Research progress of manganese exposure on abnormal GnRH release in hypothalamus affecting reproductive function / 环境与职业医学

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.

Effect of Elevated Basal LH on IVF-ET Outcomes in Patients with Polycystic Ovary Syndrome / 中山大学学报(医学科学版)

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.

A classification of genes involved in normal and delayed male puberty / 亚洲男科学杂志(英文版)

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.

Evaluation of the efficacy of GnRH-a pretreatment before total hysterectomy for adenomyosis patients: a propensity score matching analysis / 中华妇产科杂志

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.

Gonadotropin?releasing hormone agonists in prostate cancer: A comparative review of efficacy and safety

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.

Tratamiento con análogos de la hormona liberadora de gonadotrofinas (aGnRH) en niñas, niños y adolescentes / Treatment with gonadotropin-releasing hormone analogs (GnRHa) in childhood and adolescence

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.

Efficacy of dienogest versus gonadotropin-releasing hormone agonist combined with dienogest sequential therapy in the treatment of adenomyosis / 中华妇产科杂志

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.

Research progress of the efficacy and safety of 3-month depot Leuprorelin in the treatment of central precocious puberty / 中华实用儿科临床杂志

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.

Effects of Jiuwei Chushi Decoction on sex hormone and Kisspeptin protein expression of Central Precocious Puberty rats / 国际中医中药杂志

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.

Clinical efficacy of GnRH-a combined with a levonorgestrel-releasing intrauterine system (Mirena) in patients with adenomyosis and its effects on ovarian function, CA125, CA153 and CEA expression / 中国基层医药

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.

Endocrine aberrations of human nonobstructive azoospermia / 亚洲男科学杂志(英文版)

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.

Study of gonadotropin-releasing hormone antagonist in management of hormonal sensitive prostate cancer / 中华泌尿外科杂志

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.

Gran mioma uterino: manejo prequirúrgico con uso de agonistas de gnrh: reporte de un caso / Large uterine myoma: presurgical management with the use of gnrh agonists: case report

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

Ausencia de beneficio de la terapia combinada con análogo de hormona liberadora de gonadotropina (GnRHa) y hormona de crecimiento humana recombinante (rhGH) en pacientes con pubertad temprana o precoz / Lack of benefit from combined therapy with gonadotropin-releasing hormone analog (GnRHa) and recombinant human growth hormone (rhGH) in patients with early or precocious puberty

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.

Short-term Administration of Gonadotropin-releasing Hormone Agonist (Buserelin) Induces Apoptosis in Rat Ovarian Developmental Follicles

ABSTRACT Objective: To investigate the effects of buserelin on the development of follicles, apoptosis index and steroid hormones level. Methods: Twenty-four 3-month-old female rats were randomly divided into three groups: a low-dose group, a high-dose group and a control group (n = 8). Buserelin and normal saline were injected subcutaneously for 5 days. Thirty days after the first injection, the ovaries were removed for staining. Blood samples were collected and centrifuged. Their serum was used for measuring estradiol and progesterone levels, using enzyme-linked immunosorbent assay. Results: The findings revealed a significant decrease in the mean of secondary and Graafian follicles in the high-dose group compared with the control group (p = 0.037, p = 0.034, respectively). The serum estradiol level increased significantly in the high-dose group, compared with the low-dose and control groups (p = 0.027, p = 0.047, respectively). The serum progesterone level decreased, although not significantly. In contrast to the control group, the significant increase of apoptotic cell death was found in primordial, unilaminar and multi-laminar follicles in the high-dose group (p = 0.004, p = 0.049, p = 0.047, respectively). Conclusion: The findings of this study suggest that short-term administration of high-dose buserelin increases the serum estradiol level and apoptosis in the granulosa cells but has an inhibitory effect on follicular development.

A survey of urologists on gonadotropin-releasing hormone agonist therapy for prostate cancer / 中华泌尿外科杂志

Objective:To investigate the current perceptions, treatment patterns and unmet needs of androgen deprivation therapy (ADT) on treating prostate cancer (PCa) by gonadotropin-releasing hormone agonist (GnRH-a) in Chinese urologists.Methods:The survey was conducted between July 2020 and August 2020. Questionnaires were designed to investigate the urologists employed by 163 grade A tertiary hospitals from 7 districts (North, Northeast, East, South, Central, Southwest, Northwest) across China. The inclusion criteria were urologists who had the title of attending physician or above, had experience of prescribing GnRH-a, and agreed to participate in the survey. An electronic self-administered structured questionnaire was used for data collection, with a target sample size of 300, covering treatment patterns, experience of GnRH-a prescription, and unmet needs of GnRH-a.Results:There were 13 886 questionnaires had been distributed, among which 410 questionnaires had met the inclusion criteria. After excluding 110 incomplete questionnaires, 300 valid questionnaires were included in the analysis. The average number of PCa patients administered castration treatment per urologist per month was 12±8. Monthly GnRH-a injection was more often used than quarterly GnRH-a injection[(62.0±24.7)% vs. (38.0±24.7)%]. The main follow-up frequency for patients receiving GnRH-a was once a month as reported by 49.3% (148/300) of urologists. GnRH-a injection frequency (31.3%, 94/300), prostate-specific antigen (PSA) testing frequency (27.7%, 83/300) and clinical effectiveness (26.0%, 78/300) were reported as top factors determining the follow-up frequency. Only 46.0% (138/300) urologists believed that over 70.0% of the patients were completely adherent to the prescribed treatment. When deciding which GnRH-a product to be prescribed, the top 4 factors considered by urologists were effectiveness (92.0%, 276/300), adverse events (85.7%, 257/300), economic burden (76.7%, 230/300), and frequency of injection (61.3%, 184/300). The urgency of improvement for each aspect of GnRH-a therapy was evaluated with a 5-point Likert scale (from 1 (not urgent) to 5 (extremely urgent)). The top 4 aspects needing further improvement were effectiveness (4.04±0.93), economic burden (3.93±0.84), adverse events (3.90±0.90), and frequency of injection (3.60±0.93). A 5-point Likert scale (from 1 (not influential) to 5 (extremely influential)) was also applied to evaluate factors influencing patients’ quality of life and the top 4 factors were pain (4.09±0.94), psychological stress (3.61±0.90), adverse events (3.46±0.89), and discomfort caused by frequent GnRH-a injection (3.34±0.91).Conclusions:Most urologists in China hoped that GnRH-a therapy could have reduced injection frequency, improved effectiveness, reduced economic burden and decreased adverse events in order to increase patient’s adherence and to improve the effectiveness of PCa treatment as well.

GnRH-a combined fertility-sparing re-treatment in women with endometrial carcinoma or atypical endomertial hyperplasia who failed to oral progestin therapy / 中华妇产科杂志

Objective:To analyze the clinical efficacy and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based fertility-sparing re-treatment in women with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) who failed with oral progestin therapy.Methods:Forty cases with EC or AEH who failed to respond to oral progestin were included from January 2012 to December 2020 at Peking Union Medical College Hospital. Combination of GnRH-a with levonorgestrel-releasing intrauterine system (group GLI: a subcutaneous injection of GnRH-a every 4 weeks and LNG-IUS insertion constantly) or the combination of GnRH-a with aromatase inhibitor (group GAI: a subcutaneous injection of GnRH-a every 4 weeks and oral letrozole 2.5 mg, daily) were used for these patients. Histological evaluation were performed at the end of each course (every 3-4 months) by hysteroscopy and curettage. After the complete remission (CR), all patients were followed up regularly.Results:(1) Clinical characteristics:among the 40 patients with EC or AEH, the median age at diagnosis was 31 years (range: 22-40 years) and the median body mass index was 24.7 kg/m 2 (range: 18.9-39.5 kg/m 2). (2) Efficacy of fertility-sparing re-treatment: 37 (92%, 37/40) patients achieved CR, 6 (6/7) in AEH and 31 (94%, 31/33) in EC patients. The CR rate was 93% (26/28) and 11/12 in group GLI and GAI, respectively. The median time to CR was 5 months (range: 3-12 months). At the end of the first therapy course, the CR rates in AEH and EC were 5/7 and 42% (14/33), at the second course, the CR rates were 6/7 and 82% (27/33), respectively. (3) Recurrence: after 25 months of median follow-up duration (range: 10-75 months), 8 (22%, 8/37) women developed recurrence, 1/6 in AEH and 7 (23%, 7/31) in EC patients, with the median recurrence time of 18 months (range: 9-26 months). Among them, two cases who had completed childbirth chose to receive hysterectomy directly. Six patients met the criteria of fertility-preserving therapy and received conservative treatment again and 5 (5/6) of them achieved CR. (4) Pregnancy: of the 37 patients with CR, 33 desired to conceive. Ten women attempted to get pregnancy spontaneously and 23 cases with assisted reproductive technology. Fourteen (42%, 14/33) patients became pregnant, including 9 (27%, 9/33) live births, 3 (9%, 3/33) missed abortions, and 2 (6%, 2/33) miscarriages at the second trimester. Conclusions:GnRH-a based fertility-sparing re-treatment in AEH or EC patients who failed with oral progestin therapy achieved good treatment effect and reproductive outcomes. It is an encouraging alternative regime for patients who failed with oral progestin therapy.

Impact of trigger timing of gonadotropin-releasing hormone antagonist regimen for infertility patients of various ages / 中华妇产科杂志

Objective:To investigate the impact of trigger timing of gonadotropin- releasing hormone (GnRH) antagonist regimen for infertility patients of various ages.Methods:This was a retrospective study, 1 529 infertility patients who receiving GnRH antagonist regimen in Chongqing Health Center for Women and Children from January 2017 to December 2018 were divided into the advance trigger group and the standard trigger group, and further divided into three subgroups according to age:<35 years, 35-40 years,>40 years. The number of retrieved oocytes and transplantable embryos, the clinical pregnancy rate and the live birth rate among patients in the advance trigger group and standard trigger group in various age subgroups were compared.Results:(1) The gonadotropin (Gn) days among the three age subgroups were significantly shorter in the advance trigger group compared to the same-aged standard trigger group (all P<0.01), but only in the 35－40 years and >40 years subgroups, the Gn doses in the advance trigger group [(2 702±551) and (2 780±561) U] were significantly less than those in the standard trigger group (all P<0.01). In the <35 years subgroup, the number of oocytes retrieved and transplantable embryos of the advance trigger group (6.6±4.8 and 2.6±2.7) were significantly less than those of the standard trigger group (all P<0.01), but there was no difference in the number of top-quality embryos ( P=0.580); however, in the 35－40 years and >40 years subgroups, there were no significant differences between advance and standard trigger groups in terms of the afore mentioned 3 indicators (all P>0.05), only the numbers of top-quality embryos in the advance trigger group (0.6±1.0 and 0.6±0.9) were significantly higher than those in the standard trigger group (all P<0.01). (2) In the <35 years and 35－40 years subgroups, no significant differences were noted between the advance trigger group and standard trigger group with regard to the clinical pregnancy rate and live birth rate (all P>0.05); but in the >40 years subgroup, the clinical pregnancy rate of the advance trigger group was significantly higher than that of the standard trigger group [33.0% (30/91) vs 19.2% (25/130), P=0.020], and there was no statistical difference in the live birth rate ( P=0.064). (3) Multivariate logistic regression analysis showed that trigger timing was an independent predictor of clinical pregnancy rate in the >40 years subgroup ( OR=0.334, 95% CI: 0.119-0.937, P=0.037), but not an independent predictor of live birth rate ( P>0.05). Conclusions:Advance trigger in the GnRH antagonist protocol for infertility patients >40 years old could effectively reduce Gn times and Gn dosage, increase the number of top-quality embryos, and improve the clinical pregnancy rate. Therefore, compared with patients ≤40 years of age, patients >40 years might benefit more from advance trigger.

Effect of gonadotropin-releasing hormone analogue treatment in improving final adult height of children with central precocious puberty or early and fast puberty: a Meta analysis / 中国当代儿科杂志

OBJECTIVES@#To systematically evaluate the effect of gonadotropin-releasing hormone analogue (GnRHa) treatment on the final adult height of children over 6 years of age with central precocious puberty (CPP) or early and fast puberty (EFP).@*METHODS@#PubMed, MEDLINE, Embase, Cochrane Library, CNKI, and Wanfang Data were searched for related articles on GnRHa treatment for children with CPP or EFP. Stata 12.0 software was used to perform a Meta analysis of related data.@*RESULTS@#A total of 10 studies were included, and the total sample size was 720 children, with 475 children in the GnRHa treatment group and 245 children in the control group. The Meta analysis showed that compared with the control group, the GnRHa treatment group had significantly better final adult height (@*CONCLUSIONS@#GnRHa treatment is safe and effective in improving the final adult height of children over 6 years of age with CPP or EFP.

Study on Therapeutic Effect and Related Mechanism of Fuyou Granule on Precocious Puberty in SD Female Rats / 中国实验方剂学杂志

Objective:To study the effect and related mechanism of Fuyou granule on danazol-induced precocious puberty model in rats. Method:Totally 21 cages of SD female rats were randomly divided into normal group， model group， Leuprorelin（0.1 g·kg^-1） and Fuyou mixture group（37.9 g·kg^-1）， and high-dose， mid-dose and low dose Fuyou granule<italic> </italic>groups（17.0，8.5，4.3 g·kg^-1）. Rats at 5 days of age were given a single subcutaneous injection of 300 μg danazol to establish the precocious puberty model. After 10 days of modeling， drug intervention was started. Vaginal opening was examined at the age of 20 days， and the gonadal development was observed by hematoxylin-eosin （HE） staining. The levels of serum luteinizing hormone （LH）， follicle-stimulating hormone （FSH） and estradiol （E₂） were determined by radioimmunoassay. The mRNA expressions of hypothalamic gonadotropin releasing hormone （GnRH）， Kiss-1， G protein-coupled receptor 54 （GPR54） were detected by Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and the expression of GnRH cells in the hypothalamus was detected by immunohistochemistry. Result:Compared with the normal group， the vaginal opening of the model group was significantly earlier， and the uterus and ovarian coefficients were significantly increased （<italic>P</italic><0.05）， indicating that the danazol-induced precocious puberty model was successfully established. The expression levels of GnRH， Kiss-1， and GPR54 also increased significantly （<italic>P</italic><0.05）， indicating that the danazol model can activate the HPG axis in advance， thereby inducing precocious puberty<bold>. </bold>Compared with the model group， the mid-dose Fuyou granule group significantly delayed the time of vaginal opening （<italic>P</italic><0.01）， high-dose Fuyou granule group<italic> </italic>significantly reduced uterine wall thickness and uterine coefficient （<italic>P</italic><0.05，<italic>P</italic><0.01）， mid-dose group reduced ovarian coefficient and uterine wall thickness （<italic>P</italic><0.05）. All the three dosage groups of Fuyou granule significantly reduced the content of serum hormones E₂， LH and FSH （<italic>P</italic><0.05，<italic>P</italic><0.01）， reduced the expression levels of hypothalamic GnRH， Kiss-1 and GPR54 mRNA （<italic>P</italic><0.05）， and decreased the expression of GnRH cells （<italic>P</italic><0.05）. Conclusion:Fuyou granule can achieve therapeutic precocity by regulating the Kiss-1/GPR54 system and down-regulating the expression of GnRH to inhibit the activation of the HPG axis.