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PubMed2026

The association between prenatal PM2.5 constituent exposure and gestational diabetes mellitus: Exploratory analysis of the potential modifying role of thyroid hormones.

The associations of PM2.5 constituents with blood glucose and GDM remain unclear, and the interplay between PM2.5 exposure and thyroid hormone levels in relation to GDM has not been well characterized. This retrospective cohort study included 1314 pregnant women with data collected through multiple methods. A generalized linear model analyzed PM2.5-glucose links, logistic regression assessed pollutant-GDM associations, and stratified analyses explored these relationships at different thyroid hormone levels. In the study population, first-trimester exposure to SO42- and BC correlated positively with FBG, as did PM2.5 and its components in the second trimester. First-trimester SO4²⁻ exposure (OR=1.26, 95% CI: 1.06, 1.51) and second-trimester exposures to PM2.5 (OR=1.67, 95% CI: 1.19, 2.35), NO3⁻ (OR=1.34, 95% CI: 1.06, 1.68), and NH4⁺ (OR=1.33, 95% CI: 1.06, 1.65) were associated with increased GDM risk. Stratified analyses showed that second-trimester BC and OM were positively correlated with FBG in the high-TSH and low-FT4 strata, respectively. In addition, first-trimester exposure to SO42- (high TSH: OR = 1.42, 95% CI: 1.10, 1.84; low FT4: OR = 1.35, 95% CI: 1.05, 1.74) and to PM2.5 (high TSH: OR = 1.93, 95% CI: 1.14, 3.27; low FT4: OR = 1.82, 95% CI: 1.46, 2.25) in the second trimester were associated with higher odds of GDM. These findings show that PM2.5 exposure was associated with glucose dysregulation and GDM in pregnant women differently by trimester and component. Across the separate TSH- and FT4-stratified analyses, women in the high-TSH and low-FT4 strata, respectively, appeared to show greater susceptibility to air pollution-related GDM. These subgroup findings should therefore be interpreted as exploratory and require validation in future studies.

Effect modification↗

PubMed2026

GIP contributes to postprandial regulation of splanchnic blood supply in humans with type 2 diabetes: a randomised, single-blinded, placebo-controlled, crossover study.

AIMS/HYPOTHESIS: In healthy lean humans, endogenous glucose-dependent insulinotropic polypeptide (GIP) contributes significantly to the postprandial increase in arteria mesenterica superior blood flow. The vascular biology related to activation of the GIP receptor is markedly impaired in individuals with type 2 diabetes and is sometimes absent. In this population, we investigated the role of endogenous GIP on postprandial splanchnic blood flow by using the GIP receptor antagonist, GIP(3-30)NH2. The primary outcome of this study was the changes in blood flow in arteria mesenterica superior during oral glucose with or without GIP receptor antagonist infusion. METHODS: Ten participants with type 2 diabetes (age 20-80 years, BMI 20-35 kg/m2, and HbA1c >48 mmol/mol and <75 mmol/mol) were investigated in a randomised, placebo-controlled, crossover study. On four separate occasions, participants received the following treatment: oral glucose + i.v. GIP(3-30)NH2; oral glucose + i.v. saline (154 mmol/l NaCl); oral water + i.v. GIP(3-30)NH2; oral water + i.v. saline. Participants were randomly assigned to intervention groups using (random.org). Participants were unaware of allocation, while investigators were aware. No additional allocation concealment procedures were used. During all four interventions, splanchnic blood flow was measured using phase-contrast MRI in the arteria mesenterica superior, truncus coeliacus and vena portae during oral glucose (75 g) or water ingestion. The study was conducted at Rigshospitalet, Copenhagen. Liver volume and oxygenation, as well as gallbladder volume, were assessed. Blood samples were collected and analysed for insulin, C-peptide, GIP, glucagon and glucose. RESULTS: Oral glucose alone increased mean blood flow in arteria mesenterica superior by 57% (95% CI 26, 88) and this was 15% (95% CI -2, 32) lower during concomitant GIP receptor antagonist infusion, p=0.012. Infusion of GIP receptor antagonist during oral glucose treatment did also result in lower insulin secretion, C-peptide and C-peptide/glucose ratio compared with saline infusion, whereas glucagon levels and plasma glucose were unaffected. Oral water did not affect any outcomes. CONCLUSIONS/INTERPRETATION: Endogenous GIP contributes to postprandially increased splanchnic blood flow in people with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT06426823 FUNDING: This work was supported by the Novo Nordisk Foundation.

Humans↗

PubMed2026

Effects of continuous isomaltulose-containing gummy intake on interstitial glucose and salivary hormones during an 18-hole golf round: a randomized, double-blind controlled pilot study.

BACKGROUND: Golf is a prolonged, moderate-intensity sport requiring sustained physiological stability to manage cumulative stress and maintain performance. Although carbohydrate intake is commonly used to reduce fatigue, rapidly absorbed sugar-induced rapid blood glucose fluctuations may induce volatile arousal and latent metabolic stress. Isomaltulose, a slow-digesting disaccharide, provides a steadier glucose supply compared with sucrose. This exploratory pilot study examined the effects of isomaltulose intake on physiological stress markers, glycemic dynamics, and subjective responses during a competitive 18-hole golf round. METHODS: Twenty-three male collegiate golfers were randomized to either the isomaltulose group (ISO; n = 12) or the sucrose group (CON; n = 11) in a double-blind controlled trial. Participants consumed gummies containing isomaltulose or sucrose immediately after each hole (12.1 g carbohydrate per hole; total carbohydrate intake: 217.5 g). Primary outcomes were salivary stress markers [cortisol, testosterone, and dehydroepiandrosterone sulfate (DHEAS)] levels. Secondary outcomes included interstitial glucose concentration measured via continuous glucose monitoring, subjective assessments (i.e. sleepiness, relaxation, and concentration), and golf performance (18-hole score). Between-group comparisons at each time point were conducted using planned Welch's t-tests. RESULTS: No significant between-group differences were observed for 18-hole score (p = 0.38) or mean interstitial glucose concentration (p = 0.20). However, exploratory analyses revealed distinct hormonal variations; salivary DHEAS and testosterone levels were higher in the ISO group during the latter half of the round (p < 0.05), whereas both declined in the CON group. Regarding glycemic variability, the ISO group demonstrated a more stable glucose profile with a medium effect size for lower standard deviation (ISO: 14.7 ± 1.9 vs. CON: 16.7 ± 4.6 mg/dL; d = 0.58), although this difference was not significant. Conversely, subjective outcomes diverged; the CON group reported significantly greater subjective arousal (wakefulness and relaxation) (p < 0.01) relative to the ISO group. CONCLUSIONS: In conclusion, continuous intake of isomaltulose-containing gummies during an 18-hole golf round was associated with differences in selected physiological markers, including DHEAS and testosterone concentrations. However, these findings were not accompanied by improvements in objective golf performance outcomes compared with sucrose-containing gummies. Isomaltulose may influence glycemic dynamics and hormonal responses during prolonged golf play; however, the practical significance of these effects remains exploratory. Further studies with larger sample sizes and appropriate repeated-measures frameworks are needed to determine whether such physiological changes translate into meaningful performance or recovery benefits.

Humans↗

PubMed2026

Tissue origins of the plasma proteomic response to glucose ingestion in humans.

AIMS/HYPOTHESIS: Circulating proteins act as important hormonal signals of nutrient intake. We aimed to systematically characterise the time-resolved proteomic response to glucose ingestion in humans, and to assess its robustness following prolonged complete caloric restriction. METHODS: We conducted oral glucose tolerance tests (OGTTs) in 11 healthy volunteers before and after 7 days of complete caloric restriction and measured the response of >2900 targets through high-resolution plasma protein profiling. RESULTS: We identified a signature of 44 proteins that changed significantly following glucose ingestion, which was reproducible after 7 days without food, and was strongly (20-fold) enriched for 'stomach-specific' proteins. We report that annexin A10 (ANXA10) shows the most significant post-glucose change observed, similar to the trajectories of secreted hormones. We present observational human evidence from multiple sources suggesting that ANXA10 is secreted upon sensing an increase in gastric pH, with the stomach as the major contributing tissue. Despite a profound metabolic shift after 7 days of complete caloric restriction, characterised by delayed insulin secretion and postprandial hyperglycaemia, only four proteins showed robust evidence for a differential trajectory during both OGTTs. This included plasma levels of tryptophanyl-tRNA synthetase 1 (WARS), for which we found a genetic association with glucose homeostasis and coronary artery disease. CONCLUSIONS/INTERPRETATION: Our exploratory study identifies the proteomic response to glucose ingestion and demonstrates its reproducibility despite major shifts in glucose homeostasis. We characterise the gastrointestinal origin of these changes, and hypothesise a hitherto under-recognised role for sensing of changes in gastric pH on the plasma proteome.

Humans↗

PubMed2026

Molecular mechanisms of neuroendocrine regulation of molting in the Chinese mitten crab (Eriocheir sinensis): A transcriptomic analysis based on eyestalk ablation model.

Molting disability severely restricts the sustainable aquaculture of the Chinese mitten crab, yet the neuroendocrine mechanisms coordinating physiological responses remain poorly understood. Using unilateral eyestalk ablation to remove the primary source of molt-inhibiting hormone (MIH), we performed time-resolved transcriptomic profiling of the thoracic ganglion at 24 h (early premolt) and 48 h (ecdysis) post-ablation. We identified 2825 differentially expressed genes and uncovered a biphasic molecular response. At 24 h, the thoracic ganglion activates pathways associated with neuromuscular adaptation, oxidative stress, and cardiac muscle contraction. Notably, the arachidonic acid metabolism pathway is selectively rewired: cytochrome P450 ω-hydroxylases (CYP2J2, CYP4V2) are upregulated, while competing branches (epoxide hydrolase, cyclooxygenase) are suppressed, promoting local synthesis of the potent vasoconstrictor 20-HETE within the thoracic ganglion. This enzymatic switch provides a mechanistic link between MIH withdrawal and the local generation of elevated hemolymph pressure required for molting. By 48 h, the transcriptional program shifts toward chitin-based extracellular matrix remodeling, glycosphingolipid biosynthesis, and synaptic reorganization. Collectively, our findings redefine the thoracic ganglion as an active neuroendocrine integrator that translates reduced MIH signaling into phased physiological outputs, revealing a "neuro-endocrine-hemolymph pressure" regulatory axis. This study provides novel molecular targets (e.g., CYP2J2, CHS1, UGCG) for mitigating molting disability in E. sinensis aquaculture.

Animals↗

PubMed2026

Genome-wide identification, structural characterization, and evolutionary analysis of growth-related gene families in African catfish (Clarias gariepinus).

The somatotropic axis encompassing growth hormone (GH), insulin-like growth factor (IGF), myostatin (MSTN), and prolactin (PRL) signalling cascades is the master regulator of somatic growth, metabolism, and development in vertebrates. African catfish (Clarias gariepinus), a commercially pivotal aquaculture species, now possesses a chromosome-level reference genome (CGAR_prim_01v2); however, a systematic, genome-wide characterization spanning all five interconnected growth-related gene families has not previously been undertaken in this species. Here, we identified and characterized 15 growth-related genes spanning gh1, ghra, ghrb, Igf1, Igf2a, Igf2b, igf1ra, Igf1rb, Igf2r, Mstna, Mstnb, prl, prlra, prlrb, and smtlb distributed across 13 chromosomes. Complete one-to-one orthology with zebrafish confirmed strong dosage-balance conservation across >120 million years of teleost divergence. Physicochemical analysis resolved a clear biochemical dichotomy between compact, basic secreted ligands (19.88-45.81 kDa; pI up to 10.02) and large, acidic, heavily glycosylated membrane receptors (56.82-270.80 kDa; pI 4.85-5.97). Phylogenetic analysis confirmed 3R whole-genome duplication origins for all paralog pairs, while synteny analysis revealed a disruption of the ancestral gh1-prl chromosomal block in C. gariepinus, a finding that warrants further comparative and functional investigation. This genomic atlas provides the sequence and structural information including exon-intron boundaries, domain architecture, and chromosomal coordinates needed as a prerequisite for future marker-assisted selection and CRISPR-based myostatin-editing efforts in African catfish aquaculture, though translation into applied breeding outcomes will require subsequent functional and expression studies.

Animals↗

PubMed2026

Perinatal depression, maternal thyroid status and fetus/infant health and development: A systematic review.

BACKGROUND: Thyroid hormones are known to influence both maternal depression and child developmental outcomes, while maternal depression independently affects child outcomes. The potential interaction between thyroid dysfunction and depression in shaping child development remains insufficiently explored. The present study addresses such interplay. METHODS: Following PRISMA 2020 and JBI guidelines, three databases were searched through December 2025 for primary studies on maternal thyroid status, perinatal depression, and child development. Risk of bias (RoB) was assessed using validated tools. Due to clinical and methodological heterogeneity, data were synthesized narratively following SWiM guidelines. RESULTS: Eleven studies were included. Beyond independent risks for preterm birth and behavioral problems, limited evidence supports a synergistic model, while most studies likely reflect the simple co-occurrence of risks. Maternal thyroid peroxidase antibodies (TPO-Ab) were associated with child externalizing problems exclusively in the presence of clinical depression. High depressive symptoms also attenuated the cognitive benefits of prenatal iodine supplementation. Thyroid status appears to function as a risk moderator rather than a mediator. However, 50% of observational studies presented high RoB, primarily due to participant attrition. CONCLUSION: Findings are still scarce to support a synergistic risk model where specific maternal thyroid parameters (i.e. thyroid autoimmunity and iodine status) may moderate the impact of depressive symptoms on child development. Despite the high RoB in half of the studies, results highlight the need for integrated screening protocols. Simultaneously assessing mental health and thyroid status may optimize risk stratification for high-risk mother-infant dyads.

Female↗

PubMed2026

Reproductive Intentions and Fertility Preservation Among Transgender and Nonbinary Individuals: A Cross-Sectional Study in Brazil.

PURPOSE: This study evaluated reproductive intentions, fertility-related knowledge, prior fertility counseling, and factors associated with reproductive intentions among transgender and nonbinary individuals receiving care at a Brazilian public reference center. METHODS: This cross-sectional study with a qualitative component was conducted between July and November 2025 in a specialized gender-affirming care clinic in Brazil. Quantitative data included sociodemographic characteristics, reproductive history, gender-affirming hormone therapy (GAHT), and fertility-related variables. Logistic regression was used to assess factors associated with desire for future parenthood. Responses to a single open-ended question regarding perceived effects of GAHT on fertility were analyzed using thematic content analysis. RESULTS: Eighty-two participants were included (mean age 27.5 ± 7.4 years). Most identified as transgender men (65.9%), followed by transgender women (26.8%) and nonbinary individuals (7.3%); 79.3% were receiving GAHT. Although 63.4% expressed a desire for future parenthood, only 7.3% had children. Current interest in fertility preservation was reported by 20.8% (15/72). Having children (adjusted odds ratio [aOR] = 0.03; 95% confidence interval [CI]: 0.001-0.62; p = 0.023) and each additional year of GAHT duration (aOR = 0.83; 95% CI: 0.70-0.99; p = 0.038) were associated with lower odds of desiring future parenthood. Sex assigned at birth was not independently associated with reproductive intentions. Qualitative analysis revealed misconceptions, uncertainty, and conditional beliefs regarding fertility. CONCLUSIONS: Desire for future parenthood was common among transgender and nonbinary individuals, whereas engagement with fertility preservation remained limited. These findings highlight the need for longitudinal, patient-centered reproductive counseling integrated into gender-affirming care.

fertility preservation↗

PubMed2026

Clinical and endocrine correlates of genetic etiologies in severe hypospadias: Study from 34 patients.

OBJECTIVE: Hypospadias is a prevalent congenital anomaly (0.3%-1.0%); however, severe hypospadias (defined as proximal cases with the meatus at the penoscrotal junction, scrotum, or perineum) is a rare and clinically challenging entity with a multifactorial etiology. This study aimed to characterize the interrelationships among the clinical, endocrine, and genetic profiles in children with severe hypospadias. MATERIALS AND METHODS: We conducted a comprehensive analysis of 34 male patients with severe hypospadias. Preoperative hormone levels were measured using two methods: chemiluminescent immunoassay for luteinizing hormone and follicle-stimulating hormone, and liquid chromatography-tandem mass spectrometry for testosterone (T), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), 17α-hydroxyprogesterone (17α-OHP), and other steroids. Genetic analysis was conducted via whole exome sequencing. RESULTS: The diagnostic yield of clinically relevant genetic variants (including pathogenic and likely pathogenic, and variants of uncertain significance) in our cohort was 41.2% (14/34) of patients. Patients carrying these variants exhibited a more complex phenotypic profile compared to non-carriers, including a significantly higher rate of patients with ≥3 associated malformations and a greater prevalence of cryptorchidism. Furthermore, the group with clinically relevant variants showed selective elevations in adrenal-derived precursors, specifically 17α-OHP and DHEA. Correlation analysis revealed significant positive associations of both 17α-OHP levels and the T/DHT ratio with the number of associated malformations. CONCLUSION: This study reveals significant genetic heterogeneity in patients with severe hypospadias. Those carrying genetic variants was associated with more severe clinical phenotypes, while certain endocrine variations, including the elevation of adrenal-derived hormones, were also observed in this cohort.

Humans↗

PubMed2026

Serum Copeptin Rises After Tolvaptan for Hyponatraemia, but Does Not Predict Risk of Rapid Sodium Rise: Pre-Specified Secondary Analysis of the TVFR Trial.

OBJECTIVE: Hyponatraemia is a common electrolyte disorder often driven by excess arginine vasopressin (AVP). Copeptin is a stable surrogate marker co-secreted with AVP. It is unclear whether treatment of hyponatraemia with tolvaptan, an AVP-V2 receptor antagonist, impacts copeptin. We aimed to assess the effects of tolvaptan on serum copeptin, compared to fluid restriction. DESIGN: Pre-specified secondary analysis of an open-label randomised trial comparing tolvaptan or fluid restriction for 3 days. PATIENTS: Hospitalised patients with plasma sodium (pNa) 115-130 mmol/L at a single-centre tertiary hospital in Melbourne, Australia. MEASUREMENTS: Copeptin measured at baseline and completion (Day 4, or discharge if sooner). RESULTS: Copeptin results were available in 45/54 participants, randomised to tolvaptan (n = 25) or FR (n = 20). Mean baseline copeptin was 10.4 pmol/L. pNa increased in both groups, significantly more with tolvaptan as previously reported. Copeptin remained stable after FR, but significantly increased after tolvaptan (mean adjusted difference between groups over 3 days 8.4 pmol/L, 95% CI 2.1-14.6, p = 0.01). Baseline copeptin did not predict rapid sodium rise. The rise in copeptin after tolvaptan may represent an exaggerated response to osmolality rise in these patients ('reset osmostat'), or feedback mechanisms from AVP blockade. CONCLUSION: Tolvaptan increased serum copeptin compared to fluid restriction. Further research is required to determine if there is clinical utility for measuring copeptin in hyponatraemia before it is adopted into practice. TRIAL REGISTRATION: ACTRN12619001683123.

Humans↗

PubMed2026

Acute Stevia Consumption does not Alter Endocrine Responses in Individuals with Normal Weight, Overweight, and Type 2 Diabetes Mellitus.

BACKGROUND: Stevia is a plant-based non-nutritive sweetener. Acute effects of stevia ingestion on glycemia and hormonal responses have not been fully investigated. OBJECTIVE: This objective of this study was to evaluate the acute effects of beverages containing stevia alone and in combination with glucose on glycemic, hormonal, and appetite responses. METHODS: This study evaluated three cohorts of n=23 individuals with either normal weight (NW), overweight (OW), or type 2 diabetes mellitus (T2DM) for which each individual completed four test conditions in a randomized sequence crossover study design. The four test conditions were beverages containing stevia (75.6 mg steviol equivalents), water, glucose (30 g), and stevia+glucose (30 g glucose+75.6 mg steviol equivalents). Blood samples were collected before and for 180 min after beverage consumption. Assessments included net area under the curve (niAUC) and incremental maximal concentration values for plasma glucose, insulin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1, glucagon, and PYY. Appetite was assessed with visual-analog scale questions and energy consumption during an ad libitum meal. RESULTS: Responses to the stevia beverage did not differ significantly from those for water alone, and stevia + glucose did not differ significantly from glucose alone for any of the three groups. CONCLUSION: Acute stevia consumption did not materially alter responses for glycemia or hormones involved in glucose and appetite regulation, appetite ratings, or energy intake at a subsequent meal. Clinical Trial Registry number and website where it was obtained: Clinical Trials.gov Identifier: NCT05287906. Study Details | NCT05287906 | A Trial to Assess Steviol Glycosides on Acute Appetite Hormone Release | ClinicalTrials.gov.

Appetite↗

PubMed2026

Association of ERBB4 and SHBG gene polymorphisms with polycystic ovarian syndrome in South Indian women: a case-control genetic analysis.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a multifactorial endocrinological disorder with a substantial genetic component. However, the role of genes involved in follicular development and androgen regulation remains incompletely understood, particularly in South Indian populations. This study aimed to evaluate how variations in the ERBB4 and SHBG genes affect PCOS risk. METHODOLOGY: A hospital-based case-control study was conducted among 400 South Indian women, comprising 200 women with PCOS and 200 age-matched healthy controls. Genomic DNA was extracted to study SNPs at ERBB4 (rs2178575 and rs1351592) and SHBG (rs1799941 and rs727428) using ARMS-PCR genotyping. The study compared genotype and allele frequencies between cases and controls while assessing their associations with allelic, homozygous, heterozygous, dominant, recessive, and over-dominant genetic models. Genotyping accuracy was confirmed by re-genotyping and Sanger sequencing of a subset of samples. RESULTS: The ERBB4 rs2178575 polymorphism demonstrated a significant association with PCOS, as the AA genotype and A allele combination increased risk across all three genetic models, including homozygous, recessive, and allelic models. The ERBB4 rs1351592 variant was associated with 3-fold higher risk of PCOS in heterozygous and GC carriers. The SHBG rs1799941 polymorphism showed a significant link to PCOS through its effects on heterozygous and allelic states, whereas rs727428 displayed no significant connection due to its monomorphic distribution. CONCLUSION: These findings suggest that polymorphisms in ERBB4 and SHBG may contribute to PCOS susceptibility in South Indian women in a locus- and model-specific manner, revealing the intricate genetic structure that defines this medical condition.

Humans↗

PubMed2026

Glucocorticoid receptor antagonism in major depressive disorder with childhood trauma: a randomized controlled trial.

Childhood trauma (CT) is a key risk factor for major depressive disorder (MDD) onset and persistence. Hypothalamic-pituitary-adrenal (HPA) axis dysregulation may underlie this link, and preclinical studies suggest glucocorticoid receptor (GR) antagonism can reverse early life stress effects. This study tested whether the GR antagonist mifepristone reduces depressive symptoms in adults with MDD and CT. The RESET-medication study was a randomized, double-blind, placebo-controlled trial evaluating a 7-day course of mifepristone (1200 mg/day) or placebo in 158 adults with MDD and CT, assessed at baseline, 1 week, 6 weeks (primary endpoint), 3 months, and 6 months. The primary outcome was depressive symptom severity (IDS-SR) at week 6; secondary outcomes included symptom severity at other timepoints, clinical response, remission, anxiety, sleep, stress, disability, and salivary cortisol. At week 6, depressive symptoms declined in both groups, with no significant difference between mifepristone and placebo (b=-0.25, d=-0.03, 95% CI [-0.42, 0.36], pnom=0.887), and no group differences were found for secondary outcomes. Morning and evening cortisol were significantly higher with mifepristone at week 1, consistent with GR antagonism, but not at week 6. Adverse events were more frequent with mifepristone; mild and severe events occurred significantly more often, while the proportion reporting at least one adverse event was numerically higher but not statistically significant (93.6%vs. 82.5%, χ²(1)=3.60, p=0.058). Mifepristone produced the expected endocrine response but did not lead to clinical improvements in individuals with MDD and CT compared to placebo.

Humans↗

PubMed2026

Preoperative intramuscular testosterone and urethrocutaneous fistula formation after primary hypospadias repair.

INTRODUCTION: Preoperative androgen stimulation is widely used before hypospadias repair to increase penile dimensions and optimise surgical conditions. However, its impact on postoperative complications, particularly urethrocutaneous fistula formation, remains controversial. OBJECTIVE: To evaluate the association between preoperative intramuscular testosterone therapy and urethrocutaneous fistula formation in children undergoing primary hypospadias repair. STUDY DESIGN: This was a retrospective comparative analysis of prospectively collected clinical data from 111 boys undergoing primary hypospadias repair at a single tertiary pediatric urology center. Patients were divided into two groups: those who did not receive hormonal therapy (Group 1, n = 55) and those who received intramuscular testosterone enanthate (2 mg/kg administered 5 and 2 weeks before surgery; Group 2, n = 56). Preoperative penile measurements, operative characteristics, and postoperative complications were compared. The primary outcome was urethrocutaneous fistula formation. The mean follow-up duration was 11.9 months (median 7 months). RESULTS: Preoperative testosterone therapy was associated with significant increases in glans diameter and stretched penile length at the time of surgery. The hormone-treated group had a significantly higher proportion of proximal hypospadias (p = 0.001), underwent more complex urethroplasty procedures, and had longer operative times (p = 0.007). Postoperative edema and local inflammatory changes were more frequently observed in the hormone-treated group. Despite these differences, urethrocutaneous fistula occurred in four patients in each group (7.3% vs 7.1%, p = 0.357), with no statistically significant difference between groups. DISCUSSION: Despite greater baseline anatomical severity and operative complexity in the hormone-treated group, preoperative testosterone administration was not associated with an increased risk of urethrocutaneous fistula. These findings suggest that improved tissue bulk and vascularity may offset the potential adverse effects of transient inflammatory changes. CONCLUSION: Selective preoperative intramuscular testosterone therapy was not associated with increased urethrocutaneous fistula risk and may be considered a reasonable adjunct in appropriately selected patients undergoing primary hypospadias repair. CLINICAL/TRANSLATIONAL APPLICABILITY: These findings provide clinical reassurance that preoperative testosterone can be used selectively in patients with smaller penile dimensions or anticipated technical difficulty without increasing fistula risk, thereby supporting shared decision-making in clinical practice.

Humans↗

PubMed2026

Time-varying hazard rates reveal patterns of progression in HR+/HER2- metastatic breast cancer: Towards risk-adapted monitoring.

BACKGROUND: optimal imaging intervals for patients with hormone receptor-positive/HER2-negative metastatic breast cancer (MBC) remains undefined. Aim of this study was to analyze the temporal patterns of disease progression to identify high risk subgroups that may benefit from intensified monitoring. METHODS: we analyzed 149 hormone receptor-positive/HER2-negative MBC patients prospectively enrolled in the MAGNETIC.1 trial (NCT05814224) and treated with first line endocrine therapy. Hazard rates (HR) for disease progression were determined according to clinico-pathological and liquid biopsy features. RESULTS: in the overall population, two distinct progression-risk peaks emerged at 2-3 months (32.9/1000 person-months) and at 24 months (28.0/1000). Higher risk of progression was observed in lobular carcinoma (61.1) [HR 61.12 per 1000 person month (pm)], progesterone receptor-negative status (HR 39.07), fulvestrant-based treatment (HR 46.88), liver metastases (HR 59.00), and presence of ≥ 3 metastatic sites (HR 40.10). CONCLUSIONS: Hazard distribution in hormone receptor-positive/HER2-negative MBC is biphasic and modulated by readily available clinical variables. High-risk subgroups may benefit from intensified radiologic and liquid-biopsy surveillance during the first three months and around two years after treatment start.

Breast cancer↗

PubMed2026

First evaluation of a novel recombinant eCG molecule in ewes reveals a discrepancy between ovulatory response and pregnancy outcome.

This study evaluated the reproductive performance and clinical safety of a novel recombinant eCG (r-eCG) in ewes. Two weeks prior to study onset (Day 0: intravaginal progesterone device insertion), 45 ewes were randomly assigned to negative control (NC; no eCG; n = 10), positive control (PC; 400IU commercial non-recombinant eCG; n = 20), or treatment group (T; 400IU r-eCG; n = 15). Ewes were inseminated with fresh-diluted semen (200 × 106 sperm). Ultrasonography assessed follicle count/diameter (days 11, 13), ovulation (day 13), corpus luteum (CL) number/characteristics (day 20), and pregnancy (day 44). Serum progesterone was measured on day 20; Group T underwent clinical/hematological evaluations (days 0, 20, and 44). Estrus signs were more frequent (P < 0.01) in T (100%) than NC (50%), while PC (85%) did not differ. Ovulation rates were similar between T (93%) and PC (95%), but higher than NC (50%; P < 0.05). On day 13, largest follicle diameter did not differ (P > 0.05) among groups; however, fewer follicles > 2 mm occurred in PC than NC and T (P < 0.05). CL number was higher in T than PC (2.0 ± 0.3 vs. 1.0 ± 0.0, P < 0.01), while NC did not differ (1.0 ± 0.25). Conversely, pregnancy rate was higher (P < 0.05) in PC (70%) than T (28.6%) and NC (20%). Among ovulated ewes, progesterone concentration and progesterone/CL ratio did not differ among groups (P = 0.92 and P = 0.08, respectively). No relevant r-eCG-related clinical or hematological alterations occurred. In conclusion, 400IU r-eCG effectively induces estrus and ovulation without adverse effects; however, the discrepancy between ovulatory response and pregnancy rate underscores the need for further study refinement to improve fertility.

Animals↗

PubMed2026

Infertility treatment in women with epilepsy: A systematic review.

BACKGROUND: The impact of assisted reproductive technologies (ART) on seizure control in women with epilepsy remains incompletely understood. METHODS: A systematic review was conducted according to PRISMA guidelines. EMBASE, MEDLINE, CINAHL, Scopus, and the Cochrane Library were searched from inception to March 2025. Eligible studies included observational studies and case-based reports involving women undergoing infertility treatment. RESULTS: A total of 1216 publications were identified, of which four studies met the inclusion criteria, including case reports, a case series, and a cohort study. These studies included 16 women aged 25-46 years undergoing infertility treatment, all but one of whom had epilepsy. Interventions involved in vitro fertilization (IVF), ovulation induction, and hormonal therapies. Patients were treated with a range of antiseizure medications (ASMs), including carbamazepine, clobazam, lamotrigine, levetiracetam, oxcarbazepine, valproate, and zonisamide, either as monotherapy or in combination. Seizure frequency was generally stable, with most patients maintaining baseline seizure control. Seizure exacerbations were uncommon and primarily associated with hormonal therapy and reduced ASM levels, particularly reduced lamotrigine levels. Reported events included breakthrough seizures in the setting of decreased lamotrigine concentrations, seizure clusters associated with follitropin beta, and a new-onset seizure following dehydroepiandrosterone exposure. Across studies, multiple ART attempts resulted in live births with different ASM regimens, as well as in patients not receiving ASMs. CONCLUSION: Available evidence suggests that ART is feasible in women with epilepsy, with most patients maintaining stable seizure control. Hormonal therapy may affect ASM pharmacokinetics and seizure threshold, thereby warranting close monitoring. Larger prospective studies are needed to better define ASM-specific effects and optimize care.

Humans↗

PubMed2026

Effect of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy on Male Sexual Function: A Systematic Review and Meta-Analysis.

BACKGROUND: Obesity negatively impacts male sexual function and fertility through hormonal imbalances, endothelial dysfunction, and psychosocial factors. Metabolic and bariatric surgery (MBS) constitutes an effective intervention; however, procedure-stratified changes in male reproductive parameters after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) remain incompletely synthesized. METHODOLOGY: A systematic search of PubMed, Embase, Cochrane Library, Scopus, and Web of Science was conducted in November 2024. Sexual function, testosterone levels, and semen quality were included. Risk of bias was assessed using MINORS criteria. Random-effects meta-analyses were performed separately for each surgical modality, with heterogeneity quantified via I2 statistics. RESULTS: Twenty-one studies comprising 848 patients were included. Meta-analysis of pre-post data demonstrated that both RYGB and SG were independently associated with improvements in sex hormone-binding globulin and testosterone levels. In studies examining SG, significant improvements were observed in erectile function (SMD: 1.38, 95% CI: 0.66-2.10, p = 0.0002) and sperm concentration (SMD: 0.91, 95% CI: 0.56-1.26, p < 0.00001). Studies evaluating RYGB did not demonstrate statistically significant changes in erectile function (SMD: 0.62, 95% CI: -0.06 to 1.30, p = 0.07) or sperm concentration (SMD: -0.01, 95% CI: -0.45 to 0.42, p = 0.95). CONCLUSION: The meta-analytical findings suggest beneficial effects of both RYGB and SG on male hormonal parameters. Studies of SG demonstrated significant improvements in erectile function and sperm concentration. However, direct comparative analyses between the two procedures were not performed, precluding definitive conclusions regarding their relative efficacy. Future research necessitates head-to-head comparisons with standardized reproductive endpoints and extended follow-up periods.

Humans↗