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BACKGROUND: Estrogens play a critical role in parturition, and poly- and perfluoroalkyl substances (PFAS), which have estrogenic effects, have been associated with preterm birth. However, the impact of estrogens on the association between PFAS and preterm birth is unknown. OBJECTIVE: The objective of this study is to investigate if estrogens modified the association between PFAS and preterm birth, using a nested case-control study design. METHODS: A total of 371 preterm births and 508 controls were selected from a birth cohort study in China between 2016 and 2018. Perfluorobutanoic acid (PFBA), perfluorohexanesulfonic acid (PFHxS) and its branched isomer, perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS) and its branched isomer, and perfluorononanoic acid (PFNA) were quantified in maternal serum (mean gestational age of 32 wk). Estradiol and estriol were quantified in cord serum. Preterm birth was defined as live delivery at <37 gestational weeks. Causal mediation analysis was used to estimate the mediation and interaction effects of estrogen on the association between PFAS and preterm birth. Latent profile analysis was used to identify important estrogen profiles. Multiple linear regression was used to estimate associations between PFAS and preterm birth and interactions between PFAS and estrogens on preterm birth. RESULTS: Overall, higher odds ratios (ORs) of preterm birth were associated with each 1 ln-unit PFAS increase: PFBA [1.20, 95% confidence interval (CI): 1.14, 1.26], PFNA (1.30, 95% CI: 1.21, 1.39), PFOA (1.98, 95% CI: 1.54, 2.55), and PFOS (1.91, 95% CI: 1.76, 2.07) and its branched isomer (1.91, 95% CI: 1.90, 1.92). We detected statistically significant interactions between cord estradiol and PFAS on preterm birth, while no mediation effects of cord estrogen were observed. The ORs of PFOS (4.29, 95% CI: 1.31, 8.25), its branched isomer (6.71, 95% CI: 1.06, 11.91), and preterm birth were greater for participants with high cord estrogen levels than for participants with low cord estrogen levels. DISCUSSION: Our findings suggest that estrogen modified the association between maternal PFAS exposure and preterm birth. Further studies on maternal PFAS exposure and preterm birth, taking interaction effects of cord estrogens into account, are warranted. [ABSTRACT FROM AUTHOR]

Estrogen receptor (ER) is overexpressed in approximately 2/3 of breast cancer patients' lesions. Noninvasive detection of ER in vivo and dynamic monitoring of ER are crucial for individualized treatment decision-making. 16α-18F-17β-fluoroestradiol (18F-FES) positron emission tomography (PET) has been used in a variety of preclinical and clinical studies to detect ER expression. However, there is still a lack of technical specifications in China. This technical specification was jointly written by domestic experts who had experience of 18F-FES PET imaging and was formed through consultation based on their own experience and research progress in this field both domestically and internationally. This technical specification introduced the synthesis method and quality control requirements of 18F-FES, recommended its clinical application scenarios, and classified them. In addition, experts' suggestions were provided throughout the entire process systemically and detailly, including pre-imaging preparation, imaging process, image analysis (normal biological distribution, determination of ER positive and negative, lesion detection, influencing factors, false negative and false positive, report requirements), and the limitations of this imaging technique were proposed. The future application prospects were also discussed. This specification aimed to promote the standardized application of 18F-FES PET in China, achieve repeatability and comparability, and provide important molecular imaging technical support for accurate diagnosis and treatment of breast cancer. [ABSTRACT FROM AUTHOR]

The Chinese soft-shelled turtle, Pelodiscus sinensis, is an important aquaculture species in China that exhibits distinct sexual dimorphism; male individuals are economically more valuable than females. In vertebrates, several R-spondin family proteins have been associated with sex differentiation mechanisms; however, their involvement in P. sinensis sex differentiation is unclear. Exogenous hormones such as estradiol (E2) also influence the sex differentiation of P. sinensis and induce sexual reversal. In the present study, we investigated the effects of E2 on the embryonic development of P. sinensis and the expression of R-spondin 2 (Rspo2) and R-spondin 3 (Rspo3). We amplified P. sinensis Rspo2 and Rspo3 and analyzed their expression patterns in different tissues. Comparative analyses with protein sequences from other species elucidated that P. sinensis RSPO2 and RSPO3 sequences were conserved. Moreover, phylogenetic analysis revealed that P. sinensis RSPO2 and RSPO3 were closely related to these two proteins from other turtle species. Furthermore, Rspo2 and Rspo3 were highly expressed in the brain and gonads of adult turtles, with significantly higher expression in the ovaries than in the testes (p < 0.05). We also evaluated the expression of Rspo2 and Rspo3 after the administration of three concentrations of E2 (1.0, 5.0, and 10.0 mg/mL) to turtle eggs during embryonic development. The results revealed that E2 upregulated Rspo2 and Rspo3, and the expression trends varied during different embryonic developmental stages (stages 13–20). These findings lay the groundwork for future investigations into the molecular mechanisms involved in the sex differentiation of Chinese soft-shelled turtles. [ABSTRACT FROM AUTHOR]

This study was to investigate the association between sex hormone levels and metabolic syndrome (MetS) risk in female schizophrenia inpatients. In total, 93 female schizophrenia patients were enrolled based on their electronic medical records of hospitalization at the Zigong Psychiatric Research Center, China, between August 2022 to September 2022. Baseline information was collected retrospectively from medical records 6 months before. Logistic regression analysis was applied to assess the potential relationship between sex hormone levels and the risk of developing MetS. 31.2% (29/93) of the total patients, 25.5% (12/47) of the 18–49 age group, and 37.0% (17/46) of the ≥ 50 age group had a history of MetS; the newly-developed MetS prevalence among all female schizophrenia patients was 15.05% (14/93), which was slightly higher but not statistically significant in older patients (age ≥ 50) than in younger patients (age 18–49) (≥ 50 vs. 18–49, 21.74% vs. 8.5%, p = 0.074). Univariate analysis of sex hormone levels and developed MetS discovered that only high prolactin levels correlated with developed MetS in total participants (p = 0.006), especially in older patients (p = 0.004), while estradiol and testosterone levels were not associated. Furthermore, univariate logistic regression analysis of the total participants and with an adjusted model of the ≥ 50 age group confirmed the association of prolactin with MetS in all (OR = 1.016, 95%CI:1.002–1.029, p = 0.023), and older female schizophrenia patients (OR = 1.04, 95%CI: 1.01–1.07, p = 0.008). High serum levels of prolactin in older patients (age ≥ 50) were strongly correlated with the risk of developing MetS among female schizophrenia patients. [ABSTRACT FROM AUTHOR]

Objective. Our aim was to investigate the effect of age on the outcome of IVF-ET and ICSI in infertile PCOS patients under the guidance of Tiangui theory in traditional Chinese medicine. Method. This was a retrospective analysis of 532 infertile women with PCOS and 1,392 women with infertility due to tubal factors as the controls. All of the participants were divided into different age groups-aged 20–28 years, 29–35 years, and ≥36 years-according to the stages of female reproductive development in Tiangui theory as described in the Canon of Internal Medicine-Treatise of Ancient Natural Truth. We explored the effect of age on controlled ovarian hyperstimulation (including the initial dosage and duration of Gn and the estradiol level on the day of human chorionic gonadotropin administration); the numbers of retrieved oocytes, 2PN zygotes, and embryos; and the rates of fertilization, clinical pregnancy, abortion, live birth, and OHSS incidence. Results. Compared to controls, the maximum follicular diameter and the numbers of follicles with d ≥ 20 mm, retrieved oocytes, and 2PN zygotes were greater in the PCOS group with age >28 years (p < 0.05). The abortion rate of PCOS patients with age ≤28 years was higher than that of the controls. All PCOS groups and the control group showed reduced numbers of retrieved oocytes and live births with age. The difference in age was not significant in the PCOS groups but was significant in the control group (p < 0.05), and the trend in the PCOS groups was more gradual. Conclusion. The fertility of all subjects decreased with age, but PCOS patients decreased more slowly than in controls at the same age, which verified the applicability of the guiding principles of Tiangui theory in the clinic. [ABSTRACT FROM AUTHOR]

Background: Sex hormones are strongly linked to the occurrence and development of diabetes, and influence glycated hemoglobin (HbA1c) levels in diabetic population; but, the relationship between sex hormones and HbA1c in non-diabetic population remains unknown. This study aimed to explore the extent of influence of sex hormones on HbA1c levels in non-diabetic population. Methods: A total of 1409 non–diabetic subjects, including 601 men and 808 postmenopausal women were recruited from Shanghai community. HbA1c was detected using high performance liquid chromatography, and hemoglobin level was determined by sodium lauryl sulfate colorimetry. Serum estradiol (E2), total testosterone (TT), and sex hormone binding globulin (SHBG) were measured by chemiluminescent microparticle immunoassays. Results: The level of HbA1c was 5.6 (5.4–5.9) % in all subjects, with 5.6 (5.4–5.8) % in men and 5.7 (5.5–5.9) % in postmenopausal women. After adjusting for age, body mass index (BMI), and hemoglobin, E2 was positively correlated with HbA1c in men (r = 0.122, P =.003), and SHBG was inversely correlated with HbA1c (r = − 0.125, P <.001) in women. Other hormones were not correlated with HbA1c (all P >.05). Multivariate linear regression analysis showed that, except for traditional factors, such as age, hemoglobin, and BMI, E2 was another determinant of HbA1c (standardized β = 0.137, P =.003) in men; besides, in women, SHBG was another determinant of HbA1c (standardized β = − 0.178, P <.001), except for age and systolic blood pressure. Conclusion: After controlling for confounding factors, two sex hormones, as E2 and SHBG could influence HbA1c levels in non-diabetic population. [ABSTRACT FROM AUTHOR]

Study Question: Does hypo-glycosylated human recombinant FSH (hFSH18/21) have greater in vivo bioactivity that drives follicle development in vivo compared to fully-glycosylated human recombinant FSH (hFSH24)?Summary Answer: Compared with fully-glycosylated hFSH, hypo-glycosylated hFSH has greater bioactivity, enabling greater follicular health and growth in vivo, with enhanced transcriptional activity, greater activation of receptor tyrosine kinases (RTKs) and elevated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling.What Is Known Already: Glycosylation of FSH is necessary for FSH to effectively activate the FSH receptor (FSHR) and promote preantral follicular growth and formation of antral follicles. In vitro studies demonstrate that compared to fully-glycosylated recombinant human FSH, hypo-glycosylated FSH has greater activity in receptor binding studies, and more effectively stimulates the PKA pathway and steroidogenesis in human granulosa cells.Study Design, Size, Duration: This is a cross-sectional study evaluating the actions of purified recombinant human FSH glycoforms on parameters of follicular development, gene expression and cell signaling in immature postnatal day (PND) 17 female CD-1 mice. To stimulate follicle development in vivo, PND 17 female CD-1 mice (n = 8-10/group) were treated with PBS (150 µl), hFSH18/21 (1 µg/150 µl PBS) or hFSH24 (1 µg/150 µl PBS) by intraperitoneal injection (i.p.) twice daily (8:00 a.m. and 6:00 p.m.) for 2 days. Follicle numbers, serum anti-Müllerian hormone (AMH) and estradiol levels, and follicle health were quantified. PND 17 female CD-1 mice were also treated acutely (2 h) in vivo with PBS, hFSH18/21 (1 µg) or hFSH24 (1 µg) (n = 3-4/group). One ovary from each mouse was processed for RNA sequencing analysis and the other ovary processed for signal transduction analysis. An in vitro ovary culture system was used to confirm the relative signaling pathways.Participants/materials, Setting, Methods: The purity of different recombinant hFSH glycoforms was analyzed using an automated western blot system. Follicle numbers were determined by counting serial sections of the mouse ovary. Real-time quantitative RT-PCR, western blot and immunofluorescence staining were used to determine growth and apoptosis markers related with follicle health. RNA sequencing and bioinformatics were used to identify pathways and processes associated with gene expression profiles induced by acute FSH glycoform treatment. Analysis of RTKs was used to determine potential FSH downstream signaling pathways in vivo. Western blot and in vitro ovarian culture system were used to validate the relative signaling pathways.Main Results and the Role Of Chance: Our present study shows that both hypo- and fully-glycosylated recombinant human FSH can drive follicular growth in vivo. However, hFSH18/21 promoted development of significantly more large antral follicles compared to hFSH24 (P < 0.01). In addition, compared with hFSH24, hFSH18/21 also promoted greater indices of follicular health, as defined by lower BAX/BCL2 ratios and reduced cleaved Caspase 3. Following acute in vivo treatment with FSH glycoforms RNA-sequencing data revealed that both FSH glycoforms rapidly induced ovarian transcription in vivo, but hypo-glycosylated FSH more robustly stimulated Gαs and cAMP-mediated signaling and members of the AP-1 transcription factor complex. Moreover, hFSH18/21 treatment induced significantly greater activation of RTKs, PI3K/AKT and MAPK/ERK signaling compared to hFSH24. FSH-induced indices of follicle growth in vitro were blocked by inhibition of PI3K and MAPK.Large Scale Data: RNA sequencing of mouse ovaries. Data will be shared upon reasonable request to the corresponding author.Limitations, Reasons For Caution: The observations that hFSH glycoforms have different bioactivities in the present study employing a mouse model of follicle development should be verified in nonhuman primates. The gene expression studies reflect transcriptomes of whole ovaries.Wider Implications Of the Findings: Commercially prepared recombinant human FSH used for ovarian stimulation in human ART is fully-glycosylated FSH. Our findings that hypo-glycosylated hFSH has greater bioactivity enabling greater follicular health and growth without exaggerated estradiol production in vivo, demonstrate the potential for its development for application in human ART.Study Funding/competing Interest(s): This work was supported by NIH 1P01 AG029531, NIH 1R01 HD 092263, VA I01 BX004272, and the Olson Center for Women's Health. JSD is the recipient of a VA Senior Research Career Scientist Award (1IK6 BX005797). This work was also partially supported by National Natural Science Foundation of China (No. 31872352). The authors declared there are no conflicts of interest. [ABSTRACT FROM AUTHOR]

1. In the cynomolgus macaque, UDP-glucuronosyltransferases (UGTs) 1As have similar molecular and enzymatic characteristics to those of their human orthologs. However, genetic polymorphisms in major cynomolgus UGT1A1/6/9 have not been investigated. 2. We re-sequenced UGT1A1, UGT1A6, and UGT1A9 in 186 cynomolgus macaques (bred in Cambodia, China, or Indonesia) and 54 rhesus macaques and found 15, 13, and 26 non-synonymous variants, respectively. 3. Of these UGT1A1, UGT1A6, and UGT1A9 variants, respectively, 10, 9, and 12 were unique to cynomolgus macaques; 4, 1, and 2 were unique to rhesus macaques; and 1, 2, and 5 were found in both cynomolgus and rhesus macaques. The frequency of the UGT1A1 mutation G69R was 23%, 28%, and 63% in cynomolgus macaques bred in Cambodia, China, and Indonesia, respectively, and 97% in rhesus macaques. 4. The O-glucuronidation activities of liver microsomes from cynomolgus and rhesus macaques with respect to estradiol, serotonin, and propofol were measured. Among these activities, liver microsomes from cynomolgus macaques heterozygous for UGT1A1 G69R (n = 11) showed significantly reduced estradiol 3-O-glucuronidation activities compared with those from wild-type animals (n = 38). 5. These results suggest genetic variants such as UGT1A1 G69R could influence the UGT1A1-mediated glucuronidation of drugs in cynomolgus and rhesus macaques. [ABSTRACT FROM AUTHOR]

Background: Anti-Müllerian hormone (AMH) is now considered the best serum biomarker of ovarian reserve, while basal sex hormones are classic markers used for assessing ovarian reserve. The interaction between AMH and sex hormones are complicated and not sufficiently addressed. In this study, we took diminished ovarian reserve (DOR) and polycystic ovarian syndrome (PCOS) as two extremes of ovarian reserve (deficient and excessive respectively) to investigate the role of AMH and sex hormones in follicular growth. Methods: A retrospective cross-sectional survey was performed. The patients assessed AMH and basal sex hormones in the Second Hospital of Zhejiang University from April 2016 to March 2019 were involved in this study. Serum AMH and sex hormone concentrations were tested with electrochemiluminescence method. Stepwise linear regression and binary logistic regression was used to determine the predictors of AMH level and to explore the involved factors determining DOR and PCOS. Results: In the present study, we found that age and follicle-stimulating hormone (FSH) were main negative correlation factors, and luteinizing hormone (LH) and testosterone (T) were main positive factors of AMH. In DOR group, age, FSH and estradiol (E2) increased and T decreased, while in PCOS group, LH and T increased. Binary logistic regression found that age, weight, FSH, E2, and T were the significant factors which independently predicted the likelihood of DOR, and that age, body mass index (BMI), AMH, LH, and T predicted the likelihood of PCOS. Conclusions: Our study demonstrated that age, FSH, and T were factors that most closely correlated with AMH level, and T was involved in both DOR and PCOS. Since DOR and PCOS are manifested with insufficient AMH and excessive AMH respectively, it is suggested that total testosterone correlated with AMH closely and plays an important role in follicular growth. More attention should be given to testosterone level during controlled ovarian hyperstimulation (COH) process. [ABSTRACT FROM AUTHOR]

This study aimed to investigate whether chronic unpredictable mild stress (CUMS) affects follicular development in ovaries through the nerve growth factor (NGF)/high affinity nerve growth factor receptor, the Tropomyosin-related kinase A (TrkA) receptor, mediated signaling pathway and to reveal the relationship between chronic stress and premature ovarian insufficiency (POI) development. In this experiment, a CUMS rat model was constructed. It was found that serum estradiol (E2), anti-Mullerian hormone (AMH), and gonadotropin-releasing hormone (GnRH) levels decreased, while follicle-stimulating hormone (FSH) levels increased. The expression of NGF, TrkA, p75, and FSHR in ovarian tissue decreased significantly. The expression levels of TrkA and p75 protein in ovarian stroma and small follicles were observed by an immunofluorescence assay. In addition, the numbers of small follicles were significantly reduced. The expression of TrkA, p75, and FSHR in CUMS ovarian tissue was upregulated by exogenous NGF in vitro. Furthermore, after treatment with NGF combined with FSH, E2 secretion in ovarian tissue culture supernatant of CUMS rats also increased significantly. Therefore, CUMS downregulates NGF and TrkA and promotes the occurrence of POI in rats. Exogenous NGF and FSH can upregulate the NGF receptor, E2, and AMH in vitro, and improve the rat ovarian function. Future studies may associate these results with female population. [ABSTRACT FROM AUTHOR]

Objective: Assess the association between serum sex hormone level and prostate volume in men with benign prostatic hyperplasia (BPH).Material and methods: The study involved 239 BPH patients from January 2013 to June 2015 in our hospital. Each patient collected age, medical history, height, weight, body mass index, as well as a full examination of sex hormones, and transrectal ultrasound results.Results: Estradiol (E2) was significantly associated with prostate volume (r = 0.151, p = .02) and transitional zone volume (r = 0.136, p = .035). The association was more significant after adjusting age and BMI (r = 0.253 and 0.250, p <.001). Patients were divided into two groups according to prostate volume and E2, respectively. E2 in patients with prostate volume ≤50 ml was significantly lower than those with prostate volume >50 ml. Prostate volume, transitional zone volume and age were all significantly higher in the patients with E2 ≥ 160 umol/l than those in the patients with E2 < 160 umol/l. Through logistics regression, E2 (p = .012, OR = 1.004) are the only independent risk factor for prostate volume.Conclusions: E2 is significantly associated with prostate volume. High concentrations of E2 may be a risk factor for the large volume of prostate. [ABSTRACT FROM AUTHOR]

Study Question: Is there an association between peak serum estradiol (E2) level during controlled ovarian stimulation (COS) and neonatal birthweight in freeze-all cycles?Summary Answer: Peak serum E2 level during ovarian stimulation is not associated with neonatal birthweight in freeze-all cycles.What Is Known Already: Supraphysiologic E2 levels during COS have been demonstrated to generate a suboptimal peri-implantation endometrial environment and thus lead to adverse neonatal outcomes in fresh embryo transfer cycles. Previous experimental studies also suggested a potential influence of superovulation on oocyte epigenetic programming, but whether it translates into altered phenotypes of fetal growth and development remains unclear in clinical practice. By segmenting the process of COS and embryo transfer, the freeze-all policy provides a novel model to investigate the sole impact of ovarian stimulation on oocytes after ruling out the effects of hyperestrogenic milieu on endometrium in fresh cycles.Study Design, Size, Duration: A retrospective cohort study of 8501 patients who underwent their first COS cycles with a freeze-all strategy and delivered live-born singletons in subsequent frozen-thawed embryo transfer cycles from January 2007 to December 2016 at a tertiary-care academic medical center.Participants/materials, Setting, Methods: Patients were categorized into six groups according to E2 level on trigger day in regular increments of 1000 pg/mL: <1000, 1000-1999, 2000-2999, 3000-3999, 4000-4999 and ≥5000 pg/mL. Univariable and multivariable linear regression and logistic regression analysis were performed to assess the independent association between peak E2 level and measures of neonatal birthweight including absolute birthweight, Z-score, low birthweight (LBW) and small-for-gestational age (SGA).Main Results and the Role Of Chance: The six groups did not differ significantly in birthweight, Z-score or the incidence of LBW and SGA. Compared with the E2 <1000 pg/mL group, the adjusted mean difference (95% confidence interval [CI]) of stratified higher E2 groups was 17.2 (-31.0-65.5), 12.3 (-35.9-60.5), -4.1 (-51.9-43.7), -0.6 (-48.9-47.8) and -3.6 (-50.0-42.8) g for birthweight, and 0 (-0.11-0.10), 0.02 (-0.08-0.12), 0.04 (-0.06-0.14), -0.01 (-0.11-0.10) and -0.04 (-0.14-0.06) for Z-score, respectively. Regarding the outcomes of LBW and SGA, no increased risks were observed in each E2 category, with the adjusted odds ratio (95% CI) being 1.21 (0.68-2.16), 1.0 (0.58-1.90), 0.90 (0.50-1.63), 0.93 (0.51-1.69) and 1.08 (0.61-1.90) for LBW, and 0.97 (0.58-1.64), 1.06 (0.63-1.77), 0.77 (0.46-1.31), 0.71 (0.41-1.22) and 1.00 (0.60-1.65) for SGA, respectively.Limitations, Reasons For Caution: The study was retrospective in design, and other unknown confounding factors may not be included for adjustment. Furthermore, the generalization of the study finding could be limited to some extent by the majority of double cleavage-stage embryo transfer and difference in birthweight reference percentiles between Chinese and other populations.Wider Implications Of the Findings: Our observations suggest that the hyperestrogenic milieu during COS does not seem to pose adverse effects on neonatal birthweight after frozen-thawed embryo transfer, which provides reassuring information for high ovarian responders in freeze-all cycles concerning their offspring's health.Study Funding/competing Interest(s): This study was funded by the National Key Research and Development Program of China (SQ2018YFC100163) and National Natural Science Foundation of China (81571397, 81771533). The authors declare no conflict of interest. [ABSTRACT FROM AUTHOR]

Study Question: Does amphiregulin (AREG), the most abundant and important epidermal growth factor receptor (EGFR) ligand in the follicular fluid, regulate aromatase expression in human granulosa-lutein (hGL) cells?Summary Answer: AREG mediates the hCG-induced up-regulation of aromatase expression and estradiol (E2) production in hGL cells.What Is Known Already: AREG expression and secretion are rapidly induced by hCG in hGL cells and mediate physiological functions of LH/hCG in the ovary. EGFR protein is expressed in follicles not only in the pre-ovulatory phase but also throughout the luteal phase of the menstrual cycle. After the LH surge, the human corpus luteum secretes high levels of E2, which regulates various luteal cell functions. Aromatase is an enzyme responsible for a key step in the biosynthesis of E2. However, whether AREG regulates aromatase expression and E2 production in hGL cells remains unexplored.Study Design, Size, Duration: This study is an experimental study performed over a 1-year period. In vitro investigations examined the role of AREG in the regulation of aromatase expression and E2 production in primary hGL cells.Participants/materials, Setting, Methods: Primary hGL cells were obtained from women undergoing IVF treatment in an academic research center. Aromatase mRNA and protein levels were examined after exposure of hGL cells to recombinant human AREG, hCG or LH. The EGFR tyrosine kinase inhibitor AG1478, PI3K inhibitor LY294002 and siRNAs targeting EGFR, LH receptor, StAR and AREG were used to verify the specificity of the effects and to investigate the underlying molecular mechanisms. Reverse transcription quantitative real-time PCR (RT-qPCR) and western blot were used to measure the specific mRNA and protein levels, respectively. Follicular fluid and serum were collected from 65 infertile women during IVF treatment. Pearson's correlation analysis was performed to examine the correlation coefficient between two values.Main Results and the Role Of Chance: Treatment of hGL cells with AREG-stimulated aromatase expression and E2 production. Using pharmacological inhibitors and specific siRNAs, we revealed that AREG-stimulated aromatase expression and E2 production via EGFR-mediated activation of the protein kinase B (AKT) signaling pathway. In addition, inhibition of EGFR activity and AREG knockdown attenuated hCG-induced up-regulation of aromatase expression and E2 production. Importantly, the protein levels of AREG in the follicular fluid were positively correlated with the E2 levels in serum after 2 days of oocyte pick-up and in the follicular fluid of IVF patients.Large-scale Data: N/A.Limitations, Reasons For Caution: The in vitro setting of this study is a limitation that may not reflect the real intra-ovarian microenvironment. Clinical data were obtained from a small sample size.Wider Implications Of the Findings: Our results provide the first evidence that hCG-induced AREG contributes to aromatase expression and E2 production in the luteal phase of the menstrual cycle. A better understanding of the hormonal regulation of female reproductive function may help to develop new strategies for the treatment of clinical infertility.Study Funding/competing Interest(s): This work was supported by the National Natural Science Foundation of China for Young Scientists (81601253), the specific fund of clinical medical research of Chinese Medical Association (16020160632) and the Foundation from the First Affiliated Hospital of Zhengzhou University for Young Scientists to Lanlan Fang. This work was also supported by an operating grant from the National Natural Science Foundation of China (81820108016) to Ying-Pu Sun. All authors declare no conflict of interest. [ABSTRACT FROM AUTHOR]

Preterm ovarian hyperstimulation syndrome (POHS) is a rare condition with only a few reported cases. The objective of this study is to investigate the clinical characteristics of 21 POHS cases (seven from China and 14 from the literature). Suspected patients (n = 7) were referred for further confirmation and data on demographics, family history, clinical manifestations (edema developed in the vulva, the hypogastric site and the upper leg), serum and sonographic assessments (ovarian cyst/cysts, gonadotropins, and estradiol levels), the natural course of patients were documented. We did not observe substantial differences in clinical manifestations among POHS patients from China relative to that from the literature. Preterm female newborns developed edema in the vulva, the hypogastric site and the upper leg at 30–39+6 weeks of post-conception age (PCA) as the major clinical manifestations. The characteristic also included high gonadotropins and estradiol, and ovarian cysts. This condition can self-resolve. Clinical manifestations of POHS patients from China are similar to those from the literature. The pathognomonic signs of POHS include vulvar, hypogastric, and upper leg edema developed at 30–39+6 PCA along with high gonadotropins and E2 values and the presence of ovarian cysts in preterm female newborns and the syndrome can self-resolve. [ABSTRACT FROM AUTHOR]

Objective. Epilepsy is a neuronal disorder that is characterized by epileptic seizures and linked with abnormal neural functioning in the brain. Traditional Chinese medicine (TCM) formula Chaibei Zhixian decoction (CZD) has been widely used for epilepsy in China while the pharmacological mechanisms are still unclear. In the present study, systematic and comprehensive network pharmacology was utilized for the first time to reveal the potential pharmacological mechanisms of CZD on epilepsy. Methods. Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and analysis platform was utilized for the development of an ingredients-targets database. After identifying epileptic targets of CZD, their interaction with other proteins was estimated based on protein-protein interaction network created from STITCH and gene ontology (GO) enrichment analysis utilizing Cytoscape-ClueGO plugin. Results. CZD formula was found to have 643 chemical ingredients, and the potential protein targets of these ingredients were 5230, as retrieved from TCMSP database. Twenty-six protein targets were found to be associated with epilepsy. Thirteen hub genes were regulated by CZD in epilepsy, including estradiol, ESR1, ESR2, SRC, CTNNB1, EP300, MAPK1, MAPK3, SP1, BRCA1, NCOA3, CHRM1, and GSK3B. The results of GO terms analysis showed that 8 GO terms were recovered in the form of 3 clusters, including negative regulation of protein kinase B signaling, positive regulation of interleukin-1 production, and microvillus assembly. Conclusions. Network pharmacology approach provides better understanding of the underlying pharmacological mechanisms of CZD on epilepsy. Estradiol, ESR1, ESR2, CTNNB1, EP300, MAPK1, MAPK3, BRCA1, and GSK3B are likely to be important molecules regulated by CZD in treatment of epilepsy. Negative regulation of protein kinase B signaling may play vital roles in the treatment of epilepsy by CZD. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether supraphysiological estradiol (E2 ) in controlled ovarian stimulation (COS) cycles affects the subsequent frozen-thawed embryo transfer (FET) in terms of the neonatal birthweight.Design: Retrospective cohort study.Setting: University affiliated hospital.Population: In all, 2066 patients undergoing FET cycles that resulted in live singleton births between July 2011 and Dec 2016.Interventions: None.Methods: Multivariable linear regression and logistic regression was used to evaluate the association between peak E2 and birthweight outcomes.Main Outcome Measures: Birthweight, z-score adjusted for gender and gestational age, and incidence of small-for-gestational-age (SGA) and low birthweight (LBW) in singleton neonates derived from FET cycles.Results: Adjusted for confounding factors, both the absolute birthweight and the z-score of singletons following FET were negatively associated with peak E2 levels in COS. In comparison with the referent category (E2  ≤1500 pg/ml), the categories with E2  >3000 pg/ml had a significantly lower z-score. The difference (95% CI) in estimated marginal mean of birthweights between referent category and highest E2 (>8000 pg/ml) category was 104.57 g (18.13-181.06). Multiple logistic regression analyses showed that the adjusted odds ratio (95% CI) for SGA and LBW in term singletons comparing patients with E2  >3000 pg/ml with those with E2  ≤3000 pg/ml was 2.44 (1.37-4.34) and 2.32 (1.01-5.40), respectively.Conclusions: Peak E2 levels in COS cycles are negatively associated with the birthweight of singletons conceived through subsequent FET cycles.Tweetable Abstract: The birthweight following FET is affected by previous COS cycle. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to analyse the associations of left-hand digit ratio (2D:4D), digit length and puberty characteristics to show the role of prenatal hormones in development among Chinese girls.Method: A total of 318 Chinese girls aged 8-15 years were recruited using a stratified cluster sampling method. The index finger (2D), ring finger (4D) of the left hand, oestradiol and testosterone were measured, and age at menarche (AAM), breast (high and low) and pubic hair (high and low) development were recorded.Results: Girls who had experienced menarche had longer left digits (2D and 4D) and higher oestradiol, testosterone than those who had not. The high breast group had longer digits (2D and 4D), and higher oestradiol than the low breast group. With regard to pubic hair development, the high group had high 2D:4D, longer 2D and higher oestradiol, testosterone than the low group. After adjusting for oestradiol and testosterone, 4D length was positively related to occurrence of menarche. In addition, 2D and 2D:4D were significantly correlated with pubic hair development after adjusting for oestradiol, respectively.Conclusion: Prenatal hormone level may be related to the development of puberty characteristics among Chinese girls. [ABSTRACT FROM AUTHOR]

The associations between human papillomavirus (HPV) infection or hormonal exposure and cervical cancer risk are well established. However, to the best of our knowledge, the association between high endogenous estradiol levels in conjunction with HPV/HPV16 infection and the risk of cervical squamous cell carcinoma remains unknown. To investigate this, the current study conducted a matched case-control study in Shanxi Province, China, in which clinical samples were obtained from 74 females with newly diagnosed uterine cervix squamous cell carcinoma and 74 matched healthy females who were selected from 582 healthy females according to age, place of residence, marital status and menopausal status. From all participants, DNA was extracted from cells obtained from a cervical smear and serum was separated from venous blood withdrawn during days 5–8 of the menstrual cycle. HPV/HPV16 DNA and estradiol expression levels in the serum were measured by general polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Significant differences were identified in the positive HPV and HPV16 DNA expression rates between patients and controls, with odds ratios (95% confidence interval) of 3.74 (1.84–7.59) and 4.04 (1.97–8.28), respectively. Expression levels of estradiol in patients were significantly higher compared with the controls (P<0.001), however, this was only identified when the HPV16 E2 or E6 oncogene status was negative. Considering 40 ng/ml as the cut-off estradiol level, 78.38% of patients exhibited high estradiol levels, which was significantly higher than the percentage of controls (P<0.001). An additive interaction pattern was revealed between estradiol expression levels and HPV/HPV16 infection. The results suggest that among the various types of HPV, HPV16 may be most likely to cause uterine cervix squamous cell carcinoma and an abnormally high level of endogenous estradiol may further increase this risk. Therefore, estradiol therapy may represent a new treatment strategy for cases of cervical cancer associated with HPV infection. [ABSTRACT FROM AUTHOR]

Objective: To explore factors causing a premature rise in luteinizing hormone among high ovarian responders undergoing the gonadotropin-releasing hormone (GnRH) antagonist ovarian stimulation protocol.Methods: The present retrospective study included healthy women undergoing fresh cycles using a fixed GnRH antagonist protocol with a predicted high response and antral follicle count (AFC) of at least 15 at the Reproductive Medicine Center of Tongji Hospital, China, between January 1 and December 31, 2016. Treatment-related characteristics, hormone changes, and pregnancy outcomes were compared between patients who did or did not experience a premature luteinizing hormone rise.Results: There were 314 patients included; 49 experienced premature luteinizing hormone increases. Among patients who experienced a premature rise in luteinizing hormone, a lower two pronuclear embryo rate (P=0.038); fewer high-quality embryos (P=0.020); higher serum luteinizing hormone (P=0.006), progesterone (P=0.013), and estradiol (E2) levels (P=0.003) on the day of human chorionic gonadotropin administration; a lower clinical pregnancy rate (P=0.031); and a higher cancellation rate (P=0.006) were observed. AFC of at least 22 (P=0.001) and E2 of 669 pg/mL or higher at the start of GnRH antagonist administration were predictive of early (P=0.036) and late (P=0.033) premature luteinizing hormone increases.Conclusion: Earlier administration of GnRH antagonist could avoid premature luteinizing hormone increases among high ovarian responders, especially those with a starting AFC of 22 or more. [ABSTRACT FROM AUTHOR]

Background: The second-to-fourth digit ratio (2D:4D) is a marker of prenatal hormone exposure, which is negatively correlated with prenatal androgen and positively correlated with prenatal estrogen. The study was to analyze the association between 2D:4D and the first spermatorrhea to indirectly show the possible role of prenatal hormone during puberty development among boys.Method: The total of 367 boys aged 8-15 years were enrolled by using the stratified cluster sampling method. The variables of index finger (2D), ring finger (4D), height, weight, waist circumference (WC), skinfold thickness, testosterone and estradiol were measured, and the age at the first spermatorrhea was surveyed.Results: The average age at the first spermatorrhea was 12.15 years. The 2D:4D was not related to first spermatorrhea, circulating testosterone in boys (P > 0.05), however, was positively correlated with circulating estradiol (P < 0.05). The direct association (OR value) between 4D, average of index finger and ring finger (AIR) and first spermatorrhea were 2.79 and 2.29, and the mediating effect (OR value) of which were 1.95 and 2.01 by testosterone, accounting for 41.18% and 46.73% of the total effect, respectively. The 2D, MIDRL, lean body mass (LBM) were indirectly related to first spermatorrhea by testosterone, the mediating effects (OR value) were 2.11, 1.71 and 2.41, respectively.Conclusion: The prenatal androgen exposure may be directly and indirectly related to first spermatorrhea. In addition, the high prenatal estrogen exposure may be indirectly associated with first spermatorrhea by testosterone. [ABSTRACT FROM AUTHOR]

Background: Polycyclic aromatic hydrocarbons (PAHs) are a group of ubiquitous environmental pollutants. In vivo and in vitro studies have demonstrated that PAHs can alter endocrine function, yet evidence from human studies is limited.Objectives: The objective of this study was to investigate whether environmental exposure to PAHs was associated with altered reproductive hormone levels, using repeated measures of urinary OH-PAHs as biomarkers.Methods: We measured 10 monohydroxylated PAHs (OH-PAHs) in repeated urine samples from 371 men in an infertility clinic in Wuhan, China. Multivariable linear regression models were used to estimate the associations between average urinary OH-PAH levels and serum reproductive hormones, and restricted cubic spline models were further used to examine the shapes of dose-response relationships.Results: We observed dose-response associations of urinary 2-hydroxynaphthalene (2-OHNa) with decreased serum free testosterone (fT) and urinary 1-hydroxypyrene (1-OHP), 9-hydroxyphenanthrene (9-OHPh), and 9-hydroxyfluorene (9-OHFlu) with decreased serum estradiol (all P for trends <0.05). These associations were linear and significant when these four OH-PAHs were modeled as continuous variables in restricted cubic spline models. Furthermore, a U-shaped association was observed across urinary 4-OHPh levels, with lower levels of serum sex hormone-binding globulin (SHBG) at median concentrations compared with 5th and 95th percentile concentrations.Conclusion: Environmental levels of PAH exposure in our study are associated with altered reproductive hormones. However, further research is needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Objective: To explore the relationship between progesterone-follicle number (P/F) ratio and live delivery rate in patients with normal ovarian reserve undergoing cleavage-stage embryo transfer with a long gonadotropin-releasing hormone agonist cycle.Methods: The present retrospective study included data from patients younger than 38 years with normal ovarian reserve who were undergoing in vitro fertilization/intracytoplasmic sperm injection and embryo transfer at Zhongnan Hospital, Wuhan University, China, between January 1, 2009 and December 31, 2015. Patients underwent cleavage-stage fresh embryo transfer with a long gonadotropin-releasing hormone agonist cycle, and associations between P/F ratios and fertility/pregnancy outcomes were analyzed.Results: Patients with a P/F ratio of 0.11 or above had higher serum progesterone levels (P<0.001) and lower serum estradiol levels (P<0.001) on the day of human chorionic gonadotropin administration in comparison with patients with lower P/F ratios; elevated P/F ratios were also associated with fewer follicles at least 14 mm in size (P<0.001) and lower live delivery rates (P<0.001). Multiple logistic regression confirmed that P/F ratio was an independent predictor of live delivery rate (P=0.001).Conclusion: A P/F ratio of at least 0.11 was associated with lower live delivery rates in women with normal ovarian reserve undergoing cleavage-stage embryo transfer with a long gonadotropin-releasing hormone agonist cycle. [ABSTRACT FROM AUTHOR]

Objectives: To observe the effectiveness and safety of menopause-related hormone therapy (MHT) to prevent bone loss in Chinese women during the menopausal transition and early menopause, as well as to evaluate the effects of 5-year MHT on overall health to add Level I evidence for the prevention of osteoporosis using MHT.Design: This clinical study was a prospective, double-blind, randomized, parallel placebo-controlled study. Chinese women in the menopausal transition and early menopause were randomly allocated to the MHT group or the placebo group. All subjects received a 5-year intervention. The effectiveness of MHT for bone mineral density (BMD) and bone metabolism and the safety of MHT in relation to glycolipid metabolism, breast cancer, and cardiovascular disease were studied.Results: In the MHT group, women in both transition and early menopause showed a significant increase in lumbar and femoral neck BMD after the 1st year of therapy; BMD tended to decrease in the 3rd year but ultimately was sustained at stable levels that were near the baseline levels. In the placebo group, BMD decreased at both sites. Metabolism indexes and breast ultrasound examination findings did not differ significantly between the MHT and placebo groups. Three cases of breast cancer and three cases of cardiovascular disease were diagnosed during follow-up. One breast cancer case and two cardiovascular disease cases occurred in the MHT group.Conclusions: Five-year sequential therapy with estrogen and progesterone can increase or maintain the BMD of women in their menopausal transition and early menopause. This regimen had no negative effect on glycolipid metabolism and did not increase the risk of breast cancer or cardiovascular events. [ABSTRACT FROM AUTHOR]

Background. Aromatase inhibitors (AIs) are used for adjuvant therapy of breast cancer; however AIMSS (AI-Associated Musculoskeletal Symptoms) can negatively affect quality of life and compliance.Most patients in China moved to TCM (traditional Chinese medicine) for help. TB (tiger bone) is used to treat bone disease, whose main ingredients are calcium and collagen. The objective of this study was to evaluate whether the TB prevented AIMSS in postmenopausal women with ER/PR+ breast cancer. Methods. We conducted a randomized, blind, controlled study of comparing TB versus placebo for 12 weeks in postmenopausal women with breast cancer who have taken AI for less than a month. Patients completed the M-BPI, VAS, and FACT-B at baseline, 6 weeks, and 12 weeks. M-BPI and VAS were used as the primary outcomes. FACT-B was used as the secondary outcome. Serum E2 and FSH were tested every 6 weeks. Results. Of 70 evaluable cases, 8 of 35 patients (22.9%) developed new or worsening point symptoms in TB group, compared to 21 of 35 (60%) in placebo group (𝑃 < 0.001). We also found differences between 2 groups in average pain (2 to 5.6), worst pain (3.9 to 8), pain interference severity (1.9 to 5.3), stiffness (2.4 to 6.9), and joint symptom interference (1.8 to 5.7), all (𝑃 < 0.001). similar findings were seen in VAS value (3 to 6.6) at the end of intervention. HRQoL measured by FACT-B (𝑃 < 0.05) was improved. No change of serum estradiol and FSH between two groups. Conclusions. TB appeared to be effective and safe in the prevention of AIMSS. [ABSTRACT FROM AUTHOR]

Background and Objectives: The aim of this study was to explore the influence of fluoride exposure and ERα gene polymorphisms on reproductive hormone concentrations of women in accordance with endemic fluorosis residence.Methods and Study Design: A cross sectional study was conducted in Tongxu county, Henan Province, China. A total of 679 women were recruited using cluster sampling and each subject provided fasting blood and an associated urine sample. We measured the concentrations of serum gonadotropin releasing hormone (GnRH), follicle-stimulating hormone, luteinizing hormone, and estradiol and urinary fluoride.Results: In the defluoridation project group (DFPG), serum GnRH was lower in women carrying C/C genotype compared to in those carrying C/T and T/T genotypes of ERα gene rs3798577 (p<0.05). In the endemic fluorosis group (EFG), serum GnRH was lower in women carrying Pp genotype compared to in those carrying PP and pp genotypes of ERα PvuII (p<0.05). Serum GnRH in women from EFG who carried Pp, pp, Xx and xx genotypes in ERα gene PvuII and XbaI was lower than in those in the control group (CG) who carried same genotypes (p<0.05). Furthermore, serum GnRH in women from EFG was significantly lower than in those in CG, regardless of whether the women were carrying C/C, C/T or T/T genotypes of ERα rs3798577 (p<0.05). Serum estradiol concentrations in EFG were significantly lower than in CG when the women were carrying the Pp, Xx and T/T genotypes in ERα gene (p<0.05).Conclusion: Interaction of ERα gene and fluoride exposure may influence women's serum reproductive hormone concentrations. [ABSTRACT FROM AUTHOR]

Background: The role of estrogen metabolism in determining breast cancer risk and differences in breast cancer rates between high-incidence and low-incidence nations is poorly understood.Methods: We measured urinary concentrations of estradiol and estrone (parent estrogens) and 13 estrogen metabolites formed by irreversible hydroxylation at the C-2, C-4, or C-16 positions of the steroid ring in a nested case-control study of 399 postmenopausal invasive breast cancer case participants and 399 matched control participants from the population-based Shanghai Women's Health Study cohort. Odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer by quartiles of metabolic pathway groups, pathway ratios, and individual estrogens/estrogen metabolites were estimated by multivariable conditional logistic regression. Urinary estrogen/estrogen metabolite measures were compared with those of postmenopausal non-hormone-using Asian Americans, a population with three-fold higher breast cancer incidence rates. All statistical tests were two-sided.Results: Urinary concentrations of parent estrogens were strongly associated with breast cancer risk (ORQ4vsQ1 = 1.94, 95% CI = 1.21 to 3.12, Ptrend = .01). Of the pathway ratios, the 2-pathway:total estrogens/estrogen metabolites and 2-pathway:parent estrogens were inversely associated with risk (ORQ4vsQ1 = 0.57, 95% CI = 0.35 to 0.91, Ptrend = .03, and ORQ4vsQ1 = 0.61, 95% CI = 0.37 to 0.99, Ptrend = .04, respectively). After adjusting for parent estrogens, these associations remained clearly inverse but lost statistical significance (ORQ4vsQ1 = 0.65, 95% CI = 0.39 to 1.06, Ptrend = .12 and ORQ4vsQ1 = 0.76, 95% CI = 0.44 to 1.32, Ptrend = .28). The urinary concentration of all estrogens/estrogen metabolites combined in Asian American women was triple that in Shanghai women.Conclusions: Lower urinary parent estrogen concentrations and more extensive 2-hydroxylation were each associated with reduced postmenopausal breast cancer risk in a low-risk nation. Markedly higher total estrogen/estrogen metabolite concentrations in postmenopausal United States women (Asian Americans) than in Shanghai women may partly explain higher breast cancer rates in the United States. [ABSTRACT FROM AUTHOR]

Objectives: To explore the serum levels of bone resorption marker C-terminal telopeptide of type I collagen (CTX) and bone formation marker N-amino terminal propeptide of type I collagen (PINP) in Chinese women across the menopausal transition and the correlation between follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol with the bone turnover markers.Methods: A cross-sectional study was conducted on 464 healthy Chinese women, separated into pre-, peri- and postmenopausal groups based on their menstruation changes. The serum levels of CTX, PINP, FSH, LH, and estradiol were measured.Results: The serum levels of CTX and PINP were significantly higher in women in the peri- and postmenopausal groups. The serum levels of FSH were significantly correlated with the serum levels of PINP in premenopausal women. Both serum FSH and LH were positively correlated with serum CTX in perimenopausal women and postmenopausal women. Estradiol was inversely correlated with CTX in the perimenopausal group. Multiple linear regression models show the serum FSH levels were independently related to the bone turnover markers CTX and PINP.Conclusions: The elevated serum levels of FSH were independent risk factors for bone loss in peri- and postmenopausal women, and measurement of the serum FSH levels in mid-age women with irregular menses could be used in early diagnosis of postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

Despite that estradiol can reduce the risk of cardiovascular diseases in ovariectomized animals in the plains, its effect on animals at high altitude has seldom been reported. We hypothesize that estradiol can ameliorate cardiac damage to ovariectomized rats induced by chronic exposure to hypobaric hypoxia at high altitude. This study was intended to investigate whether cardiovascular magnetic resonance (CMR) imaging could reveal cardioprotective effect of estradiol on ovariectomized rats under chronic exposure to hypobaric hypoxia at high altitude. Thirty-two rats were randomized into the Control group (Plain), HH + Sham group (Hypobaric Hypoxia + Sham), HH + OVX group (Hypobaric Hypoxia + Bilateral Ovariectomy) and HH-OVX + E2 group (Hypobaric Hypoxia + Bilateral Ovariectomy + Estradiol, 50 μg/kg, 3 times a week, for 6 weeks) (n = 8 per group). Except the Control group (altitude: 500 m), rats in other groups were subcutaneously injected with 17β -estradiol or vehicle and exposed to chronic hypobaric hypoxia in Qinghai-Tibet Plateau (altitude: 4250 m), China, for 6 weeks. Biventricular cardiac function and global strain of the rats were measured by CMR and analyzed using the cine tissue tracking techniques. Biochemical tests, histopathology and electronic microscopy were used to evaluate the protective effect of estradiol on the heart tissue of ovariectomized rats exposed to a high-altitude environment. The biventricular ejection fraction and global strains decreased in the HH + OVX group compared with that in the Control group (all p < 0.05). All the aforementioned changes in the HH + OVX group ameliorated in the HH-OVX + E2 group (all p < 0.05). Estradiol also alleviated the right ventricular dilatation and hypertrophy in the HH + OVX group (all p < 0.05). In addition, histological and biochemical analyses also supported these in vivo results. Estradiol ameliorated the biventricular structural and functional damage in ovariectomized rats exposed to chronic hypobaric hypoxia at high altitude. [ABSTRACT FROM AUTHOR]

Objective: The role of estrogen in cognitive function and depressive symptoms is controversial due to discrepancies between results from randomized controlled trials (RCT) and observational studies. Mendelian randomization analysis may provide further insights concerning the role of estrogen in these outcomes as it assesses the effect of lifelong endogenous exposure but is less vulnerable to confounding than observational studies.Method: We used separate sample instrumental variable analysis to estimate the association of log 17β estradiol with cognitive function (Delayed 10 word recall, and Mini Mental State Examination (MMSE)) and depressive symptoms (Geriatric Depression Scale (GDS)) in older Chinese women of the Guangzhou Biobank Cohort Study (GBCS, n=3086). The estimate was derived based on the Wald estimator, the ratio of the association of genetic determinants (rs1008805 and rs2175898) of log 17β-estradiol with cognitive function and depressive symptoms in GBCS and the association of log 17β-estradiol with genetic determinants in the sample of young women in Hong Kong (n=236).Results: Genetically predicted 17β-estradiol was not associated with delayed 10-word recall (0.42 words per log increase in 17β-estradiol (pmol/L), 95% confidence interval (CI) -0.49 to 1.34) MMSE (0.39 per log increase in 17β-estradiol (pmol/L), 95% CI -0.87 to 1.65) or GDS (0.24 per log increase in 17β-estradiol (pmol/L), 95% CI -0.57 to 1.05).Conclusion: These results were largely consistent with evidence from RCTs and did not show any beneficial effect of estrogen on cognitive function and depressive symptoms. However, larger Mendelian randomization analyses are needed to identify any minor effects. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of recombinant human growth hormone (rhGH) on clinical outcomes of frozen-thawed embryo transfer (FET).Methods: A prospective study was conducted among 240 patients (aged ≤38years) who underwent FET cycles at a center in Hefei, China, between November 2011 and October 2012. Patients were divided into three groups on the basis of visit order: those in group A received hormone-replacement therapy (HRT) for endometrial preparation, those in group B received HRT plus simultaneous rhGH, and those in group C received rhGH on day8 of HRT.Results: Ten cycles were cancelled; 230 FET cycles were analyzed (77 in group A, 77 in group B, 76 in group C). The rates of clinical pregnancy, embryo implantation, and live birth were significantly higher in group B than in group A, as were the serum levels of estradiol and insulin-like growth factor-1 (P≤0.033 for all comparisons). Endometrial thickness and serum levels of vascular endothelial growth factor were significantly higher in group B than in groups A and C, whereas pulsatility index, resistance index, and peak systolic velocity/end diastolic velocity of the uterine arcuate artery were significantly lower (P≤0.017 for all comparisons).Conclusion: Simultaneous administration of rhGH with HRT could improve clinical outcomes after FET by increasing endometrial blood perfusion and expression of cytokines related to endometrial receptivity. [ABSTRACT FROM AUTHOR]

Objective: This study made use of the percent abdominal fat to define abdominal obesity (AbO) and examined the differential associations of general obesity (GOb) and AbO with age, metabolic and endocrine factors.Methods: Metabolic, endocrine and anthropometric factors and body composition were measured in 481 Asian men.Results: A DEXA-derived ≥25% abdominal fat (PAbdF) was used to define men with AbO. Age was directly associated with PAbdF and percent total body fat (PBF). Exercise intensity was negatively associated with PBF. Both PBF and PAbdF were associated with HDL and LDL, but have opposite correlation with triglyceride. Furthermore, both PBF and PAbdF were associated with the number of metabolic syndrome (MetS) risk factors. Men with GOb had lower levels of percent lean mass (PLM), testosterone and bioavailable testosterone, and higher insulin and glucose levels. Men with AbO had lower arm and leg fat, higher insulin levels and triglycerides.Conclusions: Men with GOb and AbO had different pattern of body composition. Age may be a contributory factor in AbO and a sedentary lifestyle may contribute to GOb. Both GOb and AbO are associated with an increased risk of MetS, with GOb more predispose to risk of diabetes, while AbO more at risk for cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The effects of parity and litter size on maternal behavior of Small Tail Han sheep was investigated at Linyi University, China. Sixty-eight ewes were observed from parturition to weaning. Continuous focal animal sampling was used to quantify the duration of maternal behaviors. Ewe feces were collected every 2 days and estradiol concentration was measured with an enzyme immunoassay kit. All lambs were weighed 24 h after parturition and again at 35 days of age. Parity increased sucking, following, grooming, low-pitched bleat, head-up and udder-refusal behavior and decreased aggressive behavior ( P < 0.01, P < 0.01, P < 0.05, P < 0.05, P < 0.05, P < 0.05, P < 0.01, respectively), and litter size showed significant effect on sucking, following and low-pitched bleat behavior ( P < 0.05, P < 0.01, P < 0.05, respectively). The lambs of multiparous ewes were significantly heavier than primiparous ewes at birth ( P < 0.01) and were significantly heavier at weaning age ( P < 0.01). Similar results were founded for birth weight and weaning weight gain in litter size ( P < 0.01, P < 0.01, respectively). Estradiol concentration in feces was higher in multiparous ewes than primiparous ewes. Parity and litter size may have effects on maternal behavior during lactation. Ewes that have 2-3 lambs may be more suitable for production of Small Tail Han sheep in China. [ABSTRACT FROM AUTHOR]

Purpose: The role of estrogen in cardiovascular health remains contested with discrepancies between findings from randomized controlled trials and observational studies. Mendelian randomization, which assesses the effect of lifelong endogenous exposure, may help elucidate these discrepancies.Methods: We used separate sample instrumental variable analysis to estimate the association of log 17β-estradiol with factors related to cardiovascular disease risk (systolic and diastolic blood pressure, lipids, fasting glucose, body mass index, waist hip ratio, and waist circumference) and Framingham score, a predictor of 10-year risk of ischemic heart disease events, in older Chinese women from the Guangzhou Biobank Cohort Study (GBCS, n = 3092). The estimate was derived using the Wald estimator, that is, the ratio of the association of genetic determinants (rs1008805 and rs2175898) of log 17β-estradiol with cardiovascular disease risk factors and Framingham score in GBCS and the association of these genetic determinants with log 17β-estradiol in a sample of young women from Hong Kong (n = 236).Results: Genetically, higher 17β-estradiol was not associated with any cardiovascular disease-related risk factor or with Framingham score (-0.01, 95% confidence interval = -1.34 to 1.31).Conclusions: Lifetime exposure to estrogen does not appear to be cardioprotective via the cardiovascular disease-related risk factors examined. [ABSTRACT FROM AUTHOR]

The intake of contaminated foods is an important exposure pathway for endocrine disrupting chemicals (EDCs). However, data on the occurrence of EDCs in foodstuffs are sporadic and the resultant risk of co-exposure is rarely concerned. In this study, 450 food samples representing 7 food categories (mainly raw and fresh food), collected from three geographic cities in China, were analyzed for eight EDCs using high performance liquid chromatography tandem mass spectrometry (HPLC–MS/MS). Besides estrone (E 1 ), other EDCs including diethylstilbestrol (DES), nonylphenol (NP), bisphenol A (BPA), octylphenol (OP), 17β-estradiol (E 2 ), 17α-ethinylestradiol (EE 2 ), and estriol (E 3 ) were ubiquitous in food. Dose-dependent relationships were found between NP and EE 2 ( r = 0.196, p < 0.05), BPA ( r = 0.391, p < 0.05). Moreover, there existed a correspondence between EDCs congener and food category. Based on the obtained database of EDCs concentration combined with local food consumption, dietary EDCs exposure was estimated using the Monte Carlo Risk Assessment (MCRA) system. The 50th and 95th percentile exposure of any EDCs isomer were far below the tolerable daily intake (TDI) value identically. However, the sum of 17β-estradiol equivalents (∑EEQs) exposure in population was considerably larger than the value of exposure to E 2 , which implied the underlying resultant risk of multiple EDCs in food should be concern. In conclusion, co-exposure via food consumption should be considered rather than individual EDCs during health risk evaluation. [ABSTRACT FROM AUTHOR]

Objective This study was designed to identify factors associated with the femoral neck bone mineral density (FNBMD) of the very elderly (aged 80 or more) Chinese males. Methods A total of 1177 very elderly Chinese males were recruited into the study, and subjected to FNBMD, biochemical parameters, bone turnover markers, and serum sex steroids assays. Univariate and multivariate regression analyses were performed to identify factors independently related to FNBMD. Results It was demonstrated that age ( β = −0.003, P = 0.035), concomitant chronic obstructive pulmonary disease (COPD, β = −0.027, P = 0.009), serum β-C-telopeptide of type 1 collagen (β-CTX, β = −0.097, P < 0.001), and parathyroid hormone (PTH, β = −0.001, P = 0.004) were negatively correlated with the FNBMD, while body mass index (BMI, β = 0.009, P < 0.001), and serum estradiol ( β = 0.001, P = 0.038) were positively related to FNBMD in very elderly Chinese males. Conclusion An integrated intervention should be implemented to increase the BMD of the very elderly males, with special attention to preventing and curing COPD, reducing serum β-CTX and PTH levels, as well as keeping a proper BMI and serum estradiol level. [ABSTRACT FROM AUTHOR]

Seventy patients with stage III or IV endometriosis were randomly assigned to 2 groups after conservative surgery. Group O (n = 35) received 3 cycles of a 28-day gonadotropin-releasing hormone agonist (GnRH-a) treatment (goserelin, 3.6 mg) starting 3-5 days postoperatively. Group M (n = 35) received the same treatment starting on days 1-5 of menstruation. Groups were further subdivided according to add-back treatment. Pre- and posttreated levels of estradiol (E2), follicle stimulating hormone (FSH), and luteinizing hormone (LH) and visual analog scale (VAS), Kupperman menopausal index (KMI), and bone mineral density (BMD) scores were recorded. The incidence of uterine bleeding was assessed. In both groups, serum levels of E2, FSH, and LH and VAS scores decreased significantly after treatment. Spotting was the most frequent bleeding pattern. During cycle 1, the bleeding time in group M was much longer that than that in group O ( P =.001), and the bleeding rate in group M was significantly higher than that in group O ( P =.024, RR = 1.185). In patients with stage III or IV endometriosis, the efficacy of GnRH-a initiated 3-5 days postoperatively was equivalent to that of GnRH-a initiated on days 1-5 of menstruation. Female patients who initiated GnRH-a treatment 3-5 days postoperatively experienced less uterine bleeding during the first cycle of treatment. [ABSTRACT FROM AUTHOR]

• 17β-Estradiol and 17α-Methyltestosterone affected the mRNA levels of sex hormone synthase Hc-Cyp17a in Hyriopsis cumingii. • Estradiol content were related to gonadal development of H. cumingii. • Hc-Cyp17a changed regularly during gonad development. • Hc-Cyp17 could play a vital role in the synthesis of sex hormones, sexual differentiation, gonadal development and functional maintenance of the H. cumingii. Estrogens and androgens that coexist in the aquatic environment could potentially affect shellfish, however, endocrine disrupting effects of them in shellfish are significant. As an important aquaculture shellfish in China, Hyriopsis cumingii has remarkable economic benefits. In this study, the effects of endocrine disrupting chemicals on the steroid synthase Hc-Cyp17a in the male and female gonads of the H. cumingii were assessed by exposing juvenile mussels to cultured waters containing 17β-Estradiol (E2) and 17α-Methyltestosterone (MT) for 28 days. At the same time, the E2 content in the four stages of gonadal development, the expression changes of Hc-Cyp17a in gonadal development and its localization in the mature gonad were measured to explore the relationship between genes and hormones. The results showed that both E2 and MT at 50 ng/L and 200 ng/L could affect the transcription level of Hc-Cyp17a , which was inhibited initially and promoted in post-development. E2 content was positively correlated with gonadal development stage, which was in mussel. By tracing the expression of Hc-Cyp17a , difference was found during different developmental periods. The expression level in ovary was higher than that in testis during gonadal development of 1/ 2/ 3-year-old mussels and showed an increasing trend with age. Furthermore, the expression levels in 6 tissues of mature individuals were measured and it showed that there was a significant difference between male and female in the gonads (p < 0.01). In situ hybridization, it suggested that Hc-Cyp17a was significantly signaled in the follicular wall and oocyte of female and in the follicular membrane of testis, respectively. These results could play a vital role in assessing and understanding the effects of aquatic environment on the endocrine system of H. cumingii. [ABSTRACT FROM AUTHOR]

Background: Mestranol is a widely used estrogen, which is converted into its active metabolite ethinyl estradiol by cytochrome P450 (CYP) 2C9. To comprehensively examine the enzymatic activity of reported CYP2C9 variants in Chinese individuals in response to mestranol, wild-type CYP2C9*1 and 35 allelic variants were highly expressed in Sf21 insect cell microsomes and used for the detection of their enzymatic values in vitro. These results showed that the majority of tested variants exhibited decreased clearance values compared to wild type, except for CYP2C9*40 and *36. Method: Insect microsomes expressing the 36 CYP2C9 variants were incubated with 0.25-8 μmol/l mestranol for 30 min at 37°C. Then, the production of the metabolite of mestranol, ethinyl estradiol, was analyzed using high-performance liquid chromatography. Results: Most CYP-catalyzed reactions were sufficiently described by classical Michaelis-Menten kinetic parameters (e.g., Km and Vmax), while 9 variants exhibited atypical or non-Michaelis-Menten kinetic values, which were largely due to the self-inhibitory effectin response to mestranol. Conclusion: This is the first report of these rare alleles for mestranol metabolism, which provides fundamental data for further clinical studies on CYP2C9 alleles for mestranol metabolism. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the effect of polycystic ovary syndrome (PCOS) on the association of aromatase activity assessed by estradiol-to-testosterone ratio (E2/T) with body mass index (BMI) in women. Methods: This was a cohort study in five centers for reproductive medicine in China. Data were collected from July 2012 to December 2013. PCOS patients (n = 785) and non PCOS, healthy, age-matched controls (n = 297) were included. Plasma sex hormones including estradiol (E2), testosterone (T), follicle stimulating hormone (FSH), and luteinizing hormone (LH) were measured by ELISA, together with BMI and E2/T being calculated, on the third day of the menstrual cycle. Aromatase activity in PCOS patients with different BMI, T and E2 levels were compared. Results: E2/T was significantly lower (P < 0.05) while BMI was significantly increased (P < 0.05) in PCOS than non-PCOS. No significant difference was observed in E2/T among different BMI subgroups of either PCOS or control. Ovarian aromatase activity was decreased in PCOS patients which was independent of BMI. Hyperestrogen promoted ovarian aromatase activity, while hyperandrogen inhibited such activity, both in a dose-dependent, biphasic manner. Conclusions: Ovarian aromatase activity was lower in PCOS, which was independent of BMI. New therapeutic strategies can be developed by targeting aromatase activity for treating PCOS women, especially those with obesity. [ABSTRACT FROM AUTHOR]

Objective. To explore the effects of puerarin to treat endometriosis (EMT) model rats and the possible regulatory mechanisms. Methods. EMT model rats were surgically induced by autotransplantion of endometrial tissues. The appropriate dosage of puerarin to treat EMT model rats was determined by observing the pathologic morphology of ectopic endometrial tissues and by detecting the levels of estradiol (E2) and prostaglandin E2 (PGE2) of both serum and ectopic endometrial tissues. The related genes and proteins of ectopic endometrial tissues were analyzed by Real-time PCR and immunohistochemistry (IHC) to explore the possible mechanisms. Results. Puerarin could reduce the levels of E2 and PGE2 and prevent the growth of ectopic endometrium tissues by inhibiting the expression of aromatase cytochrome P450 (p450arom) and cyclooxygenase-2 (cox-2); puerarin could adjust the anabolism of E2 by upregulating the expression of 17β-hydroxysteroid-2 (17β-hsd-2) and downregulating the expression of 17β- hydroxysteroid-1 (17β-hsd-1) of the ectopic endometrium tissues; puerarin could increase the expression of ERβ and improve the inflammatory microenvironment of EMT model rats. Conclusions. Our data suggest that puerarin has a therapeutic effect on EMT model rats and could be a potential therapeutic agent for the treatment of EMT in clinic. [ABSTRACT FROM AUTHOR]

Aim To report on six cases of the diagnosis and treatment of patients with complete androgen insensitivity syndrome ( CAIS) and a review of the relevant published work. Methods A retrospective analysis was performed on the clinical features, diagnosis and treatment of a total of six patients with CAIS who were admitted to our hospital between September 1985 and June 2012. All surgical patients were examined for sex chromosomes and sex hormone levels pre- and postoperatively, respectively, and underwent lower abdominal B ultrasounds and pathological examinations among other tests. Results Five of the patients were treated with castration, one patient aged 5 years was treated conservatively Tissue from surgical resections showed normal testicular tissue that comprised Leydig cells and Sertoli cells, and pathological examinations showed no sign of testicular cancer. Following corrective operations, postoperative complications, such as female secondary sexual characteristics, stagnation and osteoporosis, have not developed. Sex hormone level ratio changed significantly after being treated with castration compared with preoperative levels; mainly testosterone and estrogen decreased significantly ( P < 0.05), while luteinizing hormone and follicle-stimulating hormone significantly increased ( P < 0.05). However, prolactin did not change significantly ( P > 0.05). Conclusion The study show that removal of the testes in CAIS patients after puberty is safe and reliable. Meanwhile, it is essential to provide a hormone drug after being treated with castration. Further studies are needed to evaluate the safety and the quality of life for CAIS patients. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives The role of estrogens among men has rarely been explicitly considered. We examined differences in total, free, and bioavailable estradiol (Bio E) between young men from the United States (US) and the most economically developed part of China, that is, Hong Kong (HK). Methods Cross-sectional analysis was conducted based on 365 young men from the Third National Health and Nutrition Examination Survey in the US and 299 young Chinese men. All participants were aged from 18 to 29 years. Main outcome measures were total estradiol (E2) and calculated Bio E and free estradiol (FE). Results In both young US and Chinese men, E2 concentrations peaked at ages 25-29 years, at 43.3 pg/ml [95% confidence interval (CI) 41.9-44.8] in US men and 29.0 pg/ml (95% CI 26.2-32.0) in Chinese men. After adjustment for age and ethnicity, in all participants, US men had higher average concentrations of E2 [39.0 (95% CI 38.6-39.4) versus 28.3 (95% CI 28.3-28.4) pg/ml], FE [72.9 (95% CI 72.7-73.7) versus 56.8 (95% CI 56.6-56.9) ng/dl], and Bio E [17.9 (95% CI 17.7-18.1) versus 14.9 (95% CI 14.8-14.9) pg/ml] than HK men. Further adjustment for height or body mass index did not change the results. Conclusions Estradiol, and free and Bio E concentrations are much lower in young healthy Chinese men than US men. However, these findings based on comparison between the two assays in the two different locations need further confirmation. Am. J. Hum. Biol. 26:565-569, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Previous studies showed that Danggui-Shaoyao-San (DSS), a traditional Chinese medicinal prescription, could alleviate cognitive dysfunction of Alzheimer's disease (AD) patients. However, the mechanisms remain unclear; we have now examined the effect of DSS on SAMP8 and elucidated the possible mechanism. Animals were treated with DSS for 2 months, and step-down test and Morris water maze (MWM) test were used to evaluated cognitive abilities. The estradiol (E2), NO, and glycine in blood plasma or in hippocampus were detected to explore the possible mechanisms. The latency of SAMP8 in step-down test was shorter than that of age-matched SAMR1, and DSS increased the latency especially in female animals. In MWM test, we got similar results; SAMP8 spent more time to find the platform, and DSS decreased the time before finding the platform, with little effect on swim velocity, during the training sessions. During test session, DSS increased the time spent in target quadrant especially in female SAMP8. In female SAMP8, plasma E2, NO, and glycine were elevated in plasma or hippocampus tissue. In conclusion, DSS could ameliorate deterioration of cognition in SAMP8, especially in female animals. Increasing E2, NO, and glycine might contribute to the cognitive improvement effect of DSS in female SAMP8. [ABSTRACT FROM AUTHOR]

Simple Summary: Pelodiscus sinensis is an important aquatic economic species in China with sexual dimorphism. All-male breeding is becoming a research hotspot. Here, comparative transcriptome analyses of female, male, and pseudo-female gonads were performed. We found that the differences between males and pseudo-females were mainly related to steroid hormone synthesis at the transcriptome level. When it comes to the sox family genes, sox3 may have a role in the process of sex reversal from male to pseudo-female, when sox8 and sox9 were inhibited by exogenous estrogen. The Chinese soft-shelled turtle Pelodiscus sinensis shows obvious sexual dimorphism. The economic and nutrition value of male individuals are significantly higher than those of female individuals. Pseudo-females which are base to all-male breeding have been obtained by estrogen induction, while the gene function and molecular mechanism of sex reversal remain unclear in P. sinensis. Here, comparative transcriptome analyses of female, male, and pseudo-female gonads were performed, and 14,430 genes differentially expressed were identified in the pairwise comparison of three groups. GO and KEGG analyses were performed on the differentially expressed genes (DEGs), which mainly concentrated on steroid hormone synthesis. Furthermore, the results of gonadal transcriptome analysis revealed that 10 sex-related sox genes were differentially expressed in males vs. female, male vs. pseudo-female, and female vs. pseudo-female. Through the differential expression analysis of these 10 sox genes in mature gonads, six sox genes related to sex reversal were further screened. The molecular mechanism of the six sox genes in the embryo were analyzed during sex reversal after E2 treatment. In mature gonads, some sox family genes, such as sox9sox12, and sox30 were highly expressed in the testis, while sox1, sox3, sox6, sox11, and sox17 were lowly expressed. In the male embryos, exogenous estrogen can activate the expression of sox3 and inhibit the expression of sox8, sox9, and sox11. In summary, sox3 may have a role in the process of sex reversal from male to pseudo-female, when sox8 and sox9 are inhibited. Sox family genes affect both female and male pathways in the process of sex reversal, which provides a new insight for the all-male breeding of the Chinese soft-shelled turtle. [ABSTRACT FROM AUTHOR]

Paeonia lactiflora Pallas (PL) and Poria cocos Wolf (PC) have been traditionally used to treat inflammatory diseases reported in Dongui Bogam and Shen Nong Ben Cao Jing, traditional medical books in Korean and China, respectively. We determined the efficacies and the molecular mechanisms of PL, PC, and PL + PC aqueous extracts on androgenetic alopecia (AGA) induced by testosterone propionate in C57BL/6 mice. The molecular mechanisms of PL and PC in AGA treatment were examined using experimental assays and network pharmacology. The AGA model was generated by topically applying 0.5% testosterone propionate in 70% ethanol solution to the backs of mice daily for 28 days while the normal-control (Normal-Con; no AGA induction) mice applied 70% ethanol. The 0.1% PL (AGA-PL), 0.1% PC (AGA-PC), 0.05% PL + 0.05% PC (AGA-MIX), and 0.1% cellulose (AGA-Con; control) were supplemented in a high-fat diet for 28 days in AGA-induced mice. Positive-control (AGA-Positive) were administered 2% finasteride daily on the backs of the AGA mice. Hair growth rates decreased in the order of AGA-PL, AGA-MIX, AGA-PC, AGA-Positive, and AGA-Con after 21 days of treatment (ED21). On ED28, skins were completely covered with hair in the AGA-PL and AGA-MIX groups. Serum testosterone concentrations were lower in the AGA-PL group than in the AGA-Con group and similar to concentrations in the Normal-Con group, whereas serum 17β-estradiol concentrations showed the opposite pattern with increasing aromatase mRNA expression (p < 0.05). In the dorsal skin, DKK1 and NR3C2 mRNA expressions were significantly lower, but TGF-β2, β-Catenin, and PPARG expressions were higher in the AGA-PL and AGA-PC groups than in the AGA-Con group (p < 0.05), whereas TNF-α and IL-6 mRNA expressions were lower in the AGA-PL, AGA-MIX, and Normal-Con groups than in the AGA-Con group (p < 0.05). The phosphorylation of Akt and GSK-3β in the dorsal skin was lower in AGA-Con than normal-Con, and PL and MIX ingestion suppressed their decrease similar to the Normal-Con. In conclusion, PL or PL + PC intake had beneficial effects on hair growth similar to Normal-Con. The promotion was related to lower serum testosterone concentrations and pro-inflammatory cytokine levels, and inhibition of the steroid hormone pathway, consistent with network pharmacology analysis findings. [ABSTRACT FROM AUTHOR]

Abstract: Temporal variations in estradiol-17β (E2) and testosterone (T) levels from initiation to partially spent stages of Fujian oyster, Crassostrea angulata from China were investigated by enzyme-linked immunosorbent assay. E2 concentration varying between 95.97 and 280.98pg/g wet weight in the female gonads was higher than that in the male gonads (P <0.05), while T concentration ranging from 16.06 to 30.09pg/g wet weight in the male gonads was higher than that in the female gonads (P <0.05). Both steroids increased during sexual maturation in females and males respectively, and then decreased markedly after spawning. These findings indicated that the fluctuations in the levels of both steroids were closely related to the reproductive cycle, thus E2 and T could have a role as endogenous modulators in sex determination, development and maturation of C. angulata. In addition, a full-length cDNA (3161bp) encoding a peptide of 744 amino acids of estrogen receptor (ER) from C. angulata was obtained and the similarities of its deduced amino acid sequence to these of other molluscan species were more than 60%. caER mRNA transcript was most abundantly expressed in ovary (P <0.05) and in situ hybridization revealed that the distribution of this gene was expressed exclusively in “auxiliary cells” of ovary. Similar to the variation trends of E2, the expression of caER in the ovary continuously increased from initiation to ripeness stages (P <0.05), and then decreased sharply to the lowest level in the partially spent stage (P <0.05), whereas the caER mRNA transcript of male oyster in the testis maintained a relatively stable low level during the reproductive cycle. These findings suggested that ER may play an important role in the gonad development of oysters. [Copyright &y& Elsevier]

To investigate the effects of electroacupuncture (EA) on serum FSH, E2, and LH levels, women with primary ovarian insufficiency (POI) were treated with EA once a day, five times a week for the first four weeks and once every other day, three times a week, for the following two months, and then were followed up for three months. Serum E2, FSH, and LH levels were measured at baseline, at the end of treatment, and during followup. A total of 11 women with POI were included in this prospective consecutive case series study. Compared with baseline, patients' serum E2 increased, FSH decreased, and LH decreased (P = 0.002, 0.001, and 0.002, resp.) after EA treatment, and these effects persisted during followup. With treatment, 10 patients resumed menstruation (10/11, 90.91%), whereas one patient remained amenorrhea. During followup, two patients, including the one with amenorrhea during treatment, reported absence of menstruation. Temporary pain occurred occasionally, and no other adverse events were found during treatment. The results suggest that EA could decrease serum FSH and LH levels and increase serum E2 level in women with POI with little or no side effects; however, further randomized control trials are needed. [ABSTRACT FROM AUTHOR]

Estrogens protect the vascular system in women, but its effect in men is unclear. We evaluated the impact of estrogen on the male cardiovascular system. Of 140 Chinese males, 55 (aged 61.2 ± 3.5) were cases and 60 (aged 59.5 ± 4.6) were controls. Compared with the control group, only serum estradiol ([E2]; P < .01) levels but not testosterone ([T]; P = .21) were significantly lower in the cases. Linear and multiple regression analysis showed that serum T was positively associated with triglycerides ([TG]; r = .439, P < .01) and d-dimer (r = .258, P < .05) but negatively associated with high-density lipoprotein cholesterol (HDL-C) levels (r = −.267, P < .05) and C-reactive protein (CRP; r = −.214, P < .05). Estradiol was highly associated with TG (r = .783, P < .01) and HDL-C (r = .515, P < .01) but was negatively related with low-density lipoprotein cholesterol (LDL-C; P < .05), total cholesterol/HDL-C (P < .05), CRP (P < .01), and d-dimer (P < .01). In conclusion, serum E2 and T levels affect coronary heart disease risk factors in males. [ABSTRACT FROM PUBLISHER]

Summary: Differential osteogenic potential and responsiveness to 17β-estradiol (E2) of mesenchymal stem cells (MSCs) were found between postmenopausal women with osteoporosis (OP) and osteoarthritis (OA). These results suggest differential biological mechanisms of estrogen deficiency in regulation of bone remodeling between OP and OA. Introduction: OP and OA are two common disorders in postmenopausal women. The inverse relationship has been suggested between OP and OA, but their mechanisms that relate to estrogen deficiency are not fully understood. The aim of this study was to compare the differential responsiveness to E2 of MSCs from osteoporotic versus osteoarthritic donors. Methods: Twenty postmenopausal patients, ten with osteoporotic hip fractures and ten with hip osteoarthritis, were included into this study. MSCs were derived from cancellous bones of femoral heads from OA and OP donors and cultured in osteogenic and adipogenic medium with or without E2 added. The alkaline phosphatase (ALP) activity, calcium content, calcified nodules, lipid droplets, messenger RNA (mRNA) expression of ALP, osteocalcin (OC), collagen 1α (COL1α), peroxisome proliferators-activated receptor γ2 (PPARγ2) and lipoprotein lipase (LPL) were measured and compared between two groups with OP and OA. Results: In osteogenic medium, ALP activity, calcium content and mRNA expression of OC and COL1α in MSCs from OA were significantly higher than those from OP group. In adipogenic condition, there was no significant difference in lipid droplets formation and mRNA expression of PPARγ2 and LPL between OP and OA groups. With E2 added in osteogenic medium, ALP activity, calcium content and OC mRNA were significantly higher in OP group than in OA group, whereas E2 had no significant effect on lipid droplet formation and mRNA expression of PPARγ2 and LPL. Conclusion: Differential osteogenic potential and responsiveness to E2 of MSCs were found between postmenopausal women with OP and OA. These results may provide information for clinical application of MSCs in the differential setting of estrogen deficiency. [ABSTRACT FROM AUTHOR]

The cortex of Eucommia ulmoides Oliver is widely used to treat kidney deficiency in traditional Chinese medicine. Its leaves have recently been reported to have anti-obesity properties in metabolic syndrome-like rat models. Due to a sharp decline in estrogen production, obesity, together with osteoporosis, are common problems in postmenopausal women. In this study, we examined the potential effect of Eucommia leaf extract (ELE) in preventing osteoporosis and obesity induced by ovariectomy (OVX). Forty-six female Wistar rats were divided into six groups: Sham-Cont, OVX-Cont, and four OVX groups administered estradiol and different concentrations of ELE 1.25%, ELE 2.5%, and ELE 5%. Treatments were administered after ovariectomy at six weeks of age and continued for 12 weeks. OVX induced a significant decrease in the bone mineral density (BMD) of the lumbar, femora, and tibiae, together with a marked increase in body mass index (BMI). The administration of 5% ELE led to a significant increase in tibial and femoral BMD, as well as significantly increased bone-strength parameters when compared with OVX-Cont rats. According to the suppressed Dpd and increased osteocalcin concentrations in ELE 5% rats, we suggest that varying proportions of bone formation and bone absorption contributed to the enhanced BMD in the femora and tibiae. In addition, significant decreases in body weight, BMI and fat tissue in 5% ELE rats were also observed. These results suggest that ELE may have curative properties for BMD and BMI in OVX rats, and could provide an alternative therapy for the prevention of both postmenopausal osteoporosis and obesity. [ABSTRACT FROM AUTHOR]