Low Estrogen Levels Research Articles

Bisphenol A exposures and hormone concentrations in a cohort of women receiving aromatase inhibitor therapy for breast cancer.

e12535 Background: Bisphenol A (BPA), a widely used chemical in plastics production, has been shown to have estrogenic activity, although it is unclear whether BPA exposure alters effectiveness of aromatase inhibitor (AI) treatment among women with breast cancer. In vitro studies have indicated that at higher concentrations (≥10-4 μM), BPA inhibits aromatase expression and activity, whereas at environmentally relevant concentrations (≤10-8 μM), BPA increases aromatase expression and activity. Few in vivo studies have investigated the association between BPA exposure and estrogen concentrations among non-pregnant women. This pilot study among post-menopausal women receiving AI therapy evaluated whether BPA is detectable in participants’ urine, and the association between BPA and hormone concentrations. Methods: This study was ancillary to a larger intervention study (ClinicalTrials.gov NCT01509079), and participants provided informed consent for this ancillary study under a protocol approved by the institutional review boards of Park Nicollet Institute/HealthPartners and the University of Minnesota. AI adherence during the 4 weeks prior to the baseline visit was monitored through weekly diaries. Participants were instructed to collect spot urine collections in sterile, BPA-free polypropylene containers in the 24 hours prior to the baseline study visit. Serum hormone concentrations were measured using serum collected at the baseline study visit. The Breast Cancer Prevention Trial - Musculoskeletal Symptom (BCPT-MS) scale was used to assess AI-associated musculoskeletal syndrome symptoms at the baseline study visit. Results: Fourteen women agreed to participate in the pilot study, however one participant’s data was excluded due to substances interfering with BPA measurement. BPA was detected in urine from all 13 remaining participants. Geometric mean urinary BPA concentration (1.55 mcg/g creatinine, 95% confidence interval (CI): 0.98-2.45) was higher than concentrations reported for females (1.36 mcg/g creatinine, 95% CI: 1.23-1.51) in the 2013-14 National Health and Nutrition Examination Survey biomonitoring data. Age, body mass index, and percent body fat did not differ between women above or below the study median urinary BPA concentrations (1.49 ng/mL). Women with BPA concentrations >1.49 ng/mL had consistently lower serum estrone (5.0 vs. 7.0 pg/mL, p=0.15), estradiol (2.8 vs. 3.6 pg/mL, p=0.04), and testosterone (21.5 vs 23.8 ng/dL, p=0.28) concentrations compared to women with lower BPA concentrations. No statistically significant differences in BCPT-MS scores were observed between women with higher vs. lower urinary BPA concentrations. Conclusions: These preliminary findings suggest that BPA exposures may work in concert with AIs to lower serum estrogen levels. However, further research is needed to confirm these findings.

Sesamin Promotes Osteoporotic Fracture Healing by Activating Chondrogenesis and Angiogenesis Pathways.

Osteoporotic fracture has been regarded as one of the most common bone disorders in the aging society. The natural herb-derived small molecules were revealed as potential treatment approaches for osteoporotic fracture healing. Sesamin is a member of lignan family, which possesses estrogenic activity and plays a significant role in modulating bone homeostasis. Our previous study reported the promoting effect of sesamin on postmenopausal osteoporosis treatment. However, the role of sesamin in osteoporotic fracture healing has not been well studied yet. In this study, we further investigated the putative treatment effect of sesamin on osteoporotic fracture healing. Our study indicated that sesamin could activate bone morphogenetic protein 2 (BMP2) signaling pathway and further promotes in vitro chondrogenesis and angiogenesis activities. This promoting effect was abolished by the treatment of ERα inhibitor. In the osteoporotic bone fracture model, we demonstrated that sesamin markedly improves the callus formation and increases the cartilaginous area at the early-stage, as well as narrowing the fracture gap, and expands callus volume at the late-stage fracture healing site of the OVX mice femur. Furthermore, the angiogenesis at the osteoporotic fracture site was also significantly improved by sesamin treatment. In conclusion, our research illustrated the therapeutic potential and underlying regulation mechanisms of sesamin on osteoporotic fracture healing. Our studies shed light on developing herb-derived bioactive compounds as novel drugs for the treatment of osteoporotic fracture healing, especially for postmenopausal women with low estrogen level.

Severe COVID-19 has low testosterone, estrogen levels, and impaired sexuality

For assessing whether women with and without COVID-19 differed with regard to female genital self-image, sexual function and hormonal profile. Female genital self-image being assessed with the female genital self-image scale (FGSIS) and Female Sexual Function Index (FSFI) and laboratory investigations. The study had revealed significant differences in all domains of the FSFI except pain between the cases and the controls. The study had demonstrated significant differences in all domains of the FGSIS between the cases and the controls. The study had shown significant decline in the post-COVID-19 serum levels of total testosterone (TT), free testosterone (FT) and estradiol (E) between the two groups (P < 0.05). Positive correlations between serum TT, FT, E and FGSIS domains and total score of FGSIS in the cases were observed.

Mechanisms in Chronic Kidney Disease and Associated Cardiovascular Remodeling Contributes to the Progression of Cognitive Impairment in Women

IntroductionIn end‐stage chronic kidney disease (CKD) (stages 4‐5) the prevalence of cognitive impairment (CI) has been estimated at 30‐60%, twice the values observed in age‐ and sex‐matched controls. CKD is greater in females vs. males due to a higher risk of renal infections, especially during the pregnancy, which may result in the renal complications later in life, when the level of protective estrogen declines. Cardiovascular diseases (CVD) including hypertension and increased central arterial stiffness (CAS) accompany CKD development across all stages of this disease. CAS drives pulse pressure (PP) and pulsatile component index (PCI) increases and cerebral microvascular damage resulting in a reduction of blood supply to the brain hereby contributing to CI. Elevated PP and PCI are associated with higher mortality in CVD and CKD independently of BP. Moreover, PP is a cardiovascular risk factor independent on PCI in women &gt;55 years.HypothesisThe aim of the study was to determine whether CKD potentiates development of CI due to cardiovascular remodeling and whether CI in CKD is more pronounced in women. Furthermore, this study also aimed to determine whether reduced estrogen levels in older women with CKD contribute to the progression of CI.MethodsAll research was performed in accordance with the guidelines and regulations set forth by the Declaration of Helsinki regarding the use and enrollment of human subjects in research. A total of 26 female CKD patients (age 45‐50 years and older, CKD stage 4, GFR 15‐29, and Creatinine &gt; 1mg/dL) and 30 age and sex‐ matched healthy control patients were enrolled with exclusion criteria (history of HIV, hepatitis, malignancies, admission and/or surgery for trauma, head injury and pregnancy at time of enrollment). Blood pressure (systolic and diastolic blood pressure (SBP, DBP) was measured, clinical blood work, echocardiography (ECHO) and mini‐mental state examination (MMSE) was performed as well as levels of amyloid beta‐40 (Aβ‐40) measured. PCI was calculated as difference between peak systolic and end diastolic flow velocity, divided by the flow velocity. Estrogen levels were measured in the plasma samples. The data were analyzed by unpaired two‐tailed t‐test and Pearson correlation with P values adjusted for false discovery rate.ResultsCKD patients had higher SBP, PP, PCI, LV systolic and diastolic volume (estimated by ECHO), lower LV ejection fraction, higher plasma NT‐proBNP and AST (CVD markers), glucose, triglycerides, plasma Aβ‐40 (Alzheimer’s disease marker), BUN and creatinine (CKD markers) and lower score in MMSE vs. healthy control (p&lt;0.05). Plasma estrogen levels were significantly lower in CKD patients which correlated with the cognitive test scores and the renal function. Cognitive test results positively correlated with LV stroke volume, negatively correlated with PCI, a measurement of pulsatility of blood pressure, and negatively correlated with plasma ASP, a marker of CVD.ConclusionHigher PP, PCI, plasma Aβ‐40 and lower levels of estrogen and lower score in MMSE in female CKD patients supports our hypothesis that cardiovascular remodeling in women with CKD contributes to the development and progression of CI.

Urethral prolapse mimicking a uterine prolapse in an eight-year-old girl: A case report.

Introduction and importanceA urethral prolapse is a rare condition occurring most likely in prepubertal girls and post-menopausal women. The cause of this condition is not well known but an under-laying low level of estrogen is thought to have a role.Case presentationThis is an 8-year-old girl diagnosed with urethral prolapse, who was successfully managed by excision of the prolapsed urethral mucosa circumferentially. A three-month following up did not notice any particular challenge.Clinical discussionThe most common presenting sign is genital bleeding and the vaginal doughnut sign. Treatment of urethral prolapse should begin with medical therapy in most patients before resorting to surgical management. However, in case of bigger size, severe genital hemorrhage, and prolapsed mucosa with an appearance suggestive of vascular compromise, surgical management is the first-line option. We estimate a severe prolapse mimicking a uterine prolapse must be included in surgical management as a first-line option.ConclusionSurgical excision may be the first-line option in certain urethral prolapses given its association with quick recovery versus the effectiveness of the long-time required for estrogen use, as well as the low likelihood of successful resolution linked to estrogen use.

Unstimulated Salivary Estrogen in Postmenopausal Women With and Without Oral Dryness: A Prospective Study

Objective: This study aimed to compare the unstimulated salivary estrogen levels in postmenopausal women with and without oral dryness. Methodology: A study was carried out on 70 selected postmenopausal women, out of which 35 were in the case group and 35 were in the control group. A questionnaire related to oral dryness was given to all the patients to evaluate their response to oral dryness. Patients were asked to spit in a plastic container, and their unstimulated saliva samples were obtained and analyzed for estimation of salivary estrogen levels by ELISA technique. After analyzing the results of salivary estrogen levels, the patients in the case group with low levels of estrogen were subjected to HRT under the guidance of a gynecologist. The patients were followed after 3 months of therapy for their response to oral dryness by the questionnaire, and salivary estrogen levels were again reevaluated after the therapy. The statistical analysis was carried out using Statistical Package for Social Sciences (SPSS Inc, Chicago, IL, version 15.0 for windows). The Pearson’s correlation and Student’s unpaired t-test were used for comparisons. Results: Before hormone replacement therapy, the mean estrogen level of the case group was 1.0031, and the mean estrogen level of the control group was 4.0080 pg/ml. This suggested that the reduced levels of estrogen hormone after menopause were associated with the complaint of oral dryness in these females. The mean salivary estrogen levels in the case group after HRT were more than the levels before HRT. Conclusion: Estrogen levels were reduced in patients with oral dryness. Further, the patients receiving HRT showed significant improvement in symptoms of oral dryness.

High Estrogen Levels Cause Greater Leg Muscle Fatigability in Eumenorrheic Young Women after 4 mA Transcranial Direct Current Stimulation.

Transcranial direct current stimulation (tDCS) research has shown great outcome variability in motor performance tasks, with one possible source being sex differences. The goal of this study was to evaluate the effects of estrogen levels on leg muscle fatigability during a fatigue task (FT) after 4 mA tDCS over the left motor cortex (M1). Ten young, healthy eumenorrheic women received 4 mA anodal active or sham stimulation over the left M1 during periods of high and low estrogen levels. A fatigue index (FI) was calculated to quantify fatigability, and the electromyography (EMG) of the knee extensors and flexors was recorded during the FT. The findings showed that tDCS applied during high estrogen levels resulted in greater leg muscle fatigability. Furthermore, a significant increase in EMG activity of the right knee extensors was observed during periods of active stimulation, independent of estrogen level. These results suggest that estrogen levels should be considered in tDCS studies with young healthy women.

BONE REGENERATION IN HEALTHY AND OSTEOPOROTIC CONDITIONS. PRECLINICAL EVIDENCE.

Introduction Osteoporosis is one of the most common skeletal disorders affecting a significant percentage of people worldwide. Research data suggested that systemic diseases such as osteoporosis could act as risk factors for bone regeneration, jeopardizing the healing process and thus the predictability of bone regenerative techniques on compromised patients. The use of titanium dental implants is considered a successful and largely predictable treatment option for partial/full edentulism. However, a prerequisite for the successful implant placement in the prosthodontally ideal driven position is a minimum amount of bone at the recipient site. It is well accepted that preclinical studies in experimental models simulating healthy and systemic conditions, are one of the most important stages in the research of new biomaterials and therapeutic modalities. Aim and Methods The aim of this study is to review the potential effect of osteoporosis on guided bone regeneration in healthy and osteoporotic-like conditions in preclinical models. Material and Methods Literature search was conducted in MEDLINE and PUBMED up to March 2022. Results Research data showed significant new bone apposition in the defect sites, although a trend for less bone formation of lower quality was observed in osteoporotic compared to healthy conditions. Conclusion Evidence suggested that low level of estrogen might negatively affect the biological process of bone grafts/substitutes integration. Preclinical studies provide the possibility of better understanding the underlying mechanism of bone regeneration in compromised conditions. It is important to emphasize that optimization of these models, simulating healthy and systemic conditions, is important for future research.

Exposure to multiple pyrethroid insecticides affects ovarian follicular development via modifying microRNA expression

Pyrethroids, a class of insecticides widely used in agriculture and residential pest control, have been considered as endocrine-disrupting chemicals (EDCs). Our previous epidemiological study reported a positive association of urinary levels of pyrethroid metabolites with the risk of primary ovarian insufficiency in women, suggesting that pyrethroid exposure may be a potential risk factor for female ovarian health. In this study, female mice at gestational, lactational or peripubertal stages were exposed to eight most commonly used pyrethroids at the doses of acceptable daily intake (ADI) recommended by the World Health Organization (WHO). Gestational exposure to eight pyrethroids at ADI doses led to a significant decrease in the number of primary follicles in female offspring on postnatal day (PND) 3, and an increase in the number of atretic follicles and granulosa cell apoptosis, as well as lower estrogen and higher follicle-stimulating hormone (FSH) levels in adult female offspring. Lactational and peripubertal exposure to pyrethroid mixture had no significant effects on follicular development and ovarian functions. The data of high-throughput microRNA (miRNA) sequencing showed that 23 miRNAs were differentially expressed in the ovaries of female offspring mice on PND 1 after gestational exposure to pyrethroid mixture. The results of qPCR confirmed that miR-152-3p, miR-450b-3p and miR-196a-5p were significantly upregulated in the neonatal ovaries in the exposed group. The bioinformatic analysis indicates that the modification of the expression of ovarian miRNAs by pyrethroid exposure may disrupt the key biological processes (such as mRNA processing) and major signaling pathways (such as PI3K/Akt pathway, adipocytokine pathway and GnRH pathway) governing follicular development and ovarian functions. This study first reported that gestational exposure of female mice to multiple pyrethroids at the recommended human safe doses had irreversible adverse effects on the ovaries in female offspring in adulthood through regulating the expression of miRNAs during early developmental stages.

Estrogen as primary factor in vaginal healing in rats.

Although the effect of estrogens on wound healing is already known, its complex mechanism is not fully understood in literature. The aim of this study is to investigate the effect of estrogen on vaginal healing after surgical intervention performed in the age group with low estrogen level and in an adult group with high estrogen level. Seven young and seven adult female Wistar Albino rats were procured. For control group, one animal was chosen each from the young (Group I) and adult groups (Group II), and their vaginal tissue was removed. An incision was made to the posterior vaginal wall under anesthesia and sutured with 5-0 polyglactin in all the rats. On the seventh postoperative day, the posterior vaginal wall was excised. A semi-quantitative method was used to evaluate the histological processes and structures during wound healing. Although there were no evident differences in the evaluation of histological scoring system, the presence and distribution of new vascularization and fibroblasts showed that vaginal mucosal healing was more intense in adult rats. The effect of estrogens on vaginal mucosal healing has been discussed in several experimental studies and literature information has been presented; it has been concluded that it would be beneficial to consider the positive effect of vaginoplasty procedures.

Abstract P220: Low Levels Of Endogenous Estrogen Are Associated With Elevated Risk Of Cardiovascular Disease Mortality In Young And Middle-Aged Men In The United States

Background: While endogenous estrogen deficiency in men due to inactivating mutations of the aromatase gene results in profound metabolic dysfunction, evidence for the association of estradiol with cardiovascular disease (CVD) in men overall is inconsistent, with most studies performed among older men or patients with CVD. We investigated the association of total estradiol (E2) or free estradiol (FE2) and CVD mortality in a nationally representative sample of US men. Hypothesis: Low levels of E2 or FE2 will be associated with elevated risk of CVD mortality. Methods: Data on 954 men without CVD, cancer, diabetes and not on androgen therapy or taking anabolic steroids who participated in Phase 1 (1988 to 1991) of the third National Health and Nutrition Examination Survey and for whom E2 was measured, and were followed for mortality through to December 31, 2015 were included. Fasting serum levels of E2 were measured using competitive electrochemiluminescence immunoassays. Free estradiol was estimated from estradiol, sex hormone binding globulin, and albumin. Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). Results: The average age of participants at baseline was 35.7 (Standard deviation (SD) ±11.6) years with 11% and 6% of them reporting Black and Hispanic race and ethnicity, respectively. During a median follow-up of 25.2 years, 40 CVD deaths were recorded, with the cumulative incidence greater among men with low E2 or FE2 (Figure). Controlling for baseline age, race/ethnicity, education, systolic blood pressure, body mass index, physical activity, smoking status, alcohol intake, HDL cholesterol, c-reactive protein and total testosterone levels, a 1 log SD decrease in E2 (HR: 2.38, 95%CI: 1.11-5.00) or FE2 (HR: 1.96, 95%CI: 1.03-3.70) was associated with elevated CVD mortality. Conclusions: In this nationally representative sample of U.S young and middle-aged men, low levels of total estradiol or free estradiol were associated with elevated risk for CVD mortality.

Incidence and familial risk of premature ovarian insufficiency in the Finnish female population.

STUDY QUESTIONWhat is the incidence of premature ovarian insufficiency (POI), has the incidence of POI changed over time, and what is the risk of POI among relatives of POI women?SUMMARY ANSWERThe incidence of POI increased among females aged 15–19 years from 2007 onwards and decreased in older age groups, and among relatives of women with POI the risk of POI is significantly increased.WHAT IS KNOWN ALREADYSo far, there has been no good quality, nationwide studies of the incidence of POI. Early menopause has been associated with the elevated risk of early menopause among relatives, but the knowledge of the familial risk of POI is scarce. Lower socioeconomic status has been associated with lower age at natural menopause.STUDY DESIGN, SIZE, DURATIONPopulation-based study with 5011 women diagnosed with POI in 1988–2017. The data were collected from national registries and covers POI subjects in entire Finland.PARTICIPANTS/MATERIALS, SETTING, METHODSWomen with hormone replacement therapy reimbursement for POI were identified from Social Insurance Institution (SII). We calculated POI incidence in different age groups and studied the changes in the incidence rate over time in 5-year segments. Four population-based controls were selected from the Digital and Population Data Services Agency (DVV) for each POI woman. Family members of the POI cases and controls were identified from the DVV and linked to SII reimbursement data to identify POI diagnoses among them. The familial risk of POI was estimated with a logistical regression model.MAIN RESULTS AND THE ROLE OF CHANCEThe incidence was highest in the 35–39 age group, ranging from 73.8/100 000 women-years in 1993–1997 to 39.9/100 000 women-years in 2013–2017. From 2007, the incidence among 15- to 19-year-olds rose from 7.0 to 10.0/100 000 women-years in 2015–2017. Cumulative incidence of POI for women under 40 years in 1988–2017 was 478/100 000 women. The relative risk of POI among relatives of women with POI was 4.6 (95% CI 3.3–6.5) compared to relatives of women without POI. POI women tended to have slightly lower socioeconomic status and level of education compared to controls.LIMITATIONS, REASONS FOR CAUTIONFor some women with POI, diagnosis or reimbursement may be lacking. However, we presume that these women represent a minority due to the nature of the disease and the economic benefits of reimbursement. Some changes in the incidence of POI can reflect changes in clinical practice and changing treatments and reimbursement criteria.WIDER IMPLICATIONS OF THE FINDINGSThe risk of developing POI is significantly higher in women who have first-degree relatives diagnosed with POI. Raising awareness of the increased risk might lead to earlier diagnosis and initiation of hormonal replacement therapy, possibly preventing adverse effects of low oestrogen levels, such as osteoporosis.STUDY FUNDING/COMPETING INTEREST(S)This work was financially supported by the Oulu University Hospital. H.S. received a grant from Finnish Menopause Society. S.M.S. received a grant from the Finnish Menopause Society, the Finnish Medical Foundation and the Juho Vainio Foundation. The authors do not have any competing interests to declare.TRIAL REGISTRATION NUMBERN/A.

Gut microbiota and butyrate contribute to nonalcoholic fatty liver disease in premenopause due to estrogen deficiency.

The incidence of nonalcoholic fatty liver disease (NAFLD) in postmenopausal women has increased significantly. Estrogen plays a very important role in NAFLD, but whether NAFLD in premenopausal women was caused by estrogen deficiency was unknown. Thus, it is of great clinical significance to explore the mechanism of NAFLD in premenopausal women. Gut microbiota and its metabolites short chain fatty acids (SCFA) have been shown to play important roles in the development of NAFLD. In this study, we investigated the impact of gut microbiota and SCFA in NAFLD patients and mice caused by estrogen deficiency. We showed that premenopause NAFLD patients had much lower estrogen levels. Estrogen deficient mice, due to ovariectomy (OVX), suffered more severe liver steatosis with an elevated body weight, abdominal fat weight, serum triglycerides and deterioration in hepatic steatosis. Altered gut microbiota composition and decreased butyrate content were found in NAFLD patients and in OVX mice. Furthermore, fecal microbiota transplantation (FMT) or supplementing with butyrate alleviated NAFLD in OVX mice. The production of antimicrobial peptides (AMP) Reg3ɣ, β-defensins and the expression of intestinal epithelial tight junction, including ZO-1 and Occluding-5, were decreased in the OVX mice compared to control mice. Upregulation of PPAR-ɣ and VLDLR, downregulation of PPAR-ɑ indicated that OVX mice suffered from abnormal lipid metabolism. These data indicate that changes in the gut microbiota and SCFA caused by estrogen reduction, together with a disorder in AMP production and lipid metabolism, promote NAFLD, thus provide SCFAs derived from microbiota as new therapeutic targets for the clinical prevention and treatment of NAFLD.

Does Supplemental Estrogen Improve Bone-Related Symptoms of Female Athlete Triad in Female Athletes? A Critically Appraised Topic.

Clinical Scenario: Due to the Female Athlete Triad (Triad) being a 3-pronged syndrome, treatments can vary depending on the symptoms that clinicians focus on. With reproductive and bone health compromised, assessment and recovery methods include monitoring menstrual regularity and dual-energy X-ray absorptiometry scans. Low levels of estrogen have demonstrated negative effects on bone mineral density (BMD). Clinical Question: Does supplemental estrogen improve BMD in athletes with Female Athlete Triad symptoms? Summary of Key Findings: Supplemental estrogen does improve BMD with estrogen patches demonstrating increased improvement compared with oral contraceptive pills. Clinical Bottom Line: Restoration of regular menstruation, improvement of BMD, and ensuring optimal energy levels is the best approach for treating Triad symptoms. Transdermal patches are a new treatment option that address both menstrual function and BMD but still require further research. Strength of Recommendation: Available studies demonstrated a level 2 evidence for supplemental estrogen (oral contraceptive pills and estrogen patches) providing improvements for bone health related to the Triad.

Abstract WP252: Tamoxifen Treatment Worsens Astrocyte Activation And Mitochondrial Stress From Oxygen Glucose Deprivation

Introduction: Tamoxifen (TAM), a selective estrogen receptor modifier, is a first-line treatment option for hormone receptor positive breast cancer. TAM inhibits the downstream estrogen receptor signaling in tumor cells. Stroke risk is increased in women with low estrogen levels, such as early-onset menopause, and doubles in women after the age of 55, which corresponds with the average age of menopause. Women with breast cancer who were treated with tamoxifen had an increased risk for ischemic stroke (82%). Since stroke severity is associated with increased blood brain barrier (BBB) damage, we investigated the effects of tamoxifen on activation and mitochondrial stress in astrocytes, which is a cellular component of the BBB. Methods: Cultured female human astrocytes were treated with tamoxifen (1uM), 17ß-estradiol (10nM), or vehicle (DMSO) for 24 hours. Cells were separated into two groups: normoxic (21% O2, 25mM glucose) or oxygen and glucose deprivation (OGD) conditions 6 hours before analysis. ROS production was measured using the Cellular ROS Assay Kit (Red) and aquaporin-4 levels were visualized via immunocytochemistry. Mitochondrial function was assessed by using a Seahorse XFe96 Analyzer. Results: Tamoxifen treatment increased Aquaporin-4 protein levels (p &lt;0.0001) in cultured astrocytes after OGD compared to both vehicle (DMSO) and 17ß-estradiol treatment. While there was no significant effect, tamoxifen treated cells showed a trend toward (p =0.0732) increased ROS production after OGD compared to vehicle. Additionally, tamoxifen reduced oxygen consumption rate (p =0.0197) and basal respiration under normoxic conditions in astrocytes when compared with DMSO or 17ß-estradiol treatment. Conclusions: Tamoxifen treatment altered the expression of a water channel protein and decreased the ability to respond to oxidative stress in astrocytes. Aquaporin-4, when localized to the astrocytic end feet, facilitates edema after stroke, and ischemic stroke by definition puts brain tissue under oxidative stress. Our findings suggest tamoxifen may increase edema, which is known to impair stroke recovery. These data suggest a mechanism by which breast cancer treatment may increase the risk for severe ischemic stroke. Supported by RFAG042189 to FS

POS-981 PREMATURE OVARIAN FAILURE SECONDARY TO LOW DOSE INTRAVENOUS CYCLOPHOSPHAMIDE IN A YOUNG WOMAN WITH RELAPSED LUPUS NEPHRITIS

Cyclophosphamide (CYC) is a nonspecific cell cycle cytotoxic antiproliferative agent that is used in inducing remission in lupus nephritis (LN) and it also possesses a wide spectrum of toxicities, particularly premature ovarian failure (POF) in woman. Ovarian damage often manifests with amenorrhoea, low estrogen level and increased follicle stimulating hormone (FSH) and luteinizing hormone (LH), which resemble the hormonal changes seen at menopausal woman.

Postmenopausal Vaginal Microbiome and Microbiota.

The ovulatory cycle has a significant influence on the microbial composition, according to the action of estrogen and progesterone on the stratified squamous epithelium, due to an increase in epithelial thickness, glycogen deposition, and influence on local immunology. The 16S rRNA gene amplification and pyrosequencing study demonstrated that healthy women have community state types (CST), classified as; type “L,” with a predominance of Lactobacillus crispatus, type II, with a predominance of Lactobacillus gasseri, type III, where Lactobacillus iners predominates, and type V with a predominance of Lactobacillus jensenii. Type IV does not identify lactobacilli but a heterogeneous population of bacteria. There seems to be a relationship between increased vaginal bacterial diversity and poverty of lactobacilli with the complaining of vaginal dryness. With menopause, there appears to be a reduction in lactobacilli associated with higher serum levels of follicle-stimulating hormone (FSH) and lower estrogen levels. The evaluation of Gram-stained vaginal smears in postmenopause women must take into account the clinical-laboratory correlation. We should observe two meanly possibilities, atrophy with few bacterial morphotypes, without inflammatory, infiltrate (atrophy without inflammation), and atrophy with evident inflammatory infiltrate (atrophy with inflammation or atrophic vaginitis). The relationship between the microbiome and postmenopausal vulvovaginal symptoms seems to be related to the bacterial vaginal population. However, more robust studies are needed to confirm this impression.

Lifelong exposure to pyrethroid insecticide cypermethrin at environmentally relevant doses causes primary ovarian insufficiency in female mice

Pyrethroids are a class of widely used insecticides. Our recent epidemiological study of Chinese women reported that pyrethroid exposure was positively associated with the risk of primary ovarian insufficiency (POI). In this study, we utilized cypermethrin (CP), the most frequently detected pyrethroid in the environment, to recognize how lifelong and low-dose exposure to pyrethroids affects ovarian functions and the underlying mechanism(s). Female mice were exposed to CP at doses of human dietary intake of 6.7 μg/kg/day, an acceptable daily intake (ADI) of 20 μg/kg/day, or the chronic reference dose (RfD) of 60 μg/kg/day, starting from gestational day 0.5 until 44-week-old. We assessed effects on fertility, serum hormone levels, ovarian follicular development and ovarian transcriptomic profiles. Chronic exposure to CP at doses of ADI and RfD caused a significant reduction in the size of the primordial follicle pool on postnatal day (PND) 5 and the number of all types of follicles in 44-week-old mice, lower estrogen and higher gonadotropin levels, as well as decreased fertility. Significant increase in apoptosis and decrease in cell proliferation were observed in CP-exposed ovarian follicles from PND 5 and 44-week-old mice. Ovarian transcriptomic data showed that the pro-apoptotic protein BMF and the cell cycle inhibitor p27 were significantly up-regulated in CP-exposed ovaries. Cyp17a1, Cyp19a1 and Hsd17b1 genes involved in the key steps of steroidogenesis were down-regulated in the ovaries of female mice exposed to CP. This study first reported that lifelong exposure to CP at doses of ADI or RfD caused an ovarian phenotype similar to human POI in female mice and provided a mechanistic explanation. Our findings suggest that lifelong exposure to pyrethroids of low doses, which are recommended as ‘safe’ dosages, may have a significant impact on the ovarian health of female mammals and humans.

Effectiveness of Self Instructional Module on Knowledge RegardingOsteoporosis among Post-Menopausal Women Residing at Rural CommunityArea, Bengaluru

Menopause is a natural life event which results in lower level of estrogen and leads to osteoporosis and heart disease. The present study was undertaken to assess the existing knowledge of post-menopausal women and the effectiveness of self-instructional module SIM regarding osteoporosis and to find the association between selected demographic variables.Methods Pre- experimental design was selected and pre-test amp post-test design was considered most suitable to assess the evaluation of self-instructional module on osteoporosis. About 60 post-menopausal women were present and probability simple random sampling technique was used at selected rural areas of Bidadi. Data was collected compiled tabulated and analyzed using descriptive and inferential statistics.Results Regarding effectiveness of SIM 40.4 was the pre-test mean knowledge score followed by post-test score of 83.3 with mean enhancement of knowledge score of 42.9 which was statistically significant. The Paired rsquotrsquo test was computed and it was 34.61 which was higher than the table value and was significant at 5 level. There was significant association between pre-test scores and demographic variables like education occupation and family income at 5 level.

Low estrogen level in aged mice leads to abnormal oogenesis affecting the quality of surrounded nucleolus-type immature oocytes.

With aging, various problems in the reproductive system emerge, especially in females. However, our understanding of reproductive aging in livestock and humans is limited. We aimed to investigate reproductive changes between young and aged mice. Eight- to ten-week-old female mice were used as the young group, and 10-month-old mice were studied as the aged group. Reproductive changes were investigated from physiological, histological, cytological, and epigenetic perspectives. The estrus cycle was shortened (P <0.0001), and the estradiol (E2) concentration was lower in aged mice (P <0.01), whereas the progesterone (P4) concentration did not differ between young and aged mice (P >0.05). The histological results revealed a lower number of antral follicles in the ovary and disordered epithelial tissue structures in the oviducts in aged mice. During oogenesis, the surrounded nucleolus (SN)-type oocytes in aged mice exhibited increased mitochondrial agglutination (P <0.05) and cellular apoptosis (P <0.01) as well as decreased H3K36 triple-methylation (P <0.001). Although many defects existed, the oocytes from aged mice could normally support cellular reprogramming after somatic cell nuclear transfer. Our results indicate that the reduced levels of reproductive hormones in aged females lead to shorter estrus cycles and reduced follicular development, leading to abnormal oogenesis, particularly in SN-type immature oocytes. These results provide new insight that enhance our understanding and improve the reproductive ability of aged females.