ABSTRACT: To evaluate the relationship between uterine cesarean scar diverticulum (CSD) and subsequent infertility in patients who underwent cesarean section, and determine the effects of pelvic fluid-releasing inflammations on infertility.A retrospective analysis was designed among patients with CSD who were admitted to our hospital from January 1, 2018 to December 31, 2019. A total of 60 patients with CSD and uterine fibroids or benign ovarian tumors who underwent cesarean section were included, and divided into the CSD group and control group. Baseline characteristics of all patients were collected, and the pelvic adhesion scores and the percents of tubal patency were evaluated. Furthermore, the postoperative clinical outcomes were followed up. The levels of inflammatory factors in pelvic fluid were tested using Elisa kits.Preoperative data indicated that the size of the uterine scar diverticulum was (1.68 ±â€Š0.52) cm, the pelvic adhesion scores were higher in CSD group than control group (4.67 ±â€Š0.90 vs 0.47 ±â€Š0.90, P < .05), and 21 of 30 patients with unobstructed fallopian tubes. The levels of tumor necrosis factor-α, interleukin-1ß, and interleukin-6 in patients with CSD were obviously higher than control group (P < .05). After the follow-up, the data displayed that no CSD was found in all patients, the time of menstrual period in patients with CSD was shortened to 7.80 ±â€Š1.27 days, and the myometrial thickness at uterine scar was significantly increased (P < .05). Additionally, the pregnancy rate was increased, and 12 of 30 patients were repregnant. Correlation analysis showed that the levels of inflammatory factors (tumor necrosis factor-α, interleukin-1ß, interleukin-6), the size of uterine scar diverticulum, and the myometrial thickness at uterine scar were significantly correlated with subsequent infertility (r = 0.307, 0.083, 0.147, 0.405, 0.291, P < .05).Uterine scar diverticulum repair could improve menstrual prolongation, increased the thickness of myometrium and repregnant rate. Subsequent infertility was positively correlated with uterine scar diverticulum and the levels of inflammatory factors.

Follicular waves in ontogenesis and female fertility.

Antral follicle growth and recruitment are the basis of female reproduction. Follicular wave theory explains the recruitment, growth, and selection of antral follicles. This article is devoted to the follicular wave pattern in female reproduction throughout life. We highlight progress in understanding the rhythmic follicle changes based on clinical studies and studies on animal models. We review the follicular wave pattern before puberty, during pregnancy, and in perimenopause. Several mathematical models are known which quite accurately describe follicular wave dynamics. The follicular waves theory allows the implementation of the new approaches to ovarian stimulation. Stimulation in the luteal phase and double stimulation are used more widely nowadays for fertility preservation in cancer patients and for increasing the chances of IVF programs success in poor responder patients.

Latent Tri-lineage Potential of Human Menstrual Blood-Derived Mesenchymal Stromal Cells Revealed by Specific In Vitro Culture Conditions.

Human menstrual blood-derived mesenchymal stromal cells (MenSCs) have become not only an important source of stromal cells for cell therapy but also a cellular source for neurologic disorders in vitro modeling. By using culture protocols originally developed in our laboratory, we show that MenSCs can be converted into floating neurospheres (NSs) using the Fast-N-Spheres medium for 24-72 h and can be transdifferentiated into functional dopaminergic-like (DALNs, ~ 26% TH + /DAT + flow cytometry) and cholinergic-like neurons (ChLNs, ~ 46% ChAT + /VAChT flow cytometry) which responded to dopamine- and acetylcholine-triggered neuronal Ca2+ inward stimuli when cultured with the NeuroForsk and the Cholinergic-N-Run medium, respectively in a timely fashion (i.e., 4-7 days). Here, we also report a direct transdifferentiation method to induce MenSCs into functional astrocyte-like cells (ALCs) by incubation of MenSCs in commercial Gibco® Astrocyte medium in 7 days. The MSC-derived ALCs (~ 59% GFAP + /S100ß +) were found to respond to glutamate-induced Ca2+ inward stimuli. Altogether, these results show that MenSCs are a reliable source to obtain functional neurogenic cells to further investigate the neurobiology of neurologic disorders.

Endometrial epithelial-mesenchymal transition (EMT) by menstruation-related inflammatory factors during hypoxia.

Endometriosis is characterised by inflammation and fibrotic changes. Our previous study using a mouse model showed that proinflammatory factors present in peritoneal haemorrhage exacerbated inflammation in endometriosis-like grafts, at least in part through the activation of prostaglandin (PG) E2 receptor and protease-activated receptor (PAR). In addition, hypoxia is a well-known inducer of fibrosis that may be associated with epithelial-mesenchymal transition (EMT). However, the complex molecular interactions between hypoxia and proinflammatory menstruation-related factors, PGE2 and thrombin, a PAR1 agonist, on EMT in endometriosis have not been fully characterised. To explore the effects of hypoxia and proinflammatory factors on EMT-like changes in endometrial cells, we determined the effects of PGE2 and thrombin (P/T) on EMT marker expression and cell migration in three dimensional cultured human endometrial epithelial cells (EECs) and endometrial stromal cells (ESCs). Treatment of EECs with P/T under hypoxia stimulated cell migration, increased the expression of mesenchymal N-cadherin, vimentin and C-X-C chemokine receptor type 4 (CXCR4), and reduced the expression of epithelial E-cadherin. Furthermore, treatment with C-X-C motif chemokine ligand 12 (CXCL12), a ligand for CXCR4, increased EMT marker expression and cell migration. In ESCs, P/T or oestrogen treatment under hypoxic conditions increased the expression and secretion of CXCL12. Taken together, our data show that hypoxic and proinflammatory stimuli induce EMT, cell migration and inflammation in EECs, which was increased by CXCL12 derived from ESCs. These data imply that inflammatory mediators in retrograde menstrual fluid contribute to ectopic endometrial EMT and migration in the presence of peritoneal hypoxia.

Exogenous sex hormones, menstrual and reproductive history, and risk of non-melanoma skin cancer among women: a systematic literature review and meta-analysis.

Non-melanoma skin cancers (NMSC) are more frequent among men, but women (especially those aged < 40 years) have experienced steeper growth in their incidence rates in recent years. Hormonal factors were hypothesized to be playing a role in modulating NMSC risk, but the studies published to date provided conflicting results. We systematically reviewed and meta-analysed the studies focusing on the association between hormone-related characteristics (use of exogenous sex hormones, and aspects of menstrual and reproductive history) and the risk of NMSC among women. We included observational and experimental studies published in PubMed and EMBASE until February 2020. We calculated summary relative risk (SRR) and 95% confidence intervals (CI) by applying random effects models with maximum likelihood estimation, and used the I2 statistics to quantify the degree of heterogeneity of risk estimates across studies. Eleven independent studies encompassing a total of over 30,000 NMSC cases were included in quantitative analyses. No evidence of an increased NMSC risk emerged among ever vs. never users of oral contraceptives (SRR 1.13, 95% CI 0.88-1.45) or hormones for menopause (SRR 1.09, 95% CI 0.87-1.37). Likewise, age at menarche or at menopause and parity were not associated with NMSC risk. Heterogeneity across studies was low, and pooled results were comparable between NMSC subtypes. We found no evidence that hormonal factors play a role in the pathogenesis of NMSC among women.

Obesity is associated with heavy menstruation that may be due to delayed endometrial repair.

Heavy menstrual bleeding is common and debilitating but the causes remain ill defined. Rates of obesity in women are increasing and its impact on menstrual blood loss (MBL) is unknown. Therefore, we quantified BMI and MBL in women not taking hormones and with regular menstrual cycles and revealed a positive correlation. In a mouse model of simulated menstruation, diet-induced obesity also resulted in delayed endometrial repair, a surrogate marker for MBL. BrdU staining of mouse uterine tissue revealed decreased proliferation during menstruation in the luminal epithelium of mice on a high-fat diet. Menstruation is known to initiate local endometrial inflammation and endometrial hypoxia; hence, the impact of body weight on these processes was investigated. A panel of hypoxia-regulated genes (VEGF, ADM, LDHA, SLC2A1) showed consistently higher mean values in the endometrium of women with obesity and in uteri of mice with increased weight vs normal controls, although statistical significance was not reached. The inflammatory mediators, Tnf and Il6 were significantly increased in the uterus of mice on a high-fat diet, consistent with a pro-inflammatory local endometrial environment in these mice. In conclusion, obesity was associated with increased MBL in women. Mice given a high-fat diet had delayed endometrial repair at menstruation and provided a model in which to study the influence of obesity on menstrual physiology. Our results indicate that obesity results in a more pro-inflammatory local endometrial environment at menstruation, which may delay endometrial repair and increase menstrual blood loss.

The effects of short-term low energy availability, achieved through diet or exercise, on cognitive function in oral contraceptive users and eumenorrheic women.

To date, no research has explored the effects of low energy availability on cognitive performance using dietary and exercise regimens relevant to athletes. Twenty female participants (10 eumenorrheic, 10 oral contraceptive [OC] users) completed three 3-day conditions: 1) controlled-balanced energy availability without exercise (BAL; 45 kcal·kg lean body mass [LBM]-1·day-1); 2) diet-induced low energy availability without exercise (DIET; 15 kcal·kg LBM-1·day-1); and 3) exercise-induced low energy availability (EX; 15 kcal·kg LBM-1·day-1, including 30 kcal·kg LBM-1·day-1 treadmill running at 70% maximal oxygen uptake). A cognitive test battery was completed before and after each 3-day condition. Mental rotation test accuracy improved in the BAL condition, but there was a decline in accuracy in the EX condition (BAL, +2.5%; EX, -1.4%; P = 0.042, d = 0.85). DIET (+1.3%) was not different to BAL or EX (P > 0.05). All other measures of cognitive performance were not affected by condition (P > 0.05) and OC use did not affect cognitive responses (P > 0.05). Accuracy in the mental rotation test was impaired when low energy availability was induced through increased exercise energy expenditure. All other aspects of cognition were unaffected by 3 days of low energy availability through diet or exercise. OC use did not mediate the effect of low energy availability on cognition. Novelty: Cognitive function was not affected by 3 days of diet-induced low energy availability. Only spatial awareness was impaired during 3 days of exercise-induced low energy availability. Reproductive hormones affected spatial awareness independent of energy availability.

Analysis of sex hormones and menstruation in COVID-19 women of child-bearing age.

RESEARCH QUESTION: Does SARS-CoV-2 infection have an effect on ovarian reserve, sex hormones and menstruation of women of child-bearing age? DESIGN: This is a retrospective, cross-sectional study in which clinical and laboratory data from 237 women of child-bearing age diagnosed with COVID-19 were retrospectively reviewed. Menstrual data from 177 patients were analysed. Blood samples from the early follicular phase were tested for sex hormones and anti-Müllerian hormone (AMH). RESULTS: Among 237 patients with confirmed COVID-19, severely ill patients had more comorbidities than mildly ill patients (34% versus 8%), particularly for patients with diabetes, hepatic disease and malignant tumours. Of 177 patients with menstrual records, 45 (25%) patients presented with menstrual volume changes, and 50 (28%) patients had menstrual cycle changes, mainly a decreased volume (20%) and a prolonged cycle (19%). The average sex hormone and AMH concentrations of women of child-bearing age with COVID-19 were not different from those of age-matched controls. CONCLUSIONS: Average sex hormone concentrations and ovarian reserve did not change significantly in COVID-19 women of child-bearing age. Nearly one-fifth of patients exhibited a menstrual volume decrease or cycle prolongation. The menstruation changes of these patients might be the consequence of transient sex hormone changes caused by suppression of ovarian function that quickly resume after recovery.