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With the changes in various factors such as genetics and the environment, the incidence of childhood precocious puberty has been gradually increasing. Improving height is one of the key issues in the clinical management of precocious puberty. Currently, gonadotropin-releasing hormone analogs (GnRHa) remain the preferred treatment for precocious puberty, but their effect on height improvement is influenced by multiple factors, which may result in lower-than-expected height benefits. Combining recombinant human growth hormone (rhGH) therapy with GnRHa treatment is an alternative strategy to enhance the efficacy of GnRHa, but there is still no clear recommendation regarding the timing of their combination. Considering the current status of precocious puberty treatment, it is crucial to reevaluate the effects of GnRHa monotherapy and combination therapy with rhGH on height improvement. This article discusses strategies such as combination therapy indications to guide clinical medication and help children with precocious puberty achieve optimal height benefits.
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Child , Humans , Puberty, Precocious/drug therapy , Human Growth Hormone , Combined Modality TherapyABSTRACT
Non-peptide gonadotropin-releasing hormone antagonist(GnRH-antagonist)is a highly efficient and selective antagonist of GnRH receptor.The oral preparations(Elagolix,Relugolix and Linza-golix)had been approved for listing abroad.It shows efficacy in reducing the size of uterine fi-broid and controlling heavy bleeding.Appropriate combination of'add-back'therapy could improve the safety in medical application and patient com-pliance.Compared with other hormonal pharma-ceuticals,oral GnRH-antagonists showed promising prospects in the treatment of uterine fibroid.
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ABSTRACT Objective: Both pulsatile gonadotropin-releasing hormone (GnRH) and combined gonadotropin therapy are effective to induce spermatogenesis in men with congenital hypogonadotropic hypogonadism (CHH). This study aimed to evaluate the effect of pulsatile GnRH therapy on spermatogenesis in male patients with CHH who had poor response to combined gonadotropin therapy. Materials and methods: Patients who had poor response to combined gonadotropin therapy ≥ 6 months were recruited and shifted to pulsatile GnRH therapy. The rate of successful spermatogenesis, the median time to achieve spermatogenesis, serum gonadotropins, testosterone, and testicular volume were used for data analysis. Results: A total of 28 CHH patients who had poor response to combined gonadotropin (HCG/HMG) therapy for 12.5 (6.0, 17.75) months were recruited and switched to pulsatile GnRH therapy for 10.0 (7.25, 16.0) months. Sperm was detected in 17/28 patients (60.7%). The mean time for the appearance of sperm in semen was 12.0 (7.5, 17.5) months. Compared to those who could not achieve spermatogenesis during pulsatile GnRH therapy, the successful group had a higher level of LH60min (4.32 vs. 1.10 IU/L, P = 0.043) and FSH60min (4.28 vs. 1.90 IU/L, P = 0.021). Testicular size increased during pulsatile GnRH therapy, compared to previous HCG/HMG therapy (P < 0.05). Conclusion: For CHH patients with prior poor response to one year of HCG/HMG therapy, switching to pulsatile GnRH therapy may induce spermatogenesis.
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Background: Ovarian hyperstimulation syndrome (OHSS) has intrigued clinicians for many years because of its devastating consequences. As an iatrogenic condition resulting from elective ovarian stimulation in the quest for pregnancy, the need to completely prevent the syndrome is evident. Gonadotropin releasing hormone (GnRH) antagonist Cetrorelix has found to be effective in treatment of OHSS and some studies have found it to be helpful in prevention of this condition. Hence, we designed a hospital-based study to investigate the effect of Cetrorelix in preventing and treating OHSS in in-vitro fertilization � embryo transfer (IVF朎T) patients at risk of OHSS undergoing long and short protocol.Methods: The study includes total 102 patients undergoing controlled ovarian stimulation COS for IVF/ICSI. All cases were stimulated using long and short protocol. Depending on whether a GnRH antagonist was given after ovum pick-up (OPU) the patients were divided in two groups: Cetrorelix (antagonist) group (n=51) and control group (n=51). The study group was treated with Cetrorelix 0.25 mg for 5 days commencing on the day of ovum pick up.Results: Incidence of mild OHSS was significantly higher (p=0.01) whereas moderate to severe OHSS was significantly lower in the antagonist group (p<0.05). None of the patients had critical OHSS.Conclusions: GnRH antagonist Cetrorelix administration in early luteal phase in patients undergoing long or short protocol is effective in prevention and treatment of OHSS.
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Background: Premenstrual syndrome (PMS) is a significant clinical disorder affecting a substantial percentage of women. This study aims to investigate the existence, knowledge, and attitude of female students towards PMS.Methods: A cross-sectional descriptive study was conducted, with 250 female participants between the ages of 18 to 30 years. The participants completed a self-reporting menstrual distress questionnaire (MDQ) and a standardized health questionnaire to assess the prevalence and severity of premenstrual symptoms and also to assess the knowledge, attitude, and practice of PMS for subjective perceptions of health, stress, lifestyle, and demographic variables. The questionnaire was set in four parts, one each to assess the knowledge, the attitude, and practices regarding PMS and one to assess the gap between self-perceived PMS and actual PMS. The data were analysed using descriptive statistics.Results: The results revealed that 80% of the participants reported experiencing PMS, but only 48% met the criteria defined by the American College of Obstetricians and Gynecologists (ACOG). The most common symptoms reported were irritability, mood swings, headache, fatigue, and menstrual cramps. PMS had a significant impact on participants� normal life, with 60.4% reporting disturbances in their routine. While 51.2% believed that PMS/menstrual leave should be an option at universities, only 39.2% supported the idea at the workplace.Conclusions: Surprisingly, over 60% of participants did nothing to relieve their PMS symptoms. So, there is a significant impact of PMS in the lives of urban women and it is also a common problem all over the globe. The study underscores the need for increased awareness and education about PMS and its management, as well as the importance of promoting a stress-free environment to mitigate its impact on women抯 quality of life.
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ObjectiveTo compare the outcomes in controlled ovarian stimulation （COH） and fresh embryo transfer between women with and those without a high basal luteinizing hormone （bLH） level in polycystic ovary syndrome （PCOS）. MethodsThe clinical data of PCOS patients at the Reproductive Medicine Center of the Sixth Hospital of Sun Yat-sen University from January 2015 to December 2021 were retrospectively analyzed. They were divided into the high group （LH≥10 U/L） and normal group （LH<10 U/L） according to the bLH levels. The results of COH and pregnancy outcomes after fresh transfer were compared， including gonadotropin （Gn） initiation dose， Gn duration， total Gn dose， number of oocytes obtained， two pronuclei （2PN） rate， available embryos rate， high-quality embryos rate， blastocyst formation rate， human chorionic gonadotrophin （HCG） positive rate， clinical pregnancy rate （CPR）， spontaneous abortion rate （SAR）， ongoing pregnancy rate （OPR） and live birth rate （LBR）. The differences in hormonal trends during COH were also analyzed. ResultsThere were no statistically significant differences in age， body mass index， anti-Mullerian hormone， and type of infertility between the two groups. Compared with the normal group， the Gn initiation dose and Gn duration were not statistically significant （P>0.05）， while the total Gn dose was significantly lower （P<0.001） in the high group. The number of oocytes retrieved， 2PN rate， available embryos rate， high-quality embryos rate， and blastocyst formation rate were comparable between the two groups （all P>0.05）. After fresh embryo transfer， they had similar pregnancy outcomes in the HCG positive rate， CPR， SAR， OPR and LBR （all P > 0.05）. ConclusionsIn patients with PCOS， high bLH levels do not affect COH or pregnancy outcomes in fresh transfer cycles. Further studies are needed to determine whether LH levels need to be lowered prior to COH and whether frozen-all strategy is required in patients with elevated bLH levels.
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Manganese plays an important physiological role in the organism, and excessive manganese exposure can cause impairment of neurological and reproductive functions. Gonadotropin-releasing hormone secreted by the hypothalamus acts as an initiator to regulate reproductive functions, such as gonadal development, onset of puberty, and gonadal hormone release. But the mechanism by which manganese damages the hypothalamus leading to abnormal gonadotropin-releasing hormone release is still unclear yet. Kisspeptin, prostaglandin E2, and nitric oxide may act as stimulators to increase the release of gonadotropin-releasing hormone, while the stimulatory or inhibitory effect of γ-aminobutyric acid on the release of gonadotropin-releasing hormone is controversial. Based on current research, manganese has been less studied with Kisspeptin, and studies with prostaglandin E2, nitric oxide, and γ-aminobutyric acid mainly focused on inflammation, oxidative stress, and neurotransmitter transmission. Therefore, taking Kisspeptin, prostaglandin E2, γ-aminobutyric acid, and nitric oxide as the breakthrough points, this paper introduced the mechanism of manganese affecting the release of gonadotropin-releasing hormone in the hypothalamus through the above four pathways, and proposed that the abnormal release of gonadotropin-releasing hormone in the hypothalamus may be one of the mechanisms by which manganese regulates reproductive function, providing a new direction for the prevention and treatment of manganese-induced reproductive damage in the future.
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Puberty is a pivotal biological process that completes sexual maturation to achieve full reproductive capability. It is a major transformational period of life, whose timing is strongly affected by genetic makeup of the individual, along with various internal and external factors. Although the exact mechanism for initiation of the cascade of molecular events that culminate in puberty is not yet known, the process of pubertal onset involves interaction of numerous complex signaling pathways of hypothalamo-pituitary-testicular (HPT) axis. We developed a classification of the mechanisms involved in male puberty that allowed placing many genes into physiological context. These include (i) hypothalamic development during embryogenesis, (ii) synaptogenesis where gonadotropin releasing hormone (GnRH) neurons form neuronal connections with suprahypothalamic neurons, (iii) maintenance of neuron homeostasis, (iv) regulation of synthesis and secretion of GnRH, (v) appropriate receptors/proteins on neurons governing GnRH production and release, (vi) signaling molecules activated by the receptors, (vii) the synthesis and release of GnRH, (viii) the production and release of gonadotropins, (ix) testicular development, (x) synthesis and release of steroid hormones from testes, and (xi)the action of steroid hormones in downstream effector tissues. Defects in components of this system during embryonic development, childhood/adolescence, or adulthood may disrupt/nullify puberty, leading to long-term male infertility and/or hypogonadism. This review provides a list of 598 genes involved in the development of HPT axis and classified according to this schema. Furthermore, this review identifies a subset of 75 genes for which genetic mutations are reported to delay or disrupt male puberty.
Subject(s)
Adolescent , Male , Humans , Adult , Child , Gonadotropin-Releasing Hormone , Gonadotropins/metabolism , Hypogonadism , Testis/metabolism , Puberty/physiology , Sexual MaturationABSTRACT
Objective:To compare the effect of luteal-phase support administration of gonadotrophin-releasing hormone agonist(GnRH-a)on the outcomes of fresh embryo transfer in GnRH antagonist cycles,and explore a more appropriate protocol of luteal-phase support.Methods:A retrospective analysis was performed on the infer-tility patients who receiving in vitro fertilization or intracytoplasmic sperm injection embryo transfer(IVF/ICSI-ET)in the Reproductive Medicine Center of our hospital from January 2018 to December 2021.Our study collected clini-cal data from 674 cycles of infertility patients undergoing fresh cycle transplantation using antagonist regimens.The patients were divided into the control group(n =348)and the observation group(n =326)according to if Gn-RH-a was added to the luteal phase.The patients in control group were given standard luteal support treatment,while the patients in observation group were given multiple-dose GnRH-a 0.1mg to standard luteal support treat-ment after egg retrieval.The general data,ovulation induction and clinical outcome were compared between the two groups.Results:Between the two groups of patients,there was no statistically significant difference in age,years of infertility,body mass index(BMI),basal follicle stimulating hormone(bFSH),days and total amount of gonadotropin(Gn),chorionic gonadotropin(HCG),luteinizing hormone(LH),estradiol(E2)and progesterone(P),the number of retrieved oocytes,MII oocytes,number of embryos,normal fertilization rate,moderate to se-vere ovarian hyperstimulation syndrome(OHSS)rate,abortion rate,live birth rate,multiple pregnancy rate,inci-dence of pregnancy complications,birth weight of offspring,preterm birth rate,and birth defect rate(P>0.05).The implantation rate and clinical pregnancy rate were significantly higher in the observation group compared with control group(P<0.05).Multivariate Logistic regression analysis indicated that age and number of transferred embryos could influence the clinical pregnancy rate(OR 0.958,95%CI 0.917-1.000;OR 1.857,95%CI 1.173-2.942).Conclusions:In fresh embryo transfer cycles with GnRH antagonist protocol,on the basis of conventional luteal support,multi-dose intermittent short-acting GnRH-a for luteal support can achieve a good clin-ical outcome,and may be a suitable luteal support scheme for GnRH antagonist protocol in fresh embryo transfer cycles.
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Objective:To evaluate the efficacy of gonadotropin-releasing hormone agonist (GnRH-a) pretreatment before total hysterectomy for adenomyosis patients with uterine volume ≥12 gestational weeks and moderate or severe anemia.Methods:From January 2018 to March 2023, 689 patients who underwent total hysterectomy for adenomyosis in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. According to the preoperative medication, they were divided into study group (127 cases) and control group (562 cases). Patients in the study group underwent GnRH-a pretreatment for 3 cycles before surgery, and the control group received operation directly. SPSS 26.0 software was used to perform 1∶1 matching for the two groups of patients through the propensity score matching method. Matching variables included age, body mass index, gravidity, parity, history of pelvic and abdominal surgery, menstrual cycle, menstrual period, dysmenorrhea score, initial diagnosis of cancer antigen 125 (CA 125), uterine volume and hemoglobin value. The dysmenorrhea score, uterine volume, hemoglobin value and CA 125 level before and after GnRH-a pretreatment in the study group were compared. And the duration of operation, intraoperative blood loss, postoperative white blood cell count, perioperative blood transfusion cases, postoperative disease rate, duration of hospitalization, total hospitalization cost between the two groups were compared. Results:With propensity score matching, 119 patients in the study group and 119 patients in the control group were finally enrolled in this study. In the study group, before and after the treatment with GnRH-a, the dysmenorrhea score (7.4±1.7 vs 5.6±1.8), uterine volume [(362±160) vs (233±126) cm 3], hemoglobin value [(74.1±10.7) vs (102.5±13.5) g/L], and CA 125 level [(104±76) vs (64±51) kU/L] were statistically different (all P<0.05). There were statistical differences of operation time [(86±18) vs (116±31) minutes], intraoperative blood loss [(24±9) vs (43±22) ml], white blood cell count after 1 day of operation [(9.80±0.10)×10 9/L vs (9.90±0.10)×10 9/L], number of perioperative blood transfusion case [5.9% (7/119) vs 61.3% (73/119)], postoperative disease rate [5.0% (6/119) vs 16.0% (19/119)], hospitalization duration [(7.1±1.6) vs (7.9±1.6) days], and total hospitalization cost [(35 323±5 275) vs (37 159±5 640) yuan] between the study group and the control group (all P<0.05). Conclusion:The pretreatment of using GnRH-a before total hysterectomy for adenomyosis patients with uterine volume ≥12 gestational weeks and moderate or severe anemia is not only conducive to improving dysmenorrhea, signs of anemia, reducing uterine volume, but also conducive to the implementation of surgery, reducing intraoperative and postoperative complications, and reducing hospital costs.
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Androgen deprivation therapy (ADT) using gonadotropin?releasing hormone agonist (s) (GnRH?A) remains the backbone of advanced prostate cancer treatment. In this review, we assessed the efficacy, safety, and convenience of administration of various GnRH?A. All GnRH?A (goserelin, triptorelin, buserelin, histrelin, and leuprorelin) have comparable potential to suppress testosterone (T) levels (?50 ng/dL in a month and ?20 ng/dL in 3 months). However, goserelin has shown better efficacy in maintaining T levels ?50 ng/dL compared with leuprolide. The incidences of T escape are lower with goserelin and leuprolide than buserelin. Goserelin also has maximum benefit in prostate?specific antigen suppression. In neoadjuvant setting, when only goserelin was used, the 10?year overall survival (OS) rate was 42.6% to 86%. When either goserelin or leuprolide was used, the 10?year OS rate was 62%. As an adjuvant to radical prostatectomy, goserelin had a 10?year survival rate of 87%, and triptorelin had an 8?year survival rate of 84.6%. Goserelin further showed an absolute survival rate of 49% when used as an adjuvant to radiotherapy. The survival rates further improved when GnRH?A are used as combined androgen blockade compared with monotherapy. The frequency and severity of adverse events (hot flushes, fatigue, sexual dysfunction) are comparable among the GnRH?A. Goserelin appears to be the most convenient of all the GnRH?A for administration. Lack of conclusive comparative evidence makes it imperative to have a holistic approach of considering the patient profile and the disease characteristics to select the appropriate GnRH?A for ADT in prostate cancer.
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Desde hace varias décadas, los análogos de la hormona liberadora de gonadotrofinas (aGnRH) son el tratamiento de elección en la pubertad precoz central (PPC) en niñas y en niños. Causan una inhibición del eje hipotálamo-hipófiso-gonadal, disminuyen la secreción de gonadotrofinas, estradiol y testosterona; como consecuencia, producen una regresión de los caracteres sexuales secundarios durante el tratamiento. En los últimos años, estos análogos también se utilizan en adolescentes transgénero, en adolescentes y adultas jóvenes con enfermedades oncológicas, en algunas situaciones muy particulares en niños y niñas con talla baja, y en pacientes con trastornos del neurodesarrollo. En Argentina, los más utilizados son el acetato de triptorelina y el acetato de leuprolide en sus formas de depósito. Estos medicamentos han demostrado eficacia y seguridad. El objetivo de esta publicación es realizar una revisión y actualización del uso de los aGnRH en niños, niñas y adolescentes.
For several decades, gonadotropin releasing hormone analogs (GnRHa) are the medical treatment selected for central precocious puberty (CPP) in girls and boys. They generate an inhibition of the hypothalamus-pituitarygonadal axis decreasing LH, FSH, estradiol and testosterone secretion and, in this way, they produce a regression of secondary sexual characters under treatment. In the last years, these analogs are also used in trans adolescents, in adolescents and young adults with oncological diseases, in some very particular situations in children with short stature and in patients with neurodevelopmental disorders. In Argentina the most commonly used formulations are triptorelin and leuprolide acetate depot forms. These analogs have proven both their efficacy and their safety. The aim of this paper is to review and update about the use of GnRHa in children and adolescents.
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Humans , Male , Female , Child , Adolescent , Puberty, Precocious/drug therapy , Gonadotropin-Releasing Hormone/analogs & derivatives , Luteinizing Hormone , Gonadotropin-Releasing Hormone/therapeutic use , Leuprolide/therapeutic use , Triptorelin Pamoate/therapeutic useABSTRACT
Nonobstructive azoospermia (NOA) refers to the failure of spermatogenesis, which affects approximately 1% of the male population and contributes to 10% of male infertility. NOA has an underlying basis of endocrine imbalances since proper human spermatogenesis relies on complex regulation and cooperation of multiple hormones. A better understanding of subtle hormonal disturbances in NOA would help design and improve hormone therapies with reduced risk in human fertility clinics. The purpose of this review is to summarize the research on the endocrinological aspects of NOA, especially the hormones involved in hypothalamic-pituitary-testis axis (HPTA), including gonadotropin-releasing hormone, follicle-stimulating hormone, luteinizing hormone, prolactin, testosterone, estradiol, sex hormone binding globulin, inhibin B, anti-Müllerian hormone, and leptin. For the NOA men associated with primary testicular failure, the quality of currently available evidence has not been sufficient enough to recommend any general hormone optimization therapy. Some other NOA patients, especially those with hypogonadotropic hypogonadism, could be treated with hormonal replacement. Although these approaches have succeeded in resuming the fertility in many NOA patients, the prudent strategies should be applied in individuals according to specific NOA etiology by balancing fertility benefits and potential risks. This review also discusses how NOA can be induced by immunization against hormones.
Subject(s)
Humans , Male , Azoospermia/etiology , Follicle Stimulating Hormone , Luteinizing Hormone , Sperm Retrieval , Testis , Testosterone/therapeutic useABSTRACT
Objective:To investigate the efficacy of gonadotropin releasing hormone agonist (GnRH-a) combined with a levonorgestrel-releasing intrauterine system (Mirena) in patients with adenomyosis and its effects on ovarian function, carbohydrate antigen (CA) 125, CA153 and carcino-embryonic antigen (CEA) expression.Methods:Seventy-eight patients with adenomyosis who received treatment from September 2017 to September 2020 in Shaoxing People's Hospital were included in this study. They were randomly divided into treatment and control groups ( n = 39/group). Patients in the control group were treated with a levonorgestrel-releasing intrauterine system. Patients in the treatment group were treated with GnRH-a, once per month in the first 3 months based on treatment with a levonorgestrel-releasing intrauterine system. After 6 months of treatment, changes in dysmenorrheal relief, menstrual volume, uterine volume, endometrial thickness, ovarian function, CA125, CA153 and CEA levels relative to before treatment were compared. Results:Visual analog scale score and pictorial blood assessment chart score in the treatment group were (1.36 ± 0.28) points and (38.98 ± 5.42) points, which were significantly lower than those in the control group [(1.78 ± 0.31) points, (63.42 ± 6.75) points, t = 6.27, 17.63, both P < 0.05). Uterine volume and endometrial thickness in the treatment group were (209.74 ± 15.65) cm 3 and (7.37 ± 0.57) mm, respectively, which were significantly lower than those in the control group [(278.39 ± 20.90) cm 3, (8.63 ± 0.86) mm, t = 16.45, 7.62, P < 0.05]. There were no significant differences in serum levels of luteinizing hormone, follicle stimulating hormone and estradiol between the two groups (all P > 0.05). Serum CA125, CA153 and CEA levels in the treatment group were (26.87 ± 7.21) U/L, (23.12 ± 7.38) U/mL and (5.45 ± 0.96) μg/L, respectively, which were significantly lower than those in the control group [(49.93 ± 8.97) U/L, (38.94 ± 6.21) U/mL, (8.23 ± 1.35) μg/L, t = 12.51,10.24,10.48, P < 0.05]. Conclusion:GnRH-a combined with a levonorgestrel-releasing intrauterine system (Mirena) can markedly relieve dysmenorrhea, reduce menstrual volume, uterine volume, and endometrial thickness, has no obvious effects on ovarian function, and greatly reduce the levels of CA125, CA153 and CEA. Therefore, the combined method is a safe and effective non-surgical treatment method of adenomyosis.
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Objective:To investigate the efficacy and safety of dienogest (DNG) alone and gonadotropin-releasing hormone agonist (GnRH-a) combined with DNG sequential treatment to adenomyosis.Methods:The clinical data of 110 patients with adenomyosis attending the First Affiliated Hospital of Nanjing Medical University from December 2019 to March 2022 were retrospectively analyzed, including 40 patients treated with DNG (2 mg/day) alone (DNG group) and 70 patients treated with sequential DNG (2 mg/day) after 3-6 injections of GnRH-a (GnRH-a+DNG group). The clinical data before and after treatment were compared between the two groups.Results:(1) The dysmenorrhea visual analogue scale (VAS) scores, cancer antigen 125 (CA 125) and cancer antigen 19-9 (CA 19-9) levels at different time periods after treatment were significantly lower than before treatment in both groups (median before treatment: DNG group 70.0 mm, 68.55 kU/L, 22.45 kU/L respectively, GnRH-a+DNG group 80.0 mm, 151.50 kU/L, 20.44 kU/L respectively; all P<0.001). (2) The hemoglobin (Hb) levels of patients in both groups at different time periods after treatment were significantly higher than those before treatment (median: DNG group 102.00 g/L, GnRH-a+DNG group 94.00 g/L; all P<0.001). (3) Treatment with DNG alone did not have a significant effect on uterine volume in patients of DNG group ( P>0.05), and uterine volume decreased significantly in the 15th-24th months of GnRH-a+DNG group compared with that before treatment (median: 167.76 vs 227.77 cm 3; P<0.05). (4) There were no significant differences in hepatic and renal function and coagulation indexes between the two groups before and after treatment (all P>0.05), and no significant abnormal lesions were observed in breast tissue during the follow-up period. (5) The incidence of amenorrhea of GnRH-a+DNG group was higher than that of DNG group, and the incidences of irregular spotting bleeding and breakthrough hemorrhage were lower than those in DNG group. Conclusions:Whether DNG is used alone or in combination with GnRH-a in sequence, it could significantly relieve dysmenorrhea symptoms, improve the level of Hb, reduce the levels of CA 125 and CA 19-9 in patients with adenomyosis, with no adverse effects on coagulation and hepatic or renal function. GnRH-a sequential DNG therapy is superior to DNG alone in improving uterine bleeding patterns and controlling the growth of uterine volume in patients with adenomyosis.
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Objective:To explore the value of gonadotropin-releasing hormone (GnRH) antagonist in prostate cancer management.Methods:We retrospectively analyzed the data of 92 consecutive hormonal sensitive prostate cancer (HSPC) patients treated with GnRH antagonist from Jan 2019 to March 2022 in Fudan University Shanghai Cancer Center. The median (IQR) age at diagnosis was 70(65-76)years old. Median(IQR) serum prostate-specific antigen (PSA) level before treatment was 98.30 (32.50-436.75)ng/ml. The median (IQR) testosterone level was 12.30(1.51-18.44)nmol/L. Twenty-six(28.3%)cases were in M 0 stage, while 66(71.7%) were in M 1 stage at diagnosis. There were 67(72.8%)cases in ≥T 3 stage, and 54(58.7%)cases in N 1 stage.The Gleason score of 80(87.0%)cases was ≥8.The second generation androgen inhibitor was used in 58(63.0%)cases, and 21(22.8%)cases had specific gene mutation. Patients received a subcutaneously 240mg Degarelix in the first 28 days and 80 mg Degarelix following every 28 days. The pre-injection and 3 months post injection PSA and testosterone (T) level were collected. According to the proportion of patients with the largest decrease in PSA, the patients were divided into high response group (PSA decrease ≥99% after 3 months of use of Degarelix) and low response group (PSA decrease <99% after 3 months of use of Degarelix). Univariate and multivariate logistic analysis were used to analyze the risk factors affecting the treatment response of Degarelix. Results:Among the 92 prostate cancer patients, after 3 months Degarelix treatment, the median PSA value decreased to 0.64ng/ ml ( P <0.001), and the median testosterone value decreased to 0.45nmol/L ( P <0.001). After treatment, there were 48 cases in the high reaction group and 44 cases in the low reaction group. Before treatment, the median PSA in the high-response group was 100.00(67.11-444.25) ng/ml, higher than 88.50 (9.91-582.25) ng/ml in the low-response group, but not statistically significant ( P=0.077). The median testosterone level in the high response group was 13.82 (7.53-19.43) nmol/L, which was significantly higher than that in the low response group [4.61 (0.75-16.12) nmol/L, P =0.030]. After treatment, the median PSA in the high-response group was 0.22 (0.09-0.82) ng/ml, significantly lower than that in the low-response group [3.22 (0.19-15.88) ng/ ml, P<0.001]. The median testosterone value of the high reaction group was 0.40 (0.09-0.80) nmol/L and that of the low reaction group was 0.45 (0.02-0.65) nmol/L, which showed no significant difference ( P =0.826), and both reached the level of castration (<1.7nmol/L). Univariate analysis showed that age ≤ 65 years old was a good prognostic factor ( OR=0.333, 95% CI 0.119-0.810, P =0.017); T stage ( P =0.540), N stage ( P =0.363), M stage ( P =0.660), Gleason score ( P =0.834), application of second-generation antiandrogens ( P=0.238) and gene mutation ( P =0.525) were not related to Degarelix hyperresponsiveness. In multivariate analysis, age was the only independent favorite prognostic factors( OR=0.913, 95% CI 0.847-0.983, P=0.016). Conclusions:In the real world, GnRH antagonists significantly reduced the levels of testosterone and PSA in HSPC patients after 3 months of treatment regardless of TNM stage, Gleason score, and the second generation androgen inhibitor using.
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Objective:To observe the effect of Jiuwei Chushi Decoction on sex hormone level of serum and Kisspeptin protein expression in hypothalamus of Central Precocious Puberty (CPP) rats model.Methods:After sixty female rat were breeded from SD rats, they are randomly divided into six groups, which are normal control group, model group, Gonadorelin group, and high, medium and low dose group of Jiuwei Chushi Decoction, 10 in each group. In addition to the normal control group, the other groups were subcutaneously injected with N-methyl-DL-aspartic acid to establish CPP model. Gonadorelin group was subcutaneously injected with Gonadorelin 100 μg/(kg·d), and high, medium and low dose group of Jiuwei Chushi Decoction were intragastrated with Jiuwei Chushi Decoction extract at 5.75, 2.87 and 1.43 ml/(kg·d) respectively. The levels of Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH),Estradiol (E 2) were detected by ELISA, and the protein expressions of Gonadotropin-releasing Hormone (GnRH) and Kisspeptin in hypothalamus were detected by Western Blot. Results:Compared with the model group, the levels of LH and E 2 of the low, medium and high dose group of Jiuwei Chushi Decoction were significantly decreased ( P<0.05), while the FSH level was significantly increased ( P<0.05). The relative protein expression of GnRH (0.657±0.110, 0.536±0.152 vs. 0.912±0.219) and Kisspeptin (0.508±0.035,0.347±0.073 vs. 0.659±0.030) in the medium and high dose group of Jiuwei Chushi Decoction was lower than that of model group. Conclusion:Jiuwei Chushi Decoction could affect hypothalamic Kisspeptin protein expression, inhibite hypothalamic GnRH expression, and decrease LH and E 2 levels in the serum of CPP rats.
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Central precocious puberty (CPP) is a common pediatric endocrine disease caused by premature activation of the hypothalamic-pituitary-gonadal axis, featured by rapid development of internal and external reproductive organs and secondary sexual characteristics in girls before age 8 and boys before age 9.The gonadotropin-releasing hormone analogue (GnRHa) is the first choice for the treatment of CPP.Currently, 3.75 mg/ month sustained -release short-acting dosage form (1M depot formulations) is the most commonly used in China.The development of long-acting dosage form will reduce injection times and clinic visits.At present, the 3-month long-acting dosage form (11.25 mg 3M depot formulations) of Leprorelin microsphere has been approved in China.However, clinical practice experience of 3-month Leuprorelin acetate depot formulations is lacking in China.Therefore, in this paper, existing clinical evidence for this dosage form was reviewed to provide evidence-based medicine support for its clinical application.
ABSTRACT
Introducción: Los leiomiomas uterinos son los tumores pélvicos benignos más comunes entre las mujeres. Se estima que 60% de las mujeres llegan a tener miomatosis a lo largo de la vida (1). La necesidad de tratamiento médico y/o quirúrgico es muy importante de evaluar, ya que los fibromas son una fuente importante de morbilidad ginecológica. Objetivos: Describir el caso de un gran mioma uterino con manejo prequirúrgico de análogos de GnRH, analizando los hallazgos obtenidos en el caso según la evidencia actual. Discusión: Se reporta el caso de una mujer de 29 años sin antecedentes mórbidos conocidos, con presencia de una gran masa abdominal, motivo por el cual se realizó una ecotomografía abdominal que evidenció una masa sugerente de un gran mioma uterino subseroso. Se realizó miomectomía vía laparotomía previo tratamiento médico con análogos de GnRH. Actualmente la frecuencia de miomas de gran tamaño es poco frecuente, por lo que se busca discutir el impacto del tratamiento médico previo a la cirugía en mujeres jóvenes. Conclusiones: La experiencia con el uso prequirúrgico de agonistas de GnRH indica una ventaja en el trabajo bien definida y su uso como tratamiento coadyuvante a la cirugía está bien establecido. Sin embargo, se debe tener en cuenta la posibilidad de recurrencia de los miomas
Introduction: Uterine leiomyomas are the most common benign pelvic tumors in women. It is estimated that 60% of women develop myomatosis throughout life (1). The need for medical and / or surgical treatment is very important to assess, since fibroids are an important source of gynecological morbidity. Objectives: To describe the case of a large uterine myoma with presurgical management of GnRH analogues and to summarize updated evidence on their use. Discussion: The case of a 29-year-old woman with no known morbid history is reported, with the presence of a large abdominal mass, which is why an abdominal ultrasound scan was performed, which revealed a mass suggestive of a large subserous uterine myoma. Myomectomy was performed via laparotomy after medical treatment with GnRH analogues. Currently, the frequency of large fibroids is rare, so we seek to discuss the impact of medical treatment prior to surgery in young women. Conclusions: Experience with the presurgical use of GnRH agonists indicates a well-defined treatment advantage and its use as adjunctive treatment to surgery is well established. However, the possibility of recurrence of fibroids should be taken into account
Subject(s)
Humans , Female , Adult , Uterine Neoplasms/drug therapy , Gonadotropin-Releasing Hormone/therapeutic use , Leiomyoma/surgery , Leiomyoma/drug therapy , Gynecologic Surgical Procedures , Uterine Neoplasms/diagnostic imaging , Leiomyoma/diagnostic imagingABSTRACT
RESUMEN Conclusiones del estudio: El análisis general no indica beneficio de la terapia combinada (análogo de hormona liberadora de gonadotropina [GnRHa] + hormona de crecimiento humana recombinante [rhGH]) versus solo GnRHa, solo rhGH o ausencia de tratamiento. Sin embargo, hay beneficios en mayor o menor medida en ciertas subpoblaciones. Comentario crítico: El artículo es relevante al no haber previamente un meta-análisis sobre la terapia combinada. Por otro lado, es importante ya que la terapia combinada implica el uso de rhGH, el cual puede ser costoso, de difícil adherencia y conllevar a efectos adversos. Además, la conclusión general del artículo - no usar terapia combinada - es aplicable. Sin embargo, falta la evaluación de sesgo de publicación y de reporte selectivo, y hay conclusiones secundarias que requieren una mejor explicación. La presente revisión crítica no encuentra evidencia suficiente para sugerir que la terapia combinada pueda ser efectiva en alguna subpoblación.
ABSTRACT Study conclusions: The overall analysis does not indicate benefit of combination therapy (gonadotropin-releasing hormone analog [GnRHa] + recombinant human growth hormone [rhGH]) versus GnRHa alone, rhGH alone, or no treatment. However, there are benefits to a greater or lesser extent in certain subpopulations. Critical comment: The article is relevant as there was no previous meta-analysis on combination therapy. On the other hand, it is important since combination therapy involves the use of rhGH, which can be expensive, difficult to adhere to, and lead to adverse effects. Furthermore, the general conclusion of the article - do not use combination therapy - is applicable. However, the assessment of publication bias and selective reporting is lacking, and there are secondary conclusions that require better explanation. The present critical review does not find sufficient evidence to suggest that combination therapy may be effective in any subpopulation.