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The structure of the presentation will be 1) Pandemic-Epidemiology 2) General Pandemic-Management 3) HRT and COVID 4) Different spectrum of menopausal symptoms (Europe/Asia) 5) Different risks lead to different HRT. 1) Pandemic-Epidemiology: SARS-COVID-19 has got to be a new disease, China was the first to suffer from the pandemic starting in December 2019 with spread all over the world. Diagnosis, treatment and protective measures have started in Europe in March 2020;up from autumn 2022 in Europe the pandemic changed to endemic, but protective measures still should be continued in risk patients like in hospitals and nursing homes. Rehabilitation will for long-time be an issue like treatment of "Post-" and "Long-COVID". China pursued a zero-COVID-policy until Dec 2022. The sudden stop of almost all measures led to a sharp increase in infections, which shows that the disease will remain a global risk. 2) General Pandemic-Management: Protective measures like vaccination, surgical masks, screening/testing, isolation management, travel/residence history in high-risk regions, education of patients and families had to be the first priority, ahead of other issues such as the management of menopause. 3) HRT and COVID: Already the first prelimary data assessed in Wuhan/China have shown that women with low estradiol-levels had more severe infections with COVID. An analysis of health records of 68,466 COVID-positive patients from 17 countries showed that the fatality risk for women > 50 years receiving HRT was reduced by more than 50% compared to those women not taking HRT (Seeland, 2020). Likewise from a case-control study analyzing the self-reported data of 1.6 million UK menopausal women through the COVID-Symptoms Study Smartphone application (control populations adjusted for age, body mass index, and smoking status) was concluded, that HRT not only can be used, but even can protect from COVID-infections and/or their sequelae (Costeira, 2021). 4) The different spectrum of menopausal symptoms (independent of COVID-infections) comparing data in Europe (showing more vasomotor symptoms) and China (more somatic symptoms) will be presented, including own data. 5) Different risks during HRT consequently lead to different use of HRT, especially more transdermal estrogen combined with progesterone in Europe due to much higher VTE-risk, but more management of the high bleeding-problems in China using individualized (mostly oral) estrogen/progestogen combinations. Copyright © 2023
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Introduction: We performed matched case-control studies utilizing cohorts of postmenopausal women with ER+ breast cancer receiving adjuvant aromatase inhibitors (AI) on MA.27 [anastrozole, exemestane] or PreFace [letrozole] to assess the association between estrogen suppression after 6 months of treatment and an early breast cancer (EBC) event within 5 years of AI initiation (Clin Cancer Res 2020;26:2986-98). We found a significant 3.0-fold increase in risk of an EBC event for those taking anastrozole with levels of estrone (E1) >=1.3 pg/mL and estradiol (E2) >=0.5 pg/mL, but not for exemestane or letrozole. Given these findings we designed a prospective pharmacodynamic (PD) study to evaluate the impact of anastrozole (1 mg/day: ANA1) on E1 and E2 levels, and among those with inadequate estrogen suppression (IES: E1 >=1.3 pg/mL and E2 >=0.5 pg/mL), to evaluate the safety and PD efficacy of high-dose anastrozole (10 mg/day: ANA10), which has been found to be safe in prior clinical trials (Cancer 1998;83:1142-52). Method(s): Post-menopausal women with stage I-III, ER >=1% positive/HER2-negative breast cancer who were candidates for anastrozole were eligible after completion of locoregional therapy and chemotherapy, as clinically indicated. Women who were pre-menopausal at diagnosis were not eligible. All patients received 8-10 weeks of ANA1, after which those with adequate estrogen suppression (AES: E1< 1.3 pg/mL or E2< 0.5 pg/mL) came off study. Those with IES went on to receive ANA10 for 8-10 weeks, followed by letrozole (2.5 mg/day: LET) for 8-10 weeks. All patients were managed at their treating oncologist's discretion following study discontinuation. E1 and E2 blood levels were measured pre-treatment and after completion of each treatment cycle by a CLIA-approved liquid chromatography with tandem mass spectrometry in the Immunochemical Core Laboratory at Mayo Clinic. With a sample size of 29 patients with IES after ANA1, a one-sided binomial test of proportions with a significance level of 0.05 will have an 87% chance of rejecting the proportion with AES after ANA10 is at most 25% (Ho) when the true proportion is at least 50%. Specifically, the null hypothesis is rejected if the number of women with AES after ANA10 is 12 or more. Data lock was July 6, 2022. Result(s): Of the 161 women enrolled from April 2020 through May 2022, 3 withdrew consent prior to start of ANA1 and 2 were ineligible;thus, 156 women comprised the study cohort. Median patient age was 64 years (range 44-86), 10% of patients were of Hispanic ethnicity and/or non-white race, and 15% received chemotherapy. Six patients remain on ANA1, and 10 discontinued ANA1 due to refusal (7), adverse event (AE) (2), or COVID-19 (1). Forty-one of the remaining 140 patients (29.3% 95%CI: 21.9- 37.6%) had IES with ANA1. Nine of these 41 patients did not go on to ANA10 due to refusal (6) or AE (3). Of the 32 patients who started ANA10, 8 remain on treatment, 5 discontinued due to refusal (3) or AE (1-grade 2 urinary tract infection;1-grade 1 palpitations), and 19 had a blood draw 45 days or more after starting ANA10. No grade 3-5 AEs or grade 2 hot flashes or arthralgias were reported. Of these 19 patients, 14 achieved AES with ANA10 (73.7% 95%CI: 48.8-90.9%). All 19 patients switched to LET of which 3 remain on treatment, 1 is missing E1/E2 data, and 15 had a blood draw 45 days or more after starting LET. Of these 15 patients, 10 maintained AES, 2 acquired AES with LET, and 3 no longer had AES. Anastrozole and letrozole drug levels will be reported at the meeting. Conclusion(s): Approximately 29% of postmenopausal women with ER+/HER2- BC receiving adjuvant anastrozole 1 mg/daily had IES. A majority of these patients achieved AES with dose escalation to ANA10 without tolerability issues. E1 and E2 levels are logical biomarkers given the mechanism of action of anastrozole, and further study utilizing them to determine the optimal dose of anastrozole for a given patient should be performed.
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Objectives Data regarding the effects of pubertal suppression on mental health parameters in transgender (TG) youth are limited. Even less is known about the psychological well-being of caregivers during the time that their child's puberty is paused. We describe the impact of pubertal suppression on mental health in TG youth and their caregivers during the first 12 months of gonadotropin-releasing hormone analog (GnRHa) therapy. Methods TG youth who met clinical criteria for a puberty blocker were recruited from the gender health program at our institution. Subjects were treatment naive and anticipated to be on a blocker alone for >= 1 year. Psychological measures were obtained at baseline, 6 months, and 12 months using short-form validated questionnaires from the NIH's Patient Reported Outcomes Measurement Information System (PROMIS). Self-reports of anger, anxiety, depression, stress, and life satisfaction were obtained in TG youth. Their primary caregiver completed self-reports of anxiety, depression, and stress, while also providing proxy-reports of their child's anxiety, depression, and life satisfaction. Results Twenty-eight subjects (mean age 12.3 years +/-1.35, range 8.42-13.95) were enrolled of whom 20 were assigned female at birth (AFAB) and 8 were assigned male at birth (AMAB). To date, 12- month measures have been collected for 14/20 AFAB and 6/8 AMAB subjects. At 12-month follow up, the median time since blocker initiation was 13.6 months (range 10.7-20.6). Breast Tanner stage in subjects AFAB and testicular volume in subjects AMAB remained stable or slightly decreased over the course of the study. At 12 months, estradiol levels ranged from <15- 27 pg/mL in subjects AFAB and all values were <20 pg/mL in subjects AMAB. Testosterone values ranged from <10-49 ng/dL in subjects AFAB and 10-23 ng/dL in subjects AMAB. Using one-way repeated-measures ANOVA, no significant main effect of time on any measure of psychological functioning for TG youth or their caregivers (p>0.05) was found. Conclusions All measures of psychological well-being remained stable in TG youth and their caregivers during 12 months of pubertal suppression with a GnRHa. As puberty progresses, an increase in gender dysphoria is anticipated, and it is possible that pubertal suppression prevents a deterioration in behavioral health indices during this time period. The lack of an improvement in psychological measures may have been related to a negative impact of the COVID-19 pandemic on the mental health of our cohort.
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Objectives The COVID-19 pandemic caused stress, social isolation and physical inactivity in many. We proposed to review anthropometric/biochemical profiles in girls seen for precocious puberty (PP) (ages 5-8 years) during the pandemic (3/2020- 3/2021) compared to girls seen in the prior 2 years (2/2018-2/2020) and look at environmental and psychosocial impacts. Methods A retrospective chart review of the girls prepandemic (Pre-PD) were compared to those seen during the pandemic (PD). Criteria for PP: luteinizing hormone (LH range: 0.02-0.3 mIU/L, ECLIA, Esoterix) with >0.3 defined as pubertal;estradiol (range <36 pg/ml for age 7-9 years, LCMS, ARUP) with >=36.0 pg/ml defined as pubertal;follicle stimulating level (FSH 0.4- 6.5 IU/L ECLIA, ARUP). Girls with isolated adrenarche were excluded. Pelvic ultrasound with ovarian volumes (OVs>1cc considered pubertal) and MRI pituitary were done as indicated. Bone age/chronological age ratio (BA/CA) >1 was considered advanced. A Covid-19 impact survey was sent via a HIPAA compliant REDCap link to assess activity, sleep, and psychosocial stressors, distress on 0-10 scale (mild 0-4, moderate 5-7, severe 8-10) to families. T-tests and bivariate correlations were run (SPSS Ver 21). Results In total 56 subjects were included (pre-PD=23 vs. PD=33). A 30% increase in puberty referrals was noted during the pandemic. Weight (mean+ SD: Pre-PD vs. PD: 26.8+/-5 vs. 26.9+/-5.7 kg) and BMI (17.3+/-2.3 vs.16.8+/-2.3kg/m2). Estradiol (9.7+/-7.5 vs.21.9+/-16.6 pg/ml;p-value =0.006), random LH (1 vs. 15) were pubertal. OVs (1.75+/-1.1 vs. 2.75 cc) and BA/CA (1.1+/- 0.4 vs. 1.0+/-0.5) were seen in the two groups respectively. There was a correlation between estradiol levels and OVs in PD group (r= 0.5;p=.05). Survey results showed 61% of subjects used remote learning, 55% spent >4 hours on social media (Tik Tok, WhatsApp, etc.), 50% reported no exercise and 33% reported no social interaction. Stress was moderate with a parental report of 5.4/10, (50%essential workers, 18% lost jobs) & children reported stress level of 4.8/10. Conclusions We report an increased incidence of PP during the pandemic (perhaps due to a delay in evaluation) and a more advanced puberty (higher estradiol levels and greater OVs) compared to Pre-PD patients. Though weight gain, potentially due to inactivity, did not appear to contribute, we believe that stress, excessive social media use and/or isolation could be factors which contributed to the increased incidence of PP during the pandemic.
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Introduction: In the last 10 years, blue light (BL) sources such as tablets and phones has increased in every age group. Especially due to the Covid-19 pandemic, screen exposure has also increased in childhood. However, the effects of BL exposure in the puberty process aren't clear. We aimed to examine the effect of BL exposure and exposure time on puberty Methods: Immature eighteen 21-day-old female Sprague Dawley rats were divided into three groups consisting of six rats in each group: Control Group (CG), Experiment Group-1 (EG-1), Experiment Group-2 (EG-2). CG rats were maintained under standard conditions with 12/12-hour light-dark cycles. The rats of EG-1 and EG-2 were exposed to BL (450-470 nm / irradiance level 0.03 uW/cm2) for 6 hours and 12 hours, respectively. Rats were exposed to BL until the first signs of puberty and then they were euthanasiad. Serum FSH, LH, Estrodiol, testosterone, DHEA-S, leptin, melatonin were studied by ELISA method. Ovaries and uterus were dissected for histomorphological examination Results: The medians of the pubertal entry days of the CG, EG-1 and EG-2 were 38th, 32th, and 30th days, respectively. (p: 0.001) A negative correlation was found between the puberty entry day of the groups and the exposure to BL and the duration of exposure. (r:-0.910, p<0.001) The FSH, testosterone, DHEA-S, leptin levels of all groups were similar. (p> 0.05) However, LH and estradiol levels of EG-1 were higher compared CG. (p:0.027) There was a negative correlation between BL exposure, exposure time and melatonin levels (ro:- 0.537, p: 0.048) Ovarian tissue was compatible with pubertal period in all groups. As the BL exposure time increased, capillary dilatation and edema in the over tissue increased. Prolonged exposure caused polycystic over like (PCO-like) morphological changes and apoptosis in granulosa cells. Conclusion(s): Our study is the first to show the effects of BL exposure on puberty. In our study, we showed that exposure of BL and the duration of exposure lead to early puberty. PCO-like, inflammation and apoptosis were detected in the ovaries with the increase in BL exposure time. There are studies showing that there is an increase in cases with precocious puberty and acceleration in puberty pace during the closure period compared to the pre-pandemic period. In our study, we experimentally demonstrated the effects of BL exposure on puberty and the relationship between increased exposure time.
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Objective: To compare the role of intra-ovarian Platelet-Rich Plasma (PRP) versus marrow derived Stem-Cells (SC) instillation for improvement in ovarian-reserve (AFC,AMH, FSH). Design: A prospective comparative study. Method: 72 infertile females (20-39 years) with poor ovarian reserve (AMH <1.2 ng/ml;AFC < 5) (POSEIDON criterion) were enrolled for study between January 2020 -December 2021. The two comparative groups underwent either intra-ovarian PRP instillation (n = 42) or autologous SC transplantation (n = 30). After the two groups were matched (PRP vs. SC) for baseline characteristics (Age, AMH, AFC, FSH, Estradiol), 30 subjects in each group were compared for change in serum FSH/AMH/Estradiol levels and AFC at 1st month and 3rd month post intervention from the baseline. This was also compared between the two groups using Student t-test. The cost and procedural pain measured using Visual analog scale (VAS) were also compared. Results: After matching for baseline characteristics, significant ∼ 1.8/2 and ∼1.5/1.6fold increase in AFC at 1st/3rd month post intervention (p < 0.001) was observed after PRP instillation and SC transplantation respectively. However, PRP group fared better than SC group at 3rd month post intervention (7.07 vs. 5.60, p = 0.02), while no significant difference existed amongst the two at 1st month of follow up. Levels of Serum FSH, AMH and Estradiol (p > 0.05) did not differ significantly from the baseline at 1st and 3rd month post intervention in both the groups. Similarly, there was no significant difference between the two groups in serum FSH level (7.98 IU/ml vs. 9.62 IU/ml, p = 0.062;8.26 IU/ml vs. 9.50 IU/ml, p = 0.15), AMH level (1.62 ng/ml vs. 1.02 ng/ ml, p = 0.27;1.35 ng/ml vs. 0.95 ng/ml, p = 0.24), Estradiol level (49.12 pg/ml vs. 56.48 pg/ml p = 0.443;54.7 pg/ml vs. 61.12 pg/ml, p = 0.44) at 1st and 3rd month post intervention respectively. PRP is comparatively more cost effective and is associated with lesser pain (32.5 mm vs. 28.13 mm, p = 0.02) then SC group thus showing better compliance and acceptability. Conclusion: Both PRP and SC therapies improves the ovarian reserve markers however, response to PRP is superior to SC. Also, further to note that PRP is minimally invasive and has better compliance and acceptability. The main limitation of this study is small sample size and due to Covid pandemic inability to perform the IVF cycles to show improvement in clinical pregnancies and live births. Therefore, a large randomized trial is required to validate these results.
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Relevance: Despite the widespread use of COVID-19 vaccination worldwide, the number of studies on the impact of various types of vaccines on women’s reproductive health is limited in the scientific literature. The preliminary results of the study on the negative effect of vaccination with the Russian Gam-COVID-Vac vaccine on the ovarian reserve and the level of antiphospholipid antibodies in reproductive-aged women were first published in 2021. Objective: To evaluate the effect of the Russian combined vector vaccine against the novel coronavirus infection caused by SARS-CoV-2 on the parameters of ovarian reserve and menstrual function in reproductive-aged women. Materials and methods: A prospective interventional study included 220 women vaccinated with a combined vector vaccine Gam-COVID-Vac for the prevention of a novel coronavirus infection caused by SARS-CoV-2. The inclusion criteria were age from 18 to 45, preserved menstrual function, no history of COVID-19, negative PCR test result for SARS-CoV-2 and negative SARS-CoV-2 IgG antibody test before vaccination, no pregnancy, and no history of serious illnesses. The patients were examined twice: immediately before vaccination and 90 days after the first dose was injected. Antral follicle count was determined during the ultrasound examination of the pelvic organs. Serum levels of AMH, FSH, estradiol on the 2nd–5th day of the menstrual cycle, as well as IgG antibodies to SARS-CoV-2 were measured using enzyme immunoassay. Results: The efficacy and safety of the Russian combined vector vaccine against COVID-19 was high. The humoral immune response (specific IgG to SARS-CoV-2) was detected in 98.6% of vaccinated patients. There were no cases of severe side effects after vaccination. There were no significant changes in the hormone levels, antral follicle counts and menstrual function before and after vaccination;women of advanced reproductive age (©37 years) did not show considerable changes either. Conclusion: The results of the study indicate that vaccination with a combined vector vaccine Gam-COVID-Vac against a novel coronavirus infection caused by SARS-CoV-2 is effective and safe;it does not have a negative effect on ovarian reserve and menstrual function in reproductive-aged women.