Search Results (66)

Background: Menopause is characterised by a decline in oestrogen levels, leading to physical and psychological symptoms that significantly affect quality of life. Current parenteral oestradiol ester therapies, while effective, are often associated with side effects due to their oil-based formulations, including injection-site reactions and immune responses. Methods: In this study, we developed a water-soluble, polyethylene glycol cross-linked β-cyclodextrin (PEG–β-CD) polymer-based system for parenteral oestradiol delivery and evaluated its biocompatibility, solubility enhancement, immune compatibility, and pharmacokinetics. Results: Cytotoxicity assays using NIH-3T3 fibroblasts and RAW 264.7 macrophages showed minimal toxicity up to 10% (w/w). Phase-solubility studies demonstrated a significant increase in oestradiol solubility with the PEG–β-CD polymer, surpassing that of β-cyclodextrin or PEG alone. Dynamic light scattering and FTIR analyses confirmed successful complex formation, with submicron particles averaging 271 nm and physical incorporation of oestradiol into the polymer matrix. Macrophage activation assays and RT-qPCR analyses indicated an absence of immunogenic responses or pro-inflammatory cytokine induction. In vivo toxicity testing in Galleria mellonella larvae confirmed safety, while pharmacokinetic studies in Wistar rats revealed rapid initial absorption followed by stable, low-level serum concentrations comparable to those of commercially used oestradiol esters. Conclusions: These findings indicate that the PEG–β-CD polymer–oestradiol complex provides a safe, water-based alternative to traditional oil-based injections, with the potential to reduce side effects and improve patient compliance in postmenopausal hormone therapy. Full article

Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder linked to impaired cognition and altered dopamine neurotransmission. Emerging evidence suggests that women with ADHD experience pronounced hormone-related difficulties, with menstrual cycle-related changes in mood and cognition interfering with daily functioning and diminishing treatment efficacy. This review examines the influence of hormonal fluctuations during the menstrual cycle on cognitive functioning and ADHD symptomatology in women. A comprehensive literature search of Ovid EmBase identified studies published between 2015 and 2025 examining cognitive performance, including attention, executive functioning, working memory, and inhibitory control, across menstrual cycle phases in women with or without ADHD. Twenty-nine studies met inclusion criteria. Neurobiological measurements included hormonal assays, neuroimaging, and neurotransmitter models. Seven studies in non-clinical populations suggested that attentional processing was enhanced during the mid-luteal phase, which may be linked to higher progesterone levels. By contrast, four studies in women with ADHD and six studies in women with mood-related disorders, such as PMS or PMDD, consistently observed impairments in attention, executive function, and impulsivity during the mid-luteal and pre-menstrual phases. These objective findings parallel subjective reports of worsened cognition, heightened mood symptoms, and diminished medication efficacy during the luteal phase. Current evidence indicates that ADHD-related cognitive functioning fluctuates with the menstrual cycle, with impairments particularly evident in women with ADHD and/or comorbid mood disorders. These changes may reflect increased sensitivity to allopregnanolone, peri-menstrual oestrogen withdrawal, and the absence of compensatory neural adaptations observed in non-clinical populations. However, findings remain preliminary and sometimes contradictory due to methodological heterogeneity and small sample sizes. Further research is needed to clarify these mechanisms and, importantly, to translate theoretical insights into clinical application through female-specific diagnostic procedures and treatment strategies. Full article

Endothelial nitric oxide synthase (eNOS, NOS3) regulates steroidogenesis, redox signalling, and the vascular tone of the ovaries. Despite varying outcomes in previous studies, the prevalent NOS3 rs1799983 (Glu298Asp) polymorphism may influence endocrine function during controlled ovarian stimulation (COS). On the retrieval day, we assessed follicular-fluid hormones, day-3 hormones, and controlled ovarian stimulation (COS) outcomes (follicles, oocytes, MII oocytes, embryos) in 62 antagonist IVF/ICSI cycles classified by NOS3 genotype (GG/GT/TT). The outcomes for COS and early-cycle hormones were mostly consistent across all genotypes. A similar allele-dose pattern was seen for baseline oestradiol (GG < GT < TT), with heterozygous carriers displaying higher levels of follicular-fluid β-hCG relative to GG individuals. No changes were seen in follicle count, oocyte production, nuclear maturation, or embryo development. Baseline oestradiol and follicular β-hCG serve as the principal indications of the modest, context-dependent endocrine effects of the NOS3 rs1799983 polymorphism in antagonist cycles. To clarify the clinical significance of these intricate genotype-associated patterns, additional comprehensive, genotype-balanced investigations that include direct NO-pathway phenotyping are essential. Full article

An unhealthy prepubertal diet can have long-lasting effects throughout life. This study investigated hair concentrations of adrenal and sex steroids, in an in vivo mouse model of juvenile obesity subjected to control (CTRL), obesogenic (HFHC) diet, or nutraceutical supplementation (silymarin or coconut oil) diets. 87 3-week-old C57BL/6 mice (42 females, 45 males) were fed CTRL or HFHC diets for 8 weeks. Afterward, the CTRL group continued on CTRL diet while the HFHC diet group was divided into five groups: HFHC, HFHC→CTRL, HFHC→CTRL + silymarin (SIL), HFHC→HFHC + SIL and HFHC→HFHC + Coconut oil. At 4 weeks, the HFHC group showed increased cortisol/dehydroepiandrosterone (DHEA) ratio compared to CTRL group. At 20 weeks, the HFHC→HFHC group showed higher levels of progesterone (P4) and dehydroepiandrosterone sulfate (DHEA-S) and lower levels of estradiol (E2) compared to the CTRL→CTRL group. The switch from HFHC→CTRL was the optimal therapy because the body weight and almost all the hormones were close to those observed for the CTRL diet group. Supplement with SIL or Coconut oil reduced DHEA-S and increased in E2 compared with the endocrine setting seen with the HFHC diet. These interventions should be considered as supportive measures rather than substitutes for dietary correction. Full article

Additional progesterone administration during the luteal phase enhances reproductive outcomes in Hormone Replacement Therapy Frozen Embryo Transfer (HRT-FET) cycles in patients with low serum progesterone (P4). In this study we wanted to explore the use of urine P4 as a diagnostic tool during the luteal phase. This prospective observational cohort included a total of 464 HRT-FET cycles. The protocol entailed oral oestradiol (6 mg/24 h), followed by vaginal micronised progesterone (400 mg/12 h). On the day of blastocyst transfer, urine and serum samples were collected. Urine samples were analysed using an ARCHITECT automated immunoassay. A significant difference was found in median urine P4 between patients with serum P4 higher or lower than 11 ng/mL: 6400 ng/mL IQR [2528; 11,930] vs. 3408 ng/mL IQR [592; 6688], p < 0.001. The optimal cut-off to achieve live birth was a urine P4 ≥ 4000 ng/mL. The live birth rate was significantly higher in patients with urine P4 ≥ 4000 ng/mL, 48% (107/222) vs. 35% (45/130), respectively (p = 0.013). The odds ratio for live birth was 1.8 in patients with urine P4 ≥ 4000 ng/mL, 95% CI [1.067; 3.018], p = 0.028. The findings of the present study suggest that urine progesterone could be a valuable diagnostic tool to evaluate the need for additional progesterone in HRT-FET cycles. Full article

Organochlorine insecticides (DDTs), organophosphate insecticides (malathion), carbamate insecticides (carbaryl and thiram), pyrethroid (cypermethrin and fenvalarate) insecticides, and herbicides (glyphosate and atrazine) were selected for this study because they disrupt cervical and myometrial function in the bovine oestrous cycle. However, their potential to affect reproductive success in cattle during pregnancy has not been directly confirmed. The aim of this study was to determine the effects of the investigated pesticides on cervical contractions in pregnant cows. Cervical strips from cows at 4–6 months of gestation were treated with the eight singular pesticides (used at non-toxic, environmental dose) or oestradiol (E2) under two different conditions (37.5 °C for 24 h and 4 °C for 48 h), which were applied to assess pesticide effects under both physiological and prolonged-exposure settings. The strength of the contractions was then measured. The findings of the study demonstrated that both the carbamates and glyphosate increased the force of cervical strip contractions to a greater extent than cypermethrin. In contrast, fenvalerate was observed to induce a state of cervical relaxation, analogous to the effects of E2, while DDT, malathion and atrazine exerted no effect on cervical motor function during the period of pregnancy under investigation. These preliminary findings indicate a potential impact of pesticides on cervical function during pregnancy, but should be interpreted with caution as they are based on isolated tissue at a single concentration. Further in vivo and dose–response studies are needed to confirm their biological and clinical relevance. Full article

Sex hormones’ and menstrual cycle’s effects on cognitive performance remain unclear. This study examined cognitive differences between women across menstrual cycle phases, sex differences between women and men, and hormone–cognition associations. In total, 71 healthy young adults, aged 20–36 (42 women, 29 men), completed standardised cognitive tests measuring attention, processing speed, working memory, and visuospatial abilities. Women were tested twice: during menstrual (low-oestradiol) and pre-ovulatory (high-oestradiol) phases; men once. Hormone levels (oestradiol, progesterone, testosterone) were measured in blood samples via electrochemiluminescence immunoassay (ECLIA). Two analytical strategies were used: (1) within-subject analysis comparing women between phases, and (2) between-group comparison across three groups—women in menstrual phase, pre-ovulatory phase, and men. Women performed better during pre-ovulatory versus menstrual phase in working memory (Digit span forward: p = 0.04; Digit span backwards max: p = 0.02) and attention switching (Trail Making Test B: p = 0.01). Sex differences in processing speed were observed only during the menstrual phase (Trail Making Test A: p = 0.03; Stroop B: p = 0.04), but not in the pre-ovulatory phase. Positive correlations between oestradiol/progesterone and cognitive performance were found in men, while complex bidirectional relationships emerged in women during the menstrual phase only. Testosterone showed no significant correlations. These findings highlight hormonal status effects on cognitive sex differences. Full article

Steroid hormones are micropollutants that contaminate water worldwide and have significant impacts on human health and the environment, even at very low concentrations. The aim of this article is to provide an overview of technologies for the removal of endocrine-disrupting compounds with a focus on oestrogens (estrone E1, 17β-oestradiol E2, estriol E3), the synthetic oestrogen (17α-ethinylestradiol EE2 and bisphenol A BPA), and pharmaceuticals found in wastewater. Hormonal and pharmaceutical contaminants are mostly persistent organic compounds that cannot be easily removed using conventional wastewater treatment processes. For this reason, researchers have tried to develop more efficient tertiary wastewater treatment technologies to reduce micropollutant concentrations in wastewater. This review covers the following processes: Advanced oxidation, nanofiltration, ultrasound, electro-Fenton processes, electrolysis, adsorption, ozonation, photolysis, photocatalysis, ultrafiltration, and electrocoagulation. Attention was paid to the effectiveness of the processes in terms of eliminating hormones and pharmaceuticals from wastewater, as well as on economic and environmental aspects. The combination of different processes can be a promising treatment scheme for retaining and degrading hormonal and pharmaceutical compounds from wastewater. With hybrid technologies, the advantages of the methods are combined to maximise the removal of pollutants. However, optimal methods of wastewater treatment depend on the quality and quantity of the wastewater, as well as the residual hormonal and pharmaceutical compounds and their hazardous effects. Full article

Elevated circulating insulin levels between 80 and 100 µU/mL characterize hyperinsulinemia, which often leads to metabolic disorders such as obesity, insulin resistance, and type 2 diabetes (T2D). Elevated circulating insulin levels can directly affect vascular function and contribute to the pathophysiology of the cardiovascular system, including secondary arterial hypertension (SAH) and atherosclerosis. It is well known that hyperinsulinemia induced remodeling of the heart. However, there is no information on whether intrinsic differences exist between human vascular smooth muscle cells (VSMCs) and if in vitro mimicking hyperinsulinemia induces human VSMCs morphological and intracellular homeostasis remodeling in a sex- and sex hormones-dependent manner. Our in vitro cultured human VSMCs, coupled with quantitative 3D confocal imaging results, show that intrinsic differences exist between VSMCs from young men and women. Chronic hyperinsulinemia (80 µU/mL, 48 h treatment) increases cell and nuclear volumes associated with increased intracellular calcium (Ca²⁺) and ROS and decreased glutathione. In the absence of hyperinsulinemia, pretreatment with testosterone in VSMCs from men and oestradiol in VSMCs from women had no effect. Both sex hormones partially but not completely prevented hyperinsulinemia-induced remodeling of VSMCs from young men and women. The increase in VSMC volume may increase the thickness of the tunica media, leading to a decrease in the lumen of the blood vessel, which promotes the development of SAH and atherosclerosis in a sex-dependent manner. Full article

We aim to investigate whether chemical inhibition of NRF2 transcriptional activity (TA) influences distal colon contractions, particularly in an age-dependent manner in females, and whether it impacts oestrogen receptor signalling in female mice. This study was performed on 3 and 6-month-old female mice treated with ML385 (30 mg/kg) or a vehicle for 7 days (i.p.). The colon functionality was verified with a colon bead expulsion test; serum samples were collected for oestradiol levels, and colon samples were stored for various histological analyses. The results show that the seven-day treatment of ML385 significantly downregulated TA (p < 0.05) and impacted its contractility. Additionally, young females treated with ML385 exhibited an increase in goblet cell number and significantly increased ERα, but not ERβ, especially in older mice. It is worth noting that the basal level of the membrane oestrogen receptor GPR30 was higher in older mice within the epithelial layer, and ML385 treatment led to a downregulation of GPR30 in 6-month-old mice. In summary, ML385 decreases NRF2 TA in the colon and impacts its contractility and goblet cell numbers. Additionally, NRF2 TA influences the expression of oestrogen receptors in the colons of female mice. Full article

Background: Oestradiol has been implicated as a factor in substrate utilisation in male and mouse studies but the effect of acute changes during the menstrual cycle is yet to be fully understood. Objective: To determine the role of oestradiol in respiratory exchange ratio (RER) during exercise at various intensities. Methods: This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. From inception to November 2023, four online databases (Cochrane, SPORTDiscus, MEDline and Web of Science) were searched for relevant articles. Studies that reported a resting oestradiol measurement in naturally menstruating women with exercise at a percentage of maximal aerobic capacity (%V˙O_2max) were included. Mean and standard deviation for oestradiol, RER and exercise intensity were extracted and study quality assessed using a modified Downs and Black checklist. Risk of bias was assessed using I₂ measure of heterogeneity and Egger’s regression test, assessment of bias from methodological quality was identified by sensitivity analysis. Eligible datasets were extracted for pairwise comparisons within a meta-analysis and correlation between change in oestradiol and change in RER. Data were also pooled to produce a mean and standard deviation for RER for menstrual stage and for low and high oestradiol groups. Results: Twenty-four articles were identified, over 50% were identified as high quality. Sixteen articles included datasets eligible for meta-analysis. Eleven articles utilised a submaximal constant-load exercise intensity, finding a standardised mean difference of − 0.09 ([CI: −0.35–0.17], p = 0.5) suggesting no effect of menstrual phase on constant-load exercise RER. In six articles using incremental exercise tests to exhaustion, a standardised mean difference of 0.60 ([CI 0.00–1.19], p = 0.05) was identified towards a higher maximal RER attained in follicular compared to luteal phase. There was no correlation (R = −0.26, p = 0.2) between change in oestradiol and change in RER between phases. All 24 articles, totalling 650 participants, were included in pooled analysis. When grouped by menstrual cycle phase or when grouped by oestradiol levels, RER was higher in the follicular phase than the luteal phase at low and high constant load exercise intensities. Discussion: Findings from the pooled-analysis and meta-analysis suggest that there may be menstrual cycle phase differences in RER that are intensity dependent. These differences may be related to sex hormone levels, but this was not supported by evidence of correlation between differences in RER and differences in oestradiol. At present, it remains best practice to assess performance in the same menstrual cycle phase if seeking to assess change from baseline. Full article

Background/Objectives: Dehydroepiandrosterone (DHEA), a steroid hormone produced by the adrenal glands, plays a key role in various physiological processes, including bone health. Its age-related decline is linked to reduced bone density, though the mechanisms by which DHEA affects bone metabolism remain complex. This review summarises the diverse effects of DHEA on bone metabolism and density, highlighting its therapeutic potential; Methods: A literature search on the effects of DHEA on bone-related parameters was conducted from PubMed and Scopus using a specific search string, and after removing duplicates and irrelevant articles, 36 relevant full-text studies were included; Results: DHEA promotes osteoblast differentiation and proliferation, regulates the RANKL/OPG ratio, and inhibits osteoclastogenesis and bone resorption. Its osteogenic effects are mediated through multiple signalling pathways. In ovariectomised rat models, DHEA enhances trabecular bone volume, stimulates osteoblast proliferation, and increases oestradiol production and aromatase activity. In elderly individuals with low androgen levels, DHEA supplementation increases sulphated DHEA and oestradiol levels and improves bone mineral density, particularly in the ultra-distal radius of women and the femoral neck of men. However, the clinical use of DHEA remains debated due to inconsistent study results. Its effects on bone health may vary based on factors such as age, gender, and health conditions, emphasising the need for further research to clarify its mechanisms and optimise its use; Conclusions: In conclusion, while DHEA shows potential as a modulator of bone health, comprehensive clinical trials are required to assess its efficacy and safety, particularly in at-risk populations. Full article

Background and Clinical Significance: Abnormal uterine bleeding during the postmenopausal years is a pathological sign that may be due to simultaneous intrauterine and ovarian pathology. Granulosa cell tumours of the ovary are malignant neoplasms producing oestradiol, which leads to the abnormal proliferation of the endometrium, precancerous lesions, and endometrial carcinoma type I. Case Presentation: The authors present a clinical case of a 67-year-old woman with postmenopausal bleeding who underwent a total abdominal hysterectomy with bilateral adnexectomy, pelvic lymphadenectomy, and partial omentectomy. The histopathological examination showed a granulosa cell adult-type ovarian tumour and a malignant endometrial polyp with atypical hyperplasia of the endometrium. Conclusions: The immunohistochemical analysis of the malignant endometrial polyp confirmed the expression of oestrogen, progesterone receptors, and the biomarker Ki-67. Full article

Lactation in dairy cows implies comprehensive endocrine and metabolic changes including a systemic electrolytic reaction. Previous studies have rarely considered these specific demands due to the influence of lactation periods. Therefore, this study aimed to assess the effects of early, middle, and late lactation phases on the dynamic changes in serum concentrations of progesterone (P4), 17β-oestradiol (E2), cortisol, and some electrolytes (Ca⁺⁺, Mg⁺⁺, Na⁺, K⁺, Cl⁻, Pi) and biochemical parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), total bilirubin, urea, and iron (Fe⁺⁺) in 10 Holstein, 10 Brown Swiss, and 10 Modicana multiparous healthy dairy cows (4.2 ± 1.7 years of age) sampled at 60-day intervals throughout lactation. Lactation induced significant changes in the concentrations of P4, which peaked at >120–180 days, decreased at >240–300 days, and increased again after 300 days. Cortisol showed an opposite trend to P4, with concentrations progressively decreasing, except for the phase between >240 and 300 days, and a steep drop at >300 days compared to previous phases. Na⁺ concentrations showed the lowest values at 0–60 d and the highest ones at >180–240 days, whereas Mg⁺⁺ showed the highest values at >60–120 d and the lowest at >300 d. Significant correlations were found between P4 with cortisol, Cl⁻ and K⁺, and cortisol with Ca⁺⁺ and LDH. Significant differences in average concentrations of AST, ALT, LDH, Ca⁺⁺, Mg⁺⁺, and Fe⁺⁺ were observed among different dairy cow breeds. Understanding the dynamic changes in hormone levels, electrolytes, and biochemical parameters during different lactation phases, while considering breed differences in dairy cows, is crucial for improving herd health management and milk production in commercial dairy farms. Full article

Cadmium (Cd) exposure can induce follicular atresia and laying performance reduction in hens, which is linked to autophagy within the granulosa cells. Selenium (Se) can influence autophagy and counteract Cd toxicity. This study aimed to investigate the protective effect of Se on Cd-induced follicular atresia in laying hens. Sixty-four laying hens were randomly allocated into 4 treatments: control group: basal diet; Se group: basal diet + 0.4 mg/kg Se from selenized yeast; Cd group: basal diet + 25 mg/kg Cd from CdCl₂; and Cd+Se group: basal diet + 25 mg/kg Cd + 0.4 mg/kg Se. Compared to the Cd group, Se supplementation alleviated the ovarian pathological changes and oxidative stress in the follicles, serum, liver, and ovary, increased daily laying production, ovarian weight and F5–F1 follicle amounts, serum levels of progesterone and oestradiol, and up-regulated mTOR expression (p < 0.05), while decreasing the count of autophagic vacuoles, ovarian atresia follicle numbers, and Cd deposition, and down-regulated expression levels of autophagy-related mRNAs, including ATG5, LC3-I, and LC3-II, Beclin1, and Dynein in the follicles (p < 0.05). In conclusion, 0.4 mg/kg Se supplementation protected against Cd-induced laying performance reduction and follicular atresia, which were achieved via decreasing oxidative stress and inhibiting mTOR pathways of autophagy. Full article