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.

Use of GnRH analogues in the reduction of submucous fibroid for surgical hysteroscopy: A systematic review and meta-analysis / Uso de análogo de GnRH na redução de mioma submucoso na histeroscopia cirúrgica: Revisão sistemática e meta-análise

Abstract Objective Gonadotropin-releasing hormone analogues (GnRH-a) have been used preoperatively before hysteroscopic myomectomy to decrease the size and vascularization of the myomas, but evidence to support this practice is weak. Our objective was to analyze the use of GnRH-a in the reduction of submucous fibroid as a facilitator for surgical hysteroscopy from published clinical trials. Data sources Studies from electronic databases (Pubmed, Scielo, EMBASE, Scopus, PROSPERO), published between 1980 and December 2018. The keywords used were fibroid, GnRH analogue, submucous, histeroscopy, histeroscopic resection and their correspondents in Portuguese. Study selection The inclusion criteria were controlled trials that evaluated the GnRH-a treatment before hysteroscopic resection of submucous myomas. Four clinical trials were included in the meta-analysis. Data collection Two review authors extracted the data without modification of the original data, using the agreed form. We resolved discrepancies through discussion or, if required, we consulted a third person. Data synthesis The present meta-analysis included a total of 213 women and showed no statistically significant differences in the use of GnRH-a compared with the control group for complete resection of submucous myoma (relative risk [RR]: 0.94; 95%; confidence interval [CI]: 0.80-1.11); operative time (mean difference [MD]: - 3.81; 95%;CI : - 3.81-2.13); fluid absorption (MD: - 65.90; 95%;CI: - 9.75-2.13); or complications (RR 0.92; 95%;CI: 0.18-4.82). Conclusion The present review did not support the routine preoperative use of GnRH-a prior to hysteroscopic myomectomy. However, it is not possible to determine its inferiority when compared with the other methods due to the heterogeneity of existing studies and the small sample size.

Resumo Objetivo Análogos de hormônio liberador de gonadotrofina (GnRH-a) têm sido usados no pré-operatório de miomectomia histeroscópica para reduzir o tamanho e vascularização dos miomas, mas a evidência que suporta essa prática é fraca. Nosso objetivo foi analisar o uso de GnRH-a na redução do mioma submucoso como um facilitador de histeroscopia cirúrgica em ensaios clínicos publicados. Fonte de dados Estudos de bases de dados eletrônicas (Pubmed, Scielo, EMBASE, Scopus, PROSPERO), publicados entre 1980 e dezembro de 2018. As palavras-chave usadas foram fibroid, GnRH analogue, submucous, histeroscopy, histeroscopic resection e seus correspondentes em português. Seleção dos estudos Os critérios de inclusão foram ensaios clínicos controlados que avaliaram o tratamento com GnRH-a antes da ressecção histeroscópica de miomas submucosos. Quatro ensaios clínicos foram incluídos na meta-análise Coleta de dados Dois autores revisores extraíram os dados, sem modificarem os dados originais, usando a forma acordada. Nós resolvemos as discrepâncias através de discussão ou, se necessário, consultando um terceiro autor. Síntese dos dados A meta-análise incluiu um total de 213 mulheres e não demonstrou diferença estatisticamente significativa no uso de GnRH-a comparado com o grupo controle para ressecção completa de mioma submucoso (risco relativo [RR]: 0.94. índice de confiança [IC] 95%;: 0.80-1.11); tempo cirúrgico (diferença de média [MD]: - 3.81; IC95%;: -3.81-2.13); absorção de fluidos (MD: - 65.90; IC95%;: - 9.75-2.13); ou complicações (RR 0.92; IC95%;: 0.18-4.82). Conclusão A presente revisão sistemática não suporta o uso pré-operatório rotineiro de GnRH-a antes de miomectomia histeroscópica. No entanto, não é possível determinar sua inferioridade quando comparado aos outros métodos devido à heterogeneidade dos estudos existentes e ao pequeno tamanho da amostra.

Salud ósea en personas transgénero / Bone health in transgender subjects

Una persona transgénero es aquella en la cual el género autopercibido difiere del asignado al nacer, mientras que el término cisgénero es utilizado en aquellos individuos no trans. El tratamiento hormonal cruzado (THC) constituye una opción para lograr caracteres sexuales secundarios deseados. Es conocido que los esteroides sexuales desempeñan un rol fundamental en la adquisición de la densidad mineral ósea (DMO) durante la pubertad. Por lo tanto, el impacto del THC sobre la masa ósea se ha convertido en materia de estudio. En estadios puberales tempranos, los análogos de la hormona liberadora de gonadotrofinas (GnRH) son utilizados con un efecto reversible. Si bien la DMO parece mantenerse estable, cuando se compara con una población de referencia del mismo sexo biológico y edad, el Z-score se encuentra por debajo de lo esperado. En adultos, durante el THC no se informaron disminuciones en la DMO. Está reportado que las mujeres trans antes del inicio del TH presentan características densitométricas diferentes de los hombres cisgénero. Hasta el momento, la carga de datos para los calculadores del riesgo de fractura y el software del equipo DXA se basan en el sexo biológico y no en identidad de género. Recientemente, la International Society for Clinical Densitometry (ISCD) emitió sus recomendaciones para la evaluación de la masa ósea en personas transgénero y en aquellos individuos no conformes con el género. Si bien la ISCD sugiere realizar la evaluación únicamente en aquellos pacientes con factores de riesgo, es de importancia realizar DXA basal, sobre todo en mujeres transgénero, para determinar el riesgo inicial de dicha población. En este artículo se revisa la evidencia disponible sobre el impacto del THC en la salud ósea de personas transgénero. (AU)

Cross sex hormone therapy (CSHT) in transgender women (TW) it is an option to achieve desired secondary sexual characteristics. It is known that sex steroids play a fundamental role in the acquisition of bone mineral density during puberty, in addition to determining a different characteristic bone pattern between both biological sexes. So the impact of affirming HT on bone is it has become in subject of study. In early pubertal stages, GnRH analogs are used with a reversible effect. Although bone mineral density (BMD) seems to remain stable, when compared with a reference population of the same biological sex and age, the Z-score is lower than expected. In adults, during CSHT no decreases in BMD were reported. However, it was reported that TW prior to starting CSHT present different densitometric characteristics than cisgender men. So far, the data load for the fracture risk calculators and DXA software is based on biological sex and not gender identity. Recently the ISCD issued its recommendations for the evaluation of bone mass in transgender subjects and in those non-conforming to gender. Although the ISCD suggests performing the evaluation only in those patients with risk factors, our group recognizes that baseline DXA, especially in TW, constitutes a useful tool to determine the initial risk of this population. Our proposal arises from our own experience and from that compiled in the international literature, where it is observed that even without starting CSHT, transgender women have lower BMD. DXA. This article reviews the available evidence regarding the effect of CSHT on health bone in transgender people. (AU)

Clinical and laboratory parameters of gonadotropin-releasing hormone analog treatment effectiveness in children with precocious puberty

OBJECTIVE: There are no doubts about the clinical benefits of treatment with GnRH analogs for patients diagnosed with central precocious puberty (CPP). However, laboratory monitoring of CPP is still a matter of considerable controversy in the literature. Therefore, the main objective of this study was to evaluate the cut-off values of stimulated LH that determine gonadotrophic suppression. METHODS: Twenty-four girls, on treatment with leuprorelin acetate (LA) at 3.75 mg IM every 28 days, were studied. The clinical parameters used to indicate clinical effectiveness were regression or maintenance of sexual characteristics according to the Tanner stage, growth velocity reduction, reduction or maintenance of the difference between bone age and chronological age and maintenance or improvement of the final height prediction. For the laboratory effectiveness test, basal estradiol, LH, and FSH levels were collected before and 1 and 2 h after the administration of 3.75 mg LA. RESULTS: Eleven girls showed improvement in all clinical parameters, and their effectiveness tests were compared to those of the other patients to calculate the cut-off values, which were ≤3.64 IU/L (p=0.004*) for LH after 1 h and ≤6.10 IU/L (p<0.001*) for LH after 2 h. CONCLUSION: The LH response after the LA stimulation test, associated with clinical data and within a context of CPP, constitutes a reliable and feasible resource and can assist in monitoring the effectiveness of treatment.

Applicability of a novel mathematical model for the prediction of adult height and age at menarche in girls with idiopathic central precocious puberty

OBJECTIVES: Unfavorable predicted adult height and psychosocial inadequacy represent parameters used to guide therapeutic intervention in girls with central precocious puberty. Gonadotropin-releasing hormone analog is the first-line treatment. The aim of this study was to compare two methods used to predict adult height and assess a validated tool for predicting the age at menarche in girls with central precocious puberty. METHODS: The predicted adult height of 48 girls with central precocious puberty was calculated at diagnosis using the Bayley-Pinneau method based on average and advanced bone age tables and compared with the predicted adult height calculated using a mathematical model. In addition, the age at spontaneous menarche was predicted using the new formulae. After Gonadotropin-releasing hormone analog treatment, the predicted adult height was calculated using only the Bayley-Pinneau tables. RESULTS: The achieved adult height was within the target height range in all treated girls with central precocious puberty. At diagnosis, the predicted adult height using the Bayley-Pinneau tables was lower than that using the mathematical model. After the Gonadotropin-releasing hormone analog treatment, the predicted adult height using the Bayley-Pinneau method with the average bone age tables was the closest to the achieved adult height. Using the formulae, the predicted age at spontaneous menarche was 10.1±0.5 yr. The Gonadotropin-releasing hormone analog treatment significantly postponed this event until 11.9±0.7 yr in these "idiopathic" central precocious puberty girls, highlighting the beneficial effect of this treatment. CONCLUSION: Both initial adult height prediction methods are limited and must be used with caution. The prediction of the age at spontaneous menarche represents an innovative tool that can help in clinical decisions regarding pubertal suppression.

Use of a GnRH synthetic analog (buserelin) for estrous induction in female dogs / Utilização de análogo sintético de GnRH (buserelina) na indução do estro em cadelas

The aim of this study was to evaluate the effectiveness of a GnRH synthetic analog, as an estrous inducer in female dogs when administered during the anestrous phase, and to evaluate the pregnancy rate achieved through natural copulation. For this purpose, ten female dogs of different breeds were used. The subjects received buserelin by intramuscular injections at a dose of 2,1mcg when female dogs weighed up to 10kg (Group 1) and of 4,2mcg when the dogs weighed above 10kg (Group 2). Of the ten subjects, only three presented estrus after a single injection of buserelin: two dogs from Group 1 and one dog from Group 2 on average 7±1.29 days. The remaining seven dogs were given a second dose of buserelin, equal to the first administration. Of these, three belonged to Group 1 and four to Group 2. Four of these dogs exhibited clinical signs of estrus within, on average 9±7.3 days from the second injection. The seven female dogs that did enter estrus were fertilized successfully through natural copulation. The administration of buserelin was effective in inducing estrus in female dogs during the anestrous phase, with a maximum of two administrations.(AU)

Objetivou-se avaliar a eficácia de um análogo sintético ao GnRH como indutor de estro em cadelas em anestro e a taxa de prenhez por meio de cópula natural. Para isso, foram utilizadas 10 fêmeas caninas de diferentes raças. Cadelas de até 10kg de peso (grupo 1) foram submetidas à administração de buserelina por via intramuscular, na dose de 2,1mcg, e cadelas acima de 10kg (grupo 2) foram submetidas à mesma medicação, porém na dose de 4,2mcg. Das fêmeas em anestro, apenas três apresentaram estro com apenas uma aplicação, sendo duas do grupo 1 e uma do grupo 2, em 7±1,29 dias, em média. Em sete cadelas foi administrada mais uma dose de buserelina; destas, quatro eram pertencentes ao grupo 2 e três eram do grupo 1. Os sinais de estro ocorreram, em média, após 9±2,73 dias da segunda aplicação. As sete cadelas que manifestaram estro foram fertilizadas por meio de cópula natural. A administração de buserelina é eficiente para a indução de estro, em cadelas em anestro, em, no máximo, duas aplicações.(AU)

Indução do estro em cutias (Dasyprocta leporina) utilizando-se protocolos à base de prostaglandina isolada ou em associação com análogo de GnRH / Estrus induction in agoutis (Dasyprocta leporina) using protocols based on prostaglandin isolated or in association to GnRH analogue

Comparou-se a eficiência de protocolos para indução de estro em cutias. Em cinco fêmeas, foram administradas duas doses de cloprostenol (5µg) com intervalo de nove dias, via intraperitoneal; em outras cinco, administraram-se 30µg de análogo do hormônio liberador de gonadotrofinas (GnRH), via intravulvar, seguidos de 5µg de cloprostenol, via intraperitoneal, após sete dias e, após mais dois dias, nova dose do análogo de GnRH. A cada três dias, a ciclicidade reprodutiva dos animais foi monitorada, por meio de coleta de sangue, para dosagem hormonal, ultrassonografia ovariana e citologia vaginal. Duas das fêmeas que receberam apenas prostaglandina, as quais estavam em fase luteal no início do tratamento, manifestaram o estro aos três e seis dias após a segunda administração da droga. Já nas fêmeas que receberam a prostaglandina associada ao análogo do GnRH, duas que originalmente estavam em fase luteal apresentaram estro aos quatro dias após o tratamento, e uma outra apenas após 10 dias. Não foram evidenciadas diferenças estatísticas quanto à eficiência dos tratamentos (P>0,05). Conclui-se que, de acordo com os protocolos utilizados, o uso da prostaglandina isolada ou em associação com análogo do GnRH para a indução do estro em cutias D. leporina apresenta eficiência limitada às fêmeas que estejam em fase luteal por ocasião do início do tratamento.(AU)

We compared the efficiency of protocols for estrus induction in agoutis. Five females received double intraperitoneal administration of cloprostenol (5µg) on a 2-days interval; other five females were treated with intravulvar administration of 30µg gonadotrophin release hormone analogue (GnRH associated to intraperitoneal administration of 5µg cloprostenol after seven days and a new administration of GnRH analogue after two days. Every 3 days, the agoutis' reproductive cycle was monitored by blood collection for hormonal analysis, ovarian ultrasound and vaginal cytology. Two females, originally in luteal phase, that received isolated prostaglandin presented estrous signs at 3 and 6 days after the second drug administration. From the females that received the association, two that were originally in luteal phase presented estrus at 4 days after treatment, and one other presented estrus only after 10 days. There was no significant statistical difference regarding the efficiency of treatments for estrus induction (P>0.05). We conclude that, according to the protocols tested in the study, the use of isolated prostaglandin or its association to GnRH analogue for estrus induction in D. leporine shows an efficiency limited to the females that were in luteal phase in the beginning of the treatment.(AU)

Central precocious puberty: revisiting the diagnosis and therapeutic management

ABSTRACT Clinical and laboratory diagnosis and treatment of central precocious puberty (CPP) remain challenging due to lack of standardization. The aim of this revision was to address the diagnostic and therapeutic features of CPP in Brazil based on relevant international literature and availability of the existing therapies in the country. The diagnosis of CPP is based mainly on clinical and biochemical parameters, and a period of follow-up is desirable to define the “progressive” form of sexual precocity. This occurs due to the broad spectrum of pubertal development, including isolated premature thelarche, constitutional growth and puberty acceleration, progressive and nonprogressive CPP, and early puberty. Measurement of basal and stimulated LH levels remains challenging, considering that the levels are not always in the pubertal range at baseline, short-acting GnRH is not readily available in Brazil, and the cutoff values differ according to the laboratory assay. When CPP is suspected but basal LH values are at prepubertal range, a stimulation test with short-acting or long-acting monthly GnRH is a diagnostic option. In Brazil, the treatment of choice for progressive CPP and early puberty is a long-acting GnRH analog (GnRHa) administered once a month or every 3 months. In Brazil, formulations of GnRHa (leuprorelin and triptorelin) are available and commonly administered, including 1-month depot leuprorelin 3.75 mg and 7.5 mg, 1-month depot triptorelin 3.75 mg, and 3-month depot leuprorelin 11.25 mg. Monthly or 3-month depot GnRHa are effective and safe to treat CPP. Arch Endocrinol Metab. 2016;60(2):163-72.

Evaluation of central precocious puberty treatment with GnRH analogue at the Triangulo Mineiro Federal University (UFTM)

Objective To report our experience of treating central precocious puberty (CPP) with a GnRH analogue with respect to the final heights (FH) attained in patients who completed treatment. Subjects and methods Among 105 records of children diagnosed with precocious puberty, 62 cases (54 girls and 8 boys), who were treated with leuprolide acetate/3.75 mg/monthly, were selected, and divided into 4 groups: group 1 (G1), 25 girls who attained FH; group 2 (G2), 18 girls who completed treatment but did not reach FH; group 3 (G3), 11 girls still under treatment; and group 4 (G4), 8 boys, 5 of which attained FH. Treatment was concluded at a bone age of 12 years, and follow-up continued until FH was achieved. Results In both G1 and G2 groups, height standard deviation score (SDS), weight-SDS and percentile of body mass index (PBMI) did not show intra/intergroup differences at the beginning and at interruption of treatment, but when added, G1+G2, height-SDS and weight-SDS differed significantly (p = 0.002 and 0.0001, respectively). In G1, 19 of 25 cases attained TH, and average height gain was 16.7 cm (7.7- 27.1); there was significant difference between FH and prediction of FH at the start (PFH at start) (p = 0.0001), as well as between PFH at interruption vs TH and vs FH (p = 0.007) with FH higher than TH (p = 0.004). Significant correlation was identified between FH and height gain after treatment. Conclusion As shown by some studies, GnRH analogue treatment was effective in children with CPP reaching FH near the genetic target.

Impacto da ativação da intenção na prática da atividade física em diabéticos tipo II: ensaio clínico randomizado / Impact of the activation of intention to perform physical activity in type II diabetics: a randomized clinical trial

O diabetes mellitus, tipo II, é uma doença com alta prevalência na população adulta brasileira e que pode ser controlada, dentre outras intervenções, por meio da atividade física. Este estudo teve como objetivo avaliar o impacto de uma estratégia motivacional tradicional, bem como sua associação à estratégia de ativação da intenção, na adesão à atividade física, nos portadores do diabetes mellitus, tipo II, usuários do Sistema Único de Saúde (SUS), por meio de um ensaio clínico randomizado. Os participantes foram alocados em Grupo Controle (GC) e Grupo Intervenção (GI). Ambos os grupos receberam uma estratégia motivacional tradicional, porém, somente o GI recebeu a estratégia de ativação da intenção. Após dois meses de seguimento, observaram-se diferenças estatisticamente significativas entre os grupos, relativas à prática de caminhada (p = 0,0050), número de dias por semana (p = 0,0076), minutos por dia (p = 0,0050) e minutos por semana (p = 0,0015) de caminhada. Ao final das intervenções, observaram-se, também, diferenças na circunferência abdominal (p = 0,0048) entre os grupos. Conclui-se que a estratégia de ativação da intenção teve maior impacto na adesão à prática de atividade física e diminuição da circunferência abdominal de diabéticos, tipo II, do que a estratégia motivacional tradicional.

Type II diabetes mellitus is a highly prevalent disease among the adult Brazilian population, and one that can be controlled by interventions such as physical activity, among others. The aim of this randomized controlled study was to evaluate the impact of a traditional motivational strategy, associated with the activation of intention theory, on adherence to physical activity in patients with type II, diabetes mellitus who are part of the Unified Health System (SUS). Participants were divided into a control group (CG) and an intervention group (IG). In both groups, the traditional motivational strategy was applied, but the activation of intention strategy was only applied to the IG Group. After a two-month follow-up, statistically significant differences were verified between the groups, related to the practice of walking (p = 0.0050), number of days per week (p = 0.0076), minutes per day (p = 0.0050) and minutes walking per week (p = 0.0015). At the end of the intervention, statistically significant differences in abdominal circumference (p = 0.0048) between the groups were observed. The conclusion drawn is that the activation of intention strategy had greater impact on adherence to physical activity and reduction in abdominal circumference in type II diabetics, than traditional motivational strategy.

Avanços na etiologia, no diagnóstico e no tratamento da puberdade precoce central / Advances in the etiology, diagnosis and treatment of central precocious puberty

O início da puberdade caracteriza-se pelo aumento de amplitude e frequência dos pulsos do hormônio secretor de gonadotrofinas (GnRH) após um período de relativa supressão hormonal durante a infância. A reemergência da secreção pulsátil do GnRH resulta em aumento na secreção de gonadotrofinas, hormônio luteinizante (LH) e folículo estimulante (FSH), pela hipófise anterior e consequente ativação gonadal. A ativação prematura do eixo hipotálamo-hipófise-gonadal resulta em puberdade precoce dependente de gonadotrofinas, também conhecida como puberdade precoce central (PPC), e se caracteriza pelo desenvolvimento dos caracteres sexuais secundários antes dos 8 anos nas meninas e 9 anos nos meninos. O início do desenvolvimento puberal provém da interação complexa de fatores genéticos, nutricionais, ambientais e socioeconômicos. O diagnóstico clínico da PPC baseia-se em reconhecimento de desenvolvimento puberal progressivo, concentrações púberes de LH em condição basal e/ou após estímulo com GnRH e avanço de idade óssea. A ressonância magnética de encéfalo é útil no estabelecimento de diagnóstico diferencial entre as formas orgânica ou idiopática. Os análogos de GnRH de ação prolongada representam o tratamento de escolha da PPC. O componente genético da PPC foi recentemente fortalecido pela evidência de mutações no gene MKRN3, localizado no braço longo do cromossomo 15, em crianças com PPC familial. Nessa revisão, dados clínicos e terapêuticos da PPC serão amplamente discutidos, visando à atualização e à conduta criteriosa dessa condição clínica de grande relevância na endocrinologia pediátrica.

The onset of puberty is first detected as an increase in the amplitude and frequency of pulses of gonadotropin-releasing hormone (GnRH) after a quiescent period during childhood. The reemergence of pulsatile GnRH secretion leads to increases in the secretion of the gonadotropins, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) by the pituitary gland, and the consequent activation of gonadal function. Early activation of the hypothalamic–pituitary–gonadal axis results in gonadotropin-dependent precocious puberty, also known as central precocious puberty (CPP), which is clinically defined by the development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. Pubertal timing is influenced by complex interactions among genetic, nutritional, environmental, and socioeconomic factors. CPP is diagnosed on the basis of clinical signs of progressive pubertal development before the age of 8 years in girls and 9 years in boys, pubertal basal and/or GnRH-stimulated LH levels, and advanced bone age. Magnetic resonance imaging of the central nervous system is essential for establishing the CPP form as organic or idiopathic. Depot GnRH-analogues represent the first-line of therapy in CPP. Very recently, the genetic component of CPP was demonstrated by the evidence that the deficiency of the MKRN3 gene, located on long arm of chromosome 15, causes familial CPP in humans. In this current review, clinical and therapeutic aspects of the CPP will be discussed, contributing to adequate diagnosis and criterious approach of this relevant condition of pediatric endocrinology.

Leiomiomatose uterina: revisão / Uterine leiomyomatosis: review

Os leiomiomas uterinos são tumores monoclonais que se originam de uma mutação somática em um miócito progenitor. Representam a neoplasia benigna mais comum do útero. A causa precisa relacionada ao seu desenvolvimento ainda não foi totalmente esclarecida. As apresentações clínicas mais frequentes são o sangramento anormal, a dor e pressão pélvicas, massa pélvica não diagnosticada anteriormente e infertilidade. O diagnóstico baseia-se na história clínica, no exame físico, que pode ser completamente normal em alguns casos, e nos achados de exames complementares, como a ultrassonografia endovaginal, a histerossonografia e a ressonância magnética. O tratamento varia de acordo com a apresentação clínica e pode ser expectante, clínico ou cirúrgico.

The uterine leiomyomas are monoclonal tumors that originate from a somatic mutation in a myocyte progenitor and are the most common benign tumor of the uterus. The precise cause related to its development has not been fully clarified. The most common clinical presentations are abnormal vaginal bleeding, pelvic pain and pressure, previously undiagnosed pelvic mass, and infertility. The diagnosis is based on clinical history, physical examination, which may be completely normal in some cases, and the findings of laboratory tests such as transvaginal ultrasound, the sonohysterography, MRI. Treatment varies according to clinical presentation and may be expectant, medical or surgical.

Respuesta al tratamiento con análogos de hormona liberadora de gonadotrofinas de pacientes con pubertad precoz central en el Instituto Nacional de Salud del Niño / Response to treatment with analogues of gonadotrophin releasing hormone in patient with central precocious puberty in the Instituto Nacional de Salud del Niño

Los análogos de hormona liberadora de gonadotrofinas (GnRHa), son el tratamiento de elección de la pubertad precoz central (PPC) y a pesar de las diversas experiencias reportadas hay aspectos clínicos y auxológicos por responder. Objetivo: Describir la respuesta al tratamiento...

The analogues of gonadotrophin releasing hormone (GnRHa) are the preferred treatment for central precocious puberty (CPP); despite the various reported experiences, there are clinical and auxological issues unanswered. Objective: To describe the response to GnRHa therapy in patients with central precocious puberty, followed in the Endocrine Unit at the Instituto Nacional de Salud del Niño (INSN), Lima, Perú, between 1998 and 2008...

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.

Síndrome do ovário policístico: aspectos atuais das abordagens terapêuticas: parte 2 / Polycystic ovary syndrome: current aspects of the therapeutic interventions: part 2

A segunda parte desta revisão inclui as demais opções de tratamento da síndrome do ovário policístico (SOP). O citrato de clomifeno (CC) é utilizado na dose de 50 a 200 mg/dia durante cinco dias a partir do segundo ao quinto dia do ciclo menstrual. A taxa de ovulação após o tratamento com CC é de aproximadamente 73 por cento e a de gravidez em torno de 36 por cento. Com os análogos do GnRH ocorre redução dos níveis de gonadotrofinas e diminuição da secreção de estrógenos e androgênios. O principal risco da estimulação com gonadotrofinas é a gestação múltipla. Anastrazole e letrozole pertencem à classe dos inibidores da aromatase de terceira geração. As taxas de ovulação e gestação com letrozole variam de 54,5 a 82,4 por cento e 9 a 25 por cento, respectivamente. Não ocorreu diferença significativa nas taxas de ovulação e gestação entre o uso de 2,5 mg de letrozole em comparação com 1 mg de anatrozole. O uso da N-acetilcisteína (NAC) sugere melhora significativa da sensibilidade à insulina em mulheres com SOP. Os contraceptivos hormonais orais combinados permanecem como tratamento predominante para redução do hiperandrogenismo e das irregularidades menstruais em mulheres que não desejam engravidar. Os antiandrógenos são utilizados principalmente para diminuir as queixas de hirsutismo e o efeito será percebido em 9 a 12 meses de tratamento. Muitas mulheres se submetem à cauterização ovariana ou a laser por videolaparoscopia tendo restauração espontânea da ovulação com gravidez subsequente. Porém, os benefícios potenciais destas intervenções tendem a ser atenuados devido à formação de aderências.

The second part of this review includes other treatment options for polycystic ovary syndrome (PCOS). The clomiphene citrate (CC) is used in a dose of 50 to 200 mg/day for five days, begining from the second to fifth day or the menstrual cycle. The ovulation rate after the treatment with CC is approximately 73 percent and the pregnancy rate is about 36 percent. With GnRH analogues, there is a reduction in gonadotrophin levels and a decrease of androgen and estrogen secretion. The major risk due to stimulation with gonadotrophins is the multiple gestation. Anastrozole and letrozole belong to the class of third-generation aromatase inhibitors. The rates of ovulation and pregnancy with letrozole vary from 54.5 to 82.4 percent and from 9 to 25 percent, respectively. There was no significant difference in ovulation and pregnancy rates with the use of 2.5 mg of letrozole compared to 1 mg of anastrozole. The use of N-acetyl Cysteine (NAC) suggests significant improvement in insulin sensibility in women with PCOS. The combined oral hormonal contraceptives are still the predominant treatment to decrease hyperandrogenism and menstrual irregularities in women who do not want to get pregnant. Anti-androgens are used mainly to diminish complaints of hirsutism and the effect will be noted after 9 to 12 months of treatment. Several women undergo ovarian cauterization of with laser by videolaparoscopy having their ovulation spontaneously restored with subsequent pregnancy. However, the potential benefits of these interventions might be attenuated due to adhesion formations.

Fatores determinantes do ganho na altura em meninas com puberdade precoce central idiopática tratadas com análogo de GnRH / Predictive factors for height gain in idiopathic central precocious puberty treated with GnRH analogues

OBJETIVO: avaliar fatores determinantes de maior ganho na estatura como resultado do tratamento com GnRHa. MÉTODOS: estudo retrospectivo de 33 meninas com puberdade precoce central idiopática tratadas com GnRHa. Foram avaliadas: idade no início dos sintomas e no início do tratamento, tempo decorrido entre o início de aparecimento dos caracteres puberais e o início do tratamento, idade óssea, avanço da idade óssea, duração do tratamento com GnRHa, altura real e escore Z, altura predita e escore Z e dosagens hormonais de FSH e LH após estímulo com GnRH, que foram correlacionadas com o ganho de altura no final do tratamento, calculada pela diferença entre altura predita no final e início do tratamento. Para análise estatística foi utilizada a correlação linear de Pearson, além da regressão linear múltipla. RESULTADOS: a média de idade no início do tratamento foi 7,8±1,3 anos, com idade óssea média de 10,1±1,6 anos. O avanço da idade óssea era de 2,3±1,1 anos e foi controlado com o tratamento. O ganho em altura predita foi de 2,5±1,3 cm e foi correlacionado positivamente com o tempo decorrido entre o início dos sintomas e o início do tratamento e com o avanço da idade óssea, além de se correlacionar negativamente com o escore Z da altura no início do tratamento e com a altura predita no início do tratamento, sendo este último o principal fator determinante do ganho obtido com o tratamento. CONCLUSÕES: meninas com maior comprometimento da altura predita para a idade adulta, visualizado pelo maior desvio em relação à população (escore Z) e pelo maior avanço na idade óssea foram as que obtiveram maior benefício com o tratamento com GnRHa, não devendo ser excluídas do grupo a ser tratado.

PURPOSE: to evaluate predictive factors of response to GnRHa treatment in girls with idiopathic central precocious puberty. METHODS: a retrospective cohort study was conducted involving 33 girls diagnosed with idiopathic central precocious puberty and treated with GnRHa. The following independent variables were assessed: age at the beginning of therapy and at the onset of symptoms, time elapsed since the appearance of pubertal characteristics and the beginning of treatment, bone age, bone age advance, duration of GnRHa treatment, actual height and Z-score, predicted height and Z-score and hormone measurements of FSH and LH after GnRH stimulation, which were correlated with gain in height as a dependent variable at treatment discontinuation, calculated by the difference between the predicted height at the end and beginning of treatment. For statistical analysis, Pearson's linear correlation was used, in addition to multiple linear regression analysis. RESULTS: the mean age at the beginning of treatment was 7.8±1.3 years, with a mean bone age of 10.1±1.6 years. Bone age advance was 2.3±1.1 years and was controlled during the treatment period. Gain in predicted height was 2.5±1.3cm. It was positively correlated with time elapsed since the beginning of symptoms and the beginning of treatment and with bone age advance, while negatively correlated with the Z-score of height at the beginning of treatment and predicted height at the beginning of treatment, and the latter was the main factor determining gain from treatment. CONCLUSIONS: girls who had the most significant compromise of predicted adult height, as detected by a larger deviation from the population (Z-score) and the most considerable advance in bone age, received benefit from GnRHa therapy, and they must not be excluded from the group to be treated.

Ovarian hyperthecosis in the context of an adrenal incidentaloma in a postmenopausal woman / Coexistência de incidentaloma adrenal e hipertecose de ovário em mulher menopausada

Adrenal incidentaloma is not infrequent and can be found in hirsute women. We report a case of a 54-year-old woman with amenorrhea and hirsutism of abrupt onset and mild signs of virilization that had an adrenal incidentaloma coexisting with ovarian hyperthecosis. Basal total and free testosterone were 191 ng/dL and 179 pmol/L. Pelvic ultrasonography disclosed a right ovary with 10.3 cc and a left ovary with 9.8 cc without nodules or cysts, and computerized tomography of the abdomen disclosed a normal right adrenal gland. On the left adrenal gland a solid nodule with 0.8 cm was seen. After GnRHa administration, total testosterone was 23 ng/dL and free testosterone was 17 pmol/L. In view of a suppression of testosterone by GnRHa, the patient was submitted to a hystero-oophorectomy by laparoscopy. Symmetrically enlarged ovaries were seen. No tumor was apparent. Histology showed hyperthecosis, with foci of luteinized stromal cells. Only atretic follicles were detected. No hilar cell hyperplasia was seen. In conclusion, the presence of an adrenal mass in a hirsute woman can lead to a wrong diagnosis. In this case the suppression GnRHa test was fundamental to determine the origin of hyperandrogenemia.

Os incidentalomas adrenais não são infreqüentes e podem ser encontrados em pacientes com hirsutismo. Nesse relato, apresentamos o caso de coexistência de um incidentaloma adrenal com hipertecose de ovário, em uma mulher com 54 anos de idade com amenorréia e hirsutismo de início abrupto e sinais leves de virilização. As testosteronas total e livre basal foram de 191 ng/dL e 179 pmol/L, respectivamente. O ultra-som pélvico demonstrou o ovário direito com 10,3 cc e ovário esquerdo com 9,8 cc, sem nódulos ou cistos e a tomografia computadorizada de abdome demonstrou adrenal direita adrenal e nódulo sólido de 0,8 cm na adrenal esquerda. Após a administração de análogo de GnRH, as testosteronas total e livre foram de 23 ng/dL e 17 pmol/L, respectivamente. Considerando a supressão da concentração de testosterona pelo análogo de GnRH, a paciente foi submetida a histeroooforectomia por via laparoscópica. O diagnóstico histológico foi de hipertecose, com focos de células estromais luteinizadas. Somente folículos atréticos foram visualizados. Não se detectou hiperplasia de células hilares. Em conclusão, a presença de massa adrenal em uma paciente com hirsutismo pode levar ao diagnóstico errado. Neste caso, o teste de supressão com análogo de GnRH foi fundamental para se determinar a origem da hiperandrogenemia.