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Introduction: Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disturbance that affects many women worldwide and is characterized by chronic anovulation, hyperandrogenism, and ovarian dysfunction. Placenta-derived mesenchymal stem cells (PDMSCs) are derived from the placenta and have advantages over other sources of MSCs in terms of availability, safety, and immunomodulation. Materials and methods: In this experimental study, twenty female Wistar rats were assigned to four groups (n = 5) including control, sham, PCOS, and PCOS+PDMSCs groups. Then, PCOS was induced in the rats through administering letrozole for 21 days. PDMSCs (1 × 106 cells) were injected through the tail vein. Fourteen days after the cell infusion, evaluation was performed on the number of healthy follicles, corpus luteum, and cystic follicles as well as the levels of testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), fasting blood glucose, fasting insulin, and insulin resistance. Moreover, the serum levels of cholesterol, triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were measured. Liver function was also determined by the evaluation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Results: The number of corpus luteum and primordial, primary, secondary, and antral follicles was significantly elevated in the PCOS+PDMSCs group compared to the PCOS group. However, the number of cystic follicles significantly decreased in the PCOS+PDMSCs group. The LH and testosterone levels also decreased significantly, while FSH levels increased significantly in the PCOS+PDMSCs group. The levels of fasting blood glucose, fasting insulin, and insulin resistance notably decreased in the PCOS+PDMSCs group. Moreover, the lipid profile improved in the PCOS+PDMSCs group along with a significant decrease of cholesterol, LDL, and TG and an increase in HDL. The PCOS+PDMSCs group exhibited marked decreases in the AST and ALT levels as well. Conclusion: The results of this study suggest that PDMSCs are a potential treatment option for PCOS because they can effectively restore folliculogenesis and correct hormonal imbalances, lipid profiles and liver dysfunction in a rat model of PCOS. However, further research is needed to establish the safety and effectiveness of PDMSCs for treating PCOS. [ABSTRACT FROM AUTHOR]

Background: Neural stem and progenitor cells (NSPCs) from extra-neural origin represent a valuable tool for autologous cell therapy and research in neurogenesis. Identification of proneurogenic biomolecules on NSPCs would improve the success of cell therapies for neurodegenerative diseases. Preliminary data suggested that follicle-stimulating hormone (FSH) might act in this fashion. This study was aimed to elucidate whether FSH promotes development, self-renewal, and is proneurogenic on neurospheres (NS) derived from sheep ovarian cortical cells (OCCs). Two culture strategies were carried out: (a) long-term, 21-days NS culture (control vs. FSH group) with NS morphometric evaluation, gene expression analyses of stemness and lineage markers, and immunolocalization of NSPCs antigens; (b) NS assay to demonstrate FSH actions on self-renewal and differentiation capacity of NS cultured with one of three defined media: M1: positive control with EGF/FGF2; M2: control; and M3: M2 supplemented with FSH. Results: In long-term cultures, FSH increased NS diameters with respect to control group (302.90 ± 25.20 μm vs. 183.20 ± 7.63 on day 9, respectively), upregulated nestin (days 15/21), Sox2 (day 21) and Pax6 (days 15/21) and increased the percentages of cells immunolocalizing these proteins. During NS assays, FSH stimulated NSCPs proliferation, and self-renewal, increasing NS diameters during the two expansion periods and the expression of the neuron precursor transcript DCX during the second one. In the FSH-group there were more frequent cell-bridges among neighbouring NS. Conclusions: FSH is a proneurogenic hormone that promotes OCC-NSPCs self-renewal and NS development. Future studies will be necessary to support the proneurogenic actions of FSH and its potential use in basic and applied research related to cell therapy. [ABSTRACT FROM AUTHOR]

Background: This study investigated the effect of curcumin nanomicelle (CUR-n) on the structure of testis tissue, the process of spermatogenesis, LH, FSH, testosterone, and oxidative stress in a model of multiple sclerosis. Methods: Twenty-four male mice C57BL/6 were randomly allocated into 4 groups of 6 (1: group receiving 2% CPZ diet, 2: group receiving the diet of 2% CPZ + CUR-n with a dose of 50 mg/kg, 3: group receiving the diet of 2% CPZ + CUR-n with a dose of 100 mg/kg). The concentration of hormones (testosterone, LH and FSH), was measured by the special hormone assay ELISA kits. Measuring total antioxidant capacity (TAC) and Malondialdehyde (MDA) levels was done by spectrophotometry and calorimetric methods, respectively. Stereological analysis was done in order to explore the number of spermatogenesis cells, testis and sperm properties. Results: The results indicated that CUR-n (100 mg/kg) significantly enhanced the concentration of LH, FSH, testosterone, and TAC but reduced MDA levels. It also notably increased the quantity of spermatogonia, spermatocyte, round spermatids, long spermatids and LCs, augmented testis weight and volume, and germinal epithelium volume, improved sperm count, morphology, viability, and motility. In addition, a considerable decrease in the amount of wrinkling and disruption of the germinal epithelium was observed after intervention with CUR-n (100 mg/kg). Furthermore, a significant increase in the number of germ cells compared to the group receiving CPZ was detected. Conclusion: This study proposes that CUR-n could be a therapeutic agent for decreasing the adverse effects of MS on testis. [ABSTRACT FROM AUTHOR]

Background: Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is an endemic chronic disease which is characterized with progressive depletion of CD4 T cells and increased susceptibility to opportunistic infections. Previous studies have associated HIV infection with increased hypogonadism. However, the prevalence of hypogonadism remained poorly defined and widely ranging in various studies. This study aims to evaluate the serum gonadal hormonal levels and hypogonadism in antiretroviral therapy (ART) naïve newly diagnosed HIV infected-males in Mwanza, Tanzania. Methods: This was a comparison study involving 81 ART naïve newly diagnosed HIV-infected adult males as study group and 81 apparently healthy HIV-negative males as comparison group. The participants in the study group and comparison group were matched by body mass index and age. Serum hormones [Total testosterone (TT), follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E) were estimated. Serum testosterone < 300 ng/dl, or testosterone > 300 ng/dl with high LH and FSH (compensatory hypogonadism) were taken as markers of hypogonadism. Data were analyzed using STATA version 15. Results: The median serum testosterone level among ART naïve newly diagnosed HIV-infected adult males was significantly lower as compared to their comparison group (447 [259–534] versus 517 [396–605]; p = 0.0074) and shown to decrease with decreasing CD4 level. The median [IQR] serum FSH level among ART naïve newly diagnosed HIV-infected adult males was significantly higher than among their comparison group (3.8 [2.1–6.5] versus 2.6 [1.8–4.2]; p = 0.0086). The differences in serum LH and Estradiol were not statistically significant. Furthermore, the proportion of hypogonadism was significantly higher among ART naïve newly diagnosed HIV-infected adult males than in their comparison group (37.0% [30/81] versus 14.8% [12/81]; p = 0.0006). Out of these 30, 24 HIV-infected males had secondary hypogonadism, one had primary, and the remaining five had compensatory hypogonadism. Conclusion: Serum testosterone was lower and follicle stimulating hormone was higher among ART naïve HIV-infected males as compared to the HIV negative controls. Hypogonadism, mainly secondary, is common endocrine abnormality among ART naïve HIV-infected male patients in this study. HIV is associated with variations in gonadal hormones which may lead to sexual dysfunction in infected individuals. [ABSTRACT FROM AUTHOR]

Background: Follitropin delta is a novel recombinant follicle stimulating hormone preparation uniquely expressed in a human fetal retinal cell line by recombinant DNA technology. To date, no systematic review was available about the safety and the efficacy of the follitropin delta. The objective of this study was systematically reviewing the available literature and to provide updated evidence regarding the efficacy-safety profile of follitropin delta when compared to other gonadotropin formulations for ovarian stimulation in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles. Methods: An extensive search was performed to identify phase 1, phase 2 and phase 3 RCTs in humans focused on follitropin delta use for ovarian stimulation in IVF/ICSI cycles. The risk of bias and the overall quality of the evidence was analyzed. All data were extracted and analyzed using the intention-to-treat principle and expressed per woman randomized. Results: A total of 7 RCTs (1 phase 1 RCT, 2 phase 2 RCTs and 4 phase 3 RCTs) were included in the qualitative analysis, whereas data of three phase 3 RCTs were meta-analyzed. All trials compared personalized recombinant follitropin delta treatment versus conventional recombinant follitropin alfa/beta administration in potentially normo-responder patients who receive ovarian stimulation in GnRH antagonist IVF/ICSI cycles. No difference between two regimens was detected for clinical pregnancy rate [odds ratio (OR) 1.06; 95% confidence intervals (CI): 0.90, 1.24; P = 0.49; I2 = 26%], ongoing pregnancy rate (OR 1.15; 95%CI: 0.90, 1.46; P = 0.27; I2 = 40%), and live birth rate (OR 1.18; 95%CI: 0.89, 1.55; P = 0.25; I2 = 55%). No data were available regarding cumulative success rates. The rate of adoption of strategies to prevent ovarian hyperstimulation syndrome (OHSS) development (OR 0.45; 95%CI: 0.30, 0.66; P < 0.0001; I2 = 0%), and the rate of both early OHSS (OR 0.62; 95%CI: 0.43, 0.88; P = 0.008; I2 = 0%) and all forms of OHSS (OR 0.61; 95%CI: 0.44, 0.84; P = 0.003; I2 = 0%) were significantly lower in the group of patients treated with personalized follitropin delta treatment compared to those treated with conventional follitropin alfa/beta administration. Conclusion: Personalized follitropin delta treatment is associated with a lower risk of OHSS compared to conventional follitropin alfa/beta administration in potentially normo-responder patients who receive ovarian stimulation in GnRH antagonist IVF/ICSI cycles. The absence of cumulative data does not allow definitive conclusions to be drawn regarding the comparison of the effectiveness of the two treatments. Protocol study registration: CRD42023470352 (available at http://www.crd.york.ac.uk/PROSPERO). [ABSTRACT FROM AUTHOR]

Background: The intricate interplay of gene expression within ovarian granulosa cells (GCs) is not fully understood. This study aimed to investigate the miRNA regulatory mechanisms of ferroptosis during the process of follicle development in lamb GCs. Methods: Employing transcriptome sequencing, we compared differentially expressed mRNAs (DE-mRNAs) and miRNAs (DE-miRNAs) in GCs from lambs treated with follicle-stimulating hormone (FL) to untreated controls (CL). We further screened differentially expressed ferroptosis-related genes and identified potential miRNA regulatory factors. The expression patterns of HMOX1 and miRNAs in GCs were validated using qRT‒PCR and Western blotting. Additionally, we investigated the regulatory effect of oar-miR-134-3p on HMOX1 and its function in ferroptosis through cell transfection and erastin treatment. Results: We identified a total of 4,184 DE-mRNAs and 304 DE-miRNAs. The DE-mRNAs were mainly enriched in ferroptosis, insulin resistance, and the cell cycle. Specifically, we focused on the differential expression of ferroptosis-related genes. Notably, the ferroptosis-related genes HMOX1 and SLC3A2, modulated by DE-miRNAs, were markedly suppressed in FLs. Experimental validation revealed that HMOX1 was significantly downregulated in FL and large follicles, while oar-miR-134-3p was significantly upregulated compared to that in the CLs. HMOX1 expression was regulated by the targeting effect of oar-miR-134-3p. Functional assays further revealed that modulation of oar-miR-134-3p influenced HMOX1 expression and altered cellular responses to ferroptosis induction by erastin. Conclusion: This study suggested that oar-miR-134-3p and HMOX1 may be one of the pathways regulating ferroptosis in GCs. This finding provides new clues to understanding the development and regulatory process of follicles. [ABSTRACT FROM AUTHOR]

Background: The maximum daily dose of follitropin delta for ovarian stimulation in the first in vitro fertilization cycle is 12 μg (180 IU), according to the algorithm developed by the manufacturer, and based on patient's ovarian reserve and weight. This study aimed to assess whether 150 IU of menotropin combined with follitropin delta improves the response to stimulation in women with serum antimullerian hormone levels less than 2.1 ng/mL. Methods: This study involved a prospective intervention group of 44 women who received 12 μg of follitropin delta combined with 150 IU of menotropin from the beginning of stimulation and a retrospective control group of 297 women who received 12 μg of follitropin delta alone during the phase 3 study of this drug. The inclusion and exclusion criteria and other treatment and follow-up protocols in the two groups were similar. The pituitary suppression was achieved by administering a gonadotropin-releasing hormone (GnRH) antagonist. Ovulation triggering with human chorionic gonadotropin or GnRH agonist and the option of transferring fresh embryos or using freeze-all strategy were made according to the risk of developing ovarian hyperstimulation syndrome. Results: Women who received follitropin delta combined with menotropin had higher estradiol levels on trigger day (2150 pg/mL vs. 1373 pg/mL, p < 0.001), more blastocysts (3.1 vs. 2.4, p = 0.003) and more top-quality blastocysts (1.8 vs. 1.3, p = 0.017). No difference was observed in pregnancy, implantation, miscarriage, and live birth rates after the first embryo transfer. The incidence of ovarian hyperstimulation syndrome did not differ between the groups. However, preventive measures for the syndrome were more frequent in the group using both drugs than in the control group (13.6% vs. 0.6%, p < 0.001). Conclusions: In women with serum antimullerian hormone levels less than 2.1 ng/mL, the administration of 150 IU of menotropin combined with 12 μg of follitropin delta improved the ovarian response, making it a valid therapeutic option in situations where ovulation triggering with a GnRH agonist and freeze-all embryos strategy can be used routinely. Trial registration: U1111-1247-3260 (Brazilian Register of Clinical Trials, available at https://ensaiosclinicos.gov.br/rg/RBR-2kmyfm). [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of childbearing age. Randomized controlled trials (RCTs) have reported that exenatide and metformin are effective in the treatment of PCOS. In this meta-analysis, we aimed to compare the effectiveness and safety of exenatide alone or in combination with metformin versus metformin in patients suffering from PCOS. Methods: RCTs of exenatide therapy were identified through a search of electronic databases in November 2022 and updated in October 2023. Eligible studies were identified independently by the reviewers. Outcomes were analysed with Revman 5.4. Results: Nine RCTs among 214 studies on 1059 women with PCOS were included in the analysis, and among the nine RCTs, eight studies compared exenatide with metformin. Our meta-analysis demonstrated that exenatide was more effective than metformin in terms of pregnancy rate (RR 1.85 [95% CI 1.19,2.86] P = 0.006), sex hormone-binding globulin (SHBG) (MD 5 [95% CI 3.82,6.18] P < 0.001), and follicle-stimulating hormone (FSH) (MD 0.82 [95% 0.41,1.24] P < 0.001). The reductions in total testosterone (TT) (SMD -0.43 [95% CI -0.84, -0.03] P = 0.04) was more significant after treatment with exenatide than after treatment with metformin. In terms of safety, exenatide had a lower diarrhea rate (RR 0.11 [95% CI 0.01, 0.84]) than metformin. In the other three studies, exenatide plus metformin was compared with metformin. Exenatide combined with metformin was more effective in improving SHBG (MD 10.38[95%CI 6.7,14.06] P < 0.001), Matsuda index (MD 0.21[95%CI 0.05,0.37]) and reducing free androgen index (FAI) (MD -3.34 [-4.84, -1.83] P < 0.001), Weight (MD -2.32 [95%CI -3.89, -0.66]) and WC (MD-5.61[95%CI -8.4, -2.82] P < 0.001). The incidence of side effects between exenatide plus metformin and metformin was not statistically significant. Conclusions: Exenatide alone or in combination with metformin is more effective than metformin for women with PCOS. Considering the evidence on effectiveness and safety, exenatide alone or in combination with metformin may be a better treatment approach than metformin for women with PCOS. Trial registration: INPLASY https://inplasy.com/inplasy-protocols/ ID: 10.37766/inplasy2022.11.0055. [ABSTRACT FROM AUTHOR]

Background: Idiopathic hypogonadotropic hypogonadism (IHH) is a rare congenital or acquired genetic disorder caused by gonadotropin-releasing hormone (GnRH) deficiency. IHH patients are divided into two major groups, hyposmic or anosmic IHH (Kallmann syndrome) and normosmic IHH (nIHH), according to whether their sense of smell is intact. Here we report a case of novel compound heterozygous mutations in the GNRH1 gene in a 15-year-old male with nIHH. Case presentation: The patient presented typical clinical symptoms of delayed testicular development, with testosterone < 3.5 mmol/L and reduced gonadotropin (follicle-stimulating hormone, luteinizing hormone) levels. Two heterozygous variants of the GNRH1 gene were detected, nonsense variant 1: c.85G > T:p.G29* and variant 2: c.1A > G:p.M1V, which disrupted the start codon. Conclusions: Two GNRH1 mutations responsible for nIHH are identified in this study. Our findings extend the mutational spectrum of GNRH1 by revealing novel causative mutations of nIHH. [ABSTRACT FROM AUTHOR]

Background: A meta-analysis followed by PRISMA 2020 statement was performed aiming to present a whole prolactin and sex hormone profile in hemodialysis women. Methods: Literatures were searched in PubMed, Cochrane library, Embase, and Web of science before March 11, 2023. Trial sequential analysis (TSA) was performed to test the conclusiveness of this meta-analysis. Egger's test and trim-and-fill analysis was used to test publication bias. We took standardized mean difference (SMD) as pool effect of hormones values including prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and progesterone (P). This study was registered in PROSPERO and the number was CRD42023394503. Results: Twenty-two articles from 13 countries were analyzed. Combining the results of TSA and meta-analysis, we found that compared with healthy control, hemodialysis women had higher PRL, follicular FSH and LH values and lower P levels (PRL: I2 = 87%, SMD 1.24, 95% CI: 0.79–1.69, p < 0.00001; FSH: I2 = 0%, SMD 0.34, 95% CI: 0.13–0.55, p = 0.002; LH: I2 = 39%, SMD 0.64, 95% CI: 0.34–0.93, p < 0.00001; P: I2 = 30%, SMD − 1.62, 95% CI: -2.04 to -1.20, p < 0.00001). What's more, compared with women after renal transplantation, hemodialysis women had higher PRL levels (I2 = 0%, SMD 0.51, 95% CI: 0.25–0.78, p = 0.0001). There was not enough evidence to draw a conclusion on the comparison of hormones between regular and irregular menses hemodialysis women. Egger's test and trim-and-fill analysis didn't show significant publication bias. Conclusions: Hemodialysis women had higher serum PRL, follicular phase FSH, LH and lower serum P values compared with healthy control. PRL values of hemodialysis women were also higher than that of women after renal transplantation. [ABSTRACT FROM AUTHOR]

Background: Numerous studies suggest that sex steroids might play a role in sex disparity observed in allergic diseases in adults. However, whether sex hormones influence allergic diseases in children remains unclear. The aim of the present study was to examine the association of sex steroid hormones with allergic disease in Japanese children. Methods: The present cross-sectional study included 145 6-year-old children participating in a pilot birth cohort study in the Japan Environment and Children's Study. Data on allergic diseases were obtained from questionnaires, and serum levels of sex steroid hormones and allergen-specific IgE were measured. Logistic regression was performed to evaluate the association of sex hormones with allergic diseases. Results: After adjusted sex, amount of body fat at 6 years, parental history of allergic disease, and exposure to tobacco smoke, serum dehydroepiandrosterone sulfate level was significantly associated with reduced odds of any allergic disease (adjusted odds ratio, 0.58; 95% confidence interval, 0.36–0.93; P = 0.024) and serum follicle-stimulating hormone level was significantly associated with increased odds of any allergic disease (adjusted odds ratio, 2.04; 95% confidence interval, 1.01–4.11, P = 0.046). Dehydroepiandrosterone sulfate level showed a significant association with number of allergic diseases. Conclusions: The current study findings suggest that sex hormones may play an important role in the development of allergic diseases in prepubertal children. [ABSTRACT FROM AUTHOR]

Objective: To determine whether a reduced dose of follicle-stimulating hormone (FSH) before human chorionic gonadotropin (hCG) trigger during ovarian stimulation can affect in vitro fertilization (IVF) outcomes. Methods: This study included 347 patients with a normal ovarian response who received a reduced dose of FSH before hCG trigger for 2–3 days (Group A) and 671 patients who did not receive a reduced dose (Group B) from a university-affiliated IVF center between January 2021 and December 2022. The primary endpoint was estrogen (E2) and progesterone (P) levels on the day of hCG trigger, fresh embryo transfer cycles, laboratory outcomes, and clinical outcomes between the two groups. Results: On the day of hCG trigger, Group A had significantly lower E2 and P levels than those in Group B (3454.95 ± 1708.14 pg/mL versus 3798.70 ± 1774.26 pg/mL, p = 0.003; and 1.23 ± 0.53 ng/mL versus 1.37 ± 0.59 ng/mL, p < 0.001, respectively). The proportion of patients with P levels ≥ 1.5 ng/mL was 22.48% in Group A compared to 34.58% in Group B (p < 0.001), while the proportion of patients with E2 ≥ 5000 pg/mL was 15.27% in Group A compared to 25.93% in Group B (p < 0.001). The fresh embryo-transfer cycle rate in Group A was higher than that in group B (54.47% and 32.64%, respectively; p < 0.001). Despite the reduction in FSH dosage, there were no significant differences between groups regarding the number of oocytes retrieved, total number of mature oocytes, normal fertilization rate, cleavage rate, Day 3 top-quality rate, implantation rate, pregnancy rate per cycle, and early pregnancy loss rate. Conclusion: While a reduced dose of FSH prior to hCG trigger during ovarian stimulation did not significantly affect IVF outcomes, it was associated with lower E2 and P levels, resulting in fewer cycles with E2 ≥ 5000 pg/mL and P ≥ 1.5 ng/mL on the day of the hCG trigger. [ABSTRACT FROM AUTHOR]

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Background: Several studies have explored the connection between follicle-stimulating hormone (FSH) and nonalcoholic fatty liver disease (NAFLD). However, the impact of FSH elevation on NAFLD remains a topic of debate. Hence, this investigation aimed to evaluate the potential correlation between FSH levels and NAFLD in the aging population. Methods: This was a retrospective observational cross-sectional study between July 2017 and August 2018 in our hospital. We used data obtained from 455 patients over 60 years old. Anthropometrics and laboratory tests were performed for each patient. NAFLD was diagnosed by sonographic features and the fatty liver index (LFI). Results: Of the 455 patients, 200 (43.96%) had NAFLD on their ultrasound and 169 (37.14%) had NAFLD according to the LFI. An intraclass correlation coefficient of the two methods was 80.4% (P < 0.001). People with NAFLD on their ultrasound showed lower FSH levels (52.68 vs. 61.39 IU/L) and more unfavorable metabolic profiles. FSH was negatively correlated with age, alanine aminotransferase, estradiol, testosterone, systolic blood pressure, waist, body mass index, fasting blood glucose, postload plasma glucose and positive associated with total cholesterol, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol by Spearman correlation analysis (all P < 0.05). By controlling for all confounding factors, the odds ratios (OR) of FSH for NAFLD were determined in elderly individuals, both men and women, aged 60–70 years and over 70 years. These ORs were found to be 0.937, 0.982, 0.983, and 0.973, respectively, with corresponding 95% confidence intervals (CI) of 0.892–0.984 (P = 0.009), 0.971–0.993 (P = 0.002), 0.967–0.999 (P = 0.033), and 0.958–0.989 (P = 0.001). In addition, our findings demonstrated no significant correlation between FSH and advanced fibrosis when adjusting for potential covariates. The OR for advanced fibrosis was 0.979 (95% CI, 0.938–1.022, P = 0.339). Additionally, ROC curve analysis showed an optimal cut-off value of 66.91 for women and 15.25 for men for NAFLD diagnosis. Conclusions: There was an inverse relationship observed between levels of FSH in the blood serum and NAFLD in the elderly population. These findings suggest that reduced FSH levels might serve as a potential risk factor or biomarker for NAFLD in the elderly. [ABSTRACT FROM AUTHOR]

Janus kinase 3 (JAK3) is a member of the JAK family of tyrosine kinase proteins involved in cytokine receptor-mediated intracellular signal transduction through the JAK/STAT signaling pathway. JAK3 was previously shown as differentially expressed in granulosa cells (GC) of bovine pre-ovulatory follicles suggesting that JAK3 could modulate GC function and activation/inhibition of downstream targets. We used JANEX-1, a JAK3 inhibitor, and FSH treatments and analyzed proliferation markers, steroidogenic enzymes and phosphorylation of target proteins including STAT3, CDKN1B/p27Kip1 and MAPK8IP3/JIP3. Cultured GC were treated with or without FSH in the presence or not of JANEX-1. Expression of steroidogenic enzyme CYP11A1, but not CYP19A1, was upregulated in GC treated with FSH and both were significantly decreased when JAK3 was inhibited. Proliferation markers CCND2 and PCNA were reduced in JANEX-1-treated GC and upregulated by FSH. Western blots analyses showed that JANEX-1 treatment reduced pSTAT3 amounts while JAK3 overexpression increased pSTAT3. Similarly, FSH treatment increased pSTAT3 even in JANEX-1-treated GC. UHPLC-MS/MS analyses revealed phosphorylation of specific amino acid residues within JAK3 as well as CDKN1B and MAPK8IP3 suggesting possible activation or inhibition post-FSH or JANEX-1 treatments. We show that FSH activates JAK3 in GC, which could phosphorylate target proteins and likely modulate other signaling pathways involving CDKN1B and MAPK8IP3, therefore controlling GC proliferation and steroidogenic activity. [ABSTRACT FROM AUTHOR]

Introduction: Associations of luteinizing hormone (LH) with androgens during the menopausal transition and associations between follicle-stimulating hormone (FSH) levels and various diseases related to reproductive hormones in postmenopause have received much attention. LH and FSH are also known to be associated with activities of enzymes related to reproductive hormones. We examined the associations of LH and FSH with androgens and estrogens in each stage of the menopausal transition according to a classification from menopausal transition to postmenopause. Methods: This study was a cross-sectional design. We basically used the Stage of Reproductive Aging Workshop (STRAW) + 10. We divided the 173 subjects into 6 groups according to menstrual regularity and follicle-stimulating hormone level: mid reproductive stage (Group A), late reproductive stage (Group B), early menopausal transition (Group C), late menopausal transition (Group D), very early postmenopause (Group E) and early postmenopause (Group F). Levels of LH, FSH, dehydroepiandrosterone sulfate (DHEAS), estradiol, estrone, testosterone (T), free T, androstenedione and androstenediol were measured. Results: In Group A, LH showed significant positive correlations with androstenedione and estrone. In Group D, LH was positively associated with T and free T and was negatively associated with estradiol. In Groups B, C, D and F, LH showed significant positive correlations with FSH, and there was a tendency for an association between LH and FSH in Group E. FSH was associated with estradiol but not with estrone in Groups C and D. Conclusion: The associations of LH and FSH with reproductive hormones are different depending on the stage of the menopausal transition. Trial registration: Trial registration number 2356-1; Date of registration: 18/02/2018, retrospectively registered. [ABSTRACT FROM AUTHOR]

Purpose: To explore the efficacy and safety of individualized follitropin delta dosing, based on serum anti-Müllerian hormone (AMH) concentration and bodyweight, in a long gonadotropin-releasing hormone (GnRH) agonist protocol. Methods: Clinical outcomes after one treatment cycle are reported in women with AMH: 5–35 pmol/L. Oocytes were inseminated by intracytoplasmic sperm injection, blastocyst transfer was on Day 5 and remaining blastocysts were cryopreserved. Data collection included live births and neonatal health follow-up for all fresh/frozen transfers performed within one year after treatment allocation. Results: In total, 104 women started stimulation, of whom 101 had oocyte recovery and 92 had blastocyst transfer. The average daily dose of follitropin delta was 11.0 ± 1.6 µg and the duration of stimulation was 10.3 ± 1.6 days. The mean number of oocytes was 12.5 ± 6.4, the mean number of blastocysts was 5.1 ± 3.4, and 85% had at least one good-quality blastocyst. Following mostly single blastocyst transfer (95%), the ongoing pregnancy rate was 43%, the live-birth rate was 43%, and the cumulative live-birth rate was 58% per started stimulation. There were 6 cases of early OHSS (5.8%) graded as mild (n = 3) and moderate (n = 3) and 6 cases of late OHSS (5.8%) graded as moderate (n = 3) and severe (n = 3). Conclusion: In this first evaluation of the individualized follitropin delta dosing in a long GnRH agonist protocol, the cumulative live-birth rate was high. A randomized trial comparing follitropin delta in a long GnRH agonist protocol versus in a GnRH antagonist protocol should provide further insight into the efficacy and safety of this treatment option. Trial registration number: NCT03564509; June 21, 2018. [ABSTRACT FROM AUTHOR]

Background: Some patients develop immunoglobulin G4 (IgG4)-related hypophysitis associated with systemic diseases. More than 30 cases of IgG4-related hypophysitis have been reported. However, biopsy has rarely been performed in these patients, and none have had an associated pituitary neuroendocrine tumor (PitNET). We present a case of concurrent IgG4-related hypophysitis and PitNET. Case presentation: A 56-year-old Japanese man arrived at the hospital with visual impairment, bitemporal hemianopia, and right abducens nerve palsy. Magnetic resonance imaging revealed pituitary body and stalk swelling as well as a small poorly enhanced right anterior lobe mass. Laboratory and loading test results suggested hypopituitarism. Because IgG4 level was elevated, a systemic examination was performed; multiple nodules were found in both lung fields. The diagnosis was based on an endoscopic transnasal biopsy of the pituitary gland. A histopathological examination revealed a marked infiltration of plasma cells into the pituitary gland, which was strongly positive for IgG4. The histological features of the resected tumor were consistent with those of gonadotroph PitNET, which was immunohistochemically positive for follicle-stimulating hormone-β and steroidogenic factor-1, and no plasma cell infiltration was observed. Based on the histopathological examination results, steroid therapy was initiated, which reduced pituitary gland size and serum IgG4 levels. Discussion and Conclusions: This is the first reported case of IgG4-related hypophysitis with PitNET. Although no pathological findings indicating a relationship between the two conditions were found, we were able to preoperatively differentiate multiple lesions via detailed diagnostic imaging. [ABSTRACT FROM AUTHOR]

Prediction of individual ovarian response to exogenous gonadotropin is a cornerstone for success and safety in all controlled ovarian stimulation (COS) protocols. Providing the best FSH starting dose according to each woman's own characteristics is the key to the success of individualized treatment. The objective of this investigation was to evaluate the potential application of a novel nomogram based on antral follicle counting (AFC), anti-Müllerian hormone (AMH) and body mass index (BMI) as a tool to optimize the follicle-stimulating hormone (FSH) starting dose in women with poor ovarian response in in-vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) cycles in progestin-primed ovarian stimulation (PPOS). We performed a retrospective analysis involving 130 poor ovarian responders undergoing IVF/ICSI cycles in a PPOS protocol from June 2017 to February 2019 in our reproductive center. The individual FSH starting dose was selected according to patients' clinical history and characteristics. The influence of variables including age, BMI, AMH and AFC on the FSH starting dose was assessed through multiple regression analysis. We used the variables reaching the statistical significance for calculation for the final predictive model. In the univariate analysis, BMI, AMH and AFC were significant (P < 0.05) predictors of FSH starting dose, age was canceled. In the multivariate analysis, BMI, AMH and AFC remained significant (P < 0.05). According to the nomogram, 118 patients (90.77% of 130) would have received a higher FSH starting dose and 12 patients (9.23% of 130) a lower FSH starting dose than practice dose. The application of the nomogram based on three variables easily determined in clinical practice: BMI, AMH and AFC would lead to a more tailored FSH starting dose in women with poor ovarian response. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the predictive value of the initial screening characteristics of women with anovulatory polycystic ovary syndrome (PCOS) who did or did not respond to 2.5 mg letrozole (LET). Methods: The clinical and laboratory characteristics of women with PCOS who underwent LET treatment were evaluated. Women with PCOS were stratified according to their responses to LET (2.5 mg). The potential predictors of their responses to LET were estimated using logistic regression analysis. Results: Our retrospective study included 214 eligible patients with a response to 2.5 mg LET (n = 131) or no response to 2.5 mg LET (n = 83). PCOS patients who responded to 2.5 mg LET showed better outcomes than those who did not (2.5 mg LET) for pregnancy rate, live birth rate, pregnancy rate per patient, and live birth rate per patient. Logistic regression analyses showed that late menarche (odds ratio [OR], 1.79 [95% confidence intervals (CI), 1.22–2.64], P = 0.003), and increased anti-müllerian hormone (AMH) (OR, 1.12 [95% CI, 1.02–1.23], P = 0.02), baseline luteinizing hormone (LH)/ follicle stimulating hormone (FSH) (OR, 3.73 [95% CI, 2.12–6.64], P < 0.001), and free androgen index (FAI) (OR, 1.37 [95% CI, 1.16–1.64], P < 0.001) were associated with a higher possibility of no response to 2.5 mg LET. Conclusions: PCOS patients with an increased LH/FSH ratio, AMH, FAI, and late menarche may need an increased dosage of LET for a treatment response, which could be helpful in designing a personalized treatment strategy. [ABSTRACT FROM AUTHOR]

Background: Follitropin Delta (FD) is indicated exclusively for in-vitro fertilization however, being a gonadotropin it could be used for other purposes. A dosing algorithm exists for FD and IVF but is needed for intrauterine insemination (IUI) cycles. The objective of this study is to determine dosing for FD for the first controlled ovarian hyperstimulation (COH) cycle according to current stimulation guidelines. Results: A retrospective study of 157 subjects from a single university fertility center from January 2017 to March 2020, was performed. All patients stimulated with FD for IUI were included. The number of failed, normal, or overstimulation cycles was determined based on stimulating not more than 2 mature follicles. We then stratified the group based on the AFC, AMH, and body weight. Of 157 subjects, 49% stimulated correctly, 5.6% failed and 45.4% overstimulated. An analysis of the COH IUI cycles based on stratification and over or lack of stimulation per published guidelines found that women with a bodyweight < 80 kg or AMH ≥ 1.5 ng/ml or AFC ≥ 10 initially stimulate with FD 2.0 to 3.0mcg daily. For women with an AFC of 6–9 stimulate with Follitropin Delta 3.0mcg daily. For women with an AFC < 6 or serum AMH < 1.5 ng/ml stimulate with FD 3.0–4.0mcg daily. For women with body weight > 80 kg stimulate initially with daily with 4.0–6.0mcg FD. Conclusions: Follitropin Delta can be used safely for controlled ovarian stimulation and insemination at doses easily dispensed by the current methods of delivery, within the current published guidelines for follicle development. [ABSTRACT FROM AUTHOR]

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Correction: Biosimilar recombinant follitropin alfa preparations versus the reference product (Gonal-F®) in couples undergoing assisted reproductive technology treatment: a systematic review and meta-analysis This was based on the mean ± standard deviation (SD) number of oocytes retrieved, which was reported by Hu et al. in Table 2 of their publication (14.9 ± 0.5 for Follitrope [ I n i = 336] and 12.8 ± 0.9 for GONAL-f® [ I n i = 110]) [[2]]. When comparing the SD values reported in Table 2 [[2]] with those from the other four RCTs included our meta-analysis (NCT01121666, NCT01687712, ISRCTN74772901 and NCT03088137) [[1]], the values are unusually small and inconsistent with the range of SDs reported for the other four RCTs. [Extracted from the article]

Background: Features of metabolic syndrome such as abdominal obesity, insulin resistance, hypertension and dyslipidemia are commonly encountered in polycystic ovary syndrome (PCOS). Recent evidence has suggested an association between high serum uric acid/creatinine (UA/Cr) ratio and metabolic syndrome however, no studies have investigated this association in PCOS. The current study was conducted to investigate the relationship between UA/Cr ratio and PCOS and to identify whether UA/Cr ratio and free androgen index (FAI) have an additive interaction for detection of PCOS risk in obese women. Methods: This study enrolled 40 obese women with PCOS and 40 control women with regular menstrual cycles matched for age and body mass index (BMI). Anthropometric measurements, fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipids profile, luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), total testosterone, free androgen index (FAI), UA/Cr ratio were assessed. Results: Serum UA/Cr ratio was significantly higher in obese women with PCOS than in non-PCOS women. UA/Cr ratio was correlated with BMI, waist and neck circumferences, blood pressure, fasting insulin, HOMA-IR, lipids, LH/FSH, estradiol, DHEAS, total testosterone, FAI and SHBG. UA/Cr ratio and FAI were independent risk factors for PCOS in obese women however, the addictive interaction between UA/Cr ratio and FAI had a higher fold risk (OR: 4.3, 95% CI, 3.4–7.58) and a more significance (P = 0.002) for determination of PCOS. Conclusion: Serum UA/Cr ratio combined with FAI can exert an additive or synergistic impact on prediction of PCOS in obese women. [ABSTRACT FROM AUTHOR]

Background: Data is inconsistent and, for the most part, not sufficient to demonstrate the association between serum Prolactin (PRL) concentration within the physiologic range and the incidence rate of type 2 Diabetes Mellitus (DM) among men. Moreover, since both PRL and type 2 DM are associated with reproductive hormones, investigating these hormones might improve our understanding of how PRL might impose its effect on the incidence rate of type 2 DM. Methods: For the present study, 652 eligible men aged 29–70 with a normal baseline PRL concentration were selected from the Tehran Lipid and Glucose Study (TLGS). Participants were sub-classified into three groups (tertiles) according to the serum concentration of PRL and were followed for 15.8 years. The incidence of type 2 DM and PRL, LH, FSH, testosterone, and AMH concentrations were measured. The effect of hormonal variables on the incidence of type 2 DM was estimated using the log-binomial model, adjusted for major confounding factors. The correlations between PRL and the indicators of glucose and lipid metabolism and other hormonal variables were also explored. Results: In the unadjusted model, PRL was not significantly associated with the incidence rate of type 2 DM (RR = 0.98, 95% CI: 0.94 − 1.03). After adjusting for potential confounders, the inverse effect of AMH on the incidence rate of type 2 DM was the only significant association. The analyses also indicated a significant positive association between PRL and LH/FSH ratio (r = 0.1, P = 0.01). Conclusion: No significant association was found between serum PRL concentrations within the physiologic range and the incidence rate of type 2 diabetes mellitus among middle-aged men. Men with higher concentrations of PRL within the physiologic range tended to show higher levels of LH and LH/FSH. AMH was the only variable significantly linked to the incidence rate of type 2 DM in men. [ABSTRACT FROM AUTHOR]

Background: GnRHa treatment was established for improving final adult height (FAH) in children presenting with Idiopathic central precocious puberty (ICPP) up to age 8, while several controversies remained for older age groups. The primary objective was to evaluate whether boys diagnosed with ICPP over 9 years of chronological age (CA) could achieve a height benefit from GnRHa treatment. Methods: We retrospectively evaluated the medical records of 23 boys treated for idiopathic central precocious puberty between January 2018 and January 2021 at Jiangsu Children's Medical Center. All patients started treatment with intramuscular depot GnRHa at a dose of 80–100 μg/kg, followed by continuous intramuscular injection every 28 days at a dose of 60–80 μg/kg. The hormonal parameters, bone age/chronological age ratio, FAH, growth velocity (GV), tanner staging and body mass index (BMI) were assessed during the treatment period. Results: After one course of treatment (3 months), the basal FSH and testosterone levels were reduced, while the basal LH value was not significantly changed compared with those before treatment. Furthermore, the mean BA/CA ratio reduction was statistically significant at month 12. The mean PAH following administration of GnRHa after 12 months was statistically improved compared with those at baseline. In addition, the clinical sign of puberty and GV were significantly improved and the BMI remained unchanged as desired at month 12. Conclusions: This analysis highlighted the positive outcome on the decrease in the rate of bone maturation, with a favorable effect on progression of clinical signs of puberty. Furthermore, our study confirmed PAH was improved even in the older children at onset of treatment (ages 9–10), emphasizing the importance of personalized treatment in such population. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is diagnosed based on chronic anovulation, androgen excess (clinical and/or biochemical), and polycystic ovaries in ultrasound. The aim of the present study was to evaluate which parameters in the transvaginal ultrasound (TVUS) of ovaries could be better associated with concurrent hormonal imbalance in the women with PCOS. Methods: Using a cross-sectional design, this study focused on 61 subjects (18–40 years) with PCOS. Patients were recruited at three academic hospitals during the 2017–2019 period. PCOS was defined according to the Rotterdam criteria. The association of ovarian morphology with hormonal and metabolic feature was investigated using linear regression models, adjusted for a set of possible confounding variables including age, mensuration status and body mass index (BMI). Results: The mean volume of both ovaries was positively associated with the total testosterone level (β = 0.025, P value < 0.001), free androgen index (β = 0.041, P value < 0.001) and luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio (β = 0.032, P value = 0.004), even after adjustments made for age, mensuration status and BMI (fully-adjusted model). In contrast, in the fully-adjusted model, antral follicle count (AFC), follicle number per ovary (FNPO), ovarian area, stromal area, and ratio of stromal area to ovarian area (S/A) were not associated with androgen levels and LH/FSH ratio. In addition, after full adjustments, ovarian volume, AFC, FNPO, ovarian area, stromal area and S/A were not associated with insulin resistance, which was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR). Conclusion: Increased ovarian volume is, thus, highly predictive of hyperandrogenemia and high LH/FSH ratio in PCOS patients. [ABSTRACT FROM AUTHOR]

Background: Whether women's physical function in mid-life is related to their reproductive age is not known. The objectives of this study were to examine and compare changes in physical function in women by reproductive age, measured as time since final menstrual period (FMP), and chronological age, and to explore associations with repeatedly assessed levels of reproductive hormones.Methods: We used data from 2319 UK women with up to three repeated measurements of physical function (median length of follow up: 2 years), focusing on changes occurring in women experiencing a natural menopausal transition. The main outcome was a composite physical function score that incorporated assessments of strength (grip strength), balance (one-leg stand) and cardiorespiratory fitness (timed chair rises). Associations with time since FMP, age, and time-updated measures of anti-Müllerian hormone, follicle-stimulating hormone and luteinizing hormone were assessed by multilevel models and generalised estimating equations models adjusted for the underlying effects of chronological age and confounding by education, age at first birth and smoking.Results: The results showed that, adjusted for these confounders, time since FMP (- 0.21 SD per 10 years, 95% CI - 0.37, - 0.06) and chronological age (- 0.31 SD per 10 years, 95% CI - 0.46, - 0.15) were inversely associated with the physical function composite score. Grip strength seemed to be the main contributor to the decline in the composite score by time since FMP. There was no strong evidence of associations between any of the three reproductive hormones and the composite score.Conclusions: Physical function in women in mid-life declined with both chronological and reproductive age. The decline with reproductive age was independent of chronological age but did not seem to be driven by changes in reproductive hormones. [ABSTRACT FROM AUTHOR]

Background: Gut microbes were closely related to women's health. Previous studies reported that the gut microbes of premenopausal women were different from those of postmenopausal women. However, little was known about the relationship between gut microbiota dysbiosis and menopausal syndrome (MPS). The aim of this study was to explore the relationship between MPS and gut microbes.Methods: Patients with MPS (P group, n = 77) and healthy women (H group, n = 24) at menopause were recruited in this study. The stool specimen and clinical parameters (demographic data, follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), et al) of participants' were collected. We evaluated the differences in gut microbes by 16S ribosomal RNA gene sequencing. We used LEfSe to identify gut microbes with varying abundances in different groups. The Spearman correlation coefficients of clinical parameters and gut microbes were calculated. PICRUSt was used to predict the potential KEGG Ortholog functional profiles of microbial communities.Results: The abundance of 14 species differed substantially between the MPS and menopausal healthy women (LDA significance threshold > 2.0) according to LEfSe analysis. Using Spearman's correlation analysis, it was discovered that E2 had a positive correlation with Aggregatibacter segnis, Bifidobacterium animalis, Acinetobacter guillouiae (p < 0.05, these three species were enriched in menopausal healthy women), while FSH and LH had a negative correlation with them (p < 0.05). KEGG level3 metabolic pathways relevant to cardiovascular disease and carbohydrate metabolism were enriched in the MPS (p < 0.05), according to functional prediction by PICRUST and analyzed by Dunn test.Conclusion: There was gut microbiota dysbiosis in MPS, which is reflected in the deficiency of the abundance of Aggregatibacter segnis, Bifidobacterium animalis and Acinetobacter guillouiae related to the level of sex hormones. In MPS individuals, species with altered abundances and unique functional pathways were found. [ABSTRACT FROM AUTHOR]

Background: Monosodium glutamate (MSG) is a food ingredient that is increasingly used commercially. MSG leads to oxidative stress, consequently suppressing steroid hormone production that causes defects in male reproductive system. This study aimed to evaluate the effect of L-carnitine as an antioxidant on testicular damage in MSG-induced male rats. Methods: Sixty adult male Spargue-Dawley rats were randomly divided into six groups of ten as follows: control (water), sham (normal saline), L-carnitine (200 mg/kg b.w), MSG (3 g/kg b.w), MSG + L-carnitine 100 (3 g/kg b.w of MSG and 100 mg/kg b.w of L-carnitine), and MSG + L-carnitine 200 (3 g/kg b.w of MSG and 200 mg/kg b.w of L-carnitine). The treatment was administered by oral gavage for six months. Serum levels of Malondialdehyde (MDA), Total Anti-oxidant Capacity (TAC), LH, FSH, testosterone, and mRNA expressions of Star, Cyp11a1, and Hsd17b3 genes, and histological and stereological changes were assessed. Results: L-carnitine led to a significant decrease in the level of MDA and a significant rise in the serum levels of TAC, LH, FSH, and mRNA expression of Star and Cyp11a1 compared to the MSG group (p < 0.05). Furthermore, stereological results indicated a significant increment in the number of sexual lineage cells, the total volume of the testis, length, diameter, and volume of seminiferous tubules, the height of the germinal epithelium, sperm count, and sperm motility (p < 0.05) in MSG + L-carnitine 200 compare to MSG group. Conclusion: The study's findings demonstrated that L-carnitine due to its anti-oxidant properties, ameliorated the reproductive abnormalities in the male rats exposed to MSG. [ABSTRACT FROM AUTHOR]

Background: The WHO recommends artemisinin-based combination regimens for uncomplicated Plasmodium falciparum malaria. One such combination is artemisinin-piperaquine tablets (ATQ). ATQ has outstanding advantages in anti-malarial, such as good efficacy, fewer side effects, easy promotion and application in deprived regions. However, the data about the reproductive and endocrine toxicity of ATQ remains insufficient. Thus, we assessed the potential effects of ATQ and its individual components artemisinin (ART) and piperaquine (PQ) on the reproductive and endocrine systems in Wistar rats. Methods: The unfertilized female rats were intragastric administrated with ATQ (20, 40, and 80 mg/kg), PQ (15, 30, and 60 mg/kg), ART (2.5, 5, and 10 mg/kg), or water (control) for 14 days, respectively. The estrous cycle and serum levels of estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), prostaglandin (PG), and adrenocorticotropic hormone (ACTH) were determined. The weights of the kidney, adrenal gland, uterus, and ovaries were measured. The histopathological examinations of the adrenal gland, ovary, uterus, and mammary gland were performed. Results: Compared with the control group, there were no significant differences in the examined items of female rats in the ART groups, including general observation, estrous cycle, hormonal level, organ weight, and histopathological examination. The estrous cycle of female rats was disrupted within 4–7 days after ATQ or PQ administration, and then in a persistent dioestrus phase. At the end of administration, ATQ and PQ at three doses induced decreased PG, increased ACTH, increased adrenal weight and size, and pathological lesions in the adrenal gland and ovary, including vasodilation and hyperemia in the adrenal cortex and medulla as well as hyperplasia and vacuolar degeneration, ovarian corpus luteum surface hyperemia, numerous but small corpus luteum, and disordered follicle development. But the serum levels of E2, FSH, LH, and PRL did not change obviously. These adverse effects in ATQ or PQ treated rats could not completely disappear after 21 days of recovery. Conclusion: Based on the results of this study, ART had no obvious reproductive and endocrine effects on female rats, while ATQ and PQ caused adrenal hyperplasia, increased ACTH, decreased PG, blocked estrus, corpus luteum surface hyperemia, and disrupted follicle development in female rats. These events suggest that ATQ and PQ may interfere with the female reproductive and endocrine systems, potentially reducing fertility. [ABSTRACT FROM AUTHOR]

Background: To compare the efficacy and safety of follitropin delta in its individualized fixed-dose regimen with follitropin alfa in a conventional adjustable dosing regimen in Chinese women. Methods: This was a subgroup analysis of the randomized, multi-center, assessor-blind, non-inferiority trial (GRAPE) including 759 Chinese women (aged 20–40 years) recruited in 16 reproductive medicine clinics in China. Women were randomized in a 1:1 ratio to be treated with either follitropin delta dose based on anti-Müllerian hormone (AMH) and body weight or conventional dosing with follitropin alfa following a gonadotropin-releasing hormone (GnRH) antagonist protocol. The primary outcome was ongoing pregnancy rate assessed 10–11 weeks after embryo transfer in the fresh cycle (non-inferiority margin -10.0%). Results: 378 in the follitropin delta group and 381 in the follitropin alfa group were randomized and exposed. Non-inferiority was confirmed with respect to ongoing pregnancy with rates of 31.0% vs. 25.7% for follitropin delta compared to follitropin alfa, estimated mean difference of 5.1% (95% confidence interval (CI) -1.3% to 11.5%). The clinical pregnancy rate (35.4% vs. 31.5%, P = 0.239) and live birth rate (31.0% vs. 25.5%, P = 0.101) were comparable between the follitropin delta group and the follitropin alfa group. Overall, the individualized follitropin delta treatment resulted in fewer oocytes retrieved compared to follitropin alfa treatment (10.3 ± 6.2 vs. 12.5 ± 7.5, P < 0.001), which was mainly due to fewer oocytes (10.5 ± 6.4 vs. 13.9 ± 7.8) in women with AMH ≥ 15 pmol/L. Accordingly there was a lower incidence of early ovarian hyper-stimulation syndrome (OHSS) and/or preventive interventions (6.1% vs. 11.0%, P = 0.013). A daily follitropin delta dose of 10.2 µg (95% CI: 9.3—11.2 µg) was estimated to provide the same number of oocytes retrieved as a starting dose of 150 IU/d of follitropin alfa. Conclusion: Follitropin delta in its individualized fixed-dose regimen showed similar efficacy and improved safety compared with follitropin alfa in a conventional adjustable dosing regimen in Chinese women. Clinical trial registration number: NCT03296527. [ABSTRACT FROM AUTHOR]

Background: Several immune checkpoint inhibitors have been implemented for cancer treatment which have shown some degree of antitumor effcacy, while immune-related adverse events (irAEs) that affect multiple organ functions ensue which obviously should not be neglected. Though less common than other kinds of irAEs, Immune checkpoint inhibitors (ICIs) related Isolated ACTH deficiency (IAD) may cause long-term damage to pituitary-adrenal axis. Several case reports are available about IAD during anti-PD-1 therapy. We report the first case of immune checkpoint inhibitor-induced IAD following 3 month of sintilimab therapy. Case presentation: A 66-year-old Chinese man was diagnosed with stage IIIB lung adenocarcinoma with involving ipsilateral intrapulmonary and hilar lymph node metastasis. After 3 months of combination therapy of nedaplatin, pemetrexed and sintilimab, the patient presented with general fatigue, nausea and vomiting. Laboratory investigation at admission revealed hyponatremia and hypokalemia. Further investigation revealed adrenocorticotropic hormone and cortisol levels were far below than normal limits. His other pituitary hormone levels were normal, except for mild elevation of follicle stimulating hormone and estradiol. Cranic magnetic resonance imaging showed a normal pituitary gland. Isolated adrenocorticotropic hormone deficiency was diagnosed, and corticosteroid replacement therapy was administered, leading to a significant improvement of his symptoms while ACTH level maintaining low level. Conclusions: Our patient developed isolated ACTH deficiency during combination cancer treatment with chemotherapy and sintilimab. Although isolated ACTH deficiency due to anti-PD-1 including sintilimab therapy is rare occurrence, it can often cause severe clinical symptoms. Its diagnosis basically relies on clinical symptoms and endocrinological examination. Unlike traditional hypophysitis diagnosed by cranial MRI, pituitary MRI of IAD due to anti-PD-1 often indicates normal pituitary gland implying that over-reliance on imaging findings is not recommended. Even if clinical symptoms have relieved after corticosteroid replacement therapy was commenced, low levels of ACTH or cortisol could maintain for a long period which highlights the need for long term corticosteroid therapy. The purpose of the current report was to provide increased awareness of early detection and therapy of IAD. [ABSTRACT FROM AUTHOR]

Background: Data available support that ninety percent of male infertility cases are due to low sperm counts. There is a scarcity of data on the medicinal effects of cannabis on fertility. This study evaluated testicular function and sperm quality modulation with cannabis in rats. Methodology: Twenty-five male Wistar rats were randomly grouped into five: A, B, C, and D, each group have 5 rats. A (control): 0.2 ml 2% DMSO, B (vitamin C): 90 mg/kg body weight, C, D, and E were administered: 5 mg/kg, 10 mg/kg and 20 mg/kg body weight of ethanolic leaf extract of cannabis (ELEC) respectively. The rats were sacrificed 24 h after the last day of the 60 day oral administrations. Flavonoids were the predominant phytochemical present in the extract while quercetin, kemferol, silyman and gallic acid were identified. Results: The results showed a significant improvement (p < 0.05) in sperm quality and a significant increase in the concentrations of follicle-stimulating hormone, luteinizing hormone, triglycerides, cholesterol, and total protein determination compared to the normal control. Similarly, there was a significant increase (p < 0.05) in the activities of acid phosphatase, alkaline phosphatase, and superoxide dismutase compared to the normal control. RAC-alpha serine/threonine-protein kinase (AKT1)-silymarin complexes (-8.30 kcal/mol) and androgen receptor (AR)-quercetin complexes (9.20 kcal/mol) had the highest affinity. Conclusion: The antioxidant effects of the flavonoids in the ethanolic extract of cannabis may have protected testicular and sperm cells from oxidative damage. Biochemical processes and histopathological morphology were preserved by cannabis. The docking prediction suggests that the bioactive principle of cannabis may activate the androgenic receptors. The androgenic receptor modulation may be attributed to silymarin and quercetin. [ABSTRACT FROM AUTHOR]

Background: The gonadotropin-releasing hormone (GnRH) stimulation test is time-consuming, invasive, and costly. However, it is the diagnostic gold standard for central precocious puberty (CPP), which in girls is defined as the onset of secondary sexual characteristics before the age of 8 years accompanied by breast buds, accelerated growth, and advanced bone age. This meta-analysis was performed to compare the diagnostic value of urinary gonadotropins and the GnRH stimulation test for CPP.Methods: We searched six databases for relevant literature. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we estimated the sensitivity, specificity, area under the summary receiver operating characteristic curve (AUC), and publication bias.Results: Six eligible trials fulfilled the inclusion criteria. In the meta-analysis of urinary luteinizing hormone (ULH), after excluding the data of one study, we obtained an AUC of 0.90 (sensitivity = 0.81, specificity = 0.85). The meta-analysis of the ULH to urinary follicle-stimulating hormone (UFSH) ratio revealed an AUC of 0.8116 (sensitivity = 0.79, specificity = 0.84).Conclusion: Both the ULH level and ULH:UFSH ratio are effective and available approaches for CPP diagnosis.Trial Registration: INPLASY 2021120076 . [ABSTRACT FROM AUTHOR]

Follicle-stimulating hormone signaling is essential for the initiation and early stages of spermatogenesis. Follicle-stimulating hormone receptor is exclusively expressed in Sertoli cells. As the only type of somatic cell in the seminiferous tubule, Sertoli cells regulate spermatogenesis not only by controlling their own number and function but also through paracrine actions to nourish germ cells surrounded by Sertoli cells. After follicle-stimulating hormone binds to its receptor and activates the follicle-stimulating hormone signaling pathway, follicle-stimulating hormone signaling will establish a normal Sertoli cell number and promote their differentiation. Spermatogonia pool maintenance, spermatogonia differentiation and their entry into meiosis are also positively regulated by follicle-stimulating hormone signaling. In addition, follicle-stimulating hormone signaling regulates germ cell survival and limits their apoptosis. Our review summarizes the aforementioned functions of follicle-stimulating hormone signaling in Sertoli cells. We also describe the clinical potential of follicle-stimulating hormone treatment in male patients with infertility. Furthermore, our review may be helpful for developing better therapies for treating patients with dysfunctional follicle-stimulating hormone signaling in Sertoli cells. [ABSTRACT FROM AUTHOR]

Background: Busulfan is an antineoplastic medication that is broadly utilized for cancer treatment. It affects the testicular function and leads to sterility. The present study aimed to evaluate the effects of ellagic acid on testicular tissue changes, sexual hormones, antioxidant defense system, and caspase-9 and Bcl2 gene expression in the busulfan-induced relative sterile rat model. Methods: This is an interventional-experimental animal study that was performed on 65 Adult male rats; they were randomly divided into five groups including control (1 ml of 0.9% normal saline), ellagic acid (50 mg/kg); busulfan (10 mg/kg); and busulfan plus ellagic acid (10 mg/kg and 50 mg/kg). At the end of the experiment, blood samples were collected, and plasma levels of sex hormones, antioxidant system, apoptosis-related genes, and testis histology were assessed. Results: Busulfan reduced the levels of serum testosterone, total antioxidant capacity, gene expression of Bcl2, testicular volume, seminiferous tubule, germinal epithelium, interstitial tissue volume, and the number of spermatogonia, spermatocyte, round spermatid, elongated spermatid, Sertoli cells and Leydig cells (p < 0.05). Busulfan administration resulted in a significant increase (p < 0.05) in the level of LH, FSH, malondialdehyde, and caspase 9. Busulfan + ellagic acid (50 mg/kg) showed higher serum levels of testosterone, gene expression of Bcl-2 and antioxidant markers, and lower LH, FSH levels, and gene expression of caspase 9 compared to the Busulfan-treated rats (p < 0.05). Stereological parameters were also ameliorated in the group treated with Busulfan+ 50 mg/kg ellagic acid (p < 0.05). Conclusion: In conclusion, the consumption of ellagic acid may have beneficial effects on the antioxidant defense system, sexual hormone abnormality, and testicular tissue damage induced by busulfan. [ABSTRACT FROM AUTHOR]

Background: Infertility remains a significant public health concern. An issue with controlled ovarian stimulation (COS) is the selection of an exogenous gonadotropin (Gn) regimen, which is mainly based on urinary follicle-stimulating hormone (uFSH), recombinant follicle-stimulating hormone alfa (rFSH-alfa), and human menopausal gonadotropin (HMG). In addition, most previous studies focused on the clinical pregnancy rates or live birth rates (LBR) per transfer cycle, but not on the cumulative live birth rate (CLBR) per started cycle. The CLBR, appears to be a more comprehensive and accurate universal measure of IVF treatment success. Therefore, this study aimed to compare the cumulative live birth rate (CLBR) between rFSH-alfa and uFSH regimens for ovarian stimulation. Methods: This retrospective cohort study included patients who underwent assisted reproductive technology (ART) with gonadotropin-releasing hormone (GnRH) agonist long protocol between March 2009 and December 2018. Patients were grouped according to the Gn regimen received (rFSH-alfa or uFSH). The main outcome was CLBR, which defined as the first live birth following the use of all fresh and frozen embryos derived from a single COS cycle. Results: A total of 1078 cycles were analyzed (314 with rFSH-alfa and 764 with uFSH). The rFSH-alfa group was characterized by a higher number of retrieved oocytes (13.3 vs. 11.0) and transferable embryos (5.0 vs. 4.0), a higher fresh embryo transfer rate (35.0% vs. 26.3%), and a higher multiple birth rate among the fresh embryo transfer cycles (8.2% vs. 2.5%) (P < 0.05). There were no differences in pregnancy rate (32.7% vs. 33.8%) and LBR (25.5% vs. 26.9%) per transfer cycle (P > 0.05). No significant difference was found in clinical outcomes among the frozen embryo transfer cycles (P > 0.05). The CLBR per started cycle in the rFSH-alfa group was higher than in the uFSH group (53.5% vs. 43.1%, P < 0.05). After adjustment, rFSH-alfa was independently associated with a higher CLBR (OR = 1.56; 95%CI = 1.18–2.05; P = 0.0018). Conclusions: rFSH-alfa and uFSH have similar pregnancy rates and LBR per transfer cycle, rFSH-alfa might achieve more transferrable blastocysts and higher CLBR per started cycle compared to uFSH. [ABSTRACT FROM AUTHOR]

Objective: Women with an elevated basal FSH indicate diminished ovarian reserve and reduced oocyte and embryo numbers. DMSCs are likely to be involved in immune tolerance of pregnancy maintenance. We investigate the effect of follicle-stimulating hormones on the immunomodulatory functions of DMSCs. Methods: DMSCs were primary cultured from decidual tissue. Pretreated DMSCs with mitomycin C, combined with CD4+ T lymphocytes, DMSCs + CD4+T co-culture system was established. Different physiological dose FSH (3 ng/ml,10 ng/ml,30 ng/ml,100 ng/ml) were used to co-culture system. Cytokines (IFN-γ, IL-2, IL-4, IL-6, IL-10, TNF-α) and other proteins (FSHR, MyD88) were measured. Results: Compared with the control group (FSH (0 ng/mL) + CD4+T + DMSCs), the FSH concentration was 10, 30, and 100 ng/ml, IL-6 levels were significantly reduced (P < 0.05). IL-6, MyD88 protein expression was remarkably decreased (P < 0.05). Conclusion: FSH/FSHR could negatively regulate the immunosuppressive function of DMSCs by reducing secretion of IL-6 levels through MyD88 pathways, but upstream and downstream signalling pathways require further validation. [ABSTRACT FROM AUTHOR]

Background: Although vitamin A is known to play an important role in ovarian function, its association with ovarian insufficiency has not been reported yet. Therefore, the aim of the study was to explore the association between serum vitamin A levels and premature ovarian insufficiency (POI). Methods: This cross-sectional survey included women with POI (n = 47) and normo-ovulatory controls (n = 67) who were enrolled between December 2016 and May 2018 in Zhejiang, China. The serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Müllerian hormone (AMH), vitamin A, and total cholesterol (TC) were measured for each participant. The association of TC-adjusted vitamin A levels with the risk of POI was assessed using binary logistic regression analysis. Results: Serum vitamin A levels appeared to be slightly higher in the POI group than in the control group, but there was no evidence of a statistically significant difference (728.00 ± 176.00 µg/L vs. 503.93 ± 145.64 µg/L, p = 0.13). After adjustment for serum lipid levels, the serum vitamin A/TC ratio was significantly lower in the POI group than in the control group (143.14 ± 35.86 vs. 157.56 ± 35.21 µg/mmol, p = 0.04). Further, the serum vitamin A/TC ratio was significantly and inversely associated with POI risk (unadjusted odds ratio [OR] = 0.988, 95% confidence interval [CI]: 0.977–0.999, p = 0.04). The association remained after adjusting for confounding factors (age, BMI, annual household income, and education) (OR = 0.986, 95% CI: 0.972–0.999, p = 0.04). Conclusions: Serum vitamin A/TC ratio was inversely associated with POI risk. Therefore, the serum vitamin A/TC ratio may serve as a predictive factor for POI, and vitamin A supplementation may play help prevent or treat POI. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a common gynecologic disorder related to abnormal circadian rhythm. Therefore, we aimed to find whether the level of melatonin, a rhythm regulating hormone changed in the ovarian microenvironment in this disease.Methods: The melatonin concentrations in follicular fluid (FF) were measured in 35 PCOS and 36 non-PCOS women undergoing in vitro fertilization (IVF) treatment.Results: The FF melatonin concentration was significantly lower in PCOS women than non-PCOS women (p = 0.045) and it was found positively correlated with serum basal FSH level (r = 0.308, p = 0.013). In IVF procedures, there was no significant difference in the fertilization rate of oocytes between the two groups, but the high-quality embryogenesis rate on the third day of the PCOS group was significantly lower than that of the control group (p = 0.042), which showed a weak positive correlation with the FF melatonin concentration (rs = 0.240, p = 0.044). Furthermore, there was no significant difference in overall pregnancy outcome. The PSQI questionnaire showed that sleep disorders were more likely to exist in the PCOS group, though there was no significant difference.Conclusion: The obtained results suggested PCOS women had lower melatonin concentrations in the ovarian microenvironment. [ABSTRACT FROM AUTHOR]

Background: Ovarian stimulation during medically assisted reproduction treatment should be individualized to optimize outcomes and reduce complications. This study assessed whether use of the recombinant human follicle-stimulating hormone (r-hFSH) pen injector allowing small 12.5 IU dose increments resulted in lower r-hFSH dose per oocyte retrieved in a subgroup of patients at risk of OHSS, compared with r-hFSH injection devices allowing only 37.5 IU increments. Methods: This multicenter, comparative, observational study evaluated patients from a prospective (study group) and historical (control group) cohort. The study group enrolled 1783 patients using the redesigned r-hFSH pen injector (GONAL-f®, Merck Healthcare KGaA, Darmstadt, Germany) from a prospective phase IV, non-interventional, open-label study, conducted in Korea, Vietnam, Indonesia, and China. The control group consisted of 1419 patients from a historical study using r-hFSH devices allowing 37.5 IU increments. In the study group, 397 patients were considered at risk of OHSS; this information was unavailable for the control group, so biomarkers and patient characteristics were used to match 123 patients from the study group and control group. Each center adhered to standard practice; starting dose and intra-cycle dose adjustments were allowed at any point. The primary endpoint, amount of r-hFSH (IU) administered per oocyte retrieved, was assessed in matched patients only. Additional outcomes and safety were assessed in the overall populations. Results: Baseline characteristics were comparable between groups. Mean (SD) total dose of r-hFSH administered per oocyte retrieved in patients at risk of OHSS, was significantly lower in the study group compared with the control group (132.5 [85.2] vs. 332.7 [371.6] IU, P < 0.0001, n = 123). Implantation rate, clinical pregnancy rate, and live birth rates in the overall study and control groups were 30.0 vs. 20.6%, 50.3 vs. 40.7%, and 43.8 vs. 34.0%, respectively. OHSS incidence was significantly lower in the study group compared with the control group (27/1783 [1.5%] vs. 57/1419 [4.0%] patients, P < 0.0001). AEs were reported by 5.0% of patients in the study group. Conclusions: A significantly lower r-hFSH dose per oocyte retrieved and lower OHSS incidence were observed in patients using the redesigned injector compared with patients using other injection devices. [ABSTRACT FROM AUTHOR]

Background: Pentraxin 3 (PTX3) - a crucial humoral innate immunity component – is related to obesity and cardiovascular complications in women who suffer from polycystic ovary syndrome (PCOS). However, the circulating PTX3 level in PCOS is still debated. In this study, we aimed to evaluate PTX3 plasma levels in PCOS women of childbearing age, and find possible endocrine/metabolic factors that could affect this level. Methods: A total of 360 women were enrolled: 120 PCOS women and 240 body mass index (BMI) matched normally ovulating women. Blood samples were collected on the third day of natural menstrual cycle or from the bleeding after progesterone withdrawal. The PTX3 concentration was measured by immunoassay. Results: The PTX3 plasma level was significantly higher in PCOS women compared to controls. There was a positive correlation between PTX3 plasma level and PCOS diagnosis, overweight, cycle length, serum LH to FSH ratio, estradiol, total testosterone (TT) on the third day of menstrual cycle, antral follicle count (AFC), as well as uric acid. Multivariant linear regression analysis indicated that participants' serum PTX3 levels were proportional to the circulating TT level, existence of PCOS, basal estradiol level and AFC. Conclusions: Overall, the circulating PTX3 level was elevated in PCOS women and significantly associated with the presence of hyperandrogenism. This study provided the basis for further in-depth researches regarding PTX3 role in PCOS pathophysiology. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance and hormonal imbalances are key features in the pathophysiology of polycystic ovarian syndrome (PCOS). We have previously shown that Ficus deltoidea var. deltoidea Jack (Moraceae) can improve insulin sensitivity and hormonal profile in PCOS female rats. However, biological characteristics underpinning the therapeutic effects of F. deltoidea for treating PCOS remain to be clarified. This study aims to investigate the biochemical, hormonal, and histomorphometric changes in letrozole (LTZ)-induced PCOS female rats following treatment with F. deltoidea. Methods: PCOS was induced in rats except for normal control by administering LTZ at 1 mg/kg/day for 21 days. Methanolic extract of F. deltoidea leaf was then orally administered to the PCOS rats at the dose of 250, 500, or 1000 mg/kg/day, respectively for 15 consecutive days. Lipid profile was measured enzymatically in serum. The circulating concentrations of reproductive hormone and antioxidant enzymes were determined by ELISA assays. Ovarian and uterus histomorphometric changes were further observed by hematoxylin and eosin (H&E) staining. Results: The results showed that treatment with F. deltoidea at the dose of 500 and 1000 mg/kg/day reduced insulin resistance, obesity indices, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL), malondialdehyde (MDA), testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) to near-normal levels in PCOS rats. The levels of high-density lipoprotein cholesterol (HDL), estrogen, and superoxide dismutase (SOD) are also similar to those observed in normal control rats. Histomorphometric measurements confirmed that F. deltoidea increased the corpus luteum number and the endometrial thickness. Conclusions: F. deltoidea can reverse PCOS symptoms in female rats by improving insulin sensitivity, antioxidant activities, hormonal imbalance, and histological changes. These findings suggest the potential use of F. deltoidea as an adjuvant agent in the treatment program of PCOS. [ABSTRACT FROM AUTHOR]

Background: Poor ovarian response (POR) is among the common findings in infertile women with no significant underlying condition. The aim of this study was to investigate the intra-ovarian potential of platelet-rich plasma (PRP) administration on oocytes-dependent variables in the POR women grouped according to the POSEIDON criteria. Methods: This retrospective study was performed on POR women with no underlying condition who have undergone intra-ovarian PRP injection. As well as patients' age, the number of total and MI, MII, and GV oocytes were extracted from the files. The laboratory variables including anti-mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol were also gathered. In order to reduce any bias due to the possible differences in kits or devices, a single laboratory with the highest number of cases was selected and others were excluded from the study. Then, the included cases were grouped into four according to the POSEIDON criteria and analyzed for the mentioned variables by SPSS, version 25. The statistical significance level was set as P-value < 0.05. Results: From 383 cases, a total number of 96 women were enrolled in this study. According to the POSEIDON criteria, group 4 (Age ≥ 35 years, AMH < 1.2 ng/mL) with the ratio of 56/96 (58.3%) had the highest prevalence among others. As the analyses showed, changes in the laboratory variables (LH, FSH, AMH, and estradiol) were not significant in almost all the groups following the intervention. Regarding the total oocytes number, PRP administration caused a significant increase in the total number in all the groups (all P < 0.05). Also, the number of MII oocytes was significantly increased following the treatment in all groups except for group 2 (Age ≥ 35 years, AMH ≥ 1.2 ng/mL; all P < 0.05). Of 96 cases, 14 (14.6%) got clinically pregnant following assisted reproductive techniques which this number were significantly differed among the groups (P = 0.002). Conclusion: This study showed that PRP treatment was effective on total and MII oocyte numbers in the patients with POR, however, further studies are required. [ABSTRACT FROM AUTHOR]

Background: In this study, we aimed to evaluate the sex hormonal serum level in patients with recurrent aphthous stomatitis and compare them with healthy participants. Methods: This cross-sectional study was done on patients with recurrent aphthous stomatitis who had referred to Shiraz Dental Faculty, Oral and Maxillofacial Medicine Department during 2018–2019. The non -menopause women with recurrence of at least 3 lesions per year were enrolled in this study. The mean serum level of FSH, LH, PRL (prolactin), testosterone, DHT (Dihydrotestosterone), DHEA-S (Dehydroepiandrosterone sulfate), estradiol and progesterone of 30 participants in each group of case and control were measured and compared. The data were analyzed by SPSS version 18 and independent T-test, Mann–Whitney U test, Spearman's correlation coefficient test, Chi-square test and Fisher's test. Results: The mean serum level of DHEA-S in patients with recurrent aphthous stomatitis (RAS) was significantly lower than the control group (p value = 0.02). In addition to DHEA-S, the mean serum level of testosterone was lower in the evaluation group although this difference was not significant (p value = 0.057). Considering the effect of age on the mean serum level of sex hormones, our results revealed that only DHEA-S mean serum level was decreased by increasing the age of participants in patients with RAS (p value = 0.018). The number of participants with abnormal range of testosterone (p value < 0.0001) and progesterone (p value = 0.037) serum level was significantly more in patients with RAS. The frequency of RAS in a year did not show a significant relationship with the serum level of the evaluated hormones. Conclusion: The patients with RAS had a lower serum level of DHEA-S. The mean serum level of testosterone and progesterone was significantly abnormal in RAS patients. [ABSTRACT FROM AUTHOR]

Purpose: Recent studies have suggested the significant relationship between follicle-stimulating hormone (FSH) and non-alcoholic fatty liver disease (NAFLD) in postmenopausal women. However, it is unknown whether FSH impacts the risk of NAFLD in men. This study aimed to investigate the association between serum FSH levels and NAFLD in elderly Chinese men aged 80-98, a particular group with worse outcomes of NAFLD.Patients and Methods: A cross-sectional analysis was performed in 444 subjects in a geriatric health center. The highest quartile of serum FSH was used as reference. Hepatic steatosis was defined according to the results of liver ultrasound. Fibrosis-4 (FIB-4) Index > 2.67 was defined as advanced fibrosis.Results: Based on liver ultrasound, 108 (24.3%) subjects had NAFLD. FSH level were negatively correlated with total testosterone, estradiol, nutritional risk, and the prevalence of high education level (all P < 0.01), and positively correlated with age, luteinizing hormone, alanine aminotransferase and aspartate aminotransferase (all P < 0.05). The correlation between FSH and body mass index or antihypertensive drug usage was marginally significant (P = 0.057; P = 0.066, respectively). The percentage of subjects with NAFLD had a trend to increase following the quartiles of serum FSH (20.0% in quartile 1, 18.2% in quartile 2, 27.3% in quartile 3, and 31.6% in quartile 4). After adjustment for common pathogenic risk factors, nutritional risk, and other sex hormones, serum FSH were progressively associated with odds ratios for NAFLD. The adjusted odds ratios and 95% CIs for quartile 1, quartile 2, and quartile 3, compared with quartile 4 were 0.132 (0.034-0.516), 0.190 (0.052-0.702), and 0.404 (0.139-1.173), respectively. Obesity was not involved in the potential negative role of circulating FSH on the risk of NAFLD in our population. Furthermore, our results revealed no significant association between FSH and advance fibrosis, the OR (95% CI) for advanced fibrosis was 1.018 (0.983-1.054) (P = 0.316) after adjusting for the potential covariates, although a positive correlation of FSH and FIB-4 score was observed (r = 0.325, P = 0.001).Conclusion: Low FSH level may decrease the risk of NAFLD in elderly Chinese men. These findings warrant replication in more extensive studies. [ABSTRACT FROM AUTHOR]

Background: Equine chorionic gonadotropin (eCG), which comprises highly glycosylated α-subunit and β-subunit, is a unique member of the glycoprotein hormone family as it elicits both follicle-stimulating hormone (FSH)-like and luteinizing hormone (LH)-like responses in non-equid species. To examine the biological function of glycosylated sites in eCG, the following glycosylation site mutants were constructed: eCGβ/αΔ56, substitution of Asn56 of α-subunit with Gln; eCGβ-D/α, deletion of the O-linked glycosylation site at the carboxyl-terminal peptide (CTP) region of the β-subunit; eCGβ-D/αΔ56, double mutant. The recombinant eCG (rec-eCG) mutants were expressed in Chinese hamster ovary suspension (CHO-S) cells. The FSH-like and LH-like activities of the mutants were examined using CHO-K1 cells expressing rat lutropin/CG receptor (rLH/CGR) and rat FSH receptor (rFSHR). Results: Both rec-eCGβ/α and rec-eCGβ/αΔ56 were efficiently secreted into the CHO-S cell culture medium on day 1 post-transfection. However, the secretion of eCGβ-D/α and eCGβ-D/αΔ56, which lack approximately 12 O-linked glycosylation sites, was slightly delayed. The expression levels of all mutants were similar (200–250 mIU/mL) from days 3 to 7 post-transfection. The molecular weight of rec-eCGβ/α, rec-eCGβ/αΔ56 and rec-eCG β-D/α were in the ranges of 40–45, 37–42, and 34–36 kDa, respectively. Treatment with peptide-N-glycanase F markedly decreased the molecular weight to approximately 5–10 kDa. Rec-eCGβ/αΔ56 exhibited markedly downregulated LH-like activity. The signal transduction activity of both double mutants was completely impaired. This indicated that the glycosylation site at Asn56 of the α-subunit plays a pivotal role in the LH-like activity of eCG. Similarly, the FSH-like activity of the mutants was markedly downregulated. eCGβ-D/α exhibited markedly downregulated LH-like and FSH-like activities. Conclusions: Rec-eCGβ/α exhibits potent biological activity in cells expressing rLH/CGR and rFSHR. The findings of this study suggest that the LH-like and FSH-like activities of eCG are regulated by the N-linked glycosylation site at Asn56 of the eCG α-subunit and/or by the O-linked glycosylation sites of the eCG β-subunit. These findings improved our understanding of the mechanisms underlying both LH-like and FSH-like activities of eCG. [ABSTRACT FROM AUTHOR]

Background: The most common endocrine and metabolic disorders in premenopausal women is polycystic ovary syndrome (PCOS), characterized by hyperandrogenism, chronic anovulation, and/or ultrasound evidence of small ovarian cysts. Obesity and insulin resistance are also the main factors influencing the clinical manifestations of this syndrome. Alzheimer's disease (AD) is the most typical progressive neurodegenerative disorder of the brain, and recent studies suggest a relationship between endocrinal dysregulation and neuronal loss during AD pathology. Aim: This study aimed to evaluate the common risk factors for Alzheimer's and PCOS based on previous studies. Knowing the common risk factors and eliminating them may prevent neurodegenerative Alzheimer's disease in the future. Method: In this narrative review, international databases, including Google Scholar, Scopus, PubMed, and the Web of Science, were searched to retrieve the relevant studies. The relevant studies' summaries were categorized to discuss the possible pathways that may explain the association between Alzheimer's and PCOS signs/symptoms and complications. Results: According to our research, the factors involved in Alzheimer's and PCOS disorders may share some common risk factors. In patients with PCOS, increased LH to FSH ratio, decreased vitamin D, insulin resistance, and obesity are some of the most important factors that may increase the risk of Alzheimer's disease. Plain English summary: Polycystic ovary syndrome is a disorder of the female reproductive system that can be caused by hormonal disorders. The disease is detected by an ultrasound of the ovaries with small ovarian cysts. Obesity and insulin resistance are among the factors that can affect the clinical symptoms of this disease. Obesity due to high-fat consumption can affect cognitive functions with age. Alzheimer's is the most common disease associated with disorders in brain cells; a link between hormonal disorders and Alzheimer's has recently been reported. We conducted a review of reports and articles published in connection with polycystic ovary syndrome and neurodegenerative disorders in reputable scientific databases. Studies have shown that the factors involved in polycystic ovary syndrome and Alzheimer's disease may indicate that both diseases have common risk factors. It may be linked to the symptoms and/or complications of Alzheimer's disease and polycystic ovary syndrome. Future preclinical studies are needed to closely examine the mechanisms associated with polycystic ovary syndrome and the association with Alzheimer's. The novelty of our study is from the fact that the PCOS may be to some extent considered as a cause (exposure) among others of AD's (outcome) and the association might be confounded by some or all the risk factors assessed in this review. The nature of the method—the narrative review—is relatively subjective (in the determination of which studies to include, the way the studies are analyzed, and the conclusions drawn) and hence may not help mitigate bias. [ABSTRACT FROM AUTHOR]