Evolución del estrógeno en la anticoncepción hormonal combinada: del etinilestradiol al estetrol pasando por el estradiol / Evolution of oestrogen in combined hormonal contraception: From ethinylestradiol to estetrol via estradiol

El objetivo de este artículo ha sido el de analizar las evidencias disponibles sobre la eficacia y la seguridad de un nuevo anticonceptivo oral que contiene estetrol (E4) y drospirenona (DRSP). Para ellos se ha efectuado una revisión de la literatura que ha incluido los estudios publicados sobre esta nueva formulación anticonceptiva. Los ensayos clínicos en fase 2 y fase 3 realizados han puesto de manifiesto que la combinación E4 15mg/DRSP 3mg es eficaz para evitar el embarazo, es bien aceptada por las mujeres y no produce cambios de significado clínico en los parámetros de la coagulación. Para confirmar los resultados obtenidos en los ensayos en fase 2 y 3, es necesario un estudio en fase 4 que ponga de manifiesto el comportamiento de este nuevo anticonceptivo en la vida real.(AU)

The objective of this article was to analyse the available evidence on the efficacy and safety of a new oral contraceptive containing estetrol (E4) and drospirenone (DRSP). We conducted a literature review that included published studies on this new contraceptive formulation. Phase 2 and phase 3 clinical trials have shown that the E4 15mg/DRSP 3mg combination is effective in preventing pregnancy, is well accepted by women, and does not produce clinically significant changes in coagulation parameters. To confirm the results obtained in phase 2 and 3 trials, a phase 4 study is necessary to reveal the behaviour of this new contraceptive in real life.(AU)

¿Hay mejores parámetros diagnósticos de la luteinización precoz que el valor aislado de los niveles de progesterona o el cociente progesterona/es-tradiol el día de administración de hCG? / There are better parameters Diagnostics for premature luteinization thanisolate value of Progesterone level or progesterone/estradiol ratio on theday of hCG administration?

Objetivo: Tanto el valor absoluto de progesterona (P) como el cociente progesterona/estradiol (P/E)son utilizados para el diagnóstico de la luteinización precoz (LP), sin llegar a un acuerdo en el umbraladecuado y con resultados muy dispares en cuanto a su capacidad predictiva. El cociente P/E ha creadoademás una gran confusión entre el concepto de LP y la baja respuesta ovárica a la hiperestimulación.La única alternativa viable es encontrar un parámetro que resulte independiente del grado de respuestaovárica y los valores de estradiol.Método:Se analizaron 434 ciclos consecutivos de FIV con estimulación mediante FSH y/o LH y fre-nado hipofisario con agonistas o antagonistas de GnRH sin ningún tipo de criterio de exclusión previopara determinar la relación matemática existente entre progesterona y estradiol en el momento previoa la ovulación.Resultados:La relación empírica entre progesterona y estradiol viene establecida por la fórmula E=4P2,de la que podemos deducir las fórmulas descriptivas de P=0,5E0,5, P/E=0,5E-0,5 y P2/E=0,25, siendoP2/E la única que corresponde a una constante sin dependencia del nivel de estradiol y, por tanto, el cri-terio ideal para el diagnóstico de LP. (AU)

Introduction: Both the absolute value of progesterone (P) and the progesterone/estradiol ratio (P/E) are used for the diag-nosis of early luteinization (EL), without reaching an agreement on the appropriate threshold and with very differentresults in terms of its predictive ability. The P/E ratio has also created a great deal of confusion between the concept of LPand low ovarian response to hyperstimulation. The objective of this study is to find a parameter that is independent of the degree of ovarian response and estradiol va-lues.Methods: We analyzed 434 consecutive IVF cycles with FSH and/or LH stimulation and pituitary down regulation withagonist or antagonists without any prior exclusion criteria to determine the mathematical relationship between progesteroneand estradiol at the time prior to ovulation.Results: The empirical relationship between progesterone and estradiol is established by the formula E=4P2, from whichwe can deduce the descriptive formulas of P=0,5E0,5, P/E=0,5E-0,5 an P2/E=0,25, being P2/E the only one that corres-ponds to a constant without dependence on the estradiol level and, therefore, the ideal criterion for the diagnosis of early. (AU)

Ferritin status impact on hepcidin response to endurance exercise in physically active women along different phases of the menstrual cycle / Impacto de las reservas de ferritina sobre la respuesta de la hepcidina al ejercicio de resistencia en las mujeres físicamente activas a lo largo de las diferentes fases del ciclo menstrual

Serum ferritin has been proposed as a predictor of hepcidin concentrations in response to exercise. However, this fact has not been studied in physically-active women. Therefore, the main objective of this study was to analyse the hepcidin response at different ferritin status before and after running exercise in physically active females. Fifteen eumenorrheic women performed a 40-min running protocol at 75% of VO2peak speed in different menstrual cycle phases (early-follicular phase, mid-follicular phase and luteal phase). Blood samples were collected pre-exercise, 0h post-exercise and 3h post-exercise. For statistics, participants were divided into two groups according to their pre-exercise ferritin levels (< 20 and ≥ 20 μg/L). Through menstrual cycle, hepcidin was lower in both early follicular phase (p = 0.024; 64.81 ± 22.48 ng/ml) and mid-follicular phase (p = 0.007; 64.68 ± 23.91 ng/ml) for < 20 μg/L ferritin group, in comparison with ≥20 μg/L group (81.17 ± 27.89 and 79.54 ± 22.72 ng/ml, respectively). Hepcidin showed no differences between both ferritin groups in either pre-exercise, 0h post-exercise and 3h post-exercise. Additionally, no association between pre-exercise ferritin and hepcidin levels 3 h post-exercise (r = -0.091; p = 0.554) was found. Menstrual cycle phase appears to influence hepcidin levels depending on ferritin reserves. In particular, physically-active females with depleted ferritin reserves seems to present lower hepcidin levels during the early-follicular phase and mid-follicular phase. However, no association between ferritin and hepcidin levels was found in this study. Hence, ferritin levels alone may not be a good predictor of hepcidin response to exercise in this population. Multiple factors such as sexual hormones, training loads and menstrual bleeding must be taken into account

La ferritina sérica parece ser un predictor de la respuesta de la hepcidina al ejercicio. Sin embargo, este hecho no ha sido estudiado en mujeres físicamente activas. El objetivo fue analizar la respuesta de la hepcidina en diferentes estados de la ferritina antes y después del ejercicio. Quince mujeres eumenorreicas realizaron un protocolo de carrera de 40 minutos al 75% de la velocidad VO2pico en diferentes fases del ciclo menstrual (fase folicular temprana, fase folicular media y fase lútea). Se recogieron muestras de sangre antes del ejercicio y a las 0h y 3h después del ejercicio. Las participantes se dividieron en dos grupos según sus niveles de ferritina previos al ejercicio (< 20 y ≥ 20 μg/L). La hepcidina fue más baja tanto en la fase folicular temprana (p = 0,024; 64,81 ± 22,48 ng/ml) como en las fase folicular media (p = 0,007; 64,68 ± 23,91 ng/ml) para el grupo de ferritina < 20 μg/L en comparación con el grupo de ferritina ≥ 20 μg/L (81,17 ± 27,89 y 79,54 ± 22,72 ng/ml, respectivamen-te). La hepcidina no mostró diferencias entre ambos grupos de ferritina para ninguno de los momentos (antes del ejercicio ejercicio, 0h y 3h después del ejercicio). No se encontró ninguna asociación entre los niveles de ferritina previos al ejercicio y los niveles de hepcidina 3h posteriores al ejercicio (r = -0,091; p = 0,554). El ciclo menstrual parece influir en los niveles de hepcidina dependiendo de las reservas de ferritina. En particular, las mujeres físicamente activas con reservas de ferritina agotadas parecen presentar niveles de hepcidina más bajos durante la fase folicular temprana y la fase folicular media. Sin embargo, no se encontró ninguna asociación entre la ferritina y la hepcidina. Por lo tanto, los niveles de ferritina por sí solos pueden no ser un buen predictor de la respuesta de la hepcidina al ejercicio en esta población. Se deben tener en cuenta múltiples factores como las hormonas sexuales, las cargas de entrenamiento y el sangrado menstrual

The relation of estradiol conditions and usage length to sexual dysfunction in progesterone acetate medroxepo acceptories at Bara-Baraya public health center of Makassar

Objective: This study aims to determine the relationship between estradiol hormone levels and duration of the usage on sexual dysfunction in Depo Medroxy Progesterone Acetate acceptors. Method: Family Planning (KB/Keluarga Berencana) Depo Medroxy Progesterone Acetate as many as 43 respondents who meet the sample criteria. The sampling technique used was accidental sampling. Data analysis was performed by using chi square. Results: The results showed that there was a significant relation between levels of the hormone estradiol and the incidence of sexual dysfunction (p = 0.000), as well as the length of time using Depo Medroxy Progesterone Acetate on sexual dysfunction (p = 0.000). Conclusion: The result of data analysis is that the duration of Depo Medroxy Progesterone Acetate injection usage significantly reduces the level of the hormone estradiol which can cause sexual dysfunction in Depo Medroxy Progesterone Acetate acceptors. (AU)

Asociaciones entre el índice inflamatorio de la dieta y parámetros reproductivos masculinos / Associations between dietary inflammatory index and male reproductive parameters

Objetivo: El objetivo de este trabajo fue analizar las asociaciones entre el índice inflamatorio de la dieta (IID) y los parámetros reproductivos masculinos. Material y método: Estudio transversal realizado en 209 jóvenes universitarios sanos (18-23 años) de la Región de Murcia entre octubre 2010 y noviembre 2011. Los análisis seminales (concentración, movilidad y morfología espermática) se realizaron siguiendo los criterios de la Organización Mundial de la Salud. Se analizaron las concentraciones séricas de las hormonas folículo-estimulante, luteinizante, testosterona, inhibina B y estradiol. La ingesta dietaria fue valorada mediante un cuestionario de frecuencia alimentaria validado. El potencial inflamatorio de la dieta se valoró mediante el IID. Unos valores negativos o positivos de IID reflejaron una mayor propiedad antiinflamatoria o proinflamatoria, respectivamente. Se utilizaron modelos de regresión lineal para analizar la relación entre el IID y la calidad seminal y niveles de hormonas reproductivas tras ajustar por posibles covariables importantes. Resultados: Se mostró una asociación positiva estadísticamente significativa entre el IID y el porcentaje de espermatozoides móviles progresivos (PR) (P, tendencia = 0,03) y la movilidad espermática total (PR + NP) (P, tendencia = 0,04). No se encontraron asociaciones significativas con el resto de parámetros espermáticos, ni con las hormonas reproductivas. Conclusiones: Nuestros resultados indican que una mayor propiedad proinflamatoria de la dieta podría estar asociada con un aumento de la movilidad espermática en varones jóvenes, pero no afectaría a la concentración o morfología espermática o a las hormonas reproductivas. Sin embargo, se necesitan más estudios para confirmar estos hallazgos y extender estos resultados a otras poblaciones de varones

Objective: The aim of this work was to assess the associations between the dietary inflammatory index (DII) and male reproductive parameters. Material and method: Cross-sectional study of 209 healthy male university students (18-23 years old) recruited from October 2010 to November 2011 in Murcia Region (Southern Spain). Semen analyses (sperm concentration, motility and morphology) were carried out according to World Health Organization guidelines. Serum concentrations of follicle-stimulating and luteinizing hormones, estradiol, inhibin b and testosterone were also determined. Diet intake was assessed using a validated food frequency questionnaire. The DII assessed the inflammatory potential of one's diet. Negative or positive values of DII reflected anti-inflammatory or pro-inflammatory dietary status, respectively. Linear regression was used to analyze the relation between the DII score and semen quality parameters and reproductive hormone levels adjusting for potential important covariates. Results: We found statistically significant positive associations between the DII and progressive sperm motility (PR) (P, trend = 0.03] and total sperm motility (PR + NP) (P, trend = 0.04]. No significant associations were observed for other semen parameters or male reproductive hormones. Conclusions: Our results suggest that a pro-inflammatory dietary status may be associated with increased sperm motility in young men, but will not impact sperm count, morphology or reproductive hormones. However, further research is needed to confirm these findings and extend these results to other male populations

Protective role of broccoli extract on estradiol valerate-induced polycystic ovary syndrome in female rats

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility. The aim of this study was to investigate the protective role of broccoli extract on estradiol valerate (EV)-induced PCOS in female rats. Forty adult female rats were divided into four main groups; control, broccoli-treated, EV, single intramuscular injection of 16mg/kg)-treated, EV+broccoli (1 g/kg/day)-treated groups. The protected rats were treated orally by gastric tube daily for 4 weeks. At the end of the experiment, blood samples were collected and the ovary were subjected to histological and immunohistochemical analyses. EV treated group exhibited the characteristic features of PCOS. Disturbed ovarian cyclicity in addition to histopathological alterations, including decreased number of healthy follicles and corpora lutea, increased degenerated, cystic follicles and increased collagen fiber deposition were detected by light microscopic studies. Moreover, increased immune-reactivity for iNOS and altered proliferation index were observed by immunohistochemical assessments. Co-adminis-tration of broccoli extract improved EV-induced PCOS in rat model. In conclusion, broccoli may be an effective therapeutic candidate for the treatment of PCOS

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The possible protective effect of Bougainvillea spectabilis leaves extract on estradiol valerate-induced polycystic ovary syndrome in rats (biochemical and histological study)

Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disorder in which the level of oxidative elements in blood rises. Bougainvillea spectabilis is a plant with a potent antioxidant effect, since it contains flavonoids. The aim of this work is to explore the possible protective potency of Bougainvillea spectabilis leaves (BSL) extract on ovarian folliculogenesis using a rat model of estradiol valerate (EV) - induced PCOS. Thirty six mature female rats were divided into four groups: 1. Control group (six rats). 2. EV group (ten rats), singly injected with 2mg/kg EV subcutaneously. 3. BSL group (ten rats), given 100mg/kg BSL extract orally for 30 days. 4. EV + BSL group (ten rats), singly injected with EV subcutaneously and given 100mg/kg BSL extract orally for 30 days. Biochemical measurements of serum levels of estrogen, testosterone, LH, FSH, glucose, totals lipids, and total antioxidants were done using ELISA method. Histological (using hematoxylin & eosin and Masson's trichrome stains) and immunohistochemical (using anti cyclooxygenase 2 {COX 2}) studies were performed. This was followed by morphometric measurements and statistical analysis. PCOS caused massive primordial follicle loss and development of cystic follicles with increase in fibrosis, COX 2 immunoexpression. There was a significant reduction in LH, estrogen and glucose serum levels and increase in FSH and the antioxidant serum levels between the EV + BSL-extract-treated group compared to EV-treated group. Histomorphometric studies also showed the significant changes in the number of follicles and decreased cyst formation in the combined therapy group. There was a significant role of BSL extract in restoration of ovarian folliculogenesis and reduction of biochemical, histological and immunohistochemical changes in EV treated group

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Características socio-demográficas de las mujeres españolas con sangrado menstrual abundante. Resultados del Registro nacional de pacientes con sangrado menstrual abundante (Registro SANA) / Sociodemographic characteristics of Spanish women with heavy menstrual bleeding. Results of a national registry of patients with heavy menstrual bleeding (SANA Registry)

Objetivo. Describir las características socio-demográficas, de diagnóstico y tratamiento de las pacientes con sangrado menstrual abundante. Sujetos y métodos. Estudio observacional, transversal, multicéntrico y nacional, en mujeres en edad reproductiva (18-49 años) con sangrado menstrual abundante sin causa orgánica, en la práctica habitual de consultas de ginecología españolas. Resultados. Se incluyó a 1.039 pacientes, con una media ± desviación estándar de 37,8 ± 8,1 años. Únicamente el 52,1% acudió a la consulta por alteraciones del sangrado; el 48,0% se diagnosticó durante la consulta. Las pacientes con sangrado habitual anómalo indicaban alteraciones del sangrado relacionadas con la cantidad de forma aislada o concomitante a otras alteraciones (abundante/prolongado/irregular). Solo el 43,7% percibía cambios en el sangrado actual respecto del habitual, fundamentalmente por aumento en la cantidad. Para el tratamiento del sangrado abundante, se prescribieron anticonceptivos orales combinados (principalmente valerato de estradiol 3-2-1 mg + dienogest 3-2 μg) (63,3%), dispositivo intrauterino de levonorgestrel (14,3%) y combinaciones de tratamientos (11,9%). Conclusiones. El sangrado anómalo es prevalente, siendo una prioridad su diagnóstico mediante una evaluación adecuada (AU)

Objective. To describe the socio-demographic, diagnostic and treatment characteristics of patients with heavy menstrual bleeding. Subjects and methods. An observational, cross-sectional, multicenter, national study was conducted in women of reproductive age (18-49 years) with heavy menstrual bleeding with no organic cause attending routine gynecology consultations in Spain. Results. This study included 1,039 patients, with a mean age of 37.8 ± 8.1 years. Only 52.1% of the women attended their gynecologist due to bleeding abnormalities and 48.0% were diagnosed during the visit. Patients with longstanding abnormal bleeding reported alterations in quantity, either alone or concomitant to other abnormalities (heavy/prolonged/irregular bleeding). Only 43.7% perceived changes in current bleeding versus usual bleeding, mainly due to an increased quantity. The main drugs prescribed for the treatment of heavy bleeding were combined oral contraceptives (mainly estradiol valerate 3-2-1 mg + dienogest 3-2 μg) (63.3%), levonorgestrel intrauterine system (14.3%), and combined treatments (11.9%). Conclusions. Abnormal bleeding is prevalent. Diagnosis through appropriate assessment is a priority (AU)

Tratamiento de la atrofia vaginal a través de anillo con liberación de ultrabaja dosis de estradiol / Treatment of vaginal atrophy through a low-dose estradiol-releasing vaginal ring

La atrofia vaginal es una enfermedad crónica, a menudo no diagnosticada, que tiene un importante impacto en la salud sexual y la calidad de vida. La atrofia vaginal está causada por los cambios fisiológicos debidos a la disminución de estrógenos y son la base de una serie de síntomas que incluyen sequedad vaginal, dispareunia, prurito e irritación reportados en un 40-60% de las mujeres posmenopáusicas en Europa. El porcentaje de mujeres tratadas es menor del 30% y con un cumplimiento menor del 10% al año. El tratamiento de primera línea para la atrofia vaginal moderada-severa son los estrógenos locales. Recientemente, ha aparecido en España un nuevo tratamiento local de estrógenos, que consiste en un anillo de silicona flexible con un núcleo que contiene 2 mg de hemihidrato de estradiol. El estradiol se libera en cantidades mínimas pero continuas, con una liberación de 6,5 a 9,5 μg/día durante, al menos, 90 días. El anillo vaginal ha demostrado ser efectivo en el alivio de la sintomatología local (vaginal y urológica) y mejorando la mucosa vaginal desde el punto de vista de los hallazgos visuales exploratorios (palidez, turgencia, rugosidad, grosor), así como en cuanto al índice de maduración citológica (mayor proporción de células superficiales y una disminución de células basales, parabasales e intermedias) y pH. El anillo muestra los mismos efectos secundarios que otros tipos de estrógenos locales y es el método más elegido por las pacientes debido a la facilidad de su uso, la comodidad y la satisfacción en general (AU)

Vaginal atrophy is a chronic disease that is often undiagnosed and has a major impact on sexual health and quality of life. Vaginal atrophy is caused by physiological changes due to a decrease of estrogens. These changes are the basis of a number of symptoms including vaginal dryness, dyspareunia, itching and irritation reported in 40-60% of postmenopausal women in Europe. The percentage of treated women is less than 30%, and compliance is less than 10% per year. Local estrogens are the first-line treatment for moderate-to-severe vaginal atrophy. A new local estrogen treatment has recently become available in Spain, consisting of a flexible silicone ring with a core containing 2 mg of estradiol hemihydrate. The amount of estradiol released is minimal but in continuous quantities, with a release of 6.5 to 9.5 mcg/day for at least 90 days. The vaginal ring has been proven to be effective in relieving local symptoms (vaginal and urological), improving the vaginal mucosa based on visual examination (pale color, turgor, roughness, and thickness) and on the rate of cytologic maturation (a greater proportion of surface cells and a decrease in basal, parabasal and intermediate cells) and pH. The ring produces the same side effects as other types of local estrogen and is the most frequently chosen method by patients because of its ease of use and comfort, and the general satisfaction produced (AU)

Molécula de adhesión celular vascular 1 en menopáusicas tratadas con estradiol oral o transdérmico / Vascular cellular adhesion molecule-1 in postmenopausal women treated with oral or transdermal estradiol

Objetivo. Comparar las modificaciones de las concentraciones plasmáticas de la molécula de adhesión celular vascular 1 en menopáusicas tratadas con estradiol por vía oral o transdérmica después de 3 meses de uso. Materiales y métodos. Se realizó una investigación con una muestra de 70 pacientes menopáusicas que asistieron a la consulta de Medicina Interna, Endocrinología y Menopausia del Hospital Central «Dr. Urquinaona». Se asignó a 35 pacientes tratamiento con estradiol por vía oral (grupo A) y a 35 pacientes tratamiento con estradiol transdérmico (grupo B). Se evaluaron las concentraciones plasmáticas de la molécula de adhesión celular vascular 1 antes y después de 3 meses de tratamiento. Resultados. No se encontraron diferencias estadísticamente significativas en las características generales entre los 2 grupos antes del tratamiento (p = ns). Las concentraciones plasmáticas la molécula de adhesión celular vascular 1 demostraron una reducción después de 3 meses de tratamiento en ambos grupos (grupo A: 442,6 ± 47,9 ng/ml al inicio comparado con 386,8 ± 40,3 ng/ml después del tratamiento y grupo B: 405,0 ± 42,8 ng/ml después del tratamiento comparado con el valor promedio inicial de 445,1 ± 59,9 ng/ml; p < 0,05). Conclusión. El uso de estradiol transdérmico puede ser una alternativa eficaz al uso de estradiol por vía oral después de 3 meses de uso, debido a que ambos tratamientos producen disminuciones en las concentraciones plasmáticas la molécula de adhesión celular vascular 1 (AU)

Objective. To compare modifications of plasma concentrations of vascular cellular adhesion molecule-1 in postmenopausal women treated with oral or transdermal estradiol after 3 months of use. Materials and methods. This study included 70 postmenopausal women attending the Internal Medicine, Endocrinology and Menopause Departments at the 'Dr. Urquinaona' Central Hospital. Thirty-five patients were treated with oral estradiol (group A) and 35 patients with transdermal estradiol (group B). Plasma concentrations of vascular cellular adhesion molecule-1 were measured before and after 3 months of treatment. Results. There were no statically significant differences in general characteristics between the two treatment groups (p = ns). In both groups, plasma concentrations of vascular cell adhesion molecule-1 were reduced after 3 months of treatment (group A: 442.6 ± 47.9 ng/mL before treatment versus 386.8 ± 40.3 ng/mL after treatment, and group B: 405.0 ± 42.8 ng/mL after treatment versus an initial mean value of 445.1 ± 59.9 ng/mL; P<.05). Conclusion. Transdermal estradiol could be an effective alternative to oral estradiol after 3 months of use, since both treatments decreased plasma concentrations of vascular cell adhesion molecule-1 (AU)

Morphological evidence of the possible relevance of aromatase P450 in autoparacrine regulation and pathology of the hypophysis

Aromatase P450, the enzyme responsible for the catabolism of aromatizable androgens to estrogens is involved in sexual dimorphism and several pathologies induced by estrogenic effects. The present work reports evidence of pituitary aromatase synthesis, its regulation by gonadal steroids, and the physiological roles of aromatase on pituitary endocrine cells. The involvement of aromatase, through the auto-paracrine production of estradiol, in the pathogenesis of pituitary tumors -mainly prolactinomas- is reviewed

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Pubertad precoz periférica: disgenesia gonadal completa 46 XY / Peripheral precocious puberty: 46, XY complete gonadal dysgenesis

La pubertad precoz, a pesar de las definiciones clínicas estandarizadas y pruebas de diagnóstico disponibles, requiere, en ciertas situaciones una investigación exhaustiva y estructurada con el fin de conocer la causa. Niña de 4 años de edad, fenotípicamente de sexo femenino, enviada a la consulta de endocrinología pediátrica por pubarquia y telarquia. Se observó aceleración en la tasa de crecimiento con niveles altos de estradiol y testosterona, con determinaciones prepúberes de la hormona luteinizante y foliculoestimulante. El resto del estudio de pubertad precoz periférica mostró la presencia de gonadoblastoma bilateral. El estudio genético reveló cariotipo 46 XY con mutación c.89G> T (p.Arg30Ile) en el exón 1 del gen SRY, confirmando el diagnóstico de disgenesia gonadal completa. Los trastornos de la diferenciación sexual deben ser considerados en el abordaje y la investigación de las causas de la pubertad precoz periférica, especialmente en presencia de tumores de ovario, como gonadoblastoma y disgerminomas

Despite standard clinical definitions and availability of diagnostic tests for precocious puberty, an intensive and structured investigation is needed in order to diagnose the aetiology in particular cases. A 4-year-old, phenotypically female child was referred to paediatric endocrinology consultation for premature pubarche and thelarche. There was an acceleration of growth velocity with high levels of estradiol and testosterone, and prepubertal FSH and LH measurements. Investigation showed bilateral gonadoblastoma as the cause of the peripheral precocious puberty. Genetic studies revealed 46 XY karyotype with mutation c.89G> T (p.Arg30Ile) in exon 1 of the SRY gene, confirming the diagnosis of complete gonadal dysgenesis. Disorders of sexual differentiation must be considered in the approach and investigation of peripheral precocious puberty, especially in the presence of ovarian tumours, such as gonadoblastoma and dysgerminoma

The protective effects of 17Beta-estradiol against ischemia-reperfusion injury and its effect on pacing postconditioning protection to the heart

The role of pacing postconditioning (PPC) in the heart protection against ischemia-reperfusion injury is not completely understood. The aim of this study was to investigated if 17-Beta-estradiol (estrogen, E2), endogenous atrial natriuretic peptide (ANP), endogenous brain natriuretic peptide (BNP), and tumor necrosis factor-alpha (TNF-Alpha) are involved in PPC-mediated protection. Langendorff perfused female Wistar rat hearts were used for this study. Hearts challenged with regional ischemia for 30 min subjected to no further treatment served as a control. The PPC protocol was 3 cycles of 30 s pacing alternated between the right atrium and left ventricle (LV). Protection was assessed by recovery of LV contractility and coronary vascular-hemodynamics. Ischemia induced a significant (P < 0.05) deterioration in the heart function compared with baseline data. PPC alone or in combination with short-term E2 treatment (E2 infusion at the beginning of reperfusion) significantly (P < 0.05) improved the heart functions. Short-term E2 treatment post-ischemically afforded protection similar to that of PPC. However, long-term E2 substitution for 6 weeks completely attenuated the protective effects of PPC. Although no changes were noted in endogenous ANP levels, PPC significantly increased BNP expression level and decreased TNF-Alpha in the cardiomyocyte lysate and coronary effluent compared to ischemia and controls. Our data suggested a protective role for short-term E2 treatment similar to that of PPC mediated by a pathway recruiting BNP and downregulating TNF-Alpha. Our study further suggested a bad influence for long-term E2 substitution on the heart as it completely abrogated the protective effects of PPC

Combinación de estradiol y progesterona: un tratamiento potencialmente valioso para el ictus isquémico en humanos / Combined estradiol and progesterone: a potentially valuable therapeutic treatment for human ischemic stroke

Introduction: Ischemic stroke leads adult’s mortality and long-term disability. Thus, new therapeutic approaches are needed. Estradiol (E2) and progesterone (P4) protect a variety of neuronal cells under stroke-like conditions in vitro; and the rodent brain against injury in vivo when administered prior to the ischemic insult, namely middle cerebral artery occlusion (MCAO). But, their therapeutic value after MCAO has been hardly studied. Less is known when coadministered under this paradigm. E2 and P4 also protect the neuronal cell death in vitro from ischemic-like injury, by reducing apoptotic cell death and enhancing cell survival signals. Here, we assessed the effect of combined E2 and P4 treatment in rats after permanent MCAO (pMCAO), which best mimics human ischemic stroke, analyzing the phosphatidylinositol 3-kinase (PI3-K)/Akt/glycogen synthase kinase 3 (GSK3)/ß-catenin signal pathway and the activation status of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in the infarct core (i.e., the ipsilateral frontoparietal cortex, ipsi-Ctx). Materials and Methods: Age-matched male Wistar rats (n=48) underwent pMCAO or sham operation and received either vehicle (ethanol 1% in saline) or combined E2 and P4 (0.04 mg/kg and 4 mg/kg, respectively) treatment at 6, 24, and 48 hrs after surgery. All animals were sacrificed 6 hrs after the last treatment dose and ipsi-Ctx homogenates were analyzed by immunoblotting. Results: pMCAO downregulated the PI3-K/Akt/GSK3/ß-catenin survival pathway and activated the proapoptotic protein SAPK/JNK in the ipsi-Ctx, effects which were reversed by E2 and P4 coadministration. Conclusions: Our data show that combined E2 and P4 treatment exerts a neuroprotective effect against brain injury when administered after the ischemic insult, which is mediated by modification of the activity of PI3-K/Akt/GSK3/ß-catenin signal pathway and that of SAPK/JNK. Hence, we provide experimental evidence that combined E2 and P4 comprise a potentially valuable therapeutic treatment for human ischemic stroke (AU)

Introducción: El ictus isquémico es una principal causa de muerte y discapacidad a largo plazo en adultos. Por tanto, es necesario desarrollar nuevas terapias. El estradiol (E2) y la progesterona (P4) protegen a distintas neuronas bajo condiciones que simulan el ictus isquémico in vitro; así como el cerebro de roedores cuando se administran antes del daño isquémico in vivo, en concreto antes de la oclusión de la arteria cerebral media (MCAO). Sin embargo, su valor terapéutico tras la MCAO ha sido poco estudiado. Menos se sabe aún acerca de su efecto cuando se coadministran en esta circunstancia. Además, el E2 y la P4 previenen la muerte neuronal por daño isquémico in vitro, disminuyendo la apoptosis y aumentando las señales de supervivencia. En este estudio, evaluamos en ratas el efecto del tratamiento combinado de E2 y P4 tras la MCAO permanente (pMCAO), ya que es el modelo que mejor simula el ictus isquémico humano, analizando la via de señalización fosfatidilinositol 3-kinasa (PI3-K)/Akt/glicógeno sintasa kinasa 3 (GSK3)/ß-catenina y la activación de la proteína kinasa activada por estrés/kinasa c-Jun N-terminal (SAPK/JNK) en el núcleo del infarto (es decir, el cortex ipsilateral frontoparietal, ipsi-Ctx). Materiales y Métodos: Ratas Wistar macho de edad similar (n=48) se sometieron a pMCAO u operación sham y recibieron vehículo (etanol 1% en salino) o tratamiento combinado de E2 y P4 (0.04 mg/kg y 4 mg/kg, respectivamente) a las 6, 24, y 48 h de la cirugía. Todos los animales se sacrificaron 6 h después de la última dosis y los lisados de ipsi-Ctx se analizaron por immunoblot. Resultados: La pMCAO disminuyó la actividad de la via de supervivencia PI3-K/Akt/GSK3/ß-catenina y activó la proteína proapoptótica SAPK/JNK en el ipsi-Ctx, efectos que fueron revertidos por la coadministración de E2 y P4. Conclusiones: Nuestros datos muestran que el tratamiento combinado de E2 y P4 ejerce un efecto neuroprotector en el cerebro cuando se administra tras el daño isquémico, que está mediado por la modificación de la actividad de la via PI3-K/Akt/GSK3/ß-catenina y de la de SAPK/JNK. Por tanto, ofrecemos la prueba experimental de que la combinación de E2 y P4 es una terapia potencialmente valiosa para el tratamiento del ictus isquémico en humanism (AU)

Acute and chronic exposure of chick embryo to ethanol alters brain neurosteroid levels

Neurosteroids are modulators of neuronal function that may play important role in brain maturation. The aim of the present investigation was to study the effect of prenatal exposure to acute and chronic ethanol on brain progesterone, estradiol, and testosterone concentration on 10th and 15th days following egg incubation. Eggs were exposed to ethanol at 10 % in chronic treatment and 70 % in acute treatment. Progesterone, estradiol, and testosterone were assayed by radioimmunoassay method. It was shown that brain progesterone level was significantly decreased (P < 0.05) in chronic ethanol group on embryonic day 10, but it was significantly decreased (P < 0.05) in acute and chronic groups on embryonic day 15. Brain estradiol level was significantly increased (P < 0.05) in chronic ethanol group on embryonic day 10, and it was decreased (P < 0.05) in acute and chronic groups of ethanol on embryonic day 15. Brain testosterone was significantly increased (P < 0.05) in acute and chronic ethanol-exposed groups on embryonic days 10 and 15. Our observations suggest that ethanol may modulate neurosteroid synthesis in the brain (AU)

The effect of oral contraceptives on orthodontic tooth movement in rat

Introduction: The purpose of this study was to investigate the effect of ethinyl estradiol/norgestrel - used in some oral contraceptives- on orthodontic tooth movement in Wistar rats. Material and Methods: Forty eight female three-month old Wistar rats with an average weight of 250±25gr were divided into two experimental and control groups. One week prior to appliance insertion and during the appliance therapy period, 100 mcg/kg/day of ethinyl estradiol and 1mg/kg/days of norgestrel were administered to the experimental group by gavage; meanwhile the control group received an equivalent volume of Sodium Chloride 0.9 % (Saline). Maxillarycentral incisors were tipped distally by insertion of springs exerting 30 g force. Two, seven and fourteen days after spring insertion animals were sacrificed. The mesioincisal distance between maxillary incisors were measured. Subsequently, histological sections were prepared for histomorphometric studies. Results: 14 days after force application the orthodontic tooth movement was significantly lower in the experimental group (p<0.05). The number of osteoclasts were significantly lower in the experimental group 2, 7 and 14 days after spring insertion (p<0.05). Conclusion: Ethinyl estradiol/norgestrel (oral contraceptives) can significantly decrease the amount of tooth movement in the linear phase (AU)

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Progressive increase of glucose transporter-3 (GLUT-3) expression in estrogen-induced breast carcinogenesis

INTRODUCTION: Increased glucose uptake and glycolysis are main metabolic characteristics of malignant cells. A family of glucose transporters (GLUTs) facilitates glucose movement across the plasma membranes in a tumor-specific manner. Glucose transporter-1 (GLUT-1), GLUT-3 and recently GLUT-12, have been previously shown in breast cancer cells and are found to be associated with poor prognosis. In addition, it has been shown that estrogen plays critical roles in GLUT regulation, however, the stage-specific GLUT regulation of mammary carcinogenesis is unclear. METHODS: GLUT expression patterns were investigated in an in vitro-in vivo progressive, estrogen-induced, mammary carcinogenesis model which consisted of four cell lines, with same genetic background. In this model, different stages of tumor initiation and progression are represented, MCF-10F being the normal stage, E2 cells the transformed stage by estrogen, C5 cells, the invasive stage, and T4 cells the tumorigenic stage. In addition, loss of ductulogenesis and solid mass formation in collagen matrix and invasiveness of the cells were counted. RESULTS: Real time PCR showed that GLUT1 expression was downregulated in MCF10F after treatment with 17β-estradiol (E2), and in the invasive cell type (C5), but not in the tumor cells (T4), which had no changes compared to MCF10F. C5 and T4 cells showed the highest rate of GLUT-3 expression. These cells were also found to be associated with loss of ductulogenesis, solid mass formation and higher invasive capacity, whereas, GLUT-12 was downregulated in C5 and T4 cells. CONCLUSION: Estrogen-induced malignant transformation is associated with remarkable and progressive GLUT-3 expression, GLUT-1 re-expression at further stages, as well as GLUT-12 downregulation (AU)

Changes in lymphocyte HSP70 levels in women handball players throughout 1 year of training: the role of estrogen levels

Heat shock protein 70 (HSP70) is a chaperone that maintains protein conformation during heat stress. It has recently been observed that HSP70 may be released from cells in response to increased energy demand (e.g., exercise) and/or oxidative stress. Since HSP70 levels should change in response to athletic training, we have investigated whether blood HSP70 levels in young women handball players change over a complete training season. Thirty women handball players (12-24 years old) were divided into (..) (AU)

Expanding Sca-1(+) mammary stem cell in the presence of oestrogen and growth hormone

BACKGROUND: Sca-1 is controversial as a mammary stem cell marker in the literature, which may be due to the different isolation protocols and culture media used in different laboratories. The object of our study is to establish the Medium to promote the proliferation of mammary stem cell and explore the possibility of Sca-1 as mammary stem cell marker. METHODS: We used BM medium supplemented with different concentration of 17Β-oestradiol and GH to find out MaECM medium which promoted the proliferation of mouse mammary epithelial cells and inhibited the growth of fibroblasts. Flow cytometry was used to isolate Sca-1(+) and Sca-1(-) cell populations from cultured mammary epithelial cells. Mammary fat pad transplantation and Mammosphere- forming assay were done to confirm the stem cell potential of Sca-1(+) cells. Differentiating culture was used to detect the differentiation potential of Sca-1(+) cells. Real-time PCR was carried out to analyse the expression of mammary stem cell-related genes in Sca-1(+) cells. RESULTS: We first selected the medium suitable for mammary stem cell growth. Stem cell medium BM was used to culture mammary organoids, which generated many fibroblasts. We established MaECM medium supplemented with oestrogen and growth hormone (GH), in which oestrogen promoted mammary epithelial cell proliferation and inhibited fibroblast growth, and GH obviously enhanced the effect of oestrogen on mammary epithelial cell proliferation. Flow cytometry showed that 50% of cells were Sca-1(+) under the culture of MaECM medium. We confirmed that Sca-1(+) cells regenerated mammary outgrowths when transplanted in vivo, formed mammospheres in vitro and differentiated into luminal epithelial cells with milk-secreting function and myoepithelial cells under Matrigel culture. Furthermore, gene expression analysis by Real-time PCR revealed that Sca-1(+) cells expressed markedly higher levels of mammary stem cell-related genes in comparison to Sca-1(-) cells. CONCLUSION: Our research demonstrates that Sca-1(+) mammary stem cells can be more easily isolated when cultured in the presence of oestrogen and GH (AU)

Efecto de las hormonas sexuales sobre las concentraciones de homocisteína en preeclámpticas y embarazadas normales / Effect of sexual hormones on homocysteine concentrations in preeclamptic and normotensive pregnant women

Objetivo. Establecer los efectos de las hormonas sexuales sobre las concentraciones plasmáticas de homocisteína en preeclámpticas y embarazadas normales. Métodos. Los grupos consistieron en 35 preeclámpticas (grupo A) y 35 embarazadas normotensas (grupo B), consideradas como controles. Las muestras de sangre se recolectaron en todas las pacientes antes del parto y en el grupo de estudio (grupo A) inmediatamente después del diagnóstico. Se midieron las concentraciones de testosterona, testosterona libre, sulfato de dehidroepiandrosterona, androstenodiona, estradiol y homocisteína. Resultados. Se observaron diferencias estadísticamente significativas en la edad gestacional, presencia de proteinuria, peso de los recién nacidos y de la presión arterial sistólica y diastólica (p<0,05). Las concentraciones de testosterona, testosterona libre, sulfato de dehidroepiandrosterona y homocisteína fueron significativamente superiores en el grupo A comparado con los controles (p<0,05). Las concentraciones de estradiol se encontraron disminuidas en el grupo A comparado con los controles (p<0,05). Se encontraron correlaciones positivas fuertes de testosterona, sulfato de dehidroepiandrosterona y testosterona libre y una correlación moderada negativa con las concentraciones de estradiol con las concentraciones plasmáticas de homocisteína (p<0,05). Conclusiones. Las concentraciones plasmáticas de homocisteína son afectadas en forma positiva por testosterona, sulfato de dehidroepiandrosterona y testosterona libre y negativa por el estradiol en pacientes preeclámpticas y embarazadas normotensas (AU)

Objective. To establish the effects of sexual hormones on plasma homocysteine concentrations in preeclamptic and normotensive pregnant women. Methods. There were two groups: group A consisted of 35 preeclamptic patients and group B of 35 normotensive pregnant women used as controls. Blood samples were collected before labor in both grops and immediately after diagnosis in group A. Concentrations of testosterone, free testosterone, dehidroepiandrosterone sulphate, androstenodione, estradiol and homocysteine were measured. Results. There were statistically significant differences in gestational age, the presence of proteinuria, birthweight and systolic and diastolic blood pressure (p<0.05). Testosterone, free testosterone and dehidroepiandrosterone sulphate were significantly higher in group A than in group B (P<.05). Estradiol concentrations were significant lower in the group A than in group B (P<.05). Strong positive and significant correlations were found between testosterone, dehidroepiandrosterone sulphate and free testosterone and a moderate negative correlation was found between estradiol and plasma homocysteine concentrations (P<.05). Conclusions. In preeclamptic and normotensive pregnant women, plasma homocysteine concentrations are positively affected by testosterone, dehidroepiandrosterone sulphate and free testosterone and are negatively affected by estradiol (AU)