Gonadotropin-releasing Hormone Research Articles

Temple Syndrome: Comprehensive Clinical Study in Genetically Confirmed 60 Japanese Patients.

Temple syndrome (TS14) is a rare 14q32.2-related imprinting disorder. Here, we report comprehensive clinical findings in TS14. We obtained detailed clinical findings in 60 Japanese patients with genetically confirmed TS14, using a questionnaire to attending physicians. The 60 patients consisted of 31 with UPD(14)mat, 22 with epimutation, five with deletions, and two with UPD(14)mat or epimutation. Small for gestational age, postnatal (∼2 years of age) short stature, and central precocious puberty (CPP) were identified in 88.3%, 87.0%, and 86.0% of patients, respectively. Growth hormone therapy was performed in 32 patients, increasing the median height SDS for height from -3.4 to -2.4, and gonadotropin-releasing hormone analog therapy was performed in 32 patients, ameliorating CPP. Furthermore, the survey showed intellectual and developmental disabilities in 21.6% of patients, neurodevelopmental disorders in 21.6% of patients, obesity in 20.0% of patients, hypercholesterolemia in 26.5% of patients aged ≥6 years, diabetes mellitus in 12.8% of patients aged ≥9 years, and Silver-Russell syndrome-like and/or Prader-Will syndrome-like phenotypes in 87.7% of patients in infancy. Notably, 42.9% of patients were enrolled in special classes in childhood, whereas 98.2% of patients attended college or had jobs in adulthood. Hypercholesterolemia and diabetes mellitus were observed before the development of obesity in a substantial fraction of TS14 patients, and were controlled by oral medications in most affected patients. These results clarify the detailed clinical characteristics in TS14. On the basis of the above findings, we propose efficient diagnostic approach and pertinent clinical management for TS14 patients.

Kisspeptin and Endometriosis—Is There a Link?

This article presents a narrative review that explores the potential link between kisspeptin—a key regulator of the hypothalamic-pituitary-gonadal axis—and the pathogenesis of endometriosis. Kisspeptin plays a significant role in regulating reproductive functions by modulating the release of gonadotropin-releasing hormone (GnRH), which in turn stimulates the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Recent studies suggest that kisspeptin may also impact peripheral reproductive tissues and influence inflammatory processes involved in the development of endometriosis. Altered kisspeptin signaling has been associated with the abnormal hormonal environment observed in endometriosis, which affects menstrual cycles and ovarian function. Research indicates that women with endometriosis exhibit altered levels of kisspeptin and its receptor, KISS1R, in both eutopic and ectopic endometrial tissues, suggesting a role in disease progression, particularly in tissue invasion and lesion formation. Kisspeptin’s role in regulating matrix metalloproteinases (MMPs), enzymes essential for tissue remodeling, further supports its potential contribution to the pathophysiology of endometriosis. Moreover, kisspeptin-based therapeutic strategies are currently under investigation, with the aim of providing targeted treatments that reduce the side effects commonly associated with existing therapies. Despite promising findings, further research is needed to fully understand the mechanisms by which kisspeptin influences endometriosis.

Effects of pretreatment strategies on fertility outcomes in patients with adenomyosis

Adenomyosis is a commonly encountered pathology in women of reproductive age and frequently coexists with infertility. The effect of adenomyosis on fertility, particularly on in vitro fertilisation and intracytoplasmic sperm injection outcomes, is not well understood. Various pretreatment modalities have been used to improve pregnancy rates and live birth outcomes; however, because of a lack of high-quality evidence, there is no clear consensus on the best pretreatment option. This review was conducted through a PubMed search aiming to highlight the relationship between pretreatment and fertility in women with adenomyosis. Medical, ablative surgical, and non-surgical therapies were reviewed. According to the current literature, gonadotropin-releasing hormone agonist therapy and placement of a levonorgestrel intrauterine system are two suitable medical pretreatment strategies that can improve the clinical pregnancy rates of patients with adenomyosis. Surgical ablation of adenomyosis can also be beneficial, although surgical management can be challenging. Non-surgical thermal techniques, including high-intensity focused ultrasound ablation, percutaneous microwave ablation, and radiofrequency ablation, are much less invasive techniques that have shown effectiveness in improving fertility. Although evidence remains limited, all these procedures have demonstrated a favourable safety profile. Further studies are needed to better develop these techniques and demonstrate their effectiveness.

Combining Medication With High-Intensity-Focused Ultrasound for Adenomyosis: A Network Meta-Analysis of Randomized Controlled Trials.

This network meta-analysis aims to identify the best possible combination therapy for individuals suffering from adenomyosis. To identify pertinent research for the network meta-analysis, a comprehensive search was conducted across multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, and VIP, spanning from their commencement to February 21, 2024. The study's focus was on evaluating outcomes including visual analog scale (VAS) scores for dysmenorrhea, measurements of uterine and lesion volumes, menstrual blood loss, and the rate of disease recurrence. The findings from both direct and indirect comparisons, which were quantitatively assessed using weighted mean differences or relative risk along with their respective 95% confidence intervals, were graphically depicted in forest plots. Additionally, the ranking probability was illustrated, which indicated the likelihood of various high-intensity-focused ultrasound (HIFU) combination therapies being the most effective across each measured outcome. In the final analysis, this network meta-analysis encompassed a total of 31 articles. The results showed that HIFU combined with gonadotropin-releasing hormone agonist (GnRH-a) and progestin was more effective to decrease VAS score for dysmenorrhea than other combined therapies. HIFU combined with progestin was superior to other combined therapies in decreasing uterine volume, lesion size, and recurrence rate. HIFU combined with mifepristone was more effective to reduce menstrual volume compared to other combined therapies. The analysis suggests that regimens incorporating HIFU along with GnRH-a and progestin, or HIFU combined with progestin or HIFU combined with mifepristone might offer superior benefits in the clinical management of adenomyosis. These combined treatment approaches could potentially be more effective options for patients suffering from this condition.

Clinical impact of endogenous luteinizing hormone in frozen-thawed embryo transfer during hormone replacement cycle without gonadotropin-releasing hormone analog coadministration: Effects on pregnancy outcomes.

To assess the correlation between serum luteinizing hormone (LH) levels preceding luteal replacement initiation and outcomes of frozen-thawed embryo transfer (FET) cycles during hormone replacement therapy (HRT) without co-administration of gonadotropin-releasing hormone (GnRH) analog. We retrospectively enrolled 490 FET cycles performed between March 2018 and May 2023. Patients were categorized into quartiles based on their serum LH levels preceding luteal replacement. Multivariate logistic regression analysis was performed, with clinical pregnancy and live birth rates as dependent variables. The independent variables included women's mean age, serum LH, and estradiol levels preceding luteal replacement, and endometrial thickness during transfer. Mean age, serum estradiol, and LH levels preceding luteal replacement were 36.8 ± 0.2 years, 306.5 ± 7.7 pg/mL, and 10.3 ± 0.3 mIU/mL, respectively. The clinical pregnancy and live birth rates were 46.8% and 31.9%, respectively, and varied significantly between quartiles. Multivariate analysis revealed that younger age and higher LH levels were significantly associated with increased clinical pregnancy and live birth rates. Endogenous LH may facilitate pregnancy within FET cycles under HRT without GnRH analogs by preparing the endometrium for implantation.

Treatment trajectories among children and adolescents referred to the Norwegian National Center for Gender Incongruence.

We aimed to describe treatment trajectories, detransition and mortality rate among children and adolescents referred to the Norwegian National Center for Gender Incongruence (NCGI). The cohort included all 1258 persons under 18 years at referral to the NCGI from 2000 to 2020. Trajectories were registered until end of 2023. In total, 861/1258 (68.4%) were assigned female gender at birth (AFAB). Mean age at referral was 14.4 years. Puberty suppression with gonadotropin-releasing hormone agonists (GnRHa) was initiated among 135/1258 (10.7%), significantly more persons assigned male gender at birth (AMAB) than AFAB (p < 0.001). Gender-affirming hormonal treatment (GAHT) was initiated in 783/1258 (62.2%). The continuation rate from GnRHa to GAHT was 97%. Discharge rate from NCGI without gender-affirming medical treatment among those who attended at least one appointment, was 264/1198 (22.0%). Eighteen AFAB detransitioned after initiated GAHT, eleven due to a cessation of transgender identity. Mortality rate in the cohort until end of 2023 was 11/1258 (0.9%). Different trajectories including medical pathways and assessments without gender-affirming treatment were observed. GAHT was initiated in 783/1258 (62.2%), including eighteen AFAB detransitioning after testosterone treatment. There was a high continuation rate from GnRHa to GAHT. Various trajectories highlights the need for long-term follow-up in care.

Adult height in girls with idiopathic central precocious puberty treated with triptorelin

ObjectiveIdiopathic central precocious puberty (CPP) precipitates epiphyseal fusion of growth plates in long bones, leading to reduced adult stature. Gonadotropin-releasing hormone analogues (GnRHa) are the treatment of choice for idiopathic CPP, but their benefit on height gain is unclear. We aimed to elucidate the effects of GnRHa treatment on adult height in girls with idiopathic CPP.DesignThis prospective observational descriptive study analyzed data of girls with idiopathic CPP diagnosed at 55 centers in Spain between January 1, 1998 and December 31, 2012 included in the Spanish Society for Pediatric Endocrinology’s national registry.MethodsWe included girls with idiopathic CPP (thelarche &amp;lt; 8 years, positive LHRH stimulation test, bone age &amp;gt; 1 year older than chronological age, and normal brain imaging) treated with triptorelin (3.75 mg monthly, adjusted according to LHRH test results and clinical findings). We assessed weight, height, BMI, and secondary sexual characteristics every 6 months and bone age every 12 months until adult height (AH) was attained. The primary outcome was the difference between AH and target height (TH).ResultsA total of 465 girls (18.90% adopted) were included; we analyzed data recorded at treatment end in 358 girls and at AH in 216. Mean difference between AH and TH was -1.5 (95%CI: -2.56− -0.45) cm and between AH and PAH 2,57 (95%CI:-3.56− -1.58) cm.ConclusionsGnRHa treatment helps preserve genetic growth potential in girls with idiopathic CPP.

Dynamics of blood adipokine levels and their ratios in assisted reproductive technology programs depending on the clinical pregnancy onset

BACKGROUND: The adipokines leptin, adiponectin, and ghrelin are expressed not only in adipose tissue but also in the hypothalamic-pituitary-gonadal axis organs and the uterus. They regulate the gonadotropin-releasing hormone and gonadotropin secretion, steroidogenesis, folliculogenesis, and implantation, and serve as promising markers of assisted reproductive technology program outcomes. AIM: The aim of this study was to evaluate the dynamics of blood adipokine levels and their ratios during the controlled ovarian hyperstimulation in assisted reproductive technology programs depending on the onset of clinical pregnancy. MATERIALS AND METHODS: This study involved 51 patients undergoing infertility treatment using assisted reproductive technology in a short protocol with gonadotropin-releasing hormone antagonists. Depending on the onset of clinical pregnancy, two study groups were formed: non-pregnant (group 1, n = 22) and pregnant (group 2, n = 29). Blood leptin, adiponectin, and ghrelin levels were assessed using enzyme immunoassay at three points: assisted reproductive technology protocol start-up, the day of oocyte pick-up, and the day of embryo transfer. RESULTS: On the day of oocyte pick-up, patients in group 1 had higher leptin levels (5.47 ± 1.92 vs. 3.76 ± 0.75 ng/ml; p = 0.0004), leptin/adiponectin ratios (11.45 ± 4.50 vs. 4.73 ± 1.08; p 0.001), and leptin/ghrelin ratios (0.43 ± 0.17 vs. 0.24 ± 0.07; p 0.001). On the day of embryo transfer, patients in group 1 had higher levels of leptin (6.37 ± 2.13 vs. 3.29 ± 1.21 ng/ml; p 0.001) and adiponectin (0.75 ± 0.22 vs. 0.60 ± 0.09 ng/ml; p = 0.001), as well as ratios of leptin/adiponectin (9.06 ± 3.73 vs. 5.59 ± 2.32; p 0.001), leptin/ghrelin (0.48 ± 0.15 vs. 0.20 ± 0.07; p 0.001), and adiponectin/ghrelin (0.06 ± 0.02 vs. 0.04 ± 0.01; p 0.001). CONCLUSIONS: The data obtained indicate that blood adipokine levels change during the controlled ovarian hyperstimulation in assisted reproductive technology protocols depending on clinical pregnancy and can be used to predict its onset.

Socially dangerous sexual paraphilias: Frotteurism and necrophilia

This article deals with the study of the prevalence, etiology, pathogenesis and treatment of frotteurism and necrophilia, which are socially dangerous and are of great interest to the medical community. To summarize all available literature on frotteurism and necrophilia. Based on the PRISMA guidelines, the current review brings together all the existing literature on frotteurism and necrophilia. Socially dangerous paraphilias may be caused by biological, psychological and social factors and are treated with antiandrogens, gonadotropin-releasing hormone analogs and selective serotonin reuptake inhibitors as well as psychotherapy. Analysis of the data on the treatment of socially dangerous paraphilias revealed good results across each type of paraphilia and treatment method used, demonstrating a significant reduction in deviant behavior and paraphilic desires after the treatment and into the follow-up phase. Yet, all of these results cannot be verifiable, as conclusions about them were made based on the patients’ personal reports, which may not be objective. High-quality placebo-controlled studies on the treatment of socially dangerous paraphilias are lacking. Clinicians should be aware that the prevalence of socially dangerous paraphilias is not negligible and that people with deviant sexual urges should be encouraged to seek professional help before committing a crime or a self-injurious act. More extensive epidemiological studies are required to clarify the actual prevalence of socially dangerous paraphilias in the population and methods of their treatment alongside with destigmatization of patients with paraphilias and engaging them in treatment before they commit a crime.

A Rare Cause of Precocious Puberty - Testotoxicosis

Background: Testotoxicosis, also known as familial male-limited precocious puberty (FMPP), is a rare cause of gonadotropin-independent precocious puberty in boys due to an activating mutation in the luteinizing hormone (LH))/choriogonadotropin receptor (LHCGR) gene. Case report: A 3-year 2-month-old boy presented with acne, pubic hair, phallic growth, height accelerations, and aggressiveness. At physical examination, his height was 106cm (+2.36 SDS) and weight was 16kg (+0.77 SDS). He had Tanner stage 2 pubic hair, stretched penile length was 6 cm (&gt;2 SDS), and both testicular volumes were 5mls. Bone age was advanced at 7 years old. Testosterone level was high at 17nmol/L and the gonadotropin-releasing hormone (GnRH) stimulation test was suggestive of peripheral precocious puberty. Whole exome sequencing identified a heterozygous pathogenic variant c.1691A&gt;G (p.Asp564Gly) in the LHCGR gene which supports the diagnosis of testotoxicosis. The child was started on both aromatase inhibitor, anastrozole, and anti-androgen, spironolactone. At 6 months of treatment, there was a halt in pubertal progression with reduced height velocity from 9cm/year to 6cm/year. Conclusion: Without intervention, the patient will have rapid progressive skeletal maturation and virilization which will result in compromised final adult height and psychosocial distress.

Molecular response of canine testis to GnRH agonist: Insights into AR, HIF-1α, and HSPs expression during arrest and recovery of spermatogenesis.

Slow release gonadotropin releasing hormone (GnRH) agonist implants are frequently used for contraception in male dogs. Although the effects are fully reversible, there is still concern about the safety of the implant's mode of action. Addressing this, we investigated cellular stress and androgen receptor signaling during downregulation and recovery. Testicular tissues were sampled from dogs castrated at different time points after GnRH implant removal and compared with untreated controls. Androgen receptor (AR), hypoxia-inducible factor 1 (HIF1A) and heat shock proteins HSP72, HSP73, HSPA2, HSP90AA1 and HSP90AB1 were investigated by qPCR, and AR, HSP72, HSP73 and HSP90 immunohistochemically. While AR, HIF1A and HSP70 were upregulated at mRNA level, HSPA8, HSPA2 and HSP90AA1 expression were downregulated during spermatogenic arrest; HSP90AB1 expression did not change. Immunohistochemistry verified AR-expression in Sertoli, peritubular and Leydig cells, occasionally also in spermatogonia. Stress-inducible HSP72 was occasionally detected, while constitutive HSP73 and HSP90 were abundantly expressed by germ cells. Our results were similar with studies on seasonal breeders such as pine voles, geese, fish and soft-shelled turtles. Accordingly, GnRH implants did not impose additional cellular stress on testicular cells when compared with natural recrudescence. Since comparative data on HIF1α is scarce, we cannot draw conclusions about hypoxic conditions.

Effect of galanin-like peptide on hypothalamic kisspeptin expression in female Zucker fatty rats.

Kisspeptin and galanin-like peptide (GALP) neurons in the hypothalamic arcuate nucleus (ARC) are involved in gonadotropin-releasing hormone (GnRH) neuron-mediated pulsatile luteinizing hormone (LH) secretion. Zucker fatty (ZF) rats display a leptin receptor gene abnormality and suppressed pulsatile LH secretion. ZF rats reportedly exhibit low hypothalamic GALP and kisspeptin expression, and GALP administration induces LH release in ZF rats. Therefore, we performed a histochemical analysis to determine whether GALP-induced LH release is mediated by kisspeptin neurons in ZF rats. All ZF rats were ovariectomized and subcutaneously implanted with an estradiol tube before the central injection of GALP or vehicle. GALP administration increased the plasma LH concentration. However, no significant difference was observed in the number of Kiss1 cells and the proportion of Fos-positive Kiss1 cells. The number of c-Fos-positive GnRH neurons significantly increased after GALP administration. Our results suggest that hypothalamic GALP neurons promote LH release by activating GnRH neurons without the activation of kisspeptin neurons in the ARC.

Risk and protective factors for ASF in domestic pigs and wild boar in the EU, and mitigation measures for managing the disease in wild boar.

Five epidemiological aspects of ASF were evaluated using literature reviews, field studies, questionnaires and mathematical models. First, a literature review and a case-control study in commercial pig farms emphasised the importance of biosecurity and farming practices, including the spread of manure around farms and the use of bedding material as risk factors, while the use of insect nets was a protective factor. Second, although wild boar density is a relevant known factor, the statistical and mechanistic models did not show a clear and consistent effect of wild boar density on ASF epidemiology in the selected scenarios. Other factors, such as vegetation, altitude, climate and barriers affecting population connectivity, also played a role on ASF epidemiology in wild boar. Third, knowledge on Ornithodoros erraticus competence, presence and surveillance was updated concluding that this species did not play any role in the current ASF epidemic in affected areas of the EU. Available scientific evidence suggests that stable flies and horse flies are exposed to ASFV in affected areas of the EU and have the capacity to introduce ASFV into farms and transmit it to pigs. However, there is uncertainty about whether this occurs, and if so, to what extent. Fourth, research and field experience from affected countries in the EU demonstrates that the use of fences, potentially used with existing road infrastructure, coupled with other control methods such as culling and carcass removal, can effectively reduce wild boar movements contributing to ASF management in wild boar. Fences can contribute to control ASF in both scenarios, focal introductions and wave-like spread. Fifth, the use of gonadotropin-releasing hormone (GnRH) vaccines as an immune contraceptive has the potential, as a complementary tool, to reduce and control wild boar populations. However, the development of an oral GnRH vaccine for wild boar still requires substantial additional work.

Effect of basal luteinizing hormone/follicle-stimulating hormone ratio on clinical outcome of In Vitro fertilization in patients with polycystic ovarian syndrome: a retrospective cohort study.

The basal luteinizing hormone (LH) and the prior LH to follicle-stimulating hormone (FSH) ratio (LH/FSH) in polycystic ovarian syndrome (PCOS) are generally higher than those in non-PCOS patients and the general population. The potential negative effects of elevated LH on human reproductive function are highly controversial, as are the effects of down-regulation of LH on reproductive function. The purpose of this study was to evaluate the effect of the basal LH/FSH ratio on the live birth rate of PCOS patients undergoing in vitro fertilization (IVF) cycles. A retrospective analysis was conducted on 698 patients with polycystic ovary syndrome undergoing IVF treatments with a mild stimulation protocol (n = 95) and a gonadotropin-releasing hormone (GnRH) agonist protocol (n = 603). The basal LH/FSH ratio of 2 was used as the cut-off value for further subgroup analysis. The demographic properties, controlled ovarian hyperstimulation (COH) processes, and clinical pregnancy outcomes were compared between groups under each ovulation stimulation protocol. The live birth rate for patients with a LH/FSH ratio ≥ 2 group (56.38%, n = 149) was not statistically different from that of the ones with a ratio < 2 (53.74%, n = 454) in the GnRH agonist protocol (P = 0.576). Correspondingly, the live birth rate for the LH/FSH ratio ≥ 2 group (43.48%, n = 23) also showed no statistical difference from the ratio < 2 group (48.61%, n = 72) in the mild stimulation protocol (P = 0.668). Additionally, LH/FSH ratios had no significant effect on the live birth rate after adjusting for confounders both in the GnRH agonist protocol (adjusted OR: 1.111; 95% CI [0.467-2.642], P = 0.812) and in the mild stimulation protocol (adjusted OR: 4.057; 95% CI [0.431-38.195], P = 0.221). Furthermore, there was no significant difference in the live birth rate between different ovulation stimulation protocols in PCOS patients with the LH/FSH ratio ≥ 2. The live birth rate in IVF outcomes was not affected by an elevated basal LH/FSH ratio in patients with polycystic ovary syndrome. The choice of the GnRH agonist protocol or mild stimulation protocol for ovulation stimulation does not affect the final clinical outcomes either for PCOS patients with a basal LH/FSH ratio ≥ 2.

Expression of GnRH, Kisspeptin, and Their Specific Receptors in the Ovary and Uterus in Deslorelin-Treated Late-Prepubertal Bitches

In this study, the expression and localization of gonadotropin-releasing hormone (GnRH1) and kisspeptin (KISS1) and their specific receptors in canine ovarian and uterine tissues were investigated after the application of deslorelin acetate (Suprelorin®, 4.7 mg, Virbac, France) in the late prepubertal period. We hypothesized that prolonged treatment of prepubertal dogs with deslorelin would alter the expression of GnRH and kisspeptin genes in the uterus and ovaries. Ovarian and uterine samples of 25 dogs with an average age of 7.8 ± 0.2 months and from mixed breeds were used. Following implant insertion, dogs entered estrus (EST; n = 6); dogs without estrus (N-EST; n = 10) comprised the experimental groups. Nine dogs with placebo implants served as a control (CONT). Ovarian and uterine tissues were investigated for expression of GnRH1, GnRHR, KISS1, and KISS1R/GPR54 mRNA and protein by using IHC and RT-qPCR. In the uterus, expression of GnRH1 significantly decreased in response to deslorelin treatment in the N-EST, compared with the control group. Compared with CONT, KISS1R expression in ovarian samples was significantly lower in the EST group. Uterine protein expression of GnRH1 appeared weaker in N-EST than in CONT. While GnRH1-system members and KISS1 protein were localized in the follicles at various stages and stroma, no or only weak signals were detected for KISS1R in the ovarian samples. Deslorelin-mediated induction of puberty by changing the expression of some of the GnRH and KISS1-system members seems to have an effect on ovarian and uterine functionality. Deslorelin implants can, therefore, not be considered a valuable alternative to induce fertile estrus in late-prepubertal bitches. However, further studies with a larger number of animals are needed to clarify the effect of deslorelin-mediated induction of puberty.

Dienogest versus gonadotropin-releasing hormone analogues for the clinical treatment of endometriosis: an updated meta-analysis

Endometriosis is a chronic gynecological condition where endometrial-like tissue grows outside the uterus, leading to persistent pelvic pain, dysmenorrhea, dyspareunia, and infertility. The objective of the systematic review was to examine the efficacy and safety of Dienogest, which is a synthetic, orally active 19-nortestosterone derivative, in the treatment of women with endometriosis compared to GnRH-a, which is commonly used to treat conditions like endometriosis. We conducted a search of PubMed, Google Scholar, and Cochrane Library databases from inception until August 2024 for clinical studies, using the following keywords: ("Dienogest") and ("gonadotropin-releasing hormone analogue" or GnRH Analogues OR GnRH agonist) and (Endometriosis). Relevant randomized control trials were identified. Pooled effect estimates were calculated using a random effect model. This meta-analysis included eight randomized controlled trials (RCTs) with 1,219 patients, 602 in the dienogest group and 617 in the GnRH analogue group. Both treatments were equally effective in controlling pain, dysmenorrhea, and dyspareunia, but dienogest offered advantages. Dienogest significantly reduced the recurrence rate (RR: 0.37, 95% CI [0.15, 0.91]; p=0.03) and hot flushes (RR: 0.24, 95% CI [0.10, 0.59]; p=0.002) and protected against bone mineral density (BMD) loss. However, it increased the risk of irregular vaginal bleeding (RR: 3.61, 95% CI [1.09, 11.97]; p=0.04). Other side effects, such as headache, vaginal dryness, spotting, and alopecia, were not statistically significant. It concluded that Dienogest has comparatively fewer side effects than GnRH analogue, making it a considerably safer option for treating endometriosis.

The antidepressant-like effects of kisspeptin-10 are reversed by kisspeptin antagonist peptide 234 in male rats.

Kisspeptins are reported to be the most potent activators of the hypothalamus-pituitary-gonadal (HPG) axis known to date. Kisspeptin potently elicits gonadotropin-releasing hormone (GnRH) release and luteinizing hormone (LH) secretion, even in the pre-pubertal period. Beyond the hypothalamus, kisspeptin is also expressed in limbic and paralimbic brain regions, which are areas of the neurobiological network primarily implicated in emotional behaviors alongside sexual functions. Therefore, an increasing body of studies has implicated kisspeptin as having many influences on emotional behaviors. The study was set out to explore if the kisspeptin/GPR54 signaling system is required for the anti-depressant-like effect of kisspeptin-10 (KP-10), besides the regulation of the HPG axis. To test this concept, peptide 234 (P234), a kisspeptin antagonist, was given to the male rats, and its modulatory effect on the anti-depressant-like effects of kisspeptin was investigated by using a forced swimming test (FST). The study has also sought to know whether kisspeptin can exert its effects through adrenergic and serotonergic receptors. To investigate this, the agents yohimbine (Yoh), an alpha-2 adrenergic receptor antagonist, and cyproheptadine (Cry), a non-selective 5-HT2 serotonergic receptor antagonist, were administered in the experiments. Our results indicate that, in rats, the anti-depressant-like effects of KP-10 in a modified rat FST are mediated by GPR54 receptors, since the kisspeptin antagonist peptide 234 reversed kisspeptin-induced anti-depressant-like effects. Our data also demonstrate that the anti-depressant-like effects of kisspeptin, at least in part, are mediated by an interaction of the alpha-2 adrenergic and 5-HT2 serotonergic receptors.

Reproductive efficiency in Bos indicus and Bos indicus crossed: impact of timed artificial insemination (TAI) using a progesterone and estradiol benzoate-based protocol

ABSTRACT Data from 15,342 bovine females subjected to timed artificial insemination (TAI) were analysed with the objective of assessing the pregnancy rate (PR) and its association with breed, number of uses of intravaginal implant, body condition score (BCS), animal categories, number of AI, and estrus expression before TAI. The protocol involved administering intravaginal progesterone + estradiol benzoate (day zero), progesterone removal + prostaglandin F2α+estradiol cypionate + equine chorionic gonadotropin (day 8) and TAI + gonadotropin-releasing hormone (day 10) in animals without estrus. Crossbred cows demonstrated higher PR. Non-suckling cows, those with 1st – and 2nd-use implants, and a single-dose implant demonstrated higher PR between categories; the BCS (>2.75–3.5) resulted in better overall PR. There were no differences in the general PR between number of AI. 2nd-use implants resulted in a better overall PR. Primiparous cows resulted better PR with 3rd-use implants. Animals in estrus before TAI demonstrated a higher PR. In conclusion, this study observed no significant differences in general PR among number of AI. Second-use implants were effective. Crossed and non-suckling cows, and 1st – and 2nd-use and single-dose implants exhibited higher fertility. Estrus before TAI favoured PR.

Adult Height in Girls with Central Precocious Puberty with Onset after 6 Years: Effects of Gonadotropin-Releasing Hormone Analog Therapy

Introduction: Precocious puberty (PP), which is sometimes divided into gonadotropin-dependent or gonadotropin-independent PP, is a pathological condition characterized by premature secretion of gonadal steroids resulting in the early development of secondary sexual characteristics. Girls younger than 6 years with idiopathic gonadotropin-dependent PP (referred to as central PP or CPP) who receive gonadotropin-releasing hormone analog (GnRHa) therapy experience an increase in their adult height (AH) in contrast to girls who are aged 6 years or more, who show no consistent pattern of increase even with GnRHa therapy. Methods: In total, 133 girls aged 6 years or more who visited any one of the seven study centers between April 2000 and March 2020 and who met the diagnostic criteria for PP in Japan were retrospectively examined. The participants were divided into a treatment (n = 56) and no-treatment group (n = 77). The AH and target height (TH) were compared between the groups, and the factors influencing the AH were examined. Results: The patients receiving GnRHa therapy achieved significantly greater increase in their AH, AH − TH, and predicted AH at the age of 6, 7, and 8 years (6 ≤ years < 9) than those without the treatment. The TH and height at the start and end of treatment influenced the AH of the former group. Conclusion: GnRHa therapy was effective in improving the AH in girls with CPP onset at the age of 6, 7, or 8 years. The TH was a strong determinant of the AH.

Successful Live Birth Outcome in A Patient with Empty Follicle Syndrome: A Case Report and Literature Review.

Here, we report on a rare case of a successful live birth in a patient with empty follicle syndrome. A 35-year-old woman with ovulatory disorder and a 4-year history of primary infertility conducted in vitro fertilization-embryo transfer (IVF-ET) treatment in our hospital. The patient experienced six controlled ovarian stimulation cycles. In the first two cycles, despite adequate ovarian response, normal development of multiple follicles, and normal serum estradiol (E2) levels, no oocytes were retrieved from these mature follicles during the aspiration procedure. The patient was diagnosed with "empty follicle syndrome". Whole exome sequencing (WES) identified a missense mutation in the luteinizing hormone/chorionic gonadotropin receptor (LHCGR). In subsequent cycles, we try to increase the trigger dosage, combine gonadotropin-releasing hormone agonists (GnRH agonist) with human chorionic gonadotropin (HCG) for a dual trigger, supplement with luteinizing hormone (LH)-like active substances during the stimulation process, and extend the time between triggering and oocyte retrieval. In the end, successful oocyte retrieval and pregnancy were achieved.