Managing the menopause during the pandemic

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

A rare case of central post-stroke pain in a patient with migraine and lacunar infarcts in the medulla oblongata

Studies about headaches associated with acute ischemic stroke in patients suffering from migraine were limited, and therefore we present a clinical case of central post-stroke pain (CPSP) in a 47-year-old woman with migraine and lacunar infarcts in the medulla oblongata and also possible mechanisms of CPSP in patients with migraine. Magnetic resonance imaging of the brain revealed lacunar infarction in the medulla oblongata on the right (vertebral artery basin) and a single focus of gliosis in the parietal lobe on the right. Magnetic resonance angiography of cerebral vessels showed the fetal type of structure of both posterior cerebral arteries. This clinical case is a complex clinical situation of a combination of secondary headaches (post-stroke) in a patient with a primary headache (migraine), which was successfully treated by the combined administration of first-line drugs for the treatment of neuropathic pain in a patient with lacunar infarcts in the medulla oblongata. The treatment of CPSP is a difficult task due to the insufficiently unexplored mechanisms of development, the most effective approaches are those aimed at reducing the increased excitability of neurons.Copyright © 2023, Indian Association of Biomedical Scientists. All rights reserved.

The Role of Estradiol in Modifying Circadian Rhythms, Sleep Regularity and Risk for Depression During the Pubertal Transition

Background: The pubertal transition (PT) is characterized by dramatic reproductive hormone fluctuations, a developmental circadian delay, and significant changes in sleep and wake patterns. The PT also marks an abrupt divergence between the sexes in risk for depression and sleep disorders that remains elevated for females across the reproductive lifespan, implicating ovarian hormones (i.e., estradiol (E2)) as a common pathway of risk. Notably, inconsistent schedules during the COVID-19 pandemic have contributed to greater sleep irregularity (especially for adolescents), which is associated with affective impairment and inferior clinical outcomes. The objective of this research is to characterize the pathophysiological impact of E2 on sleep disturbances, endocrine rhythm dysregulation and depressive symptoms in peripubertal females. Method(s): 44 peripubertal females (ages 11-14, within 1-year post-menarche) provided daily hormone (E1G-urinary metabolite of E2) and mood assessments for one menstrual cycle and completed an 8-day sleep assessment (actigraphy, daily sleep diaries), with cortisol and melatonin circadian measurement (over four days) starting at day 7 of the following menstrual cycle. Minute-to-minute consistency in sleep/wake state over 24-hrs was calculated to index sleep regularity (SRI). Result(s): A multiple regression model predicted depressive symptoms (CES-DC) from follicular menstrual cycle phase E1G-AUC, sleep regularity index (SRI), cortisol and melatonin AUCs (F(4,18) = 3.833, p=.020, R2=.46). E1G, cortisol-AUC (p<.05) and SRI (marginally, p=.08) contributed to the prediction. Conclusion(s): Results suggest that greater sleep irregularity, greater follicular estradiol and blunted cortisol may contribute to increased depressive symptoms in peripubertal females, providing mechanistic insight into the estradiol-related sleep and affect disruptions experienced during the pubertal transition. Funding Source: K01MH121575;Foundation of Hope for Research and Treatment of Mental Illness (NC) Keywords: Puberty, Sleep Disturbances, Estradiol, Circadian Rhythms, Depressive SymptomsCopyright © 2023

The effect of coronavirus disease 2019 severity on male sexual functions among patients on follow-up after hospital discharge

Objectives Severe acute respiratory syndrome coronavirus 2 has infected millions of people worldwide with extensive affection and damage to body systems and organs;hence, the study of post-coronavirus disease (COVID) sequences is mandatory. Till now, reports are upcoming on the considerable effects of COVID-19 on male sexual health with no final data. Patients and Methods: Our cohort study included 76 male COVID-19-infected patients, confirmed positive via nasopharyngeal PCR swab. The rationale of this study was to estimate the influence of clinical, laboratory, and radiological severity parameters of COVID-19 on male erectile dysfunction based on erectile scores and male sex hormones (follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol). Result(s): Our results have demonstrated a highly statistically significant correlation between COVID-19 severity (mild, moderate, and severe cases) and both erectile scores (erection hardness score and International Index of Erectile Dysfunction-5) and testosterone hormones at first and third month after COVID (P0.001), except for testosterone level at third month and COVID-19 severity, which showed a statistically significant difference, with P value of 0.031. Conclusion(s): The current study correlated the effect of COVID-19 severity in the terms of clinical, laboratory, and radiological presentations on male sexual dysfunction (erectile scores and testosterone hormone) at first and third month after hospital discharge, with statistical significance being highly affected in severe rather than moderate and mild cases. This strengthens the obvious effect of COVID-19 infection on male sexual dysfunction. Copyright © 2023 The Egyptian Journal of Chest Diseases and Tuberculosis.

Anastrozole dose escalation for optimal estrogen suppression in postmenopausal early stage breast cancer: A prospective trial

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.

Vitamin D and estrogen steroid hormones and their immunogenetic roles in Infectious respiratory (TB and COVID-19) diseases

The role of steroid hormones against infectious diseases has been extensively studied. From immunomodulatory action to direct inhibition of microorganism growth, hormones D3 (VD3) and 17beta-estradiol (E2), and the genetic pathways modulated by them, are key targets for a better understanding pathogenesis of infectious respiratory diseases (IRD) such as tuberculosis (TB) and the coronavirus disease-19 (COVID-19). Currently, the world faces two major public health problems, the outbreak of COVID-19, accounting for more than 6 million so far, and TB, more than 1 million deaths per year. Both, although resulting from different pathogens, the Mtb and the SARS-CoV-2, respectively, are considered serious and epidemic. TB and COVID-19 present similar infection rates between men and women, however the number of complications and deaths resulting from the two infections is higher in men when compared to women in childbearing age, which may indicate a role of the sex hormone E2 in the context of these diseases. E2 and VD3 act upon key gene pathways as important immunomodulatory players and supporting molecules in IRDs. This review summarizes the main roles of these hormones (VD3 and E2) in modulating immune and inflammatory responses and their relationship with TB and COVID-19.Copyright © Sociedade Brasileira de Genetica.

Variation of the COVID-19 characteristics between genders

During the current COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), males have been observed to be more susceptible to severe or even fatal courses of COVID-19 compared to females, although infection rates are comparable. There is also evidence that women are at higher risk of developing long COVID syndrome. Here, we review how sex-specific differences in immune response, susceptibility to various comorbidities, SARS-CoV-2 entry pathways, and the endocrine stress axis might contribute to the variation of COVID-19 characteristics between both sexes. Behavioral and lifestyle factors are considered as well as the influence of sex hormones and sex chromosomes. A better understanding of the underlying immunologic, metabolic, and endocrine mechanisms that contribute to sexual dimorphism in COVID-19 could lead to sex-specific treatment strategies for severe COVID-19 courses and improve outcomes for these patients. © 2023 Elsevier Inc. All rights reserved.

Post-COVID Parosmia in Women May be Associated with Low Estradiol Levels.

We aimed to investigate the effects of female gender hormones on post-COVID parosmia in females. Twenty-three female patients aged 18-45 who had COVID-19 disease in the last 12 months were included in the study. Estradiol (E2), prolactin (PRL), luteotrophic hormone (LH), follicular stimulating hormone (FSH), and thyroid stimulating hormone (TSH) values were measured in the blood of all participants and a parosmia questionnaire was applied for the subjective evaluation of olfactory function. Values between 4 and 16 were obtained as parosmia score (PS), and the lowest PS showed the most severe complaint. The mean age of the patients was 31 (18-45). According to the PS, patients with a score of 10 or less were classified as Group 1, and patients above 10 were considered Group 2. The age difference between Groups 1 and 2 was statistically significant and younger patients were found to have more complaints of parosmia (25 and 34, respectively, p-value 0.014). It was found that patients with severe parosmia had lower E2 values and there was a statistically significant difference (p-value 0.042) between groups 1 and 2 in terms of E2 values (34 ng/L and 59 ng/L, respectively). There was no significant difference between the two groups in terms of PRL, LH, FSH, TSH levels, or FSH/LH ratio. It may be recommended to measure E2 values in female patients whose parosmia continues after COVID-19 infection. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03612-9.

Biochanin A as a modulator of the inflammatory response: An updated overview and therapeutic potential.

Uncontrolled inflammation and failure to resolve the inflammatory response are crucial factors involved in the progress of inflammatory diseases. Current therapeutic strategies aimed at controlling excessive inflammation are effective in some cases, though they may be accompanied by severe side effects, such as immunosuppression. Phytochemicals as a therapeutic alternative can have a fundamental impact on the different stages of inflammation and its resolution. Biochanin A (BCA) is an isoflavone known for its wide range of pharmacological properties, especially its marked anti-inflammatory effects. Recent studies have provided evidence of BCA's abilities to activate events essential for resolving inflammation. In this review, we summarize the most recent findings from pre-clinical studies of the pharmacological effects of BCA on the complex signaling network associated with the onset and resolution of inflammation and BCA's potential protective functionality in several models of inflammatory diseases, such as arthritis, pulmonary disease, neuroinflammation, and metabolic disease.

Bioinformatics and system biology approach to identify the influences of COVID-19 on primary sjogren's syndrome patients

Background: Primary Sjogren's syndrome (pSS) is a chronic, systemic, inflammatory autoimmune disease in which existing studies have found the presence of pSS-specific antibodies anti-SSA/ Ro in acute infection with COVID-19.1 The emergence of this phenomenon makes us aware that in the context of the long-term epidemic of COVID-19, it is necessary to further study the molecular mechanisms of the high susceptibility of pSS patients to COVID-19. Method(s): The gene expression profiles of 8 COVID-19 datasets and 5 pSS datasets were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between COVID-19 and PSS were identified using the limma software package and Weighted Gene Co-expression Network Analysis (WGCNA). A Venn diagram was used to discover common upregulated DEGs. To explore the possible pathogenesis of both diseases, common signaling pathways were explored by enriching DEGs using Gene Ontology (GO) and the Kyoto Gene and Genome Encyclopedia (KEGG) pathway. Protein-protein interactions (PPIs) were established to identify hub genes and key modules. The analysis of key gene expression characteristics by The Connectivity Map was used to predict potentially effective drugs. Finally, the CIBERSORT method was used to comprehensively evaluate the immune infiltrates of patients with COVID-19 and PSS to study the mechanisms that may have a common immune response or immune cell infiltration. Result(s): A total of 82 upregulated DEGs were identified in both COVID-19 and PSS (Figure 1 A-E). Functional enrichment analysis illustrated the important role of enhanced signaling pathways in response to virus defense and interferon-alpha in both diseases (Figure 1F).Three key modules including 25 hub genes were identified (Figure 1G). The correlation analysis of immune cell infiltration showed the expression of B cells memory resting decreased and NK cells resting increased significantly in the two diseases (Figure 1H, I). Finally, estradiol in drug prediction outcomes has been shown to reduce susceptibility to COVID-19 and its severity through its involvement in regulating immune cells, while the most common manifestation of dry eye in pSS patients is strongly associated with low estrogen. Conclusion(s): High defense response to virus and response to interferon-alpha in pSS patients might be a crucial susceptible factor for COVID-19 and predictive drugs such as estradiol, suggested by susceptibility genes common to COVID-19 and pSS, may help in the clinical treatment of both diseases.

Effects of COVID-19 on sexual health in men with suspected infertility using semen analysis and serum hormone profile: A single-center experience

Aim: To evaluate the effect of COVID-19 on sex hormone levels between men who have recovered from COVID-19 infection and men who have never been infected.Method: This study included 80 men who applied to the Infertility Clinic with a diagnosis of primary or secondary infertility. Semen analysis was performed twice, before COVID-19 and after the treatment of COVID-19 disease. In addition, Luteinizing hormone (LH), Follicle-stimulating hormone (FSH), testosterone (T), and 17β-estradiol (E2) levels were compared between the men after COVID-19 disease and uninfected men.Results: There was a significant difference in progressive sperm motility and immobility before and after the COVID-19 disease. Progressive sperm motility was decreased after COVID-19 disease while immobility was increased after COVID-19. The serum T level was lower and the E2 level was higher in men after COVID-19 disease compared to uninfected men.Conclusions: COVID-19 may adversely affect gonadal functions by causing to more deterioration of the hormone levels and semen parameters in infertile males. Therefore, gonadal function evaluation, including semen and sex-related hormones examination, is required to follow up the male COVID-19 patients with a reproductive plan.

Effect of 12 Months of Pubertal Suppression on Psychological Parameters in Transgender Youth and their Caregivers

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.

Impact of Environmental and Psychosocial stressors on Precocious Puberty seen in Girls during the COVID-19 Pandemic

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.

Blue Light Exposure and Exposure Duration Effects on Rats' Puberty Process

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.

Effect of COVID-19 infection on sex hormone levels in hospitalized patients: A prospective longitudinal study in Iran.

Introduction: This study aimed to evaluate the levels of sex hormones in patients with COVID-19 in Ahvaz, Iran. Methods: A prospective longitudinal study was conducted at Razi hospital, Ahvaz, Iran, from July 2020 to Febuary 2021. The levels of sex hormones including estradiol, progesterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), and total and free testosterone were measured in 162 patients with COVID-19 infection during hospitalization and 1 month after discharge. A demographic questionnaire and a checklist were used to collect the data. Mann-Whitney U test, χ 2 test, Fisher's exact test, Wilcoxon test, and logistic regression were used to analyze the data. Results: Sex hormones were assessed in 162 patients at baseline; however, a month after discharge, only 69 patients provided consent for assessment, and 9 had passed away. The estradiol level was 407.70 ± 623.37 and 213.78 ± 407.17 pg/ml in female patients with severe and moderate diseases at baseline, respectively which reduced to 195.33 ± 380.04 and 58.20 ± 39.45 pg/ml after discharge (p = 0.011 and p = 0.001). The alteration in the levels of progesterone, LH, and FSH were not significant.The level of LH in both groups of male patients with severe (6.64 ± 2.91 IU) and moderate disease (6.42 ± 4.44 IU) was high, which reduced after discharge (4.16 ± 2.44 and 3.93 ± 3.15 IU, respectively), but this decrease was significant only in the patients with severe disease (p < 0.0001). The alteration of FSH and free testosterone were not significant. The level of testosterone was 1.19 ± 0.73 and 1.46 ± 1.22 ng/ml at baseline in patients with severe and moderate diseases which increased to 2.64 ± 1.25 ng/ml, p < 0.0001, and 2.54 ± 0.93 ng/ml, p = 0.001, respectively after discharge. Conclusion: Our findings showed that the level of estradiol in female patients increased significantly while the level of testosterone in male patients decreased during the active phase of infection. Due to the attrition of patients in the follow-up period, more studies are needed to confirm these results.

Early prediction of efficacy of endocrine therapy (ET) in metastatic breast cancer (MBC): Pilot study with [18F]fluoro-estradiol-17β (18F-FES) PET/CT

Background: Estrogen receptors (ER) are predictive of endocrine responsiveness. However, 30% of ER+ BC patients will relapse despite adjuvant ET and 10 to 20% of metastatic lesions loose the expression of ER. The early identification of endocrine resistant patients may help to improve treatment strategies, especially in the light of innovative drugs recently approved. In the ET-FES trial we evaluated 18F-FES CT/PET as a prediction tool for endocrine responsiveness in ER+ MBC. The ET-FES study was funded by the ERANET-Transcan project. Methods: MBC patients with ER+/HER2- disease, were eligible for the ET/FES study. All patients underwent a baseline [18]F-FES PET/CT in addition to conventional procedures. Patients were classified as endocrine sensitive if overall Standardized Uptake Value (SUV) ≥ 2 and received ET;patients with SUV <2 were randomized to receive ET or chemotherapy (CT). The prognostic role of [18]F-FES PET/CT was assessed for PFS and OS by univariate and multivariate analyses. The primary endpoint was disease progression rate (DPR) at 6 months. Results: From April 2015 to October 2020 146 patients, from 7 EU centers were enrolled: of them, 115 with a mean SUV >2 received ET and 30 with SUV <2 were included in the randomized study. Median follow up was 18.4 months (range 8.0 to 38.3 months) in endocrine sensitive patients (SUV > 2) versus 10.1 months (range 8.0 to 36.8) in patients with SUV <2. Overall, at the time of this analysis 67 patients (45.9%) had disease progression and 37 (25.3%) died. DPR at 6 months was 57% in patients with SUV >2 vs 50% in SUV <2 randomized to ET and 57% in case of CT. DPR at 12 months was 35% vs 17% and 14%, respectively. Median PFS was 7.3 months (IQR 3.8 – 17.3) vs 5.2 (IQR 3.1 – 9.4) vs 7.7 months (IQR 3.0 – 14.0), respectively. OS rate at 12 months was 31% versus 17% versus 14%. Conclusions: The ET-FES clinical trial was prematurely interrupted, due to COVID-19 pandemic. The discriminating ability of this assay was high, leading to a personalized endocrine approach;a considerable proportion of patients with a mean SUV >2 is still on ET. Clinical trial identification: EudraCT 2013-000287-29. Legal entity responsible for the study: Alessandra Gennari - Università del Piemonte Orientale. Funding: AIRC. Disclosure: All authors have declared no conflicts of interest.

Associations of resting and peak fat oxidation with sex hormone profile and blood glucose control in middle-aged women.

BACKGROUND AND AIMS: Menopause may reduce fat oxidation. We investigated whether sex hormone profile explains resting fat oxidation (RFO) or peak fat oxidation (PFO) during incremental cycling in middle-aged women. Secondarily, we studied associations of RFO and PFO with glucose regulation. METHOD AND RESULTS: We measured RFO and PFO of 42 women (age 52-58 years) with indirect calorimetry. Seven participants were pre- or perimenopausal, 26 were postmenopausal, and nine were postmenopausal hormone therapy users. Serum estradiol (E2), follicle-stimulating hormone, progesterone, and testosterone levels were quantified with immunoassays. Insulin sensitivity (Matsuda index) and glucose tolerance (area under the curve) were determined by glucose tolerance testing. Body composition was assessed with dual-energy X-ray absorptiometry; physical activity with self-report and accelerometry; and diet, with food diaries. Menopausal status or sex hormone levels were not associated with the fat oxidation outcomes. RFO determinants were fat mass (ß = 0.44, P = 0.006) and preceding energy intake (ß = -0.40, P = 0.019). Cardiorespiratory fitness (ß = 0.59, P = 0.002), lean mass (ß = 0.49, P = 0.002) and physical activity (self-reported ß = 0.37, P = 0.020; accelerometer-measured ß = 0.35, P = 0.024) explained PFO. RFO and PFO were not related to insulin sensitivity. Higher RFO was associated with poorer glucose tolerance (ß = 0.52, P = 0.002). CONCLUSION: Among studied middle-aged women, sex hormone profile did not explain RFO or PFO, and higher fat oxidation capacity did not indicate better glucose control.

NIGHT SWEATS IN AN ELDERLY FEMALE

CASE: 74 year old woman with history of anxiety, depression, and nonsecretory adrenal adenoma presented with two months of progressive night sweats. Initially, she described waking up damp all over, but without needing to change her sheets. Her weight had been stable, and she denied recent travel. Her recent health changes included starting sertraline and receiving the Moderna COVID vaccines. Her other medications included atorvastatin and lisinopril. Her vital signs were all within normal range and her physical exam was unremarkable. Night sweats described were mild, so work up began with checking a CBC with differential and a TSH level. Initial labs were normal. However, the patient called a week later with night sweats that were worsening. She also recalled being treated for tuberculosis at age fifteen. This prompted additional bloodwork including Quantiferon, ACTH, androstenedione, estradiol, testosterone, progesterone, and DHEAS levels, as well as urine catecholamines and metanephrines. Additionally, it was noted sertraline could be a potential cause of night sweats. The dose was halved with the goal to taper off and discontinue the medication. All lab results came back within normal limits, so CT scans of the chest/ abdomen/ pelvis were ordered, and blood cultures collected. Imaging showed an unchanged adrenal adenoma and blood cultures had no growth. Ultimately, after five months of symptoms, her night sweats completely resolved five weeks after stopping sertraline. IMPACT/DISCUSSION: When working up night sweats, first, the severity of symptoms should be determined and medications reviewed. Mild night sweats with no associated red flag symptoms (weight loss, lymphadenopathy, and fever) do not need immediate or extensive work up. Further work up is essential in the setting of any red flag symptoms. Without a clear etiology, the work up includes the following items: chest radiography along with bloodwork including Quantiferon test, CBC, TSH, HIV serology, and CRP. If these results are normal then a CT of the chest, abdomen, and pelvis could be obtained as well as a bone marrow biopsy. Little evidence exists to guide an exact order of workup for night sweats, so it remains the clinician's responsibility to determine which tests to prioritize. Classes of medications that tend to cause night sweats are cholinergics and anti-depressants. Anti-depressants most associated with night sweats include TCAs and SNRIs. Sertraline has been implicated as a cause of night sweats, but little data exists as to how often this occurs and how often severe presentations like the one described occur. Given that selective serotonin reuptake inhibitors are a first line treatment in depression, recognizing this adverse effect is important in primary care and could prevent unnecessary extensive work ups for night sweats. CONCLUSION: -An initial step in evaluating persistent night sweats should be medication review -Many antidepressants including sertraline can have night sweats as an adverse effect.

The association between serum estradiol level and stress score with sexual function in women admitted to shohadaye yaftabad hospital (simultaneously with the outbreak of Coronavirus

Introduction: Sexual function is a part of human life and behavior and is a multidimensional phenomenon that is influenced by a variety of biological, psychological, and social factors. Estradiol is the hormone which is directly related to the level of sexual function. Prevalence of Covid 19 virus causes severe mental and physical stress which may result in reduced sexual function. This study was performed aimed to determine the association between serum estradiol levels and stress score with sexual function in women referred to Shohadaye Yaftabad Hospital (simultaneously with the outbreak of coronavirus). Methods: This correlational study was performed in 2021 on 223 pregnant women aged 18-35 years referred to the gynecology clinic of Shohadaye Yaftabad Hospital (simultaneously with the outbreak of coronavirus). The women underwent venous blood sampling in the follicular phase and then completed the demographic characteristics (including personal information), the Sexual Function Index (FSFI), and the DOS Stress Questionnaire. Data were analyzed using SPSS software (version 21) and Pearson correlation test and one-way analysis of variance. P<0.05 was considered statistically significant. Results: According to the Pearson correlation test, the mean of the total score of sexual function had a significant inverse correlation with stress (p <0.001, r =0.983). In other words, the more stress reduced the score of sexual function. Also, based on this test, estradiol levels have a positive correlation with sexual function (p =0.001, r = -0.223). Conclusion: According to this research, the stressful conditions including the coronavirus pandemic resulted in reduction of sexual function and estradiol levels.

Comparison of intraovarian instillation of platelet-rich plasma versus stem-cells for ovarian rejuvenation

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.