Estrogen Group Research Articles

Yeast Hydrolysate and Postmenopausal Osteoporosis

We used an ovariectomy (OVX) rat model to test whether yeast hydrolysate (YH) has therapeutic effects on postmenopausal osteoporosis-induced bone loss. The rats were separated into five treatment groups: the sham group (sham operation); the control group (no treatment after OVX); the estrogen group (estrogen treatment after OVX); YH 0.5% group (drinking water supplementation with 0.5% YH after OVX); and the YH 1% group (drinking water supplementation with 1% YH after OVX). In addition, the YH treatment restored serum testosterone concentration in the OVX rats up to the normal level. Further, YH treatment affected bone markers; a significant increase in serum calcium concentration was observed after adding YH to the diet. The levels of serum alkaline phosphatase, osteocalcin, and cross-linked telopeptides of type I collagen were reduced by YH supplementation, unlike those in the no-treatment control. Although not statistically significant, YH treatment in OVX rats improved trabecular bone microarchitecture parameters. These results show that YH may ameliorate the bone loss caused by postmenopausal osteoporosis because of the normalization of serum testosterone concentration.

The relationship between estrogen and subsequent growth restriction among adolescents with heavy menstrual bleeding at menarche.

We sought to evaluate the impact of estrogen-containing treatment for heavy menstrual bleeding (HMB) on subsequent height compared to progesterone-only or non-hormonal treatment when initiated at menarche. We performed a retrospective chart review of adolescent females aged 10-15 years who presented to an institution-affiliated outpatient, inpatient, or emergency setting for management of HMB within three months of menarche. Growth records over a 2 year period starting at menarche were recorded, and comparisons made among patients treated with 1) estrogen, 2) progesterone, and 3) non-hormonal methods (controls). Groups were compared using bivariate analysis with Chi-square or Fisher's exact test and linear regression. In an analysis of 80 patients at 24months, the mean increase in height from menarche was 6.4cm among controls (n=54), 7.2cm among the progesterone-only group (n=10), and 3.8cm among the estrogen group (n=16). The estrogen group's increase in height was significantly lower than the control group's, by a mean of 1.8cm (p=0.04). Change in height did not differ significantly between the progesterone and control groups (p=0.87). Additionally, for every year younger at menarche, there was 1 fewer cm of growth (change in height) at 24months after menarche (p<0.002). Estrogen-containing treatment for HMB initiated within three months of menarche was associated with reduced growth at 24months compared to progesterone-only or non-hormonal methods. The clinical applicability of the estrogen group's 1.8cm absolute reduction in height may have considerable significance for those who are shorter at baseline.

The effect of oestrogen dose and duration in programmed frozen cycles on obstetric outcomes and placental findings

Research questionDoes programmed frozen embryo transfer (FET) with high-dose oestrogen affect obstetric outcomes and placental findings? DesignA retrospective cohort of live singleton deliveries at a single institution between 2009 and 2017, including deliveries attained by IVF with programmed FET; oocyte recipients were excluded. High-dose oestrogen was defined as a daily dose >6 mg throughout treatment. All placentas were evaluated regardless of complication status and the Amsterdam classification was used to analyse findings. ResultsA total of 57 deliveries in the high-dose oestrogen group were compared with 274 controls. The high-dose oestrogen group displayed significantly longer duration of oestrogen treatment (18.8 ± 4.9 versus 13.3 ± 2.7 days, P < 0.001), total cumulative oestrogen dose (149.7 ± 46.1 versus 80.3 ± 16.8 mg, P < 0.001) and lower endometrial thickness (8.5 ± 1.4 versus 9.8 ± 1.7 mm, P < 0.001). After adjustment for confounders, higher dose oestrogen was found to be associated with a lower average birthweight (coefficient –252.4 g, 95% confidence interval [CI] –483.5 to –21.2), a higher rate of low-birthweight neonates (adjusted odds ratio [aOR] 4.88, 95% CI 1.05 to 22.57), bilobated placentas (aOR 3.36, 95% CI 1.04 to 10.89), accessory lobes (aOR 8.74, 95% CI 1.24 to 61.5), accelerated villous maturation (aOR 2.06, 95% CI 1.09 to 3.87), retroplacental haematoma (aOR 5.39, 95% CI 1.11 to 26.13) and maternal malperfusion lesions (aOR 1.46, 95% CI 1.04 to 2.05). ConclusionA higher daily oestrogen dose in programmed FET is associated with low birthweight and placental changes, although this may relate to altered endometrial properties and not to the treatment itself.

Menopausal hormone therapy and the risk of cataracts in postmenopausal women in South Korea.

Postmenopausal women have a higher prevalence of cataracts than men of a similar age. This study aimed to evaluate the effects of menopausal hormone therapy (MHT) on lens opacities in postmenopausal women. This retrospective cohort study analysed population-based health insurance data in South Korea collected from 2002 to 2019. To determine the risk factors associated with cataract, postmenopausal women (N= 2,506,271) were grouped according to post-MHT use. The treatment group was further divided into the following subgroups: tibolone, combined oestrogen plus progestin by manufacturer, oral oestrogen, combined oestrogen plus progestin by physician and topical oestrogen groups. The main outcome measure was the prevalence of cataracts. The control group comprised 463,151 postmenopausal women who had never used MHT after menopause, while the treatment group included 228,033 postmenopausal women who had used MHT continuously for at least 6months. The treatment group had a higher incidence of cataracts than the control group based on Cox proportional hazards ratio analysis. Low socioeconomic status and high parity were identified as risk factors for cataracts, and reduced risk of cataracts was associated with living in rural areas and drinking alcohol. Women undergoing post-MHT, including tibolone, had a higher incidence of cataracts. Cataract development should be a concern when examining postmenopausal patients using MHT.

Microablative fractional radiofrequency for sexual dysfunction and vaginal Trophism: A randomized clinical trial

ObjectivesTo evaluate Microablative Fractional Radiofrequency (MAFRF) as a possible option in treating vaginal atrophy. MethodsThis was a randomized, controlled clinical trial with postmenopausal women diagnosed with vaginal atrophy. The treatment consisted of three sessions of MAFRF, compared to vaginal estrogen administration and an untreated control group. Assessments occurred at baseline and 90 days. The primary endpoints were sexual function, evaluated by the Female Sexual Function Index (FSFI), and vaginal health, assessed by the Vaginal Health Index (VHI). Secondary outcomes included vaginal microbiota composition (Nugent score) and epithelial cell maturation (Maturation Value ‒ MV). ResultsOne hundred and twenty women (40 in each group) were included. Concerning the FSFI, both groups, MAFRF (median 4.8 [3.6‒6.0]) and vaginal estrogen (mean 4.7 ± 1.1), experienced improved sexual desire when compared to the control group (median 3.6 [2.4‒4.8]). Regarding the total score of VHI, the authors observed an improvement in the mean of the MAFRF (23.7 ± 2.0) and vaginal estrogen groups (23.5 ± 1.9) when compared to the control (14.8 ± 2.9). The Nugent score was reduced in the MAFRF and estrogen groups (p < 0.01) compared to the control group. Lastly, the MV was modified after treatment with MAFRF (p < 0.01) and vaginal estrogen (p < 0.001). No differences existed between the MAFRF and vaginal estrogen groups in the studied variables. No adverse effects were reported following the MAFRF protocol. ConclusionsRadiofrequency was comparable in efficacy to estrogen administration for treating vulvovaginal atrophy. It deserves consideration as a viable option in managing this condition.

Pseudotargeted metabolomics analysis of pine pollen intervention in the liver of premature ovarian failure rats

Premature ovarian failure (POF) is a prevalent gynecological disease. In traditional Chinese medicine, it is believed that POF is directly related to abnormal function of the liver and kidneys. As such, regulation of the liver metabolism through the use of medicinal and edible substances is important for the treatment of POF. Pine pollen, a traditional Chinese medicinal and edible pollen variety, contains various active substances, such as sex hormones and phytohormones, which have been used to inhibit inflammation, regulate the immune system, and protect reproductive tissues. Using ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-MS/MS), this study examined the influence of pine pollen on the liver metabolome of cyclophosphamide-induced POF model Sprague Dawley (SD) rats. The variations in the metabolites present in the liver tissue of control SD rats, model SD rats, and SD rats treated with various doses of pine pollen or estrogen were analyzed using principal component analysis (PCA) in combination with orthogonal partial least squares discriminant analysis (OPLS-DA) and other multivariate statistical methods to reveal the mechanism of pine pollen intervention in the livers of POF SD rats. An animal model experiment was conducted using six groups of ten-week-old rats. Cyclophosphamide was administered intraperitoneally to the model group and four intervention groups at a dosage of 60 mg/kg for 1 d followed by a dosage of 10 mg/kg for 14 d. Within the following four weeks, each of the four intervention groups received the intragastric administration of 0.1, 0.5, or 1.5 g/kg bodyweight (BW) of pine pollen, or 0.075 g/kg BW of conjugated estrogens (positive control). Equal quantities of normal saline were administered to the control and cyclophosphamide-treated model groups. Subsequently, the rat livers were subject to pseudotargeted metabolomics, and a total of 687 liver metabolites were discovered using both positive and negative ions. The metabolites differing in content were screened using the t-test (p<0.05) and the fold change (FC>2 or <0.5) in univariate analysis, and the variable importance in projection (VIP>1) in multivariate analysis. It was found that in comparison with the control group, the contents of 32 metabolites significantly increased, while those of 28 metabolites significantly decreased in the model group. The majority of these metabolites were involved α-linolenic acid metabolism, vitamin B6 metabolism, and purine metabolism, along with the lysine degradation and glycolysis/gluconeogenesis metabolic pathways. Compared with the cyclophosphamide-induced model group, the estrogen group exhibited increased levels of 47 metabolites and decreased levels of 29 metabolites, wherein 34 metabolites were restored to the levels found in the control group. These metabolites mainly involved the vitamin B6, lysine, glycolysis/gluconeogenesis, arginine and proline, and cysteine and methionine metabolic pathways. In the low/medium/high-dose pine pollen groups, the contents of 34/32/34 metabolites increased, the contents of 30/37/24 metabolites decreased, and the contents of 47/38/34 metabolites were restored to the levels found in the control group, respectively. These metabolites were mainly involved in vitamin B6 metabolism, purine metabolism, and the glycolysis/gluconeogenesis metabolic pathway. These results therefore indicate that the restoring effect of pine pollen is equivalent or superior to that of conjugated estrogen. Additionally, based on the known metabolic pathways, it appears that when estrogen interferes with the liver metabolism, the key metabolic pathways that become affected are the arginine and proline metabolism and cysteine and methionine metabolism pathways. In contrast, pine pollen intervention affected existing metabolic pathways that were known to be disordered by cyclophosphamide. The use of pine pollen may therefore restore the levels of many metabolites. It should be noted that 23 overlaps exist between the estrogen-restored metabolites and the pine pollen-restored metabolites, including a variety of acylcarnitines, such as ACar 10∶0. As a result, pine pollen extract may be able to normalize the liver metabolic abnormalities induced by POF. This study therefore establishes a theoretical reference for the development of functional applications for pine pollen and for the treatment of POF.

Comparison of the effect of licorice vaginal cream and estrogen vaginal cream on sexual function of postmenopausal women: An RCT.

Menopause is a stage in woman's life that some women experience in middle age and some at a younger age (premature menopause). Low levels of ovarian hormones, during menopause can lead to various complications. Menopause is one of the factors that can affect a woman's sexual function. The present study was conducted to compare the effect of licorice vaginal cream and estrogen vaginal cream on the sexual function of postmenopausal women. In this randomized clinical trial study, 82 postmenopausal women who were referred to health centers in Ilam, Iran from July to November 2020 were randomly divided into 2 groups (n = 41/each). One group was given estrogen vaginal cream 2%, and the other vaginal licorice cream 2%. Participants used the 2 medications for 14-day periods each. We used the finite randomization method. Data collection questionnaires, including a demographic information questionnaire before treatment and a female sexual function index questionnaire were completed before, one month after the medication, and 2 months after using the medication. The mean score of sexual function in the licorice group was 17.86 4.37 and increased to 20.31 4.63 at the end of the study. The mean score of sexual function in the estrogen group was 17.14 3.99 and increased to 22.97 5.09 at the end of the study (p = 0.015). The effect of estrogen vaginal cream on the sexual function of postmenopausal women was greater than licorice vaginal cream.

Menopausal hormone therapy and the risk of cataract in postmenopausal women in South Korea

AbstractPurpose: Postmenopausal women have a higher prevalence of cataract than similar‐aged men. This study aimed to evaluate the effects of menopausal hormone therapy on lens opacity in postmenopausal women.Methods: This retrospective cohort study analysed population‐based health insurance data in South Korea collected from 2002 to 2019. To determine the risk factors associated with cataract, postmenopausal women (N = 2 506 271) were grouped according to postmenopausal hormone therapy use. The treatment group was further divided into the following subgroups: tibolone, combined oestrogen plus progestin by manufacturer, oral oestrogen, combined oestrogen plus progestin by physician, and topical oestrogen groups. The main outcome measure was the prevalence of cataract.Results: The control group comprised 463 151 postmenopausal women who had never used menopausal hormone therapy after menopause, while the treatment group included 228 033 postmenopausal women who had used menopausal hormone therapy continuously for at least 6 months. The treatment group had a higher incidence of cataract than the control group based on Cox proportional hazards ratio analysis. Low socioeconomic status and high parity were identified as risk factors for cataract, and reduced risk of cataract was associated with living in rural areas and drinking.Conclusions: Women undergoing postmenopausal hormone therapy, including tibolone, had a higher incidence of cataract than those who were not. Old age, low socioeconomic status, and high parity were risk factors for cataract. Our findings may help physicians identify postmenopausal women at a greater risk of developing cataract.

Rapid AOP Method for Estrogens Removal via Persulfate Activated by Hydrodynamic Cavitation

The production and use of manufactured chemicals have risen significantly in the last few decades. With interest in preserving and improving the state of the environment, there is also growing interested in new technologies for water purification and wastewater treatment. One frequently discussed technological group is advanced oxidation processes (AOPs). AOPs using sulphur-based radicals appear to reduce the volume of organic contaminants in wastewater significantly. The use of persulfate has excellent potential to successfully eliminate the number of emerging contaminants released into the environment. The main disadvantage of sulphur-based AOPs is the need for activation. We investigated an economically and environmentally friendly solution based on hydrodynamic cavitation, which does not require heating or additional activation of chemical substances. The method was evaluated for emerging contaminant removal research, specifically for the group of steroid estrogens. The mixture of estrone (E1), 17β-estradiol (E2), estriol (E3), and 17α-ethinylestradiol (EE2) was effectively eliminated and completely removed during a treatment that lasted just a few seconds. This novel method can be used in a broad spectrum of water treatment processes or as the intensification of reactions in chemical engineering technologies.

Association of Vaginal Estradiol Tablet With Serum Estrogen Levels in Women Who Are Postmenopausal

Half of women who are postmenopausal have genitourinary discomfort after menopause. Recommended therapies include low-dose vaginal estrogen. Individuals with a history of breast cancer or venous thromboembolism may have concerns about the safety of this intervention. To compare serum estrogen concentrations with the use of vaginal estrogen, 10 μg, tablet vs placebo in women who are postmenopausal. This is a secondary, post hoc analysis of data from a randomized clinical trial of treatment for moderate to severe genitourinary syndrome in women who are postmenopausal. The study was conducted at Kaiser Permanente Washington Health Research Institute and the University of Minnesota from April 11, 2016, to April 23, 2017. Measurements and data analysis were performed from November 3, 2020, to September 23, 2022. Participants were randomly assigned to vaginal estradiol tablet (10 μg/d for 2 weeks and then twice weekly) plus placebo gel (3 times weekly) or dual placebo for 12 weeks. In this post hoc analysis, baseline and week 12 serum estradiol, estrone, and sex hormone-binding globulin (SHBG) concentrations were measured by a chemiluminescent assay. Week 12 values of the 3 analytes were compared by baseline participant characteristics. Linear models compared week 12 estradiol concentrations between treatment groups, adjusted for baseline characteristics. A total of 174 women, mean (SD) age 61 (4) years, were included. Those in the estrogen group (n = 88) were more likely to have higher geometric mean (SD) week 12 serum estradiol concentrations (4.3 [2.2 pg/mL]) than those in the placebo group (n = 86) (3.5 [2.1] pg/mL) (P = .01). Adjusted for pretreatment hormone concentrations, age, clinical site, and body mass index, assignment to the estrogen vs placebo treatment group was significantly associated with higher week 12 estradiol concentrations (23.8% difference; 95% CI, 6.9%-43.3%). Most (121 of 174 [69.5%]) participants had enrollment serum estradiol concentrations higher than 2.7 pg/mL. Of women starting treatment at estradiol levels lower than or equal to 2.7 pg/mL, 38.1% (8 of 21) in the estrogen group and 34.4% (11 of 32) in the placebo group had estradiol concentrations higher than 2.7 pg/mL after 12 weeks of study participation (P = .78). Treatment assignment was not associated with week 12 estrone or SHBG concentrations. In this secondary analysis of a randomized clinical trial, a significant, although small, increase in serum estradiol levels was noted after 12 weeks of vaginal estrogen administration. The clinical relevance of this small increase is uncertain. ClinicalTrials.gov Identifier: NCT02516202.

Relationship between Menopausal Hormone Therapy and Oral Cancer: A Cohort Study Based on the Health Insurance Database in South Korea.

The association between the development of oral cavity cancer and sex hormones is unclear and inconsistent. This study aimed to evaluate the relationship between menopausal hormone therapy (MHT) and oral cavity cancer in menopausal women in Korea. In this retrospective cohort study, data were provided by the Korean National Health Insurance Service regarding a screening examination conducted from 1 January 2002 to 31 December 2019. Postmenopausal patients aged ≥40 years were considered, including 333,072 women in the MHT group and 847,558 women in the non-MHT group. Participants were divided into MHT types (tibolone, combined estrogen plus progestin by manufacturer, estrogen, combined estrogen plus progestin by physician, and topical estrogen), and the risk factors for oral cavity cancer development were analyzed. There was no significant association between smoking, alcohol consumption, age at menarche, and age at menopause with oral cavity cancer in postmenopausal women. However, the oral estrogen (hazard ratio [HR]: 1.633; 95% confidence interval [CI]: 1.35–1.976) and tibolone groups (HR: 1.633; 95% CI: 1.35–1.976) were associated with an elevated risk of oral cavity cancer. The results of this study suggest that MHT increases the risk of oral cavity cancer in postmenopausal women.

Effect of oral estrogen supplement on gonadotropin-induced intrauterine insemination: A retrospective cohort study

Aim: The effect of estrogen on gonadotropin-induced intrauterine insemination (GI-IUI) is not well studied. Furthermore, risk factors for clinical pregnancy rates are not clearly defined. This study aimed to evaluate the effects of oral estrogen supplementation and clinical pregnancy rates on GI-IUI.&#x0D; Material and Method: Patients treated with primary and secondary infertility were retrospectively analyzed between September 2016 and September 2019. IUI session was performed after ovarian stimulation with human chorionic gonadotropin. Patients were supplemented with a vaginal gel containing progesterone and oral estrogen (Group A) or only the vaginal gel (Group B). The differences between the groups in pregnancy rate and endometrial thickness and the risk factors associated with clinical pregnancy were determined as primary and secondary outcomes, respectively.&#x0D; Results: A total of 112 couples were evaluated, where the mean age for females was 31.3±6.1 years. Group A and Group B had 33 (29.5%) and 79 patients (70.5%), respectively. Duration of infertility, number of follicles, and endometrial thickness were significantly different between the two groups. The rate of pregnancy was significantly higher in Group A (51.5%) than in Group B (19%) (p=0.001). There were significant differences between positive and negative pregnancy cases in terms of age, type and duration of infertility, estradiol level, motile sperm number and morphology, number of follicles, and endometrial thickness. The follicle count and estradiol levels were significant risk factors for clinical pregnancy.&#x0D; Conclusion: Estrogen has a positive effect on pregnancy rates in GI-IUI. The follicle number and estradiol level can be used as a risk factor for IUI.

Differing effects of oral conjugated equine estrogen and transdermal estradiol on vitamin D metabolism in postmenopausal women: a 4-year longitudinal study.

The aim of this study was to examine the effect of either conjugated equine estrogen or transdermal estradiol on vitamin D metabolism in postmenopausal women. Twenty-five women from the Kronos Early Estrogen Prevention Study who were randomized to conjugated equine estrogen 0.45 mg/d and 20 women who were treated with transdermal estradiol 50 mg/d (patch replaced weekly) were analyzed in the present study. All participants received micronized progesterone for 12 days per month. There was no significant treatment effect on serum total 25-hydroxyvitamin D over 48 months in either study group, and there were no significant differences between treatment arms. In contrast, at 12 months, directly measured free 25-hydroxyvitamin D was significantly higher in the transdermal estradiol group than in the conjugated equine estrogen group. Directly measured free 25-hydroxyvitamin D subsequently increased significantly from 12 to 48 months in both treatment arms. Calculated free 25-hydroxyvitamin D was also significantly higher in the transdermal estradiol group at 36 months. Vitamin D-binding protein decreased significantly in both treatment groups from 12 to 48 months, but at 48 months, least square mean values were no different based on treatment assignment. Directly measured free 25-hydroxyvitamin D levels, but not serum total 25-hydroxyvitamin D levels, are different within the first 12 months of estrogen replacement depending on the preparation. However, this difference is transient, in that there were no differences at 36 or 48 months. These findings suggest that there may be a short-term benefit to prescribing transdermal estradiol for women who are either vitamin D deficient or vitamin D insufficient.

Bone marrow mesenchymal stem cells combined with estrogen synergistically promote endometrial regeneration and reverse EMT via Wnt/β-catenin signaling pathway

BackgroundIntrauterine adhesion (IUA) is a clinical disease characterized by the uterine cavity occlusion caused by the damage of the endometrial basal layer. Bone marrow mesenchymal stem cells (BMSCs) transplantation have the potential to promote endometrial regeneration mainly through paracrine ability. Estrogen is an indispensable and important factor in the repair of endometrial damage, which has been reported as a promising and adjunctive therapeutic application for stem cell transplantation therapy. This study aims to investigate the synergistic effect of BMSCs and estrogen on improving the endometrial regeneration and restoring the endometrium morphology in a dual damage model of IUA in rabbits and the underlying molecular mechanisms.MethodsBMSCs were isolated and identified by adipogenic and osteogenic differentiation and flow cytometry assays. The rabbit IUA animal model was established by a dual damage method of mechanical curettage and lipopolysaccharide infection. Additionally, we investigated the therapeutic impact of both BMSCs and estrogen either separately or in combination in a rabbit model. The retention of PKH26-labeled BMSCs was observed by vivo fluorescence imaging.The number of endometrial glands and the degree of fibrosis were observed by H&E and Masson staining respectively. Western blotting, Immunohistochemistry and immunofluorescence staining were performed to detect biomarkers related to endometrial epithelium, endometrial fibrosis and EMT. Finally, the protein expression of core molecules of Wnt/β-catenin pathway was detected by Western blotting.ResultsPKH26-labeled fluorescence results revealed that BMSCs appeared and located in the endometrial glands and extracellular matrix area when orthotopic transplanted into the uterine cavity. Histological assays showed that remarkably increasing the number of endometrial glands and decreasing the area of endometrial fibrosis in the BMSCs combined with estrogen treatment group. Moreover, downregulated expression of fibrosis markers (fibronectin, CollagenI, a-SMA) and interstitial markers (ZEB1, Vimentin, N-cadherin), as well as upregulated E-cadherin expression were found in the combined group. Further study of in vivo staining revealed that fluorescence intensity of CK7 was stronger in the combined group than that of direct BMSCs intrauterine transplantation, while vimentin showed the opposite results. Moreover, the protein levels of β-catenin, Axin2, C-myc, CycinE of Wnt/β-catenin signaling pathway increased in the BMSCs combined with estrogen group than in the other treatment groups.ConclusionBMSCs combined with estrogen can promote the differentiation of stem cells into endometrial epithelial cells to facilitate the regeneration of damaged endometrium. The potential mechanism of the synergistic effect may inhibit the occurrence of EMT by activating the Wnt/β-catenin signaling pathway.

Human umbilical cord blood-derived MSCs trans-differentiate into endometrial cells and regulate Th17/Treg balance through NF-κB signaling in rabbit intrauterine adhesions endometrium

PurposeThe fundamental cause of intrauterine adhesions (IUAs) is the destruction and reduction in stem cells in endometrial basal layer, resulting in endometrial reconstruction very difficult. The purpose of this study was to investigate the effects and underlying mechanism of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) on the endometrial reconstruction after transplantation.MethodshUCB-MSCs were isolated and identified by flow cytometry, osteogenic, adipogenic and chondrogenic differentiation assays. The rabbit IUA models were established and set five groups (control, 14/28th day after surgery, estrogen and hUCB-MSCs treatment). The number of endometrial glands and the fibrosis rate were evaluated using HE and Masson staining, respectively. Endometrial proliferation, angiogenesis and inflammation were evaluated by immunohistochemical staining of ER, Ki-67and TGF-β1, respectively. Single-cell RNA sequencing (scRNA-seq) was applied to explore the cell differentiation trajectory after hUCB-MSCs transplanted into IUA endometrium. Finally, molecular mechanism of hUCB-MSCs repairing damaged endometrium was investigated by RNA sequencing, qRT-PCR and Western blot assays.ResultsAfter transplantation of the hUCB-MSCs, the increase in endometrial gland number, estrogen receptor (ER) and Ki-67 expression, and the decrease in fibrosis rate and TGF-β expression (P < 0.05), suggested the endometrial repair, angiogenesis and inflammatory suppression. The therapeutic effect of hUCB-MSCs was significantly improved compared with 28th day after surgery and estrogen group. ScRNA-seq demonstrated that the transplanted hUCB-MSCs can trans-differentiate into endometrial cells: epithelial, fibroblast and macrophage. RNA sequencing of six IUA samples combined with qRT-PCR and Western blot assays further revealed that hUCB-MSCs may regulate Th17/Treg balance through NF-κB signaling, thus inhibiting the immune response of damaged endometrium.ConclusionsOur study demonstrated that hUCB-MSCs can repair damaged endometrium through trans-differentiation, immunomodulatory capacities and NF-κB signaling, suggesting the treatment value of hUCB-MSCs in IUA.

Effects of Estrogen on Proliferation and Apoptosis of Osteoblasts through Regulating GPER/AKT Pathway.

This experiment was carried out to study the effects of estrogen on the proliferation and apoptosis of osteoblasts through regulating the G protein-coupled estrogen receptor (GPER)/protein kinase B (AKT) pathway. For this aim, osteoblasts were cultured in vitro and divided into control group, estrogen group and inhibitor group after passage. The osteoblasts in the control group were cultured normally, estrogen intervention was made in the estrogen group and G15 inhibitor intervention was made in the inhibitor group. After intervention for 24 h, osteoblasts were collected for detection. The positive expression of GPER and the double-positive expression of Tom20/Lamp2 were detected via immunofluorescence assay. The protein expressions of GPER, AKT and phosphorylated (p)-AKT were detected via Western blotting. The mRNA expression of GPER was detected via qPCR. Moreover, the autophagosomes were observed under a transmission electron microscope, and the apoptosis and cell proliferation were detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and cell counting kit-8 (CCK8) assay, respectively. Results of the immunofluorescence assay revealed that the positive expression of GPER in the estrogen group was higher than that in the control group and inhibitor group (p<0.05), while the double-positive expression of Tom20/Lamp2 in the estrogen group was lower than that in control group and inhibitor group (p<0.05). According to the results of Western blotting, the relative protein expression of AKT had no differences among the three groups (p>0.05), while the relative protein expressions of GPER and p-AKT in the estrogen group were higher than those in the control group and inhibitor group (p<0.05). The results of qPCR showed that the relative mRNA expression of GPER in the estrogen group was higher than that in the control group and inhibitor group (p<0.05). There were a small number of autophagosomes in osteoblasts in the control group and inhibitor group, while the number of autophagosomes in osteoblasts was smaller in the estrogen group. Besides, the estrogen group had a remarkably lower apoptosis rate of osteoblasts than the control group and inhibitor group and a remarkably higher proliferation rate than the control group and inhibitor group. Then estrogen can inhibit the mitochondrial autophagy of osteoblasts by regulating the GPER/AKT pathway, thereby inhibiting apoptosis and promoting cell proliferation.

The comparative effects of estrogen and tacrolimus on crushed sciatic nerve regeneration in male mice: functional and histopathological evaluation.

Some pharmacological agents can be effective for peripheral nerve injuries treatments. Present study was aimed to apply different agents and to compare the nerve regenerative effects following crushed sciatic nerve injuries. Twenty-four adult male mice were conducted in this study. Standard unilateral left side sciatic nerve crush was performed with 2.00 mm width mosquito hemostat forceps. The mice were randomly divided into four groups with the same numbers in each group which received subcutaneously, estrogen (group I), tacrolimus (group II), the combination of estrogen and tacrolimus (group III), and saline 0.90%. Functional recovery, histopathology, and immunohistochemistry (IHC) were performed on days 14th and 28th. Walking track analysis on day 14th showed no significant difference between experimental groups, however, they showed significant difference compared to the control group. At the same time, experimental groups showed similar results of inflammatory cell infiltration, axonal edema, and count with significant differences compared to control group. At the end of the study, group I and III showed a significant difference in functional recovery between group II and control. After fourth week significant histopathological difference of axonal count was observed in group III. On day 28th, only IHC assessment in group III showed more glial fibrillary acidic protein (GFAP) expression compared to the same group on day 14th. This study revealed subcutaneous administration of combined estrogen and tacrolimus could be effective with acceptable results in nerve regeneration.

Sexual Function in Postmenopausal Women With Symptomatic Pelvic Organ Prolapse Treated Either with Locally Applied Estrogen or Placebo: Results of a Double-Masked, Placebo-Controlled, Multicenter Trial

Local estrogen therapy (LET) has beneficial effects on genitourinary atrophy; however it is currently unclear if LET improves sexual function in postmenopausal women with pelvic organ prolapse (POP). To evaluate if LET vs placebo results in an improved sexual function in postmenopausal women with symptomatic POP. We performed a secondary analysis of sexual outcomes of a previous randomized controlled trial comparing LET and placebo in 120 postmenopausal women (60/group) with symptomatic POP stage ≥3 and planned prolapse surgery. Women were randomly assigned to receive local estrogen or placebo cream 6 weeks preoperatively. The effect of therapy vs placebo was assessed with ANOVA with interaction effect of time*group and a multivariable linear regression model was built to assess the impact of different variables on sexual function before therapy. We evaluated the sexual function score in sexually active women of our study population using the German Pelvic Floor Questionnaire at recruitment time and again after 6 weeks of treatment. Among 120 randomized women, 66 sexually active women remained for final analysis. There was no significant difference in the change of the sexual function score over time between the treatment groups (difference in changes in score from baseline to 6 weeks for Estrogen group vs control group was -0.110 with 95% CI -0.364 to 0.144) Multivariable analysis showed that no independent risk factor for unsatisfying sexual function score could be identified. Based on our results, LET has no beneficial effect on sexual function in postmenopausal women with POP. Main strength of our study lies in the study design and in the use of a condition- specific questionnaire. As this is a secondary analysis, this study may be insufficiently powered to identify differences in sexual data between groups. LET had no impact on female sexuality in postmenopausal women with POP. Marschalek M-L, Bodner K, Kimberger O, et al. Sexual Function in Postmenopausal Women With Symptomatic Pelvic Organ Prolapse Treated Either with Locally Applied Estrogen or Placebo: Results of a Double-Masked, Placebo-Controlled, Multicenter Trial. J Sex Med 2022;19:1124-1130.

Topical estrogen application promotes cutaneous wound healing in db/db female mice with type 2 diabetes.

Female sex hormones are beneficial effects for wound healing. However, till date, whether topical estrogen application can promote cutaneous wound healing in diabetes remains unclear. Therefore, the present study aimed to validate the effect of topical estrogen application on cutaneous wound healing in a type 2 diabetes db/db mice model. In total, 22 db/db female mice with type 2 diabetes and eight C57BL/6J female mice were subjected to two full-thickness wound injuries. The mice were divided into the db/db, db/db + estrogen, db/db + vehicle, and wild type (WT) groups. Wound healing was assessed until day 14. The db/db group had a significantly high wound area ratio (wound area/initial wound area) on days 3–14 and a significantly low re-epithelialization ratio on days 7 and 14. Moreover, their angiogenesis ratio was significantly low on day 7 and high on day 14. In contrast, compared with the db/db group, the db/db + estrogen group had a significantly lower wound area ratio on days 1–14 and angiogenesis ratio on day 14, thereby indicating early withdrawal of new blood vessels, as well as a significantly higher re-epithelialization ratio on days 7 and 14 and Ym1+ M2 macrophage/macrophage ratio on day 7. Moreover, microarray analysis showed that the top 10 upregulated or downregulated genes in the db/db group were reversed by estrogen treatment, particularly on day 14, in comparison with the WT group. Thus, topical estrogen application reduced the wound area, promoted re-epithelialization and angiogenesis, and increased the number of M2 macrophages in mice with type 2 diabetes. Furthermore, it improved the differential regulation of genes in db/db mice. Therefore, such treatment can enhance cutaneous wound healing in female mice with type 2 diabetes.

Association between pharmaceutical modulation of oestrogen in postmenopausal women in Sweden and death due to COVID-19: a cohort study

ObjectiveDetermine whether augmentation of oestrogen in postmenopausal women decreases the risk of death following COVID-19.DesignNationwide registry-based study in Sweden based on registries from the Swedish Public Health Agency (all individuals...