The administration of GnRH and its agonists benefits various aspects of bovine reproductive programs, encompassing physiological stages such as estrous synchronization, post-insemination, pregnancy, and the postpartum period. The positive impact of GnRH administration in overcoming challenges like repeat breeder cows, early embryonic loss prevention, and the management of cystic ovarian disease (COD) is thoroughly surveyed. Furthermore, this review focuses on the significance of GnRH administration during the postpartum period, its role in ovulation induction, and how it enhances the productivity of embryo transfer (ET) programs. An emerging feature of this field is introduced, focusing on nano-drug delivery systems for GnRH agonists, and the potential benefits that may arise from such advancements are highlighted. While this review offers valuable insights into various applications of GnRH in bovine reproduction, it emphasizes the crucial need for further research and development in this field to advance reproductive efficiency and health management in dairy cattle.

GnRH is essential for the regulation of mammalian reproductive processes. It regulates the production and release of pituitary gonadotropins, thereby influencing steroidogenesis and gametogenesis. While primarily produced in the hypothalamus, GnRH is also produced in peripheral organs, such as the gonads and placenta. GnRH analogs, including agonists and antagonists, have been synthesized for the reproductive management of animals and humans. This review focuses on the functions of hypothalamic GnRH in the reproductive processes of cattle. In addition to inducing the surge release of LH, the pulsatile secretion of GnRH stimulates the pituitary gland to release FSH and LH, thereby regulating gonadal function. Various GnRH-based products have been synthesized to increase their potency and efficacy in regulating reproductive functions. This review article describes the chemical structures of GnRH and its agonists. This discussion extends to the gene expression of GnRH in the hypothalamus, highlighting its pivotal role in regulating the reproductive process. Furthermore, GnRH is involved in regulating ovarian follicular development and luteal phase support, and estrus synchronization is involved. A comprehensive understanding of the role of GnRH and its analogs in the modulation of reproductive processes is essential for optimizing animal reproduction.

BACKGROUND: Endogenous sex steroids influence the pubertal growth spurt and adult height. However, the impact of puberty suppression and sex steroids on growth in transgender adolescents is sparsely studied.
OBJECTIVE: We investigated pubertal growth, serum IGF-I and IGFBP-3, and adult height of transgender adolescents receiving hormone therapy.
METHODS: Observational study of a national cohort (2016-2023) comprising 219 transgender adolescents <18 years of age. Treatment consisted of gonadotropin-releasing hormone agonist (GnRHa) combined with estradiol or testosterone (adjusted to serum concentrations between 0 and +2 standard deviations (SDs) corresponding to the gender identity).
RESULTS: Adult height was within ±2 SD for sex assigned at birth.Most trans girls reached adult height within references of girls. For trans girls (bone age ≤15 years before treatment), a growth spurt was observed during estradiol therapy. IGF-I and height SDS declined during oral estradiol administration (-0.13 SDS per month, p=0.059, and -0.02 SDS, p=0.001, respectively). We observed significantly lower adult height compared to target height for trans girls (-2.7 cm, p=0.01), and significant differences between height SDS before treatment and at adult height (-0.35 SDS, p<0.001).Half of the trans boys remained short (<-2 SD) compared to references for boys, and most completed growth spurt before initiation of treatment. IGFBP-3 declined following testosterone treatment. There was a significant difference between height SDS before treatment and at adult height (-0.17 SDS, p<0.001).
CONCLUSIONS: The minor reduction in adult height of trans girls after hormone treatment may be beneficial to some, whereas trans boys did not experience height gain.

Spermatogonial stem cell (SSC) acquisition of meiotogenetic state during puberty to produce genetically diverse gametes is blocked by drugs collectively referred as \'puberty blocker\' (PB). Investigating the impact of PB on juvenile SSC state and function is challenging due to limited tissue access and clinical data. Herein, we report largest clinically annotated juvenile testicular biorepository with all children with gender dysphoria on chronic PB treatment highlighting shift in pediatric patient demography in US. At the tissue level, we report mild-to-severe sex gland atrophy in PB treated children. We developed most extensive integrated single-cell RNA dataset to date (>100K single cells; 25 patients), merging both public and novel (52 month PB-treated) datasets, alongside innovative computational approach tailed for germ cells and evaluated the impact of PB and aging on SSC. We report novel constitutional ranges for each testicular cell type across the entire age spectrum, distinct effects of treatments on prepubertal vs adult SSC, presence of spermatogenic epithelial cells exhibiting post-meiotic-state, irrespective of age, puberty status, or PB treatment. Further, we defined distinct effects of PB and aging on testicular cell lineage composition, and SSC meiotogenetic state and function. Using single cell data from prepubertal and young adult, we were able to accurately predict sexual maturity based both on overall cell type proportions, as well as on gene expression patterns within each major cell type. Applying these models to a PB-treated patient that they appeared pre-pubertal across the entire tissue. This combined with the noted gland atrophy and abnormalities from the histology data raise a potential concern regarding the complete \'reversibility\' and reproductive fitness of SSC. The biorepository, data, and research approach presented in this study provide unique opportunity to explore the impact of PB on testicular reproductive health.

The lipid profile is affected following menstrual cessation (MC). We aimed to evaluate the effects of goserelin-induced MC and subsequent menstrual restoration (MR) on lipid metabolism. Premenopausal women with histologically verified endometriosis (n = 15) received goserelin monthly for 6 months (6mο), resulting in MC, and were followed-up for another 6 months after MR (12mο). Serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein a ([Lp(a)] and lipidomics were measured at baseline, 6mo and 12mo. Shotgun quantitative deep lipidomics were determined at the level of lipid class category, subclass, species, and fatty acyl chain lengths and degree of saturation. TC (p = 0.006), LDL-C (p = 0.028), HDL-C (p = 0.002), and apoA1 (p = 0.013) increased during goserelin-induced MC and remained practically unchanged during MR. TG, apoB, and Lp(a) did not change. From the deep lipidomics analysis, multivariate statistical analysis demonstrated profound alterations in lipid species with MC, whereas no statistically valid models could be fitted for the restoration period. In conclusion, GnRH-analog-induced MC alters lipid profiles at various levels, from standard blood lipid and lipoprotein profiles to several lipid species as detected by lipidomics analysis. Changes largely persist for at least 6 m after MR.

The objective of this study was to describe the effect of the third-generation GnRH antagonist, acyline, on ovarian follicular population and serum anti-Müllerian hormone (AMH) concentrations in female dogs. Four late anestrous bitches were administered 330 μg/kg SC acyline every 10 days for 60 days and followed up for 45 days. Blood samples were drawn on days -1, 15, 30, 45, 60, 75, 90 and 105 for AMH determination. Then, the females were ovariectomized and the excised ovaries were gross and histologically evaluated. The total ovarian follicles were counted. None of the female dogs presented estrus during treatment. Only one bitch presented an ovulatory estrus 20 days after treatment. The total number of ovarian follicles in these bitches was 96,200.10 ± 26,125.12, with 84.13%, 11.36%, 7.8% and 0.01% corresponding to primordial, primary, secondary and antral structures, respectively. Pretreatment AMH concentrations were 0.62 ± 0.17 ng/mL. This hormone varied throughout the study period (p < 0.01), diminishing to nadir values during treatment to then rapidly recover after its effect (0.2 ± 0.05 vs. 0.67 ± 0.22 ng/mL; p < 0.01). Acyline rapidly and reversibly prevented the initiation of cycling without affecting follicle count but diminishing serum AMH concentrations.

Oocytes/embryo cryopreservation and ovarian function suppression with gonadotropin-releasing hormone (GnRH) agonists (GnRHas) are two established strategies for preserving fertility in patients with cancer, frequently both being offered to the same woman. As the first injection of GnRHa should be administered before chemotherapy, it is usually performed in the luteal phase of the urgent controlled ovarian stimulation (COS) cycle. The GnRHa flare-up effect on recently stimulated ovaries may cause ovarian hyperstimulation syndrome (OHSS) and this risk may discourage some oncologists to offer an ovarian function preservation method with proven efficacy. We suggest the long-acting GnRHa as an option to trigger ovulation for egg retrieval in oncological patients, whenever ovarian suppression during chemotherapy is planned.
We retrospectively analyzed prospectively collected data from all consecutive ovarian stimulation cases in oncological patients for oocyte cryopreservation from 2016 to 2021 in a single academic referral center. The COS was performed according to good clinical practice standards. Since 2020 long-acting GnRHa trigger was offered to all patients for whom ovarian suppression after cryopreservation was planned. All other patients served as controls, stratified for the triggering method used: highly purified chorionic gonadotrophin 10 000 UI or short-acting GnRHa 0.2 mg.
Mature oocytes were collected, with the expected maturation rate, in all the 22 cycles triggered with GnRHa. The mean number of cryopreserved oocytes was 11.1 ± 4, with a maturation rate of 80% (57%-100%), versus 8.8 ± 5.8, 74% (33%-100%) with highly purified chorionic gonadotrophin and 14 ± 8.4, 80% (44%-100%) with short-acting GnRHa. No case of OHSS was observed after long-acting GnRHa triggering and by 5 days after egg retrieval most patients had reached luteinizing hormone levels showing suppression.
Our preliminary data show that long-acting GnRHa is efficacious in inducing the final oocytes\' maturation, reducing OHSS risk and suppressing ovarian function by the start of chemotherapy.

Precocious puberty is a common presentation to pediatricians with a significant overlap between physiology and pathology. While most girls with precocious puberty have no identifiable cause, boys are more likely to have a pathological cause. The trend of earlier onset of thelarche with slow pubertal tempo has led to a significant increase in the number of girls presenting with precocious puberty. Advanced growth, bone age, uterine maturation, and elevated LH suggest rapidly progressive puberty. The critical issues in evaluating a child presenting with precocious puberty include its confirmation, exclusion of physiological variants, identification of the cause, and determining the need for treatment. Step-wise evaluation with emphasis on clinical parameters provides cost-effective assessment. Gonadotropin-releasing hormone (GnRH) analogs remain the mainstay of treatment for central precocious puberty but should be restricted to individuals with rapidly progressive puberty and compromised final height. The management of rarer forms of peripheral precocious puberty (McCune Albright syndrome, congenital adrenal hyperplasia, and testotoxicosis) involves using experimental drugs under the guidance of specialists.

OBJECTIVE: The histrelin implant has been used to treat central precocious puberty (CPP) for more than 15 years. Although approved for annual use, limited published reports suggest that a single implant is efficacious well beyond a year. Our objective was to report our long-term experience using a single histrelin implant for more than 12 months in children with CPP.
METHODS: We performed a retrospective study of 170 children with central precocious puberty treated with a single histrelin implant for more than 1 year.
RESULTS: Implants were left in situ for an average of 24 months. Pubertal development regressed or remained stable in the vast majority of patients and biochemical suppression was maintained. No correlation between time since an implant was placed and complications such as implant breakage or a second incision was seen.
CONCLUSIONS: A single histrelin implant provides excellent pubertal suppression well beyond a year. Extended use of a single histrelin implant should be considered standard of care in children with CPP.

Spanning from bench to bedside, the history of normal and precocious puberty is characterized by a series of remarkable advances that have illuminated reproductive physiology and profoundly impacted clinical care. Early recognition of the hypothalamic and pituitary control of ovarian and testicular function led to the identification of GnRH as the key driver of pubertal onset. Decades later, discovery of the kisspeptin system further refined our understanding of human reproductive neuroendocrinology. Development of long-acting analogs of GnRH revolutionized the treatment of precocious puberty worldwide and ushered in the current era of an ever-expanding therapeutic armamentarium. Identification of monogenic etiologies of precocious puberty has further illustrated the exquisite complexity that comprises neurosecretory modulation of the hypothalamic GnRH neuron and may well lead to exciting novel targeted therapies.