Layer-By-Layer Designed Spark-Type AuCuPt Alloy with Robust Broadband Absorption to Enhance Sensitivity in Flexible Detection of Estriol by a Lateral Flow Immunoassay.

Excessive intake of estrogen poses significant health risks to the human body; hence, there is a necessity to develop rapid detection methods to monitor its levels of addition. Gold nanoparticles (AuNPs), commonly utilized as colorimetric signal labels, find extensive application in lateral flow immunoassay (LFIA). However, the detection sensitivity of traditional AuNPs-LFIA is typically constrained by low molar extinction coefficients and reliance on a single signal. Herein, in this work, unique spark-type AuCuPt nanoflowers modified with tannic acid (AuCuPt@TA) were precisely designed by reasonable layer-by-layer element composition and green modification. The obtained AuCuPt displays robust broadband absorption spanning the visible to near-infrared spectrum, showcasing a notable molar extinction coefficient of 2.38 × 1012 M-1 cm-1 and a photothermal conversion efficiency of 48.5%. Based on this, selecting estriol (E3) as a model analyte, colorimetric/photothermal dual-signal LFIA (CLFIA and PLFIA) was developed. Limits of detection (LOD) of the CLFIA and PLFIA were achieved at 0.033 ng mL-1 and 0.021 ng mL-1, respectively, which represent a 9.3- and 14.6-fold improvement compared to the visual LOD of AuNPs-LFIA. Moreover, the application feasibility of the immunoassay was further evaluated in the milk and pork with satisfactory recoveries ranging from 86.21% to 117.91%. Thus, this work has enhanced the performance of LFIA for E3 detection and exhibited enormous potential for other sensing platform construction.

Measuring serum oestrogen levels in breast cancer survivors using vaginal oestrogens: a systematic review.

PURPOSE: Vaginal oestrogens can be used to treat genitourinary symptoms in women with early breast cancer. Studies evaluating vaginal oestrogens have commonly measured serum oestrogen levels as a surrogate marker of safety, but methods vary. We sought to summarise the data on serum oestrogen measurement in women with breast cancer using vaginal oestrogens to better understand the methods, levels and reliability. METHODS: We searched Medline, Embase, CENTRAL, SCOPUS and CINAHL from inception to October 2023 for clinical studies where serum oestrogen was measured in women with a history of early breast cancer using vaginal oestrogens. Studies with a reported testing methodology were included. RESULTS: Nine studies met the inclusion criteria for this systematic review. Methods used to measure oestradiol and oestriol in selected studies included mass spectrometry and immunoassays; several studies used more than one with variable concordance. Mass spectrometry detected oestradiol levels down to a lower limit between 1.0 pg/mL and 3.0 pg/mL. Immunoassays such as ELISA (enzyme-linked immunosorbent assay), ECLIA (enhanced chemiluminiscence immunoassay) and RIA (radioimmunoassay) had lower detection limits ranging between 0.8 pg/mL and 10 pg/mL. Studies were heterogeneous in testing techniques used, timing of testing, and the population including with subsequent varying results in the effect on oestrogens reported. CONCLUSIONS: Adopting consistent and standardised methods of measuring oestrogens in clinical trials involving women with early breast cancer on vaginal oestrogens is critical. Serum oestrogens are used as a surrogate marker of safety in this population, and good-quality data are necessary to enable clinicians and patients to feel confident in prescribing and taking vaginal oestrogens. Mass spectrometry, although more expensive, gives more reliable results when dealing with very low levels of oestrogens often found in women on aromatase inhibitors, compared to immunoassays.

Reference data on estrogen metabolome in healthy pregnancy.

INTRODUCTION: Estrogen hormones and their metabolites are implicated in the maintenance of healthy pregnancy and adequate fetal development. Abnormal levels were related to increased risk of pregnancy complications, particularly preeclampsia. Our aims were (1) to develop a methodological platform for the comprehensive assessment of estrogen metabolome in pregnancy; (2) to collect healthy reference data for relevant elements of estrogen metabolome in each trimester; (3) to assess unconjugated fractions of the estrogen metabolome, (4) to assess the dominant metabolic pathways of estrogen compounds. METHODS: We enrolled healthy pregnant mothers between gestational week 5-15 (on the confirmation of pregnancy; 79 samples), gestational weeks 19-27 (70 samples), and gestational week 34-39 (54 samples). A method employing liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed to assess estrone, 17-beta-estradiol, estriol levels, and their metabolites as conjugated and unconjugated forms. Descriptive statistics were used to characterize the level of compounds in each trimester. RESULTS: Estrone, 17-beta-estradiol and estriol levels are dramatically increasing with the advancement of pregnancy. Measured levels were in a very wide range. 17-beta-estradiol is neither glucuronated nor sulphated. To the contrary, estriol and estrone are significantly conjugated; unconjugated fraction is <15% of total hormone levels in any trimester. Regarding metabolism, 4-methoxy-estradiol and 17-epiestriol were not detected. CONCLUSION: We concluded that (1) the levels of estrogen compounds and metabolites increase with advancing gestational age; (2) the wide ranges of levels challenge the establishment of a healthy reference range for clinical purposes; (3) 17-beta-estradiol is not conjugated significantly; (4) 4-methylation and 17-epimerization pathways of estrogens are negligible with our LC-MS/MS method.

Accurate Structures and Rotational Constants of Steroid Hormones at DFT Cost: Androsterone, Testosterone, Estrone, ß-Estradiol, and Estriol.

A comprehensive analysis of the structural, conformational, and spectroscopic properties in the gas phase has been performed for five prototypical steroid hormones, namely, androsterone, testosterone, estrone, ß-estradiol, and estriol. The revDSD-PBEP86 double-hybrid functional in conjunction with the D3BJ empirical dispersion and a suitable triple-ζ basis set provides accurate conformational energies and equilibrium molecular structures, with the latter being further improved by proper account of core-valence correlation. Average deviations within 0.1% between computed and experimental ground state rotational constants are reached when adding to those equilibrium values vibrational corrections obtained at the cost of standard harmonic frequencies thanks to the use of a new computational tool. Together with the intrinsic interest of the studied hormones, the accuracy of the results obtained at DFT cost for molecules containing about 50 atoms paves the way toward the accurate investigations of other flexible bricks of life.

Green rGO/FeNPs nanocomposites activated peroxydisulfate for the removal of mixed 17ß-estradiol and estriol.

Reduced graphene oxide/iron nanoparticles (rGO/FeNPs) synthesized by the chemical method have been used in Fenton oxidation of organic contaminants, yet little is known about biosynthesized rGO/FeNPs using green tea extract (GT) as how to activate persulfate in sulfate radical-based advanced oxidation processes. In this study, rGO/FeNPs were used to activate peroxydisulfate (PDS) for 17ß-estradiol (ßE2) and estriol (E3) removal. The rGO/FeNPs-PDS system removed 83.6% of ßE2 and 62.5% of E3 within 240 min, which was confirmed by a combination of adsorption and degradation via both radical and non-radical pathways. Four main reactive species in ßE2 and E3 degradation were observed, i.e., hydroxyl radical (·OH), sulfate radical (SO4·-), singlet oxygen (1O2) and electron transfer, with the respective contributions of ·OH (32.9 and 34.7%), SO4·- (16.1 and 19.7%), 1O2 (12.2 and 14.1%) and electron transfer (8.0 and 7.2%). Analysis of X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR), Electron Paramagnetic Resonance (EPR) and electrochemical measurements all indicated that beside the well-known role of Fe, CO from rGO through the generation of ·OH, SO4·-, 1O2 and electron transfer, as well as GT through electron transfer also participated in the activation of PDS. Finally, the degradation pathways of ßE2/E3 were proposed. Overall, this study provides a new insight into the biosynthesis of rGO/FeNPs to activate PDS for the oxidation of mixed emerging contaminants.

Impact of vaginal estriol on serum hormone levels: a systematic review.

The genitourinary syndrome of menopause (GSM) affects up to 84% of postmenopausal women and may significantly reduce the quality of life in some. For symptom relief, there are several non-hormonal and hormonal vaginal products available. In Europe, vaginal estriol (E3) is the most frequently chosen estrogen for GSM treatment. The aim of this systematic review was to assess the impact of vaginal E3 on serum sex hormone levels, an outcome that has been previously used to assess safety in similar products. In our review, we did not find any alterations in serum estrone, estradiol, testosterone, progesterone and sex hormone binding globulin levels after vaginal E3 application. In contrast, some studies showed a minimal and transient decrease in serum gonadotropin levels, which however remained within the postmenopausal range. Similarly, only a few studies reported a minimal and transient increase of serum E3 levels, with the rest reporting no changes. The lack of clinically relevant long-term changes in serum sex hormone levels supports the current literature providing evidence about the safety of vaginal E3 products.

Association between aneuploidy screening analytes and adverse outcomes in twin gestations.

OBJECTIVES: To evaluate associations between serum analytes used for genetic screening and obstetric complications among twin pregnancies. METHODS: This cohort included twins delivered at a tertiary care hospital from 2009 to 2017. Abnormal levels of pregnancy associated plasma protein (PAPP-A), first and second trimester human chorionic gonadotropin (hCG), alpha fetoprotein (AFP), estriol, and inhibin, reported as multiples of the median (MoM), were defined as <5 %ile or >95 %ile for our cohort. Associations between abnormal analytes and preterm delivery, small for gestational age, and pregnancy-associated hypertension were calculated using Fisher's exact test. RESULTS: A total of 357 dichorionic/diamniotic and 123 monochorionic/diamniotic twins were included. Among dichorionic/diamniotic twins, elevated AFP (>3.70 MoM) was associated with increased preterm delivery <34 weeks (44.4 vs. 16.5 %, p=0.007), while elevated inhibin (>4.95 MoM) was associated with increased preterm delivery<37 weeks (94.1 vs. 58.8 %, p=0.004). For monochorionic/diamniotic twins, elevated inhibin (>6.34 MoM) was associated increased preterm delivery <34 weeks (66.7 vs. 24.8 %, p=0.04) and hypertension (66.7 vs. 21.4 %, p=0.03). CONCLUSIONS: Selected abnormal analyte levels were associated with increased rates of adverse outcomes in twin pregnancies, which differed by chorionicity. Our findings assist providers in interpreting abnormal analyte levels in twin pregnancies and may help to identify those at increased risk for adverse outcomes.

Conversion of estriol to estrone: A bacterial strategy for the catabolism of estriol.

Natural estrogens, including estrone (E1), 17ß-estradiol (E2), and estriol (E3), are potentially carcinogenic pollutants commonly found in water and soil environments. Bacterial metabolic pathway of E2 has been studied; however, the catabolic products of E3 have not been discovered thus far. In this study, Novosphingobium sp. ES2-1 was used as the target strain to investigate its catabolic pathway of E3. The metabolites of E3 were identified by high performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) combined with stable 13C3-labeling. Strain ES2-1 could almost completely degrade 20 mg∙L-1 of E3 within 72 h under the optimal conditions of 30°C and pH 7.0. When inoculated with strain ES2-1, E3 was initially converted to E1 and then to 4-hydroxyestrone (4-OH-E1), which was then cleaved to HIP (metabolite A6) via the 4, 5-seco pathway or cleaved to the B loop via the 9,10-seco pathway to produce metabolite with a long-chain ketone structure (metabolite B4). Although the ring-opening sequence of the above two metabolic pathways was different, the metabolism of E3 was achieved especially through continuous oxidation reactions. This study reveals that, E3 could be firstly converted to E1 and then to 4-OH-E1, and finally degraded into small molecule metabolites through two alternative pathways, thereby reducing E3 pollution in water and soil environments.

Correlation between maternal serum biomarkers and the risk of fetal chromosome copy number variants: a single-center retrospective study.

OBJECTIVE: To explore the association between the concentration of maternal serum biomarkers and the risk of fetal carrying chromosome copy number variants (CNVs). METHODS: Pregnant women identified as high risk in the second-trimester serological triple screening and underwent traditional amniotic fluid karyotype analysis, along with comparative genomic hybridization array (aCGH)/copy number variation sequencing (CNV-seq), were included in the study. We divided the concentration of serum biomarkers, free beta-human chorionic gonadotropin (fß-hCG), alpha fetoprotein (AFP) and unconjugated estriol (uE3), into three levels: abnormally low, normal and abnormally high. The prevalence of abnormally low, normal and abnormally high serum fß-hCG, AFP and uE3 levels in pregnant women with aberrant aCGH/CNV-seq results and normal controls was calculated. RESULTS: Among the 2877 cases with high risk in the second-trimester serological triple screening, there were 98 chromosome abnormalities revealed by karyotype analysis, while 209 abnormalities were detected by aCGH/CNVseq (P＜0.001) . The carrying rate of aberrant CNVs increased significantly when the maternal serum uE3 level was less than 0.4 multiple of median (MoM) of corresponding gestational weeks compared to normal controls, while the carrying rate of aberrant CNVs decreased significantly when the maternal serum fß-hCG level was greater than 2.5 MoM compared to normal controls. No significant difference was found in the AFP group. CONCLUSION: Low serum uE3 level (<0.4 MoM) was associated with an increased risk of aberrant CNVs.

Development of a molecularly imprinted polymer on silanized graphene oxide for the detection of 17-estradiol in wastewater.

This research article demonstrates the synthesis, characterization, and electrochemical evaluation of a molecularly imprinted polymer (MIP) on the surface of silanized graphene oxide (silanized GO), which is nanostructured and used to quantify 17-estradiol (E2) in wastewater. As characterization methods, X-ray diffraction (XRD), Raman spectroscopy, dynamic scattering light (DSL), scanning electron microscope (SEM), and Fourier transform infrared spectroscopy (FTIR) were utilized to examine the synthesized GO, silanized GO, MIP-GO composite, and non-imprinted polymer (NIP)-GO (NIP-GO) composite. FTIR results confirmed the successful synthesis of GO composites. Raman study confirmed the synthesis of monolayer silanized GO, MIP-GO composite, and NIP-GO composite. Surface morphology revealed that after polymerization, the surface of silanized GO sheet-like morphology is covered with nanoparticles. Adsorption kinetics studies revealed that adsorption follows the pseudo-second-order kinetics. Further, we studied the performance of a MIP-GO-based sensor by optimizing the effects of pH, scan rate, and incubation period. The linear calibration was achieved between the oxidation peak current and E2 concentration from 0.1 to 0.81 ppm, with a detection limit of 0.037 ppm. The selectivity of the MIP-GO composite was also checked by using other estrogens, and it was found that E2 is 3.3, 0.5, and 1.4 times more selective than equilin, estriol, and estrone, respectively. The composite was successfully applied to the wastewater samples for the detection of E2, and a good percentage of recoveries were achieved. It suggests that the reported composite can be applied to real samples. PRACTITIONER POINTS: An innovative electrochemical sensor was developed for selective detection of 17-estradiol through molecularly imprinted polymer fabricated on the surface of silanized GO (MIP-GO composite). The developed method was comprehensively validated and found to be linear in the range of 0.1 to 0.8 ppm of 17-estradiol, with 0.037 ppm of limit of detection and 0.1 ppm of limit of quantification, respectively. The developed MIP-GO-composite-based electrochemical sensor was found 3.3, 0.5, and 1.4 times more selective for 17-estradiol than equiline, estriol, and estrone, respectively. The applicability of a developed sensor was also checked on wastewater samples, and a good percent recovery was obtained.

Estriol and commensal microflora strains regulate innate lymphoid cells functional activity in multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease in which the immune system attacks myelin basic protein of nerve axons. Recently, there has been growing interest in studying the role of a newly described population of immunity cells - innate lymphoid cells (ILCs) in the pathogenesis of the disease. At the same time, it was found that during pregnancy there is a weakening of Th1-mediated autoimmune pathologies manifestations, including MS. In this work, we studied phenotypic characteristics of ILC in MS patients in comparison with healthy donors after 48 h incubation with pregnancy hormone estriol (E3) and commensal microflora cells. To activate ILC, strains of Ecsherichia coli K12 and Lactobacillus plantarum 8R-A3 were used. ILC phenotype was assessed by flow cytometry using monoclonal antibody staining. It has been established that E3 and bacterial factors are able to regulate the maturation of ILC subtypes and their cytokines in different ways. In general, the studied factors influence the phenotypic changes in ILC cells, leading to the transition from one type to another, both in healthy donors and in MS patients.

The Physiologic Role and Use of Estriol.

Obtaining estrogen balance with a physiologic estriol and estradiol ratio is an important aspect of physiologic bioidentical hormone restoration therapy. Risks, including that of breast cancer, should be minimized while attempting to obtain the protective benefits and symptom management with therapy. Estriol plays a central role in protecting against breast cancer and should be considered an integral part of therapy for any patient with lower than normal physiologic levels.

Comparison of the effect of noninvasive radiofrequency with vaginal estrogen and vaginal moisturizer in the treatment of vulvovaginal atrophy in postmenopausal women: a randomized clinical trial.

OBJECTIVE: To compare the effect of noninvasive radiofrequency (RF) with vaginal estrogen (E), and vaginal moisturizer (M) on improving vulvovaginal atrophy (VVA) in women with genitourinary syndrome of menopause. METHODS: A total of 32 postmenopausal women who met the inclusion criteria were randomized into three intervention arms to receive one of the following treatments: three sessions of noninvasive RF therapy (RF arm); intravaginal estriol cream 1 mg applied daily for 2 weeks, followed by 1 mg applied two times weekly or 1 mg of estradiol vaginal fast-dissolving film applied daily for 2 weeks, followed by 1 mg applied two times weekly (E arm); and intravaginal moisturizer two times a week (M arm). Assessments at baseline and after 4 months were conducted using Vaginal Health Index score, Vaginal Maturation, visual analog scale for VVA symptoms (dyspareunia, dryness, and burning), and Menopause Rating Scale (MRS) for urogenital symptoms. Vaginal wall biopsies were administered to participants who consented, pretreatment and posttreatment (at baseline and after 4 months of follow-up). RESULTS: After 4 months, the Vaginal Health Index showed an increase of 6.6 points in mean total score in the RF arm, also in the E arm (+7.3 points), with no significant improvement in the M arm (+1.5 points) (interaction effect: RF, E ≠ M, P < 0.001). Regarding vaginal maturation, there was a significant increase in superficial cells in the E arm (+31.3), with no significant changes in the RF (+9.3) and M (-0.5) arms (interaction effect: E ≠ M, P < 0.001). Vaginal pH decreased significantly in the E arm (-1.25), with a similar response in the RF arm (-1.7), with no significant improvement in the M arm (-0.25) (interaction effect: RF, E ≠ M, P < 0.001).There was a significant improvement in the MRS score for VVA symptoms in the three intervention arms, with no predominance of any arm, whereas the improvement in the total MRS score for urogenital symptoms showed a predominance of the RF arm (ΔRF: -7.8; ΔE: -3.5; ΔM: -2.3; RF ≠ E, M). According to histopathologic analysis, there was no statistically significant increase in glycogenation ( P = 0.691) or epithelial cone height ( P = 0.935), despite an increase in the median delta (difference between pretreatment and posttreatment) in the three intervention arms (glycogenation: RF arm Δ = +118.4%; E arm Δ = +130.9%; M arm Δ = +24.9%; epithelial cone height: RF arm Δ = +33.5%; E arm Δ = +18.6%; M arm Δ = +22.3%). CONCLUSION: The effect of noninvasive RF on the treatment of vulvovaginal symptoms of genitourinary syndrome of menopause was similar to vaginal estrogen, except for hormonal cytology, and superior to vaginal moisturizer, with improvement in some histomorphometric parameters. These findings are promising, especially for the population that cannot or prefers not to use vaginal estrogen therapy.

Metabolism of endogenous and exogenous estrogens in women.

Estrogens regulate important processes in reproductive, skeletal, cardiovascular, and central nervous systems that impact women's overall health. Understanding endogenous and exogenously administered estrogen metabolism is vital to determining therapeutic estrogen levels. The present review provides an overview of estrogen metabolites formed in non-pregnant and pregnant women, and those resulting from exogenous estrogen administration. There are four principal endogenous estrogens: estrone (E1), estradiol (E2), estriol (E3), and estetrol (E4). E4, which is produced only in pregnancy, has emerged recently as an estrogen with significant therapeutic potential. E1, E2, and E3 undergo extensive metabolism primarily through phase I (hydroxylation, oxidation, reduction) and phase II (primarily conjugation) reactions, whereas E4 undergoes only phase II reactions. Exogenous estrogens commonly used for menopausal treatment and/or contraception, including micronized E2, conjugated equine estrogens, and ethinyl estradiol, also undergo phase I and phase II reactions, but differ widely in the types of metabolites formed. The mechanisms by which estrogen metabolites are formed and their excretion in urine, bile, and feces, are still poorly understood. We highlight areas that require further research to foster a better understanding of how estrogen metabolism impacts dosing of oral estrogens for therapeutic use, as well as the physiological regulation of endogenous estrogens.

Occurrence and distribution of steroid hormones (estrogen) and other contaminants of emerging concern in a south indian water body.

Steroid hormones (SHs) are among the important classes of Contaminants of Emerging Concern (CECs) whose detection in aquatic environments is vital due to their potential adverse health impacts. Their detection is challenging because of their lower stability in natural conditions and low concentrations. This study reports the presence of steroid hormones in a major river system, the Periyar River, in Kerala (India). Water samples were collected from thirty different river locations in the case of SHs and five locations within these in the case of other CECs. These were subjected to LC-MS/MS and LC-Q-ToF/MS analyses. Five SHs, estriol, estrone, 17 ß estradiol, progesterone, and hydroxy progesterone, were separated and targeted using MS techniques. The studies of the water samples confirmed the presence of the first three estrogens in different sampling sites, with estrone present in all the sampling sites. The concentration of estrone was detected in the range from 2 to 15 ng/L. Estriol and estradiol concentrations ranged from 1.0 to 5 ng/L and 1-6 ng/L, respectively. The hormones at some selected sites were continuously monitored for seven months. The chosen areas include the feed water sites for the drinking water treatment plants across the river. The monthly data revealed that estrone is the only SHs detected in all the samples in the selected months. The highest concentration of SH was found in August. Twelve CECs belonging to pharmaceuticals and personal care products were identified and quantified. In addition, 31 other CECs were also identified using non-target analysis. A detailed study of the hormone mapping reported here is the first from any South Indian River.

Endocrine Disruptors and Estrogens in Human Prostatic Tissue.

Endocrine disruptors (EDs) are ubiquitous substances both in the environment and everyday products that interfere with the hormonal system. Growing evidence demonstrates their adverse effects on the organism, including the reproductive system and the prostate, owing to their (anti)estrogenic or antiandrogenic effects. Since EDs can interact with steroid hormone actions on-site, understanding the levels of intraprostatic EDs in conjunction with steroids may hold particular significance. The aim of this study was to develop and validate a method for determining estrogens, various groups of EDs (bisphenols, parabens, oxybenzone and nonylphenol) and phytoestrogens in their unconjugated and conjugated forms in prostate tissue by liquid chromatography-tandem mass spectrometry, and subsequently analyze 20 human prostate tissue samples. The method enabled 20 compounds to be analyzed: estrogens (estrone, estradiol, estriol), bisphenols (bisphenol A- BPA, BPS, BPF, BPAF, BPAP, BPZ, BPP), parabens (methyl-, ethyl-, propyl-, butyl-, benzyl- paraben), oxybenzone, nonylphenol and phytoestrogens (daidzein, genistein, equol) with LLOQs between 0.017-2.86 pg/mg of tissue. The most frequently detected EDs in prostate tissues were propylparaben (conjugated and unconjugated forms in 100 % of tissues), methylparaben (unconjugated in 45 % and conjugated in 100 %), ethylparaben (unconjugated in 25 % and conjugated in 100 % BPA (unconjugated in 35 % and conjugated in 60 % and oxybenzone (both forms in 45 % To the best of our knowledge, this is the first study detecting EDs, phytoestrogens and estriol conjugate (E3C) in the prostate. E3C was the most abundant estrogen in prostatic tissue. This highlights the need for further explorations into estrogen metabolism within the prostate.

Distribución de esteroides estrogénicos en plantas de tratamiento de aguas residuales municipales / Distribution of estrogenic steroids in municipal wastewater treatment plants

En la actualidad, existe una preocupación creciente por la presencia de estrógenos en el medio acuático, donde pueden ser introducidos a partir de aguas residuales después de su eliminación incompleta en las plantas de tratamiento. Las aguas residuales sistemáticamente reciben estrógenos naturales y sintéticos, y por lo tanto una comprensión más profunda de la suerte de ellos en el medio ambiente es necesaria. Se evaluaron los niveles de estrógenos en los efluentes de las Plantas de Tratamiento de Aguas Residuales (PTARs) Penha e Ilha do Governador, ambos de tipo convencional de flujo continuo de lodo activado con aireación prolongada. Fue utilizado como el parámetro de determinación de algunos compuestos de interés como estrógenos naturales [estrona (E1), 17β-estradiol (E2), estriol (E3)) y sintéticos (17α-etinilestradiol (EE2)]. Las muestras individuales se recogieron posteriormente al tratamiento de cada PTAR y después de los procedimientos de laboratorio se realizó la determinación de estrógenos basado en la extracción en fase sólida (SPE) y la cromatografía líquida de alta resolución con detector de arreglo de diodos (HPLC-DAD). Las concentraciones fueron de: 0,7 a 5,2 μg/l y de 0,5 a 5,6 de E1; 0,9 a 7,7 y 1,2 a 9,2 μg/l para E2; 2,01 a 6,09 y 1,07 a 4,08 μg/l para EE2 en PTAR Penha y PTAR Ilha do Governador, respectivamente. La capacidad de eliminación de estrógenos fue eficaz, pero denota que la eliminación sistemática de la población es en la actualidad alta. Se recomienda instalar mecanismos para mitigar el consumo exagerado de estas sustancias o implementar una eliminación completa más eficaz.

Currently, there is a growing concern over the presence of estrogens in the aquatic environment, where they can be introduced from wastewater after their incomplete elimination in the treatment plants. Wastewater systematically receives natural and synthetic estrogens, and thus a deeper understanding of the fate of them in the environment is extremely necessary. It was evaluated estrogen levels in the effluent from the Sludge Wastewater Treatment Plants (SWTPs) Penha and Ilha do Governador, both of type conventional continuous-flow activated sludge with extended aeration. The determination of some target compounds as natural estrogens was used as the evaluation parameter [estrone (E1), 17β-estradiol (E2), estriol (E3) and synthetic (17α-ethinylestradiol (EE2)]. Individual samples were collected posterior treatment of each SWTP, and after laboratory procedures, the determination of estrogens was performed by a method based on solid phase extraction (SPE) and high performance liquid chromatography-diode array detector (HPLC-DAD). Concentrations ranged from 0.7 to 5.2 μg/l and from 0.5 to 5.6 for E1; 0.9 to 7.7 and 1.2 to 9.2 μg/l for E2; 2.1 to 6.9 and 1.7 to 4.8 μg/l for EE2 at SWTPs Penha and Ilha do Governador, respectively. The removal capacity of estrogens despite its effectiveness denotes that the systematic elimination by the population is high nowadays and urging mechanisms to mitigate the exaggerated consumption or to implement most effective complete removal.

Measurement of serum estrogen and estrogen metabolites in pre- and postmenopausal women with osteoarthritis using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry

Although 17β-estradiol (E2) deficiency has been linked to the development of osteoarthritis (OA) in middle-aged women, there are few studies relating other estrogens and estrogen metabolites (EMs) to this condition. We developed a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method to measure the levels of six EMs (i.e., estrone, E2, estriol, 2-hydroxyestrone, 2-hydroxyestradiol, and 16a-hydroxyestrone) in healthy pre- and postmenopausal women and women with OA. This method had a precision ranging from 1.1 to 3.1% and a detection limit ranging from 10 to 15 pg. Compared to healthy women, serum-free E2 was lower in the luteal and postmenopausal phases in women with OA, and total serum E2 was lower in postmenopausal women with OA. Moreover, compared to healthy women, total serum 2-hydroxyestradiol was higher in postmenopausal women with OA and total serum 2-hydroxyestrone was lower in both the luteal and follicular phases in women with OA. In conclusion, our HPLC-ESI-MS/MS method allowed the measurement of multiple biochemical targets in a single assay, and, given its increased cost-effectiveness, simplicity, and speed relative to previous methods, this method is suitable for clinical studies.

Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

OBJECTIVE: To determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10%) combined with estriol (0.1%) + estradiol (0.25%) for relieving postmenopausal symptoms. METHODS: A total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. RESULTS: An improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05) after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04±4.9 to 57.12±4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. CONCLUSION: The nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women. .