The effect of anastrozole therapy on final height and sex hormone levels in pubertal boys receiving growth hormone therapy

ABSTRACT Objective: This research aimed to evaluate retrospectively the effect of anastrozole on height gain and sex hormone levels in pubertal boys receiving growth hormone (GH). Materials and methods: Pubertal boys who received both GH and anastrozole (GH+A) were one-to-one matched with boys who received only GH (GH-Only) for chronological and bone age, pubertal stage and height before the GH initiation, treatment duration and midparental height. Anthropometric measurements throughout treatment and adult heights were compared between the groups. Sex hormone levels were evaluated longitudinally in the GH+A group. Results: Forty-eight cases (24 in each group) were included. There was no statistical difference in adult height between the GH+A and GH-Only (p = 0.071). However, when the analysis was limited to those receiving anastrozole for at least 2 years, mean adult height was higher in the GH+A than in the GH-Only group (173.1 ± 6.2/169.8 ± 5.6 cm, p = 0.044). Despite similar growth rates between the two groups, bone age advancement was slower in the GH+A than in the GH-Only in a mean anastrozole treatment period of 1.59 years (1.37 ± 0.80/1.81 ± 0.98 years, p = 0.001). The greatest increase for FSH, LH, total and free testosterone and decrease for estradiol levels were observed in the third month after anastrozole was started, albeit remaining within the normal ranges according to the actual pubertal stages. Conclusions: Using anastrozole with GH for at least 2 years decelerates the bone age advancement resulting in adult height gain with no abnormality in sex hormone levels. These results suggest anastrozole can be used as an additional treatment to GH for further height gain in pubertal boys.

Relationship between semen parameters, serum InhB, and INSL-3 levels, and the degree of varicocele

Abstract Background Varicocele is an abnormal expansion of the pampininias venous plexus in the scrotum, resulting in impaired sperm production and reduced sperm quality. The exact pathophysiological mechanism leading to varicocele-related infertility has not been fully elucidated. Although treatable, varicocele may lead to male infertility. Objective To investigate the relationship between semen parameters, serum InhB and INSL-3 levels, and the degree of varicocele in male patients. Methods Serum InhB and INSL-3 were detected. To evaluate the relationship between semen parameters and serum InhB and INSL-3 levels. To evaluate the value of semen parameters and serum InhB and INSL-3 levels in distinguishing disease severity in patients with varicocele. Results Serum INSL-3 in patients with varicocele decreased with the severity of the disease. Serum INSL-3 was positively correlated with total sperm count and frequency of normal sperm morphology. There was a weak correlation between serum InhB and semen volume, concentration, and total sperm. Patients with different disease severity were similar within the groups, with partial overlap or similarity between varicocele Grade I and Grade II, and significant differences between Grade III and Grade I and II. Semen volume, concentration, total sperm, normal sperm morphology, and serum InhB and INSL-3 levels could distinguish the degree of varicocele. Conclusion Semen parameters and the combination of serum InhB and INSL-3 levels in patients with varicocele are closely related to the severity of the disease. Serum INSL-3 is expected to be a potential biomarker for early clinical intervention.

Effect of treatment with growth hormone on body composition and metabolic profile of short children born small for gestational age / Efeito do tratamento com hormônio de crescimento na composição corporal e no perfil metabólico de crianças nascidas pequenas para a idade gestacional com baixa estatura

ABSTRACT Objective: To assess the effect of recombinant growth hormone (rGH) on body composition and metabolic profile of prepubertal short children born small for gestational age (SGA) before and after 18 months of treatment. Methods: It is a clinical, non-randomized, and paired study. Children born SGA, with birth weight and/or length <-2 standard deviations (SD) for gestational age and sex, prepubertal, born at full term, of both genders, with the indication for treatment with rGH were included. The intervention was performed with biosynthetic rGH at doses ranging from 0.03 to 0.05 mg/kg/day, administered subcutaneously, once a day at bedtime. Total lean mass (LM) and total fat mass (FM) were carried out using dual-energy X-ray absorptiometry (DXA), and the metabolic profile was assessed for insulin, glycemia, IGF-1 levels and lipid profile. Results: Twelve patients (nine girls, 8.17±2.39 y) were evaluated; three patients dropped out of the study. There was an increase of LM adjusted for length (LMI) (p=0.008), LMI standard deviation score (SDS) adjusted for age and sex (p=0.007), and total LM (p<0.001). The percentage of body fat (BF%) and abdominal fat (AF) remained unaltered in relation to the beginning of treatment. Among the metabolic variables, blood glucose remained within normal levels, and there was a reduction in the number of participants with altered cholesterol (p=0.023). Conclusions: The effect of rGH treatment was higher on LM than in FM, with increased LM adjusted for length and standardized for age and sex. Glycemia remained within the normal limits, and there was a decreased number of children with total cholesterol above the recommended levels.

RESUMO Objetivo: Avaliar o efeito do hormônio de crescimento recombinante (rHC) na composição corporal e no perfil metabólico de crianças pré-púberes com baixa estatura, nascidas pequenas para a idade gestacional (PIG) antes e depois de 18 meses de tratamento. Métodos: Estudo clínico, não randomizado e pareado. Foram incluídas crianças nascidas PIG, com peso e/ou altura ao nascer <-2 desvios padrão (DP) para idade gestacional e sexo, pré-púberes, nascidas a termo, de ambos os sexos, com indicação de tratamento com rGH. A intervenção foi realizada com rGH biossintético com doses variando de 0,03 a 0,05 mg/kg/dia, administrado por via subcutânea, uma vez ao dia ao deitar-se. A massa magra total (LM) e a massa gorda total (MG) foram determinadas por meio de absorciometria de raios X de dupla energia (DXA), e o perfil metabólico foi avaliado com dosagens de insulina, glicemia, IGF-1 e perfil lipídico. Resultados: Doze pacientes (nove meninas, 8,17±2,39 anos) foram avaliados; três pacientes abandonaram o estudo. Houve aumento da LM ajustada para estatura (LMI) (p=0,008), LMI standard deviation scores (SDS) ajustada para idade e sexo (p=0,007) e LM total (p<0,001). O percentual de gordura corporal (GC%) e gordura abdominal (AF) permaneceu inalterado em relação ao início do tratamento. Entre as variáveis metabólicas, a glicemia manteve-se na normalidade, e houve redução do número de participantes com colesterol alterado (p=0,023). Conclusões: O efeito do tratamento com HCr foi maior na MM do que na MG, com o aumento da MM ajustada para altura e padronizada para idade e sexo. A glicemia permaneceu normal e houve redução do número de crianças com colesterol total acima do recomendado.

Genetic diagnosis of congenital hypopituitarism in Turkish patients by a target gene panel: novel pathogenic variants in GHRHR, GLI2, LHX4 and POU1F1 genes

ABSTRACT Objective: Congenital hypopituitarism (CH) is a rare disease characterized by one or more hormone deficiencies of the pituitary gland. To date, many genes have been associated with CH. In this study, we identified the allelic variant spectrum of 11 causative genes in Turkish patients with CH. Materials and methods: This study included 47 patients [21 girls (44.6%) and 26 boys (55.4%)] from 45 families. To identify the genetic etiology, we screened 11 candidate genes associated with CH using next-generation sequencing. To confirm and detect the status of the specific familial variant in relatives, Sanger sequencing was also performed. Results: We identified 12 possible pathogenic variants in GHRHR, GH1, GLI2, PROP-1, POU1F1, and LHX4 in 11 patients (23.4%), of which six were novel variants: two in GHRHR, two in POU1F1, one in GLI2, and one in LHX4. In all patients, these variants were most frequently found in GLI2, followed by PROP-1 and GHRHR. Conclusion: Genetic causes were determined in only 23.4% of all patients with CH and 63% of molecularly diagnosed patients (7/11) from consanguineous families. Despite advances in genetics, we were unable to identify the genetic etiology of most patients with CH, suggesting the effect of unknown genes or environmental factors. More genetic studies are necessary to understand the etiology of CH.

Manejo de la neoplasia trofoblástica gestacional. A propósito de un caso

La enfermedad trofoblástica gestacional es definida como un grupo heterogéneo de lesiones, las cuales surgen a partir del epitelio trofoblástico de la placenta luego de una fertilización anormal. Se presenta el caso de una paciente de 35 años de edad, con diagnóstico de neoplasia trofoblástica gestacional posmolar en etapa I, que se detectó tras estudios imagenológicos de seguimiento y determinación de la hormona gonadotropina coriónica humana, para lo cual llevó tratamiento con quimioterapia y terapéutica de mantenimiento con metotrexato por 5 días o metotrexato/ácido folínico por 8 días, hasta la normalización de la gonadotropina coriónica humana. Lo más relevante es que, aunque estos tumores abarcan menos del 1 % de los tumores ginecológicos, representan una amenaza para la vida de las mujeres en edad reproductiva.

Gestational trophoblastic disease is defined as a heterogeneous group of lesions, which arise from the trophoblastic epithelium of the placenta after abnormal fertilization. The case of a 35-year-old female patient is presented with a diagnosis of posmolar gestational trophoblastic neoplasia in stage I, which was detected after follow-up imaging studies and determination of human chorionic gonadotropin, for which she underwent chemotherapy treatment and maintenance therapy with methotrexate for 5 days or methotrexate/folinic acid for 8 days, until normalization of human chorionic gonadotropin The most relevant thing is that, although these tumors comprise less than 1% of gynecological tumors, they represent a threat to the life of women of reproductive age.

Pharmacotherapy plan for metastatic hormone-sensitive prostate cancer：a network meta-analysis / 中国药房

OBJECTIVE To determine the optimal therapeutic plan for metastatic hormone-sensitive prostate cancer （mHSPC）， and to provide reference for clinical decision-making. METHODS Retrieved from Medline， Embase， BIOSIS preview， the Cochrane Library and ClinicalTrials. gov systematically， randomized controlled trials about mHSPC therapy， with overall survival （OS） and radiographic progression-free survival （rPFS） as efficacy outcomes and the incidence of serious adverse events （SAEs） as safety outcome， were collected during the inception-Mar. 2022. Two researchers independently screened the literature， extracted data， and evaluated the risk of bias for the included study before conducting a Bayesian network meta-analysis. RESULTS Eight studies with 9 437 patients were finally included. The effectiveness and safety of 7 therapy plans were compared [abiraterone acetate， apalutamide， darolutamide+docetaxel， docetaxel， enzalutamide， standard non-steroidal antiandrogen （SNA） in addition to ADT， and ADT alone]. In terms of efficacy index， the most beneficial regimen （except for ADT+SNA） for OS was ADT+darolutamide+docetaxel （HR＝0.54， 95%CI of 0.44-0.66）， followed by ADT+abiraterone acetate （HR＝0.64，95%CI of 0.57- 0.71）， apalutamide （HR＝0.65， 95%CI of 0.53-0.79）， enzalutamide （HR＝0.66， 95%CI of 0.53-0.82）； the least beneficial regimen for OS was ADT+docetaxel （HR＝0.79， 95%CI of 0.71-0.88）. The most beneficial regimen （except for ADT+SNA） for rPFS was ADT+enzalutamide （HR＝0.39， 95%CI of 0.30-0.50）， followed by ADT+apalutamide （HR＝0.48， 95%CI of 0.39- 0.60）， abiraterone acetate （HR＝0.57， 95%CI of 0.51-0.64）， docetaxel （HR＝0.62， 95%CI of 0.56-0.69）. The results of the tumor- loading subgroup analysis were the same. In terms of safety， ADT+darolutamide+docetaxel （OR＝25.86， 95%CI of 14.08-51.33）， and ADT+docetaxel （OR＝23.35， 95%CI of 13.26-44.81） were associated with markedly increased SAEs； the incidence of SAEs caused by ADT+abiraterone acetate （OR＝1.42，95%CI of 1.10-1.82） was slightly increased， and those of other therapy plans had no significant difference. CONCLUSIONS Compared with ADT alone， ADT+ darolutamide+docetaxel may provide the most significant OS benefit， but the incidence of SAEs is increased greatly； compared with ADT+docetaxel， ADT+abiraterone acetate， apalutamide or enzalutamide provide more OS benefits. ADT+enzalutamide provide optimal rPFS benefits with no increased SAEs.

Relación entre hormona paratiroidea alterada y fracturas óseas en pacientes en hemodiálisis

Contexto: Las fracturas óseas en pacientes en hemodiálisis son frecuentes y agregan una grave incapacidad y morbimortalidad; se han relacionado a alteraciones óseo-minerales, aunque su asociación con las alteraciones de la hormona paratiroidea es controversial. Objetivo: determinar la relación entre hormona paratiroidea intacta (PTH) alterada y fracturas óseas en pacientes en hemodiálisis. Metodología: se realizó un estudio transversal y analítico en 250 pacientes en hemodiálisis atendidos en el Hospital Víctor Lazarte Echegaray (La Libertad, Perú) entre el 2015 y el 2020. Los pacientes se clasificaron de acuerdo con su valor de PTH (alterada si PTH 300 pg/ml) y la presentación de fracturas óseas. La asociación entre PTH alterada y la presencia de fracturas óseas se determinó al usar un análisis bivariado y multivariado; los resultados se presentan como odds ratio (OR) considerando un valor p significativo si < 0,05. Resultados: se evaluaron 250 pacientes, 69 tuvieron PTH alterada (27,6 %) y 181 tuvieron PTH normal (72,4 %); asimismo, 42 tenían fracturas óseas (16,8 %) y 208 no tenían fracturas óseas (83,2 %). De los 42 pacientes con fracturas óseas, 22 presentaron PTH alterada (52,4 %) y 20 PTH normal (47,6 %); de los 208 pacientes sin fracturas óseas, 47 presentaron PTH alterada (22,6 %) y 161 PTH normal (p = 0,001) (77,4 %). Así, tener PTH alterada se asoció a la presencia de fracturas óseas con un OR de 3,77 (IC 95 %: 1,90-7,49) en el análisis bivariado y un OR de 2,85 (IC 95 %: 1,19-6,82) en el análisis multivariado. Las covariables que se asociaron a presencia de fracturas óseas fueron: tener más de 60 años (OR: 2,74, IC 95 %: 1,12-6,69) y tener más de cinco años en hemodiálisis (OR: 6,72, IC 95 %: 2,98-15,13). Conclusiones: la hormona paratiroidea alterada se relaciona con fracturas óseas en pacientes en hemodiálisis.

Background: Bone fractures in patients on dialysis are frequent and impose a high burden of disability and multimorbidity. They have been linked to mineral-bone disorders but its association with parathyroid hormone remains controversial. Purpose: To determine the relationship between altered parathyroid hormone (PTH) and bone fractures in hemodialysis patients. Metthodology: A cross-sectional, analytical study was conducted in 250 hemodialysis patients attending Hospital Víctor Lazarte Echegaray from 2015 to 2020. Patients were classified according to whether their PTH was altered (PTH 300 pg/ml) and whether bone fractures were present. The association between altered PTH and the presence of bone fractures was determined using bivariate and multivariate analysis; the results are presented as odds ratio (OR) considering a significant p-value if <0.05. Results: 250 patients were evaluated in which 69 (27.6%) had altered PTH, 181 (72.4%) had normal PTH; likewise, 42 (16.8%) had bone fractures and 208 (83.2%) had no bone fractures. Of the 42 patients with bone fractures, 22 (52.4%) had altered PTH and 20 (47.6%) had normal PTH; of the 208 patients without bone fractures, 47 (22.6%) had altered PTH and 161 (77.4%) had normal PTH (p=0.001). Altered PTH was associated with the presence of bone fractures with OR: 3.77 (95% CI: 1.90-7.49) in the bivariate analysis and with OR: 2.85 (95% CI: 1.19-6.82) in the multivariate analysis. The covariates that were associated with the presence of bone fractures were being over 60 years (OR: 2.74, 95% CI: 1.12-6.69) and having been on hemodialysis for more than 5 years (OR: 6.72, 95% CI: 2.98-15.13). Conclusions: Altered parathyroid hormone is related with bone fractures in hemodialysis patients.

La relación entre la transición a la menopausia y los trastornos del estado de ánimo / The relationship between menopause transition and mood disorders

Este estudio tuvo como objetivo examinar la relación entre la transición a la menopausia y los trastornos del estado de ánimo, específicamente la ansiedad y la depresión. Se llevó a cabo una revisión narrativa de la literatura relevante sobre la transición a la menopausia y los trastornos del estado de ánimo. Se revisaron estudios que se enfocaron en el impacto de los cambios hormonales durante la menopausia en el bienestar psicológico y se evaluaron diversas opciones de tratamiento para los trastornos del estado de ánimo. La disminución de los niveles hormonales de estrógenos y progesterona durante la menopausia puede llevar a diversos cambios psicológicos, como ansiedad y depresión. La terapia hormonal con estrógenos solo o en combinación con progesterona puede mejorar los síntomas depresivos en mujeres en la menopausia, pero este tratamiento no está exento de riesgos. Otros tratamientos no hormonales, como la terapia cognitivo-conductual, el ejercicio y una buena higiene del sueño, también pueden ser efectivos para manejar los trastornos del estado de ánimo. Se concluyó que existe una compleja interacción entre factores hormonales, biológicos y psicosociales para desarrollar intervenciones efectivas que mejoren el bienestar psicológico de las mujeres en la menopausia.

This study aimed to examine the relationship between menopause transition and mood disorders, specifically anxiety and depression. The authors conducted a narrative review of relevant literature on menopause transition and mood disorders. They reviewed studies that focused on the impact of hormonal changes during menopause on psychological well-being and evaluated various treatment options for mood disorders. The decline in estrogen and progesterone hormone levels during menopause can lead to various psychological changes, such as anxiety and depression. Hormonal therapy with estrogen alone or in combination with progesterone can improve depressive symptoms in menopausal women, but this treatment is not without risks. Other non-hormonal treatments, such as cognitive-behavioral therapy, exercise, and good sleep hygiene, can also be effective in managing mood disorders. The study highlights the need for recognition of the complex interplay between hormonal, biological, and psychosocial factors in developing effective interventions to improve the psychological well-being of menopausal women. Further research is needed to fully understand the potential relationship between menopause transition and mood disorders.

Protective Effects and Mechanisms of Huangqi Decoction Against Radiation-Induced Bystander Effects / Efectos Protectores y Mecanismos de la Decocción de Huangqi Contra los Efectos Secundarios Inducidos por la Radiación

SUMMARY: The 12C6+ heavy ion beam irradiation can cause bystander effects. The inflammatory cytokines, endocrine hormones and apoptotic proteins may be involved in 12C6+ irradiation-induced bystander effects. This study characterized the protective effects and mechanisms of Huangqi decoction (HQD) against 12C6+ radiation induced bystander effects. Wistar rats were randomly divided into control, 12C6+ heavy ion irradiation model, and high-dose/medium-dose/low-dose HQD groups. HE staining assessed the pathological changes of brain and kidney. Peripheral blood chemical indicators as well as inflammatory factors and endocrine hormones were detected. Apoptosis was measured with TUNEL. Proliferating cell nuclear antigen (PCNA) expression was determined with real-time PCR and Western blot.Irradiation induced pathological damage to the brain and kidney tissues. After irradiation, the numbers of white blood cells (WBC) and monocyte, and the expression of interleukin (IL)-2, corticotropin-releasing hormone (CRH) and PCNA decreased. The damage was accompanied by increased expression of IL-1β, IL-6, corticosterone (CORT) and adrenocorticotropic hormone (ACTH) as well as increased neuronal apoptosis. These effects were indicative of radiation-induced bystander effects. Administration of HQD attenuated the pathological damage to brain and kidney tissues, and increased the numbers of WBC, neutrophils, lymphocyte and monocytes, as well as the expression of IL-2, CRH and PCNA. It also decreased the expression of IL-1β, IL-6, CORT and ACTH as well as neuronal apoptosis. HQD exhibits protective effects against 12C6+ radiation-induced bystander effects. The underlying mechanism may involve the promotion of the production of peripheral blood cells, inhibition of inflammatory factors and apoptosis, and regulation of endocrine hormones.

La irradiación con haz de iones pesados 12C6+ puede provocar efectos secundarios. Las citoquinas inflamatorias, las hormonas endocrinas y las proteínas apoptóticas pueden estar involucradas en los efectos secundarios inducidos por la irradiación 12C6+. Este estudio caracterizó los efectos y mecanismos protectores de la decocción de Huangqi (HQD) contra los efectos externos inducidos por la radiación 12C6+. Las ratas Wistar se dividieron aleatoriamente en grupos control, modelo de irradiación de iones pesados 12C6+ y grupos de dosis alta/media/baja de HQD. La tinción con HE evaluó los cambios patológicos del cerebro y el riñón. Se detectaron indicadores químicos de sangre periférica, así como factores inflamatorios y hormonas endocrinas. La apoptosis se midió con TUNEL. La expresión del antígeno nuclear de células en proliferación (PCNA) se determinó mediante PCR en tiempo real y transferencia Western blot. La irradiación indujo daños patológicos en los tejidos cerebrales y renales. Después de la irradiación, disminuyó el número de glóbulos blancos (WBC) y monocitos, y la expresión de interleucina (IL)-2, hormona liberadora de corticotropina (CRH) y PCNA. El daño estuvo acompañado por una mayor expresión de IL-1β, IL-6, corticosterona (CORT) y hormona adrenocorticotrópica (ACTH), así como un aumento de la apoptosis neuronal. Estas alteraciones fueron indicativas de efectos inducidos por la radiación. La administración de HQD atenuó el daño patológico a los tejidos cerebrales y renales, y aumentó el número de leucocitos y monocitos, así como la expresión de IL-2, CRH y PCNA. También disminuyó la expresión de IL-1β, IL-6, CORT y ACTH, así como la apoptosis neuronal. HQD exhibe mecanismos protectores contra los efectos externos inducidos por la radiación 12C6+. El mecanismo subyacente puede implicar la promoción de la producción de células sanguíneas periféricas, la inhibición de factores inflamatorios y la apoptosis y la regulación de hormonas endocrinas.

Survivin expression as a prognostic marker for breast cancer

SUMMARY OBJECTIVE: Due to the speed of development observed in breast cancer, several studies aimed at discovering new biomarkers have been carried out in order to arrive at an early diagnosis. As survivin plays a fundamental role in the evasion of apoptosis in tumor cells, the aim of this study was to verify the expression profile of the survivin gene in paraffin-embedded breast tumor samples and associate it with the clinical characteristics of the patients. METHODS: This is a cross-sectional study, for which 100 tumor samples were obtained from cancer patients treated throughout the year 2019 at Instituto de Mama do Cariri (Juazeiro do Norte, in the state of Ceará). This study included women over 30 years old who had confirmed breast cancer through anatomopathological examination but excluded those with non-neoplastic breast comorbidities, other neoplasms, or chronic diseases. Survivin gene expression was assessed by quantitative polymerase chain reaction. RESULTS: The expression of survivin is associated with the lack of expression of estrogen (p=0.027) and progesterone (p>0.0005) receptors. It means that survivin expression is higher in patients in which labeling was absent for estrogen receptor and progesterone receptor. CONCLUSION: Our data reinforce that survivin expression is higher in estrogen receptor-patients, thus representing an additional prognostic tool.

Menopausia quirúrgica en pacientes con mutación BRCA, el papel de la terapia hormonal / Surgical Menopause in Patients with BRCA Mutation, the Role of Hormone Therapy

Introducción: las mujeres con mutación BRCA1/2 (mBRCA) tienen un riesgo aumentado de desarrollar cáncer de mama (CM) y ovario (CO). La salpingo-oforectomía bilateral (SOB) se asocia con la reducción del riesgo del 80% para CO y un 50% para CM. Se recomienda realizarla entre los 35 y 40 años. Como consecuencia se produce una menopausia prematura, con un impacto negativo sobre la calidad de vida por la presencia de síntomas climatéricos, aumento del riesgo de enfermedad cardiovascular, osteoporosis y riesgo de alteración cognitiva. La terapia hormonal (THM) es el tratamiento más eficaz para la prevención de estos síntomas. Estado del arte: distintos estudios han demostrado un mayor riesgo de CM en mujeres posmenopáusicas que reciben THM en particular con terapia combinada, estrógeno + progesterona (E+P). Según el metanálisis de Marchetti y cols., en las mujeres portadoras de mBRCA que recibieron THM, no hubo diferencias en el riesgo de CM comparando E solo con E+P. En el estudio de Kotsopoulos, incluso se encontró un posible efecto protector en aquellas que usaron E solo. Otro estudio en portadoras sanas demostró que, en las mujeres menores de 45 años al momento de la SOB, la THM no afectó las tasas de CM. Sin embargo, en las mujeres mayores de 45 años, las tasas de CM fueron más altas. Como el esquema de E+P se asocia con un mayor riesgo relativo (RR) de CM, las dosis de progestágenos utilizados se deberían limitar, eligiendo derivados naturales de progesterona, de uso intermitente para disminuir la exposición sistémica. Según diferentes guías internacionales, a las portadoras de mBRCA sanas que se someten a una SOB se les debe ofrecer THM hasta la edad promedio de la menopausia. Conclusión: la menopausia prematura disminuye la expectativa de vida; es por ello que una de las herramientas para mejorar y prevenir el deterioro de la calidad de vida es la THM. El uso de THM a corto plazo parece seguro para las mujeres portadoras de mBRCA que se someten a una SOB antes de los 45 años, al no contrarrestar la reducción del riesgo de CM obtenida gracias a la cirugía. (AU)

Introduction: women with BRCA1/2 (mBRCA) mutation have an increased risk of developing breast (BC) and ovarian (OC) cancer. Bilateral salpingo-oophorectomy (BSO) is associated with an 80% risk reduction for OC and 50% for BC. The recommended age for this procedure is 35 to 40 years. The consequence is premature menopause, which hurts the quality of life due to the presence of climacteric symptoms, increased risk of cardiovascular disease, osteoporosis, and a higher risk of cognitive impairment. Hormone therapy (MHT) is the most effective treatment for preventing these symptoms. State of the art: different studies have shown an increased risk of BC in postmenopausal women receiving MHT, particularly with combined therapy, estrogen + progesterone (E+P). According to the meta-analysis by Marchetti et al., in women carrying mBRCA who received MHT, there was no difference in the risk of BC compared to E alone with E+P. In the Kostopoulos study, there was also a possible protective effect in those who used E alone. Another study in healthy carriers showed that in women younger than 45 years at the time of BSO, MHT did not affect BC rates. However, in women older than 45 years, BC rates were higher. As the E+P scheme is associated with a higher RR of BC, the doses of progestogens should be limited, choosing natural progesterone byproducts of intermittent use to decrease systemic exposure. According to various international guidelines, healthy mBRCA carriers undergoing BSO should be offered MHT until the average age of menopause. Conclusion: premature menopause decreases life expectancy, which is why one of the tools to improve and prevent deterioration of quality of life is MHT. Short-term use of MHT appears safe for women with mBRCA who undergo BSO before age 45 as it does not counteract the reduction in the risk of MC obtained by surgery. (AU)

Association Between Hormone Therapy and Weight Gain in the Menopause Transition and After Menopause: A Systematic Review and Meta-Analysis

Objectives: to conduct a systematic review and meta-analysis in order to assess whether hormone therapy (HT) increases weight in women in the menopausal transition and after menopause. Method: this article proposes an update to the systematic review published in 2005 by the Cochrane Library (Kongnyuy EJ et al 2005) with reference to studies assessing weight changes in women receiving HT from 1986 to 2005. Following PRISMA recommendations, we included randomized controlled trials (RCTs) ) from May 2005 onwards from Medline, Embase, and the Cochrane CENTRAL databases. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated. Two authors independently assessed the risk of biases in the selected studies. Results: ten RCTs were included, totaling 2,588 HT users and 764 non-users. Different regimens, dosages, and routes of administration in HT users were analyzed and compared to non-users. The results did not show statistically significant differences for most of the HT regimens evaluated. There was significant weight gain only in patients using EEC alone at dosages of 0.45 mg/day and 0.3 mg/day when compared to placebo (p 0.01); as well as in patients receiving esto-progestative combinations of 0.5 mg/day 17-beta-estradiol (E2) + 100 mg/day progesterone, with a 0.7 kg weight increase (p 0.032). On the other hand, the combinations of 1 mg/day estradiol valerate + 3 mg/day drospirenone showed a -1.0 kg reduction (p = 0.04), whereas a -0.2 kg reduction (p = 0.001) was identified in patients using 1 mg /day estradiol (E) + 0.5 mg norethisterone acetate (NETA). Tibolone therapy showed no statistically significant changes in weight. After performing a meta-analysis, the comparative results between users and non-users showed that there was a slight weight increase (+0.279 kg ; CI -1.71 to 2.27) in patients using 0.625 mg/day conjugated equine estrogen (CEE) + 2.5 mg/day medroxyprogesterone acetate (MPA). As for the patients receiving 2.5 mg/day Tibolone, weight gain (+0.670 kg; CI from -1.14 to 2.48) was also observed in them. However, these increases were not significant when compared to non-HT users. Conclusions: most regimens studied showed that patients using HT in the menopausal transition and after menopause did not show significant weight gain. The only combination that showed weight gain was 0.5 mg/day 17-beta-estradiol (E2) + 100 mg/day progesterone observed, while there was weight reduction in patients using 1 mg/day estradiol valerate + 3 mg/day drospirenone and 1 mg/day estradiol (E) + norethisterone acetate.

Objetivo: realizar uma revisão sistemática e meta-análise para avaliar se a terapia hormonal (TH) aumenta o peso em mulheres na transição menopausal e após a menopausa. Métodos: este artigo propõe uma atualização da revisão sistemática publicada em 2005 pela Cochrane Library (Kongnyuy EJ et al., 2005) com referência a estudos avaliando mudanças de peso em mulheres recebendo TH de 1986 a 2005. Seguindo as recomendações do PRISMA, incluímos ensaios clínicos randomizados (RCTs) de maio de 2005 em diante do Medline, Embase e dos bancos de dados Cochrane CENTRAL. Diferenças médias padronizadas (SMD) e intervalos de confiança de 95% (IC) foram calculados. Dois autores avaliaram independentemente o risco de vieses nos estudos selecionados. Resultados: foram incluídos dez ECRs, totalizando 2.588 usuários de HT e 764 não usuários. Diferentes esquemas, dosagens e vias de administração em usuários de HT foram analisados e comparados a não usuários. Os resultados não mostraram diferenças estatisticamente significativas para a maioria dos esquemas de TH avaliados. Houve ganho de peso significativo apenas nos pacientes que usaram apenas EEC nas doses de 0,45 mg/dia e 0,3 mg/dia quando comparados ao placebo (p 0,01); assim como em pacientes recebendo combinações estoprogestativas de 0,5 mg/dia de 17-beta-estradiol (E2) + 100 mg/dia de progesterona, com aumento de peso de 0,7 kg (p 0,032). Por outro lado, as combinações de 1 mg/dia de valerato de estradiol + 3 mg/dia de drospirenona apresentaram redução de -1,0 kg (p = 0,04), enquanto foi identificada redução de -0,2 kg (p = 0,001) nas pacientes que usaram 1 mg /dia estradiol (E) + 0,5 mg de acetato de noretisterona (NETA). A terapia com tibolona não mostrou alterações estatisticamente significativas no peso. Após realizar uma meta-análise, os resultados comparativos entre usuárias e não usuárias mostraram que houve um leve aumento de peso (+0,279 kg ; IC -1,71 a 2,27) em pacientes em uso de 0,625 mg/dia de estrogênio equino conjugado (CEE) + 2,5 mg/dia de acetato de medroxiprogesterona (MPA). Quanto aos pacientes que receberam Tibolona 2,5 mg/dia, também foi observado ganho de peso (+0,670 kg; IC de -1,14 a 2,48). No entanto, esses aumentos não foram significativos quando comparados aos não usuários de HT. Conclusões: a maioria dos esquemas estudados mostrou que as pacientes em uso de TH na transição menopausal e após a menopausa não apresentaram ganho de peso significativo. A única combinação que apresentou ganho de peso foi 0,5 mg/dia de 17-beta-estradiol (E2) + 100 mg/dia de progesterona, enquanto houve redução de peso nas pacientes que usaram 1 mg/dia de valerato de estradiol + 3 mg/dia de drospirenona e 1 mg/dia estradiol (E) + acetato de noretisterona.

Tratamiento con hormona de crecimiento en niños nacidos pequeños para la edad gestacional. Experiencia de un centro / Growth hormone treatment in small for gestational age children. A single-center experience

Introducción. Los pequeños para la edad gestacional (PEG) suelen tener una talla final 1 DE bajo la media. Se diferencian tres grupos según antropometría al nacimiento: de peso reducido (PRN), de longitud reducida (LRN) o ambos. Objetivos. Describir las características de los pacientes PEG atendidos en el Servicio de Endocrinología Pediátrica de un hospital de tercer nivel, y analizar la evolución de niños PEG sin crecimiento recuperador a los 4 años de edad, en tratamiento con hormona del crecimiento (GH), según su diagnóstico. Métodos. Estudio retrospectivo de pacientes PEG atendidos desde 2004 hasta 2021. Resultados. Se estudiaron 89 PEG; 44/89 iniciaron tratamiento con GH (11/44 PRN, 8/44 LRN y 25/44 ambos). La edad media al diagnóstico fue de 3,87 años; la talla media al inicio del tratamiento fue de -2,99 DE en los PEG diagnosticados por PRN, -2,85 DE en aquellos diagnosticados por LRN y -3,17 DE en los diagnosticados por bajo PRN y LRN. La talla final fue de -1,77, -1,52 y -1,23 DE, respectivamente, lo que supone una ganancia total de 1,22, 1,33 y 1,93 DE, respectivamente, alcanzando así su talla diana con una diferencia de 0,36 ± 0,08 DE. Conclusión. Menos de la mitad de los PEG derivados a la consulta precisaron tratamiento con GH, por no tener la edad de 4 años aún, o haber completado el crecimiento recuperador. Aquellos pacientes PEG según peso y longitud al nacimiento presentaron percentiles peores al diagnóstico y una mayor respuesta a GH.

Introduction. Small for gestational age (SGA) children usually have a final height of 1 SD below the mean. Three groups are established based on anthropometric characteristics at birth: low birth weight (LBW), short birth length (SBL), or both. Objectives. To describe the characteristics of SGA patients seen at the Department of Pediatric Endocrinology of a tertiary care hospital and to analyze the course of SGA children without catch-up growth at 4 years of age who were receiving treatment with growth hormone (GH), according to their diagnosis. Methods. Retrospective study of SGA patients seen between 2004 and 2021. Results. A total of 89 SGA children were studied; 44/89 started treatment with GH (11/44 LBW, 8/44 SBL, and 25/44 both). Their mean age at diagnosis was 3.87 years; their mean height at treatment initiation was -2.99 SD in SGA children diagnosed by LBW, -2.85 SD in those with SBL, and -3.17 SD in those with both LBW and SBL. Their final height was -1.77, -1.52, and -1.23 SD, respectively, with a total gain of 1.22, 1.33, and 1.93 SD, respectively, thus reaching their target height with a difference of 0.36 ± 0.08 SD. Conclusion. Less than half of SGA children referred to the clinic required treatment with GH because they were not yet 4 years old or had not completed their catch-up growth. SGA patients according to birth weight and length had worse percentiles at diagnosis and a greater response to GH.

The Pyramid of Transgender Health Therapeutics

Transgender care needs a multidisciplinary team approach. The awareness about transgender health has increased over the past few years in India. The pyramid of transgender health helps to demystify the care of transgender individuals. The 7 S's of lifestyle modification need to be followed in the routine clinical care of transgender individuals. The individuals also need psychological care and support, metabolic and medical care, endocrine management, and later surgery in some cases. The policy makers can use the pyramid to decide about financial help to the community for their holistic care. The physicians involved in the care of transgender individuals can also take guidance about comprehensive care and management of transgender and gender diverse individuals.

A cross-sectional study to assess hypothyroid status of pregnant women at 12–16 weeks of gestation

Background: Physiological changes occur during pregnancy. These changes include metabolic, hematologic, cardiovascular, renal, and respiratory changes. In some cases, these changes may alter and lead to complications which result in adverse pregnancy outcomes. In India, hypothyroidism in pregnancy has a prevalence of 4.8–11%. Aims and Objectives: The aim of this study was to estimate the prevalence of hypothyroidism in pregnant women at 12–16 weeks of gestation. Materials and Methods: A cross-sectional study was planned on pregnant women attending the ANC clinic of Outpatient Department of Obstetrics and Gynecology at K.L. E’S Dr Prabhakar Kore Hospital and Medical Research Center Belagavi. Serum thyroid stimulating hormone (TSH) was estimated in the study participants. Serum TSH levels >4.5 ?IU/ml were labeled as hypothyroid pregnant women. Results: In our study, the prevalence of hypothyroidism was observed to be 8.68%. Conclusion: Hence, we conclude that all pregnant women should be screened for hypothyroidism at earlier weeks of gestation.

Ovarian reserve in adolescent girls with autoimmune thyroiditis

ABSTRACT Objectives: To assess serum anti-Müllerian hormone (AMH) levels as an ovarian reserve marker in adolescent girls with autoimmune thyroiditis (AIT) and explore the relationship of this marker with autoimmunity and thyroid function biomarkers. Subjects and methods: This study included 96 adolescent girls with newly diagnosed AIT and 96 healthy, age- and sex-matched controls. All participants were evaluated with detailed history taking and physical examination, thyroid ultrasound, and measurement of levels of thyroid-stimulating hormone (TSH), free thyroxin (FT4), free triiodothyronine (FT3), antithyroid peroxidase antibodies (TPOAb), antithyroglobulin antibody (TGAb), estradiol, total testosterone, and anti-Müllerian hormone (AMH) levels. The LH/FSH ratio was also calculated. Among 96 patients evaluated, 78 were overtly hypothyroid and 18 were euthyroid. AMH levels were significantly lower in participants with overt hypothyroidism and euthyroidism compared with controls. Results: Serum levels of AMH correlated negatively with age, body mass index (BMI) standard deviation score (SDS), and TPOAb, TGAb, and TSH levels but positively with FT4 levels. In multivariate analysis, AMH levels correlated significantly with age (odds ratio [OR] = 1.65, 95% confidence interval [CI] 1.18-2.32, p = 0.05), BMI SDS (OR = 2.3, 95% CI, 2.23-3.50, p = 0.01), TSH (OR = 2.43, 95% CI 1.5-2.8, p = 0.01), and TPOAb (OR = 4.1, 95% CI 3.26-8.75, p = 0.001). Conclusions: Ovarian reserve of adolescent girls with AIT, as measured by serum AMH levels, is affected by thyroid autoimmunity and hypothyroidism, indicating a possible need for ovarian reserve monitoring in these patients.

Climatério e lúpus eritematoso sistêmico / Climacteric and systemic lupus erythematosus

O lúpus eritematoso sistêmico é uma doença crônica, complexa e multifatorial que apresenta manifestações em vários órgãos. O seu acometimento ocorre 10 vezes mais no sexo feminino do que no masculino. É uma doença com uma clínica variada e com graus variados de gravidade, causando fadiga, manifestações cutâneas, como rash malar, fotossensibilidade, queda de cabelo e manifestações musculoesqueléticas, como artralgia, mialgia e atrite. Podem ocorrer flares (crises), que se caracterizam por aumento mensurável na atividade da doença. No climatério, no período da pré-menopausa, o lúpus eritematoso sistêmico ocorre com mais frequência, podendo ocorrer também na pós-menopausa. Algumas doenças são mais frequentes na fase do climatério, e a presença do lúpus pode influenciar na sua evolução, como a doença cardiovascular, osteoporose e tromboembolismo venoso. A terapia hormonal oral determina aumento do risco de tromboembolismo venoso no climatério, e na paciente com lúpus eritematoso sistêmico há aumento dos riscos de flares e de trombose. Em vista disso, a terapia hormonal é recomendada apenas para pacientes com lúpus eritematoso sistêmico estável ou inativo, sem história de síndrome antifosfolípides e com anticorpos antifosfolípides negativa, devendo-se dar preferência para a terapia estrogênica transdérmica, em menor dose e de uso contínuo. Na paciente com lúpus eritematoso sistêmico ativo ou com história de síndrome antifosfolípides ou com anticorpos antifosfolípides positiva, recomenda-se a terapia não hormonal, como os antidepressivos. (AU)

Systemic lupus erythematosus is a chronic, complex, multifactorial disease that manifests in several organs. Its involvement occurs 10 times more in females than in males. It is a disease with a varied clinic and varying degrees of severity, causing fatigue, skin manifestations such as malar rash, photosensitivity, hair loss and musculoskeletal manifestations such as arthralgia, myalgia and arthritis. Flare may occur, which are characterized by measurable increase in disease activity. In the climacteric, in the premenopausal period, systemic lupus erythematosus occurs more frequently, and may also occur in the postmenopausal period. Some diseases are more frequent in the Climacteric phase and the presence of lupus can influence its evolution, such as cardiovascular disease, osteoporosis and venous thromboembolism. Oral hormone therapy determines an increased risk of venous thromboembolism in the climacteric and in patients with systemic lupus erythematosus there is an increased risk of flares and thrombosis. In view of this, hormone therapy is only recommended for patients with stable or inactive systemic lupus erythematosus, without a history of antiphospholipid syndrome and with antiphospholipid antibodies, giving preference to transdermal estrogen therapy, at a lower dose and for continuous use. In patients with active systemic lupus erythematosus or with a history of antiphospholipid syndrome or positive antiphospholipid antibodies, non-hormonal therapy, such as antidepressants, is recommended. (AU)

Effect of applications of 1-MCP and ethylene on the ripening and degreening process of banana fruits cv. Barranquillo

The banana cv. Barranquillo (Musa acuminata, AAA, 'Gros Michel') is a highly desired fruit because of its productive potential and organoleptic quality but various aspects of the ripening process are unknown. The objective of this research was to evaluate the effect of applications of 1-MCP and ethylene on the ripening and degreening process. Two experiments were carried out at room temperature with fruits harvested at commercial maturity. The first four treatments evaluated maturation: control, ethylene, 1-MCP, and 1-MCP + ethylene. In the second experiment, different concentrations of ethylene based on ethephon (0, 100, 500 and 1000 µL L-1) were evaluated. The fruits treated with 1-MCP decreased the ripening process, and 1-MCP was a good alternative for conserving the fruits; the ethylene had opposite results. The color index of the skin, weight loss, firmness, total soluble solids, and maturity ratio had changes associated with the presence of ethylene. In the second experiment, the ethylene applications between 100 and 500 µL L-1 sufficiently stimulated degreening but accelerated the ripening process.

El banano cv. Barranquillo (Musa acuminata, AAA, 'Gros Michel') es un fruto muy apetecido por su potencial productivo y calidad organoléptica, pero se desconocen varios aspectos del proceso de maduración. El objetivo de esta investigación fue evaluar el efecto de la aplicación de 1-MCP y etileno en la maduración y en el proceso de desverdizado. Se realizaron dos experimentos a temperatura ambiente y con frutos cosechados en madurez comercial; en el primero, se evaluaron cuatro tratamientos, para entender la regulación de la maduración, estos fueron: testigo, etileno, 1-MCP y 1-MCP+etileno. En el segundo experimento, se evaluaron diferentes concentraciones de etileno, a base de etefon (0, 100, 500 y 1000 µL L-1). Los frutos tratados con 1- MCP presentaron una disminución en el proceso de maduración, por tanto, el 1-MCP, se convierte en una buena alternativa de conservación, mientras que con etileno, el proceso fue opuesto. Se evidenció que el índice de color de la epidermis, la pérdida de peso, la firmeza, los sólidos solubles totales y la relación de madurez se consideran cambios asociados a la presencia de etileno. En el segundo experimento se encontró que, aplicaciones de etileno entre 100 y 500µL L-1, se consideran suficientes para estimular el desverdizado, pero aceleran el proceso de maduración.

Manejo del Síndrome de Hiperestimulación Ovárica / Management of Ovarian Hyperstimulation Syndrome

INTRODUCCIÓN: El síndrome de hiperestimulación ovárica es una respuesta exagerada del ovario a los tratamientos hormonales para estimular la formación de óvulos. OBJETIVO: Describir el caso clínico de una mujer con síndrome de hiperestimulación ovárica; revisar el abordaje, manejo, tratamiento y cómo prevenirlo. CASO CLÍNICO: Paciente femenina de 37 años, multigesta, en tratamiento con metformina por Síndrome de ovario poliquístico , que presenta infertilidad secundaria a factor tubárico, que desarrolló un cuadro moderado de síndrome de hiperestimulación ovárica como consecuencia de la aplicación de las técnicas de fertilización in vitro (Folitropina alfa humana recombinante (GONAL-F®) y Cetrolerelix (CETROTIDE®); al cuarto día del procedimiento de aspiración folicular presenta dolor pélvico intenso, disuria, deposiciones diarreicas, ecografía abdominal y vaginal evidencia líquido libre en cavidad alrededor de 1000cc, además de ovarios tanto derecho e izquierdo con volumen de 102 mL y 189 mL respectivamente. Paciente es ingresada para realizar tratamiento hidratación parenteral, Enoxaparina 40mg subcutánea, Cabergolina 0.5mg vía oral, alta a las 72 horas. DISCUSIÓN: Las claves para la prevención del síndrome de hiperestimulación ovárica son la experiencia con la terapia de inducción de la ovulación y el reconocimiento de los factores de riesgo para el síndrome de hiperestimulación ovárica. Los regímenes de inducción de la ovulación deberían ser altamente individualizados, monitorizados cuidadosamente y usando dosis y duración mínimas del tratamiento con gonadotropinas para conseguir la meta terapéutica. CONCLUSIONES: El síndrome de hiperestimulación ovárica constituye la complicación más temida durante el uso de inductores de la ovulación; el conocimiento de factores de riesgo, puede prevenir o evitar que llegue a ser de un caso severo, lo cual puede causar mayor morbilidad o hasta mortalidad. La vitrificación se convierte en la técnica que permite prevenir el síndrome de hiperestimulación ovárica, junto con esta técnica hay 2 alternativas: la inducción con análogo de la hormona liberadora de gonadotropina o el uso de agonistas dopaminérgicos.

INTRODUCTION: Ovarian hyperstimulation syndrome is an exaggerated response of the ovary to hormonal treatments to stimulate egg formation. OBJECTIVE: To describe the clinical case of a woman with ovarian hyperstimulation syndrome; to review the approach, management, treatment and how to prevent it. CLINICAL CASE: 37-year-old female patient, multigestation, under treatment with metformin for polycystic ovary syndrome, presenting infertility secondary to tubal factor, who developed a moderate picture of ovarian hyperstimulation syndrome as a consequence of the application of in vitro fertilization techniques (recombinant human follitropin alfa (GONAL-F®) and Cetrolerelix (CETROTIDE®); On the fourth day of the follicular aspiration procedure she presents intense pelvic pain, dysuria, diarrheic stools, abdominal and vaginal ultrasound shows free fluid in the cavity of about 1000cc, in addition to right and left ovaries with a volume of 102 mL and 189 mL respectively. Patient was admitted for parenteral hydration treatment, Enoxaparin 40mg subcutaneous, Cabergoline 0.5mg orally, discharged after 72 hours. DISCUSSION: The keys to prevention of ovarian hyperstimulation syndrome are experience with ovulation induction therapy and recognition of risk factors for ovarian hyperstimulation syndrome. Ovulation induction regimens should be highly individualized, carefully monitored, and using minimal doses and duration of gonadotropin therapy to achieve the therapeutic goal. CONCLUSIONS: Ovarian hyperstimulation syndrome constitutes the most feared complication during the use of ovulation inducers; knowledge of risk factors, may prevent or avoid it from becoming a severe case, which may cause increased morbidity or even mortality. Vitrification becomes the technique that allows preventing ovarian hyperstimulation syndrome, along with this technique there are 2 alternatives: induction with gonadotropin-releasing hormone analog or the use of dopaminergic agonists.

Growth hormone effect on body composition of children born small for gestational age: a systematic review

Abstract Objective The present study aimed to evaluate the effects of GH treatment on the body composition of children born with SGA. Methods This study is a systematic review of the literature. CINAHL, Embase; Medline/Pubmed, Scopus and Web of Science were searched from inception to March 2022. Results Four studies met the inclusion criteria, with an intervention time of 1 to 3 years, using doses from 0.03 to 0.07 mg/kg/day of GH. Bone densitometry by dual-energy X-ray absorptiometry (DXA) with whole-body scans was the most used method to assess body composition. Most studies (n= 3) had SGA children as a control group with the same characteristics as the case group; the mean age was similar between the groups (minimum of 5.1 ± 1.4 years and maximum of 6.7 ± 1 0.8 years) and all participants had an average height ≤ -3DP. The Lean Mass (LM) and Fat Mass (FM) outcomes of the studies were not presented in a standardized manner; thus, they cannot be compared. There was a significant increase in LM in the group treated with GH in relation to the pre-treatment period and in comparison, to the untreated control group. Three studies showed a significant decrease in FM at the end of the intervention period, and in two studies, this decrease occurred in the control group. Conclusions Despite the differences in the presentation of results and in the evaluation periods, the results of the studies showed that growth hormone favors the gain and maintenance of lean mass, and it also affects fat mass reduction and redistribution.