Search Results (209)

Background/Objectives: Finasteride and dutasteride are 5α-reductase inhibitors that block the conversion of testosterone to dihydrotestosterone, reducing androgenic stimulation of tissues such as the prostate and hair follicles. Used mainly for benign prostatic hyperplasia and androgenic alopecia, finasteride selectively inhibits type-2 5α-reductase isoenzyme, while dutasteride inhibits both type-1 and type-2. Although sexual adverse effects like erectile dysfunction are well-documented, emerging evidence suggests possible neuropsychiatric reactions—including depression, suicidal ideation, and cognitive decline—potentially linked to reduced neurosteroid synthesis, such as that of allopregnanolone. Causality cannot be inferred from spontaneous reporting data. This study aimed to assess pharmacovigilance signals for psychopathological disorders associated with finasteride and dutasteride in the FAERS database. Methods: Cleaned FAERS data referring to years up to 2025 after deduplication were analyzed, excluding non-serious cases and those without the drug as the sole suspect (MedDra 29.0). Reporting Odds Ratios (RORs) with 95% CIs were calculated to compare psychiatric reactions between finasteride and dutasteride. Python 3.11 was used to screen and summarize relevant cases, accounting for differences in total case numbers. Results: This pharmacovigilance study analyzed FAERS data to assess the neuropsychiatric and sexual adverse reactions associated with finasteride and dutasteride. Depression, anxiety, suicidality, and libido-related issues were reported more frequently for finasteride, especially in younger men using low-dose therapy for alopecia. Potential mechanisms include reduced neurosteroid synthesis, androgen/sex-hormone axis disruption, altered hippocampal neurogenesis, and dopaminergic changes. Conclusions: A baseline psychiatric assessment and the regular monitoring of mood, sexual function, and suicidal ideation are recommended. Limitations include under-reporting, reporting bias, and a lack of incidence data. The findings underscore the need for ongoing surveillance and controlled studies to clarify the clinical significance of these signals. Full article

Background: Benign prostatic hyperplasia (BPH) is an age-associated urological condition defined by abnormal multiplication of both stromal and epithelial components within the prostate. Calamagrostis arundinacea (CA), a species of perennial grass native to East Asia, has been recognized for its anti-inflammatory and antioxidant biological activities. The present study examined whether CA extract could attenuate prostatic enlargement induced by testosterone propionate (TP) in rats. Methodology: To establish the experimental model, rats received subcutaneous TP injections (3 mg/kg/day) for four consecutive weeks. During the same period, an extract of CA (150 mg/kg/day) was orally administered. Results: TP-treated animals developed significant prostatic enlargement, whereas CA supplementation markedly reduced prostate weight and significantly decreased circulating dihydrotestosterone (DHT) and testosterone levels. Microscopic analysis demonstrated that CA mitigated glandular epithelial thickening and suppressed hyperplastic alterations. In addition, CA reduced proliferating cell nuclear antigen (PCNA) expression and increased apoptotic cell numbers, as evidenced by TUNEL staining. Gene expression analysis further revealed significant downregulation of insulin-like growth factor-2 (Igf-2), transforming growth factor-β (Tgf-β), and vascular endothelial growth factor (Vegf), in CA-treated prostates. Moreover, CA inhibited activation of the PI3K/Akt/mTOR signaling cascades by reducing phosphorylation of Akt and mTOR. Conclusions: Overall, these results indicate that CA extract alleviates testosterone-induced BPH through suppression of growth-related signaling cascades and induction of apoptosis, suggesting its potent value as a phytotherapeutic strategy for BPH management. Full article

Background/Objectives: Benign prostatic hyperplasia (BPH) is a multifactorial condition associated with androgen imbalance, oxidative stress, and chronic inflammation, leading to growing interest in food-derived bioactive compounds with multitarget activity. This study aimed to investigate the biological effects of a nutraceutical combination of Gastrodiae elata Blume extract and coenzyme Q10 (Q10), focusing on mechanisms relevant to prostate physiological balance using food-relevant in vitro models. Methods: An intestinal epithelial barrier model (Caco-2) was employed to assess intestinal tolerance and permeability of the tested compounds. Subsequently, a prostate epithelial–stromal co-culture exposed to dihydrotestosterone (DHT) was used to reproduce BPH-like cellular conditions. Oxidative stress, inflammatory mediators, androgen-related pathways, and markers of proliferation and apoptosis were evaluated following simulated intestinal passage. Results: The combined formulation showed no cytotoxic effects and demonstrated efficient intestinal permeability. After intestinal passage, the combination significantly reduced oxidative stress and inflammatory responses in the prostate co-culture, decreasing reactive oxygen species and pro-inflammatory mediators, including NF-κB, TNF-α, and IL-1β. In parallel, the formulation modulated androgen-related pathways by reducing 5-α-reductase activity and DHT levels while supporting testosterone homeostasis. Across some of the evaluated endpoints, the combined formulation tended to show more pronounced protective effects compared with the individual components. Conclusions: These results suggest that a combination of Gastrodiae elata and coenzyme Q10 may have a positive effect on prostate health. In the nutraceutical field, this food-based formulation could help support prostate health, probably through antioxidant, anti-inflammatory, and hormonal control mechanisms. Further studies using advanced experimental models are warranted. Full article

Androgen receptor (AR) signaling is crucial for mediating male-typical behaviors across vertebrates. Enzalutamide (ENZ) and apalutamide (APA) are two second-generation androgen receptor inhibitors (SGARIs) that have been primarily used in the treatment of prostate cancer. However, these drugs still possess side effects, and there remains limited information regarding their behavioral and neurophysiological impacts following chronic exposure in non-mammalian animal models, particularly in fish. Thus, this study aimed to evaluate the behavioral alterations in adult male zebrafish (Danio rerio) following exposure to specific AR blockers (ENZ and APA) and an activator, dihydrotestosterone (DHT), to provide a comprehensive comparison between each tested drug. Adult male zebrafish were exposed via aqueous immersion to each compound at a 1 ppm concentration for ~2 weeks and were subjected to a battery of behavioral tests. From the results, both AR blockers were found to slightly compromise fish locomotion, with contrary results observed in DHT-treated fish, which displayed an increased locomotor activity together with slight alterations in fish exploratory behaviors. Furthermore, ENZ also caused a tightened shoal formation in zebrafish, while exposure to APA was observed to slightly diminish the fear response of fish. On the other hand, the DHT-treated group displayed a higher level of aggression compared to the vehicle control group. In conclusion, functional modulation of androgen receptor signaling leads to significant alterations in male zebrafish behavior, particularly affecting fear responses, aggression, and anxiety-related behaviors. We believe that these findings could contribute to a deeper understanding of the relationship between androgens and behaviors in vertebrates, especially zebrafish. Full article

Benign prostatic hyperplasia (BPH) is a significant health issue among ageing men, with ongoing research focused on elucidating its underlying mechanisms and improving experimental models. Testosterone Propionate (TP) is the first line of choice for the induction of BPH in experimental rodent models. However, TP’s controlled status as a Schedule III drug in the United States and a Class C drug in the UK presents challenges in obtaining TP for experimental use, giving preference to the sulpiride model since it is easily obtained as an alternative for the induction and study of BPH. A comprehensive literature search was conducted across multiple electronic databases, including PubMed/MEDLINE, Embase, and Web of Science. The primary PubMed search strategy included combinations of Medical Subject Headings (MeSH) and free-text terms: (“Benign prostatic hyperplasia induction” OR “and rodent models’’) AND (“Testosterone Propionate model”) AND (“sulpiride model”). Studies were included if they induced BPH (using testosterone or sulpiride models). Titles and abstracts were screened for relevance; eligible articles underwent full-text review, with data extracted thematically. No formal risk-of-bias scoring was used due to the narrative approach; instead, studies were appraised by design, rigor, plausibility, and evidence. This study reviewed published and publicly available data, so no ethical approval was required. Although both TP and sulpiride induce BPH via various mechanisms, this review provides a comparative analysis of these two commonly utilised models for studying BPH. In the TP approach, castrated rodents receive daily subcutaneous injections for 4 weeks, resulting in dihydrotestosterone (DHT)-mediated epithelial hyperplasia predominantly affecting the ventral prostate lobes. Conversely, the sulpiride model is non-invasive, employs intact animals treated with sulpiride, and induces hyperprolactinemia-mediated BPH via interactions with androgen and oestrogen receptor pathways that stimulate prostatic stromal and epithelial proliferation, particularly in the lateral and dorsal lobes, representing an alternative method. We also highlight the strengths and limitations of TP and sulpiride in replicating clinical symptoms and examine the toxicological effects of sulpiride on the kidney, testis, liver, and brain. We recommend the sulpiride model for the induction and studying of BPH, as it is readily accessible and closely mimics the pathogenesis of BPH in humans, unlike the TP model, which requires castration. Full article

Emerging evidence suggests that certain cestodes, including Taenia solium, may actively modulate the host’s hormonal and immune environment to facilitate their survival. This study aimed to determine whether patients diagnosed with neurocysticercosis (NCC) exhibit immunoendocrine alterations associated with infection. A clinical study was conducted in Honduras, enrolling 11 adult NCC patients (9 female, 2 male) and 11 age- and sex-matched healthy controls. Serum concentrations of seven hormones and two cytokines were evaluated. Compared to controls, NCC patients showed significantly elevated levels of 17β-Estradiol (E2), Progesterone (P4), Androstenedione (A4), Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), Interleukin-6 (IL-6), and Interleukin-10 (IL-10). Conversely, Free testosterone (FT) and Dihydrotestosterone (DHT) levels were significantly reduced. These findings support the hypothesis that T. solium may manipulate host immunoendocrine pathways to promote its establishment and persistence within the central nervous system. Full article

Background: FAM64A is highly expressed in various cancers (e.g., breast cancer, ovarian cancer), indicating that it promotes tumorigenesis and progression by facilitating epithelial–mesenchymal transition. In the genitourinary system, dihydrotestosterone promotes the expression of FAM64A by binding of the androgen receptor to the FAM64A promoter, thereby enhancing the proliferation, migration, and cell cycle progression of androgen-dependent prostate cancer cell lines. However, its specific role in the initiation and progression of bladder cancer remains unclear. FAM64A overexpression has been observed in cancers such as breast and prostate; however, its role in bladder cancer (BLCA) is less understood. Muscle-invasive BLCA (MIBC) has a poor prognosis, with five-year survival rates below 50%. This study explores FAM64A’s molecular mechanisms and therapeutic potential in BLCA. Methods: FAM64A expression was analyzed using TCGA data and clinical BLCA tissues. Functional assays (CCK-8, wound-healing, Transwell) assessed proliferation, migration, and invasion following FAM64A modulation. Western blotting was used to evaluate EMT markers (Vimentin, Slug) and proteins involved in the PI3K/AKT pathway. Bioinformatics (TCGA/GTEx) identified FAM64A-correlated genes, followed by KEGG pathway analysis. Taselisib (PI3K/AKT inhibitor) validated pathway involvement. Results: FAM64A was upregulated in BLCA and correlated with advanced tumor stage, T-stage, and grade. Knockdown suppressed proliferation, migration, and invasion, while overexpression exacerbated these effects. FAM64A promoted G2/M progression (via Cyclin B1/Ki67) and EMT (via Vimentin/Slug). KEGG analysis linked FAM64A to the PI3K/mTORC2/AKT signaling pathway. Taselisib reversed FAM64A-induced EMT and malignant phenotypes. Conclusions: FAM64A drives BLCA progression via PI3K/mTORC2/AKT-mediated EMT, serving as a potential prognostic biomarker and therapeutic target for metastatic BLCA. Full article

In the male body, zinc accumulates most abundantly in prostatic cells, where it plays a key role in producing high amounts of citrate in seminal fluid. Intraprostatic accumulation of Zn increases during the development of benign prostatic hyperplasia (BPH), one of the most common diseases in men over 50 years of age. Continuing our investigations on intraprostatic androgens, in this study, we analyzed the mineral content (Zn, Ca, Cu, K, Mg, Mn, and Na) in the transitional zone (TZ) of the prostate using inductively coupled plasma optical emission spectrometry (ICP-OES). The concentrations of testosterone (T) and dihydrotestosterone (DHT) were determined by liquid chromatography–mass spectrometry (LC-MS). Group-wise and correlation analyses demonstrated a descriptive trend toward a volume-dependent increase in Zn concentrations within TZ tissue, whereas other elements exhibited heterogeneous covariance patterns; intraprostatic hormone levels, although elevated in larger prostates, showed no consistent linear correlations with elemental concentrations. Given the observational design of the present study, the reported tissue Zn profiles cannot be interpreted as evidence supporting supplementation in BPH, and any potential clinical implications warrant evaluation in rigorously designed interventional studies. Full article

Recurrent pregnancy loss (RPL) is defined as the loss of two or more pregnancies before the 22nd gestational week and affects 10–15% of clinical pregnancies. Despite extensive diagnostics, over 50% of RPL cases remain unexplained, suggesting an important role for immunological mechanisms. Sex hormones (SH) are key regulators of immune responses during pregnancy; however, their influence on immune checkpoint proteins (ICPs) is poorly understood. This study evaluated the effects of progesterone, β-estradiol, and dihydrotestosterone (DHT) on ICP expression on immune cells, including Treg, NK, NKT, TC, Th, and T cells, collected from pregnant women and patients with unexplained RPL (uRPL). Peripheral blood mononuclear cells from 20 pregnant women and 20 uRPL patients were cultured for 48 h with SH. The expression of the first generation of ICPs—PD-1 and TIM-3—and the second—LAG-3, TIGIT, and VISTA—on T, NK, and NKT cells was analyzed by the flow cytometry method. In pregnant women, SH exerted modest effects, with DHT increasing VISTA and LAG-3 expression, while progesterone and estradiol mainly upregulated LAG-3 and TIM-3 on cytotoxic cells. In contrast, uRPL immune cells showed pronounced SH sensitivity, characterized by increased TIM-3 and VISTA expression and reduced TIGIT expression, particularly after DHT stimulation. In conclusion, SH modulates ICP expression in a cell-specific manner, with stronger effects observed in uRPL patients’ lymphocytes. These findings highlight a potential role for hormonal and ICP-targeted strategies in RPL management. Full article

Zearalenone (ZEA) is a mycotoxin commonly found in animal feed and is associated with pronounced reproductive toxicity. However, most studies on ZEA’s reproductive effects have focused on female monogastric animals, while research on male ruminants remains limited. This study aimed to investigate the cytotoxic and metabolic mechanisms underlying ZEA-induced damage in goat Leydig cells (LCs). The CCK8 assay was first used to determine the effective ZEA concentration (IC₅₀ ≈ 20 μM), and a cytotoxicity model was subsequently established. The model’s validity was confirmed using qRT-PCR, transmission electron microscopy, flow cytometry, and JC-1 staining. Results showed that ZEA significantly reduced LCs viability in a dose-dependent manner, decreased mitochondrial membrane potential, induced cell cycle arrest, and triggered apoptosis. Targeted and untargeted metabolomics analyses revealed that ZEA disrupts steroidogenic pathways and alters steroid hormone secretion, resulting in elevated levels of progesterone, corticosterone, and androstenedione, and reduced dihydrotestosterone levels. Furthermore, 52 significantly altered metabolites were identified, predominantly enriched in glycerophospholipid metabolism, choline metabolism, and neurotransmitter vesicle pathways, with corresponding changes in gene expression. Collectively, this study has confirmed that ZEA causes harm to the reproductive cells of male goats in multiple aspects, underscoring the link between metabolic dysregulation and reproductive impairment, and offering a foundation for evaluating ZEA’s impact on goat reproductive performance. Full article

Androgenetic alopecia (AGA) is closely associated with oxidative stress and vascular dysfunction, which disrupt nutrient delivery to hair follicles and promote follicle miniaturization. Dihydrotestosterone (DHT) exposure impairs human dermal microvascular endothelial cell (HDMEC) function by inducing mitochondrial disruption, excessive reactive oxygen species (ROS) accumulation, and reduced angiogenic capacity. This study evaluated the protective effects of dihydroisoquinolinone piperidinylcarboxy pyrazolopyridine (DPP), a novel 15-hydroxyprostaglandin dehydrogenase (15-PGDH) inhibitor identified through the AI-based discovery platform DeepZema^®, in DHT-exposed HDMECs. DPP markedly reduced intracellular and mitochondrial ROS levels, restored mitochondrial membrane potential, and increased ATP production, thereby alleviating oxidative stress and supporting mitochondrial function. DPP also enhanced endothelial cell migration and capillary-like tube formation, demonstrating the restoration of angiogenic capacity that is essential for sustaining perifollicular vascularization. Moreover, DPP mitigated stress-associated signaling by reducing the phosphorylation of ERK, JNK, and p38 within the MAPK pathway, thereby suggesting the reestablishment of endothelial homeostasis under DHT-induced stress. Collectively, these findings indicate that DPP preserves endothelial function under DHT-driven oxidative conditions. We suggest that DPP may exert complementary protective effects on both vascular and follicular compartments, supporting its potential relevance in hair follicle regeneration. Full article

Alopecia is a multifactorial disorder in which immune, endocrine, metabolic, and microbial systems converge within the follicular microenvironment. In alopecia areata (AA), loss of immune privilege, together with interferon-γ- and interleukin-15-driven activation of the JAK/STAT cascade, promotes cytotoxic infiltration, whereas selective inhibitors, including baricitinib, ritlecitinib, and durvalumab, restore immune balance and permit anagen reentry. In androgenetic alopecia (AGA), excess dihydrotestosterone and androgen receptor signaling increase DKK1 and prostaglandin D2, suppress Wnt and β-catenin activity, and drive follicular miniaturization. Combination approaches utilizing low-dose oral minoxidil, platelet-rich plasma, exosome formulations, and low-level light therapy enhance vascularization, improve mitochondrial function, and reactivate metabolism, collectively supporting sustained regrowth. Elucidation of intracellular axes such as JAK/STAT, Wnt/BMP, AMPK/mTOR, and mitochondrial redox regulation provides a mechanistic basis for rational, multimodal intervention. Advances in stem cell organoids, biomaterial scaffolds, and exosome-based therapeutics extend treatment from suppression toward structural follicle reconstruction. Recognition of microbiome and mitochondria crosstalk underscores the need to maintain microbial homeostasis and redox stability for durable regeneration. This review synthesizes molecular and preclinical advances in AA and AGA, outlining intersecting signaling networks and regenerative interfaces that define a framework for precision and sustained follicular regeneration. Full article

Androgens have been shown to be linked to cancer progression, particularly in hormone-dependent cancers such as prostate and breast cancer, but also other cancers. Amyloid precursor protein (APP), which has primarily been studied in Alzheimer’s disease, is gaining recognition for its role in tumor growth and survival. While APP overexpression and androgen receptor (AR) signaling are each associated with cancer progression, the connection between androgens and APP processing in cancer has not been thoroughly investigated. This systematic review was conducted through a comprehensive search of PubMed, Scopus, Web of Science, and EMBASE between 2000 to 2024 for studies examining the effects of androgens on APP and its cleavage enzymes in cancer. Five experimental studies met the inclusion criteria, covering prostate and breast cancer models. Data were extracted and synthesized narratively due to heterogeneity in methods and outcomes. Three studies reported that dihydrotestosterone (DHT) or AR agonists increased the expression and nuclear translocation of ADAM10, a key α-secretase enzyme in the non-amyloidogenic APP processing pathway. Two studies identified APP as an androgen-responsive gene, showing that androgens upregulated APP expression in prostate and breast cancer cells and promoted the proliferation of cancer cells. Inhibition or knockdown of APP and ADAM10 reduced proliferation, supporting their roles in tumor progression. Androgen signaling modulates APP processing in cancer, particularly through the non-amyloidogenic pathway; however, significant knowledge gaps remain. Further studies are needed to explore the interaction between androgens and APP processing in other cancer types, as well as to elucidate downstream signaling pathways regulated at the gene expression level. Full article

Background/Objectives: Silver nanoparticles (AgNPs), used in industry and medicine, can have a negative impact on the human organism, particularly on the reproductive system, while polyphenolic supplementation may reduce oxidative stress (OS) and enhance male reproductive potential. The aim of this study was to investigate the effects of anthocyanin-rich blackcurrant pomace (BC) on sex steroid hormone metabolism and the OS indicator in the testes of rats following exposure to AgNPs. Methods: Adult rats were fed with a control feed (CTR) or diet supplemented with a 2% BC (BC group). The rats from AgNano and AgNano+BC groups were treated with 20 nm AgNPs (30 mg/kg/day for 28 days by gavage). Results: The plasma testosterone (T) and plasma dihydrotestosterone (DHT) concentrations were decreased in all experimental groups compared to the control (CTR) animals. The co-treatment of animals with AgNPs and BC resulted in decreased oestrogen receptor (ESR2) levels in the testes as compared to rats fed with a diet with BC alone, and the up-regulation of mRNA level of genes involved in T synthesis and metabolism (StAr, Cyp11a1, Hsd17b3, Hsd3b3, Cyp19a1, and Srd5a1), and steroid hormone signalling (AR, ESR1, and ESR2) compared to the Ctr group. The addition of BC to the diet of rats treated with AgNPs resulted in decreased protein carbonyls in the testes as compared to AgNPs-treated animals. Conclusions: The study demonstrated that relatively low AgNPs administration to rats was associated with increased oxidative stress in the gonads. Incorporating BC into the animals’ feed mitigated AgNPs-induced oxidative stress and stimulated the expression of genes involved in steroid synthesis and metabolism in testes. The bioactive compounds in blackcurrant pomace have plausible mechanisms to influence reproductive health. Full article

Resistance exercise (RE) is a well-known modality to increase skeletal muscle strength and hypertrophy. While both high-load (HL) and low-load (LL) RE stimulate skeletal muscle growth, the effects of RE load on androgen-regulated genes remain unclear. Further, the relationship between circulating and intramuscular androgen-associated targets and muscular strength and mass has not been well defined. Purpose: This investigation therein aimed to examine acute gene and hormone responses to volume- and intensity-equated RE at different loads, examining their relationships with lean body mass (LBM), strength, and circulating and intramuscular androgen-related biomarkers. Methods: Ten resistance-trained males completed one-repetition maximum (1RM) testing, as well as body composition testing, before two volume- and intensity-equated RE sessions, separated by a 7–10 day crossover period. Serum and skeletal muscle samples were collected at baseline, 3 h, and 24 h post-exercise to assess testosterone (TST), dihydrotestosterone (DHT), AR protein, AR mRNA, and AR–DNA binding. Pearson correlations evaluated any potential associations between LBM, strength, and androgen/AR biomarkers. Results: Training load did not significantly impact gene expression, but time effects were observed, whereby MyoD peaked 3 h post-exercise (2.03 ± 1.64 fold; p = 0.005), while AR mRNA decreased at 24 h (0.54 ± 0.42 fold; p = 0.021) versus baseline. LBM also correlated with bench press (r = 0.607, p = 0.048) and leg press (r = 0.705, p = 0.015) 1RM. Serum total TST correlated with leg press 1RM (r = 0.909, p = 0.012), while serum-free TST correlated with AR mRNA fold-change (r = 0.392, p = 0.001) and AR–DNA binding (r = 0.287, p = 0.021). Intramuscular DHT correlated with intramuscular TST (r = 0.415, p < 0.001) and AR protein (r = 0.421, p < 0.001). Lastly, fold changes in AR mRNA were correlated with MyoD mRNA fold changes (r = 0.785, p = 0.007) along with IGF1-Ea mRNA fold changes being significantly correlated with both myogenin mRNA fold changes (r = 0.865, p = 0.001) and AR-DNA binding (r = −0.727, p = 0.017). Conclusions: Despite no observable load-specific effects, RE elicited time-dependent increases in MyoD and AR mRNA expression. This reinforces prior LBM and maximal muscular strength relationship evidence whilst also lending new insights into circulating and intramuscular androgen interactions with AR. Full article