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The cyclical changes in sex hormones across the menstrual cycle (MC) are associated with various biological changes that may alter resting metabolic rate (RMR) and body composition estimates. Hormonal contraceptive (HC) use must also be considered given their impact on endogenous sex hormone concentrations and synchronous exogenous profiles. The purpose of this study was to determine if RMR and dual-energy X-ray absorptiometry body composition estimates change across the MC and differ compared with HC users. This was accomplished during a 5-week training camp involving naturally cycling athletes (n = 11) and HC users (n = 7 subdermal progestin implant, n = 4 combined monophasic oral contraceptive pill, n = 1 injection) from the National Rugby League Indigenous Women's Academy. MC phase was retrospectively confirmed via serum estradiol and progesterone concentrations and a positive ovulation test. HC users had serum estradiol and progesterone concentrations assessed at the time point of testing. Results were analyzed using general linear mixed model. There was no effect of MC phase on absolute RMR (p =.877), relative RMR (p =.957), or dual-energy X-ray absorptiometry body composition estimates (p >.05). There was no effect of HC use on absolute RMR (p =.069), relative RMR (p =.679), or fat mass estimates (p =.766), but HC users had a greater fat-free mass and lean body mass than naturally cycling athletes (p =.028). Our findings suggest that RMR and dual-energy X-ray absorptiometry body composition estimates do not significantly differ due to changes in sex hormones in a group of athletes, and measurements can be compared between MC phases or with HC usage without variations in sex hormones causing additional noise. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exercise is an effective method for preventing and treating osteoporosis, but it is unclear whether its effect on postmenopausal osteoporosis is related to changes in bone autophagy levels. OBJECTIVE: To observe the effects of exercise via cellular autophagy on the morphology and mechanical properties of bone tissue in ovariectomized rats, and to explore the mechanism of exercise on bone mass in ovariectomized rats from the perspective of autophagy. METHODS: A rat model of postmenopausal osteoporosis was established, and a 24-week moderate-intensity exercise was used for intervention. After the experiment, serum estradiol levels were measured by ELISA, and bone mineral density and bone microstructure of the cortical and trabecular bone were detected by micro-CT. The biomechanical indicators of the tibia were tested by a three-point bending test. Autophagosomes were observed by transmission electron microscopy. The expression of LC3 and ATG7 proteins was analyzed by western blot. RESULTS AND CONCLUSION: The serum estradiol level in the ovariectomized group was significantly lower than that of the sham-operation group and ovariectomized+exercise group (P < 0.01). The body mass of rats in each group increased, and the order was the ovariectomized group > the ovariectomized+exercise group > the sham-operation group > the sham-operation+exercise group. The bone mineral density and bone mass of rats in all groups significantly increased (P < 0.01), but the increase in the ovariectomized group was significantly lower than that of the other groups, and the increase in the ovariectomized+exercise group was significantly higher than that of the ovariectomized group. Compared with the sham-operation group, the bone mineral density of the tibial cancellous bone in the sham-operation+exercise group was significantly increased (P < 0.01), while the bone mineral density in the ovariectomized and ovariectomized+exercise groups was significantly decreased (P < 0.01). Compared with the ovariectomized+exercise group, the ovariectomized group showed significantly lower bone volume fraction, number of trabeculae, and bone mineral density of cancellous bone (P < 0.05), extremely significantly lower trabecular thickness (P < 0.01), and significantly higher mean trabecular pattern factor, trabecular separation, and structural model index (P < 0.01). Compared with the ovariectomized group, the LC3-II/LC3-I ratio and the relative expression of ATG7 protein significantly increased in the ovariectomized+exercise group (P < 0.05). Compared with the sham-operation and ovariectomized groups, the number of autophagosomes increased in the sham-operation+exercise and ovariectomized+exercise groups, respectively. To conclude, moderate-intensity treadmill exercise can improve the bone microstructure and biomechanical properties of the tibial cancellous bone and increase bone mass in ovariectomized rats by increasing serum estradiol levels and bone autophagy levels. [ABSTRACT FROM AUTHOR]

A non-genetic transgenerational inhibitory effect on sexual reproduction has been demonstrated in Brachionus plicatilis in relation to environmental predictability. Indeed, clones of this species from more predictable environments do not respond to sex-inducing cues during several generations after leaving diapause. Notwithstanding, the molecular basis of this effect is still unknown. In this work, the expression level of genes related to the synthesis of sex hormones and to a potential epigenetic signalling mechanism were tracked along successive generations from diapausing eggs in clones of B. plicatilis populations inhabiting ponds with different level of environmental predictability. The selected genes were (1) the 17-β-dehydrogenase gene (edh), involved in the synthesis of 17-β-estradiol hormone in rotifers, and (2) the DNMT2 gene (meth), as a candidate epigenetic mechanism of control. According to expectations, results showed an increasing expression of edh across generations in clones from those the more predictable ponds. This finding provides a putative role of estradiol in the transgenerational effect. However, no differences were found in the meth gene neither across generations nor regarding the environmental predictability. Despite this, we point out alternatives for future research on the inherited gene regulation mechanism behind the transgenerational effect. [ABSTRACT FROM AUTHOR]

A role for prenatal steroid hormones in the etiology of autism has been proposed, but evidence is conflicting. Here, we examined serum levels of maternal estradiol, testosterone, 17-hydroxyprogesterone (OHP), and cortisol from the first trimester of gestation (mean = 10.1 weeks) in relation to the odds of diagnosed autism with and without co-occurring intellectual disability (ID) in the offspring (n = 118 autism with ID, n = 249 autism without ID, n = 477 control). Levels of maternal hormones were measured using highly sensitive liquid chromatography tandem mass spectrometry, standardized according to gestational timing of sample collection, and analyzed with restricted cubic spline logistic regression models adjusting for child's sex and maternal health, demographic, and socioeconomic factors. We observed significant nonlinear associations between maternal estradiol, 17-OHP, and cortisol with autism, which varied with the presence of co-occurring ID. Compared to mean levels, lower levels of estradiol were associated with higher odds of autism with ID (odds ratio for concentrations 1 SD below the mean = 1.66; 95% CI, 1.24–2.11), while higher cortisol levels were associated with lower odds (odds ratio for 1 SD above the mean = 0.55; 95% CI, 0.36–0.88). In contrast, higher 17-OHP was associated with increased odds of autism without ID (odds ratio for 1 SD above the mean = 1.49; 95% CI, 1.11–1.99). We observed no evidence for interaction with sex of the child. These findings support the notion that the maternal steroid hormonal environment in early pregnancy may contribute to autism, but also emphasize the complex relationship between early-life steroid exposure and autism. [ABSTRACT FROM AUTHOR]

Glecaprevir/pibrentasvir (GLE/PIB) is an approved guideline‐recommended chronic hepatitis C virus infection treatment. GLE/PIB coadministration with ethinyl oestradiol (EE) is not recommended in current labels owing to a Phase 1 study observing Grade ≥2 alanine aminotransferase (ALT) elevation in 2 out of 12 healthy women cotreated for 11 days with GLE/PIB and oral contraceptive (OC) containing 35 μg/250 μg EE/norgestimate. No Grade ≥2 elevation was observed with low‐dose (20 μg) EE (n = 14). This Phase 1 study examined safety/tolerability of GLE/PIB coadministered with an OC containing low‐dose EE using a larger sample size and longer treatment duration. Healthy premenopausal women were treated with EE/levonorgestrel alone (20/100 μg, Cycles 1–2), followed by coadministration with GLE/PIB (300/120 mg; Cycles 3–4). A safety criterion of special interest was a confirmed Grade ≥2 ALT elevation (>3× upper normal limit). Adverse events (AEs) and study drugs concentrations were examined. Of 85 enrolled women, 72 initiated combined GLE/PIB + EE/levonorgestrel treatment, 66 completed the study and 19 discontinued prematurely (non‐safety reason, n = 16; AE [deemed unelated to GLE/PIB], n = 3). No participant met the safety criterion of special interest of confirmed Grade ≥2 ALT elevation. No serious/Grade ≥3 AEs were reported. Study drug concentrations were within the expected ranges. GLE/PIB in combination with an OC containing low‐dose EE was generally well tolerated with no confirmed Grade ≥2 ALT elevation and no evidence of drug‐induced liver injury. No pattern to the reported AEs and no new safety issues were identified. This was a Phase 1 study of healthy volunteers, not a registered clinical trial. [ABSTRACT FROM AUTHOR]

Objective: Human choriogonadotrophin (hCG) treatment of gonadotrophin‐deficient infertile men uses hCG of urinary (uhCG) or recombinant (rhCG) origin, but these treatments have not been compared nor are there studies defining rhCG dosing in men. Design: hCG products were studied in randomized cross‐over single‐dose studies of standard (Study 1, 1500 IU and 62.5 µg, respectively) or high (Study 2, 5000 IU and 250 µg) dose and a multi‐dose population pharmacology study of hCG use. Participants: Eight (Study 1) and seven (Study 2) volunteers in cross‐over and 52 gonadotrophin‐deficient men in the multi‐dose study Measurements: In cross‐over studies, serum testosterone (T), dihydrotestosterone (DHT) and estradiol by liquid chromatography‐mass spectrometry (LCMS) and serum hCG, LH, FSH, SHBG and T (observational study) by immunoassays. Results: After standard and high‐dose injection, serum hCG and testosterone responses had similar timing and peak concentrations except for a mildly lower early (<48 h) serum testosterone with uhCG. In the multi‐dosing study, both hCGs had similar pharmacokinetics (pooled half‐life 5.8 days, p <.001), while serum testosterone concentrations were stable after injection and did not differ between hCG products. Bench testing verified that 20% of pens from 4/10 individuals were used inappropriately. Conclusions: Although hCG pharmacokinetics are not formally bioequivalent, the similar pharmacodynamic effects on serum testosterone indicate that at the doses tested both hCGs provide comparable clinical effects. The starting dose of rhCG for treating gonadotrophin‐deficient men should be 62.5 µg (6 clicks) of the rhCG pen. [ABSTRACT FROM AUTHOR]

Research suggests that estradiol may moderate fear extinction. It is unclear whether these results generalize to exposure therapy. The aim of the current study was to determine whether estradiol moderates outcomes in exposure therapy among women with anxiety disorders. Participants were 35 women with a primary diagnosis of an anxiety disorder who participated in the study as part of routine care at an anxiety specialty clinic. Endogenous estradiol was assessed via saliva. They provided subjective distress ratings before (pre) and after (post) an exposure session, as well as after a brief delay (recall). Contrary to predictions, there were no significant differences in exposure outcomes between the high and low estradiol groups. However, among participants with primary obsessive-compulsive disorder (OCD), results were partially consistent with the hypotheses. Women with lower estradiol initially demonstrated more improvement in subjective distress from pre- to post-exposure, but after the delay, significantly greater distress (attenuated extinction recall). Results suggest that women with lower estradiol may respond less favorably to exposure therapy for OCD relative to women with higher estradiol. These findings await replication in larger samples with longer recall delays. Should replication occur, these results may inform the use of estradiol to augment exposure therapy. [ABSTRACT FROM AUTHOR]

Objective: To report the protocol of a study evaluating the efficacy of transdermal oestradiol (E2) gel in reducing the adverse effects of androgen deprivation therapy (ADT), specifically on sexual function, and to assess the utility of E2 in combination with supervised exercise. Study Design and Methods: The primary endpoint of this open‐label Phase IIA randomized controlled trial is the efficacy of transdermal E2 gel. Secondary endpoints include: (i) the occurrence of ADT‐induced adverse effects; (ii) the safety and tolerability of E2; (iii) the impact of E2 with or without exercise on physical, physiological, muscle, and systemic biomarkers; and (iv) quality of life. The trial will recruit high‐risk PCa patients (n = 310) undergoing external beam radiation therapy with adjuvant subcutaneous ADT. Participants will be stratified and randomized in a 1:1 ratio to either the E2 + ADT arm or the ADT‐only control arm. Additionally, a subset of patients (n = 120) will be randomized into a supervised exercise programme. Results: The primary outcome is assessed according to the efficacy of E2 in mitigating the deterioration of Expanded Prostate Cancer Index Composite sexual function domain scores. Secondary outcomes are assessed according to the occurrence of ADT‐induced adverse effects, safety and tolerability of E2, impact of E2 with or without exercise on physical performance, body composition, bone mineral density, muscle size, systematic biomarkers, and quality of life. Conclusion: The ESTRACISE study's innovative design can offer novel insights about the benefits of E2 gel, and the substudy can reinforce the benefits resistance training and deliver valuable new novel insights into the synergistic benefits of E2 gel and exercise, which are currently unknown. Trial Registration: The protocol has been registered in euclinicaltrials.eu (2023‐504704‐28‐00) and in clinicaltrials.gov (NCT06271551). [ABSTRACT FROM AUTHOR]

Background: The accurate prediction of pregnancy outcomes in in vitro fertilization (IVF) cycles is crucial. While several studies have been conducted on the predictive power of serum estradiol (E2) and β-hCG concentrations post-embryo transfer (ET) for pregnancy outcomes, there is debate on the predictive value of E2. The objective of this study was to investigate the predictive efficacy of combining serum E2 and β-hCG levels on early reproductive outcomes 12 days after embryo transfer. Methods: A total of 1521 patients with β-hCG positive values on day 12 following frozen-thawed embryo transfer (FET) with natural endometrial preparation cycles (NCs) were gathered in affiliated Women's Hospital of Jiangnan University. Using logistic regression, the relationship between pregnancy outcome and early serum E2 and β-hCG concentrations was examined. The receiver-operating characteristic (ROC) analysis was used to assess the predictive accuracy of the serum E2 and β-hCG concentrations. Results: Notable distinctions were observed in the serum E2 and β-hCG levels on the twelfth day following FET with NCs between the groups classified as clinical pregnancy group (CP Group) and biochemical pregnancy group (BP Group). In addition, the cutoff values for E2 and β-hCG on day 12 following FET with NCs in cleavage embryo group (CE Group) were 129.25 pg/mL and 156.60 mIU/mL, respectively. The threshold values for E2 and β-hCG for the blastocyst group (B Group) were 174.45 pg/mL and 217.70 mIU/mL. Serum E2 day12 and β-hCG day12 were found to be substantially linked with clinical pregnancy by logistic regression analysis. Conclusions: Serum E2 and β-hCG concentrations were found to be significantly different between the CP Group and BP Group in infertility women underwent FET with NCs. Our retrospective cohort study's findings suggest that the combination of early E2 and β-hCG levels on day 12 post-FET could be used as a predictive tool to evaluate the likelihood of both positive and negative pregnancy outcomes in FET with NCs. [ABSTRACT FROM AUTHOR]

Estrogens are believed to modulate cognitive functions in part through the modulation of synaptic transmission in the cortex and hippocampus. Administration of 17β‐estradiol (E2) can rapidly enhance excitatory synaptic transmission in the hippocampus and facilitate excitatory synaptic transmission in rat lateral entorhinal cortex via activation of the G protein‐coupled estrogen receptor‐1 (GPER1). To assess the mechanisms through which GPER1 activation facilitates synaptic transmission, we assessed the effects of acute 10 nM E2 administration on pharmacologically isolated evoked excitatory and inhibitory synaptic currents in layer II/III entorhinal neurons. Female Long‐Evans rats were ovariectomized between postnatal day (PD) 63 and 74 and implanted with a subdermal E2 capsule to maintain continuous low levels of E2. Electrophysiological recordings were obtained between 7 and 20 days after ovariectomy. Application of E2 for 20 min did not significantly affect AMPA or NMDA receptor‐mediated excitatory synaptic currents. However, GABA receptor‐mediated inhibitory synaptic currents (IPSCs) were markedly reduced by E2 and returned towards baseline levels during the 20‐min washout period. The inhibition of GABA‐mediated IPSCs was blocked in the presence of the GPER1 receptor antagonist G15. GPER1 can modulate protein kinase A (PKA), but blocking PKA with intracellular KT5720 did not prevent the E2‐induced reduction in IPSCs. GPER1 can also stimulate extracellular signal‐regulated kinase (ERK), a negative modulator of GABAA receptors, and blocking activation of ERK with PD90859 prevented the E2‐induced reduction of IPSCs. E2 can therefore result in a rapid GPER1 and ERK signaling‐mediated reduction in GABA‐mediated IPSCs. This provides a novel mechanism through which E2 can rapidly modulate synaptic excitability in entorhinal layer II/III neurons and may also contribute to E2 and ERK‐dependent alterations in synaptic transmission in other brain areas. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodResultsConclusionThe main purpose of this study was to elucidate the anti-apoptotic effects of curculigoside (CUR) on ovarian granulosa cells (GCs) in a mouse model of cyclophosphamide (CTX)-induced premature ovarian failure (POF).Intraperitoneal injection of CTX (100 mg/kg body weight) induced POF in mice. Thirty-six female mice were divided into six groups: blank group; POF model group; low-dose CUR group; medium-dose CUR group; high-dose CUR group; and estradiol benzoate group. Mice were orally administered for 28 consecutive days. Twenty-four hours after the completion of treatment, mice were weighed and euthanized, and blood was collected from the eyeball under anesthesia. The ovaries were surgically separated and weighed, and the ovarian index was calculated. Hematoxylin–eosin (HE) staining was used to observe follicular development and corpus luteum morphology in the ovaries. Serum levels of follicle stimulating hormone (FSH), anti-Müllerian hormone (AMH) and estradiol (E2) were measured. Superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) content and malondialdehyde (MDA) levels in ovarian tissue were determined. The GC apoptosis level was measured. Western blotting was used to detect protein expression levels of Beclin-1, LC3, P62, AKT, p-AKT, mTOR and p-mTOR in the ovaries.The results showed that CUR can improve body weight and ovarian index; promote follicular development and reduce follicular atresia; improve FSH, AMH and E2 levels; downregulate MDA levels and restore antioxidant enzyme activity; inhibit the autophagy level; activate the AKT/mTOR signaling pathway; and alleviate GC apoptosis.CUR improves POF by activating the AKT/mTOR signaling pathway, inhibiting autophagy and alleviating GC apoptosis. [ABSTRACT FROM AUTHOR]

We compared the efficacy of 4 mg drospirenone (DRSP) progestin-only pills (POPs) versus combined oral contraceptive pills (COCs) containing 0.02 mg of ethinyl estradiol (EE) and 0.075 mg of gestodene (GS) in ovulation inhibition and inducing unfavorable cervical mucus changes using a delayed-starting approach. This randomized controlled trial involved 36 participants aged 18–45 years. The major outcomes included ovulation inhibition assessed using the Hoogland and Skouby score, and cervical mucus permeability, assessed using the modified World Health Organization score. The results demonstrated ovulation inhibition rates of 77.8% for the EE/GS group and 88.9% for the DRSP group. The risk ratio and absolute risk reduction were 0.50 (95% confidence interval [CI]: 0.10, 2.40) and − 0.11 (95% CI: − 0.35, 0.13), respectively, satisfying the 20% non-inferiority margin threshold. The median time to achieve unfavorable cervical mucus changes was comparable between the DRSP (3 days, interquartile range [IQR]: 6 days) and EE/GS (3.5 days, IQR: 4 days) groups. However, the DRSP group had a higher incidence of unscheduled vaginal bleeding (55.56% vs. 11.11%; p = 0.005). DRSP-only pills, initiated on days 7–9 of the menstrual cycle, were non-inferior to EE/GS pills in ovulation inhibition. However, they exhibited delayed unfavorable cervical mucus changes compared to the standard two-day backup recommendation. Clinical trial registration: Thai Clinical Trials Registry (TCTR20220819001) https://www.thaiclinicaltrials.org/show/TCTR20220819001. [ABSTRACT FROM AUTHOR]

To enhance our understanding of teleost reproductive physiology, we identified six Sichuan bream (Sinibrama taeniatus) vitellogenin genes (vtg1-6) and characterized their sequence structures. We categorized them into type Ⅰ (vtg1,4,5 and 6), type Ⅱ (vtg2) and type Ⅲ (vtg3) based on differences in their subdomain structure. The promoter sequence of vtgs has multiple estrogen response elements, and their abundance appears to correlate with the responsiveness of vtg gene expression to estrogen. Gene expression analyses revealed that the vitellogenesis of Sichuan bream involves both heterosynthesis and autosynthesis pathways, with the dominant pathway originating from the liver. The drug treatment experiments revealed that 17β-estradiol (E2) tightly regulated the level of vtg mRNA in the liver. Feeding fish with a diet containing 100 μg/g E2 for three weeks significantly induced vtg gene expression and ovarian development, leading to an earlier onset of vitellogenesis. Additionally, it was observed that the initiation of vtg transcription required E2 binding to its receptor, a process primarily mediated by estrogen receptor alpha in Sichuan bream. The findings of this study provide novel insights into the molecular information of the vitellogenin gene family in teleosts, thereby contributing to the regulation of gonadal development in farmed fish. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) binds to angiotensin‐converting enzyme 2 (ACE2) on host cells, via its spike protein, and transmembrane protease, serine 2 (TMPRSS2) cleaves the spike‐ACE2 complex to facilitate virus entry. As rate‐limiting steps for virus entry, modulation of ACE2 and/or TMPRSS2 may decrease SARS‐CoV‐2 infectivity and COVID‐19 severity. In silico modeling suggested the natural bioactive flavonoid quercetin can bind to ACE2 and a recent randomized clinical trial demonstrated that oral supplementation with quercetin increased COVID‐19 recovery. A range of cultured human cells were assessed for co‐expression of ACE2 and TMPRSS2. Immortalized Calu‐3 lung cells, cultured and matured at an air–liquid interface (Calu‐3‐ALIs), were established as the most appropriate. Primary bronchial epithelial cells (PBECs) were obtained from healthy adult males (N = 6) and cultured under submerged conditions to corroborate the outcomes. Upon maturation or reaching 80% confluence, respectively, the Calu‐3‐ALIs and PBECs were treated with quercetin, and mRNA and protein expression were assessed by droplet digital PCR and ELISA, respectively. SARS‐CoV‐2 infectivity, and the effects of pre‐ and co‐treatment with quercetin, was assessed by median tissue culture infectious dose assay. Quercetin dose‐dependently decreased ACE2 and TMPRSS2 mRNA and protein in both Calu‐3‐ALIs and PBECs after 4 h, while TMPRSS2 remained suppressed in response to prolonged treatment with lower doses (twice daily for 3 days). Quercetin also acutely decreased ADAM17 mRNA, but not ACE, in Calu‐3‐ALIs, and this warrants further investigation. Calu‐3‐ALIs, but not PBECs, were successfully infected with SARS‐CoV‐2; however, quercetin had no antiviral effect, neither directly nor indirectly through downregulation of ACE2 and TMPRSS2. Calu‐3‐ALIs were reaffirmed to be an optimal cell model for research into the regulation of ACE2 and TMPRSS2, without the need for prior genetic modification, and will prove valuable in future coronavirus and respiratory infectious disease work. However, our data demonstrate that a significant decrease in the expression of ACE2 and TMPRSS2 by a promising prophylactic candidate may not translate to infection prevention. [ABSTRACT FROM AUTHOR]

Transgender persons face a greater burden of HIV compared to cisgender counterparts. Concerns around drug–drug interactions (DDIs) have been cited as reasons for lower engagement in HIV care and lower pre‐exposure prophylaxis (PrEP) uptake among transgender populations. It is therefore imperative for hormone therapy, PrEP and antiretroviral therapy providers to understand the DDI potential between these therapies.Studies of tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) PrEP with feminizing hormone therapies (FHTs) show reduced plasma tenofovir concentrations, but intracellular concentrations of tenofovir‐diphosphate are not reduced. Efficacy of PrEP is expected to be maintained despite this interaction. Masculinizing hormone therapies have no effect on tenofovir concentrations but may increase FTC to a nonclinically relevant extent. No interactions between FHT and cabotegravir or tenofovir alafenamide have been demonstrated. Administration of TDF/FTC PrEP has no effect on hormone levels in transmen or transwomen. PrEP is expected to be effective and safe in transpersons and should be provided to high‐risk individuals regardless of gender affirming hormone use.Enzyme inducing/inhibiting antiretroviral therapy may decrease or increase, respectively, the concentrations of FHT and masculinizing hormone therapy. Unboosted integrase inhibitors or enzyme neutral non‐nucleoside reverse transcriptase inhibitors are not expected to affect and are not affected by gender affirming hormones and can be considered in transmen and transwomen. Overlapping toxicities including weight gain, dyslipidaemia, cardiovascular disease and bone density effects should be considered, and antiretroviral modifications can be made to minimize toxicities. Interactions between supportive care medications should be assessed to avoid chelation interactions and hyperkalaemia. [ABSTRACT FROM AUTHOR]

Artificial insemination (AI) centres select bulls as calves according to their genetic breeding values and raise them until the first semen collection; yet, a high dropout rate of reared bulls is a problem for AI centres. Potential hormonal indicators of bull sexual maturation (cortisol, dehydroepiandrosterone (DHEA), testosterone, oestradiol, insulin‐like growth factor 1 (IGF‐1)) were observed and evaluated in relation to the performance parameters to perhaps identify candidate biomarkers allowing an early selection of bulls as suitable sires. Blood samples from 102 German Holstein calves at 4 ± 1, 8 ± 1 and 12 ± 2 months of age from six AI centres were analysed using validated immunoassays for cortisol, DHEA, testosterone, oestradiol and IGF‐1. Semen analyses included native and thawed diluted semen. Bulls were classified at the first semen collection into groups with good versus poor performance (GP vs. LP). After 2 years, the subsequent differentiation was done in high (HPP), medium (MPP) and low performance persistency (LPP). Age at first semen collection was an important factor for sperm quality. Cortisol concentrations decreased with age, but the cortisol/DHEA ratio decreased with age only in GP bulls (p <.05). Oestradiol and testosterone concentrations both correlated with libido behaviour (p <.05). Testosterone and IGF‐1 concentrations were higher at the time of first semen collection in GP bulls and increased with age (p <.05). In conclusion, testosterone and IGF‐1 concentrations at first semen collection are associated with performance at first semen collection and future performance persistency, and might be useful early biomarkers for consistent sperm producing bulls on AI centres. [ABSTRACT FROM AUTHOR]

Exposure to glyphosate-based herbicides (GBH) and consumption of cafeteria (CAF) diet, which are widespread in Western society, seem to be associated with endometrial hyperplasia (EH). Here, we aimed to evaluate the effects of a subchronic low dose of GBH added to the CAF diet on the rat uterus. Female Wistar rats were fed from postnatal day (PND)21 until PND240 with chow (control) or CAF diet. Since PND140, rats also received GBH (2 mg of glyphosate/kg/day) or water through food, yielding four experimental groups: control, CAF, GBH, and CAF+GBH. On PND240, CAF and CAF+GBH animals showed an increased adiposity index. With respect to the control group, no changes in the serum levels of 17β-estradiol and progesterone were found. However, progesterone levels were higher in the CAF+GBH group than in the CAF and GBH groups. In the uterus, both studied factors alone and in combination induced morphological and molecular changes associated with EH. Furthermore, the addition of GBH provoked an increased thickness of subepithelial stroma in rats fed with the CAF diet. As a consequence of GBH exposure, CAF+GBH rats exhibited an increased density of abnormal gland area, considered preneoplastic lesions, as well as a reduced PTEN and p27 expression, both tumor suppressor molecules that inhibit cell proliferation, with respect to control rats. These results indicate that the addition of GBH exacerbates the CAF effects on uterine lesions and that the PTEN/p27 signaling pathway seems to be involved. Further studies focusing on the interaction between unhealthy diets and environmental chemicals should be encouraged to better understand uterine pathologies. [ABSTRACT FROM AUTHOR]

The oestrogenic component of combined oral contraceptives (COCs) has changed over years with the aim of reducing oestrogen-related side effects and risks, whilst maintaining oestrogen beneficial effects, particularly on cycle control. To describe the pharmacological profiles of different oestrogens commonly used in COCs to provide insights on contraceptive prescription tailored to women's needs. All COCs ensure a high contraceptive efficacy. COCs containing the natural oestrogens oestradiol (E2), oestradiol valerate (E2V) and estetrol (E4) have limited impact on liver metabolism, lipid and carbohydrate metabolism, haemostasis and sex hormone binding globulin levels, compared with ethinylestradiol (EE). COCs with E2 and E2V appear also to entail a lower elevation of the risk of venous thromboembolism vs. EE-containing pills. No epidemiological data are available for E4-COC. E2- and E2V-containing COCs seem to exert a less stabilising oestrogenic effect on the endometrium compared with EE-COCs. The E4-COC results in a predictable bleeding pattern with a high rate of scheduled bleeding and minimal unscheduled bleeding per cycle. Based on in vitro and in vivo animal data, E4 seems to be associated with a lower effect on cell breast proliferation. Today various COCs contain different oestrogens. Prescribers must be familiar with the different properties of each oestrogen for a tailored contraceptive recommendation, considering their safety and contraceptive efficacy, as well as women's needs and preferences. For contraceptive pills physicians can choose among different oestrogens, besides many progestins. Natural oestrogens have less metabolic impact vs EE, while EE and E4 seem to provide a better cycle control. Knowing the different oestrogen characteristics is crucial for adjusting pill prescription to women's needs and desires. [ABSTRACT FROM AUTHOR]

To correlate the sexual desire levels with sexual hormone binding globulin and free androgen index in women taking different types of hormonal contraceptives (HCs) containing ethinylestradiol (EE), oestradiol valerate (E2V), 17β-oestradiol (E2), or estetrol (E4), combined or in phasic formulation with different progestogens having antiandrogenic properties. Three hundred and sixty-seven women (age range 18-46) participated in the study. SHBG and total testosterone (TT) were measured, and the Free Androgen Index (FAI) was calculated. The Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale (FSDS) questionnaires were used to assess sexual function and distress, respectively. The highest SHBG values and the lowest FAIs were obtained of women on HCs containing EE than those of women on HCs containing E2V/17β E2 or E4 (p < 0.001). Desire scores and FSFI total scores were lower in women on HCs with EE than in those using HCs containing E2V, 17β E2, or E4 (p ≤ 0.001). The women who were on HCs containing EE reported FSDS levels higher than those containing all the other types of oestrogen. Finally, sexual desire and FSFI total scores had a negative correlation with the SHBG values and a positive correlation with FAI percentage (p ≤ 0.0001). A minority of women using HCs with EE might experience a decreased sexual desire. This was not observed in women on HCs containing E2V, 17 E2, or E4. To avoid HC discontinuation, due to sexual desire reduction, HCs having minor antiandrogenic effects could be taken into consideration. [ABSTRACT FROM AUTHOR]

In avian embryos, xenoestrogens induce abnormalities in reproductive organs, particularly the testes and Müllerian ducts (MDs). However, the molecular mechanisms remain poorly understood. We investigated the effects of ethynylestradiol (EE2) exposure on gene expression associated with reproductive organ development in Japanese quail embryos. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis revealed that the left testis containing ovary-like tissues following EE2 exposure highly expressed the genes for steroidogenic enzymes (P450scc , P45017α, lyase , and 3β-HS D) and estrogen receptor-β, compared to the right testis. No asymmetry was found in these gene expression without EE2. EE2 induced hypertrophy in female MDs and suppressed atrophy in male MDs on both sides. RNA sequencing analysis of female MDs showed 1,366 differentially expressed genes between developing left MD and atrophied right MD in the absence of EE2, and these genes were enriched in Gene Ontology terms related to organogenesis, including cell proliferation, migration and differentiation, and angiogenesis. However, EE2 reduced asymmetrically expressed genes to 21. RT-qPCR analysis indicated that genes promoting cell cycle progression and oncogenesis were more highly expressed in the left MD than in the right MD, but EE2 eliminated such asymmetric gene expression by increasing levels on the right side. EE2-exposed males showed overexpression of these genes in both MDs. This study reveals part of the molecular basis of xenoestrogen-induced abnormalities in avian reproductive organs, where EE2 may partly feminize gene expression in the left testis, developing as the ovotestis, and induce bilateral MD malformation by canceling asymmetric gene expression underlying MD development. [ABSTRACT FROM AUTHOR]

Background: Oestrogen deficiency increases bone resorption, contributing to osteoporosis development. Yet, the mechanisms mediating the effects of oestrogen on osteoclasts remain unclear. This study aimed to elucidate the early metabolic alteration induced by RANKL, the essential cytokine in osteoclastogenesis and 17‐beta‐oestradiol (E2) on osteoclast progenitor cells, using RAW 264.7 macrophage cell line and primary bone marrow‐derived macrophages as biological models. Results: This research demonstrated that, in osteoclast precursors, RANKL stimulates complex I activity, oxidative phosphorylation (OXPHOS) and mitochondria‐derived ATP production as early as 3 h of exposure. This effect on mitochondrial bioenergetics is associated with an increased capacity to oxidize TCA cycle substrates, fatty acids and amino acids. E2 inhibited all effects of RANKL on mitochondria metabolism. In the presence of RANKL, E2 also decreased cell number and stimulated the mitochondrial‐mediated apoptotic pathway, detected as early as 3 h. Further, the pro‐apoptotic effects of E2 during osteoclast differentiation were associated with an accumulation of p392S‐p53 in mitochondria. Conclusions: These findings elucidate the early effects of RANKL on osteoclast progenitor metabolism and suggest novel p53‐mediated mechanisms that contribute to postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

To study whether midluteal serum estradiol (E2) levels are associated with the live birth rate in hormone replacement therapy frozen embryo transfer (HRT-FET) cycles in patients with optimal midluteal serum progesterone (P4) levels. Observational prospective cohort study. Public fertility clinic. A total of 412 women had an HRT-FET cycle single blastocyst transfer from January 2020 to November 2022. The HRT-FET cycle priming regimen included oral E2 (6mg/24 h) administered in the evening, followed by vaginal P4 (400mg/12 h). Serum E2 and P4 levels were measured using a standardized method, 2–4 hours after the latest P4 administration and 9–14 hours after E4 administration on the day of blastocyst transfer, day 6 of P4 administration. Patients with serum P4 levels (<11 ng/mL [35 nmol/L]) on the day of transfer received additional rectal P4 (400mg/12 h). No additional E2 dose was administered. The primary outcome was the live birth rate (LBR) in relation to E2 levels at blastocyst transfer day. The optimal serum E2 levels correlating with ongoing pregnancy were ≥292 pg/mL and <409 pg/mL (≥1,070 pmol/L and <1,500 pmol/L). The LBR was 59% (60/102) when E2 levels were within this range, whereas a significantly lower LBR of 39% (101/260) was seen in patients when E2 levels were <292 pg/mL (<1,070 pmol/L) and of 28% (14/50) when E2 levels were ≥409 pg/mL (≥1,500 pg/mL). In a logistic regression analysis, adjusting for serum P4 level ≥11 ng/mL or <11 ng/mL (≥35 nmol or <35 nmol/L) on the day of transfer, body mass index, age at oocyte retrieval, day 5 or 6 vitrified blastocysts, and blastocyst score, the adjusted risk difference of live birth was −0.21 (−0.32; −0.10) when the E2 level was <292 pg/mL (<1,070 pmol/L) and −0.31 (−0.45; −0.18) when the E2 level was ≥409 pg/mL (≥1,500 pmol/L) compared with E2 levels ≥292 pg/mL and <409 pg/mL (≥1,070 and <1,500 pmol/L). Importantly, only 25% of patents had optimal levels. The study shows a significant association between serum E2 levels and reproductive outcomes in an HRT-FET cohort in which optimal serum P4 levels were secured. Midluteal serum E2 levels are associated with the LBR in HRT-FET cycles, and E2 levels should neither be too high nor too low. EudraCT No.: 2019-001539-29. [ABSTRACT FROM AUTHOR]

Aims: The current work describes the development of mechanistic vaginal absorption and metabolism model within Simcyp Simulator to predict systemic concentrations following vaginal application of ring and gel formulations. Methods: Vaginal and cervix physiology parameters were incorporated in the model development. The study highlights the model assumptions including simulation results comparing systemic concentrations of 5 different compounds, namely, dapivirine, tenofovir, lidocaine, ethinylestradiol and etonogestrel, administered as vaginal ring or gel. Due to lack of data, the vaginal absorption parameters were calculated based on assumptions or optimized. The model uses release rate/in vitro release profiles with formulation characteristics to predict drug mass transfer across vaginal tissue into the systemic circulation. Results: For lidocaine and tenofovir vaginal gel, the predicted to observed AUC0‐t and Cmax ratios were well within 2‐fold error limits. The average fold error (AFE) and absolute AFE indicating bias and precision of predictions range from 0.62 to 1.61. For dapivirine, the pharmacokinetic parameters are under and overpredicted in some studies due to lack of formulation composition details and relevance of release rate used in ring model. The predicted to observed AUC0‐t and Cmax ratios were well within 2‐fold error limits for etonogestrel and ethinylestradiol vaginal ring (AFEs and absolute AFEs from 0.84 to 1.83). Conclusion: The current study provides first of its kind physiologically based pharmacokinetic framework integrating physiology, population and formulation data to carry out in silico mechanistic vaginal absorption studies, with the potential for virtual bioequivalence assessment in the future. [ABSTRACT FROM AUTHOR]

The article offers information on the comparison of venous thromboembolism (VTE) risk between ethinyl estradiol-levonorgestrel combined oral contraceptives (COCs). Topics include the historical development of COCs with reduced ethinyl estradiol content to lower VTE risk, the introduction of E2-based COCs with E2 valerate and dienogest, and a pooled analysis of two large prospective observational cohort studies (INAS-SCORE and INAS-OC) to characterize VTE risk in a larger population.

Purpose: The aim of this study was to investigate and compare the levels of luteinizing hormone (LH), testosterone (T), estradiol (ES), sex hormone-binding globulin (SHBG), and insulin-like growth factor 1 (IGF-1) in master sprint (MS) and master endurance (ME) athletes. Additionally, the possible associations between these hormones, body composition, and lipid profile with athletic performance (% of performance in relation to the current world record) were analyzed. Materials andMethods: The participants were all men: (i) 34 MS (51.0 ± 6.8 years); and (ii) 32 ME (51.7 ± 9.4 years). Student's t-tests for independent samples were performed to compare all variables between groups. Results: MS had a significantly higher (p =.008) average IGF-1 (154.78 ± 29.85 ng/mL) when compared to ME (129.92 ± 25.48 ng/mL). Performance was significantly correlated with IGF-1 (r = 0.424). The MS group had a moderately lower body fat than ME athletes (MS 12.54 ± 4.07 vs. ME 14.60 ± 4.12; p =.078; d = 0.503). Conclusions: Thus, strength/power training exercise/sport seems to be more beneficial for obtaining a higher IGF-1 compared to aerobic/distance exercise/sport. In addition, LH, T, ES, and SHBG were similar between the two groups of athletes and were comparable to the reference values of younger adults. [ABSTRACT FROM AUTHOR]

Introduction: Gastroesophageal Reflux Disease (GERD) is a common clinical disorder characterised by the reflux of stomach contents into the oesophagus, primarily due to the temporary relaxation of the Lower Oesophageal Sphincter (LES). The aetiology of GERD is multifactorial. The prevalence of GERD in females has been found to sharply increase throughout the postmenopausal period compared to the reproductive phase. Aim: To study the relationship between serum oestrogen levels in premenopausal and postmenopausal women with GERD. Materials and Methods: In this cross-sectional study, 60 patients with GERD were divided into 30 premenopausal and 30 postmenopausal groups. The study subjects underwent high-resolution oesophageal manometry. The Cobas e 411 immunoassay analyser was utilised to measure serum oestrogen levels through electrochemiluminescence. The independent, unpaired Student's t-test was employed to analyse the collected data. Results: The statistical analysis revealed that the mean reduced LES pressure of 9.76±3.80 mmHg and the mean reduced Oesophagogastric Junction Contractile Integral (EGJ-Cl) of 14.503±10.64 mmHg were lower in women with postmenopausal GERD who exhibited lower oestrogen levels compared to those with premenopausal GERD. An increase in LES pressure was also associated with an increase in EGJ-CI, demonstrating a statistically significant positive linear correlation between LES pressure and EGJ-CI. The p-value <0.05 was deemed highly statistically significant. Conclusion: Parameters such as basal LES pressure and EGJCl were observed to be reduced in postmenopausal women with GERD who had low oestrogen levels. This study suggests that oestrogen plays a crucial role in safeguarding the oesophageal epithelium against the reflux of gastric contents. [ABSTRACT FROM AUTHOR]

Copper is an indispensable trace element in metabolism. This study aimed to investigate the relationship between copper and reproductive health, and possibly provide new insights for diagnosis and treatment. This study was based on data extracted from the NHANES database (2013–2014 and 2015–2016). The t-test, ANOVA, Chi-square test, multiple linear regression, and restricted cubic spline analysis were used. Serum copper levels were significantly higher in women with gestational diabetes than in those without gestational diabetes (P = 0.0150). Women with higher copper levels and smoking habits tended to deliver overweight babies (P = 0.028). Women with diabetes had higher serum copper and were prone to deliver overweight babies (P = 0.024). Serum copper levels showed a positive relationship with sex hormone-binding globulin (SHBG) levels (P < 0.0001). In this study, serum copper levels were found to be associated with reproductive health in women. Further studies are required to draw causal inferences. [ABSTRACT FROM AUTHOR]

Background: Premenstrual syndrome (PMS) is a pathological condition characterized by a series of abnormal physical, psychological, and behavioral symptoms. We evaluated the effectiveness of laparoscopic sleeve gastrectomy (LSG) in the treatment of patients with obesity and PMS. Methods: In this case–control study, 131 patients with obesity (BMI ≥ 27.5 kg/cm2) diagnosed with moderate-to-severe PMS from March 2018 to March 2022 were prospectively selected to undergo LSG or not at their own discretion. Participants self-reported their PMS severity using the Premenstrual Syndrome Screening Tool. Among them, 68 patients chose LSG surgery, and 63 control group patients were followed up without surgery. Data were recorded at baseline and at 3 months post-treatment. We used a multivariate analysis to assess the improvement in PMS symptoms and associated factors. Results: Of the 131 patients with obesity and PMS, the improvement rate of PMS in the LSG group was 57.35% (n = 39), while the improvement rate of PMS in the control group was 25.40% (n = 16). Furthermore, our study revealed that surgery is an independent factor affecting the improvement of patients with PMS. Additionally, there was a correlation between alcohol use, T2DM and obesity-related metabolic diseases, and BMI with PMS. The changes in BMI, testosterone, and estradiol(E2) levels may also contribute to the improvement of patients with obesity and PMS. Conclusion: LSG can improve the management of obesity in patients with PMS to some extent. Changes in BMI, testosterone, and E2 may be indicative of improvement in patients with obesity and PMS. [ABSTRACT FROM AUTHOR]

Objective: The hypothalamic-pituitary-gonadal axis is active during minipuberty, the timing of which coincides with infantile colic. To the best of our knowledge, the relationship between these entities has not been previously investigated. Methods: Saliva samples were collected from 15- to 60-day-old term infants (n=139) between 9 am and 5 pm. Group 1 included infants with infantile colic (n=68, 54.4% female) while the remaining healthy infants constituted Group 2 (n=71, 47.9% female). Salivary levels of estradiol (Esal) in females and testosterone (Tsal) in males were measured by ELISA in duplicate. Results: The median (25th-75th centile) age and birth week for all infants were 33 (29-43) days and 39 (38.1-40) weeks, respectively. Levels of Tsal in males [Group 1, 73.35 (59.94-117.82) pg/mL vs Group 2, 77.66 (56.49-110.08) pg/mL, p=0.956] and Esal in females [Group 1, 3.91 (2.76-5.31) pg/mL vs Group 2, 4.03 (1.63-12.1) pg/mL, p=0.683] were similar. However, in subjects with infantile colic (Group 1), Esal and body mass index (BMI) standard deviation scores of females were slightly correlated (Group 1, rs = 0.393, p=0.016 vs. Group 2, rs = 0.308, p=0.076) and there was a significant correlation between the sampling time and Tsal in males (Group 1, rs = 0.469, p=0.009 vs. Group 2, rs = -0.005, p=0.976). Conclusion: Random salivary sex steroid levels were similar in infants with and without infantile colic. However, in subjects with infantile colic, Esal levels in females were positively correlated with BMI and Tsal levels were higher later in the day among males. Thus, sex steroid production may be altered during minipuberty in subjects with infantile colic. [ABSTRACT FROM AUTHOR]

Menopause increases the risk for Parkinson's disease (PD), although the underlying biological mechanisms have not been established in patients. Here, we aimed to understand the basis of menopause-related vulnerability to PD. Main motor and non-motor scores, blood levels of estradiol, testosterone, follicle-stimulating hormone, and luteinizing hormone, CSF levels of total α-synuclein, amyloid-β-42, amyloid-β-40, total tau, and phosphorylated-181-tau were examined in 45 women with postmenopausal-onset PD and 40 age-matched controls. PD patients had higher testosterone and lower estradiol levels than controls, and the residual estradiol production was associated with milder motor disturbances and lower dopaminergic requirements. In PD but not in controls, follicle-stimulating hormone levels correlated with worse cognitive scores and CSF markers of amyloidopathy and neuronal loss. In conclusion, menopause-related hormonal changes might differentially contribute to clinical-pathological trajectories of PD, accounting for the peculiar vulnerability to the disease. [ABSTRACT FROM AUTHOR]

Fixed‐dose combination (FDC) therapies can enhance patient convenience and adherence to prescribed treatment regimens. Elagolix is a novel oral gonadotropin‐releasing hormone receptor antagonist approved for management of moderate to severe pain associated with endometriosis and heavy menstrual bleeding associated with uterine fibroids. Hormonal add‐back therapy can attenuate the reversible hypoestrogenic effects of elagolix. An FDC formulation containing elagolix/estradiol (E2)/norethindrone acetate (NETA) 300/1/0.5 mg as the morning dose and an elagolix 300 mg capsule as the evening dose, were evaluated in 2 bioequivalence studies including the effects of food. Study 1 in premenopausal women assessed the bioavailability of the elagolix 300‐mg capsule relative to the commercially available elagolix 300‐mg tablet. Study 2 in postmenopausal women, elagolix/E2/NETA (300 mg/1 mg/0.5 mg) FDC capsule was assessed relative to the elagolix 300‐mg tablet coadministered with E2/NETA 1‐mg/0.5‐mg tablet, the regimen that was studied in Phase 3 uterine fibroid studies. Under fasting conditions, the test elagolix 300‐mg capsule was bioequivalent to the reference elagolix 300‐mg tablet. Under fasting conditions, the elagolix/E2/NETA FDC capsule was bioequivalent to the coadministered elagolix 300‐mg tablet and E2/NETA 1/0.5‐mg tablet. Following administration of elagolix/E2/NETA FDC capsule after a high‐fat breakfast, elagolix mean maximum concentration (Cmax) and area under the plasma concentration‐time curve (AUC) were 38% and 28% lower, relative to fasting conditions. NETA mean Cmax was 51% lower and AUC from time 0 to infinity was 20% higher, while baseline‐adjusted total estrone mean Cmax and AUC were 46% and 14% lower, respectively. No safety concerns were identified. These results enabled bridging the elagolix/E2/NETA FDC capsule. [ABSTRACT FROM AUTHOR]

Objective. During in vitro fertilization-embryo transfer (IVF-ET) treatment, the reproductive endocrine regulatory mechanisms hold pivotal importance. Specifically, the serum estradiol ( E 2 ) level during ovulation emerges as a critical factor influencing pregnancy outcomes. This retrospective study aimed to comprehensively compare two common clinical regimens based on the grouping of serum E 2 levels and the number of oocytes retrieved on the trigger day. Our objective was to evaluate the pregnancy outcomes in IVF-ET patients across different ovarian response groups, exploring the efficacy of the dual-trigger and single-trigger regimens to provide valuable insights for optimizing clinical strategies in the context of IVF-ET. Methods. A retrospective analysis was conducted on the clinical data of 2778 infertile patients who underwent ART (IVF/ICSI). Subsequently, a detailed statistical analysis was performed on 1032 patients following an antagonist regimen. Participants were categorized into single-trigger and dual-trigger groups based on real-world trigger protocols, considering different ovarian responses. Comprehensive statistical assessments were conducted on baseline characteristics, ovulation induction, and pregnancy outcomes. Results. Baseline characteristics and cycle parameters among the three patient groups (high ovarian response, normal response, and poor response) exhibited no significant differences between the dual-trigger and single-trigger regimen groups. Despite the dual-trigger regimen utilizing a significantly lower HCG dose, no notable discrepancies were observed in laboratory results and pregnancy outcomes (embryo transfer rate, pregnancy rate, and live birth rate) for normal and high responders. Remarkably, E 2 levels were higher in the dual-trigger group compared to the single-trigger group. In high and normal responders, the dual-trigger regimen demonstrated increased oocyte counts and oocyte acquisition rates, coupled with decreased transfer cancellation rates attributed to ovarian hyperstimulation syndrome (OHSS). Intriguingly, patients with a poor ovarian response experienced no graft cancellations due to OHSS prevention in either group. Conclusion. For patients with high and normal ovarian responses, the utilization of a dual-trigger regimen on the trigger day effectively mitigates the risk of OHSS. Our large sample study supports the substitutability of the dual-trigger regimen over the single-trigger regimen without compromising pregnancy outcomes. However, this conclusion is not applicable to patients with poor ovarian responses. The results of this study highlight the necessity of adopting a customized and individualized treatment approach that should be based on the patient's ovarian response. Additionally, recognizing the pivotal role of the endocrine environment in influencing pregnancy outcomes and the occurrence of OHSS, further exploration of the effects of different triggering regimens on endocrine parameters is warranted. Such investigations will contribute to enhancing the reproductive outcomes of IVF-ET technology. [ABSTRACT FROM AUTHOR]

Background: Reproduction in women is at risk due to exposure to chemicals that can disrupt the endocrine system during different windows of sensitivity throughout life. Steroid hormone levels are fundamental for the normal development and function of the human reproductive system, including the ovary. This study aims to elucidate steroidogenesis at different life-stages in human ovaries. Methods: We have developed a sensitive and specific LC-MS/MS method for 21 important steroid hormones and measured them at different life stages: in media from cultures of human fetal ovaries collected from elective terminations of normally progressing pregnancy and in media from adult ovaries from Caesarean section patients, and follicular fluid from women undergoing infertility treatment. Statistically significant differences in steroid hormone levels and their ratios were calculated with parametric tests. Principal component analysis (PCA) was applied to explore clustering of the ovarian-derived steroidogenic profiles. Results: Comparison of the 21 steroid hormones revealed clear differences between the various ovarian-derived steroid profiles. Interestingly, we found biosynthesis of both canonical and "backdoor" pathway steroid hormones and corticosteroids in first and second trimester fetal and adult ovarian tissue cultures. 17α-estradiol, a less potent naturally occurring isomer of 17β-estradiol, was detected only in follicular fluid. PCA of the ovarian-derived profiles revealed clusters from: adult ovarian tissue cultures with relatively high levels of androgens; first trimester and second trimester fetal ovarian tissue cultures with relatively low estrogen levels; follicular fluid with the lowest androgens, but highest corticosteroid, progestogen and estradiol levels. Furthermore, ratios of specific steroid hormones showed higher estradiol/ testosterone and estrone/androstenedione (indicating higher CYP19A1 activity, p < 0.01) and higher 17-hydroxyprogesterone/progesterone and dehydroepiandrosterone /androstenedione (indicating higher CYP17A1 activity, p < 0.01) in fetal compared to adult ovarian tissue cultures. Conclusions: Human ovaries demonstrate de novo synthesis of non-canonical and "backdoor" pathway steroid hormones and corticosteroids. Elucidating the steroid profiles in human ovaries improves our understanding of physiological, life-stage dependent, steroidogenic capacity of ovaries and will inform mechanistic studies to identify endocrine disrupting chemicals that affect female reproduction. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) is more prevalent in post- compared to pre-menopausal women. The underlying mechanisms are not fully understood. Data in humans is confounded by age and co-morbidities. We investigated the effects of ovariectomy and estrogen replacement on the left ventricular (LV) gene expression of pro-inflammatory and pro-fibrotic factors involved in HFpEF and putative regulating miRNAs. Nine-week-old C57BL/6 female mice were subjected to ovariectomy (OVX) or SHAM operation. OVX and SHAM groups were sacrificed 1-, 6-, and 12-weeks post-surgery (T1/SHAM; T1/OVX; T6/SHAM; T6/OVX, T12/SHAM). 17β-estradiol (E2) or vehicle (VEH) was then administered to the OVX groups for 6 weeks (T12/OVX/E2; T12/OVX/VEH). Another SHAM group was sacrificed 12-weeks post-surgery. RNA and miRNAs were extracted from the LV apex. An early 3-fold increase in the gene expression of IL-1α, IL-6, Mmp9, Mmp12, Col1α1, and Col3α1 was observed one-week post-surgery in T1/OVX vs. T1/SHAM, but not at later time points. miRNA-26a was lower in T1/OVX vs. T1/SHAM and was inversely correlated with Col1α1 and Col3α1 expression 1-week post-surgery (r = −0.79 p < 0.001; r = −0.6 p = 0.007). miRNAs-26a, 29b, and 133a were significantly higher, while Col1α1, Col3α1, IL-1α, IL-6, Tnfα, Mmp12, and FasL gene expression was significantly lower in E2- compared to vehicle-treated OVX mice. miRNA-26a was inversely correlated with Col3α1 in T12/OVX/ E2 (r = −0.56 p = 0.02). OVX triggered an early increase in the gene expression of pro-inflammatory and pro-fibrotic factors, highlighting the importance of the early phase post-cessation of ovarian function. E2 replacement therapy, even if it was not immediately initiated after OVX, reversed these unfavorable changes and upregulated cardiac miRNA-26a, previously unknown to be affected by menopausal status. [ABSTRACT FROM AUTHOR]

Local estrogen therapy has been explored as an alternative to conventional testosterone therapy in children requiring urethroplasty for hypospadias. Our objective is to evaluate if preoperative estrogen stimulation reduces post-urethroplasty complications and enhances penile dimensions. A systematic search was conducted on various databases, selecting only randomized controlled trials (RCTs) that tested estrogen on hypospadias patients under 18 years. Articles underwent sorting following PRISMA guidelines and bias risk was assessed using the JBI clinical appraisal tool for RCTs. Out of 607 screened records, 10 underwent full-text review, and 4 randomized controlled trials (RCTs) were selected for analysis. The total patient cohort across studies was 387 with 174 in the estrogen group. All studies utilized topical estrogen, but in different formulations and timings. Prudence is necessary for interpreting results due to variations in formulation, timing, and hypospadias type across studies. Limited by a small number of studies and outcome presentation non-uniformity, the review suggests no change in penile dimensions or postoperative complications with topical estrogen. Further research is needed to explore wound-healing properties of estrogen in hypospadias through animal and human studies. Registration and protocol: Registered in Prospero CRD42024502183. [ABSTRACT FROM AUTHOR]

In the pathogenesis of polycystic ovary syndrome (PCOS), despite the importance of autophagy and transforming growth factor-β1 (TGF-β1), there is scarce information about their inter-relationship. Therefore, here we assessed the correlations between beclin-1, a cornerstone in autophagy, and TGF-β1 in a letrozole-induced PCOS rat model. Accordingly, a total of 45 female adult albino Wistar rats were randomly assigned into control, vehicle (carboxymethyl cellulose), and PCO groups. To establish the PCOS model, letrozole (1.0 mg/kg body wt., p.o.) was given once daily for three successive weeks. Circulating levels of luteinizing hormone, follicle-stimulating hormone, testosterone, estradiol, and progesterone were assayed along with ovarian total antioxidant capacity (TAC), protein carbonyl content (PCC), beclin-1 level, and TGF-β1 level. Ovarian morphology and ultrastructure were examined by hematoxylin and eosin staining and electron microscopy, respectively. Compared to control groups, hormonal levels and ovarian morphology in the letrozole-exposed animals indicated the successful construction of the PCOS model. Further, the PCO group exhibited an oxidative stress status reflected by a significant decrease in ovarian TAC and a significant elevation in the PCC. Moreover, ovarian beclin-1 and TGF-β1 levels were significantly increased with an enhancement of autophagy as revealed by electron microscopy. In multiple linear regression models, only TGF-β1 was observed in the final model where it explained the 62.3% variability of Beclin-1. In conclusion, the ovarian level of TGF-β1 might be a determinant factor of beclin-1 level in PCOS which may provide new insight into the pathophysiology and therapy of the disease. [ABSTRACT FROM AUTHOR]

In rodents, loss of estradiol (E2) reduces brown adipose tissue (BAT) metabolic activity. Whether E2 impacts BAT activity in women is not known. BAT oxidative metabolism was measured in premenopausal (n = 27; 35 ± 9 yr; body mass index = 26.0 ± 5.3 kg/m2) and postmenopausal (n = 25; 51 ± 8 yr; body mass index = 28.0 ± 5.0 kg/m2) women at room temperature and during acute cold exposure using [11C]acetate with positron emission tomography coupled with computed tomograph. BAT glucose uptake was also measured during acute cold exposure using 2-deoxy-2-[18F]fluoro- d -glucose. To isolate the effects of ovarian hormones from biological aging, measurements were repeated in a subset of premenopausal women (n = 8; 40 ± 4 yr; BMI = 28.0 ± 7.2 kg/m2) after 6 mo of gonadotropin-releasing hormone agonist therapy to suppress ovarian hormones. At room temperature, there was no difference in BAT oxidative metabolism between premenopausal (0.56 ± 0.31 min−1) and postmenopausal women (0.63 ± 0.28 min−1). During cold exposure, BAT oxidative metabolism (1.28 ± 0.85 vs. 0.91 ± 0.63 min−1, P = 0.03) and net BAT glucose uptake (84.4 ± 82.5 vs. 29.7 ± 31.4 nmol·g−1·min−1, P < 0.01) were higher in premenopausal than postmenopausal women. In premenopausal women who underwent gonadotropin-releasing hormone agonist, cold-stimulated BAT oxidative metabolism was reduced to a similar level (from 1.36 ± 0.66 min−1 to 0.91 ± 0.41 min−1) to that observed in postmenopausal women (0.91 ± 0.63 min−1). These results provide the first evidence in humans that reproductive hormones are associated with BAT oxidative metabolism and suggest that BAT may be a target to attenuate age-related reduction in energy expenditure and maintain metabolic health in postmenopausal women. NEW & NOTEWORTHY: In rodents, loss of estrogen reduces brown adipose tissue (BAT) activity. Whether this is true in humans is not known. We found that BAT oxidative metabolism and glucose uptake were lower in postmenopausal compared to premenopausal women. In premenopausal women who underwent ovarian suppression to reduce circulating estrogen, BAT oxidative metabolism was reduced to postmenopausal levels. Thus the loss of ovarian function in women leads to a reduction in BAT metabolic activity independent of age. [ABSTRACT FROM AUTHOR]

This parallel‐arm, phase I study investigated the potential cytochrome P450 (CYP)3A induction effect of NBI‐1065845 (TAK‐653), an investigational α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor potentiator in phase II development for major depressive disorder. The midazolam treatment arm received the sensitive CYP3A substrate midazolam on Day 1, followed by NBI‐1065845 alone on Days 5–13; on Day 14, NBI‐1065845 was administered with midazolam, then NBI‐1065845 alone on Day 15. The oral contraceptive treatment arm received ethinyl estradiol–levonorgestrel on Day 1, then NBI‐1065845 alone on Days 5–13; on Day 14, NBI‐1065845 was administered with ethinyl estradiol–levonorgestrel, then NBI‐1065845 alone on Days 15–17. Blood samples were collected for pharmacokinetic analyses. The midazolam treatment arm comprised 14 men and 4 women, of whom 16 completed the study. Sixteen of the 17 healthy women completed the oral contraceptive treatment arm. After multiple daily doses of NBI‐1065845, the geometric mean ratios (GMRs) (90% confidence interval) for maximum observed concentration were: midazolam, 0.94 (0.79–1.13); ethinyl estradiol, 1.00 (0.87–1.15); and levonorgestrel, 0.99 (0.87–1.13). For area under the plasma concentration–time curve (AUC) from time 0 to infinity, the GMRs were as follows: midazolam, 0.88 (0.78–0.98); and ethinyl estradiol, 1.01 (0.88–1.15). For levonorgestrel, the GMR for AUC from time 0 to the last quantifiable concentration was 0.87 (0.78–0.96). These findings indicate that NBI‐1065845 is not a CYP3A inducer and support its administration with CYP3A substrates. NBI‐1065845 was generally well tolerated, with no new safety signals observed after coadministration of midazolam, ethinyl estradiol, or levonorgestrel. [ABSTRACT FROM AUTHOR]

Intracranial dural arteriovenous fistulae (DAVFs) represent a subset of cerebral vascular malformations associated with significant morbidity and mortality. In Japan, DAVF exhibits sex-based differences in anatomical distribution, with female predominance in the cavernous sinus (CS) and male predominance in the transverse sinus (TS). Nevertheless, the pathophysiology of DAVF is not fully understood, and hormonal influences are hypothesized to play a role in its development. This study aimed to investigate changes in the concentrations of sex steroid hormones between intracranial and peripheral sampling sites in patients with CS- and TS-DAVF. We recruited 19 patients with CS-DAVF (n = 12) and TS-DAVF (n = 7) in this study. Blood hormone measurements were obtained from peripheral and jugular bulb samples during endovascular intervention. Hormone concentrations were analyzed using enzyme-linked immunosorbent assay kits, and statistical analyses were performed. Our study revealed a higher prevalence of CS-DAVF in females and TS-DAVF in males, which is consistent with previous studies. Estradiol concentration was significantly lower in the jugular bulb compared with in the periphery in both patients with CS- and TS-DAVF. This decrease in estradiol was observed irrespective of the patient's sex and independent of follicle-stimulating hormone levels. These findings indicate a local decrease in estradiol levels within the intracranial vasculature of patients with DAVF. This suggests a potential multifactorial role of estradiol in the pathomechanism of DAVFs, warranting further investigation to understand its influence on DAVF formation and potential targeted therapies, thereby enhancing patient outcomes. [ABSTRACT FROM AUTHOR]

17ß-Estradiol (E2) is an endocrine-disrupting chemical that has become a matter of concern across the globe for more than a decade due to potential health risks. This study reports facile methods to fabricate label-free aptasensor based on the non-Faradaic impedance mode using amine-functionalized graphene oxide polypyrrole (NH2-GO/PPy)-modified gold interdigitated electrode for direct capacitive detection of 17β-estradiol. The as-prepared NH2-GO/PPy nanocomposites have been successfully characterized by field-emission scanning electron microscopy (FESEM), atomic force microscopy, Fourier transform infrared spectroscopy, and electrochemical impedance spectroscopy. The results show that NH2-GO/PPy/IDE was able to detect E2 binding through aptamer conformational change by simply observing the capacitance change before and after immobilization. In addition, the biosensor showed a dynamic range of detection from 100 nM to 1 pM with a low detection limit of about 0.13 pM. The recoveries result also presented in this paper was validated using HPLC exhibited high sensitivity for bisphenol-A (BPA) detection and was successfully applied to detect E2 in real water samples with good recoveries. [ABSTRACT FROM AUTHOR]

Context Reliable estradiol (E2) reference intervals (RIs) are crucial in pediatric endocrinology. Objectives This study aims to develop a sensitive ultra-performance liquid chromatographic tandem mass spectrometry (UPLC-MS/MS) method for E2 in serum, to establish graphically represented RI percentiles and annual RIs for both sexes, and to perform a systematic literature comparison. Methods First, a UPLC-MS/MS method for E2 was developed. Second, graphically represented RI percentiles and annual RIs covering 0-18 years were computed (cohort of healthy children [1181 girls and 543 boys]). Subsequently, RIs were compared with published data by systematic searches. Results Lower limit of quantification was 11 pmol/L, indicating high sensitivity. Estradiol first peaked during mini-puberty in both sexes (girls up to 192 pmol/L; boys up to 225 pmol/L). As could be expected, girls showed higher pubertal E2 (up to 638 pmol/L). However, boys' RIs (up to 259 pmol/L) overlapped considerably. We found 4 studies in the literature that also used LC-MS/MS to determine E2 and published RIs for the complete pediatric age range. Reference intervals varied considerably. Pre-pubertal and pubertal phases were present in all studies. Higher E2 during the time of mini-puberty in both sexes was documented in 3 studies including ours. Conclusions Variability of RIs for E2 between studies illustrates the importance of laboratory-specific RIs despite using a LC-MS/MS reference method. In boys, the striking E2 peak during mini-puberty as well as high pubertal E2 without phenotypic estrogenization in regular male puberty indicates that the role of E2 in children and, especially in boys, requires better functional understanding. [ABSTRACT FROM AUTHOR]

Chronotype, an individual's preferred sleep-wake timing, is influenced by sex and age. Men sometimes report a later chronotype than women and older age is associated with earlier chronotype. The sex-related changes in chronotype coincide with puberty and menopause. However, the effects of sex hormones on human chronotype remain unclear. To examine the impact of 3 months of gender-affirming hormone therapy (GAHT) on chronotype in transgender persons, this study used data from 93 participants from the prospective RESTED cohort, including 49 transmasculine (TM) participants starting testosterone and 44 transfeminine (TF) participants starting estrogens and antiandrogens. Midpoint of sleep and sleep duration were measured using the ultra-short Munich ChronoType Questionnaire (µMCTQ). After 3 months of GAHT, TM participants' midpoint of sleep increased by 24 minutes (95% CI: 3 to 45), whereas TF participants' midpoint of sleep decreased by 21 minutes (95% CI: −38 to −4). Total sleep duration did not change significantly in either group. This study provides the first prospective assessment of sex hormone use and chronotype in transgender persons, showing that GAHT can change chronotype in line with cisgender sex differences. These findings provide a basis for future studies on biological mechanisms and clinical consequences of chronotype changes. [ABSTRACT FROM AUTHOR]

Alcohol use disorder (AUD) constitutes a critical public health issue and has sex-specific characteristics. Initial evidence suggests that progesterone and estradiol might reduce or increase alcohol intake, respectively. However, there is a need for a better understanding of how the menstrual cycle in females and the ratio of progesterone to estradiol in females and males influence alcohol use patterns in individuals with AUD. In this sex-separated multicenter longitudinal study, the authors analyzed 12-month data on real-life alcohol use (from 21,460 smartphone entries), menstrual cycle, and serum progesterone-to-estradiol ratios (from 667 blood samples at four individual study visits) in 74 naturally cycling females and 278 males with AUD between 2020 and 2022, using generalized and general linear mixed modeling. Menstrual cycle phases were significantly associated with binge drinking and progesterone-to-estradiol ratio. During the late luteal phase, females showed a lower predicted binge drinking probability of 13% and a higher predicted marginal mean of progesterone-to-estradiol ratio of 95 compared with during the menstrual, follicular, and ovulatory phases (binge drinking probability and odds ratios vs. late luteal phase, respectively: 17%, odds ratio=1.340, 95% CI=1.031, 1.742; 19%, odds ratio=1.523, 95% CI=1.190, 1.949; and 20%, odds ratio=1.683, 95% CI=1.285, 2.206; difference in progesterone-to-estradiol ratios, respectively: −61, 95% CI=−105.492, −16.095; −78, 95% CI=−119.322, −37.039; and −71, 95% CI=−114.568, −27.534). In males, a higher progesterone-to-estradiol ratio was related to lower probabilities of binge drinking and of any alcohol use, with a 10-unit increase in the hormone ratio resulting in odds ratios of 0.918 (95% CI=0.843, 0.999) and 0.914 (95% CI=0.845, 0.988), respectively. These ecologically valid findings suggest that high progesterone-to-estradiol ratios can have a protective effect against problematic alcohol use in females and males with AUD, highlighting the progesterone-to-estradiol ratio as a promising treatment target. Moreover, the results indicate that females with AUD may benefit from menstrual cycle phase-tailored treatments. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Guidelines for monitoring of medications frequently used in the gender-affirming care of transgender and gender-diverse (TGD) adolescents are based on studies in adults or other medical conditions. In this study, we aimed to investigate commonly screened laboratory measurements in TGD adolescents receiving gender-affirming hormone therapy (GAHT). METHODS: TGD adolescents were recruited from 4 study sites in the United States before beginning GAHT. Hemoglobin, hematocrit, hemoglobin A1c, alanine transaminase, aspartate aminotransferase, prolactin, and potassium were abstracted from the medical record at baseline and at 6, 12, and 24 months after starting GAHT. RESULTS: Two-hundred and ninety-three participants (68% designated female at birth) with no previous history of gonadotropin-releasing hormone analog use were included in the analysis. Hemoglobin and hematocrit decreased in adolescents prescribed estradiol (-1.4 mg/dL and -3.6%, respectively) and increased in adolescents prescribed testosterone (+1.0 mg/dL and 13.9%) by 6 months after GAHT initiation. Thirteen (6.5%) participants prescribed testosterone had hematocrit > 50% during GAHT. There were no differences in hemoglobin A1c, alanine transaminase, or aspartate aminotransferase. There was a small increase in prolactin after 6 months of estradiol therapy in transfeminine adolescents. Hyperkalemia in transfeminine adolescents taking spironolactone was infrequent and transient if present. CONCLUSIONS: Abnormal laboratory results are rare in TGD adolescents prescribed GAHT and, if present, occur within 6 months of GAHT initiation. Future guidelines may not require routine screening of these laboratory parameters beyond 6 months of GAHT in otherwise healthy TGD adolescents. [ABSTRACT FROM AUTHOR]

Objective To investigate the causal relationship between tea intake and sex hormone levels by two -sample Mendelian randomization analysis. Methods Single nucleotide polymorphisms related to tea intake were screened from tlie genome -wide association study as genetic instrumental variables. Five Mendelian randomized methods including simple model, weighted model, inverse variance weighted (IVW) analysis, weighted median method, and MR-Egger metliod were used to study the causal association between tea intake and sex hormone levels, which was evaluated by the 0 value. Remits A total of 41 SNPs were included in this study. The results of inverse variance weighting method showed that tea intake could increase the level of bioavailable testosterone 0=0.073: P < 0.05) and decrease the level of estradiol (j8=-0»023, P < 0.05). The estimated results of MR-Egger effect showed that tea intake could increase the level of bioavailable testosterone 俗二 0.179, P<0.05) and decrease the level of estradiol (B=-0.049, P<0.05), and the weighted median method also found that tea could increase the level of bioavailable testosterone 13=0.120, P<0.05) and decrease the level of extradiol (j8=-0»047, P<0.05), consistent with the results of IVW method. MR-Egger regression method showed that there was no horizontal pleiotropy, leaving one method and Cochran s Q statistics test showed no heterogeneity, and the direction of single SNP was correct. Conclusion Tea intake can up-regulate testosterone level and down-regulate estradiol level. Reasonable tea intake will contribute to the effective intervention of sex hormone-related diseases and provide important reference for the prevention and treatment of clinical diseases. [ABSTRACT FROM AUTHOR]

17β-Estradiol (E2) is the typical endocrine disruptor of steroidal estrogens and is widely used in animal husbandry and dairy processing. In the environment, even lower concentrations of E2 can cause endocrine dysfunction in organisms. Herein, we have developed a novel molecularly imprinted ratiometric fluorescent sensor based on SiO2-coated CdTe quantum dots (CdTe@SiO2) and 7-hydroxycoumarin with a post-imprint mixing strategy. The sensor selectively detected E2 in aqueous environments due to its two fluorescent signals with a self-correction function. The sensor has been successfully used for spiking a wide range of real water and milk samples. The results showed that the sensor exhibited good linearity over the concentration range 0.011–50 μg/L, obtaining satisfactory recoveries of 92.4–110.6% with precisions (RSD) < 2.5%. Moreover, this sensor obtained an ultra-low detection limit of 3.3 ng/L and a higher imprinting factor of 13.66. By using estriol (E3), as a supporting model, it was confirmed that a simple and economical ratiometric fluorescent construction strategy was provided for other hydrophobic substances. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to compare the effects of fasting for 48 h on the evoked insulin and glucose responses in males and females, and to explore factors such as stress and estrogen levels that might influence these responses. Methods: Healthy, nonobese male (n = 14) and female (n = 14) subjects underwent 48-h fasting trial. Changes in glucose tolerance and insulin levels in response to the oral glucose tolerance test, subjectively perceived stress and catecholamine concentrations were measured in all participants. Estrogen levels were also measured in the female participants during the 48-h fast. Results: Glucose area under the curve (AUC) values increased similarly in both sexes after 48-h fasting (P < 0.05), but females displayed a greater rise in insulin AUC values than males (P < 0.05). Fasting increased plasma epinephrine concentrations in both sexes (P < 0.05), whereas plasma norepinephrine concentrations and subjective stress increased only in females (P < 0.05). Plasma 17-β-estradiol concentrations in females decreased after fasting (P < 0.05). Conclusion: Fasting for 48 h induced a similar glucose intolerance in females and males, despite decreased 17-β-estradiol levels and greater psychological and physiological stress in females. These differences represent a plausible explanation for the gender-based differences observed in insulin responses. Trial registration: Retrospectively registered on ClinicalTrials.gov (NCT05545943) in September 19, 2022. [ABSTRACT FROM AUTHOR]

The direct electrochemical oxidation of 17‐β‐estradiol (E2) at conventional electrodes gives weak current signals making detection at trace levels difficult, as required for clinical and environmental applications. In order to strengthen the electrochemical behavior of E2, a simple and sensitive sensor has been realized based on a graphite screen printed electrode (GSPE) functionalized according to a two‐step procedure: i) drop‐casting deposition of gold nanoparticles (AuNPs); ii) electropolymerization of methylene blue (MB). The final PMB‐AuNPs‐GSPE platform was characterized by scanning electron microscopy (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The pH value was optimized in order to obtain the best detection efficiency and the highest peak current response was obtained at pH 7.0. The synergistic contributions of both AuNPs and PMB allowed the proposed sensor to show a wide linear range from 0.5 to 125.0 μmol L−1 with a LOD of 41 nmol L−1, long‐term stability and good reproducibility (RSD=2.9 % for n=10). Moreover, the sensor was able to distinguish E2 from several interfering compounds commonly present in urine and river water as well as from other endocrine‐ disrupting chemicals (EDCs), denoting its high specificity to E2 molecule. Finally, the developed electrode platform was successfully applied to the determination of E2 in both human urine and river water samples without any purification step under the standard addition method. [ABSTRACT FROM AUTHOR]

The article highlights the changes in safety labeling approved by the U.S. Food and Drug Administration (FDA) from October to December 2023. Topics mentioned include the life-threatening respiratory depression caused by opioid Actiq, the risks associated with the use of central nervous system depressant benzodiazepines, and the interaction of Actiq with cytochrome P450 3A4.

Background Adult female acne (AFA) is characterized by a relapsing eruption of acne in women aged ≥ 25 years. It can be slower to respond to traditional adolescent acne treatments. Usually, androgens promote acne by stimulating sebum production, while oestrogens have the -opposite effect by reducing sebum output when present in adequate quantities. Oestradiol is a female sex hormone that has its highest absolute serum levels and highest oestrogenic activity during the reproductive years. Peel-off facial masks have been suggested to intensify the effect of added active ingredients by forming an occlusive film after drying. Objectives To study the safety and efficacy of weekly topical oestradiol 0.05% in the treatment of AFA. Methods Twenty women with AFA were subjected to once-weekly application of an oestradiol 0.05% mask or placebo mask to either side of their face for 8 weeks. An acne lesion count was performed at baseline, at each visit and 8 weeks post-treatment. Results At the end of the treatment period, the treated side showed significant improvement in comedones, papules and pustules. Although lesion counts increased 2 months post-treatment, they remained significantly less common on the oestradiol-treated side compared with the side of the face treated with placebo. No side-effects were reported. Limitations included the small number of patients studied and the short follow-up period. The oestradiol effect was not studied at the cellular or molecular levels. Conclusions Topical oestradiol peel-off masks may be a promising convenient, safe and effective treatment for AFA. [ABSTRACT FROM AUTHOR]