Lower Estradiol Levels Research Articles

P-620 First step for personalized luteal support in frozen-thaw embryo transfer: Understanding the factors associated with serum progesterone concentrations on embryo transfer day

Abstract Study question What factors determine serum progesterone (P) concentration on embryo transfer (ET) day after artificially prepared (AP) cycles receiving intramuscular progesterone (IM-P)? Summary answer Lower serum P concentrations on ET day in AP frozen-thaw cycles are associated with high body mass index(BMI) and low estradiol(E2) levels on ET day. What is known already Large sample sized studies reported low serum P levels on ET day in AP cycles related to low success rates. There are limited studies evaluating the pregnancy rates in patients with low serum P on ET day after the rescue doses. These studies included the patients who received vaginal P. There is no study evaluating rescue doses with low serum P concentration after IM-P. Common sense is that personalization of luteal phase support may increase the success rates. To adjust the P dosages, patient and cycle characteristics need to be analyzed for prediction of low serum P concentration. Study design, size, duration This retrospective cohort study conducted at Bahçeci Ankara IVF Center between November 2019 and February 2022. The study included 637 single or double frozen-thawed blastocyst transfers undergoing AP endometrium receiving 100 mg IM-P after incremental oestrogen treatment. Serum P concentrations were evaluated from the blood samples which were obtained between 117-119 hours after the first IM-P administration and 21±2 hours after last IM-P administration. Participants/materials, setting, methods A total of 637 patients, first frozen-thawed blastocyst ET cycles were analyzed. The mean age, BMI, duration of oestrogen treatment, ET day E2 and ET day P concentration of the study population were 31.9±5.1 years, 26.7 ±4.7 kg/m2, 13.9±1.3 days, 266.1±90.9 pg/ml and 30.2±9.3 ng/ml respectively. Correlation analysis for patient and cycle characteristics and serum P concentrations were evaluated. Multivariate linear regression analysis was performed to determine the independent factors. Main results and the role of chance The overall live birth rate in total study group was 50.7% (323/637). Female age, serum P concentrations on ET day, and number of embryos transferred were significantly associated with live birth. Bivariate correlation analysis revealed that ET day P concentrations were negatively correlated to BMI (r:-0.12, p: 0.002) and positively correlated to ET day E2 concentrations (r:0.14, p:0.001). However, no correlation to female age, causes of infertility, E2, P and LH concentrations on P administration day, duration of oestrogen treatment and presence or absence of GnRH agonist suppression. When a multivariate linear regression was performed to correct potential confounders, increasing BMI presented a negative correlation to ET day serum P concentrations (p = 0.003; 95% CI -0.384 to -0.079 ). On the contrary, significant positive correlations to ET day serum P concentrations were shown with ET day E2 levels (p = 0.01; 95% CI 0.003 to 0.018). Other patient and cycle characteristics were not found to be an independent factor for ET day P concentration. Limitations, reasons for caution The retrospective nature of the study is the main limitation. Only patients with IM-P were included therefore the results cannot be extrapolated to other P administration forms and needs to be validated. After determining the low serum P threshold in large sample size, the parameters should be re-evaluated. Wider implications of the findings Monitoring P levels and adjusting the doses of P administration (via personalization) may have a positive impact on outcome. Not only patient and cycle characteristics, also pharmacokinetic and pharmacogenetic studies are warranted to optimize luteal phase support. Personalization of the luteal phase can be achieved by this way. Trial registration number NA

Sex steroid hormone levels associated with dopamine D2/3 receptor availability in people who smoke cigarettes.

Sex differences exist in tobacco smoking. Women have greater difficulty quitting smoking than men. Tobacco smoking is driven by the reinforcing effects of nicotine, the primary addictive component in cigarettes. Nicotine binds to nicotinic acetylcholine receptors, facilitating dopamine release in striatal and cortical brain regions. Dysregulated dopamine D2/3 receptor signaling in the dorsolateral prefrontal cortex (dlPFC) is associated with cognitive deficits such as impairments in attention, learning, and inhibitory control that impede quit attempts. Sex steroid hormones, such as estradiol and progesterone, influence drug-taking behaviors, through dopaminergic actions, suggesting that their influence may explain sex differences in tobacco smoking. The goal of this study was to relate dlPFC dopamine metrics to sex steroid hormone levels in people who smoke and healthy controls. Twenty-four (12 women) people who smoke cigarettes and 25 sex- and age-matched controls participated in two same-day [11C]FLB457 positron emission tomography scans, one before and one after amphetamine administration. D2R availability (BPND) at baseline and after amphetamine administration was calculated. On the same day, plasma samples were collected for the analysis of sex steroid hormone levels: estradiol, progesterone, and free testosterone. Women who smoke had trending lower levels of estradiol than their sex-matched counterparts. Men who smoke had higher levels of estradiol and trending higher levels of free testosterone than their sex-matched counterparts. Among women only, lower estradiol levels were significantly associated with lower pre-amphetamine dlPFC BPND. This study demonstrated that lower estradiol levels are associated with lower dlPFC D2R availability in women which may underlie difficulty resisting smoking.

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.

Sarcopenia in Perimenopausal and Postmenopausal Women in a Tropical Country [ID: 1377057

INTRODUCTION: Improving health services worldwide has led to a gradually aging population. Sarcopenia has been identified as an important contributor to health costs in elderly women in developed countries. The lifestyle and access to medical services is vastly different in the developing countries like India. The present research was conducted to study the status of sarcopenia among perimenopausal and postmenopausal women of India. METHODS: Institutional review board approval for the study was obtained from institutional ethical committee. Women aged 40 years or more, having no complaints, and coming to hospital as companions were enrolled after taking consent. A detailed history was taken and activity levels were classified according to the ICATUS 2016 (International Classification for Time-Use Statistics). Muscle strength was evaluated by handgrip strength, gait speed, and appendicular skeletal mass measurement. Serum estradiol, vitamin D3, fasting plasma glucose, and fasting insulin levels were also assessed. RESULTS: A total of 50 women were enrolled. 80% (n=40) of women had a sedentary lifestyle while the remaining reported light activity. Sarcopenia was noted in 16% (n=8) and showed a significant association with increasing age (P<.001). None of the women less than 62 years of age had sarcopenia. All women with sarcopenia had a sedentary lifestyle. Women with low body mass index were more likely to have sarcopenia. Low serum estradiol and serum vitamin D3 levels were significantly correlated to sarcopenia (P<.001). CONCLUSION: Sarcopenia is an emerging problem. Counseling of women for good nutrition and an active lifestyle can help prevent or delay the onset of sarcopenia. Poor nutrition status of women in developing countries needs to be addressed to combat the problem.

Cadmium and lead implication in testis cancer; is there a connection?

Testis cancer (TC) is the most common malignancy of young men. Current evidence from studies, alongside genetics and hormonal status, suggests a significant role of toxic metals, cadmium (Cd) and lead (Pb), in the origin and development of TC. Besides oxidative stress and endocrine disruption, interaction with bioelements is one of the critical mechanisms of Cd and Pb toxicity and malign transformation. This study aimed to investigate metal levels in blood, healthy, and tumor testis tissue and to reveal hormone, oxidative status, and bioelements levels in patients with TC. The study enrolled 52 patients with TC and 61 healthy volunteers. Toxic metals and bioelements levels were analyzed by atomic absorption spectrophotometry (AAS) while electrochemiluminescence immunoassay (ECLIA) and spectrophotometry methods were used for hormone and oxidative parameters evaluation. Significantly higher blood Cd levels were depicted in TC cohort. Furthermore, blood Cd elevation was associated with a 1.98 higher probability of TC developing. However, a metal concentration between healthy and tumor testis tissue did not differ significantly. Lower levels of estradiol and testosterone, established in a cohort of TC patients, followed the significant role of hormones in TC development. At the same time, ischemia-modified albumin (IMA) has been recognized as a parameter with very good accuracy as a potential diagnostic marker for TC. The study revealed different distribution patterns of copper (Cu) and zinc (Zn) in the three compartments of the patients, as well significant correlation between essential metals Cu/Zn and toxic metals Cd/Pb indicating metal-metal interactions as pivotal mechanisms of metals toxicity.

Associations of urinary organophosphate esters metabolites with asthma and lung function in adolescents.

Organophosphate esters (OPEs) are ubiquitously detected in environments and their exposure may affect respiratory health. However, epidemiological evidence, particularly among adolescents, is very limited. We aimed to investigate the associations of urinary OPEs metabolites with asthma and lung function among adolescents and to identify potential effect modifiers. Included were 715 adolescents aged 12-19 years old participating in the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Multivariable binary logistic regression and linear regression were used to assess associations with asthma and lung function, respectively. Stratified analyses were conducted to assess the effect modifications of serum sex hormones, vitamin D levels, and body mass index (BMI). After multivariable adjustment, we found that bis(2-chloroethyl) phosphate (BCEP) (3rd tertile [T3] vs 1st tertile [T1], OR = 1.87, 95% CI: 1.08, 3.25; P-trend=0.029) and diphenyl phosphate (DPHP) (T3 vs T1, OR = 2.52, 95%CI: 1.25, 5.04; P-trend=0.013) were associated with elevated odds of asthma in all adolescents. Sex-stratified analyses revealed that associations of these two OPEs metabolites tended to be stronger in males. Meanwhile, BCEP and the molecular sum of OPEs metabolites (∑OPEs) were significantly associated with declined lung function, either in all adolescents or by sex. Furthermore, stratified analyses revealed that positive associations of OPEs metabolites with asthma tended to be stronger among adolescents with insufficient levels of Vitamin D (VD < 50 nmol/L), relatively high levels of total testosterone (≥356 ng/dL and ≥22.5 ng/dL for males and females, respectively), or low levels of estradiol (<19.1 pg/mL and <47.3 pg/mL for males and females, respectively). Certain urinary OPEs metabolites, especially DPHP and BCEP, were associated with elevated odds of asthma and declined lung function in adolescents. Such associations might be partly modified by levels of VD and sex steroid hormones. The observed associations of urinary OPEs metabolites with increased risk of asthma and declined lung function highlight the potential hazard of OPEs exposure to respiratory health among adolescents.

The Estrous Cycle Influences the Effects of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase Inhibition in the Anxiety-Like Behavior in Rats.

Background: Sex differences in the response to the anxiety-related effects of cannabinoid drugs have been reported, with females being more sensitive than males. Evidence suggests that, according to sex and estrous cycle phase (ECP), the content of the endocannabinoids (eCBs) N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) varies in brain areas involved in the anxiety-like behavior. Methods: Considering the lack of studies evaluating sex and ECP differences in the eCB system in anxiety, using URB597, a fatty acid amide hydrolase inhibitor, or MJN110, a monoacylglycerol lipase inhibitor, we explored the effects of increasing AEA or 2-AG levels, respectively, in cycling and ovariectomized (OVX) female adult Wistar rats, as well as males, subjected to the elevated plus maze. Results: The administration of URB597 (0.1 or 0.3mg/kg; intraperitoneally) either increased or reduced the percentage of open arms time (%OAT) and open arms entries (%OAE), being anxiolytic in diestrus and anxiogenic in estrus. No effects were observed in proestrus or when all ECPs were analyzed together. Both doses produced anxiolytic-like effects in males. In OVX females, the anxiolytic-like effect of URB597 0.1 was associated with low levels of estradiol, whereas the anxiogenic-like effect of URB597 0.3 was spared by estradiol pretreatment. The systemic administration of MJN110 3.0 mg/kg reduced the risk assessment behavior (RAB), suggesting an anxiolytic-like effect independent of the ECP. When considering the ECP, MJN110 3.0 increased the %OAT and reduced the RAB, being anxiolytic in estrus and diestrus. No effects were observed in proestrus. Both doses of MJN110 were anxiogenic in males. In OVX females, the anxiolytic-like effect of MJN110 was dependent on low estradiol levels. Conclusion: Together, our findings support the evidence that females react differently to the effects of cannabinoids in the anxiety-like behavior; in addition, AEA and 2-AG modulation elicits anxiety-like responses that are closely influenced by hormone levels, mainly estradiol.

Alzheimer’s Disease and Premature Ovarian Insufficiency

Estradiol promotes neuronal growth, transmission, survival, myelinization, plasticity, synaptogenesis, and dendritic branching and it improves cognitive function. Alzheimer’s disease (AD) is characterized by amyloid plaques, neurofibrillary tangles, and the loss of neuronal connection in the brain. Genomic analysis has concluded that hypoestrogenism influences the APOE gene and increases the risk of AD. Premature ovarian insufficiency (POI) is defined as oligo/amenorrhea in women below 40 years of age, low estradiol, and high-gonadotropin levels. Early symptoms and signs of POI must be detected in time in order to prevent subsequent complications, such as Alzheimer’s disease. Meta-analysis has shown favorable effects of estrogen in preventing Alzheimer’s. We measured some of the typical markers of AD in women with POI such as interleukin 6 (IL-6), interleukin 8 (IL-8), tissue necrosis factor α (TNFα), TAU1, TREM2, and amyloid precursor proteins (APP). While FSH, LH, and IL-8 were significantly higher in POI group, compared to controls, testosterone and DHEAS were lower. A significant decrease in IL-6 was found in the POI group during a 6-month therapy, as well as an increase in amyloid precursor proteins. CONCLUSION: Neurological complications of POI, such as declining short-term memory, cognitive function, and dementia, have to be promptly stopped by initiating estro-progestogen therapy in POI. A long-term continuation of the therapy would be strongly advised.

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

The online version contains supplementary material available at 10.1007/s12070-023-03612-9.

Biomarkers for rapid H-reflex operant conditioning among females.

Operant conditioning of a spinal monosynaptic pathway using the Hoffman reflex (H-reflex) is well established in animal and human studies. There is a subset within the human population (∼20% nonresponders) who are unable to up train this pathway suggesting some distinct or unique identifying characteristics. Importantly, females, who have a nine times higher rate of injury during human performance activities than men, have been understudied in areas of CNS neuroplasticity. Our long-term goal is to understand if innate ability to rapidly up train the H-reflex is predictive of future performance-based injury among females. In this study, we primarily determined whether healthy, young females could rapidly increase the H-reflex within a single session of operant conditioning and secondarily determined if electro-physiological, humoral, cognitive, anthropometric, or anxiety biomarkers distinguished the responders from nonresponders. Eighteen females (mean age: 24) participated in the study. Overall, females showed a group main effect for up training the H-reflex (P < 0.05). Of the cohort, 10 of 18 females met the criteria for up training the H-reflex (responders). The responders showed lower levels of estradiol (P < 0.05). A multivariate stepwise regression model supported that extracellular to intracellular water ratio (ECW/ICW) and H-max/M-max ratio explained 60% of the variation in up training among females. These findings support that females can acutely upregulate the H-reflex with training and that electro-physiological and hormonal factors may be associated with the up training.NEW & NOTEWORTHY Young females who acutely increase their H-reflexes with operant conditioning had lower levels of estradiol. However, the best predictors of those who could up-train the H-reflex were baseline H-reflex excitability (H-max/M-max) and extracellular to intracellular water ratio (ECW/ICW). Future studies are warranted to understand the complex relationship between operant conditioning, human performance, and injury among active young females.

NOTCH1- and CD117-positive stem cells in human endometrium and their implications for successful implantation

To investigate the quantity of 2 stem cell types in the endometrial stroma of women undergoing invitro fertilization and their association with steroid hormone signaling and implantation success after embryo transfer. Prospective cohort study. Private hospital. A total of 109 patients undergoing invitro fertilization. Not applicable. Immunohistochemistry staining of endometrial biopsies taken during the midluteal phase using antibodies against NOTCH1 and CD117 was performed. The percentage of endometrial stromal cells positive for these markers was determined. The link of these stem cell percentages with the serum progesterone and estradiol levels and the endometrial expression of their respective receptors were assessed. After embryo transfer, the quantity of stained cells for each marker was also compared according to implantation outcome. The percentage of NOTCH1+ stromal cells ranged from 0.003%-2.112% (median, 0.062%) and was significantly higher than that of CD117+ cells, which ranged from 0.000%-0.210% (median, 0.020%) (Z = -7.035). The percentage of NOTCH1+ stem cells showed no difference between the studied serum hormone level groups and no relationship with the expression of their receptors in the endometrium. In contrast, the number of CD117+ cells significantly differed between patients with high and low levels of serum progesterone (cutoff, 14.9 ng/mL) and estradiol (cutoff, 135.6 pg/mL). Furthermore, the quantity of CD117+ stem cells was positively correlated with the progesterone receptor (R = 0.277) and estradiol receptor (R= 0.318) expression levels in the endometrium. Although the quantity of NOTCH1+ cells did not differ between the 2 implantation groups, the median percentage of CD117+ cells was significantly higher in patients with successful implantation than in those with unsuccessful implantation (0.03% vs. 0.01%, respectively). The cutoff value for the percentage of CD117+ cells predicting successful implantation was 0.018% (area under the curve, 0.66; 95% confidence interval, 0.56-0.77; sensitivity, 63.1%; specificity, 61.4%). This study indicates that the quantity of certain stem cell types (CD117+), but not others (NOTCH1+), in the functional endometrium is associated with implantation success and sex hormone signaling during the midluteal phase. These findings highlight the role of CD117+ cells in preparing the endometrium for embryo implantation, and their quantity may be an indirect indicator of endometrial receptivity.

Effects of the herbicide ametryn on development and thyroidogenesis of bullfrog tadpoles (Aquarana catesbeiana) under different temperatures.

Thyroid hormones (TH) are essential for the metamorphosis of amphibians and their production can be influenced by environmental stressors, such as temperature fluctuations, and exposure to aquatic pollutants, such as herbicides. In the present study we evaluated the influence of different temperatures (25 and 32 °C) on the effects of the herbicide ametryn (AMT, 0 - control, 10, 50 and 200 ng.L−1) for 16 days on thyroidogenesis of bullfrog tadpoles. Higher temperature and AMT exposure caused a delay in the development of tadpoles, despite no differences were noted in weight gain and total length of the animals. Levels of triiodothyronine (T3) and thyroxine (T4) were not altered neither by AMT nor by temperature, but the highest temperature caused a decrease in total area and number of follicles in the thyroid gland. Transcript levels of thyroid hormone receptors alpha and beta (TRα and TRβ) and iodothyronine deiodinase 3 (DIO3) were lower at 32 °C, which is consistent with developmental delay at the higher temperature. Tadpoles exposed to 200 ng.L−1 of AMT at 25 °C also presented delayed development, which was consistent with lower TRα and DIO3 transcript levels. Lower levels of estradiol were noted in tadpoles exposed to AMT at the higher temperature, being also possibly related to a developmental delay. This study demonstrates that higher temperature and AMT exposure impair thyroidgenesis in bullfrog tadpoles, disrupting metamorphosis.

Endocrine disruption and reproductive impairment of methylparaben in adult zebrafish.

Methylparaben (MeP) is one of the most frequently used preservatives in our daily products. However, it is becoming an aquatic pollutant of emerging concern. To reveal the endocrine disruption mechanism and reproductive impairment of MeP, the present study exposed adult zebrafish to 0, 1, 3, and 10μg/L (0, 6.6, 19.7, and 65.7nM) of MeP for 28 days. The results showed that subchronic exposure to 10μg/L of MeP significantly increased the gonadosomatic index in zebrafish. Spermatogenesis and oogenesis were blocked by MeP at concentrations as low as 1μg/L. Furthermore, parental exposure to MeP induced developmental deficits in offspring larvae, by increasing mortality, stimulating precocious hatching, and elevating heart rate. Blood concentrations of estradiol, testosterone, and 11-keto-testosterone were consistently lowered in MeP exposure groups. Transcriptional results evidenced that the disturbance in steroidogenesis and feedback regulation mechanisms along the hypothalamic-pituitary-gonadal axis underlay the imbalance of sex hormones. In line with the low estradiol level, hepatic production of vitellogenin (VTG) was significantly down-regulated, subsequently leading to a deficiency of VTG supply during oogenesis. To our knowledge, this is the first study to provide systemic insight about the antiestrogenic activity and reproductive toxicity of MeP.

PS-B11-11: IMPLICATIONS OF OBESITY ON MALE FERTILITY HORMONES

Background: The prevalence of obesity is alarming, with prevalence reported from 24 to 36% in developed worlds and a global estimate of adult obesity at over 11%. The relationship between obesity and infertility in men has been emphasized in multiple studies. However, there is a paucity of studies on the disparity between obese and overweight men fertility profiles. Therefore, this study aims to investigate the sex hormones distribution in overweight and obese men. Method: A retrospective case-control study on reproductive hormones in obese and overweight participants was conducted on 789 NHANES 2015–2016 survey data. Of the 789 participants, 229 were control, 270 were overweight, and 290 were obese between 18–80 years of age. We compared the mean plasma level of testosterone, estradiol, and Sex Hormone Binding Globulin (SHBG) among the groups using one-way ANOVA and mean differences using Tamhane post hoc tests. Results: There was a significant increase in the mean testosterone, and SHBG levels in the control group compared with overweight and obese subjects. However, a significant increase in mean estradiol was observed in the obese compared with overweight and control groups. Interestingly, there was no significant difference in the estradiol level between the control and overweight groups. There was a significant increase in BMI in the obese group compared with overweight, and control groups. Conclusion: Obesity has negative feedback effects on testosterone and SHBG production. However, an unknown mechanism contributes to the lower estradiol level in overweight relative to obese men. Therefore, there is a need to research the molecular basis of fertility hormone metabolism in obese and overweight men.

HER2 mRNA Levels, Estrogen Receptor Activity and Susceptibility to Trastuzumab in Primary Breast Cancer.

While the results thus far demonstrate the clinical benefit of trastuzumab in breast cancer (BC), some patients do not respond to this drug. HER2 mRNA, alone or combined with other genes/biomarkers, has been proven to be a powerful predictive marker in several studies. Here, we provide evidence of the association between HER2 mRNA levels and the response to anti-HER2 treatment in HER2-positive BC patients treated with adjuvant trastuzumab and show that this association is independent of estrogen receptor (ER) tumor positivity. While HER2 mRNA expression was significantly correlated with HER2 protein levels in ER-negative tumors, no correlation was found in ER-positive tumors, and HER2 protein expression was not associated with relapse risk. Correlation analyses in the ER-positive subset identified ER activity as the pathway inversely associated with HER2 mRNA. Associations between HER2 levels and oncogene addiction, as well as between HER2 activation and trastuzumab sensitivity, were also observed in vitro in HER2-positive BC cell lines. In ER-positive but not ER-negative BC cells, HER2 transcription was increased by reducing ligand-dependent ER activity or inducing ER degradation. Accordingly, HER2 mRNA levels in patients were found to be inversely correlated with blood levels of estradiol, the natural ligand of ER that induces ER activation. Moreover, low estradiol levels were associated with a lower risk of relapse in HER2-positive BC patients treated with adjuvant trastuzumab. Overall, we found that HER2 mRNA levels, but not protein levels, indicate the HER2 dependency of tumor cells and low estrogen-dependent ER activity in HER2-positive tumors.

Insights into the implication of obesity in hypogonadism among adolescent boys.

This research aimed at uncovering the mechanisms behind obesity-related hypogonadism in adolescent boys and to investigate the association between anthropometric characteristics and testicular functions of these boys. This study included 60 adolescent boys (12-18 years) with exogenous obesity (BMI≥95th percentile) and 30 age matched lean controls (BMI=15th-85th percentile). Full clinical examination, anthropometric measurements and pubertal assessment were performed. Laboratory investigations included hemoglobin, hematocrit, lipid panel, LH, FSH, free and total testosterone, inhibin B and estradiol. The results indicated the presence of positive family history of obesity in 85% of obese boys vs. 40% of the lean counterparts. Concerning SBP of obese boys, 7%were hypertensive (95th percentile), 25% were prehypertensive (between 90th and 95th percentiles) while, DBP findings showed that 33% are hypertensive and 33% are prehypertensive. Meanwhile, 13.3% of lean controls were prehypertensive. Anthropometric measurements and lipid profile values revealed a significant difference between obese and lean boys. Compared to obese boys the normal weight boys had higher levels of free testosterone (21.15±2.90pg/mL vs. 11.38±3.96pg/mL, p<0.001), total testosterone (10.59±6.63ng/dL vs. 3.23±1.70ng/dL, p<0.001), FSH (7.33±3.75mIU/mL vs. 5.63±3.96mIU/mL, p=0.026) and inhibin B (83.28±27.66pg/mL vs. 62.90±17.85pg/mL, p=0.001) and they registered lower level of estradiol (18.48±7.33pg/mL vs. 40.20±7.91pg/mL, p<0.001). In obese boys, BMI SDS significantly correlated with lipid profile and estradiol whereas, it showed significant negative correlation with LH, free and total testosterone and inhibin B. Penile length significantly correlated with LH while it revealed significant negative correlation with cholesterol. This study evidenced a close association between obesity and hypogonadism in adolescent boys which could be due to the increased estradiol level and decreased T/E2 ratio.

DOES TYPE OF TRIGGER INFLUENCE OOCYTE MATURITY IN PATIENTS UNDERGOING OOCYTE CRYOPRESERVATION, EMBRYO BANKING AND IN VITRO FERTILIZATION CYCLES USING LETROZOLE?

Letrozole is an aromatase inhibitor that is used during oocyte cryopreservation cycles to lower estradiol levels in patients with conditions such as breast cancer, lymphoma, seizures, BRCA mutation carriers and history of venous thromboembolic events (VTE). Many studies have determined that using letrozole has no effect on the number of oocytes retrieved or maturity. The purpose of this study is to determine if the type of trigger affected the percent of mature oocytes retrieved in patients undergoing controlled ovarian stimulation with letrozole.

Blood Levels Of Hormones, Cytokines And Leukocyte Content Versus Hypertrophic Scar Laser Treatment Outcome

The goal was to identify the changes in blood levels of hormones, cytokines, and the number of leukocytes associated with the success of laser treatment of hypertrophic scars. Material and Methods — The lipid, hormonal, cytokine and leukocyte composition of blood was studied in 15 women with normotrophic scars (Group 1) and 30 women with hypertrophic scars (Group 2). Blood was taken before treatment on days 5-7 of the menstrual cycle, followed by laser treatment. The clinical parameters of scars were assessed before treatment and 3 months after it, and two subgroups were identified: with a successful treatment outcome (2a) and with an unsuccessful outcome (2b). A retrospective analysis of blood composition was performed in each subgroup. The data were processed using the methods of nonparametric statistics. The differences were considered statistically significant at p&lt;0.05. Results — At a successful treatment outcome, the clinical parameters of scars were associated with low estradiol level, high progesterone content and high number of segmented neutrophils. These changes create conditions for scar hypertrophy, but retain the body’s capability of responding to the treatment by inflammatory process with normotrophic scarring. At an unsuccessful treatment outcome, the scar hypertrophy was restored under conditions of low blood content of luteinizing hormone, and high levels of growth hormone and transforming growth factor β. Conclusion — Features of changes in the blood levels of hormones, cytokines, and leukocyte content are associated with the success of laser treatment of hypertrophic scars.

Low endogenous estradiol levels are associated with elevated risk of cardiovascular disease mortality in young and middle-aged men in the United States

Background and aimsEvidence for the association of total estradiol (E2) with cardiovascular disease (CVD) in young men is limited. We investigated the association of total E2 or free estradiol (FE2) and CVD mortality in a nationally representative multiracial sample of young and middle-aged men in the United States. MethodsData were from 954 men without CVD, cancer, diabetes and not on androgen therapy or taking anabolic steroids, who participated in the National Health and Nutrition Examination Survey (1988–1991), for whom E2 was measured, and were followed for mortality through to 2015. Fasting serum levels of E2 were measured using competitive electrochemiluminescence immunoassays. Free estradiol was estimated from the levels of estradiol, sex hormone binding globulin, and albumin. International Classification of Diseases codes were used to define CVD mortality. Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). ResultsThe average age of participants at baseline was 35.7 ± 11.6 years, with 11% and 6% reporting Black and Hispanic race and ethnicity, respectively. During a median follow-up of 25.2 years, 40 CVD deaths were recorded. Controlling for baseline demographic and CVD risk factors, and total testosterone levels, a 1 standard deviation decrement in log E2 (HR: 2.33, 95%CI: 1.11–5.00) or FE2 (HR: 1.89, 95%CI: 1.01–3.57) was associated with elevated risk of CVD mortality. This elevated risk was largely limited to non-Hispanic White men. ConclusionsIn this study, low levels of E2 or FE2 were associated with elevated risk of CVD mortality.

Exposure to phthalates, phenols, and parabens mixture and alterations in sex steroid hormones among adolescents

Exposure to phthalates (PAEs), phenols, and parabens has been linked with sex hormone imbalance; however, previous studies were predominantly limited to adults and failed to examine the combined effects of these chemicals mixture among adolescents. Thus, we used the data from the National Health and Nutrition Examination Survey (2013-2016) to explore the associations of urinary PAEs, phenols, and parabens biomarkers with sex hormones among participants aged 12-19 years old (n=613). Latent class analysis (LCA) and quantile-based g-computation (QGC) were applied to assess the associations of the latent exposure profiles and chemicals mixture with sex hormone indicators, including steroid hormones and sex hormone binding globulin (SHBG), in adolescents and by sex. Using LCA, four latent classes were identified among all participants. Compared with the class characterized by "Low exposure", the class represented by "High PAEs" [mono (2-ethyl-5-carboxypentyl) phthalate (MECPP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and monobenzyl phthalate (MBZP)] had lower level of estradiol (E2) [β=-0.249, 95% confidence interval (CI): -0.419, -0.08], free androgen index (FAI) (β=-0.258, 95%CI: -0.512, -0.005) and free testosterone (FT) (β=-0.248, 95%CI: -0.496, -0.001) among male adolescents. These results were echoed by the results in QGC analyses, where PAEs mixture was negatively associated with E2 (β=-0.137, 95% CI: -0.263, -0.011), FAI (β=-0.198, 95%CI: -0.387, -0.008) and FT (β=-0.189, 95%CI: -0.375, -0.002) among male adolescents. By contrast, the associations of the identified latent classes or chemicals mixture with sex hormone indicators were generally nonsignificant among female counterparts, except for a positive association between PAEs mixture and SHBG (β=0.121, 95%CI: 0.012, 0.23). Our study demonstrated that exposure to PAEs, particularly MECPP, MEHHP, and MBZP, would be a threat to the sex hormone homeostasis of male adolescents.