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1.
J Med Life ; 17(1): 109-115, 2024 Jan.
Article En | MEDLINE | ID: mdl-38737668

Polycystic ovary syndrome is the most common cause of oligo-ovulation and anovulation among women of reproductive age, contributing to infertility. This study aimed to compare the effects of green tea tablets and metformin on ovulation, menstrual cycle regularity, and antioxidant biomarkers in women with polycystic ovary syndrome (PCOS). In this clinical trial study, 94 women with PCOS were randomly assigned to three groups: green tea (n = 33), metformin (n = 29), and control (n = 32). Menstrual status and oxidative stress parameters, including total antioxidant capacity, thiol, and lipid peroxidation, were compared before and 3 months after the intervention among all three groups. Data analysis was conducted using SPSS software version 22 and employing the analysis of variance and paired t-tests. Following the intervention, the mean menstrual cycle duration in the green tea, metformin, and control groups was 32.22 ± 12.78, 48.72 ± 37.06, and 48.53 ± 31.04 days, respectively (P = 0.040). There was no statistically significant difference between the three groups in terms of biochemical, hormonal, and antioxidant indices before and after the intervention (P > 0.05). The intake of green tea tablets was associated with better outcomes in regulating the menstrual cycle in women with PCOS.


Menstrual Cycle , Metformin , Ovulation , Polycystic Ovary Syndrome , Tablets , Tea , Humans , Polycystic Ovary Syndrome/drug therapy , Female , Metformin/therapeutic use , Metformin/pharmacology , Menstrual Cycle/drug effects , Adult , Ovulation/drug effects , Young Adult , Antioxidants/therapeutic use , Oxidative Stress/drug effects
2.
J Occup Environ Med ; 65(7): e491-e495, 2023 07 01.
Article En | MEDLINE | ID: mdl-37130820

OBJECTIVE: The aim of the study is to examine changes in work productivity and daily activity impairment among women by starting ethinylestradiol (EE)/drospirenone (DRSP) for perimenstrual symptoms. METHODS: Participants were women who were newly prescribed EE/DRSP at 25 gynecological clinics in Japan. Eligible participants recorded daily intake of EE/DRSP and the Work Productivity Activity Impairment Questionnaire General Health every 2 weeks for 3 months by smartphone app. A linear mixed-effects model was used to see changes in work productivity impairment and activity impairment relative to baseline. RESULTS: A total of 222 participants were eligible. Work productivity impairment recovered by 20.0% (95% confidence interval, 14.1%-26.0%) at 1 m and maintained for 2 months. Activity impairment recovered by 20.1% (95% confidence interval, 15.5%-24.7%) at 1 m and thereafter. CONCLUSIONS: Improvements in work productivity and daily activities were observed at 1 m after EE/DRSP initiation, with a sustained effect thereafter.


Lynestrenol , Menstrual Cycle , Menstruation Disturbances , Work Performance , Prospective Studies , Smartphone , Humans , Male , Female , Adolescent , Young Adult , Adult , Androstenes/therapeutic use , Mineralocorticoid Receptor Antagonists/therapeutic use , Japan , Activities of Daily Living , Lynestrenol/therapeutic use , Menstruation Disturbances/drug therapy , Menstrual Cycle/drug effects , Treatment Outcome
3.
Toxicology ; 465: 153031, 2022 01 15.
Article En | MEDLINE | ID: mdl-34774661

Per- and poly-fluoroalkyl substances (PFAS) are widespread environmental contaminants frequently detected in drinking water supplies worldwide that have been linked to a variety of adverse reproductive health outcomes in women. Compared to men, reproductive health effects in women are generally understudied while global trends in female reproduction rates are declining. Many factors may contribute to the observed decline in female reproduction, one of which is environmental contaminant exposure. PFAS have been used in home, food storage, personal care and industrial products for decades. Despite the phase-out of some legacy PFAS due to their environmental persistence and adverse health effects, alternative, short-chain and legacy PFAS mixtures will continue to pollute water and air and adversely influence women's health. Studies have shown that both long- and short-chain PFAS disrupt normal reproductive function in women through altering hormone secretion, menstrual cyclicity, and fertility. Here, we summarize the role of a variety of PFAS and PFAS mixtures in female reproductive tract dysfunction and disease. Since these chemicals may affect reproductive tissues directly or indirectly through endocrine disruption, the role of PFAS in breast, thyroid, and hypothalamic-pituitary-gonadal axis function are also discussed as the interplay between these tissues may be critical in understanding the long-term reproductive health effects of PFAS in women. A major research gap is the need for mechanism of action data - the targets for PFAS in the female reproductive and endocrine systems are not evident, but the effects are many. Given the global decline in female fecundity and the ability of PFAS to negatively impact female reproductive health, further studies are needed to examine effects on endocrine target tissues involved in the onset of reproductive disorders of women.


Endocrine Disruptors/adverse effects , Endocrine System Diseases/chemically induced , Environmental Exposure/adverse effects , Environmental Pollutants/adverse effects , Fertility/drug effects , Hydrocarbons, Fluorinated/adverse effects , Menstrual Cycle/drug effects , Reproduction/drug effects , Endocrine System Diseases/metabolism , Endocrine System Diseases/physiopathology , Female , Humans , Infertility, Female/chemically induced , Infertility, Female/metabolism , Infertility, Female/physiopathology , Pregnancy , Pregnancy Complications/chemically induced , Pregnancy Complications/metabolism , Pregnancy Complications/physiopathology , Prognosis , Risk Assessment , Risk Factors
4.
Nitric Oxide ; 118: 39-48, 2022 01 01.
Article En | MEDLINE | ID: mdl-34774755

Recent reports have acknowledged the underrepresentation of women in the field of dietary nitrate (NO3-) research. Undoubtedly, greater participation from women is warranted to clarify potential sex differences in the responses to dietary NO3- interventions. However, careful consideration for the effects of sex hormones - principally 17ß-estradiol - on endogenous nitric oxide (NO) synthesis and dietary NO3- reductase capacity is necessary for improved interpretation and reproducibility of such investigations. From available literature, we present a narrative review describing how hormonal variations across the menstrual cycle, as well as with menopause, may impact NO biosynthesis catalyzed by NO synthase enzymes and NO3- reduction via the enterosalivary pathway. In doing so, we address methodological considerations related to the menstrual cycle and hormonal contraceptive use relevant for the inclusion of premenopausal women along with factors to consider when testing postmenopausal women. Adherence to such methodological practices may explicate the utility of dietary NO3- supplementation as a means to improve vascular function among women across the lifespan.


Biomedical Research/methods , Menopause/drug effects , Menstrual Cycle/drug effects , Nitrates/pharmacology , Dietary Supplements , Estradiol/metabolism , Female , Humans , Menopause/metabolism , Menstrual Cycle/metabolism , Nitric Oxide/biosynthesis , Nitric Oxide/metabolism , Sex Factors
5.
J Psychopharmacol ; 35(12): 1523-1535, 2021 12.
Article En | MEDLINE | ID: mdl-34872406

BACKGROUND: Acute hypoxia, which is panicogenic in humans, also evokes panic-like behavior in male rats. Panic disorder is more common in women and susceptibility increases during the premenstrual phase of the cycle. AIMS: We here investigated for the first time the impact of hypoxia on the expression of panic-like escape behavior by female rats and its relationship with the estrous cycle. We also evaluated functional activation of the midbrain panic circuitry in response to this panicogenic stimulus and whether short-term, low-dose fluoxetine treatment inhibits the hyper-responsiveness of females in late diestrus. METHODS: Male and female Sprague Dawley rats were exposed to 7% O2. Females in late diestrus were also tested after short-term treatment with fluoxetine (1.75 or 10 mg/kg, i.p.). Brains were harvested and processed for c-Fos and tryptophan hydroxylase immunoreactivity in the periaqueductal gray matter (PAG) and dorsal raphe nucleus (DR). RESULTS: Acute hypoxia evoked escape in both sexes. Overall, females were more responsive than males and this is clearer in late diestrus phase. In both sexes, hypoxia induced functional activation (c-Fos expression) in non-serotonergic cells in the lateral wings of the DR and dorsomedial PAG, which was greater in late diestrus than proestrus (lowest behavioral response to hypoxia). Increased responding in late diestrus (behavioral and cellular levels) was prevented by 1.75, but not 10 mg/kg fluoxetine. DISCUSSION: The response of female rats to acute hypoxia models panic behavior in women. Low-dose fluoxetine administered in the premenstrual phase deserves further attention for management of panic disorders in women.


Behavior, Animal/drug effects , Diestrus/drug effects , Dorsal Raphe Nucleus/drug effects , Fluoxetine/pharmacology , Hypoxia/complications , Panic/drug effects , Periaqueductal Gray/drug effects , Selective Serotonin Reuptake Inhibitors/pharmacology , Sex Characteristics , Animals , Disease Models, Animal , Female , Male , Menstrual Cycle/drug effects , Panic Disorder/drug therapy , Rats , Rats, Sprague-Dawley , Selective Serotonin Reuptake Inhibitors/administration & dosage
6.
Mol Hum Reprod ; 27(11)2021 11 02.
Article En | MEDLINE | ID: mdl-34581822

Uterine natural killer cells are regulated via surface inhibitory receptors for IL15 and galectin-9 (LGALS9) secreted by endometrial stromal cells (ESCs). However, the mechanism that regulates LGALS9 mRNA levels in ESCs is unclear. The aim of this study is to clarify the transcriptional regulation of LGALS9 in ESCs. Here, LGALS9 mRNA expression levels significantly decreased in the endometrial tissue in the early- to mid-secretory phase, and recovered in the mid- to late-secretory phase, compared to that in the proliferative phase. In ESCs, LGALS9 mRNA expression significantly decreased following estradiol + medroxyprogesterone acetate treatment for 1 day and increased after 12 days compared to that in the control. The transcriptional activity of the LGALS9 upstream region was upregulated by heart and neural crest derivatives expressed 2 (HAND2) and downregulated by forkhead box O1 (FOXO1). In ESCs, HAND2 expression significantly increased throughout the 12 days treatment with steroid hormones, whereas FOXO1 expression significantly increased on Day 1, reached a plateau, and significantly increased again after 6 days of treatment. Levels of FOXO1 phosphorylation (pFOXO1) remained unchanged after a 3-day treatment of ESCs with steroid hormones, but significantly increased following a 12-day treatment. pFOXO1 could not bind to the DNA and was thus unable to directly suppress LGALS9 transcription. Therefore, expression level of HAND2 and phosphorylation status of FOXO1 may determine LGALS9 mRNA expression. This study provides a novel molecular mechanism underlying the transcriptional regulation of LGALS9 mRNA in ESCs, which could be valuable in the treatment of diseases associated with decidualization failure.


Basic Helix-Loop-Helix Transcription Factors/metabolism , Endometrium/metabolism , Forkhead Box Protein O1/metabolism , Galectins/metabolism , Menstrual Cycle/metabolism , Stromal Cells/metabolism , Transcription, Genetic , Adult , Basic Helix-Loop-Helix Transcription Factors/genetics , Endometrium/drug effects , Estradiol/pharmacology , Female , Forkhead Box Protein O1/genetics , Galectins/genetics , Humans , Medroxyprogesterone Acetate/pharmacology , Menstrual Cycle/drug effects , Menstrual Cycle/genetics , Middle Aged , Phosphorylation , Stromal Cells/drug effects , Transcription, Genetic/drug effects
7.
Reprod Biol Endocrinol ; 19(1): 60, 2021 Apr 23.
Article En | MEDLINE | ID: mdl-33892741

BACKGROUND: Low serum progesterone on the day of frozen embryo transfer (FET) is associated with diminished pregnancy rates in artificial endometrium preparation cycles, but there is no consensus on whether strengthened luteal phase support (LPS) benefits patients with low progesterone on the FET day in artificial cycles. This single-centre, large-sample retrospective trial was designed to investigate the contribution of strengthened LPS to pregnancy outcomes for groups with low progesterone levels on the FET day in artificial endometrium preparation cycles. METHODS: Women who had undergone the first artificial endometrium preparation cycle after a freeze-all protocol in our clinic from 2016 to 2018 were classified into two groups depending on their serum progesterone levels on the FET day. Routine LPS was administered to group B (P ≥ 10.0 ng/ml on the FET day, n = 1261), and strengthened LPS (routine LPS+ im P 40 mg daily) was administered to group A (P < 10.0 ng/ml on the FET day, n = 1295). The primary endpoint was the live birth rate, and the secondary endpoints were clinical pregnancy, miscarriage and neonatal outcomes. RESULTS: The results showed that the clinical pregnancy rate was significantly lower in group A than in group B (48.4% vs 53.2%, adjusted risk ratio (aRR) 0.81, 95% confidence interval (CI) 0.68, 0.96), whereas miscarriage rates were similar between the two groups (16.0% vs 14.7%, aRR 1.09, 95% CI 0.77, 1.54). The live birth rate was slightly lower in group A than in group B (39.5% vs 43.3%, aRR 0.84, 95% CI 0.70, 1.0). Birthweights and other neonatal outcomes were similar between the two groups (P > 0.05). CONCLUSIONS: The results indicated that the serum progesterone level on the FET day was one of the risk factors predicting the chances of pregnancy in artificial endometrium preparation cycles, and strengthened LPS in patients with low progesterone on the FET day might help to provide a reasonable pregnancy outcome in artificial cycles, although further prospective evidence is needed to confirm this possibility.


Fertility Agents, Female/therapeutic use , Luteal Phase/drug effects , Menstrual Cycle/drug effects , Ovulation Induction/methods , Progesterone/blood , Adult , China , Cryopreservation , Embryo Transfer/methods , Embryo, Mammalian , Female , Freezing , Humans , Infant, Newborn , Infertility/blood , Infertility/therapy , Male , Pregnancy , Pregnancy Rate , Retrospective Studies , Treatment Outcome
8.
Am J Reprod Immunol ; 86(2): e13412, 2021 08.
Article En | MEDLINE | ID: mdl-33641250

PROBLEM: Changes in sex hormones during the menstrual cycle and contraceptive vaginal ring (CVR) use influence immunity within the female genital tract, but the magnitude of these effects and their anatomical location are unclear. METHOD OF STUDY: In a prospective study, 29 women were assessed at three-time points: follicular phase, luteal phase, and one month after initiation of the ethinyl estradiol/etonogestrel CVR (NuvaRing®, Merck). We performed microarrays on endocervical cytobrushes and measured immune mediators in cervicovaginal fluid, adjusting for bacterial vaginosis and the presence of blood. We compared these results to public gene expression data from the fallopian tubes, endometrium, endo- and ectocervix, and vagina. RESULTS: Immune-related gene expression in the endocervix and immune mediators in cervicovaginal fluid increased during CVR use versus both menstrual phases, and in the follicular versus luteal phase. The antimicrobial protein granulysin was high during CVR use, intermediate in the follicular phase, and nearly absent from the luteal phase. Re-analysis of public gene expression data confirmed increased immune-related gene expression in the endocervix during the follicular phase. However, in the fallopian tube, endometrium, and vagina, the follicular phase showed immunosuppression. CONCLUSIONS: Immune-related genes in the cervicovaginal tract were highest during CVR use, intermediate in the follicular phase, and lowest in the luteal phase. Granulysin is a potential biomarker of menstrual phase: Frequently detected in follicular samples, but rare in luteal. Lastly, immunological differences between the follicular and luteal phases vary throughout the female genital tract.


Antigens, Differentiation, T-Lymphocyte/immunology , Contraceptive Agents, Female/administration & dosage , Contraceptive Devices, Female , Desogestrel/administration & dosage , Ethinyl Estradiol/administration & dosage , Immunity, Mucosal/drug effects , Menstrual Cycle , Adult , Female , Humans , Menstrual Cycle/drug effects , Menstrual Cycle/immunology , Middle Aged
9.
J Ethnopharmacol ; 272: 113931, 2021 May 23.
Article En | MEDLINE | ID: mdl-33607202

ETHNOPHARMACOLOGICAL RELEVANCE: A combination of Trachyspermum ammi L., Curcuma longa L., Cuminum cyminum L., Trigonella foenum-graecum L., Foeniculum vulgare Mill., Anethum graveolens L and Zingiber officinale Roscoe is used as immunity booster and reproductive efficiency enhancing agents in folklore medicine. AIM OF THE STUDY: The present study aimed to assess the immunomodulatory, uterine cleansing and reproduction enhancing effects of polyherbal mixture in post-partum buffaloes. MATERIALS AND METHODS: Enzyme linked immunosorbent assay (ELISA) was used to investigate the effects of polyherbal mixture feeding on for quantification of neutrophil functions and blood progesterone hormone estimation. Ultrasonography was used to assess the status of uterine involution, fluid in uterus and ovarian follicular status. Quantitative real time PCR (qRT-PCR) was used to measure the expression of chemokine genes CXCR1, CXCR2 AND IL-8. Artificial insemination with cryopreserved semen was used to breed the animals. Reproductive efficiency parameters were assessed using standard calculation methods. RESULTS: Neutrophil functions and transcriptional abundance of chemokine genes were significantly (P < 0.05) higher in buffaloes supplemented with polyherbal mixture compared to buffaloes in control group. The rate of cervical and uterine involution was significantly (P < 0.05) higher in treatment group compared to control group. The service period was shorter, days to first insemination was earlier and the number of services per conception was lower in buffaloes supplemented with polyherbal mixture compared to the buffaloes in control group. The proportion of buffaloes with large ovarian follicles within 28 days of post-partum was also significantly (P < 0.05) higher in treatment group compared to the control group. CONCLUSIONS: The polyherbal mixture used in the study improved the immunity of the buffaloes, facilitated early involution of cervix and uterus, efficient cleansing of lochia and improved subsequent fertility. It has the potential to be used in dairy animals for improving post-partum reproductive efficiency.


Buffaloes/immunology , Buffaloes/metabolism , Menstrual Cycle/drug effects , Plants, Medicinal , Postpartum Period , Uterus/drug effects , Animals , Cervix Uteri/drug effects , Dietary Supplements , Female , Immunity, Innate/genetics , Neutrophils/metabolism , Ovulation/drug effects , Peroxidase/blood , Postpartum Period/drug effects , Postpartum Period/physiology , Progesterone/blood , Reproduction/drug effects , Uterus/diagnostic imaging
10.
Clin Nutr ; 40(6): 4106-4112, 2021 06.
Article En | MEDLINE | ID: mdl-33610422

AIM: The aim of this randomized trial was to find whether resveratrol could improve menstrual dysfunction, clinical signs (i.e., acne and hair loss), and the biochemical evidence of hyperandrogenism in the women with PCOS. METHODS: Women, in the age range of 18-40 years, diagnosed with PCOS, as defined by the Rotterdam criteria, and no other known cause of abnormal menstruation, were recruited. Participants were randomized based on a 1:1 ratio, to either 1000 mg resveratrol or 1000 mg placebo daily groups, for a period of 3 months. RESULTS: Seventy-eight patients were randomized: 39 to the resveratrol group and 39 to placebo. Results were analyzed according to the intention-to-treat principle. At the end of study, it was found that women who received resveratrol had a statistically higher regular menstruation rate, as compared to those who got placebo (76.47% vs. 51.61%; p = 0.03), and lower hair loss (32.10% vs. 68.00%; p = 0.009). We also found no significant differences between the two groups in terms of ovarian and adrenal androgens, sex hormone binding globulin (SHBG) levels, free androgen index (FAI), glycoinsulinemic metabolism and lipid profile. Moreover, the resveratrol treatment did not interfere with the thyroid, liver and kidney functions. The negative effect of resveratrol on the body composition was also observed, though not influencing changes in the weight, relative to the placebo group. CONCLUSION: Resveratrol improved menstrual cyclicity and hair loss, even though levels of androgens, insulin and lipids remained unchanged.


Hyperandrogenism/drug therapy , Menstrual Cycle/drug effects , Polycystic Ovary Syndrome/blood , Polycystic Ovary Syndrome/drug therapy , Resveratrol/therapeutic use , Adolescent , Adult , Alopecia/blood , Alopecia/drug therapy , Alopecia/etiology , Androgens/blood , Body Composition/drug effects , Female , Humans , Hyperandrogenism/blood , Hyperandrogenism/etiology , Insulin/blood , Intention to Treat Analysis , Lipids/blood , Polycystic Ovary Syndrome/complications , Treatment Outcome , Young Adult
11.
Eur Rev Med Pharmacol Sci ; 25(1): 447-454, 2021 01.
Article En | MEDLINE | ID: mdl-33506935

OBJECTIVE: Multiple sclerosis (MS) is a demyelinating, chronic, and progressive autoimmune disease of the central nervous system that causes the loss of axons and grey matter, and has a high prevalence in young female patients. Fingolimod is an oral treatment agent that acts by blocking the passage of the T lymphocytes responsible for the pathogenesis of MS from lymphoid tissue into the peripheral blood. We aimed to research the effects of menstrual cycles on leukocytes and lymphocyte levels in RRMS (relapsing-remitting MS) patients who received fingolimod treatment. PATIENTS AND METHODS: This study was performed to determine the most suitable phase of the menstrual cycle in patients with RRMS for follow-up assessment of lymphopaenia levels after fingolimod treatment. The study population consisted of 41 RRMS patients receiving fingolimod therapy and 33 healthy women of reproductive age. Complete blood counts were performed in three different phases of the menstrual cycle, and the two groups were compared. Variability in the total leukocyte, lymphocyte, and neutrophil immune cell numbers between cycles was examined. RESULTS: The results indicated that total leukocyte, neutrophil, and lymphocyte levels were decreased in RRMS patients receiving fingolimod treatment, but these changes were not related to the phase of the menstrual cycle. In our study, leukocyte levels in healthy individuals were significantly lower in the proliferative phase than in other phases. CONCLUSIONS: The results indicated that lymphocyte monitoring in RRMS patients receiving fingolimod treatment can be performed at any stage of the menstrual cycle.


Fingolimod Hydrochloride/pharmacology , Lymphopenia/drug therapy , Menstrual Cycle/drug effects , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Adolescent , Adult , Cell Proliferation/drug effects , Female , Humans , Leukocytes/drug effects , Lymphocyte Count , Lymphocytes/drug effects , Lymphopenia/blood , Lymphopenia/pathology , Menstrual Cycle/blood , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/blood , Multiple Sclerosis, Relapsing-Remitting/pathology , Neutrophils/drug effects , Young Adult
12.
Cells ; 11(1)2021 12 29.
Article En | MEDLINE | ID: mdl-35011664

Immune system functionality has been commonly assessed by a whole-blood or isolated-cell stimulation assay. The aim of this study was to determine whether cytokine production in whole-blood-stimulated samples is influenced by age, sex, and smoking. A descriptive cross-sectional study in 253 healthy participants aged 18-55 years was conducted. Whole blood samples were stimulated for 24 h with LPS and concentrations of IL-6, IL-10, and TNF-α were determined in the culture media. Among parameters considered, statistical regression analysis indicated that smoking (change in R2 = 0.064, p < 0.001) and sex (change in R2 = 0.070, p < 0.001) were the main predictors for IL-10 production, with higher values for women and non-smokers. Age was also found to be a significant predictor (change in R2 = 0.021, p < 0.001), with higher values for younger ages. Age (change in R2 = 0.089, p = 0.013) and smoking (change in R2 = 0.037, p = 0.002) were found to be negative predictors for IL-6 production. Regarding TNF-α-stimulated production, age (change in R2 = 0.029, p = 0.009) and smoking (change in R2 = 0.022, p = 0.022) were found to be negative predictors. Furthermore, sex (change in R2 = 0.016, p = 0.045) was found to be a significant predictor, with lower values for women. In conclusion, sex, age, and smoking were found to be independent determinants of stimulated cytokine production. While female sex is associated with higher IL-10 and lower TNF-α production, aging and smoking are associated with lower IL-6, IL-10, and TNF-α production.


Blood Cells/metabolism , Cytokines/biosynthesis , Cytokines/blood , Lipopolysaccharides/pharmacology , Sex Characteristics , Smoking/blood , Adult , Age Factors , Blood Cells/drug effects , Body Mass Index , Female , Humans , Linear Models , Menstrual Cycle/drug effects
13.
J Sleep Res ; 30(4): e13239, 2021 08.
Article En | MEDLINE | ID: mdl-33348471

Sleep spindles benefit declarative memory consolidation and are considered to be a biological marker for general cognitive abilities. However, the impact of sexual hormones and hormonal oral contraceptives (OCs) on these relationships are less clear. Thus, we here investigated the influence of endogenous progesterone levels of naturally cycling women and women using OCs on nocturnal sleep and overnight memory consolidation. Nineteen healthy women using OCs (MAge  = 21.4, SD = 2.1 years) were compared to 43 healthy women with a natural menstrual cycle (follicular phase: n = 16, MAge  = 21.4, SD = 3.1 years; luteal phase: n = 27, MAge  = 22.5, SD = 3.6 years). Sleep spindle density and salivary progesterone were measured during an adaptation and an experimental night. A word pair association task preceding the experimental night followed by two recalls (pre-sleep and post-sleep) was performed to test declarative memory performance. We found that memory performance improved overnight in all women. Interestingly, women using OCs (characterized by a low endogenous progesterone level but with very potent synthetic progestins) and naturally cycling women during the luteal phase (characterized by a high endogenous progesterone level) had a higher fast sleep spindle density compared to naturally cycling women during the follicular phase (characterized by a low endogenous progesterone level). Furthermore, we observed a positive correlation between endogenous progesterone level and fast spindle density in women during the luteal phase. Results suggest that the use of OCs and the menstrual cycle phase affects sleep spindles and therefore should be considered in further studies investigating sleep spindles and cognitive performance.


Contraceptives, Oral/pharmacology , Memory Consolidation/drug effects , Menstrual Cycle/drug effects , Menstrual Cycle/psychology , Sleep/drug effects , Female , Humans , Mental Recall/drug effects , Young Adult
14.
J Clin Endocrinol Metab ; 106(4): 1022-1040, 2021 03 25.
Article En | MEDLINE | ID: mdl-33382900

CONTEXT: Low-grade chronic inflammation is commonly seen in polycystic ovary syndrome (PCOS) patients with elevated levels of inflammatory cytokines in the endometrium. OBJECTIVE: This work aimed to increase the limited understanding of the mechanisms underlying cytokine synthesis and increased endometrial inflammation in PCOS patients. METHODS: Endometrial biopsy samples were collected from non-PCOS (n = 17) and PCOS (n = 22) patients either during the proliferative phase of the menstrual cycle or with hyperplasia. Endometrial explants were prepared from PCOS patients and underwent pharmacological manipulation in vitro. The expression and localization of toll-like receptor 2 (TLR2)/4, key elements of innate immune signal transduction and nuclear factor κB (NFκB) signaling pathways, and multiple cytokines were comprehensively evaluated by Western blotting, immunohistochemistry, and immunofluorescence in endometrial tissues. RESULTS: We demonstrated the distribution of protein expression and localization associated with the significantly increased androgen receptor, TLR2, and TLR4-mediated activation of interferon regulatory factor-7 (IRF-7) and NFκB signaling, cytokine production, and endometrial inflammation in PCOS patients compared to non-PCOS patients with and without endometrial hyperplasia. In vitro experiments showed that 5-dihydrotestosterone (DHT) enhanced androgen receptor, TLR4, IRF-7, and p-NFκB p65 protein expression along with increased interferon α (IFNα) and IFNÉ£ abundance. The effects of DHT on IRF-7, p-NFκB p65, and IFN abundance were abolished by flutamide, an antiandrogen. Although 17ß-estradiol (E2) decreased p-IRF-7 expression with little effect on TLR-mediated IRF7 and NFκB signaling or on cytokine protein levels, exposure to metformin alone or in combination with E2 suppressed interleukin-1 receptor-associated kinase 4 (IRAK4), p-IRF-7, IRF-7, IκB kinase α (IKKα), p-NFκB p65, IFNÉ£, and tumor necrosis factor α protein expression. CONCLUSION: Cytokine synthesis and increased endometrial inflammation in PCOS patients are coupled to androgen-induced TLR4/IRF-7/NFκB signaling, which is inhibited by metformin treatment.


Androgens/pharmacology , Endometrium/drug effects , Metformin/pharmacology , Polycystic Ovary Syndrome , Adult , Cytokines/biosynthesis , Endometrial Hyperplasia/metabolism , Endometrial Hyperplasia/pathology , Endometrium/metabolism , Endometrium/pathology , Female , Humans , Interferon Regulatory Factor-7/metabolism , Menstrual Cycle/drug effects , Menstrual Cycle/metabolism , Multiprotein Complexes/metabolism , Multiprotein Complexes/physiology , NF-kappa B/metabolism , Polycystic Ovary Syndrome/metabolism , Polycystic Ovary Syndrome/pathology , Protein Binding , Signal Transduction/drug effects , Signal Transduction/physiology , Toll-Like Receptor 4/metabolism
15.
Eur J Appl Physiol ; 121(3): 793-801, 2021 Mar.
Article En | MEDLINE | ID: mdl-33289860

PURPOSE: Asprosin, an orexigenic hormone that stimulates hepatic glucose release, is elevated in insulin resistance and associated with obesity. Plasma asprosin concentrations may also be related to female sex hormone levels; higher levels are reported in women with polycystic ovary syndrome (PCOS) but this may be related to peripheral insulin resistance also associated with PCOS. Clarification of female-specific factors influence on the plasma asprosin response is crucial for studies investigating asprosin. Therefore, this study determined the association of menstrual phase, oral contraceptive (OC) use (as a pharmacological influence on sex hormone levels) and training status (as a physiological influence on sex hormone levels) on plasma asprosin levels in pre-menopausal women. METHODS: Fasting plasma asprosin, 17ß-estradiol (E2) and progesterone, were assessed in 32 healthy untrained and trained women with regular menstrual cycles (non-OC; n = 8 untrained, n = 6 trained) or using OC (n = 10 untrained, n = 8 trained) during early follicular, late follicular and mid-luteal menstrual phases (or the time-period equivalent for OC users). RESULTS: Asprosin was lower in OC (0.75 ± 0.38 ng mL-1) than non-OC users (1.00 ± 0.37 ng mL-1; p = 0.022). Across a cycle, asprosin was highest in the early follicular equivalent time-point in OC users (0.87 ± 0.37 ng mL-1) but highest in the mid-luteal phase in non-OC users (1.09 ± 0.40 ng mL-1). Asprosin concentrations varied more across a cycle in untrained than trained women, with higher concentrations in the early follicular phase compared to the late follicular and mid-luteal (training status-by-menstrual phase interaction p = 0.028). CONCLUSION: These findings highlight the importance of considering OC use, menstrual cycle phase and to a lesser extent training status when investigating circulating asprosin concentrations in females.


Contraceptives, Oral/administration & dosage , Estradiol/blood , Exercise/physiology , Fasting/blood , Fibrillin-1/blood , Menstrual Cycle/physiology , Progesterone/blood , Adult , Female , Humans , Menstrual Cycle/drug effects , Menstruation , Young Adult
16.
Medicine (Baltimore) ; 99(50): e23630, 2020 Dec 11.
Article En | MEDLINE | ID: mdl-33327341

BACKGROUND: Previous cesarean scar defect (PCSD) is a gynecological disease that can cause bleeding after intercourse, prolonging menstrual period, intermenstrual bleeding, dysmenorrhea, and even lead to infertility. Chinese herbal medicine plays an important role in the treatment of gynecological diseases in China and East Asia. This study aims to assess the efficacy and safety of Chinese herbal medicine for PCSD. METHODS: We search the following databases: PubMed, the Cochrane Library, Chinese Biomedical Literature Database (CB), Chinese Science and Technique Journals Database (VIP), EMBASE, Chinese National Knowledge Infrastructure Database (CNKI), and the Wanfang Database. Other sources will also be searched like Google Scholar and gray literature. All databases mentioned above are searched from the start date to the latest version. Randomized controlled trials will be included which recruiting PCSD participants to assess the efficacy and safety of Chinese herbal medicines against controls (placebo or other therapeutic agents). Primary outcomes will include the size of PCSD, menstrual cycle, menstrual phase, menstrual volume, duration of disease, security index. Two authors will independently scan the searched articles, extract the data from attached articles, and import them into Endnote X8 and use Microsoft Excel 2013 to manage data and information. We will assess the risk of bias by Cochrane tool of risk of bias. Disagreements will be resolved by consensus or the participation of a third party. All analysis will be performed based on the Cochrane Handbook for Systematic Reviews of Interventions. The meta-analysis in this review will use RevMan 5.3 software. RESULTS: The study aims to evaluate the efficacy and safety of the treatment that Chinese herbal medicine for PCSD. CONCLUSION: This study of the meta-analysis could provide evidence for clinicians and help patients to make a better choice. INPLASY REGISTRATION NUMBER: INPLASY202090080.


Cesarean Section/adverse effects , Cicatrix/drug therapy , Cicatrix/etiology , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/adverse effects , Endometriosis/prevention & control , Female , Humans , Menstrual Cycle/drug effects , Randomized Controlled Trials as Topic , Research Design , Surgical Wound Infection/prevention & control , Meta-Analysis as Topic
17.
J Agric Food Chem ; 68(45): 12631-12640, 2020 Nov 11.
Article En | MEDLINE | ID: mdl-33140642

Lauric acid (LA) has been implicated in the prevention/treatment of obesity. However, the role of LA in modulating an obesity-related female reproductive disorder remains largely unknown. Here, female mice were fed a control diet, high-fat diet (HFD), or HFD supplemented with 1% LA. The results demonstrated that the HFD-induced estrous cycle irregularity and the reduction of serum follicle-stimulating hormone (FSH) were alleviated by LA supplementation. In possible mechanisms, LA supplementation led to significant increase in serum lipid metabolites such as sphingomyelin and lysophosphatidylcholine containing LA (C12:0) and the improvement of glucose metabolism in mice fed HFD. Moreover, impaired body energy metabolism and weakened brown adipose tissue (BAT) thermogenesis of HFD-fed mice were improved by LA supplementation. Together, these findings showed that LA supplementation alleviated HFD-induced estrous cycle irregularity, possibly associated with altered serum lipid metabolites, improved glucose metabolism, body energy metabolism, and BAT thermogenesis. These findings suggested the potential application of LA in alleviating obesity and its related reproductive disorders.


Lauric Acids/administration & dosage , Menstruation Disturbances/drug therapy , Thermogenesis/drug effects , Animals , Diet, High-Fat/adverse effects , Dietary Supplements/analysis , Energy Metabolism/drug effects , Female , Humans , Lipid Metabolism/drug effects , Menstrual Cycle/drug effects , Menstruation Disturbances/metabolism , Menstruation Disturbances/physiopathology , Mice , Mice, Inbred C57BL
18.
Drug Test Anal ; 12(11-12): 1620-1628, 2020 Nov.
Article En | MEDLINE | ID: mdl-33125822

The intra-individual stability of growth hormone (GH) biomarkers IGF-I, P-III-NP, calculated GH-2000 score in relation to growth hormone-releasing hormone (GHRH) (Somatorelin) administration, menstrual cycle, and hematological parameters were investigated in four men and eight women, respectively. Moreover, the hematological parameters hemoglobin (Hb) and percentage of reticulocyte (RET%) were statistically analyzed in relation to the GH biomarker parameters for the GHRH administration study and the menstrual cycle study. Longitudinal monitoring of IGF-I and/or GH-2000 score proved to be a viable approach to detect the GHRH intake in men, as all four participants show values above individually calculated thresholds (calculated as mean ± 3SD from three baseline samples). The intra-individual variation for IGF-I, P-III-NP, and calculated GH-2000 score in women, over two consecutive menstrual cycles, was investigated and established to be higher (coefficients variations [CVs] between 12% and 186%) than in men (CVs between 3% and 12%). The GHRH administration did not influence the hematological parameters. A strong positive correlation between Hb and IGF-I (Rs = 0.73, p < 0.0001) and a borderline weak correlation between RET% and IGF-I (Rs = 0.28, p = 0.054) were noticed in the women. No correlation for the P-III-NP and the hematological parameters was seen for the females in the menstrual cycle study. The results fortify previous studies that longitudinal monitoring of IGF-I and/or GH-2000 score may be a promising method to detect doping with GH and GH stimulating agents in men, whereas the large intra-individual variation noted in women indicates that longitudinal monitoring of these biomarker may be harder to evaluate in women.


Growth Hormone-Releasing Hormone/administration & dosage , Human Growth Hormone/blood , Insulin-Like Growth Factor I/metabolism , Menstrual Cycle/blood , Peptide Fragments/blood , Procollagen/blood , Administration, Intravenous , Adolescent , Adult , Biomarkers/blood , Cohort Studies , Doping in Sports/prevention & control , Female , Humans , Longitudinal Studies , Male , Menstrual Cycle/drug effects , Young Adult
19.
Curr Opin Endocrinol Diabetes Obes ; 27(6): 373-379, 2020 12.
Article En | MEDLINE | ID: mdl-33027071

PURPOSE OF REVIEW: This review seeks to evaluate the impact of environmental exposures on the menstrual cycle length detailing timing of exposure on pathophysiology. RECENT FINDINGS: Recent literature has examined the relationship between menstrual cycle length and environmental exposures including air pollutants, parabens, and polybrominated biphenyls. SUMMARY: Research is limited but suggest importance of further research in evaluating environmental exposures and menstrual cycle length.


Environmental Exposure , Environmental Pollutants/toxicity , Menstrual Cycle/drug effects , Menstrual Cycle/physiology , Environmental Exposure/adverse effects , Environmental Exposure/statistics & numerical data , Female , Humans , Menstruation Disturbances/chemically induced , Menstruation Disturbances/epidemiology , Time Factors
20.
Reprod Biol Endocrinol ; 18(1): 102, 2020 Oct 15.
Article En | MEDLINE | ID: mdl-33059712

BACKGROUND: Patients found to be poor ovarian responders (POR) are a challenging patient population for any assisted reproduction technology. Despite attempts at various controlled ovarian stimulation schemes, reproductive outcomes in this patient population have not improved. In recent years, the DuoStim protocol (both follicular and luteal phase stimulation during the same menstrual cycle) has shown a potential for use in patients with POR. METHODS: This retrospective study reviewed the medical records of 304 women who were diagnosed as POR and underwent the DuoStim protocol. We compared follicular phase stimulation (FPS) data and luteal phase stimulation (LPS) data of the same patients. We also compared the effects of different trigger drugs including urine human chorionic gonadotropin (uHCG; 10,000 IU), recombinant human chorionic gonadotropin (rHCG; 250 µg), and gonadotropin-releasing hormone agonist (GnRH-a; 0.2 mg) at the FPS and LPS stages. RESULTS: POR undergoing the DuoStim protocol resulted in a significantly higher number of oocytes retrieved, normal fertilised oocytes, cleaved embryos, cryopreserved embryos, and good quality embryos at the LPS stage than at the FPS stage. Trigger drugs at the FPS stage did not affect the FPS stage data. Regardless of the stage, rHCG and GnRH-a yielded significantly more cryopreserved embryos and good quality embryos than uHCG. CONCLUSION: The use of GnRH-a or rHCG as the trigger drug may be better than uHCG in both the FPS and LPS stages for POR undergoing the DuoStim protocol. This will increase the number of good quality embryos at the LPS stage. We found that the LPS stage results in more oocytes (and therefore more embryos) than the FPS stage.


Fertility Agents, Female/therapeutic use , Infertility, Female/drug therapy , Ovulation Induction/methods , Adult , Chorionic Gonadotropin/therapeutic use , Chorionic Gonadotropin/urine , Drug Resistance/drug effects , Female , Fertility Agents, Female/classification , Follicular Phase/drug effects , Follicular Phase/physiology , Gonadotropin-Releasing Hormone/agonists , Gonadotropin-Releasing Hormone/therapeutic use , Humans , Infertility, Female/therapy , Luteal Phase/drug effects , Luteal Phase/physiology , Menstrual Cycle/drug effects , Menstrual Cycle/physiology , Oocytes/drug effects , Oocytes/physiology , Oogenesis/drug effects , Oogenesis/physiology , Recombinant Proteins/therapeutic use , Retrospective Studies , Treatment Outcome
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