Congenital hypogonadotropic hypogonadism (CHH) in boys and adolescents requires age- and developmentally appropriate treatment to address androgen deficiency, testicular maturation, pubertal development, and ultimately fertility. The dynamic physiology of the hypothalamic-pituitary-testicular axis necessitates therapeutic strategies that differ substantially between infancy and adolescence.

Objective: To investigate the current status of clinical practice and the implementation of existing guidelines for endometriosis in China, and to provide a reliable basis for relevant continuing medical education and future guideline revisions. Methods: A nationwide cross-sectional survey was conducted using convenience sampling. Doctors in obstetrics and gynecology or reproductive medicine were invited to complete an online questionnaire. The main survey contents included: the availability of specialized endometriosis clinics at the respondents' hospitals; the respondents' experience in diagnosing and surgically managing endometriosis; and their awareness and implementation of established clinical practice guidelines. Statistical analysis was performed on the collected valid questionnaires. Results: A total of 651 respondents from 30 provinces, municipalities, and autonomous regions across China participated, with 633 valid questionnaires collected. Obstetricians and gynecologists accounted for 92.73% (587/633) of the respondents, and over 90% held the professional title of attending physician or higher. 83.41% (528/633) of the respondents had performed or participated in surgical treatment for endometriosis. Compared to data from the survey in 2018, several indicators showed improvement: the establishment of specialized endometriosis clinics [9.97% (149/1 494) vs 22.91% (145/633)], the clinical implementation of the long-term management concept for endometriosis [35.54% (531/1 494) vs 54.34% (344/633)], and the routine clinical use of endometriosis fertility index scoring system [18.74% (280/1 494) vs 37.31% (197/528)]. Pain or dysmenorrhea (96.52%, 611/633) was the most valued diagnostic basis, and "alleviating or eliminating pain" (94.94%, 601/633) was the top treatment goal."How to prevent and protect fertility impaired by endometriosis" (91.82%, 438/477) was the most anticipated topic for future guideline updates. 68.09% (431/633) of the respondents preferred combined estrogen-progestogen regimens for perimenopausal endometriosis, and 84.36% (534/633) of the respondents reported utilizing an add-back regimen to alleviate menopausal symptoms induced by gonadotropin-releasing hormone agonist. Furthermore, 90.36% (572/633) of the respondents reported observing mental and psychological disorders in patients with endometriosis. Conclusions: This survey provides contemporary insights into the diagnosis and management of endometriosis in China, revealing a clear trend toward increasingly standardized and refined practices. Furthermore, the survey identifies unmet clinical expectations regarding current guidelines, thereby providing valuable references for the panel to more effectively promote and guide the advancement of clinical practices for endometriosis in China.

Childhood obesity is consistently associated with earlier pubertal timing, particularly in girls, whereas its relationship with true central precocious puberty (CPP), defined by premature activation of the hypothalamic-pituitary-gonadal (HPG) axis, is less clearly established. An increased frequency of CPP diagnoses and referrals was reported during the COVID-19 pandemic, alongside changes in body weight, lifestyle, sleep, and psychosocial exposures. Human studies link excess adiposity to hyperleptinemia, insulin resistance, reduced adiponectin, altered sex-steroid bioavailability, and systemic low-grade inflammation, and associate these features with earlier pubertal development-consistently in girls, less so in boys. However, such associations do not establish that obesity directly induces premature hypothalamic activation. Mechanistic understanding of how these peripheral signals may influence pubertal timing derives predominantly from experimental models. The arcuate nucleus kisspeptin/neurokinin B/dynorphin (KNDy) network, a key component of the gonadotropin-releasing hormone (GnRH) pulse generator, interacts with hypothalamic metabolic circuits. In animal models of obesity and overnutrition, altered leptin and insulin signaling, mitochondrial reactive oxygen species generation, and activation of microglia and astrocytes remodel the mediobasal hypothalamus through inflammatory and stress-responsive pathways, including IKKβ/NF-κB and JNK signaling and altered Nrf2-mediated antioxidant defenses. At the molecular level, metabolic status interacts with the epigenetic machinery governing Kiss1 expression: in rodent models of overnutrition, accelerated loss of SIRT1-mediated repression at the Kiss1 promoter facilitates pubertal activation. Human genetic evidence establishes MKRN3 and DLK1 as causes of familial CPP, but evidence that obesity modifies these pathways to induce sporadic CPP is insufficient. Similarly, gut microbial metabolites have been linked experimentally to pubertal timing, and antioxidant micronutrients such as selenium, zinc, and vitamins C and E may be altered in pediatric obesity, yet a specific role in CPP remains unproven. Collectively, current evidence supports a working model in which metabolic, inflammatory, redox, glial, and epigenetic pathways may converge on hypothalamic reproductive circuits to influence pubertal timing in susceptible children. Direct evidence in children with CPP-of hypothalamic oxidative stress, glial activation, Nrf2 dysfunction, SIRT1 remodeling, or microbiome-mediated activation-remains limited or absent. Lifestyle optimization is appropriate for improving metabolic health in children with obesity, whereas antioxidant, micronutrient, and microbiome-targeted interventions should be considered investigational with respect to CPP. Longitudinal pediatric studies that distinguish earlier pubertal timing from true CPP, and that integrate metabolic phenotyping with validated measures of HPG-axis activation, are needed to test this framework.

This report explores the case of a young, normal-responder nulligravida with peritoneal endometriosis and recurrent implantation failure, with poor embryo quality during multiple failed attempts at IVF treatment. The patient underwent Dienogest (Visabelle®) pretreatment followed by a combination protocol of Stop GnRH-agonist/GnRH-antagonist for controlled ovarian stimulation, culminating in a natural cycle frozen-thawed embryo transfer with modified luteal phase support. This combined approach produced several high-quality embryos leading to a successful singleton pregnancy. These findings provide new insights into addressing endometriosis-associated infertility and repeated IVF failure.

Pulsatile secretion of luteinising hormone (LH) reflects episodic activity of hypothalamic gonadotrophin-releasing hormone (GnRH) neurons and is essential for reproductive function. Plasmalogens are ether phospholipids enriched in neuronal membranes; however, their role in neuroendocrine regulation of reproduction remains unclear. We examined the effects of ethanolamine and choline plasmalogens on LH pulsatility in vivo and investigated GPR61 expression in bovine hypothalamic tissues and relevant cell lines. The oestrous cycles of 15 Holstein heifers were synchronised, and blood samples were collected at 10 min intervals for 8 h. Ethanolamine plasmalogens, choline plasmalogens or vehicle were administered intravenously. LH concentrations were measured by radioimmunoassay, and LH pulses were identified using the Pulsar algorithm. GPR61 expression was examined by RT-PCR, Western blotting and immunofluorescence in bovine hypothalamic tissues and in cell lines. LH pulse frequency showed a significant treatment × time interaction (p < .01) and increased after ethanolamine plasmalogen administration (Holm-adjusted p = .0084), whereas no significant changes were observed after choline plasmalogen or control treatments. Mean LH concentrations showed a significant effect of time (p < .01), whereas neither the treatment effect nor the treatment × time interaction was significant. LH pulse amplitude was unaffected. GPR61 was expressed in GnRH neurons in the bovine hypothalamus, including the preoptic area, arcuate nucleus and median eminence, and was also detected in GT1-7 and LβT2 cells. Ethanolamine plasmalogens are associated with increased LH pulsatility in vivo and GPR61 expression in GnRH neurons, suggesting a potential role for plasmalogen composition in the neuroendocrine regulation of reproduction.

Neuropsychiatric conditions such as depression, anxiety, and stress-related disorders are increasingly associated with Polycystic Ovary Syndrome (PCOS). Evidence suggests that these conditions are not only linked to the metabolic features of PCOS but also share common underlying mechanisms, including hormonal imbalance, neuroendocrine dysfunction, chronic inflammation, and epigenetic changes. Epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs (ncRNAs) regulation, may act as important links between endocrine abnormalities and changes in brain function. In this review, we summarize current evidence connecting PCOS with psychiatric disorders through disruptions in the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes, neurotransmitter imbalance, and metabolic dysregulation. Altered activity of DNA methyltransferases and locus-specific methylation changes in stress-responsive genes, including FKBP5, have been associated with dysregulated HPA function. Similarly, histone-modifying enzymes such as histone deacetylases (HDAC1/2) and enhancer of zeste homolog 2 contribute to transcriptional changes in genes involved in synaptic plasticity and neuroendocrine regulation under conditions of hyperandrogenism and insulin resistance. In addition, epitranscriptomic regulation via N[6]-methyladenosine (m6A) modification, mediated in part by fat mass and obesity-associated protein (FTO), influences neuronal activity of gonadotropin-releasing hormone and neurotransmitter signaling. Dysregulated ncRNAs, including microRNAs (miR-34a, miR-155, miR-93, and miR-221) and long ncRNAs (XIST, H19, and MALAT1), further connect inflammatory and metabolic disturbances with neuronal function. Therefore, this review links PCOS to psychiatric disorders through alterations in the HPG and HPA axes, neurotransmitter imbalance, metabolic dysfunction, and epigenetic reprogramming. We further propose an integrated neuroendocrine-epigenetic framework to explain psychiatric vulnerability in PCOS and discuss future directions for precision-targeted therapeutic strategies.

Thoracic endometriosis is a rare manifestation of extra pelvic endometriosis and it is often missed because of its variable clinical presentation. A 33-year-old woman undergoing evaluation for secondary subfertility presented with a three-year history of cyclical periumbilical pain, swelling and occasional catamenial bleeding. Contrast-enhanced CT (CECT) abdomen and pelvis demonstrated an umbilical soft tissue nodule consistent with umbilical endometriosis which was histologically confirmed. Incidentally this CECT also revealed a right-sided pleural effusion with a pleural-based nodule despite absence of respiratory symptoms. Thoracentesis yielded haemorrhagic exudative fluid, while thoracoscopy showed multiple nodules and haemorrhagic cysts on parietal and visceral pleura. Histopathology and immunohistochemistry confirmed pleural endometriosis. The patient subsequently developed a pneumothorax requiring chest tube repositioning and was treated with gonadotropin-releasing hormone (GnRH) analogue therapy, resulting in complete symptomatic and radiological resolution at follow-up. Hormonal therapy was later discontinued to pursue conception; however, recurrence of pleural effusion occurred, necessitating continuation of the medication. This case highlights the silent and multifocal nature of extra-pelvic endometriosis.

Heat stress (HS)-induced male reproductive dysfunction is usually interpreted within a testis-centered framework, whereas the contribution of central neuroendocrine disturbance remains less well defined. In the present study, a repeated HS mouse model was used to examine whether taurine pretreatment attenuates reproductive dysfunction by integrating local testicular endpoints with HPG-axis-related and hypothalamic inflammatory readouts. Male C57BL/6J mice were assigned to control, HS + vehicle, and HS + taurine groups. Mice in the HS groups were exposed to 40 ± 1 °C for 1 h daily for 14 consecutive days, and taurine was administered intraperitoneally before each heat exposure. Sperm parameters, testicular histopathology, inflammatory, oxidative, apoptotic, endocrine, and hypothalamic microglial endpoints were assessed. Repeated HS impaired sperm motility and concentration, increased abnormal sperm morphology, and caused marked histopathological injury in the testes. These changes were accompanied by increased testicular inflammation, oxidative stress, and apoptosis. HS also disrupted HPG-axis hormone homeostasis, as reflected by altered hypothalamic Gnrh expression, pituitary Lhb and Fshb expression, and circulating reproductive hormone levels. In parallel, repeated HS was associated with hypothalamic microglial activation, increased inflammatory responses, and increased microglia-GnRH overlap. Taurine pretreatment significantly attenuated sperm dysfunction and testicular injury, reduced inflammatory, oxidative, and apoptotic alterations, partially restored endocrine homeostasis, and reduced hypothalamic microglial responses. Together, these findings show that taurine alleviates repeated HS-induced male reproductive dysfunction with coordinated improvements in testicular injury, endocrine imbalance, and hypothalamic inflammatory responses. However, the hypothalamic findings are associative and do not establish causality.

Immunocontraceptive vaccines have emerged as a promising, non-invasive strategy for regulating fertility in wildlife, domestic animals, and humans, particularly in species such as elephants where conventional population control methods are often impractical or ethically challenging. These vaccines act by eliciting immune responses against critical reproductive targets, thereby disrupting gametogenesis, fertilization, or endocrine regulation. The major categories include gonadotropin-releasing hormone (GnRH)-based vaccines, zona pellucida (ZP)-based vaccines, and gamete-specific antigen vaccines. Anti-GnRH vaccines induce neutralizing antibodies that suppress the hypothalamic-pituitary-gonadal axis by inhibiting luteinizing hormone and follicle-stimulating hormone secretion, ultimately blocking steroidogenesis and gamete production. In contrast, ZP-based vaccines target oocyte surface glycoproteins, preventing sperm binding and fertilization. Emerging molecular targets, including sperm-egg interaction proteins such as IZUMO1 and JUNO, offer enhanced specificity. These vaccines predominantly stimulate humoral immune responses, with antigen-specific antibody production playing a central role, although cell-mediated immunity may contribute to sustained effects. In elephants, vaccines such as porcine zona pellucida (PZP) and GnRH-based formulations (e.g., GonaCon) have shown variable success in inducing reversible infertility, though challenges remain regarding booster requirements, duration of efficacy, and potential side effects. Advances in scientific technologies, particularly peptide engineering and viral-vector platforms, have contributed significantly to the development of immunocontraceptive vaccines by enhancing antigen specificity, immunogenicity, and overall vaccine performance. However, variability in immune responses, species-specific efficacy, and ethical considerations continue to limit widespread application. This review aims to help understanding the molecular and immunological mechanisms are essential for optimizing safe, effective, and sustainable fertility control strategies.

The gonadotropin-releasing hormone (GnRH) superfamily also includes corazonin-type (CRZ-type) signaling systems, yet their molecular features and transduction mechanisms remain poorly defined in cephalopods. Here, we cloned the full-length cDNAs of the CRZ-type peptide precursor OmCRZP and its cognate receptor OmCRZR from Octopus minor. OmCRZP encodes an 89-residue precursor containing a conserved dodecapeptide (pQNYHFSNGWHPG-NH2), and OmCRZR encodes a 407-residue seven-transmembrane G protein-coupled receptor. Phylogenetic analyses placed OmCRZP within the cephalopod CRZ clade and OmCRZR within the corazonin receptor (CRZR) clade. Expression profiling showed that OmCRZP was predominantly expressed in the brain and white body, whereas OmCRZR exhibited high expression in the brain, systemic heart, branchial heart, and white body with developmental upregulation in circulatory tissues. Fluorescence in situ hybridization detected overlapping ligand and receptor signals in several brain lobes involved in sensory integration, motor control, and visceral regulation, suggesting autocrine or paracrine signaling. Strong OmCRZR signals were additionally detected in cardiac tissue. Immunofluorescence further confirmed the widespread distribution of the mature peptide in the neuropil of nearly all brain lobes examined. In HEK293T cells, synthetic OmCRZ induced receptor internalization, intracellular Ca[2+] mobilization and transient ERK1/2 phosphorylation without activating the cAMP pathway. These results establish the molecular architecture and Ca[2+]/ERK-coupled signaling of a cephalopod CRZ-type system and provide a framework for exploring its neuromodulatory functions.

Hormone-dependent cancers, particularly estrogen receptor-positive breast cancer and androgen receptor-driven prostate cancer, contribute substantially to global cancer-related morbidity and mortality. Endocrine therapy has long been the mainstay of treatment for these tumors because of its specific mechanism and good safety profile. The long-term success of common hormone-based treatments is often undermined by resistance, both intrinsic and acquired, disease recurrence, and the activation of compensatory pathways that tumor cells have adapted to. To overcome these challenges, it has been necessary to develop high-quality hormone-based biopharmaceuticals that target the molecular level, enhance pharmacokinetics, and apply precision medicine strategies. The goal of this literature review is to provide an update on progress in hormone-based biopharmaceuticals for cancer management, with a particular focus on preventing endocrine resistance in hormone-dependent cancers. Among the treatments mentioned in the review, most are oral selective estrogen receptor degraders (SERDs) for ER-positive breast cancer, oral gonadotropin-releasing hormone antagonists for prostate cancer, genomically guided combination therapy that integrates inhibitors of the CDK4/6 and PI3K/AKT/mTOR signaling pathways, and next-generation androgen receptor (AR) degraders based on proteolysis-targeting chimera (PROTAC) technology. There is new evidence that these biopharmaceutical methods may be able to treat patients better over longer periods. For those who are less responsive, these approaches are even more effective when paired with proper biopharmaceutical methods, as in the case of hormone therapy. While targeted protein degradation and biomarker-driven combination therapies are repositioning drug development away from receptor blockade, the latter remains the mainstay of treatment. However, these developments do not eliminate concerns related to long-term safety, cost-effectiveness, appropriate patient selection, and resistance to novel agents. The path for hormone-based biopharmaceuticals in personalized cancer therapy requires continuous translational research and clinical validation to determine the best place.