Tratamiento del síndrome genitourinario de la menopausia con láser CO2 en pacientes de Clínica Estrella / Treatment for genitourinary syndrome of menopause with CO2 laser in Clinica Estrella patients

El síndrome genitourinario de la menopausia se refiere a los signos y síntomas relacionados a la disminución estrogénica dando como resultado una atrofia vaginal, esto ocasiona un gran impacto negativo en las actividades cotidianas de las mujeres, existen varios tratamientos para aliviar y resolver los síntomas, siendo los más frecuentes la incontinencia urinaria por esfuerzo y resequedad vaginal. Dentro de los distintos tratamientos, el láser tiene como objetivo la restauración de la mucosa vaginal, estimulando los fibroblastos para obtener la neo colagenogenesis y vascularización, recuperando su funcionalidad y obteniendo mejoría de los síntomas junto con la calidad de vida de las pacientes

Genitourinary syndrome of menopause refers to a group of signs and symptoms related to the decreased estrogen and as a result, the vaginal atrophy, this has a great negative impact on the daily activities of women, there are several treatments to alleviate and resolve the symptoms, the most frequent being stress urinary incontinence and vaginal dryness. Among the different treatments, the laser aims to restore the aavaginal mucosa, stimulating fibroblasts to obtain neo-collagen oogenesis and revascularization, recovering their functionality and obtaining an improvement in symptoms along with the quality of life of patients

Tratamiento de hipoparatiroidismo con parathormona recombinante humana [rhPTH(1-84)] / Hypoparathyroidism treated with recombinant human parathyroid hormone [rhPTH(1-84)]

El hipoparatiroidismo (hipoPTH) es una enfermedad infrecuente caracterizada por hipocalcemia y niveles inapropiadamente bajos o ausentes de parathormona. Presentamos el caso de un hombre de 25 años, deportista de alto rendimiento, con antecedente de hipoPTH secundario a tiroidectomía total dos años antes por cáncer papilar multifocal bilateral tiroideo, estadificado como T3 N1b M0, derivado por hipocalcemia sintomática. Presentaba calcemias promedio de 7mg%, síntomas de hipocalcemia en reposo y múltiples internaciones. Inicialmente, se optimizó tratamiento convencional con aporte de calcio vía oral hasta 12g/día, vitamina D y calcitriol, sin mejoría clínica ni bioquímica. Se descartaron malabsorción y complicaciones crónicas de hipoPTH. Se evidenció a través de cuestionario de salud SF-36 disminución de la calidad de vida. Se indicó sustitución con parathormona recombinante humana [rhPTH(1-84)] 50μg/día subcutánea con posterior ascenso a 75μg y reducción progresiva de la medicación por vía oral. Actualmente se encuentra asintomático, sin requerimiento de calcio ni vitamina D, mantiene calcemias de 9mg%, realiza actividad deportiva y demuestra marcada mejoría en la calidad de vida según cuestionario SF-36 (36-Item Short Form Health Survey).

Hypoparathyroidism (HypoPT) is a rare disease characterized by low calcium and inappropriately low circulating parathormone levels. We present the case of a 25-year-old high-performance athlete male, with history of HypoPT after total thyroidectomy for papillary thyroid carcinoma (T3 N1b M0) two years before, who was referred to our clinic for symptomatic hypocalcemia. The patient reported serum calcium average levels of 7mg%, presented symptoms of hypocalcemia at rest and had multiple hospital admissions. First, standard treatment was optimized by calcium supplementation up to 12g/d and active vitamin D, not showing clinical or biochemical improvement. Malabsorption and complications of chronic HypoPT were ruled out. The 36-Item Short Form Health Survey (SF-36) demonstrated an impaired quality of life (QoL). Full-length recombinant human parathyroid hormone [rhPTH(1-84)] therapy was started with 50μg/d subcutaneous, and later adjusted to 75μg/d and the oral treatment gradually decreased. Currently, he is asymptomatic, with serum calcium levels above 9mg%, without receiving oral medication. He performs sports activity and shows marked improvement in quality of life according to SF-36 questionnaire.

Personalized approach to growth hormone replacement in adults

ABSTRACT Growth hormone (GH) deficiency (GHD) in adults is well-characterized and includes abnormal body composition, reduced bone mass, an adverse cardiovascular risk profile, and impaired quality of life. In the early 1990s, it was also shown that patients with hypopituitarism without GH replacement therapy (GHRT) had excess mortality. Today, GHRT has been shown to decrease or reverse the negative effects of GHD. In addition, recent papers have shown that mortality and morbidity are approaching normal in hypopituitary patients with GHD who receive modern endocrine therapy including GHRT. Since the first dose-finding studies, it has been clear that efficacy and side effects differ substantially between patients. Many factors have been suggested as affecting responsiveness, such as sex, age, age at GHD onset, adherence, and GH receptor polymorphisms, with sex and sex steroid replacement having the greatest impact. Therefore, the individual tailoring of GH dose is of great importance to achieve sufficient efficacy without side effects. One group that stands out is women receiving oral estrogen replacement, who needs the highest dose. Serum insulin-like growth factor-1 (IGF-1) is still the most used biochemical biomarker for GH dose titration, although the best serum IGF-1 target is still debated. Patients with GHD due to acromegaly, Cushing's disease, or craniopharyngioma experience similar effects from GHRT as others. Arch Endocrinol Metab. 2019;63(6):592-600

Human chorionic gonadotropin monotherapy for the treatment of hypogonadal symptoms in men with total testosterone > 300 ng/dL

ABSTRACT Purpose The 2018 American Urological Association guidelines on the Evaluation and Management of Testosterone Deficiency recommended that 300 ng/dL be used as the threshold for prescribing testosterone replacement therapy (TRT). However, it is not uncommon for men to present with signs and symptoms of testosterone deficiency, despite having testosterone levels greater than 300 ng/dL. There exists scant literature regarding the use of hCG monotherapy for the treatment of hypogonadism in men not interested in fertility. We sought to evaluate serum testosterone response and duration of therapy of hCG monotherapy for men with symptoms of hypogonadism, but total testosterone levels > 300 ng/dL. Materials and Methods We performed a multi-institutional retrospective case series of men receiving hCG monotherapy for symptomatic hypogonadism. We evaluated patient age, treatment indication, hCG dosage, past medical history, physical exam findings and serum testosterone and gonadotropins before and after therapy. Descriptive analysis was performed and Mann Whitney U Test was utilized for statistical analysis. Results Of the 20 men included in the study, treatment indications included low libido (45%), lack of energy (50%), and erectile dysfunction (45%). Mean testosterone improved by 49.9% from a baseline of 362 ng/dL (SD 158) to 519.8 ng/dL (SD 265.6), (p=0.006). Median duration of therapy was 8 months (SD 5 months). Fifty percent of patients reported symptom improvement. Conclusions Treatment of hypogonadal symptoms with hCG for men who have a baseline testosterone level > 300 ng/dL appears to be safe and efficacious with no adverse events.

Resolution of fatty liver disease after growth hormone replacement in a pediatric survivor of thyroid cancer / Resolución de enfermedad hepática grasa posterior al reemplazo con hormona de crecimiento en un paciente pediátrico sobreviviente a cáncer de tiroides

Abstract Background A rare case of primary papillary thyroid cancer (PTC) and growth hormone (GH) deficiency in a pediatric patient is described. In addition, the patient developed fatty liver disease attributed to GH deficiency. Case report A 10-year-old male with a history of PTC with extension to the cervical nodes detected at 5 years of age was referred to the endocrinology consultation due to a low growth rate. On examination, GH deficiency was detected (height −3.51 standard deviations and low insulin-like growth factor-1 levels). This hormonal deficiency was not associated with thyroid cancer or treatment. Furthermore, elevated transaminases (~300 IU/ml), lipids, and fally liver disease by ultrasound were detected. These data suggested fatty liver disease, which was attributed to GH deficiency. Regardless of the risk of recurrence, somatotropin was administered due to liver dysfunction and very short stature of the patient. A considerable improvement in growth, transaminases, and lipid profile was observed. At present, at 14 years of age, resolution of hepatic steatosis and a considerable increase in his growth rate without recurrence of thyroid cancer 9 years after its diagnosis and 4 years after the initiation of GH treatment are confirmed. Conclusions GH therapy could be a good therapeutic option for pediatric cancer survivors to address impaired growth and fatty liver disease. However, additional medical evidence based on clinical trials is necessary to determine the benefits.

Resumen Introducción Se presenta el caso de un paciente pediátrico con una asociación de cáncer papilar de tiroides (CPT) y deficiencia de hormona de crecimiento (HC) que no ha sido descrita previamente. Además, presenta enfermedad hepática grasa atribuida a la deficiencia hormonal. Caso clínico Paciente de sexo masculino con antecedente de CPT con extensión a los ganglios cervicales diagnosticado a los 5 años de edad. Es referido a los 10 años por talla baja, sin datos de recurrencia del CPT. En el abordaje diagnóstico se detecta deficiencia de HC basándose en una estatura 3.51 desviaciones estándar por debajo de la media y niveles bajos de factor de crecimiento insulínico tipo 1. Adicionalmente, se detectó elevación de transaminasas (~300 IU/ml), dislipidemia y esteatosis hepática en el ultrasonido. Después de los estudios de extensión, la enfermedad hepática grasa se atribuyó a la deficiencia de HC. A pesar del riesgo de recurrencia del cáncer de tiroides, se decidió dar tratamiento con HC debido a la afectación hepática y de crecimiento. El paciente presentó una evolución satisfactoria y actualmente, a la edad de 14 años, la esteatosis hepática está resuelta, presenta una mejoría considerable en su estatura y no ha tenido recurrencia del cáncer de tiroides 9 años después del diagnóstico y 4 años después del inicio del tratamiento con HC. Conclusiones El tratamiento con HC puede ser una adecuada opción terapéutica para sobrevivientes de cáncer en la edad pediátrica con afectación en el crecimiento y esteatosis hepática. Sin embargo, se requieren estudios con mayor evidencia científica y seguimiento a largo plazo para apoyar esta afirmación.

La terapia hormonal de la menopausia ¿disminuye el riesgo de enfermedades crónicas? / Does menopause hormone therapy reduce the risk of chronic diseases?

The hormonal deficit of post menopause is not only linked to the classic hot flashes, but also to a higher risk of chronic diseases. Menopausal hormone therapy (MHT) adequately treats climacteric symptoms and can prevent some chronic diseases such as osteoporosis. The Women's Health Initiative (WHI) study, which indicated risks of MHT in elderly postmenopausal women, caused a massive withdrawal of this therapy. But, in recent years the results of the WHI have been challenged by methodological problems and by several studies indicating that, if MHT is initiated early and the non-oral route is preferred, the risks could be minimized and it could improve not only the quality of life but also reduce the risk of chronic diseases. However, the US Preventive Services Task Force (USPSTF) recommends against the use of MHT for the prevention of chronic diseases, a position that has been challenged by publications of the North American Menopause Society and the International Menopause Society. This controversy persists so far. We report data that suggest a preventive role of MHT in perimenopausal women.

Influence of growth hormone replacement on neurological and psychomotor development. Case report / Influência da reposição do hormônio do crescimento no desenvolvimento neuropsicomotor. Relato de caso

ABSTRACT The height response to the use of growth hormone in short height cases has already been confirmed in the literature. The influence of the insulin-like growth factor 1 (GH-IGF1) axis components on development, function, regeneration, neuroprotection, cognition, and motor functions has been evaluated in experimental studies and in adults with central nervous system lesions. However, there is still little research on the clinical impact of hormone replacement on neurological and psychomotor development. This report presents the case of a patient with excellent weight-height recovery and, even more surprisingly, neurological and psychomotor development in response to use of growth hormone. The result strengthens the correlation between experimental and clinical findings related to cerebral plasticity response to growth hormone in children. A preterm male patient with multiple health problems during the neonatal and young infancy period, who for six years presented with a relevant deficit in growth, bone maturation, and neurological and psychomotor development. At six years of age, he had low stature (z-score −6.89), low growth rate, and low weight (z-score −7.91). He was incapable of sustaining his axial weight, had not developed fine motor skills or sphincter control, and presented with dysfunctional swallowing and language. Supplementary tests showed low IGF-11 levels, with no changes on the image of the hypothalamus-pituitary region, and bone age consistent with three-year-old children — for a chronological age of six years and one month. Growth hormone replacement therapy had a strong impact on the weight-height recovery as well as on the neurological and psychomotor development of this child.

RESUMO A resposta estatural ao uso de hormônio do crescimento na baixa estatura já está comprovada na literatura. A influência dos componentes do eixo fator de crescimento semelhante à insulina tipo 1 (GH-IGF1) sobre desenvolvimento, função, regeneração, neuroproteção, cognição e funções motoras tem sido avaliada em estudos experimentais e em adultos com lesão de sistema nervoso central. No entanto, ainda são poucas as pesquisas sobre o impacto clínico da reposição hormonal no desenvolvimento neuropsicomotor. Este relato apresenta o caso de um paciente com excelente recuperação pôndero-estatural e, de forma ainda mais surpreendente, de desenvolvimento neuropsicomotor, em resposta ao uso de hormônio do crescimento. O resultado observado fortalece a correlação entre achados experimentais e clínicos, no que diz respeito à resposta da plasticidade cerebral ao hormônio do crescimento em crianças. Paciente do sexo masculino nasceu pré-termo com múltiplos agravos no período neonatal e de lactente jovem, e que, por 6 anos, apresentou deficit relevante do crescimento, na maturação óssea e do desenvolvimento neuropsicomotor. Aos 6 anos de idade, apresentava baixa estatura (escore Z de −6,89), baixa velocidade de crescimento e baixo peso (escore Z de −7,91). Era incapaz de sustentar o peso axial, não tinha desenvolvido habilidade motora fina e nem controle esfincteriano, e apresentava também disfunção na deglutição e na linguagem. Exames complementares mostraram IGF1 baixo, sem alterações na imagem da região hipotálamo-hipofisária e idade óssea compatível com 3 anos — para a idade cronológica de 6 anos e 1 mês. A terapia de reposição com hormônio do crescimento promoveu forte impacto na recuperação pôndero-estatural e também do desenvolvimento neuropsicomotor desta criança.

Intensidad y evolución del síndrome climatérico y su relación con los factores de riesgo para aterosclerosis / Intensity and Evolution of the Climacteric Syndrome and Its Relation with Atherosclerosis Risk Factors

Introducción: el estudio del climaterio y la menopausia tiene gran importancia y vigencia por su morbilidad asociada. Objetivo: determinar la presencia de factores de riesgo ateroscleróticos con la intensidad y evolución del síndrome climatérico en este grupo. Métodos: estudio prospectivo y de intervención en mujeres de 40 a 59 años con síndrome climatérico a las que se les aplicó terapia hormonal -previo consentimiento informado- y se observó la respuesta evolutiva al mismo. Resultados: las variables estudiadas: sobrepeso, obesidad, sedentarismo, hábito de fumar, circunferencia de cintura, hipertensión arterial y diabetes mellitus tipo 2; así como la sobrecarga de género que tenían dichas mujeres, tuvieron relación con la presencia y evolución desfavorable del síndrome climatérico. La obesidad y el sobrepeso son las de mayor influencia sobre la evolución de este síndrome. La otra variable de mayor importancia fue el hábito de fumar. En orden de importancia le siguió el sedentarismo. Conclusiones: los factores de riesgo para aterosclerosis estudiados se asociaron con síndrome climatérico más intenso y con una evolución desfavorable del mismo, aporte científico de esta investigación, lo que también ocurrió con la sobrecarga de género. El aumento de la circunferencia de cintura, el índice de masa corporal elevado y el tabaquismo fueron los factores de riesgo de mayor importancia en la evolución desfavorable de dicho síndrome(AU)

Introduction: The study of climacteric and menopause has great importance and validity due to its associated morbidity. Objective: Determine the presence of atherosclerotic risk factors with the intensity and evolution of the climacteric syndrome in this group. Methods: A prospective and interventional study was carried out in women aged 40 to 59 years with climacteric syndrome who received hormone therapy - previous informed consent. The evolutionary response was observed. Results: The variables studied (overweight, obesity, sedentary lifestyle, smoking habits, waist circumference, arterial hypertension and type 2 diabetes mellitus), these women gender overload were related to the presence and unfavorable evolution of the climacteric syndrome. Obesity and overweight are the most influential on this syndrome evolution. The other major variable was smoking. In order of importance, sedentary followed. Conclusions: The atherosclerosis risk factors studied were associated with a more intense climacteric syndrome and with an unfavorable evolution of them, which is the scientific contribution of this research. Increased waist circumference, high body mass index and smoking habits were the most important risk factors for the unfavorable evolution of this syndrome(AU)

A boy with Prader-Willi syndrome: unmasking precocious puberty during growth hormone replacement therapy

SUMMARY Prader-Willi syndrome (PWS) is a genetic disorder frequently characterized by obesity, growth hormone deficiency, genital abnormalities, and hypogonadotropic hypogonadism. Incomplete or delayed pubertal development as well as premature adrenarche are usually found in PWS, whereas central precocious puberty (CPP) is very rare. This study aimed to report the clinical and biochemical follow-up of a PWS boy with CPP and to discuss the management of pubertal growth. By the age of 6, he had obesity, short stature, and many clinical criteria of PWS diagnosis, which was confirmed by DNA methylation test. Therapy with recombinant human growth hormone (rhGH) replacement (0.15 IU/kg/day) was started. Later, he presented psychomotor agitation, aggressive behavior, and increased testicular volume. Laboratory analyses were consistent with the diagnosis of CPP (gonadorelin-stimulated LH peak 15.8 IU/L, testosterone 54.7 ng/dL). The patient was then treated with gonadotropin-releasing hormone analog (GnRHa). Hypothalamic dysfunctions have been implicated in hormonal disturbances related to pubertal development, but no morphologic abnormalities were detected in the present case. Additional methylation analysis (MS-MLPA) of the chromosome 15q11 locus confirmed PWS diagnosis. We presented the fifth case of CPP in a genetically-confirmed PWS male. Combined therapy with GnRHa and rhGH may be beneficial in this rare condition of precocious pubertal development in PWS.

Testosterone and Voluntary Exercise, Alone or Together Increase Cardiac Activation of AKT and ERK1/2 in Diabetic Rats / Testosterona e Exercício Voluntário, Individualmente ou em Conjunto, Aumentam a Ativação Cardíaca de AKT e ERK1/2 em Ratos Diabéticos

Abstract Background: Impaired angiogenesis in cardiac tissue is a major complication of diabetes. Protein kinase B (AKT) and extracellular signal regulated kinase (ERK) signaling pathways play important role during capillary-like network formation in angiogenesis process. Objectives: To determine the effects of testosterone and voluntary exercise on levels of vascularity, phosphorylated Akt (P- AKT) and phosphorylated ERK (P-ERK) in heart tissue of diabetic and castrated diabetic rats. Methods: Type I diabetes was induced by i.p injection of 50 mg/kg of streptozotocin in animals. After 42 days of treatment with testosterone (2mg/kg/day) or voluntary exercise alone or in combination, heart tissue samples were collected and used for histological evaluation and determination of P-AKT and P-ERK levels by ELISA method. Results: Our results showed that either testosterone or exercise increased capillarity, P-AKT, and P-ERK levels in the heart of diabetic rats. Treatment of diabetic rats with testosterone and exercise had a synergistic effect on capillarity, P-AKT, and P-ERK levels in heart. Furthermore, in the castrated diabetes group, capillarity, P-AKT, and P-ERK levels significantly decreased in the heart, whereas either testosterone treatment or exercise training reversed these effects. Also, simultaneous treatment of castrated diabetic rats with testosterone and exercise had an additive effect on P-AKT and P-ERK levels. Conclusion: Our findings suggest that testosterone and exercise alone or together can increase angiogenesis in the heart of diabetic and castrated diabetic rats. The proangiogenesis effects of testosterone and exercise are associated with the enhanced activation of AKT and ERK1/2 in heart tissue.

Resumo Fundamento: Angiogênese prejudicada em tecido cardíaco é uma das principais complicações das diabetes. As vias de sinalização da proteína-quinase B (AKT) e a quinase regulada por sinal extracelular (ERK) exercem um importante papel durante a formação de uma rede similar à capilar no processo de angiogênese. Objetivos: Determinar os efeitos da testosterona e exercícios voluntários sobre os níveis de vascularidade, AKT fosforilada (P- AKT) e ERK fosforilada (P-ERK) sobre o tecido cardíaco de ratos diabéticos e castrados diabéticos. Métodos: A diabetes tipo 1 foi induzida através de injeção intraperitoneal de 50 mg/kg de estreptozotocina em animais. Após 42 dias de tratamento com testosterona (2mg/kg/dia) ou exercícios voluntários, individualmente ou em conjunto, as amostras de tecidos cardíacos foram coletadas e usadas para avaliação histológica e determinação de níveis de P-AKT e P-ERK através do método ELISA. Resultados: Os nossos resultados mostraram que a testosterona ou os exercícios aumentaram a capilaridade, os níveis de P-AKT, e P-ERK nos corações de ratos diabéticos. O tratamento de ratos diabéticos com testosterona e exercícios obteve um efeito sinérgico sobre a capilaridade, níveis de P-AKT, e P-ERK no coração. Além disto, na capilaridade do grupo diabético castrado, os níveis de P-AKT e P-ERK diminuíram significativamente no coração, ao passo que o tratamento com testosterona ou o treinamento com exercícios reverteu tais efeitos. O tratamento simultâneo de ratos diabéticos castrados com testosterona e exercícios obteve um efeito aditivo sobre os níveis de P-AKT e P-ERK. Conclusão: Nossas descobertas sugerem que a testosterona e exercícios, em conjunto ou individualmente, podem aumentar a angiogênese nos corações de ratos diabéticos e castrados diabéticos. Os efeitos favoráveis à angiogênese da testosterona e dos exercícios estão associados à ativação reforçada de AKT e ERK1/2 no tecido cardíaco.

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.

Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2) and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX) spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12 weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α) was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women.

Sangramento anormal durante terapia hormonal na pré e perimenopausa: racional para manejo clínico / Abnormal bleeding during perimenopause hormone therapy: insights for clinical management

Este estudo tem como objetivo rever o estado da arte e racional para guiar a conduta no sangramento anormal durante a terapia hormonal combinada sequencial na perimenopausa. Antes de iniciar a terapia, é essencial excluir qualquer condição pélvica anormal, identificar as mulheres com maior risco de sangramento e moldar o regime às características clínico-laboratoriais de cada paciente. Na perimenopausa, particularmente na mulher que ainda mantém secreção ovariana de estrogênio ou mesmo estrogênio-progesterona, o regime de escolha é o combinado sequencial. Tatear a dose individualmente é recomendável nos primeiros meses de uso. Qualquer ação para parar o sangramento deve ser baseada na identificação correta da causa subjacente. É importante observar se o sangramento ocorre na fase estrogênica ou progestogênica da combinação utilizada, se o seu início foi precedido de longo tempo de sangramento normal, se houve introdução de medicação concomitante e se a ingesta tem sido regular. O tratamento consiste no ajuste da dose do estrogênio ou do progestogênio, na troca do progestogênio para outro com maior impacto sobre o endométrio, ou na troca do regime combinado sequencial para o combinado contínuo, como medida de exceção.(AU)

The current study aimed to review the state of art and provide a rational approach to the diagnosis and treatment of abnormal bleeding during combined sequential hormone therapy (HT). Before starting, it is essential to exclude any pelvic abnormal condition, to identify those women with higher risk of bleeding and to tailor the regimen to the needs of individual women. During perimenopause, particularly in women still keeping ovarian secretion, the choice is the combined sequential regimen. It is recommended to titer the dosis individually. Any action to stop the bleeding must be based on correct identification of the underlying cause. It is important to consider whether the bleeding started in the strogenic or progestogenic phases of the combined regimen, if the abnormal bleeding was preceded of long-term normal bleeding or if any concomitant medication was prescribed. The core treatment consists of estrogen/progestogen dose adjustment, change of the progestogen, or change of the sequential to the combined continuos regimen an exceptional measure.(AU)

Impacto da hormonioterapia associada ao escore de predição de Wells no diagnóstico de trombose venosa profunda em mulheres submetidas a ecografia vascular / Impact of hormone therapy linked to wells prediction score in the diagnosis of deep vein thrombosis in women submitted to vascular ultrasound

Introdução: A trombose venosa profunda (TVP) apresenta elevada morbimortalidade. O escore de Wells foi elaborado para melhorar a capacidade diagnóstica pré-teste para TVP. O objetivo deste estudo foi ajustar o escore de Wells para pacientes brasileiras e incluir a variável hormonioterapia (HT), comparando acurácia e poder de reclassificação do novo escore com o original de Wells. Método: Estudo observacional transversal em que foi realizada regressão logística para incluir a variável hormonioterapia (HT) ao Escore de Wells, criando um novo escore (escore HT), que foi calibrado e ajustado para a população estudada. A qualidade dos dados foi avaliada pela estatística Kappa. Resultados: Foram estudadas 461 pacientes com idade de 56,1 ± 20,8, das quais 103 tiveram diagnóstico ecográfico de TVP. O escore HT incluiu sete variáveis, pacientes que obtiveram pontuação de -4 a 0 foram consideradas de baixo risco; de 1 a 3, moderado risco; e de 4 a 11, alto risco para TVP, com calibração adequada (valor p = 0,59). A área sob a curva ROC para o escore HT foi 0,92 (IC 95% 0,90 - 0,95) e para o escore de Wells foi de 0,87 (IC 95% 0,84 – 0,91), mostrando diferença estatisticamente significativa (p < 0,05).Conclusão: A inclusão da hormonioterapia a um modelo de predição clínica demonstrou maior acurácia comparativamente ao modelo de Wells.

Introduction: Deep venous thrombosis (DVT) presents high morbidity and mortality. The Wells score is designed to improve the pretest diagnosing capacity for DVT. The purpose of this study was to adjust the Wells score for Brazilian patients and include the variable hormone therapy (HT), comparing accuracy and power of reclassification of the new score with Wells’ original score.Methods: Cross-sectional observational study in which logistic regression was performed to include the variable hormone therapy (HT) to the Wells score, creating a new score (HT score), which has been calibrated and adjusted for the population studied. Data quality was evaluated by the Kappa statistics.Results: We studied 461 patients aged 56.1 ± 20.8, of which 103 had sonographic diagnosis of DVT. The HT score included seven variables: patients who achieved a score of -4 to 0 are considered low risk; 1 to 3, moderate risk; and 4 to 11, high risk for DVT, withproper calibration (p = 0.59). The area under the ROC curve for the HT score was 0.92 (95% CI 0.90 — 0.95) and for the Wells score it was 0.87 (95% CI 0.84 — 0.91), showing a statistically significant difference (p < 0.05).Conclusion: The inclusion of hormone therapy into a clinical prediction model showed higher accuracy compared to the model of Wells.

Outcomes of Prostate Biopsy in Men with Hypogonadism Prior or During Testosterone Replacement Therapy

Introduction: The relationship between Testosterone Replacement Therapy (TRT) and prostate cancer remains controversial. Most TRT studies show no change in prostate specific antigen (PSA) but some men do have PSA rise or develop an abnormal digital rectal exam (aDRE). Our objective was to examine the biopsy results of men with symptomatic hypogonadism before or during therapy. Materials and Methods: Data was extracted from our medical record on men with hypogonadism who had a prostate biopsy within the past 4 years done by 3 Urologists with guideline driven practice patterns. Results: 96 men were identified. Mean age at biopsy was 63 (range 40–85) and median PSA was 3.78ng/dL (0.5–662). Of the 61 men not on TRT, median PSA was 4.34 (0.5 to 662) and mean total testosterone 254 (191–341). There were 29 (47.5%) prostate cancers found (6 Gleason score 6, 13 Gleason score 7, 10 Gleason score 8 or 9). Of the 35 men on TRT, median PSA was 3.27 (0.5 to 13.7). The %PSA increase ranged from 2 to 251% (mean 93.5%). Mean total testosterone was 383 (146–792). Of the 14 men treated < 2 years, none had cancer. Of the 21 men treated 2 or more years 5 had cancer (2 Gleason score 6, 3 Gleason score 7). Conclusions: Men with hypogonadism and a clinical indication for biopsy often have prostate cancer, many high grade. No men with an initial PSA rise on TRT had cancer. Men on long term TRT should be monitored with PSA and DRE per guidelines.

Clinical Practice Guidance for the Use Of Clomiphene Citrate in Male Hormone Replacement Therapy (HRT).

Introduction: Inhibition of pituitary gonadotropin secretion in men by testosterone (T) is principally mediated by aromatization to estrogen (E), which inhibits hypothalamic secretion of gonadotropin-releasing hormone (GnRH). Material and Methods: Longitudinal clinical investigation unit-based evaluation of the clinical and biochemical response to E-receptor blockade. Initial monotherapy with 50 mg of clomiphene citrate (CC) daily for a period of 9 months, with diurnal morning peak testosterone and luteinizing hormone (LH) levels evaluated at three-month intervals thereafter. Th e patient then resumed hormone replacement therapy (HRT) using T cream with adjuvant CC therapy. Main Outcome Measures were Baseline and stimulated T and LH levels; eff ect on sexual function. Result(S): CC therapy resulted in complete normalization of pulsatile gonadotropin secretion, serum T level, and sexual function. Conclusion(S): Isolated hypogonadotropic hypogonadism (IHH) may result from an acquired defect of enhanced hypothalamic sensitivity to E-mediated negative feedback. Whereas direct T replacement therapy can further suppress endogenous gonadotropin secretion, treating IHH men with gonadotropins can stimulate endogenous T secretion and enhance fertility potential. Reversal of gonadotropin defi ciency with CC was found to have a similar biological eff ect.

Manejo de la mujer en transición menopáusica, menopausia y post-menopausia / Management of women in menopausal transition, menopause and post-menopause

El concepto actual de Salud Integral de la Mujer, y en especial de la Mujer Menopáusica, requiere que los grupos científicos relacionados con este tema, elaboren programas con dicho enfoque integral y que los mismos sean puestos en práctica a nivel público y privado. En atención a lo anterior, la Asociación Costarricense de Climaterio, Menopau-sia y Osteoporosis (ACCMYO) ha elaborado estas guías de Manejo de la Mujer en transición Menopáusica, Menopausia y Post-menopausia...

Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

OBJECTIVE: To determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10%) combined with estriol (0.1%) + estradiol (0.25%) for relieving postmenopausal symptoms. METHODS: A total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. RESULTS: An improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05) after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04±4.9 to 57.12±4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. CONCLUSION: The nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women. .