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.

Diagnostic value of urinary luteinizing hormone levels in the monitoring of precocious puberty treatment

ABSTRACT Objective To determine whether first-voided urinary LH (FV-ULH) - level measurement can adequately assess pubertal suppression as much as standard tests can. Subjects and methods The study group included patients with central precocious puberty and rapidly progressing early puberty who received up to 3 - 4 doses of GnRHa therapy monthly and did not have adequate hormonal suppression after GnRH stimulation (90-minute LH level > 4 IU/L). Design: All of the participants underwent an LHRH test just after admission to the study. According to the stimulated peak LH levels, the patients were divided into 2 groups and followed until the end of the first year of treatment. The concordance between FV-ULH and stimulated LH levels was assessed. Results The FV-ULH levels in patients with inadequate hormonal suppression were significantly high compared to patients with adequate hormonal suppression. FV-ULH levels were very strongly correlated with stimulated LH levels (r = 0.91). Its correlation with basal LH levels was significant (r = 0.65). However, this positive correlation was modestly weakened after the first year of treatment. The cutoff value for FV-ULH of 1.01 mIU/mL had the highest sensitivity (92.3%) and specificity (100%). Conclusion FV-ULH levels, using more reliable and sensitive assay methods, can be used to monitor the adequacy of GnRHa therapy.

Investigation of the effect of GnRH (deslorelin) on the histochemical structure of salivary glands in rats / Investigación del efecto de la GnRH (deslorelina) sobre la estructura histoquímica de las glándulas salivales en ratas

This study was planned to determine the histochemical alterations of the submandibular gland by implantation of long-term GnRH (deslorelin 4.7 mg). Eighteen Wistar albino rats were used in the study. Alcian blue (AB; pH: 2.5), periodic acid-Schiff (PAS) staining was performed to determine the microscopic structure and histochemical structure of the GI submandibular gland. The Avidin-Biotin Complex (ABC) method was used to determine the immunohistochemical reactivity of lectin. After GnRH implantation, the organs were examined and atrophies were observed in organs. In the group in which the implants were removed, it was determined that there was no atrophy; organ structures and microscopic examination were similar to the control group. At the end of the study, submandibular gland was fixed in 10 % buffered formaldehyde. In three groups, PAS and AB histochemical staining revealed similar reactions. Immunohistochemically, lectin activity was found to react positively.

Este estudio se planificó para determinar las alteraciones histoquímicas de la glándula submandibular mediante la implantación de GnRH a largo plazo (deslorelina 4,7 mg). Dieciocho ratas Wistar albinas se utilizaron en el estudio. Para determinar la estructura microscópica e histoquímica de la glándula submandibular, se realizó una tinción con azul alcián (AA; pH: 2.5) y ácido peryódico de Schiff (PAS). El método Avidin-Biotin Complex (ABC) se utilizó para determinar la reactividad inmunohistoquímica de la lectina. Después de la implantación de GnRH, se examinaron los órganos y se observó atrofia en ellos. En el grupo en el que se retiraron los implantes, no se observó atrofia. Las estructuras orgánicas y el examen microscópico fueron similares al grupo control. Al final del estudio, la glándula submandibular se fijó en formaldehído tamponado al 10 %. En tres grupos, la tinción histoquímica de PAS y AA reveló reacciones simila4res. Inmunohisto-químicamente, se encontró que la actividad de la lectina reaccionó positivamente.

Does lower dose of long-acting triptorelin maintain pituitary suppression and produce good live birth rate in long down-regulation protocol for in-vitro fertilization? / 华中科技大学学报（医学）（英德文版）

The effects of pituitary suppression with one-third depot of long-acting gonadotropin-releasing hormone (GnRH) agonist in GnRH agonist long protocol for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) were investigated. A retrospective cohort study was performed on 3186 cycles undergoing IVF/ICSI with GnRH agonist long protocol in a university-affiliated infertility center. The pituitary was suppressed with depot triptorelin of 1.25 mg or 1.875 mg. There was no significant difference in live birth rate between 1.25 mg triptorelin group and 1.875 mg triptorelin group (41.2% vs. 43.7%). The mean luteinizing hormone (LH) level on follicle-stimulating hormone (FSH) starting day was significantly higher in 1.25 mg triptorelin group. The mean LH level on the day of human chorionic gonadotrophin (hCG) administration was slightly but statistically higher in 1.25 mg triptorelin group. There was no significant difference in the total FSH dose between the two groups. The number of retrieved oocytes was slightly but statistically less in 1.25 mg triptorelin group than in 1.875 mg triptorelin group (12.90±5.82 vs. 13.52±6.97). There was no significant difference in clinical pregnancy rate between the two groups (50.5% vs. 54.5%). It was suggested that one-third depot triptorelin can achieve satisfactory pituitary suppression and produce good live birth rates in a long protocol for IVF/ICSI.

Informe técnico sobre cobertura de triptorelina para preservación ovárica e infliximab para enfermedad de injerto contra el huésped refractario a corticoides post trasplante de progenitores hematopoyéticos en niños / Technical report on triptorelin coverage for ovarian preservation and infliximab for graft-versus-host disease in post-transplant recipients of hematopoietic progenitors in children

El Fondo Intangible Solidario de Salud solicita las evaluaciones de las tecnologías: triptorelina para preservación ovárica en mujeres que tienen indicaciones de recibir quimioterapia por câncer de mama; Infliximab para el tratamiento de la enfermedad de injerto contra el huésped refractario a corticoides post trasplante de progenitores hematopoyético en niños. Las indicaciones solicitadas para evaluación de las tecnologías triptorelina e infliximab no corresponden a la indicación terapéutica referida en ficha técnica proporcionada por la industria por lo que se desestima su evaluación para cobertura por el Seguro Integral de Salud.

Development of a subcutaneous endometriosis rat model

PURPOSE: To present a rat model of subcutaneous endometriosis for the study of pathophysiology and the effects of drugs. METHODS: Fifty three-month-old female Wistar rats (Rattus norvergicus) were distributed into one control group and four treatment groups: estradiol (2.5; 5; 10mg/kg sc), medroxyprogesterone acetate (0.5; 2; 5mg/kg sc), triptorelin pamoate (0.18; 0.56mg/kg sc) and acetylsalicylic acid (3mg/kg per os). The animals were autoimplanted subcutaneously with 4x4-mm uterine fragments to induce endometriosis. The endometriomas were measured on days 1, 7, 14 and 21. The relative dry and wet weights of the endometrioma were used to evaluate response to the drug. Endometrial -like tissue was confirmed by histology. The greatest weight gain was observed on day 14 (relative wet weight: 29.1 ± 6.7mg%, relative dry weight: 5.3 ± 0.9mg %). Treatments were administered between day 5 and day 14. RESULTS: The relative wet weight of the hemiuterus in the 10mg/kg estradiol group differed significantly from control and the other two estradiol groups (p=0.0001). In the medroxyprogesterone acetate group the weight decreased significantly but this decrease was not dose-dependent. Weight reduction was also significant in the triptorelin pamoate and the acetylsalicylic acid groups. CONCLUSION: The model of subcutaneous endometriosis is reproducible, low-cost and easy to perform, and suitable for the study of pathophysiology and the effects of drugs. .

Significant adverse reactions to long-acting gonadotropin-releasing hormone agonists for the treatment of central precocious puberty and early onset puberty

PURPOSE: Long-acting gonadotropin-releasing hormone agonists (GnRHa) are commonly used to treat central precocious puberty (CPP) in Korea. Although rare, there have been reports on the characteristic of adverse reactions of GnRHa in CPP among the Korean population. This study was intended to report on our clinical experience regarding significant adverse reactions to long-acting GnRHa in CPP and early onset puberty and to evaluate the prevalence rate of serious side effects. METHODS: This retrospective study included children with CPP and early onset puberty, who were administered monthly with long-acting GnRHa (leuprolide acetate, triptorelin acetate) at the outpatient clinic of Department of Pediatrics, at Inha University Hospital, between January 2011 and December 2013. We analyzed the clinical characteristics of patients who experienced significant adverse reactions and evaluated the prevalence rate. RESULTS: Six serious side effects (0.9%) were observed among total of 621 CPP and early onset puberty children with GnRHa therapy. The number of sterile abscess formation was four in three patients (4 events of 621). Anaphylaxis occurred in only one patient, and unilateral slipped capital femoral epiphysis (SCFE) in another one patient. Anaphylaxis occurred after the 6th administration of the monthly depot triptorelin acetate. Unilateral SCFE developed in GnRHa therapy. CONCLUSION: Sterile abscess formation occurred in 0.6% of CPP and early onset puberty patients from the administration of a monthly depot GnRHa therapy. The occurrences of anaphylaxis and SCFE are extremely rare, but can have serious implications on patients. Clinicians should be aware of these potential adverse effects related to GnRHa therapy in CPP.

Sterile Abscess Formation Associated with Two Different Forms of Gonadotropin-Releasing Hormone Agonist in Central Precocious Puberty

Long-acting formulations of gonadotropin-releasing hormone (GnRH) agonists are indicated for treating central precocious puberty. Leuprolide acetate and triptorelin acetate are widely used in Korea. Local reactions related to GnRH agonists, including erythematous macules, granulomas, subcutaneous nodules, and sterile abscesses, are the most side effects and sterile abscesses occur in less than 2-3% of treated patients. We report on two patients who had been injected with leuprolide acetate for the treatment of central precocious puberty and who subsequently presented with a sterile abscess at the injection sites. After the patients were switched to triptorelin acetate, one patient had another subcutaneous abscess at the injection site, and the other patient had no further problems. There are many theories as to the cause of these local reactions, but the mechanism has still not been elucidated. Further studies are required to identify the mechanism and the relationship between treatment effect and local reaction.

Sterile Abscess Formation Associated with Two Different Forms of Gonadotropin-Releasing Hormone Agonist in Central Precocious Puberty

Long-acting formulations of gonadotropin-releasing hormone (GnRH) agonists are indicated for treating central precocious puberty. Leuprolide acetate and triptorelin acetate are widely used in Korea. Local reactions related to GnRH agonists, including erythematous macules, granulomas, subcutaneous nodules, and sterile abscesses, are the most side effects and sterile abscesses occur in less than 2-3% of treated patients. We report on two patients who had been injected with leuprolide acetate for the treatment of central precocious puberty and who subsequently presented with a sterile abscess at the injection sites. After the patients were switched to triptorelin acetate, one patient had another subcutaneous abscess at the injection site, and the other patient had no further problems. There are many theories as to the cause of these local reactions, but the mechanism has still not been elucidated. Further studies are required to identify the mechanism and the relationship between treatment effect and local reaction.

Manejo de las terapias hormonales para el tratamiento del cáncer de próstata avanzado hormonodependiente: evaluación fármaco: económica del tratamiento con Degarelix û Firmagon frente a Triptorelina genérica / Management of hormonal therapy for the treatment of advanced hormone-dependent prostate cancer: A pharmacoeconomics assessment of the use of Degarelix û Firmagon compared to generic triptorelin

Objetivo: Evaluación farmacoeconómica de dos tratamientos con drogas de distinto mecanismo de acción: Degarelix y triptorelina en el manejo de pacientes con cáncer de próstata avanzado hormonodependiente. Material y método: Se realizó una revisión de la literatura sobre el tratamiento estándar de estos pacientes, efectos tempranos y tardíos de las terapias existentes y además una valoración de Costo Integral del Tratamiento usando el tarifario de Essalud. Resultados: El Costo Integral del Tratamiento, es S/ 10 793 para un paciente que usa Degarelix y S/ 12 251 para un paciente que usa triptorelina genérica; es decir, la terapia con el antagonista de la GnRH genera un ahorro de S/ 1 458 por paciente. Conclusiones: Este ahorro representa S/ 1 008 017 para el total de pacientes con cáncer de próstata avanzado hormonodependiente que se atienden en Essalud, a nivel nacional, con la ventaja adicional que Degarelix no genera costos adicionales por complicaciones producto del efecto Flare.

Objective: This is a pharmacoeconomic evaluation of two therapy schedules using drugs with different modes of action: Degarelix and triptorelin in the treatment of patients with advanced hormone-dependent prostate cancer. Methods: We reviewed the literature on the standard treatment for these patients, early and late effects of existing therapies, and we also performed a valuation using the Comprehensive Cost Treatment EsSalud (Peruvian Social Security) rates. Results:The Comprehensive Cost Treatment is S/. 10 793 for a patient using Degarelix and S/. 12 251 for a patient using generic triptorelin, so the therapy with the GnRH antagonist generates S/. 1 458 savings per patient. Conclusions: This represents S/. 1,008,017 savings for all patients with advanced hormone-dependent prostate who attend to EsSalud, with the added advantage that there are no extra costs with the use of Degarelix because of the absence of complications due to any flare effect.

Clinical values of single or repeated triptorelin stimulating test in the differential diagnosis between idiopathic hypogonadotropic hypogonadism and constitutional delayed puberty / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the values of single or repeated luteinizing hormone (LH) releasing hormone analogue (triptorelin) stimulating test in the differential diagnosis between idiopathic hypogonadotropic hypogonadism (IHH) and constitutional delayed puberty (CDP).</p><p><b>METHODS</b>Male patients (n = 133) without puberty onset after the age of 14 were recruited for triptorelin stimulating test and were followed up for 24 - 48 months until the diagnosis were confirmed: 86 were IHH and the other 47 were CDP. Repeated triptorelin stimulating tests were conducted in 9 IHH patients and 13 CDP patients one year after the first stimulating tests with an attempt to evaluate the dynamic change of hypothalamus-pituitary-testis axis function. The relationship between the final diagnosis and the peak LH value (LH(max)), and the changes of repeated LH(max) were investigated.</p><p><b>RESULTS</b>In the single triptorelin stimulating test, LH(max) was (1.9 +/- 1.2) U/L in IHH group, which was significantly lower than that in CDP group [(13.7 +/- 8.3) U/L] (P < 0.01); 75 IHH patients (87.2%) had a LH(max) lower than 4 U/L, while only 2 CDP patients (4.3%) had a LH(max) lower than 4 U/L. When LH(max) < 4U/L was used as a criteria for the diagnosis of IHH, the single triptorelin stimulating test had a sensitivity of 87.2%, a specificity of 95.7%, and a positive predictive value of 97.4%. The repeated triptorelin stimulating tests performed one year later showed that the LH(max) in the 9 IHH patients increased from (4.7 +/- 2.5) U/L to (5.1 +/- 3.3) U/L (P = 0.78), while that in the 13 CDP patients increased from (10.7 +/- 3.3) U/L to (24.5 +/- 5.7) U/L (P < 0.05).</p><p><b>CONCLUSIONS</b>A single triptorelin stimulating test is highly effective in differentiating IHH from CDP. For some patients without definitive diagnosis, a repeated triptorelin stimulating test performed one year later may provide more valuable information on the dynamic change of the hypothalamus-pituitary-testis axis function.</p>

Clinical effects of shen-nourishing and menstruation-regulating method combined with triptorelin acetate injection on patient with luteinized unruptured follicle syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the clinical effects of Shen-nourishing and menstruation-regulating method (SNMRM) combined with Triptorelin Acetate Injection (TAI) on patients with luteinized unruptured follicle syndrome (LUFS).</p><p><b>METHODS</b>Sixty-two LUFS patients were randomly assigned to the treatment group and the control group. TAI was given to patients in the control group while SNMRM + TAI was given to those in the treatment group. The ovulation rate and the pregnancy rate were observed in the two groups.</p><p><b>RESULTS</b>The ovulation rate in the treatment group was higher than that in the control group, but without significant difference (85.53% versus 79.07%, P > 0.05). The pregnancy rate was significantly higher in the treatment group than in the control group (56.25% vs 30.00%, P < 0.05).</p><p><b>CONCLUSION</b>Treatment of LUFS by SNMRM + TAI could improve the ovulation rate and the pregnancy rate, indicating that LUFS patients' ovary functions could be improved by using different menstruation regulating methods during different follicular development phases.</p>

Protocolo largo con análogos de GnRH versus protocolo corto con antagonistas: ¿existen diferencias en cuanto a los resultados de los ciclos de FIV-ICSI? / Protocol with GnRH analogues vs antagonists of GnRH: exist differences in the results of the IVF-ICSI cycles?

Objetivo: Valorar si existen diferencias en los resultados de los ciclos de FIV-ICSI en función del protocolo de estimulación empleado. Método: Estudio retrospectivo descriptivo de pacientes infértiles que fueron sometidas a ciclos de FIV-ICSI en el Hospital Universitario La Paz, entre los meses de enero y septiembre de 2010, comparando un protocolo largo de estimulación con análogos de GnRH vs un protocolo corto con antagonistas de GnRH. Las variables analizadas fueron: tasa de gestación, necesidad de cancelación del ciclo, dosis total de gonadotropinas requerida durante la estimulación, niveles de estradiol sérico el día de la administración de la hCG, número de folículos puncionados, complejos obtenidos, número de ovocitos maduros y de embriones conseguidos. Resultados: No hubo diferencias estadísticamente significativas en los resultados de los ciclos en función del protocolo de estimulación empleado, en ninguna de las variables analizadas. Conclusiones: Este estudio no encontró diferencias en los resultados de los ciclos de FIV-ICSI con relación al uso de análogos o antagonistas de GnRH. Es necesarios más estudios con mayores tamaños muestrales para definir qué tipo de pacientes serían subsidiarias de recibir cada tratamiento para conseguir resultados óptimos.

Aims: To assess if there exist any differences in the results of the IVF-ICSI cycles depending on the stimulation protocol employed. Methods: Retrospective descriptive study of infertile patients who underwent IVF-ICSI cycles at La Paz University Hospital, between January and September 2010, comparing sitmulation protocol with GnRH agonists vs antagonists of GnRH. The variables analyzed were pregnancy rate, cancellation rate, total dose of gonadotropin required for stimulation, serum estradiol levels on the day of hCG administration, number of follicles punctured, complexes obtained, number of mature oocytes and of embryos obtained. Results: No statistically significant differences where found in the results of cycles depending on the protocol of stimulation used in any of the variables analyzed. Conclusions: This study didn't find any difference in the outcome of IVF-ICSI cycles in relation to the use of GnRH agonists or antagonists. We need more studies with larger sample sizes to determine which is the best treatment to each patient in order to achieve optimal results.

Effect of GnRH Analogs Leuprolide-Acetate and Triptorelin on Bone Mineral Density in Girls with Central Precocious Puberty / 대한소아내분비학회지

PURPOSE: The objective of this study was to evaluate the effect of gonadotropin releasing hormone analog (GnRHa) treatment on bone mineral density (BMD) in girls with central precocious puberty (CPP). Further we investigated the differences in the effect on BMD by using the GnRHa leuprolide-acetate and triptorelin. METHODS: Sixty-one females with CPP were enrolled in the study, the lumbar spine BMD was measured by dual energy x-ray absorptiometry before treatment, after one year (n = 61) and after two years (n = 24) of treatment. Lumbar spine BMD standard deviation scores (SDS) were compared according to chronological age (CA) and bone age (BA) for the whole group, as well as for the group A, treated with leuprolide-acetate (n = 40), and the group B, treated with triptorelin (n = 21). RESULTS: All subjects showed significant increment in BMD during treatment (P < 0.05). Lumbar spine BMD SDS for CA and BA showed no significant changes before and during treatment. Group A and group B, within each group, showed no significant changes in lumbar spine BMD SDS for CA and BA during treatment. CONCLUSION: Our study suggests that lumbar spine BMD was not impaired in girls treated with GnRHa for CPP and both leuprolide-acetate and triptorelin showed comparable effects on lumbar spine BMD during treatment.

Ovarian Hyper-Response to Administration of an GnRH-Agonist Without Gonadotropins

Several case reports have indicated that a small subgroup of patients may develop ovarian hyperstimulation following the administration of gonadotropin-releasing hormone agonists (GnRHa) without gonadotropins. However, since only few such cases have been published, it is unclear what course to follow in subsequent cycles after ovarian hyperstimulation in the first cycle using only GnRHa. A 33-yr-old woman was referred to in vitro fertilization for oocyte donation. A depot preparation (3.75 mg) of tryptorelin without gonadotropins induced ovarian multifollicular enlargement with high estradiol level, and was followed by human chorionic gonadotropin administration and oocyte retrieval. In a subsequent cycle of the same patient, a low dose of tryptorelin (0.05 mg) did not induce ovarian hyperstimulation, and resulted in clinical pregnancy. This report shows potential management of ovarian hyperstimulation following the administration of GnRHa without gonadotropins.

Phosphatase and tensin homolog gene inhibits the effect induced by gonadotropin-releasing hormone subtypes in human endometrial carcinoma cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Type I gonadotropin-releasing hormone (GnRH-I) agonists have been applied for the treatment of steroid-dependent tumors such as breast carcinoma, ovarian cancer and prostatic carcinoma. But the mechanism has not been clarified yet. There are few reports about the treatment of endometrial carcinoma using GnRH-I agonists. Type II GnRH (GnRH-II) is a new subtype of GnRH. Our aim was to investigate the effects of GnRH-I agonists and GnRH-II on estrogen receptor-negative human endometrial carcinoma cells and the effect from phosphatase and tensin homolog gene (PTEN) to them.</p><p><b>METHODS</b>A lentiviral vector-mediated RNAi method was used to establish a PTEN-negative HEC-1A cell clone (HEC-1A-ND). MTT and flow cytometry were used to detect the cell proliferation, cell cycle and apoptosis of HEC-1A, HEC-1A-NC and HEC-1A-ND cells after treatment with GnRH-I agonist Triptorelin (10(-11) mol/L to 10(-5) mol/L) or GnRH-II (10(-11) mol/L to 10(-5) mol/L). Western blotting was used to detect AKT and ERK1/2 activation after treatment with different concentrations of Triptorelin or GnRH-II for 30 minutes in the above mentioned three kinds of cells.</p><p><b>RESULTS</b>Triptorelin and GnRH-II induced apoptosis and inhibited proliferation of HEC-1A, HEC-1A-ND and HEC-1A-NC in a dose-dependent manner. This effect was augmented in HEC-1A-ND cells in which PTEN gene was knocked-down. Furthermore, Triptorelin and GnRH-II inhibited the AKT and ERK activity in HEC-1A-ND cells.</p><p><b>CONCLUSIONS</b>Triptorelin and GnRH-II can promote apoptosis rate and inhibit cell proliferation of estrogen receptor-negative endometrial carcinoma cells in a dose-dependent manner. PTEN gene can inhibit the effects of Triptorelin or GnRH-II on human endometrial carcinoma cells.</p>

Comparison of Alarelin and Triptorelin in the long-protocol ovulation induction in in vitro fertilization and embryo transfer / 中华男科学杂志

<p><b>OBJECTIVE</b>To compare the pituitary down-regulatory effects of the two gonadotropin-releasing hormone agonists Alarelin and Triptorelin in the long protocol of ovulation induction in in vitro fertilization and embryo transfer (IVF-ET).</p><p><b>METHODS</b>We included in this study 122 patients aged 24-39 years treated by IVF-ET for secondary infertility, with 10-20 pre-antral follicles and obstruction of the fallopian tube. Seventy-eight of them received Alarelin, and the other 44 Triptorelin. Comparative analyses were made on the pituitary down-regulatory effects of the two gonadotropin-releasing hormone agonists and the clinical outcomes of IVF-ET.</p><p><b>RESULTS</b>No premature LH surge and ovulation, nor severe hyperovarian stimulation syndrome was found in either group. There were no significant differences between the two groups in the mean dose and duration of gonodatropin treatment, the numbers of oocytes retrieved, mature oocytes and top-quality embryos, and the rates of 2PN, multi-sperm fertilization, cleavage, embryo transfer, embryo implantation, clinical pregnancy and early miscarriage (P > 0.05), but the rate of cancelled cycles was significantly higher in the Triptorelin than in the Alarelin group (P < 0.05).</p><p><b>CONCLUSION</b>Alarelin and Triptorelin can achieve similar pituitary down-regulatory effects and clinical outcomes in IVF-ET when used in the long protocol of ovulation induction.</p>

anticancer activity compared between triptorelin and a new gonadotropin releasing hormone analogue

Gonadotropin releasing hormone [GnRH] plays a key role in reproduction. This decapeptide is synthesized and released by hypothalamus and induces the pituitary gonadotrop cells to release pituitary gonadotropin hormones. In some extrapituitary compartments GnRH and its receptor act as part of the autocrine regulatory system of cell proliferation. The anticancer activity of GnRH and its analogues has been observed by many researchers. In this study the anticancer activity of a new analogue of GnRH and triptorelin was investigated by cell proliferation assay. Results indicate that proliferation of human breast and ovarian cancer cell lines are dose-dependently inhibited. The inhibitory efficiency of the new analogue is proved to be higher than the original triptorelin. In addition to its antimitogenic activity, evidence was found for the involvement of the apoptotic mechanism in the action of the new analogue and triptorelin. In conclusion, the new analogue can be considered as a good pharmaceutical candidate