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.

Uso de agonista de GnRH para inducir ovulación en ciclos de hiperestimulación ovárica controlada: experiencia de Clínica Monteblanco, Santiago, Chile / Use of GnRH agonist to induce ovulation cycles controlled ovarian hyperstimulation: experience of Monteblanco Clinic, Santiago, Chile

Objetivo: Presentar la experiencia de la Unidad de Medicina Reproductiva de Clínica Monteblanco con el uso de análogos GnRh para la inducción final de la maduración ovocitaria. Método: Se registraron los casos de IVF/ICSI durante el año 2012 en los que se indujo la maduración final ovocitaria con análogos GnRh (Lupron®). Todos los ciclos fueron estimulados con FSHr (Puregon®) y gonadotrofina urinaria altamente purificada (Menopur®), para la prevención del alza prematura de LH, el día 5° de estimulación se agregó diariamente antagonista de GnRh. La maduración ovocitaria final se realizó con 1,25 mg de acetato de leuprolide (Lupron®), posteriormente se realizó aspiración folicular bajo guía ecográfica. Todos los embriones obtenidos fueron vitrificados y transferidos en ciclos posteriores. Resultados: Entre enero y diciembre del año 2012 se registraron 110 pacientes cuya inducción de maduración final ovocitaria se realizó con acetato de leuprolide. El promedio de ovocitos recuperados fue de 21, la proporción de ovocitos maduros fue de 72 por ciento y la frecuencia de fecundación fue de 64 por ciento. No hubo ningún caso de síndrome de hiperestimulación ovárico severo. Conclusiones: En los casos presentados de inducción de la maduración ovocitaria final con acetato de leuprolida, los resultados obtenidos son óptimos en términos de número de ovocitos en metafase II recuperados y en frecuencia de fecundación, mostrando ser una alternativa eficiente en la prevención del síndrome de hiperestimulación ovárico severo, sin alterar el pronóstico de las pacientes.

Objective: To present the experience of the Reproductive Medicine Unit of Clinica Monteblanco inducing oocyte final maturation by GnRh analogue administration. Methods: We analysed all IVF/ICSI cases performed in 2012, in which final oocyte maturation was induced by administration of GnRH analogue (Lupron®). Controlled ovarian hyperstimulation was achieved bydaily rFSH (Puregon®) and highly purified urinary gonadotropin (Menopur®) administration. In order to prevent premature LH rise, on the 5th day of stimulation daily GnRH antagonist (Orgalutran®) was added. Final oocyte maturation was induced by the administration of 1.25 mg leuprolide acetate (Lupron®). Follicular aspiration was subsequently performed under ultrasound guidance. All embryos were vitrified and transferred in a subsequent cycle. Results: We registered 110 patients. The mean number of recovered oocytes was 21; the proportion of mature oocytes was 72 percent, and the fecundation rate reached was 64 percent. No case of severe ovarian hyperstimulation syndrome (OHSS) was recorded. Conclusions: In this cohort, the use of leuprolide acetate for induce final oocyte maturation demonstrated to be an efficient alternative to induce oocyte final maturation, while preventing OHSS.

Eficacia de leuprolide 11, 25 mg para supresión de testosterona en pacientes con cáncer prostático / Leuprolide s efficacy 11, 25 mg for suppression of testosterone in patients with prostatic cancer

Introducción: Los agonistas LHRH son de elección en bloqueo androgénico por cáncer prostático. En base a pacientes castrados se considera un bloqueo adecuado una testosterona total plasmática < 50 ng/dl. Se ha sugerido controlar la testosterona total por la posibilidad de no lograr una supresión adecuada. Material y método: Entre junio de 2008 a marzo de 2009 se midió el nivel de testosterona total al tercer mes de administrada una dosis de leuprolide 11,25 mg IM. Los exámenes se realizaron en la mañana y en el mismo laboratorio. En un grupo de pacientes se estimó peso, talla e índice de masa corporal (IMC) y se evaluó su asociación con los niveles de testosterona alcanzados. Resultados: Se evaluaron 81 pacientes, la edad promedio fue 76,4 años. La testosterona total plasmática promedio fue 33,9 ng/dl. En 12/81 pacientes (14,8 por ciento) el nivel de testosterona fue menos 50 ng/dl. No se observó asociación entre la duración de hormonoterapia y los niveles de testosterona. En 40 pacientes se estimó peso, talla e IMC sin encontrarse asociación de estas variables con el nivel de testosterona. En los pacientes en que se aumentó la dosis a leuprolide 22,5 mg se obtuvo una adecuada supresión de testosterona. Conclusión: En los pacientes en tratamiento con agonistas LHRH se debe medir el nivel de testosterona plasmática dada la posibilidad de un bloqueo inadecuado. En pacientes en tratamiento con leuprolide 11,25 mg y testosterona menos 50 ng/dl el aumento de la dosis a 22,5 mg lograría un nivel de testosterona en rangos de castración quirúrgica.

Introduction: The agonistas are LHRH of election in blockage androgenic for prostatic cancer. On the basis of castrated patients considers an adequate blockage a total plasmatic testosterone < 50 ng/dl. The total testosterone for the possibility to not to achieve an adequate suppression has been suggested to control. Material and method: Between June 2008 to March 2009 leuprolide’s dose measured the level of total testosterone itself to person under administration’s third month 11.25 mg IM. The exams had done in the morning and at the same laboratory. Weight, size and index of muscle mass (IMC) were estimated in patients’ group and his association with the levels of testosterone caught up with was evaluated. Results: We evaluated 81 patients, the mean age was 76.4 years. The total testosterone the average plasmatic was 33.9 ng/dl. In 12/81 patient (14.8 percent) the level of testosterone was > 50 ng/dl. we did not observe association between hormonoterapia’s duration and the levels of testosterone. Weight, size and IMC without finding association of these variables with the level of testosterone were estimated in 40 patients. We got an adequate suppression from testosterone in the patients that 22.5 mg increased itself the dose in to leuprolide. Conclusion: LHRH must try on in the patients in treatment with agonistic the level of plasmatic testosterone once the possibility of an inadequate blockage was given. In patients in treatment with leuprolide 11.25 mg and testosterone > 50 ng/dl the increase of the dose to 22.5 mg would achieve a level of testosterone in ranges of surgical castration.

GnRH Agonist Therapy to Protect Ovarian Function in Young Korean Breast Cancer Patients

The increased survival of patients with breast cancer has given rise to other problems associated with the complications of chemotherapy. One major complication is premature ovarian failure, an especially harmful outcome for women of reproductive age. This study was performed to evaluate the efficacy of GnRH agonist (GnRHa) treatment on protecting ovarian function in young breast cancer patients (30.59+/-5.1 yr) receiving chemotherapy after surgery. Twenty-two women were enrolled and given subcutaneous injections of leuprolide acetate (3.75 mg) every 4 weeks during chemotherapy. Follow-up laboratory tests (luteinizing hormone [LH], follicle stimulating hormone [FSH], and estradiol) were performed 1, 3, and 6 months after chemotherapy. Menstruation patterns and clinical symptoms were followed up for a mean duration of 35.6+/-1.7 months. FSH and LH levels were normal in all patients 6 months after completing chemotherapy (8.0+/-5.3, 4.4+/-2.7 mIU/mL, respectively). During follow-up, none of the patients complained of menopausal symptoms and 81.8% experienced recovery of menstruation. This report is the first trial of GnRHa as a treatment modality to protect ovarian function during adjuvant chemotherapy in young Korean breast cancer patients.

Uso de meia dose de agonista do GnRH de depósito para supressão hipofisária em ciclos de fertilização in vitro / Half-dose long-acting form of GnRH agonist for pituitary suppression in cycles of in vitro fertilization

OBJETIVO: descrever a experiência de um serviço de reprodução assistida com a utilização de meia dose de agonista do GnRH de depósito para a supressão hipofisária em ciclos de fertilização in vitro (FIV). MÉTODOS: estudo prospectivo em que foram avaliados ciclos de FIV ou "intracytoplasmatic sperm injection" (ICSI) utilizando meia dose de acetato de leuprolide de depósito, iniciado na fase lútea média do ciclo menstrual, no período de agosto de 2005 a março de 2006. Foi administrado FSH recombinante para indução ovariana controlada em dose variada. O hCG era administrado quando pelo menos um folículo atingisse 19 mm de diâmetro máximo. Realizou-se FIV ou ICSI nos oócitos maduros de acordo com fator de infertilidade. Transferiram-se até quatro embriões por paciente no segundo ou terceiro dia após a captação. O uso de progesterona foi iniciado no mesmo dia da coleta oocitária. A dosagem sérica de beta-hCG foi realizada no 14° dia após a coleta dos oócitos. Foram avaliados os seguintes parâmetros: número de ciclos aspirados, ciclos cancelados e ciclos transferidos, quantidade total de FSH utilizado, número de oócitos maduros, taxa de fertilização, número de embriões transferidos, taxa de implantação embrionária e taxa de gestação clínica. RESULTADOS: 109 ciclos de FIV/ICSI utilizaram o protocolo descrito. A média de idade das pacientes foi 34,9 anos. A taxa de cancelamento foi de 1,8 por cento dos ciclos iniciados. Foram utilizadas 1.905 UI de gonadotrofina, em média, por ciclo iniciado. Um total de 86,5 por cento dos oócitos obtidos eram maduros, e a taxa de fertilização foi de 76,3 por cento. A média de embriões transferidos foi 2,7. As taxas de gestação por aspiração e por transferência foram 25,2 e 25,7 por cento, respectivamente. Um total de 26,3 por cento das gestações eram gemelares e 5,3 por cento, trigemelares. CONCLUSÃO: a administração de meia dose (1,87 mg) de acetato de leuprolide de depósito para bloqueio hipofisário pode ser...

PURPOSE: to evaluate the experience of an assisted reproduction center that uses depot administration of half-dose of GnRH agonist for pituitary suppression in assisted reproductive cycles. METHODS: prospective study that evaluated in vitro fertilization or intracytoplasmatic sperm injection (IVF/ICSI) cycles utilizing half-dose of leuprolide acetate between August 2005 and March 2006. Recombinant FSH was administered for controlled ovarian induction based on the protocol. hCG was administered when at least one follicle reached 19 mm in diameter. IVF or ICSI was performed according to infertility factor. Up to four embryos were transferred on the second or third day after oocyte retrieval. Progesterone supplementation was initiated on the same day of oocyte retrieval, and after 14 days beta-hCG was measured. The following parameters were evaluated: number of aspirated cycles, cancelled cycles, transferred cycles, total dose of FSH employed, number of mature oocytes retrieved, fertilization rate, number of transferred embryos, embryo implantation rate, and pregnancy rate. RESULTS: A hundred and nine IVF/ICSI cycles were initiated. The mean age of the patients was 34.9 years. We observed 1.8 percent of cancellation rate. The mean total dose of gonadotrophins employed was 1,905 IU per cycle. We obtained 86.5 percent of mature oocytes and the fertilization rate was 76.3 percent. The mean number of embryos transferred was 2.7. Pregnancy rates per aspiration and per transfer were 25.2 and 25.7 percent, respectively. Of those who reached pregnancy, 26.3 percent were twins and 5.3 percent were triplets. CONCLUSIONS: the half-dose of GnRH depot employed for pituitary suppression was a useful alternative for ovarian stimulation in IVF cycles because it is comfortable and practical for the patient, besides its low cost.

Incidence Rate of Injection-Site Granulomas Resulting from the Administration of Luteinizing Hormone-Releasing Hormone Analogues for the Treatment of Prostatic Cancer

PURPOSE: Granulomas resulting from the administration of luteinizing hormone-releasing hormone analogues (LH-RH analogues) are thought to be very rare. We report on our clinical experience with injection-site granulomas that result from the administration of LH-RH analogues, and we evaluate the incidence rate of these granulomas. MATERIALS AND METHODS: We used the clinical records of 118 patients who were administered LH-RH analogues in 2005. We describe the clinical data of patients who experienced injection-site granulomas and evaluated the incidence rate. RESULTS: Five patients demonstrated injection-site granulomas due to LH-RH analogue administration. The incidence rate was 4.2% (5 of 118 patients). Most of the granulomas occurred after the first or second administration of 11.25mg of leuprorelin acetate. CONCLUSION: The occurrence of granulomas resulting from the administration of LH-RH analogues was thought to be very rare. Our study, however, revealed a higher incidence rate than expected, especially for leuprorelin acetate.

Efectividad de la terapia con leuprolide acetato de depósito cada tres meses en pubertad precoz central / Effectiveness of Leuprolide acetate therapy every three months in central precocious puberty

Background: Precocious puberty may reduce final adult height, and affected children may suffer social and emotional problems. The efficacy of treatment with a long acting agonist analogue of the gonadotropin releasing hormone (aLHRH) has been well demonstrated. Aim: To evaluated the efficacy of a new formulation of aLHRH (leuprolide, Lupron ®) for the suppression of gonadotropin activation and clinical signs of puberty. Material and methods: Eleven children (ten females) with idiopathic central precocious puberty, with a mean chronological age of 7.5±1.8 years and a bone age of 9.7±1.8 years were recruited. Testicular volume in the male was 15 ml. In females, Tanner stage for breast development was between 2-4 and mean ovarian volume was 2.3±0.8 ml. They were treated during 18 months with aLHRH, 11.25 mg administered intramuscularly every three months. Results: Clinical, hormonal and ultrasonographic signs of puberty regressed in all patients. The degree of suppression of LH was 87.7±5.1% at the end of the 18 months. No significant changes in bone mineral content were observed during the treatment period. Conclusions: Leuprolide (aLHRH) 11.25 mg, injected every three months, is effective for the control of central precocious puberty and allows to reduce the number of yearly injections from 12 to 4.

Duplicação da hipófise e da haste hipofisária: relato de um caso e revisão da literatura / Duplication of pituitary gland and stalk: case report and review of the literature

Os autores relatam um caso de uma paciente do sexo feminino, com idade cronológica de sete anos, idade óssea de 11 anos, aparecimento de mamas Tanner III bilateralmente, cuja investigação diagnóstica confirmou quadro de puberdade precoce dependente de gonadotrofinas, e a ressonância magnética da hipófise evidenciou duplicação da haste e da glândula hipofisária associada a hamartoma hipotalâmico.

The authors report a case of a female patient with chronological age of 7 years and bone age of 11 years, presenting with bilateral breast stage Tanner III and gonadotrophin-dependent precocious puberty. Magnetic resonance imaging of the sellar region demonstrated duplication of the pituitary gland and stalk associated with a hypothalamic hamartoma.

The effects of depot leuprorelin on IVF.

The trial studied the effects of depot leuprorelin on the IVF cycle and was done on nine couples. A single intramuscular injection of depot leuprorelin was given to the woman a couple days before ovulation. Seven days after ovulation, the serum progesterone level was measured and showed the same normal level as the natural ovulatory cycle. The progesterone levels varied from 12.59 to 96.0 ng/ml. On day three of the menstruation, the hormonal profiles showed a complete pituitary and ovarian suppression. FSH, LH and estrogen levels were less than 4.1 mIU/ml, 2.8 mIU/ml and 9.4 pg/ml respectively. The hMG stimulation took 11 days on average (9-15 days). A hundred and two oocytes were retrieved and among these there were 86 mature oocytes (84.3%). All oocytes were inseminated despite prematurity and resulted in 82.35 per cent fertilization. Normal fertilization occurred in 77.45 per cent (79/102). Good embryos developed in 58.23 per cent (46/79). No more than three embryos were transferred. Four women conceived, among them there was a set of twins. The implantation rate was 44.44 per cent (4/9). One abortion was found in the early first trimester. The take home baby rate was 33.33 per cent (3/9).

Tratamiento de la endometriosis con análogos de GnRH y estudio comparativo / Treatment of endometriosis with GnRH analogues: a comparative study

Objetivo. Evaluar la efectividad del tratamiento de la endometriosis con análogos de GnRH. Material y método. Se estudió a 100 mujeres divididas aleatoriamente en dos grupos: uno tratado con danazol (testigo) y uno con GnRH (experimental). Todas las mujeres contaban con un estudio laparoscópico y al término del tratamiento fueron sometidas a una segunda intervención. Resultados: La remisión de los síntomas y las lesiones endometriósicas fueron similares en ambos grupos, al igual que la tasa de embarazos, con la ventaja de que los efectos secundarios fueron menores en el grupo experimental. Conclusión. Los análogos de GnRH son una buena alternativa en las mujeres con intolerancia al danazol

Informe preliminar con análogos del GnRh de depósito y cirugía en el tratamiento de la endometrosis / Preliminary report with analogous of the GnRh of depot and surgery in the treatment of the endometriosis

El objetivo de este informe es mostrar nuestra experiencia preliminar en el tratamiento sucesivo y combinado quirúrgico y médico con análogos del GnRh de depósito (Lupron 3.75) e hiperestimulación ovárica controlada con gonadotrofinas (H.M.G.H.C.G.) en el tratamiento de la endometrosis. Se evaluó un grupo de 61 pacientes que consultaron por infertilidad en el Instituto de Ginecología y Fertilidad de Bs. As. entre el 1 de octubre de 1992 y el 31 de mayo de 1994. En todas ellas se realizó una laparoscopia para diagnóstico y estadificación de la endometrosis según la clasificación revizada de la Sociedad Americana de Fertilidad, realizándose en el mismo acto los procedimientos quirúrgicos (coagulación, lisis, quistectomia, etc.) según fuera necesario. Todas las pacientes fueron medicadas con Lupron 3.75 una ampolla mensual durante un período de 6 meses posteriores a la cirugía. Del total de 61 pacientes 24 (39,3 por ciento) se embarazaron, de las cuales 15 lo logró en forma espontánea, 13 (54.1 por ciento) en el primer semestre postratamiento 2 (8.3 por ciento) en el segundo semestre. 25 pacientes fueron estimuladas con gonadotrofinas, a partir del 6to. mes de finalizado el Lupron por un período de tres meses y 9 (37.5 por ciento) de ellas lograron el embarazo. En conclusión los resultados obtenidos sugieren que el tratamiento quirúrgico y médico con análogos del Gn-Rh y gonadotrofinas son útiles en el tratamiento de la endometrosis, permitiendo acortar el período en que se obtiene el embarazo logrando además una adecuada tolerancia y aceptación por parte de la paciente