The effectiveness of the drug Divigel in patients with surgical menopause

Twenty women with surgical menopause aged40-50years received parenteral hormonal replacement therapy with estradiol (preparation Divigel) for the period of 12 months. Twenty healthy women formed the control group. The following indeces were estimated during the study: menopausal Kuppermans index, and the leveloffollicle-stimulatinghormone and estradiol in blood serum. Kuppermans index remarkably decreased in the course of treatment (p0,05). Decrease of FSH level was associated with stable growth of estradiol level (p0,05). The absence of manifested side effects and considerable change of body build index, the possibility of choosingthe minimal effective doze individually allow to apply HRT with Divigel more widely.

The Concentrations of Cholesterol and Reproduction Hormones in Serum of Rabbits Doe That Consumed Moringa oleifera Leaf Extracts

This study was conducted to examine the effect of various kinds of Moringa leaf extracts on cholesterol, estradiol, FSH, LH levels and litter size in rabbit does. The extracts used were hexane fraction extract (HeEF), ethanol fraction extract (EtEF) and ethanol rough extract (EtCE) from moringa leaf flour. Seven treatments were administered including extracts in pellets at a dose of 0, 0.13% HeEF, 0.26% HeEF, 0.37 EtEF, 0.74% EtEF, 0.54% EtCE and 1.08% EtCE. Each treatment was reduplicated on 4 rabbits. Cholesterol levels, estradiol, LH and FSH blood serum, mating readiness and litter size were measured, which results showed that the treatment significantly (P <5%) lowered the cholesterol level and increased the estradiol level in blood serum. On the other hand, the treatment had no significant effect on FSH, LH and litter size levels except at LH levels 2 hours after mating.

The Effect of Chemotherapy on Estradiol Levels in Patients with HER 2-Overexpression Breast Cancer in Dr Moewardi General Hospital, Surakarta, Indonesia

AIM: This study aims to evaluate the effect of adjuvant chemotherapy on estradiol levels in patients with HER 2-overexpression breast cancer in a developing country. METHODS: This comparative study with pre- and post-design model observation approach, involving patients with HER 2-overexpression breast cancer who had undergone surgery and had never received chemotherapy or hormonal therapy before, who were then given adjuvant chemotherapy. Estradiol levels were measured before and after chemotherapy. The study was carried out in the surgical oncology division of RSUD Dr. Moewardi (RSDM) Surakarta from January 2020-December 2020. Descriptive data are presented in a frequency table based on age, menstrual status, parity status, breastfeeding status, contraception, contraception duration, family history, stage, and histological grade. Before and after chemotherapy in patients with breast cancer, the estradiol levels employed the paired sample t-test of the Wilcoxon rank test because the data did not meet the normality assumption. RESULTS: From the total data of 21 patients, 15 patients experienced a decrease in estradiol levels after chemotherapy, while six patients underwent an increase. The mean estradiol level before chemotherapy was 89.41 pg/ml, whereas the mean estradiol level after chemotherapy was 55.90 pg/ml. It indicates a difference in the decrease in estradiol levels of 33.51 pg/ml. The statistical test results also obtained a p-value of = 0.033 (p < 0.05), which signifies a significant difference between estradiol levels before and after chemotherapy. Thus, chemotherapy is effective in lowering estradiol levels in patients with breast cancer. CONCLUSION: Chemotherapy affects decreasing estradiol levels in patients with HER2 overexpression breast cancer.

Effect of Nigella sativa on Estradiol Levels and Menopausal Symptoms in Post-Menopausal Females

Introduction: Menopause is the permanent cessation of menses, typically occurs in women of 45-55 years. Menopause is associated with a number of somatic, psychological and sexual symptoms due to decline in estradiol levels resulting in poor quality of life of postmenopausal females. Aims & Objectives: The purpose of the current study was to determine the effect of Nigella sativa on menopausal symptoms and estradiol levels in postmenopausal females. Place and duration of study: Department of Physiology PGMI, Lahore for 8 weeks. Material & Methods: It was an interventional study conducted on 30 postmenopausal females. Nigella sativa was administered in the dose of 1g/day after breakfast for a period of 8 weeks. Menopausal Rating Scale (MRS) was filled and blood sample was taken before and after giving Nigella sativa for estradiol and testosterone levels. Data was analyzed by paired t-test using SPSS-21 and p- value less than 0.05 was considered significant. Results: The result of the study showed that there was statistically significant reduction in the overall score of MRS (p = 0.001) and in all its domains, somatic (p=0.001), psychological (p=0.001) and urogenital (p=0.017). There was also significant improvement in blood estradiol level after 8 weeks of Nigella sativa administration (p= 0.021). Conclusion: Nigella sativa supplementation increases estradiol level and decreases menopausal symptoms severity as indicted by significant reduction in the 3 domains of MRS and may be used by postmenopausal females on regular basis to improve their quality of life.

Testosterone and Estradiol as Novel Prognostic Indicators for HBV-Related Acute-on-Chronic Liver Failure

Background: HBV-related acute-on-chronic liver failure (HBV-ACLF) has a high short-term mortality and urgently needs an early warning system with simplicity and high accuracy. Previous studies show that sex hormones play potential roles in the progression of HBV-related liver diseases.Aims: To explore the effect of testosterone and estradiol on the occurrence and prognosis of HBV-ACLF.Methods: A prospective cohort of 300 chronic hepatitis B (CHB) patients was enrolled among which 108 were diagnosed with HBV-ACLF at admission and 20 developed to HBV-ACLF during hospitalization. We compared the level of serum testosterone and estradiol of patients with varied ACLF background, disease severity and cirrhosis conditions and analyzed the predictive ability of short-term prognosis. A novel prognostic model involving testosterone was developed and further validated in the HBV-ACLF group.Results: The baseline estradiol level of HBV-ACLF group was significantly higher while testosterone was lower than that of non-ACLF group. The estradiol level increased while the testosterone level decreased as the number of organ failures increased. Testosterone had high accuracy in predicting the short-term mortality in HBV-ACLF (AUROC = 0.726) and estradiol did better in predicting the occurrence of ACLF during hospitalization (AUROC = 0.695). The novel prognostic model involving testosterone (TATIM model) was proved to have considerable prediction efficiency in HBV-ACLF cohort with or without cirrhosis.Conclusion: Testosterone could be utilized as short-term prognostic indicator for HBV-related ACLF and estradiol can help to predict its occurrence. TATIM model is a novel prognostic model for HBV-related ACLF with simplicity and good performance irrespectively of liver cirrhosis.Clinical Trial Registration Number: This study was based on a sub-cohort from the prospective multicenter cohort (NCT02457637).

P–325 The impact of letrozole on endometrial thickness in IVF cycles

Study question Does daily administration of letrozole during IVF stimulation affect endometrial thickness ? Summary answer Patients treated with letrozole during fresh IVF cycles had a thinner endometrium on the day of trigger compared to patients who did not receive letrozole. What is known already Letrozole supplementation is commonly used during fertility preservation for breast cancer patients to reduce peak estrogen levels with no adverse effects on embryo outcomes. Studies in poor responders have found that letrozole use resulted in a shorter duration of stimulation and a lower total dose of gonadotropin, with no detrimental effect on IVF outcomes. In normal responders, studies have shown an increase in blastocysts obtained, but have not yet shown an increase in clinical pregnancy rates. There is concern that when a fresh embryo transfer is planned letrozole use may negatively affect endometrial thickness and subsequently diminish pregnancy rates. Study design, size, duration In a retrospective cohort study between January 2009 and June 2019 at a single academic fertility center, we compared the endometrial thickness in 97 cancer patients who underwent IVF-fertility preservation with daily letrozole use to 158 cancer patients who underwent IVF-fertility preservation without letrozole. Participants/materials, setting, methods All women diagnosed with cancer were referred for fertility preservation prior to gonadotoxic treatment exposure and were less than 40 years old at the time of oocyte retrieval. All patients who received letrozole started on day one of stimulation and continued until the day of oocyte retrieval. The primary outcome was endometrial thickness on the day of trigger. The secondary outcomes were number of oocytes retrieved, number of MII retrieved, and maximal estradiol level. Main results and the role of chance During the study period, 336 cancer patients underwent fertility preservation. Eighty-one patients were excluded; 50 because they had an intrauterine device or were on long term oral contraceptives and 31 because endometrial thickness was not documented. Of the remaining 255 patients, 86 had breast cancer, 95 had a hematological cancer and 74 had various other cancers. Ninety-seven cancer patients treated with letrozole were compared to 158 cancer patients who did not receive letrozole. Patients who received letrozole were significantly older (34 vs 28yrs, P &lt; 0.0001). There were no significant differences in baseline characteristics such as BMI, AFC nor in the total duration for stimulation. Endometrial thickness on the day of trigger was significantly less in letrozole treated patients (8 vs 9mm, P &lt; 0.003). There were no significant differences in total number of oocytes retrieved (12.5 vs 11, P = 0.126) nor in the number of mature oocytes (8 vs 8, P = 0.312). Patients in the letrozole group received a higher total gonadotropin dose (2680IU vs 1980IU, P = 0.016). The maximum estradiol level was significantly lower in patients treated with letrozole (1068 vs 3838ml/dl, P = &lt;0.0001). A regression analysis showed that using letrozole during stimulation decreased the endometrial thickness by 0.81mm (CI –1.37 to –0.253, P = 0.005). Limitations, reasons for caution The retrospective nature of this study could have introduced selection and misinformation bias. We report on cancer patients where all oocytes or embryos were vitrified. Without fresh embryo transfer data, it is unclear if a thinner endometrium due to letrozole will effect the implantation or pregnancy rate. Wider implications of the findings: As the use of letrozole expands beyond cancer patients and poor responders, it is important to understand the impact on the endometrium. This study shows that letrozole reduces endometrial thickness. However, the effect on endometrial function remains unknown. Further study is needed before letrozole can be used with fresh transfers. Trial registration number 2020–6370

O-078 Predictive factors of autologous Oocyte Post-warming Survival rate

Study question Are there any clinical or paraclinical predictive factors of Oocyte Post-warming Survival (OPS) rate? Summary answer Woman age, Body mass Index, estradiol level on triggering day and estradiol/oocyte ratio are critical predicting factors that should be considered before performing oocyte vitrification. What is known already Since the development and the validation of oocyte vitrification, we vitrify oocytes in different medical situations for patients who benefit ICSI. Although the OPS rate in our centre is satisfying, occasionally, it happens to be lower. OPS is dependent on quality of oocyte as demonstrated by the difference of OPS in oocyte donation/autologous cycles. The present study questions the existence of clinical and paraclinical factors predicting in OPS. In order to tackle this issue, we have assessed several parameters related to the woman and to her response to hormonal treatment known to influence oocyte quality in relation to OPS Study design, size, duration A retrospective observational study of 786 autologous oocyte vitrification cycles was performed from October 2011 to July 2018 in 5 situations: cycles where only a part of mature collected oocytes were vitrified [1] Partial oocyte vitrification program(n = 605), [2] Patients opposed to embryo cryopreservation(n = 2) and oocyte freeze-all cycles for the following reasons [3] Uncontrolled Ovarian hyperstimulation( = 89), [4] Unfavorable uterine environment/receptivity(n = 71) and [5] Absence of spermatozoa(n = 20). 1175 warming cycles were analyzed to identify predictive factors for OPS. Participants/materials, setting, methods Oocytes were vitrified/warmed using Kitazato media and system. The ratio of OPS survival was measured between the number of intact oocytes and the number of warmed oocytes. The factors assessed as potential predictors of OPS were: woman age, body mass Index (BMI), Estradiol level on triggering day (E2), E2/ number of recovered oocytes (EOR), number of recovered oocytes and maturity ratio (number of mature oocytes/number of recovered oocytes). Statistics were performed using SPSS software. Main results and the role of chance A total of 1175 studied warming cycles were performed and 5421 oocytes were warmed with a mean OPS rate of 84,6% (±22,6). OPS rates were comparable in all situations: [1] 3084/3688 (83,6%), [2] 6/6 (100%), [3] 931/1121 (83,1%), [4] 393/458 (85,8%), [5] 125/148 (84,5%). The mean woman age (33,2 years±4,9 vs 33,1 years ±4,3), mean woman BMI (23,1 kg/m2±3,9 vs 22,9 kg/m2±4,2), mean E2 (2587,7pg/ml±1140,5 vs 2513,2pg/ml±1098,7), mean EOR (207,5pg/ml±119,4 vs 196,0pg/ml ±119,4), mean number of total recovered oocytes (15,0±6,8 vs 14,7±6,8), mean maturity ratio (85,4%±13,7 vs 86,0%±14,2) showed no statistical difference in women with reduced OPS (≤85%) as compared to women with standard OPS (&gt;85%). Subgroups analyses revealed significant higher occurrence of reduced OPS in advanced age women (&gt;40years) (OR = 2,4; [95%CI:1,3-4,4] p &lt; 0,05) as compared to women of other age categories: &lt; 30years (OR = 0,5; [95%CI:0,2-0,9]), 30-35years (OR = 0,4; [95%CI:0,2-0,7]), 36-40years (OR = 0,2; [95%CI: 0,3-0,5]). The combination of advanced age with abnormal BMI ( &lt; 18,5 or &gt; 24,9kg/m2: OR = 7,3[95%CI:1,6-34,0] p &lt; 0,01), or elevated E2 (&gt;3000pg/ml: OR = 3,3[95%CI:1,0-11,0] p &lt; 0,05) or atypical EOR ( &lt; 140 or &gt; 250pg/ml: OR = 3,7[1,1-12,2] p &lt; 0,05) amplified the risk of reduced OPS. Women with abnormal BMI combined with elevated E2 (OR = 2,1[95%CI:1,1-3,9] p &lt; 0,05) or atypical EOR (OR = 1,6[95%CI:1,0-2.6] p &lt; 0,05) were also at higher risk of reduced OPS. Limitations, reasons for caution Oocyte vitrification is a manual technique that depends on the skill of the operator. Inter-operator variability was not taken into account in our statistical analyses neither were data regarding ovarian stimulation protocols nor were infertility etiologies. Wider implications of the findings This work enabled to identify patient or treatment related factors that highly influence the outcome of oocyte vitrification/warming cycles. Our findings will likely help refining criteria for the selection of candidate patients for oocyte vitrification or to cancel bad prognosis cycles. Trial registration number NA

Ovarian function suppression in premenopausal patients with concurrent endocrine therapy use.

6574 Background: The addition of ovarian function suppression (OFS) to endocrine therapy (ET) for premenopausal women with high risk, hormone receptor-positive breast cancer improves disease outcomes. However, in the SOFT-EST study, up to 17% of patients receiving gonadotropin-releasing hormone agonists (GnRHa) did not have appropriate ovarian suppression within the first year of treatment. Few studies have explored the long-term effectiveness of OFS to maintain estrogen suppression. Guidelines for estradiol monitoring during OFS therapy are not clearly defined. Methods: We performed a retrospective, single institution review of all patients who received concurrent GnRHa injections and ET since 2010. Only estradiol concentrations that were assessed during OFS treatment were abstracted from the medical record and included in the analysis. The primary endpoint was the percentage of patients with a non-suppressed estradiol concentration (defined as standard estradiol or high-sensitivity estradiol ≥ 10 pg/ml) identified during OFS cycle 2 ( > 35 days after OFS initiation) and/or later cycles. The secondary endpoint, which included only those patients with estradiol assessment within 35 days of OFS initiation, was the percentage of patients with a non-suppressed estradiol level when measured within the first 35 days after OFS initiation. For both cohorts, differences in age, body mass index (BMI), and previous chemotherapy use were summarized via multivariable logistic regression. Results: 148 patients received concurrent OFS and ET. Patients were excluded because of lack of estradiol assessment during OFS therapy (n = 13) and non-compliance with GnRHa injections (n = 4). The average age and BMI were 43.1 years and 29.1 kg/m2, respectively. 35 of 131 patients (26.7%) had at least one non-suppressed estradiol level during OFS cycle 2 and/or later cycles. The median time to detection of non-suppression was 250 days (range: 53 – 2573 days). Patients whose estradiol concentration remained suppressed throughout treatment with OFS and ET were more likely to be older (OR 1.12 [95% CI 1.05-1.22], p =.02), have a lower BMI (OR 0.88 [95% CI 0.82-0.94], p <.001), and have received chemotherapy (OR 6.30 [95% CI 2.06-20.8], p =.002). For the secondary endpoint, 20 of 83 patients (24.1%) had a non-suppressed estradiol level within 35 days of OFS initiation. Lower BMI was associated with achieving ovarian suppression by 35 days (OR 0.85 [95% CI 0.77-0.93], p <.001); no association was noted for age or chemotherapy. Conclusions: More than one-fourth of patients in this “real world” population had at least one non-suppressed estradiol level during treatment, both the month after the initial OFS dose and at later time points. Patients on OFS, especially those on aromatase inhibitor therapy and those at increased risk of non-suppression, may require frequent and long-term estradiol monitoring during treatment.