Serum Estradiol Research Articles

Trans 10, cis 12-conjugated linoleic acid reduced reproductive ability by disrupting the estrus cycle in female mice

Trans 10, cis 12-conjugated linoleic acid reduced reproductive ability by disrupting the estrus cycle in female mice

Mechanistic insights into EGCG's preventive effects on obesity-induced precocious puberty through multi-omics analyses.

Epigallocatechin gallate (EGCG) has demonstrated potential effects on obesity-induced precocious puberty, but the underlying mechanisms remain unclear. Female mice were randomly assigned into control (CON), EGCG-treated (EGCG), high-fat diet (HFD), and HFD with EGCG treatment (HFDEGCG) groups. Key measurements included body weight, vaginal opening time, and serum sex hormone levels. The gut microbiota was analyzed through 16S rRNA sequencing, fecal metabolites were assessed via metabolomics, and the hypothalamic transcriptome was examined using RNA sequencing. EGCG mitigated weight gain and delayed vaginal opening in mice with obesity-induced precocious puberty. Additionally, it reduced serum estradiol levels and decreased the number of mature ovarian follicles in the HFDEGCG group compared to the HFD group. EGCG treatment partially reversed HFD-induced dysbiosis by increasing the abundance of beneficial bacteria such as Akkermansia. Metabolomic analysis revealed significant alterations in tryptophan metabolism, while transcriptome analysis identified genes involved in metabolic pathways. Correlation analyses underscored the importance of the gut-brain axis in mediating EGCG's effects. Overall, EGCG prevents obesity-induced precocious puberty by modulating the gut microbiota, altering metabolic pathways, and regulating hypothalamic gene expression.

Minipuberty period of children with atopic dermatitis compared to healthy children.

Atopic dermatitis (AD) is an inflammatory, pruritic, noncontagious, chronic relapsing skin disease. Skin barrier abnormalities, excessive T helper 2 activity, and immune dysregulation are held responsible. Androgens have a negative effect on the integrity of the epidermal skin barrier, while estrogen has a positive effect. We aimed to investigate whether hormones make a difference between healthy children and children with AD during minipuberty. A total of 96 infants (postnatal 4-13 weeks), 48 diagnosed with AD and 48 controls, were included. Each group consisted of 23 girls (47.9%) and 25 boys (52.1%). Anthropometric examinations and hormone measurements were compared. The two groups, having similar age, sex, body mass index, and weight-for-length standard deviation scores, were compared. Serum free thyroxine (FT4) levels were found to be lower and insulin-like growth factor binding protein-3 (IGFBP3) levels were found to be higher in children with AD (p < 0.001 and p = 0.038, respectively). In girls with AD, estradiol, FT4, and insulin-like growth factor-1 (IGF-1) levels were found to be lower, but thyroid-stimulating hormone (TSH) levels were found to be higher (p = 0.023, p < 0.001, p = 0.038, and p = 0.034, respectively). In boys with AD, the FT4 level was found to be lower (p = 0.023). Serum FT4 and TSH levels were within normal reference ranges in all comparisons. Especially in girls with AD, decreased estradiol and IGF-1 levels were observed compared to the controls during minipuberty. In the logistic regression model, decreased levels of serum estradiol, dehydroepiandrosterone sulfate, FT4, and IGF-1, and increased levels of IGFBP3 were associated with an increased likelihood of exhibiting atopic dermatitis.

Effects of a simple method for determining the time of insemination and different methods on artificial insemination in common bottlenose dolphins (Tursiops truncatus).

In this study, we examined the usefulness of a simpler and more feasible method for determining the optimal timing of artificial insemination and the conditions for its success in six female common bottlenose dolphins. Pregnancy was successfully achieved in five dolphins by performing intrauterine insemination, using chilled semen stored for less than 3 days or frozen semen within 24 hr of exhibiting a peak serum estradiol (E2) level of 100 pg/mL or higher or on the day with a serum E2 level of approximately 100 pg/mL, measured with a simple measuring device. We concluded that the determining the optimal timing of intrauterine insemination by measuring serum E2 levels is a simpler and more useful method compared with the conventional approach.

Cytosine–guanine–guanine repeats of FMR1 gene negatively affect ovarian reserve and response in Chinese women

Research questionDo cytosine–guanine–guanine (CGG) repeats of the FMR1 gene affect ovarian function, ovarian response and assisted reproductive technology (ART) outcomes in Chinese women? DesignA retrospective cohort study of 5869 women who underwent 8932 ART cycles at Women's Hospital, School of Medicine, Zhejiang University between January 2018 and June 2021. Basic hormone level, oocyte yield, embryo quality and the rate of live birth were considered as main outcome measures to evaluate the effects of CGG repeats on ovarian function, ovarian response and ART outcomes. ResultsThe CGG repeats were negatively related to serum anti-Müllerian hormone (AMH), oestradiol, antral follicle count (AFC) and oocyte yield. A significant association was found between serum AMH, oestradiol and AFC even after age was controlled for. No statistically significant association, however, was found between CGG repeats and embryo quality or live birth rate. Ovarian function mediated the association between CGG repeats and ovarian response. ConclusionIncreased CGG repeats on the FMR1 gene were associated with diminished ovarian function and poor ovarian response, and ovarian function played an intermediary role in the relationship between CGG repeats and ovarian response.

Kuntai capsule attenuates premature ovarian insufficiency by activating the FOXO3/SIRT5 signaling pathway in mice: A comprehensive study using UHPLC-LTQ-Orbitrap and integrated pharmacology

Ethnopharmacological relevanceClassical prescriptions are not only a primary method of clinical treatment in traditional Chinese medicine (TCM) but also represent breakthroughs in the inheritance and development of this field. Kuntai capsule (KTC), a formulation based on a classical prescription, comprises six TCMs: Rehmanniae Radix Praeparata, Coptidis Rhizoma, Paeoniae Radix Alba, Scutellariae Radix, Asini Corii Colla, and Poria. This formulation possesses various beneficial effects, such as nourishing yin and blood, clearing heat and purging fire, and calming the nerves and relieving annoyance. The investigation of the efficacy and mechanism of KTC in regulating anti-aging factors in the treatment of premature ovarian insufficiency (POI) is not only a prominent topic in classical prescription research but also a crucial issue in the treatment of female reproductive aging using TCM. Aim of the studyTo evaluate the therapeutic effect of KTC on POI and its underlying mechanism. Materials and methodsHealthy and specific pathogen-free (SPF) female Kunming mice aged 6–8 weeks were selected. After acclimatization, the mice were randomly divided into a control, model, and high, middle, and low dose groups of KTC (1.6, 0.8, and 0.4 mg/kg, respectively). Except for the control group, the animals in the other groups were administered a single intraperitoneal injection of 120 mg/kg cyclophosphamide and 30 mg/kg Busulfan to induce the model of POI. After modeling, the mice were treated with the corresponding drugs for 7 days. Serum and ovarian tissues were collected, and the levels of serum follicle-stimulating hormone (FSH), estradiol (E2), and superoxide dismutase 2 (SOD2) were determined using enzyme-linked immunosorbent assay (ELISA). The chemical composition of KTC was characterized and analyzed using ultra-high-pressure liquid chromatography-linear ion trap-Orbitrap tandem mass spectrometry. A “drug-component-target-pathway-disease” network was constructed using network pharmacology research methods to identify the key active components of KTC in treating POI and to elucidate its potential mechanism. The protein expression of the FOXO3/SIRT5 pathway was detected by western blotting. ResultsCompared to the model group, the high-dose group of KTC showed a significant increase in ovarian index, significant increase in levels of E2 and SOD2, and a significant decrease in FSH levels. Through systematic analysis of the chemical constituents of KTC, 69 compounds were identified, including 7 organic acids, 14 alkaloids, 28 flavonoids, 15 terpenoids, 2 lignans, 2 phenylpropanoids, and 1 sugar. Based on network pharmacology research methods, it was determined that KTC exerts its therapeutic effect on POI through multiple components (paeoniflorin and malic acid), multiple targets (FOXO3 and SIRT5), and multiple pathways (prolactin signaling pathway, longevity regulating pathway, and metabolic pathways). The accuracy of the network pharmacology prediction was further validated by detecting the protein expression of SIRT5 and FOXO3a, which showed a significant increase in the middle and high-dose groups of KTC compared to the model group. ConclusionsKTC may effectively treat POI through a multi-component, multi-target, multi-pathway approach, providing an experimental basis for using KTC based on classical prescriptions in the treatment of POI.

Sex hormone mediated change on flexion reflex.

It has been shown that estrogen and progesterone receptors are expressed in the spinal cord; therefore, fluctuation in their concentrations may affect the spinal network and modulate the control of movement. Herein, we assessed the neuro-modulatory effect of sex hormones on the polysynaptic spinal network by using a flexion reflex network as a model system. Twenty-four healthy eumenorrheic women (age 21-37 years) were tested every other day for one menstrual cycle. Serum estradiol and progesterone were acquired at the time of testing. The flexion reflex of the tibialis anterior was elicited by sending an innocuous electrical stimulus directly to the posterior tibial nerve or plantar cutaneous afferent. Analyses were performed for each menstrual cycle phase: the follicular phase and the luteal phase. Increases in estradiol or progesterone concentrations were not associated with reflex duration or root mean squared (RMS) amplitude in either the follicular or luteal phases. In the luteal phase, an increase in the estradiol concentration was associated with a longer latency of the reflex (b = 0.23, p = 0.038). The estradiol × progesterone interaction was found towards significance (b = -0.017, p = 0.081). These results highlight the potential synergistic effect of estradiol and progesterone and may provide indirect confirmatory evidence of the observed modulatory effect.

Research on liposomal hydrogels loaded with "Liu Zi Tang" compound Chinese medicine for the treatment of primary ovarian insufficiency

IntroductionPrimary ovarian insufficiency (POI) is marked by reduced estrogen production and irregular ovulation, often resulting in lowered fertility or infertility. The traditional Chinese medicine "Liu Zi Tang" (LZT) has displayed promising outcomes in treating POI. Yet, conventional oral LZT administration poses challenges, including gastrointestinal irritation and the liver's first-pass effect. Thus, a novel drug delivery approach is imperative. MethodThis research incorporated the extracts of traditional Chinese medicine LZT into a novel liposome type, leading to the creation of LZT-glycerol plasmid/chitosan hydrogel (LZT-Gly-Lip/CS Gel) drug-carrier patches for achieving transdermal gradual-release drug delivery. The POI model was established in rats through intraperitoneal injection of vinylcyclohexene dioxide (VCD). A total of twenty-four 4-week-old female SD rats were distributed randomly among four groups: negative control (NC), vinylcyclohexene dioxide model (VCD), LZT/chitosan hydrogel treatment (VCD+LZT/CS Gel), and LZT glycerol liposome/chitosan hydrogel treatment (VCD+LZT-Gly-Lip/CS Gel). The therapeutic efficacy was evaluated by observing and analyzing the rats' body weight, diverse organ indices, serum hormone levels, and histopathological sections. ResultRats treated with LZT-Gly-Lip/CS Gel manifested significant enhancements in body weight (243.0 ± 11.0 g), serum estradiol concentration (64.362 ± 6.461 pg/mL), and uterus index (0.34 ± 0.05 %), demonstrating outcomes approaching normal levels (245.3 ± 12.0 g, 74.280 ± 8.903 pg/mL, 0.32 ± 0.10 %, respectively). DiscussionThese results confirm the effectiveness of LZT-Gly-Lip/CS Gel as a promising transdermal drug delivery system for addressing POI.

Correlation of serum kisspeptin and leptin with non-obstructive azoospermia: A cross-sectional study in a subset of Karachi population.

To determine the association of serum kisspeptin, leptin, and other hormonal profile with non-obstructive azoospermia (NOA) in infertile male subjects. This cross-sectional study was conducted at Australian Concept Infertility Medical Center, and Ziauddin University, Karachi from March 2018 to March 2020. The duration of the study was two years. Serum samples of 106 azoospermic participants were taken. Division of the subjects was done on a histological basis into obstructive azoospermia (OA) n=36, NOA n=70 which were further divided into spermatid maturation arrest (SMA), n=41, and sertoli cell-only syndrome (SCOS) n=29. Serum kisspeptin and leptin were measured by ELISA (Cloud-Clone Corp). The follicle-stimulating hormone (FSH) (p<0.01), luteinizing hormone (LH) (p<0.01), thyroid-stimulating hormone (TSH) (p<0.01), and estradiol (p<0.01) was significantly high in the NOA group. However, kisspeptin was significantly decreased (p<0.01) in the NOA group. In the multivariate analysis after adjusting for other variables, the results showed that with the decrease in kisspeptin, the chances of being NOA were increased. Moreover, with the increase in Leptin, FSH, LH, and TSH the chances of being NOA were significantly enhanced. Serum kisspeptin, leptin, FSH, LH, TSH, and estradiol can be a potential marker for NOA in terms of better diagnosis, targeted therapeutic management, and the decision to proceed with surgical intervention.

Mendelian randomization indicates causal effects of estradiol levels on kidney function in males.

Chronic kidney disease (CKD) is a public health burden worldwide. Epidemiological studies observed an association between sex hormones, including estradiol, and kidney function. We conducted a Mendelian randomization (MR) study to assess a possible causal effect of estradiol levels on kidney function in males and females. We performed a bidirectional two-sample MR using published genetic associations of serum levels of estradiol in men (n = 206,927) and women (n = 229,966), and of kidney traits represented by estimated glomerular filtration rate (eGFR, n = 567,460), urine albumin-to-creatinine ratio (UACR, n = 547,361), and CKD (n = 41,395 cases and n = 439,303 controls) using data obtained from the CKDGen Consortium. Additionally, we conducted a genome-wide association study using UK Biobank cohort study data (n = 11,798 men and n = 6,835 women) to identify novel genetic associations with levels of estradiol, and then used these variants as instruments in a one-sample MR. The two-sample MR indicated that genetically predicted estradiol levels are significantly associated with eGFR in men (beta = 0.077; p = 5.2E-05). We identified a single locus at chromosome 14 associated with estradiol levels in men being significant in the one-sample MR on eGFR (beta = 0.199; p = 0.017). We revealed significant results with eGFR in postmenopausal women and with UACR in premenopausal women, which did not reach statistical significance in the sensitivity MR analyses. No causal effect of eGFR or UACR on estradiol levels was found. We conclude that serum estradiol levels may have a causal effect on kidney function. Our MR results provide starting points for studies to develop therapeutic strategies to reduce kidney disease.

The concentration of anti-muller hormone in the blood serum of reindeer depends on the level of sex hormones

Reindeer husbandry is the leading branch of agriculture for the regions of the Far North. Reindeer (Rangifer tarandus) remains poorly studied from the point of view of genetics and reproduction, which hinders the intensification of development of the industry. Research is being actively conduct in the field of genetics of the productive qualities of reindeer, but the formation and functioning of its reproductive system has been little study. Hormonal regulation of the reproductive process and the formation of hormonal status at key stages of the reproductive cycle is a significant aspect of animal reproduction. Reindeer are characterized by a pronounced seasonality of reproduction, and the study of hormonal regulation of the reproductive cycle is the main aspect of the further use of assisted reproductive technologies. The work is devoted to the analysis of the level of anti-Mullerian hormone in females during the breeding season. The studies were carried out on reindeer farms of the MAU “Directorate of the Territory of Traditional Natural Resources Management of Soyots”, Buryatia, (female, n=29). The dependence of the concentration of anti-Müllerian hormone (AMH), which is a generally accepted indicator of the female ovarian reserve, on the concentration of sex hormones (progesterone, estradiol, testosterone and luteinizing hormone) in the blood serum of females was study. Hormone levels were determined by enzyme immunoassay. A higher content of sex hormones - testosterone, estradiol, progesterone and luteinizing hormone was revealed in the group of women with an AMH concentration of &gt;1 ng/ml than in the group of women with an AMH concentration of &lt;1 ng/ml. The significance of the differences in progesterone was p&lt;0.05, and in estradiol – p&lt;0.001. A low concentration of AMH (&lt;1 ng/ml), characterizing a reduced ovarian reserve of female reindeer, corresponds to a reduced concentration of sex hormones that support reproductive function, and, conversely, a high concentration of AMH (&gt;1 ng/ml), and, accordingly, a high ovarian reserve the reserve corresponds to an increased concentration of sex hormones - testosterone, estradiol, progesterone and luteinizing hormone.

Association of intrauterine synechiae with pituitary gonadotrophin pulse patterns: A pilot study

Background Intrauterine synechiae (IS) is an acquired uterine condition that occurs when scar tissues (adhesions) form within the uterus and/or cervix, causing menstrual disturbance. However, approximately 50% of patients with IS are refractory to treatment. Therefore, other endocrine disturbances, such as gonadotropin disturbance, may affect treatment success. Study aim To analyze gonadotropin levels in women with and without IS. Methods Ten women with refractory IS experiencing amenorrhea since at least 6 months and nine with normal menstrual cycles (control group) were included in this study. Blood sample were collected every 10 minutes during a 4-h period. The serial ultrasound was performed in both groups for evaluating the cycle phase. Blood was collected when the follicles size was between 5–10 mm. Serum LH, FSH, progesterone and estradiol concentrations were measured. To detect LH and FSH pulses, the technique proposed by Santen and Bardin was adopted; therefore, one pulse was defined as a 20% increase in the concentrations as to the preceding point, followed by an important decrease. Results No differences were observed between the study groups at baseline. Estradiol levels were lower in the IS group than in the control group, but the difference was not statistically significant. During the first hour of monitoring, cumulative FSH pulsatile frequency of IS group was lower than one of control. Conclusion Our data suggest that the estradiol levels of IS participants are lower than those of women with normal menstrual cycle. The role of this finding in the physiology of uterine synechiae requires further investigation.

Effects of Different Exercise Modalities on Sex Hormones and Anxiety and Depression in Female Drug Addicts

To explore the effects of different exercise modes on sex hormones and anxiety and depression of female drug addicts. METHODS: A random sampling method was used to include 30 female drug addicts who met the criteria from the Female Compulsory Drug Rehabilitation Center in Nanan District, Chongqing, China, who were randomly divided into a yoga group (n=10), a physical fitness group (n=10), and a control group (n=10), and underwent intervention training for a period of 12 weeks, 3 times per week, 1 h each time. The subjects' serum luteinizing hormone (LH), pituitary prolactin (PRL), and estradiol (E2) levels were quantitatively detected and analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) before and after the intervention. RESULTS: Changes in sex hormone levels of female drug addicts showed that serum luteinizing hormone (LH), pituitary prolactin (PRL), and estradiol (E2) levels were reduced compared with those of the control group. 12 weeks of different training interventions were able to regulate sex hormones, and hormone levels of the Yoga group and the Physical Fitness group were all significantly reduced (P&lt;0.01), and the Yoga group was significantly lower than the Physical Fitness group and the control group (P&lt;0.05); and reduced anxiety (HAHA), and reduced anxiety (HAHA). And reduce anxiety (HAHA) and depression (SDS) status.

Sex hormone-binding globulin exerts sex-related causal effects on lower extremity varicose veins: evidence from gender-stratified Mendelian randomization.

The association between serum sex hormones and lower extremity varicose veins has been reported in observational studies. However, it is unclear whether the association reflects a causal relationship. Besides, serum sex hormone-binding globulin (SHBG) has been rarely studied in lower extremity varicose veins. Here, we aim to investigate the association between serum levels of SHBG, testosterone, and estradiol and the risk of lower extremity varicose veins using Mendelian randomization (MR). We obtained genome-wide association study summary statistics for serum SHBG levels with 369,002 European participants, serum testosterone levels with 424,907 European participants, serum estradiol levels with 361,194 European participants, and lower extremity varicose veins with 207,055 European participants. First, a univariable MR was performed to identify the causality from SHBG and sex hormone levels to lower extremity varicose veins with several sensitivity analyses being performed. Then, a multivariable MR (MVMR) was performed to further assess whether the causal effects were independent. Finally, we performed a gender-stratified MR to understand the role of genders on lower extremity varicose veins. Genetically predicted higher serum SHBG levels significantly increased the risk of lower extremity varicose veins in the univariable MR analysis (OR=1.39; 95% CI: 1.13-1.70; P=1.58×10-3). Sensitivity analyses and MVMR (OR=1.50; 95% CI:1.13-1.99; P=5.61×10-3) verified the robustness of the causal relationships. Gender-stratified MR revealed that higher serum SHBG levels were associated with lower extremity varicose veins in both sexes. However, the OR of serum SHBG levels on lower extremity varicose veins risk in females (OR=1.51; 95% CI: 1.23-1.87; P=1.00×10-4) was greater than in males (OR=1.26; 95% CI: 1.04-1.54; P=1.86×10-2). Serum SHBG levels are positively related to lower extremity varicose veins risk in both sexes, especially in females. This may partly explain the higher prevalence of varicose vines among females.

Effect of zinc intake on association between fluoride exposure and abnormal sex steroid hormones among US pubertal males: NHANES, 2013-2016.

Excessive fluoride exposure can disturb the balance of sex hormones. Zinc is essential for sex hormone synthesis and spermatogenesis. But it is not clear how zinc affects the relationship of fluoride exposure with abnormal sex steroid hormones. Here, a total of 1008 pubertal males from the National Health and Nutrition Examination Survey (NHANES) in two cycles (2013-2014, 2015-2016) were enrolled. The concentrations of water fluoride and plasma fluoride and the levels of serum testosterone, estradiol, and sex hormone binding globulin (SHBG) were measured. Two 24-h dietary recall interviews were conducted to assess the dietary zinc intake. The relationships of fluoride exposure and zinc intake with sex hormones were examined using linear regression and logistic regression models, while the generalized additive model was used to evaluate their non-linear relationship. Our findings revealed that for every two-fold increase in plasma fluoride concentration, testosterone levels decreased by 7.27% (95% CI - 11.49%, - 2.86%) and estradiol levels decreased by 8.73% (95% CI - 13.61%, - 3.57%). There was also significant non-linear association observed between zinc intake and SHBG levels. Being in the first tertile of plasma fluoride had a 60% lower risk of high SHBG (OR = 0.40, 95% CI 0.18, 0.89) compared with being in the second tertile. When compared to the first tertile, being in the second tertile of zinc intake was associated with a 63% (OR = 0.37, 95% CI 0.14, 0.98) lower risk of high SHBG. Furthermore, we observed an interactive effect between the plasma fluoride and zinc intake on estradiol and SHBG, as well as the risk of high SHBG (P-interaction < 0.10). These findings suggest that fluoride exposure and zinc intake can affect sex steroid hormone levels and the risk of high SHBG. Notably, zinc intake may alleviate the increased risk of high SHBG and the abnormal changes of estradiol and SHBG caused by higher fluoride exposure.

Effect of baseline oestradiol serum concentration on the efficacy of anastrozole for preventing breast cancer in postmenopausal women at high risk: a case-control study of the IBIS-II prevention trial

An increased risk of breast cancer is associated with high serum concentrations of oestradiol and testosterone in postmenopausal women, but little is known about how these hormones affect response to endocrine therapy for breast cancer prevention or treatment. We aimed to assess the effects of serum oestradiol and testosterone concentrations on the efficacy of the aromatase inhibitor anastrozole for the prevention of breast cancer in postmenopausal women at high risk. In this case-control study we used data from the IBIS-II prevention trial, a randomised, controlled, double-blind trial in postmenopausal women aged 40-70 years at high risk of breast cancer, conducted in 153 breast cancer treatment centres across 18 countries. In the trial, women were randomly assigned (1:1) to receive anastrozole (1 mg/day, orally) or placebo daily for 5 years. In this pre-planned case-control study, the primary analysis was the effect of the baseline oestradiol to sex hormone binding globulin (SHBG) ratio (oestradiol-SHBG ratio) on the development of all breast cancers, including ductal carcinoma in situ (the primary endpoint in the trial). Cases were participants in whom breast cancer was reported after trial entry and until the cutoff on Oct 22, 2019, and who had valid blood samples and no use of hormone replacement therapy within 3 months of trial entry or during the trial. For each case, two controls without breast cancer were selected at random, matched on treatment group, age (within 2 years), and follow-up time (at least that of the matching case). For each treatment group, we applied a multinominal logistic regression likelihood-ratio trend test to assess what change in the proportion of cases was associated with a one-quartile change in hormone ratio. Controls were used only to determine quartile cutoffs. Profile likelihood 95% CIs were used to indicate the precision of estimates. A secondary analysis also investigated the effect of the baseline testosterone-SHBG ratio on breast cancer development. We also assessed relative benefit of anastrozole versus placebo (calculated as 1 - the ratio of breast cancer cases in the anastrozole group to cases in the placebo group). The trial was registered with ISRCTN (number ISRCTN31488319) and completed recruitment on Jan 31, 2012, but long-term follow-up is ongoing. 3864 women were recruited into the trial between Feb 2, 2003, and Jan 31, 2012, and randomly assigned to receive anastrozole (n=1920) or placebo (n=1944). Median follow-up time was 131 months (IQR 106-156), during which 85 (4·4%) cases of breast cancer in the anastrozole group and 165 (8·5%) in the placebo group were identified. No data on gender, race, or ethnicity were collected. After exclusions, the case-control study included 212 participants from the anastrozole group (72 cases, 140 controls) and 416 from the placebo group (142 cases, 274 controls). A trend of increasing breast cancer risk with increasing oestradiol-SHBG ratio was found in the placebo group (trend per quartile 1·25 [95% CI 1·08 to 1·45], p=0·0033), but not in the anastrozole group (1·06 [0·86 to 1·30], p=0·60). A weaker effect was seen for the testosterone-SHBG ratio in the placebo group (trend 1·21 [1·05 to 1·41], p=0·011), but again not in the anastrozole group (trend 1·18 [0·96 to 1·46], p=0·11). A relative benefit of anastrozole was seen in quartile 2 (0·55 [95% CI 0·13 to 0·78]), quartile 3 (0·54 [0·22 to 0·74], and quartile 4 (0·56 [0·23 to 0·76]) of oestradiol-SHBG ratio, but not in quartile 1 (0·18 [-0·60 to 0·59]). These results suggest that serum hormones should be measured more routinely and integrated into risk management decisions. Measuring serum hormone concentrations is inexpensive and might help clinicians differentiate which women will benefit most from an aromatase inhibitor. Cancer Research UK, National Health and Medical Research Council (Australia), Breast Cancer Research Foundation, and DaCosta Fund.

Human Bone Marrow Derived-Mesenchymal Stem Cells Treatment for Autoimmune Premature Ovarian Insufficiency.

Premature ovarian insufficiency (POI) is a relatively common gynecologic endocrine disorder, which is hypogonadism associated with amenorrhea, increased levels of gonadotropins, and hypoestrogenism. POI resulting from ovarian autoimmunity is a poorly understood clinical condition lacking effective treatments. This study is aimed to investigate the therapeutic effect of mesenchymal stem cells (MSCs) on autoimmune premature ovarian insufficiency. In this study, in vivo and in vitro experiments were conducted to clarify the therapeutic effects and possible mechanisms of human bone marrow-derived MSCs (hBMSCs) on autoimmune POI, and to provide an experimental evidence for the treatment of autoimmune POI by hBMSCs. Noteworthy, in this study, we used interferon-gamma (IFN-γ) to induce autoimmune inflammation in human granulosa cell line KGN, simulating the pathophysiological changes of granulosa cells in autoimmune POI, and therefore sought to establish an in vitro cell model of autoimmune POI, which is still lacking in experimental methodology. And we found that, in vitro, co-culture of hBMSCs could promote granulosa cell proliferation, inhibit apoptosis, improve hormone synthesis capacity, and reduce the occurrence of pyroptosis; and in vivo, hBMSCs resulted in improved estrous cycle disorders in autoimmune POI mice, increased serum estradiol, decreased follicle-stimulating hormone, improved ovarian morphology, increased number of primordial and primary follicles, decreased number of atretic follicles, and decreased ovarian granulosa cell apoptosis. hBMSCs have therapeutic effects on autoimmune POI both in vitro and in vivo.

#383 : The Correlation Between Serum Estradiol, Luteinizing Hormone (LH), and Progesterone on Day Human Chronic Gonadotropin (hCG) with In Vitro Fertilisation (IVF) Outcome

Background and Aims: Serum estradiol, LH, and progesterone have been studied for many years as they were considered to have relation with the pregnancy outcome in IVF procedure. The aim of this study is to determine the serum estradiol, LH, progesterone, biochemical pregnancy, clinical pregnancy, and ongoing pregnancy distribution of IVF patients; and to determine the correlation between serum estradiol, LH, and progesterone on day hCG with IVF outcome. Method: This is an observational study that was conducted in Yasmin IVF Clinic from 2013 until 2021. There were 416 samples. The serum estradiol, LH, and progesterone were collected from the IVF patient on day hCG. The IVF outcomes were collected by hCG blood test (biochemical pregnancy), USG (clinical pregnancy), and being checked after several months (ongoing pregnancy). The statistical analysis used IBM SPSS Statistics 26. Results: The serum estradiol, LH, progesterone, biochemical pregnancy, clinical pregnancy, and ongoing pregnancy were distributed abnormally. There is no significant difference between serum estradiol on hCG day with biochemical pregnancy (p=0.81), clinical pregnancy (p=0.205), and ongoing pregnancy (p=0.117). There is no significant difference between serum LH on hCG day with biochemical pregnancy (p=0.606), clinical pregnancy (p=0.45), and ongoing pregnancy (p=0.396). There is no significant difference between serum progesterone on hCG day with biochemical pregnancy (p=0.363), clinical pregnancy (p=0.942), and ongoing pregnancy (p=0.352). Conclusion: There is no significant difference between serum estradiol, LH, and progesterone on day hCG with IVF outcome.

#129 : The Ratio of Luteal Phase Serum Progesterone and Estradiol Can be Used to Predict Pregnancy in Frozen Embryo Transfer Cycles

Background and Aims: Low serum progesterone (P) levels on day of embryo transfer (ET) and luteal phase have been associated with poorer pregnancy outcome. This study aimed to know if serum estradiol (E2) and P levels during mid and late luteal phase are related with ongoing pregnancy. Method: The serum E2 and P levels from mid luteal phase (5 days after ET) to the day of the [Formula: see text]-hCG check (11 days after ET) in both fresh and frozen embryo transfer (FET) cycles was investigated between January 2019 and December 2021. Eligible patients were reproductive aged women with a normal uterus. Single blastocyst transfer cycles were included. Estradiol valerate (2 mg/bid) was started from day 3 of cycle as hormone replacement and vaginal micronized P (400 mg/bid) was started 5 days before ET in all FET cycles. The 2-degree polynomial fitted data were analysed and logistic linear model and ROC analysis were performed to assess E2 and P4 polynomial coefficients as a predictive test for ongoing pregnancy. Results: A total of 388 patients were included. The overall pregnancy rate was 43.8% and 31.3% for FET and fresh ET, respectively. On day 5 post ET, the serum P levels correlated significantly with ongoing pregnancy and live birth rates, especially in FET cycles. The ROC curve showed that there is a significant day 5 post ET predictive value of serum P4/E2 levels for pregnancy rate, being the AUC (95% CI) = 0.596 (0.539–0.653) for the combination of both fresh and FET cycles; and 0.611 (0.548–0.674) for FET cycles, with best cut-off values of 0.079 and 0.077, respectively. Conclusion: Serum P levels in mid and late luteal phase days are associated with pregnancy outcome both in fresh and frozen ET cycles. Ongoing pregnancies can be predicted using the day 5 post ET serum P4/E2 levels.

#332 : A Rare Case Report of Mixed Gonadal Dysgenesis with MOS 46, XY, 47,XY+21, 45,X Karyotype

Background and Aims: Mixed gonadal dysgenesis is a condition of unusual and asymmetrical gonadal development leading to an unassigned sex differentiation. A number of differences have been reported in the karyotype, most commonly a mosaicism 45, X/46, XY. We herein report an interesting case of mixed gonadal dysgenesis. Method: We present a rare patient case with mixed gonadal dysgenesis as a disorder of sex development (DSD) and a new pattern of chromosome in the karyotype, undergoing laparoscopic procedure for sex correction. Results: A 20-year-old person, reared as female presented with complaints of genital ambiguity and primary amenorrhoea along with lack of secondary sexual characters, but without short stature and Turner’s stigmata.Karyotype analysis revealed Mos 46, XY, 47,XY+21, 45,X karyotypeLuteinizing hormone (LH) was 18.3 mIU/ml and follicle-stimulating hormone (FSH) was 70,07 mIU/ml. Serum estradiol level was 35,9 pg/ml and prolactin was 25,8 ng/ml). Magnetic resonance imaging (MRI) pelvis with contrass (with ultrasonogrphy correlation) revealed uterus hypoplasia with right ovarian-like structures. View of corpus uteri measuring 1× 1.5× 0.8 cm with cervix building length 1 × 0.5 cm were visualized laparoscopically. The right tube and left tube (include bilateral fimbare) appear to be normal in shape and size. Right gonad with base in corpus uteri, white color, elongated ligament-like shape 0.5 × 0.3 × 0.8 cm, no follicle visible. The left gonad was seen with its base at the corpus uteri, white in color and elongated like a ligament uk 0.5 × 0.4 × 0.8cm, no follicles visible. Both gonads biopsied. Conclusion: Histopathology is still awaiting results. The patient was managed with a multidisciplinary approach and fertility issues discussed with the patient’s family.