Search Results (328)

Background/Objectives: Androgen deprivation therapy (ADT) is the mainstay of prostate cancer treatment, especially in advanced disease. In particular, the gonadotropin-releasing hormone agonists (aGnRH) reduce the production of gonadotropin and, therefore, of testosterone. In about 10% of patients, the non-pulsatile stimulation of GnRH receptor initially causes a surge in LH and testosterone, defined as the “flare-up phenomenon”, leading to increased bone pain, spinal cord compression, bladder outlet obstruction and cardiovascular issues. To mitigate this effect, combining a first-generation antiandrogen agent (FGA) with aGnRH is recommended. However, second-generation anti-androgens, such as apalutamide, bind selectively and irreversibly to the androgen receptor (AR), exhibiting a more efficient inhibition of the AR pathway. Methods: This is a descriptive retrospective study of 27 patients (pts) with mHSPC, treated at a single center (“Santa Maria delle Grazie” Hospital in Pozzuoli, ASL Napoli 2 Nord, Italy) between June 2022 and April 2024. Patients received apalutamide monotherapy for 14 days followed by continuous combination with aGnRH plus apalutamide. Serum PSA and testosterone levels were measured at baseline, at day 14 (after 13 days of apalutamide monotherapy), at day 28 (after an additional 15 days of apalutamide plus a aGnRH), and at day 60. Results: PSA levels decreased from a mean of 45.2 (±63.1) ng/mL at baseline to a mean of 12.6 (±23.4) ng/mL at day 14 and to 3.3 ng/mL (±6.0) at day 28 of treatment. After 14 days of apalutamide monotherapy, 21 patients (77.8%) achieved a >50% PSA reduction and 4 (14.8%) a >90% PSA reduction. The number of patients with undetectable PSA was one (3.7%) at day 14, two (7.4%) at day 28, and nine (33.3%) at day 60. The mean serum testosterone levels were 6.56 (±4.46) ng/mL at baseline, 6.58 (±4.42) ng/mL at day 14, and 2.40 (± 3.38) ng/mL at day 28. No significant difference in PSA and testosterone level reduction during treatment emerged between subgroups of patients with low- vs. high-volume disease. Conclusions: Apalutamide alone is a viable option for mitigating the flare-up phenomenon, avoiding first generation anti-androgen therapy, and it can achieve rapid and deep biochemical control. Full article

Background: Uterine fibroids (UFs) and endometriosis are gynecological conditions that significantly increase morbidity among women of reproductive age. Relugolix, a novel gonadotropin-releasing hormone receptor antagonist, is approved in combined therapy for the management of symptoms related to these disorders. However, its potential impact on bone mineral density (BMD) and osteoporosis risk should be considered when using a gonadotropin-releasing hormone (GnRH) antagonist. This systematic review aims to evaluate the effects of daily relugolix intake in monotherapy and combination therapy on BMD, ensuring safe long-term management. Methods: A systematic literature review was conducted following PRISMA 2020 guidelines. Searches were performed in PubMed, Medline, and the Cochrane Library. Relevant clinical guidelines from international societies were also reviewed. Studies assessing the impact of relugolix on BMD were selected, and data on treatment efficacy, adverse effects, and bone health outcomes were synthesized. Results: Relugolix monotherapy has been associated with significant BMD loss due to its potent estrogen-suppressing effect. To mitigate this, combination therapy with estradiol and norethisterone acetate has been developed. Although initial monotherapy before transitioning to combination therapy results in transient BMD reduction, clinical trials have demonstrated that relugolix combination therapy maintains BMD over two years while effectively reducing endometriosis- and UF-related symptoms. Conclusions: Relugolix combination therapy is an effective and well-tolerated treatment for UFs and endometriosis, minimizing the risk of hypoestrogenism-related bone loss while maintaining clinical benefits. Although monotherapy may lead to transient BMD reduction, combination therapy appears to stabilize bone health. Full article

Objectives: Research on the immunocastration vaccine is of great significance for animal management. In this study, the gonadotropin-releasing hormone (GnRH) ferritin nanoparticle vaccine was constructed using Spy Catcher-Spy Tag (SC-ST) as a delivery system; Methods: The Spy Catcher was constructed to fuse with the expression vector pET-30a-SF of ferritin nanoparticles. Two polypeptides, STG1: Spy Tag-GnRH I-PADRE and STG2: Spy Tag-GnRH I-GnRH II, coupled to SF in vitro to form two nanoparticles, were designed and synthesized to detect castration effects in mice. We mixed them with the adjuvant MONTANIDE ISA 206 VG to explore the adjuvant’s effect on immunogenicity; Results: All immunized groups produced anti-GnRH specific antibodies after the second immunization, which was significantly higher in the immunized group and the combined adjuvant group than in the control group, and the immune response could still be detected at the 12th week. The concentrations of testosterone, follicle-stimulating hormone, and luteinizing hormone in serum were significantly decreased. The number of sperm in the epididymis of mice in each immune group was significantly reduced, and the rate of sperm deformity was high; Conclusions: The two ferritin-based GnRH nanoparticles developed in this study can significantly cause testicular atrophy, decreased gonadal hormone concentration, decreased sperm count, and increased deformity rate in male mice. These findings provide experimental evidence supporting their potential application in animal immunocastration. Full article

Kallmann syndrome (KS) is a form of hypogonadotropic hypogonadism (HH) characterized by gonadotropin-releasing hormone (GnRH) deficiency and anosmia due to defective neuronal migration. While traditionally considered irreversible, cases of spontaneous improvement of HH have been reported, suggesting residual GnRH neuronal function in some individuals. We present a case of a 29-year-old man with KS who exhibited spontaneous recovery of endogenous testosterone production following the cessation of long-term androgen therapy without the use of alternative hormonal agents. After ceasing testosterone therapy for several months, the patient’s total testosterone levels normalized (407–424 ng/dL), accompanied by increased secondary sexual characteristics, stable gonadotropin levels, and normal testicular volume. Persistent anosmia was noted, suggesting that restoration of reproductive endocrine function can occur independently of olfactory recovery. Genetic testing identified heterozygous mutations in PCSK1 and HS6ST1, genes implicated in GnRH regulation and KS pathogenesis. This case highlights the potential role of genetic variation in spontaneous HH improvement and underscores the need for individualized management strategies, including periodic reassessment of gonadal function and fertility potential. Further research is needed to elucidate the mechanisms driving spontaneous HH improvement, identify predictive biomarkers of reversibility, and explore therapeutic strategies that may promote endogenous GnRH activity in select patients with KS. Full article

This study investigated the effects of dietary Gonadotropin-releasing hormone (GnRH) and domperidone on the reproductive performance of Devario devario during a 40-day trial. Five treatment groups received varying doses of GnRH (100, 50, 25, 12.5 µg/kg body weight) in combination with domperidone (50, 25, 12.5, 6.25 mg/kg body weight), embossed in a gel-based diet alongside a control group without the exogenous hormones. Reproductive performance was examined by measuring the gonadosomatic index, fecundity, reproductive hormone levels, and histological features of the gonads, blood parameters, and antioxidant enzyme activity. The T1 group (100 µg GnRH + 50 mg domperidone) exhibited the highest GSI in both sexes. The histological analysis of testes from T1, T2 (50 µg GnRH + 25 mg domperidone), and T3 (25 µg GnRH + 12.5 mg domperidone) groups revealed an increased presence of late-stage spermatids and spermatozoa. In females, the T2 group produced the highest proportion of advanced-stage oocytes and demonstrated the greatest absolute fecundity (1300 ± 23 eggs). However, the control group showed the highest fertilization and hatching rates. Testosterone levels were significantly elevated in the T3 group, while vitellogenin levels increased in the T1 and T2 groups. Antioxidant enzyme activity varied, with the T1 group displaying higher superoxide dismutase activity in gills and liver, and the T2 group showing increased SOD activity in muscle and brain. Improvements in haematological parameters were observed across all treatments. These results suggest that an optimal dose of 50 µg GnRH + 25 mg domperidone can enhance reproductive performance in D. devario. Full article

Objectives: Our aim is to report an uncommon pituitary activation occurring during the desensitization phase of the gonadotropin-releasing hormone agonist (GnRHa) long protocol, a cornerstone of medically assisted reproduction (MAR) therapy, in a young woman. Results: We present a case of a 33-year-old female patient with secondary infertility, who exhibited a prolonged and asynchronous follicular development during ovarian stimulation using the GnRH antagonist protocol. Therefore, during a repeat attempt, the long GnRH agonist protocol was employed. Surprisingly, rather than achieving suppression with the agonist, ultrasound detected many large follicles in both ovaries, accompanied by extremely elevated estrogen levels, indicating imminent ovarian hyperstimulation syndrome (OHSS). This unusual phenomenon was also observed during a subsequent attempt using the long protocol in another reproductive center. As part of the work-up to identify the underlying etiology, contrast-enhanced magnetic resonance imaging (MRI) of the sella turcica was performed, which revealed an 11 × 13 × 10 mm pituitary macroadenoma without evidence of pathological hormone secretion. The luteinizing hormone-releasing hormone (LHRH) stimulation test showed a normal luteinizing hormone and follicle-stimulating hormone response. Other abnormalities of the hypothalamo–hypophyseal–target-organ axis were not found. Neurosurgical intervention was deemed unnecessary; radiological follow-up of the lesion was recommended. Conclusions: In this case, the clinical presentation was markedly different from the expected suppressive effects of GnRH agonist therapy, with profoundly elevated estrogen levels and clinical signs of imminent OHSS. Notably, hypersensitivity of the adenohypophysis was not demonstrated following a single physiological LHRH stimulation test. However, the presence of a pituitary adenoma identified on MRI raises the possibility that gonadotropin receptor function was altered by the lesion—an effect revealed only after repeated GnRH agonist exposure, resulting in a paradoxical stimulatory response. Full article

Objective: To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and clinical, hormonal, and auxological features in girls with idiopathic central precocious puberty (CPP). Methods: This retrospective study included 122 girls diagnosed with idiopathic CPP. Participants were stratified into three groups based on serum 25(OH)D concentrations: deficient (<20 ng/mL), insufficient (20–30 ng/mL), and sufficient (>30 ng/mL). Clinical and hormonal parameters were compared across groups. Spearman’s correlation and multiple linear regression analyses were used to explore the relationship between vitamin D levels and peak luteinizing hormone (LH) response to gonadotropin-releasing hormone (GnRH) stimulation. Results: No significant differences were observed among the vitamin D groups in terms of age at diagnosis, body mass index (BMI), or other auxological measures. However, serum 25(OH)D levels showed a weak but significant positive correlation with LH peak values (rho = 0.23, p = 0.037). In multivariable regression analysis, vitamin D levels remained an independent predictor of LH peak (β = 0.125, p = 0.036), whereas BMI standard deviations (SDS), growth velocity SDS, and age at diagnosis did not show significant associations. Conclusions: Higher serum vitamin D levels are independently associated with greater LH peak responses in girls with idiopathic CPP. These findings support a potential modulatory role of vitamin D in the neuroendocrine mechanisms underlying pubertal onset and warrant further prospective studies to clarify its clinical relevance. Full article

Gonadotropin-Releasing Hormone (GnRH) is a crucial neuropeptide that regulates reproductive functions in vertebrates. The study identifies and characterizes (GnRH) in the brain of Tenualosa ilisha, an iconic and lucrative Clupeiform fish from River Ganga, India. The current study aimed to analyze the GnRH gene in T. ilisha using an in silico study. The GnRH gene of T. ilisha comprises a full-length nucleotide sequence of 605 base pairs with an open reading frame of 312 base pairs, which encodes 103 deduced amino acids (aa), respectively. It was found that leucine (L) is the most abundant amino acid in the GnRH protein. Additionally, the ligand interactions of the GnRH were analyzed using computational approaches. The structural validation showed an excellent stereochemical quality of the GnRH protein sequence, with over 88% of residues in Ramachandran plot-favored regions. The binding site prediction revealed 6 ligand-binding pockets, with the largest pocket containing 12 amino acids. After ADME screening, 16 drug-like compounds were docked to GnRH protein. Top five ligands N-Ac-(4-Cl-Phe)-Trp-Lys-AlaNH2, LHRH_LYS (6), Seabream_GnRH, Leuprolide, and LHRH_Des-tyr (5) had binding affinities ranging from −7.5 to −5.6 kcal/mol. The stable binding site was confirmed by 100 ns molecular dynamics simulations, with RMSD values below 10 Å and key residues retaining ligand contacts. The GnRH-protein resulted in the development of a suitable peptide sequence of T. ilisha, showing similarity with the similar anadromous American shad (Alosa sapidissima). This will certainly aid in future therapeutic and captive breeding advances, thereby fostering the culture and conservation of the wild species. Full article

Background/Objectives: Puberty is a critical stage in sheep development when reproductive capability is established, but the hormonal mechanisms underlying this transition remain incompletely understood. This study aimed to investigate the dynamic changes in estradiol (E2) levels and the expression patterns of estrogen receptors (ERα and ERβ) during puberty in Duolang sheep, a breed characterized by early sexual maturity and high reproductive efficiency. Methods: A total of 18 female Duolang sheep were assigned to three developmental stages (n = 6 per group): prepuberty (145 days), puberty (within 0 h of first estrus), and postpuberty (+3 days). Serum E2 concentrations and the mRNA and protein levels of ERα and ERβ were assessed in the hypothalamus, pituitary, and ovary. Additionally, primary ovarian granulosa cells (GCs) were isolated and stimulated in vitro with increasing concentrations of E2 (0–1000 ng/mL) to evaluate the dose-dependent expression of ERα, ERβ, and gonadotropin-releasing hormone (GnRH). Results: E2 levels peaked at the onset of puberty and declined thereafter. ERα expression in the hypothalamus and pituitary decreased during puberty but rebounded postpuberty, indicating a role in negative feedback regulation. In contrast, ovarian ERα expression reached its highest level during puberty, while ERβ expression in the ovary gradually increased from prepuberty to postpuberty. In GCs, ERα exhibited a biphasic expression pattern, peaking at 250 ng/mL E2 and decreasing at higher concentrations. ERβ and GnRH expression levels increased in a dose-dependent manner. Conclusions: These findings suggest that ERα primarily mediates E2 feedback within the hypothalamus–pituitary axis, whereas ERβ is associated with ovarian development and may regulate GnRH expression during the pubertal transition. The study provides new insights into the hormonal regulation of puberty in Duolang sheep and offers potential biomarkers for improving reproductive efficiency through targeted breeding strategies. Full article

Precocious puberty, defined as the onset of secondary sexual characteristics before age 8 in girls, presents a diagnostic challenge in distinguishing between normal variants and pathological conditions requiring intervention. Central precocious puberty (CPP) results from early activation of the hypothalamic–pituitary–gonadal axis, whereas peripheral precocious puberty (PPP) arises from excess sex steroid production independent of gonadotropins. Benign variants, including premature thelarche and premature adrenarche, require careful differentiation to prevent unnecessary treatment. This review explores the physiological mechanisms governing puberty, the epidemiological trends influencing its early onset, and the genetic and environmental factors contributing to its variability in female children. A structured diagnostic approach incorporating clinical evaluation, hormone assessments, imaging studies, and genetic insights is discussed. Management strategies vary depending on the etiology, with gonadotropin-releasing hormone analogs recommended for CPP and targeted therapies for PPP. In contrast, benign variants often necessitate observation and periodic follow-up. Given the increasing prevalence of early puberty, further research is essential to refine diagnostic thresholds and optimize treatment protocols. Early and accurate identification of precocious puberty ensures appropriate intervention, mitigating potential risks associated with early maturation, including compromised adult height and psychosocial challenges. Full article

Controlling low ambient temperatures and ammonia levels is critical for effective environmental management in poultry houses during winter, as both represent persistent stressors affecting bird health and productivity. However, evidence regarding their combined long-term effects on the physiological responses of laying hens remains limited. In this study, 576 eighteen-week-old Hy-Line Brown hens were randomly assigned to six treatments (8 replicates with 12 birds per replicate each treatment) and housed in environmentally controlled chambers for 20 weeks: T1 (8 °C, ≤5 ppm ammonia), T2 (8 °C, 20 ppm ammonia), T3 (8 °C, 45 ppm ammonia), T4 (20 °C, ≤5 ppm ammonia; control), T5 (20 °C, 20 ppm ammonia), and T6 (20 °C, 45 ppm ammonia). Plasma samples were collected at 22, 26, 30, 34, and 38 weeks to evaluate physiological stress biomarkers (corticosterone, CORT; total antioxidant capacity, T-AOC), immunoglobulins (IgG, IgM, and IgA), and reproductive hormones (luteinizing hormone, LH; follicle-stimulating hormone, FSH; estradiol, E2). At 38 weeks, hypothalamus, pituitary, and spleen tissues were collected to assess the relative mRNA expression of gonadotropin-releasing hormone (GnRH), FSH, tumor necrosis factor-α (TNF-α), and interleukins (IL-1β, IL-6, and IL-10). Results showed that both cold and ammonia stress reduced antioxidant capacity, disrupted immune homeostasis, and altered reproductive hormone profiles. Cold exposure induced acute immunoendocrine alterations with partial physiological adaptation over time, whereas ammonia exerted progressive and cumulative damage, including elevated immunoglobulins (IgG and IgM) and downregulation of GnRH and FSH expression. Combined exposure significantly upregulated TNF-α and IL-1β expression, suggesting a synergistic inflammatory response. These results highlight complex, parameter-specific interactions between cold and ammonia stressors, emphasizing the need for targeted environmental strategies. Stage-specific interventions—thermal regulation in early laying and ammonia control in later phases—are recommended to safeguard hen health and optimize productivity under winter conditions. Full article

Lymph node metastases are common in advanced ovarian cancer and are associated with poor prognosis. Accurate intraoperative identification of lymph node metastases remains a challenge in ovarian cancer surgery due to the lack of tumor-specific intraoperative imaging tools. Here, we developed a gonadotropin-releasing hormone receptor (GnRHR)-targeted near-infrared (NIR) fluorescent probe, GnRHa-PEG-Rh760, through conjugation of a GnRH analog peptide with the Rh760 fluorophore and polyethylene glycol (PEG). A non-targeted probe (PEG-Rh760) served as control. In mouse models of subcutaneous xenografts, peritoneal and lymph node metastases derived from ovarian cancer cells, GnRHa-PEG-Rh760 showed superior tumor-specific accumulation. NIR fluorescence imaging revealed strong fluorescence signals localized to primary tumors, peritoneal lesions, and metastatic lymph nodes with no off-target signals in normal lymph nodes. The spatial co-localization between the NIR fluorescence of GnRHa-PEG-Rh760 and tumor-derived bioluminescence clearly confirmed the probe’s target specificity. GnRHa-PEG-Rh760 mainly accumulated in the tumor and liver and was gradually cleared at 96 h post-injection. The retention of fluorescence signals in normal ovary tissue further validated GnRHR-mediated binding of the probe. Notably, GnRHa-PEG-Rh760 exhibited excellent biocompatibility with no observed systemic toxicity as evidenced by hematologic and histopathologic analyses. These data demonstrate the potential of GnRHa-PEG-Rh760 as an intraoperative imaging agent, providing real-time fluorescence imaging guidance to optimize surgical precision. This study highlights the value of receptor-targeted molecular imaging probes in precision cancer surgery. Full article

Introductions: Precocious puberty initiated at a very young age causes a severe loss in height potential and should be treated with gonadotropin-releasing hormone agonists (GnRHa). Controversial findings exist regarding the efficacy of GnRHa treatment in girls with central precocious puberty (CPP) onset around the age of 8. This research assessed the impact of GnRHa treatment on the final height (FAH) of 117 girls diagnosed with CPP within this age group. Methods: This retrospective study included 117 CPP girls diagnosed at around age 8 (7–9 years old). Girls who started treatment between the ages of 8 and 9 (n = 71) and 7 and 8 (n = 46) were divided into groups 1 and 2, respectively. Predicted height (PAH), target height (TH), and FAH were calculated from medical records. Girls’ PAH, TH, and FAH were also compared between groups. Results: At beginning of treatment, the girls’ average ages were 8.59 ± 0.27 in group 1 and 7.50 ± 0.47 in group 2. In groups 1 and 2, GnRHa therapy durations were 1.97 ± 0.54 and 2.91 ± 0.61, respectively. There were no significant differences in TH (160.53 ± 5.49 vs. 160.57 ± 4.94), PAH (158.72 ± 5.23 vs. 158.35 ± 5.57), and FAH (162.42 ± 5.32 vs. 162.14 ± 5.70) between groups. FAH improved 4 cm from PAH in both (p = 0.001). Multivariate linear regression analysis showed that baseline height SDS was the main FAH predictor (Beta: 0.572, p = 0.001). Conclusions: GnRHa may improve FAH even if the treatment is delayed after age 8. However, as this improvement is limited for this age group, the therapy option should be individualized and should not be considered for all children. Full article

Sex-related differences are found not only in the reproductive system but also across various biological systems, such as the cardiovascular system. Compared with premenopausal women, cardiovascular disease (CVD) tends to occur more frequently in adult men and postmenopausal women (Post-MW). Also, during the reproductive years, sex hormones synthesized and released into the blood stream affect vascular function in a sex-dependent fashion. Estrogen (E2) interacts with estrogen receptors (ERs) in endothelial cells, vascular smooth muscle, and the extracellular matrix, causing both genomic and non-genomic effects, including vasodilation, decreased blood pressure, and cardiovascular protection. These observations have suggested beneficial effects of female sex hormones on cardiovascular function. In addition, the clear advantages of E2 supplementation in alleviating vasomotor symptoms during menopause have led to clinical investigations of the effects of menopausal hormone therapy (MHT) in CVD. However, the findings from these clinical trials have been variable and often contradictory. The lack of benefits of MHT in CVD has been related to the MHT preparation (type, dose, and route), vascular ERs (number, variants, distribution, and sensitivity), menopausal stage (MHT timing, initiation, and duration), hormonal environment (progesterone, testosterone (T), gonadotropins, and sex hormone binding globulin), and preexisting cardiovascular health and other disorders. The vascular effects of sex hormones have also prompted further examination of the use of anabolic drugs among athletes and the long-term effects of E2 and T supplements on cardiovascular health in cis- and transgender individuals seeking gender-affirming therapy. Further analysis of the effects of sex hormones and their receptors on vascular function should enhance our understanding of the sex differences and menopause-related changes in vascular signaling and provide better guidance for the management of CVD in a gender-specific fashion and in Post-MW. Full article

The issue of stray cats and dogs is a global concern with considerable implications for animal welfare and public health. This review aims to provide an updated and comprehensive analysis of non-surgical contraceptive methods tested in studies controlled in vivo in feline and canine females. Immunocontraception via vaccination against gonadotropin-releasing hormone (GnRH), the luteinizing hormone receptor, zona pellucida proteins, and sperm, or use of viral-vectored delivery, is yet developing. Hormonal treatment (progestins, androgens, or GnRH) analogs act directly to block the reproductive axis. However, it produced essential side effects. Analogs of kisspeptin, non-steroid anti-inflammatory drugs such as firocoxib, and delivery of cytotoxins to the pituitary have shown non-conclusive results. Additional methods have also been tested, such as intraovarian injection of necrosing compounds or intravaginal and intrauterine devices. At present, neither of these methods offers permanent sterility that can replace surgical sterilization techniques. To our knowledge, none are currently authorized by the Food and Drug Administration (FDA) or the European Medicines Agency (EMA) for contraceptive methods or sterilization of cats or dogs. Therefore, it is necessary to continue the development of a compound that warrants the sterility of cats and dogs. Full article