Search Results (3,504)

Testicular germ cell tumors (TGCTs) are the most common solid malignancy in young men and are highly curable, making reproductive and endocrine survivorship central concerns. Gonadal dysfunction is often attributed to orchiectomy and gonadotoxic therapy, yet semen and hormonal abnormalities may already be present at diagnosis. This narrative review synthesizes evidence obtained before orchiectomy and, where explicitly identified, broader pretreatment or pre-gonadotoxic evidence. Pre-orchiectomy studies generally report reduced sperm concentration, total sperm count, and progressive motility, together with impaired Sertoli and Leydig cell function. Tumor-derived human chorionic gonadotropin (hCG) can mask reduced Leydig reserve; in hCG-negative men, research-derived testosterone-to-luteinizing hormone and calculated free testosterone-to-luteinizing hormone ratios may aid risk stratification but lack standardized diagnostic cutoffs. Proposed contributors include testicular dysgenesis, contralateral impairment, germ cell neoplasia in situ, local tumor effects, and oxidative or proteomic alterations, although evidential support varies. These findings support fertility counseling at diagnosis, sperm cryopreservation before orchiectomy when feasible without delaying treatment, selected use of onco-microTESE when no usable ejaculate is available, and hCG-aware endocrine follow-up. Full article

Progressive resistance exercise training (RET) enhances skeletal muscle mass in healthy postmenopausal women (HEAs) and breast cancer survivors (BCSs) undergoing endocrine therapy. MicroRNAs (miRNAs) are recognized as key epigenetic regulators of exercise-induced adaptations, functioning as tumor suppressors, oncomiRs, and modulators of skeletal muscle homeostasis. Nevertheless, the impact of RET on circulating miRNA profiles in this population remains largely unexplored. This study aimed to explore the effects of a 12-week progressive RET program on plasma miRNAs associated with tumor biology and skeletal muscle regulation in HEAs and BCSs. Five HEAs and five BCSs undergoing endocrine therapy completed a 12-week supervised progressive RET program (3 sessions/week, 60–80% 1RM). Plasma samples were collected before and after intervention, and candidate miRNA expression was quantified by qRT-PCR, normalized to hsa-miR-16-5p, and analyzed using the 2^−ΔΔCt method. At baseline, no significant differences were observed between HEA and BCS in tumor suppressor miRNAs (miR-let-7f-5p, miR-125a-5p, miR-342-3p), oncomiRs (miR-21-5p, miR-155-5p, miR-221-3p), or skeletal muscle–related miRNAs (miR-206-3p, miR-486-5p) (p > 0.05). The only exception was miR-375-3p, which showed increased expression in HEA vs BCS (p = 0.037). After 12 weeks of RET, The BCS group showed increases in miR-125a-5p (p = 0.050) and miR-342-3p (p = 0.048) with significant group × time interactions that remained significant after Benjamini–Hochberg False Discovery Rate (BH-FDR) correction (FDR-adjusted p = 0.042 for both). Both groups displayed a nominal increase in miR-375-3p (p = 0.042), which did not remain significant after FDR correction. No significant changes were detected for miR-let-7f-5p or the analyzed oncomiRs in either group. Both miR-206-3p and miR-486-5p exhibited upward trends in the BCS group (p > 0.05). In this exploratory study, 12-week RET program was associated with selective changes in plasma miRNA expression in the HEA and BCS groups, suggesting that this training regimen may act as an epigenetic modulator of circulating miRNAs involved in tumor suppression and skeletal muscle homeostasis. Full article

Background: Postpartum hypogalactia is a prevalent obstetric complication worldwide, closely associated with excessive oxidative stress and impaired antioxidant defense in mammary tissue. Current hormone-based therapies carry endocrine disruption risks, while natural antioxidant bioactive agents such as extracellular vesicles (EVs) are largely limited by rapid in vivo clearance and poor tissue retention. Methods: We constructed an injectable gelatin methacryloyl (GelMA) hydrogel system to encapsulate chemically induced mammary epithelial cell-derived EVs (CiMECs-EVs) and systematically evaluated their antioxidant and lactogenic activities via multi-omics analysis, cellular functional assays and a bromocriptine-induced murine hypogalactia model. Results: CiMECs-EVs induced a functional mammary epithelial-like phenotype in fibroblasts in a dose-dependent manner with functional cargo enriched in glutathione metabolism and redox-regulatory miRNAs. The GelMA matrix protected EV integrity and enabled sustained release, and the composite system significantly ameliorated mammary duct structure and lactation function in vivo with specific mammary tropism and no systemic toxicity, outperforming free EV treatment. Conclusions: This study presents a safe protein biomacromolecule-based antioxidant delivery platform that effectively restores mammary redox balance and antioxidant defenses, providing a promising non-hormonal therapeutic strategy for postpartum hypogalactia. Full article

Doxorubicin (DOX) is an antineoplastic agent commonly used in cancer therapy that is known for its testicular toxicity. DOX-induced testicular injury involves inflammation, reactive oxygen species, and oxidative stress. Centella asiatica exhibits anti-inflammatory and antioxidant properties. The present experimental study aimed to determine the potential protective efficacy of Centella asiatica in a rat model of doxorubicin-induced testicular toxicity. Rats were randomly assigned to four groups: healthy control (HC), CA, DOX, and CA + DOX (CADX). An oral dose of 200 mg/kg Centella asiatica was administered to the CA and CADX groups. The HC and DOX groups received saline. One hour later, DOX (7.5 mg/kg) was intraperitoneally injected into the DOX and CADX groups on days 1, 4, and 7. Centella asiatica markedly attenuated the DOX-induced increase in malondialdehyde, nitric oxide, and pro-inflammatory cytokine levels, while preventing the decrease in superoxide dismutase activity in testicular tissue (p < 0.001). Centella asiatica reduced the severity of DOX-induced morphological damage in testicular tissue (p < 0.05). Moreover, it partially restored reproductive hormone function. In conclusion, Centella asiatica demonstrates significant potential in mitigating DOX-induced oxidative damage, attenuating testicular injury and preserving the functional integrity of the male reproductive system. Full article

Background/Objectives: Experimental and observational studies suggest that sex steroids may modulate disease-avoidance mechanisms and disgust-related responses, but longitudinal evidence in transgender individuals undergoing gender-affirming hormone therapy (GAHT) remains limited. This study investigated whether endocrine changes occurring during the first four months of GAHT were associated with changes in disgust sensitivity, body odor disgust, and perceived vulnerability to disease. Methods: A prospective observational study was conducted in 25 transgender adults (12 transmasculine [FtM] and 13 transfeminine [MtF]) evaluated before initiating GAHT (T0) and after four months of treatment (T1). Participants completed the Three Domains of Disgust Scale (TDDS), the Body Odor Disgust Scale (BODS), and the Perceived Vulnerability to Disease Scale (PVD). Serum testosterone and estradiol concentrations were measured at both time points. Within-group changes were assessed using Wilcoxon signed-rank tests, and associations between hormonal and psychometric changes were explored using Spearman correlations. Results: Among FtM participants, PVD increased significantly following treatment (p = 0.039), whereas no significant changes were observed in pathogen disgust, sexual disgust, moral disgust, or body odor disgust. Greater increases in testosterone were associated with greater reductions in moral disgust (ρ = −0.671, p < 0.05). Among MtF participants, pathogen disgust increased significantly after four months of GAHT (p = 0.015). Greater increases in estradiol were associated with higher moral disgust (ρ = 0.587, p < 0.05) and lower perceived vulnerability to disease (ρ = −0.748, p < 0.01). In addition, testosterone changes were positively associated with changes in sexual disgust (ρ = 0.570, p < 0.05). Conclusions: In this small exploratory cohort, changes in circulating sex steroids during the first four months of GAHT were statistically associated with changes in selected dimensions of disgust sensitivity and perceived vulnerability to disease. The findings are hypothesis-generating and require confirmation in adequately powered longitudinal studies. Full article

Efficient and reproducible generation of functional stem cell-derived β cells (sBC) remains a major challenge for basic research and cell replacement therapy, partly due to incomplete understanding of endocrine induction during differentiation and challenges with clinical scale-up. Here, we dissect the individual contributions of commonly used endocrine differentiation factors on pancreatic progenitor maintenance, endocrine commitment, and hormone subset generation in a scalable 3D differentiation system. We demonstrated that starting pluripotent stem cell cluster size is a critical determinant for downstream sBC generation. We also verify that a commonly employed combination of endocrine induction molecules efficiently drives endocrine lineage commitment but yields limited β-cell generation. Detailed analysis of the effects of individual endocrine induction molecules revealed distinct effects: EGF or KGF preserved NKX6.1⁺ progenitors without induction of endocrine differentiation; Notch or BMP inhibition robustly induced endocrine marker expression but concurrently reduced NKX6.1 expression, resulting in predominant generation of glucagon-expressing cells; retinoic acid, thyroid hormone (T3), or TGFβ inhibition maintained high NKX6.1 levels while also promoting efficient insulin⁺ endocrine differentiation. These findings indicate NKX6.1 protein maintenance as a key determinant of human β-cell generation and show that endocrine differentiation factors exert divergent effects on lineage progression. Full article

Background/Objectives: The effects of hormone replacement therapy (HRT) after primary treatment on survival outcomes in women with cervical cancer (CC) remain unclear. This nationwide cohort study evaluated the association between post-primary treatment HRT and overall survival (OS) in women with CC. Methods: We identified 15,261 women aged ≤60 years with CC who received primary treatment using the Korean Health Insurance Review and Assessment Service database. HRT users were defined as women who received HRT prescriptions for ≥28 days within one year after completion of primary treatment. Stabilized inverse probability of treatment weighting (IPTW) was used to reduce baseline differences between HRT users and non-users, followed by multivariable Cox regression to further adjust for potential confounding. Landmark analyses were performed to address potential immortal time bias. Results: Among 15,261 women, 4118 (27.0%) received HRT. In IPTW-weighted analyses, HRT use was significantly associated with improved OS in both multivariable models (adjusted HR, 0.544; 95% CI, 0.502–0.590; p < 0.001 and adjusted HR, 0.653; 95% CI, 0.574–0.742; p < 0.001, respectively). This association was generally maintained in landmark analyses at 1, 3, and 5 years after diagnosis and remained significant across localized, regional, and distant disease in stage-stratified analyses. The association was most consistently observed among women with squamous cell carcinoma. Conclusions: Post-primary treatment HRT was associated with improved OS in women with CC. Further prospective studies are needed to clarify the clinical implications of this association. Full article

Background/Objectives: Antibiotics are widely used in clinical practice, yet their potential effects on endocrine homeostasis remain insufficiently recognized. This review summarizes endocrine adverse effects associated with selected antibacterial agents, their proposed mechanisms, and clinical relevance. Methods: A narrative literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science from database inception to 10 August 2026. Clinical, pharmacovigilance, case-based, animal, in vitro, and ex vivo studies were considered. Results: Reported disturbances include SIADH-related hyponatremia, hypoglycemia, altered thyroid hormone metabolism, changes in hypothalamic–pituitary–adrenal axis activity, aldosterone dysregulation, and reproductive hormone disturbances. Selected cephalosporins and carbapenems have been associated with changes in prolactin secretion, thyroid-related parameters, and gonadal function. Fluoroquinolones have been associated with dysglycemia, while effects on reproductive hormone pathways have been reported predominantly in experimental models. Selected macrolides may influence glucocorticoid metabolism and KCNJ5-dependent aldosterone production. Linezolid has been linked to hyponatremia and hypoglycemia, while metronidazole may affect pituitary hormone secretion. Trimethoprim–sulfamethoxazole may contribute to hyponatremia, hyperkalemia, hypoglycemia, and thyroid dysfunction. The supporting evidence is heterogeneous and ranges from case reports and pharmacovigilance analyses to experimental studies. Human clinical evidence is strongest for selected disturbances of glucose and electrolyte homeostasis, whereas many reported reproductive, pituitary, thyroid, and adrenal effects remain supported predominantly by experimental or case-based evidence. Conclusions: Many proposed mechanisms remain incompletely established and cannot be directly extrapolated to routine practice. Awareness of these complications may support earlier recognition, targeted biochemical monitoring, and safer antibiotic therapy, particularly in older, critically ill, or renally impaired patients and those exposed to polypharmacy. Full article

Introduction: Male infertility is a complex global health challenge, with emerging evidence suggesting that vitamin D plays a pivotal role in testicular function and spermatogenesis. This systematic review and meta-analysis aimed to evaluate the impact of vitamin D supplementation on semen parameters and reproductive hormones in infertile men. Methods: A comprehensive search of electronic databases (PubMed, Cochrane Library, and Web of Science) was conducted to identify randomized controlled trials (RCTs) investigating vitamin D supplementation in infertile males. Primary outcomes included Follicle-Stimulating Hormone (FSH), total testosterone, and Sex Hormone-Binding Globulin (SHBG). Secondary outcomes focused on semen quality, specifically volume, concentration, and motility. Data were pooled using fixed-effects or random-effects models based on heterogeneity (I²). Results: Analysis of six trials (n = 696) revealed that vitamin D supplementation significantly increased total testosterone levels compared to controls (SMD: 0.38; 95% CI: 0.13, 0.62; p = 0.002), with no statistical heterogeneity (I² = 0%). In contrast, no significant differences were observed for FSH (SMD: 0.01; 95% CI: −0.28, 0.29; p = 0.96) or SHBG (SMD: 0.95; 95% CI: −0.12, 2.02; p = 0.08). For semen parameters, supplementation was associated with notable improvements in sperm concentration and progressive motility, whereas semen volume remained largely unchanged across the included studies. High heterogeneity in SHBG results (I² = 91%) suggests that individual study characteristics, such as baseline vitamin D deficiency, may influence hormonal responses. Conclusions: Vitamin D supplementation selectively enhances endocrine function by increasing testosterone levels and improves functional semen parameters in infertile men. These findings support the use of vitamin D as a cost-effective adjuvant therapy, though its impact on definitive fertility outcomes, such as live birth rates, requires further large-scale clinical investigation. Full article

Background: Chronic autoimmune thyroiditis (CAT) is characterized by persistent autoimmune activity and increased oxidative stress, which may contribute to thyroid follicular injury and disease progression. Photobiomodulation (PBM) has shown potential beneficial effects on thyroid function and autoimmunity; however, its independent effect on systemic antioxidant status, particularly serum glutathione (GSH), has not been established. This study aimed to evaluate the effect of thyroid-directed PBM on serum GSH concentrations and thyroid-related outcomes in treatment-naïve euthyroid women with CAT. Methods: This prospective, non-randomized, open-label, parallel-group comparative interventional study included 50 treatment-naïve euthyroid women with CAT. Participants were allocated to receive either thyroid-directed transdermal PBM (n = 25) or selenium plus vitamin D supplementation (n = 25). The primary outcome was the change in serum GSH concentration. Secondary outcomes included changes in thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), anti-thyroid peroxidase antibodies (anti-TPO), anti-thyroglobulin antibodies (anti-Tg), thyroid volume, and anthropometric parameters. Assessments were performed at baseline (T0), after the intervention period (T1), and three months after intervention completion (T2). Results: A significant time × group interaction was observed for serum GSH concentrations (F = 19.101, p < 0.0001). Significant interactions were also observed for anti-TPO (F = 7.513, p = 0.001), anti-Tg (F = 7.389, p = 0.002), and thyroid volume (F = 13.081, p < 0.0001). In the PBM group, GSH increased from baseline to T1 and remained higher at T2, while TSH, anti-TPO, anti-Tg, and thyroid volume decreased, and FT3 and FT4 increased. No significant longitudinal changes in GSH or thyroid autoantibodies were observed in the supplementation group. No participant in the PBM group required levothyroxine (LT4) initiation during follow-up, whereas 24% of participants in the supplementation group initiated LT4 therapy at T1, with some requiring dose escalation by T2. Conclusions: Thyroid-directed PBM was associated with improved systemic GSH status and favorable changes in thyroid autoimmunity, thyroid function parameters, and thyroid volume compared with selenium plus vitamin D supplementation in treatment-naïve euthyroid women with CAT. These findings suggest that modulation of oxidative stress may represent one potential biological pathway underlying the observed effects of PBM. Larger randomized controlled studies with longer follow-up are required to confirm these findings and define the clinical role of PBM in autoimmune thyroid disease. Full article

Background/Objectives: The prognostic nutritional index (PNI) has been associated with outcome in metastatic breast cancer, but studies in CDK4/6 inhibitor-treated patients have used cohort-derived thresholds and examined only the pretreatment value. We assessed the PNI as a continuous variable, compared it with inflammatory indices, and examined whether repeated measurement added information. Methods: We reviewed 192 consecutive patients with hormone receptor–positive, HER2-negative metastatic breast cancer treated with a CDK4/6 inhibitor and endocrine therapy at a single centre. We calculated the PNI, neutrophil-to-lymphocyte ratio (NLR), and systemic inflammation response index (SIRI) before treatment and recalculated them before cycles 2 and 3. The Cox models were adjusted for age, liver metastasis and line of therapy; no threshold was derived from these data. Results: The median follow-up was 44.9 months. Each one-point increase in the baseline PNI was independently associated with lower hazards of progression (HR 0.952, 95% CI 0.923–0.983) and death (HR 0.919, 95% CI 0.884–0.956), corresponding to HR 0.782 (95% CI 0.670–0.918) and HR 0.656 (95% CI 0.540–0.799) per five-point increase. For overall survival, in formal comparisons on identical patient sets, neither the NLR nor the SIRI added prognostic information to a model containing the PNI (likelihood ratio p = 0.383 and p = 0.335), whereas the PNI added information to models containing either ratio (p < 0.001 and p = 0.004). In exploratory landmark analyses, change in the PNI added little to the baseline value; apparent associations between increases in the NLR or SIRI by cycle 3 and overall survival did not persist after winsorisation of extreme change scores. Conclusions: Baseline PNI, analysed as a continuous variable and without a data-derived threshold, was independently associated with progression-free and overall survival in this cohort. For overall survival, neither baseline inflammatory ratio added detectable prognostic information beyond the index, and repeated measurement during treatment added little to the baseline value, although the confidence intervals do not exclude modest effects. Because all patients received a CDK4/6 inhibitor and no comparator arm was available, these findings support a prognostic rather than a predictive interpretation, and external validation is required before the index can inform clinical decisions. Full article

Introduction and Clinical Significance: Skeletal dysplasias comprise a genetically heterogeneous group of disorders with substantial phenotypic overlap, often complicating diagnosis. Clinical exome sequencing (CES) can facilitate molecular diagnosis in children with unexplained disproportionate short stature. Case Presentation: An 8-year-old boy presented with severe short stature (−3.24 SDS), brachydactyly, relative macrocephaly, broad nasal bridge, and mild calf hypertrophy. Endocrine evaluation confirmed growth hormone deficiency (GHD). Following negative SHOX testing, CES identified a heterozygous likely pathogenic IHH variant (c.446G>A; p.Arg149His), establishing the diagnosis of brachydactyly type A1 (BDA1). Recombinant human growth hormone (rhGH), initiated for GHD, resulted in improved growth velocity and height SDS. Transient unilateral prepubertal gynecomastia developed during treatment and resolved after temporary rhGH withdrawal, with no recurrence following reinitiation. Conclusions: This case highlights the diagnostic value of CES in children with disproportionate short stature after unrevealing targeted testing and illustrates that GHD may coexist with IHH-related skeletal dysplasia. An integrated genetic and endocrine evaluation can refine diagnosis, identify coexisting treatable endocrine disorders, and guide individualized management. Full article

Lipedema and obesity are often misdiagnosed or clinically confused yet arise via distinct mechanisms, complicating diagnosis and treatment. This review synthesizes evidence differentiating these conditions across genetic, hormonal, inflammatory and mechanical pathways to identify therapeutic targets. Lipedema may involve genetic predisposition (forkhead box C2 [FOXC2], prospero homeobox 1 [PROX1]), hormonal dysregulation with aberrant aromatase activity, and altered adipogenesis (peroxisome proliferator-activated receptor gamma [PPARγ], CCAAT/enhancer-binding protein [C/EBP]). A proinflammatory microenvironment with macrophage M1/M2 imbalance, elevated interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and extracellular matrix remodeling is hypothesized to drive fibrosis. Emerging evidence implicates gut-derived endotoxemia (lipopolysaccharide [LPS]-toll-like receptor 4 [TLR4]-nuclear factor kappa-B [NF-κB]) and mechanotransduction (Yes-associated protein [YAP]/transcriptional coactivator with PDZ-binding motif [TAZ]) in adipocyte hypertrophy and treatment resistance. Obesity involves systemic metabolic dysfunction with visceral adiposity and cardiometabolic comorbidities. Lipedema patients maintain metabolic health, exhibit gluteofemoral fat distribution and experience neuropathic pain via nociceptor sensitization (transient receptor potential vanilloid 1 [TRPV1] and ankyrin 1 [TRPA1]) with central amplification. Weight-loss interventions are ineffective, necessitating targeted strategies. Promising targets include TLR4 antagonism, vascular endothelial growth factor C/vascular endothelial growth factor receptor-3 (VEGF-C/VEGFR3) modulation for lymphatic enhancement, YAP/TAZ inhibition and neuromodulators for pain. Physical therapy functions as a biological modifier targeting inflammation, lymphatic drainage and mechanotransduction. This review highlights promising but largely hypothesis-generating molecular insights and calls for validated biomarkers, rigorous clinical trials, and mechanism-based therapies. Many of the pathways discussed require further confirmation in human studies. Full article

Background/Objectives: Intranasal delivery is a promising noninvasive approach to enhance central nervous system drug delivery in Parkinson’s disease (PD), potentially bypassing the blood–brain barrier and minimizing gastrointestinal side effects. This review summarizes clinical trials and translational evidence for intranasal PD therapies by treatment options and intent, highlighting key challenges in efficacy, pharmacokinetics, and safety. Methods: We reviewed human clinical trials, preclinical and pilot studies, and pharmacokinetic investigations of intranasal therapies for PD. Comparisons to established treatments were included in context. Only PD-specific clinical studies were analyzed. Therapies were grouped by rescue, antioxidant/metabolic/hormonal, and biologic or cell-based approaches, with continuous-delivery systems reviewed separately. Results: Intranasal rescue therapies, such as apomorphine, provide rapid improvement during OFF episodes (periods when the effects of PD medications fade and symptoms reappear), but tolerability issues and nasal irritation limit usage. Early-phase studies suggest intranasal delivery enables quick symptom relief and favorable pharmacokinetics, though most trials are small and focus on feasibility. New approaches include antioxidants, neurotrophic factors, gene therapy, and cell-based methods, with advanced formulations enhancing nasal retention and brain uptake. However, more translational evidence and long-term safety data are needed. Conclusions: Intranasal therapies for PD offer rapid rescue and expand options beyond standard drugs. Large, well-designed trials are needed to confirm efficacy, long-term safety, and optimal formulations. Intranasal delivery remains an emerging but potentially transformative strategy requiring further clinical research. Full article

Vulvovaginal candidiasis (VVC) is one of the most common superficial fungal infections affecting women. A particularly challenging issue is the treatment of recurrent vulvovaginal candidiasis (RVVC)—defined as ≥4 episodes of VVC within 12 months—which affects 5–8% of women with VVC. The development of VVC is influenced by many risk factors related to the host organism and behaviour, including disturbances in the vaginal microflora, hormonal fluctuations, diabetes, hygiene and sexual behaviour. Although C. albicans remains the primary species causing this infection, infections caused by other species, such as Nakaseomyces glabratus and Pichia kudriavzevii, are becoming increasingly common, partly due to the widespread use of azole antifungal drugs and growing drug resistance. Therefore, this publication focuses on a review of the newest literature concerning the epidemiology, diagnosis, current approaches to antifungal susceptibility testing and treatment according to global guidelines. According to the literature, precise species identification and drug susceptibility testing are crucial to avoid therapeutic errors and drug resistance. Moreover, new antifungal drugs such as tetrazoles (oteseconazole) and triterpenoids (ibrexafungerp) are entering clinical practice, offering high efficacy against resistant strains. Probiotics used as adjuvant therapy help restore the homeostasis of the vaginal microbiome; however, due to inconsistent evidence, they are currently not included in treatment recommendations. Full article