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This project aims to develop eligibility criteria for menopausal hormone therapy (MHT). The tool should be similar to those already established for contraception A consortium of scientific societies coordinated by the Spanish Menopause Society met to formulate recommendations for the use of MHT by women with medical conditions based on the best available evidence. The project was developed in two phases. As a first step, we conducted 14 systematic reviews and 32 metanalyses on the safety of MHT (in nine areas: age, time of menopause onset, treatment duration, women with thrombotic risk, women with a personal history of cardiovascular disease, women with metabolic syndrome, women with gastrointestinal diseases, survivors of breast cancer or of other cancers, and women who smoke) and on the most relevant pharmacological interactions with MHT. These systematic reviews and metanalyses helped inform a structured process in which a panel of experts defined the eligibility criteria according to a specific framework, which facilitated the discussion and development process. To unify the proposal, the following eligibility criteria have been defined in accordance with the WHO international nomenclature for the different alternatives for MHT (category 1, no restriction on the use of MHT; category 2, the benefits outweigh the risks; category 3, the risks generally outweigh the benefits; category 4, MHT should not be used). Quality was classified as high, moderate, low or very low, based on several factors (including risk of bias, inaccuracy, inconsistency, lack of directionality and publication bias). When no direct evidence was identified, but plausibility, clinical experience or indirect evidence were available, "Expert opinion" was categorized. For the first time, a set of eligibility criteria, based on clinical evidence and developed according to the most rigorous methodological tools, has been defined. This will provide health professionals with a powerful decision-making tool that can be used to manage menopausal symptoms.

Resumen: Los estudiantes de medicina necesitan adquirir una serie de conocimientos, habilidades y actitudes que les capaciten para el desempeño de la medicina. La facultad de Medicina de la Universidad Miguel Hernández de Elche incluyó en su plan de estudios del Grado en Medicina 4 asignaturas denominadas «talleres integrados» en las que se desarrollan diversas actividades docentes para integrar conocimientos y habilidades clínicas de varias disciplinas y fomentar la adquisición de competencias transversales. En este artículo describimos la organización y métodos didácticos empleados en la asignatura «Talleres integrados II» como un elemento de reflexión para compartir la experiencia con la comunidad educativa en medicina. Esta asignatura integra las siguientes materias: bases generales de la cirugía, farmacología clínica, patología general, inmunología y alergia, dermatología, epidemiología y demografía sanitaria, microbiología, obstetricia y oftalmología. Es una asignatura con 4,5 créditos prácticos y utiliza elementos docentes como práctica hospitalaria guiada por objetivos, participación de alumnos y talleres prácticos, simulación, prueba evaluación de competencias objetiva estructurada, y presentación clínica en formato Pecha Kucha, lo que potencia la integración de conocimientos y el aprendizaje activo con adquisición de competencias y habilidades prácticas muy pertinentes para el futuro médico. Abstract: Medical students need to acquire a range of knowledge, skills, and attitudes that will prepare them for medical clinical practice. The School of Medicine of Miguel Hernández University (Elche, Spain) includes, in its Medical Degree curriculum, 4 subjects called “Talleres integrados” (Integrated Workshops-II). Diverse teaching activities are developed to integrate knowledge and clinical skills of several disciplines, and to promote the acquisition of transversal skills. A description is presented of the organisation and didactic methods used in the Integrated Workshops-II subject as an element for reflection and to share the experience with the educational community in medicine. This subject integrates the following: general bases of surgery, clinical pharmacology, general pathology, immunology and allergy, dermatology, epidemiology and health demography, microbiology, obstetrics and ophthalmology. It is a subject with 4.5 practical credits and uses teaching elements such as hospital practice guided by objectives, student participation and practical workshops, simulation, objective structured clinical examination (OSCE), and presentation of cases in Pecha Kucha format, all of which enhances the integration of knowledge and active learning with acquisition of skills and practical skills very pertinent for the future doctor. Palabras clave: Talleres integrados, Enseñanza, Medicina, Competencias, Evolución Clínica Objetiva Estructurada, Portafolio, Keywords: Integrated workshops, Teaching, Medicine, Competencies, Objective Structured Clinical Examination, Portfolio

Tissue-selective estrogen complex (TSEC) is projected as a progestogen-free option for the treatment of estrogen deficiency symptoms in postmenopausal, non-hysterectomized women. TSEC combines the benefits of estrogen with a selective estrogen receptor modulator (SERM), in this case bazedoxifene acetate (BZA), which has an antagonistic effect on the endometrium, thus avoiding the use of progestins. The authorized TSEC combination (conjugated estrogens [CE] 0.45 mg/BZA 20 mg) for the alleviation of vasomotor symptoms has been demonstrated in randomized clinical trials compared with placebo or menopausal hormone therapy (MHT). In addition, TSEC has shown improvements in quality of life and vaginal atrophy. In respect to MHT using progestins, the benefits of TSEC are found mainly in the bleeding pattern, amenorrhea rate, and reduction in mammary repercussion (i.e., breast tenderness and radiological density). The objective of this guide will be to analyze the efficacy and safety of TSEC consisting of CE/BZA in postmenopausal women.

Most important ovarian hormones are estrogens, progestins, and androgens. Menopausal ovarian failure supposes a hormonal deprivation with variable repercussions for women, like symptomatology with negative effects on quality of life, and changes of future risks of some important and prevalent pathologies. Hormone therapy is the etiologic treatment for avoiding all of that, but introduces some modifications in those risks, and has collateral effects. In addition, many types of composition, formulations, doses, routes, and schemes are available for HT, with relevant differences on pharmacokinetics, efficacy, or collateral effects which can be even targets for selection, like bleeding pattern or lipid profile. So topics like information, indication, selection of HT, acceptance, and compliance are difficult in many cases and require knowledge and experience for the health-care provider. In this chapter, we review and discuss all of those topics, the treatment plan, and the follow-up questions.

Denosumab is a new drug developed for the treatment of osteoporosis. Moreover, increasing evidences link denosumab with benefits in cancer, an area of interest for those in charge of the postmenopausal health. Denosumab has shown efficacy in the control of bone loss associated with hypogonadic states created by chemotherapy in breast and other cancers. Moreover, some studies reveal efficacy in reducing the progression of metastases. A panel of experts from the Spanish Menopause Society has met to develop usage recommendations based on the best available evidence.

Tibolone is a drug with complex tissue-specific action that exhibits a combination of estrogenic, progestogenic, and slight androgenic activity. Its variable profile explains its clinical effects, depending on the target tissue where it is metabolized, its metabolites' affinity for and potency in hormone receptors, and probable enzymatic activity modulation.In recent reviews and clinical trials, the effectiveness of tibolone in alleviating different hot flush menopause symptoms, mainly in mood and sexuality disorders, has been noted. In Spain, tibolone is the most prescribed hormonal treatment, and one of the most common complaints among postmenopausal women is change in sexual drive. For such reason, a panel of experts from the Spanish Menopause Society met to develop usage recommendations based on the best evidence available.

A randomised and controlled experimental study was carried out to determine the effect of short and long series of treatment with recombinant human interferon-alpha-2b on surgically induced endometriosis in rats.Ninety-six Wistar adult female rats, which had undergone an autotransplant into the peritoneal cavity of four endometrial fragments measuring 4.5mm at the side, were randomly divided into three groups. One third of the animals were manipulated like the treated animals but were not given treatment and served as control (group C). Another third (group S) were treated with three doses (one every 48 h, 100,000 U per dose) of recombinant human interferon-alpha-2b (subcutaneous route), and the last third (group L) were treated with fifteen doses of interferon (100,000 U every 48 h).Before interferon was administered, there were no differences between groups in the average growth of experimental endometriosis per animal (17.3±6.7, 18.1±9.2, 16.4±5.6mm in groups C, S and L respectively). After the treatment, experimental endometriosis per animal was significantly smaller in the groups treated with interferon than in the control non-treated group (p0.001), and in the group treated with 15 doses versus the group treated with 3 doses (p0.05), (17.6±7.5, 14.0±9.5, 9.4±6.0mm in groups C, S, and L respectively). While the implants of the animals in the control group showed no change in size throughout the study (120 days) (+1.96% of variation), the mean size of the implants in the treated rats decreased, (22.7% with the short and 42.8% with the long series of treatment with interferon). Only one implant in group C (0.8%) disappeared, while this occurred in 27 cases (22.5%) in group S (p0.001) and in 45 (37.5%) in group L (p0.001 versus group C and p0.05 versus group S).The long series of treatment with human interferon-alpha-2b was more effective than the short one in reducing the size of surgically induced endometriosis in the peritoneal cavity of the rat.

Perimenopause is an imprecise period in woman over 40 years of age, which comprises the time between the moment that the first changes in the menstrual cycle appear and the year following the definitive cessation of the menses. Besides irregular bleeding, many women also complain of hot flashes and other characteristic symptoms of postmenopause. Moreover, most of them are concerned about the future impact that these events may have on their health, such as needing health exams or continuing to use contraceptive methods. A panel of experts from the Spanish Menopause Society has met to establish diagnostic and therapeutic guidelines for this period based on the best available evidence.

Background: To analyze the therapeutic results of recombinant interleukin-2 (rIL-2) left in the cysts after transvaginal ultrasound (US)-guided drainage of endometriomas as an alternative to surgery. Methods: Prospective and randomized clinical trial. A total of 25 consecutive patients were included. Two transvaginal US-guided punctures were performed, and 3 million IU of rIL-2 were left in the aspirated cysts once (group I) or both (group II) times according to randomization. Main Outcome Measures: Clinical results, prevented surgeries, and recurrences. Results: Results were moderate or good in only 16% of subjects at 3 months and in 33% of subjects at 6 months after treatment in group I; these numbers were 66 and 33%, respectively, in group II. Differences were not statistically significant. However, the evolution of symptoms, endometriomas, and CA-125 revealed the low efficacy of rIL-2 left intracyst as well as a poor control of the clinical manifestations. After 1 year, 20% (group I) and 73% (group II) of patients had to be operated; after 2 years, these numbers were 55 and 82%, respectively. Conclusions: Treatment of endometriomas with transvaginal US-guided drainage and rIL-2 left in the cysts, without using endometrial suppressive therapy with GnRH analogues as done in previous studies, has low efficacy. Recurrences are even more frequent after the use of two rIL-2 doses.

Objetivo: Dado el creciente interes en los paises occidentales acerca de la utilizacion de ciertas plantas para el tratamiento de los sintomas relacionados con la menopausia, la Asociacion Espanola para el Estudio de la Menopausia (AEEM) ha evaluado el papel de la Cimicifuga racemosa en el tratamiento de los sintomas climatericos sobre la base de las mejores evidencias disponibles. Material y metodos. Se reunio un panel de expertos, clinicos e investigadores, en el campo de la fitoterapia. Los estudios seleccionados se obtuvieron mediante una busqueda electronica que incluyo buscadores de Internet, MEDLINE (1985-mayo 2008) y el Registro de Ensayos Clinicos Controlados Cochrane. Resultados: La mayoria de los estudios publicados en los ultimos anos estan realizados con el extracto isopropanolico de Cimicifuga racemosa. La dosis mas estudiada ha sido 40 mg/dia y ha demostrado obtener una reduccion moderada de las sofocaciones, sobre todo en las mujeres con sofocos mas intensos, y una mejoria del estado de animo. Utilizada a las dosis recomendadas, no hay riesgo relevante desde el punto de vista hepatico. Los datos disponibles sobre su efecto en la enfermedad cardiovascular, el hueso, la funcion cognitiva y la piel son muy escasos o inexistentes. Conclusiones: La Cimicifuga racemosa es un tratamiento eficaz en el alivio de los sintomas vasomotores, al menos en una poblacion adecuada de mujeres peri y posmenopausicas, si bien se precisan mejores ensayos clinicos con suficiente numero de pacientes incluidas y mayor duracion del estudio.

Objetivo: Este estudio describe el perfil, las actitudes, conocimiento y expectativas de las pacientes con osteoporosis posmenopausica. Sujetos y metodos: Estudio epidemiologico, transversal, realizado en Espana. Participaron pacientes en tratamiento para osteoporosis posmenopausica > 45 anos. Se recogieron antecedentes personales y familiares, enfermedades y farmacos concomitantes, habitos toxicos, dieteticos y de actividad fisica, tipo de diagnostico, tratamiento y cumplimiento. Todas las pacientes cumplimentaron un cuestionario de 17 preguntas sobre las actitudes, el conocimiento y las expectativas en relacion con su afeccion. Resultados: Se incluyo a 1.179 pacientes con osteoporosis posmenopausica validas, con una edad media ± desviacion estandar de 59,89 ± 7,53 anos. Solo el 22,6% mostro un conocimiento aceptable sobre la osteoporosis. Al 74,6% de las pacientes les preocupaba su enfermedad mucho/ bastante. El 53,3% describio su estado de salud como excelente/bueno. No obstante, el 63,6% indico que necesitaba mas informacion sobre la osteoporosis. Conclusiones: Este estudio ha evidenciado la necesidad de promover el correcto conocimiento de las pacientes con osteoporosis posmenopausica sobre su afeccion.

Resumen Objetivos Conocer la distribucion de los factores de riesgo asociados con la osteoporosis posmenopausica en la poblacion espanola. Pacientes y metodos Estudio observacional multicentrico de 1.779 mujeres posmenopausicas. En funcion del diagnostico densitometrico, se dividieron en 3 grupos: a) 450 mujeres con osteoporosis; b) 766 con osteopenia, y c) grupo control formado por 479 mujeres con valores de densidad mineral osea normal. Resultados Los factores de riesgo conocidos de osteoporosis se presentan en nuestras pacientes con similar distribucion que en otros estudios. Ademas, se observa un efecto protector de la dieta basada en alimentos vegetales, junto al consumo moderado de alcohol, pescado y productos lacteos. Conclusion Se confirmo la importancia de los factores de riesgo conocidos de osteoporosis. Ademas, en nuestra poblacion se identifico el papel protector de la ingesta abundante de los alimentos que se incluyen en la llamada dieta mediterranea.

In the present study, the authors look at an association of genetic variants within estrogen synthesis and signaling pathways and age at menarche (AAM) in Spanish women. They analyzed 9 polymorphisms in 6 different genes in 714 well-characterized postmenopausal women from Spain. They performed a quantitative trait locus study of these markers individually or in digenic combinations in relation to AAM. None of the studied markers, with the exception of the follicle-stimulating hormone receptor (P = .013), were significantly associated with AAM in the Spanish population, and no marker demonstrated an association of statistical significance after multiple testing corrections (P > .0055). In contrast, linear regression analysis suggests epistatic interactions including ESR1 and ESR2 loci in relation to AAM in the series (P = .003). The results suggest that epistatic interactions of ESR1 and ESR2 alleles could be associated with advancing AAM among Spanish women.

Resumen Objetivo Existe un interes creciente en los paises occidentales acerca de la utilidad de las isoflavonas de la soja para el tratamiento de los sintomas y enfermedades relacionadas con la menopausia y el envejecimiento, que se ha traducido en la aparicion de un importante numero de publicaciones, muchas de las cuales presentan resultados contradictorios. La Asociacion Espanola para el Estudio de la Menopausia (AEEM) ha evaluado el papel de las isoflavonas en la salud de la mujer menopausica, basandose en las mejores evidencias disponibles. Material y metodos Se reunio un panel de expertos, clinicos e investigadores en el campo de las isoflavonas. Los estudios seleccionados se obtuvieron mediante una busqueda electronica que incluyo buscadores de internet, Medline (1966- marzo de 2007) y el Registro de Ensayos Clinicos Controlados Cochrane. Resultados Las diferentes revisiones y metaanalisis sobre los efectos de las isoflavonas en la salud de la mujer son controvertidos. La diversidad de resultados puede deberse, entre otras causas, a la falta de uniformidad de los compuestos estudiados. En relacion con la dosis y el contenido en genisteina, se han demostrado efectos beneficiosos en el perfil lipidico, como antioxidantes, asi como una reduccion moderada de los sofocos. Algunos estudios sugieren un efecto positivo en la masa osea. Los datos disponibles en otros aspectos, como la mama, canceres dependientes de los estrogenos, funcion cognitiva y piel, entre otros, son escasos. Conclusiones En diversas situaciones, las isoflavonas pueden ser una alternativa terapeutica en el climaterio, si bien antes de poder proceder a la realizacion de recomendaciones generales acerca del consumo de preparados de isoflavonas, se necesitan ensayos clinicos especificos, de diseno adecuado, con preparados normalizados en cuanto al contenido en isoflavonas y sus tipos, y con suficiente numero de pacientes y tiempo de estudio.

The aim of this double-blinded study was to determine changes in leukocyte populations in blood, peritoneal lavage fluid, eutopic and ectopic endometrium after treatment with recombinant rat interleukin-2 (IL-2) using an in vivo experimental model of rat endometriosis. The in vivo model involved transplanting four square fragments of autologous endometrium onto the inner surface of the abdominal wall in 20 Wistar rats. The control group was constituted by 20 sham-operated rats. Both groups were randomly treated (1-month interval treatment) with 2 intraperitoneal doses of glucose solution (5%) that did or did not contain recombinant IL-2, and animals were sacrificed 4 weeks after the last dose of treatment. Blood and peritoneal lavage were obtained during the initial and final laparotomy, whereas eutopic and ectopic endometrium were collected at the end of the experiment. Endometriotic implants were measured in each laparotomy to determine any change in size. Leukocyte populations were analyzed by flow cytometry and immunofluorescence microscopy. Cytometric results were similar in blood and peritoneal lavage. CD25+ and natural killer (NK) cell levels in peripheral blood were lower in rats with endometriosis treated with IL-2, whereas NK cells increased in lavage compared to placebo group. The percentage of macrophages and dendritic cells in blood were higher in all rats treated with IL-2, as well as peritoneal dendritic cells. Implant size of these rats decreased significantly, showing a greater number of activated lymphocytes, macrophages, NK and dendritic cells inside them. In conclusion, recombinant IL-2 induced recruitment of activated leukocytes into endometriotic-like foci, and this was related to a reduction of the implant size, suggesting potential effectiveness of IL-2 as an immunomodulatory agent in this pathology.

Osteoporosis is a common disease with multiple environmental and genetic risk factors involved. Using a marker-by-marker approach, the role of different estrogen-related genes has been analyzed in different populations, but most of these studies ignore the complex multigenic nature of human osteoporosis. Looking for markers related to osteoporosis, we have analyzed five single nucleotide polymorphisms located in genes related to the estrogen pathway, Follicle Stimulating Hormone Receptor (FSHR) gene, the CYP19 aromatase (CYP19A1) gene, the Estrogen Receptor alpha (ESR1) gene, the Estrogen Receptor beta (ESR2) gene and the Nuclear Receptor Interacting Protein 1 (NRIP1) gene in 265 unrelated postmenopausal women. We have obtained nominal P values for the NRIP1 Gly75Gly and ESR2 *39AG markers (P=0.013 and P=0.02 respectively), but no gene seems to be associated after multiple test corrections. Reanalysis of this study using 437 postmenopausal women confirmed our results and only detect marginal effects for ESR2 marker (P=0.045). By contrast, multilocus analysis predicted epistatic interactions between ESR1, ESR2 and NRIP1 loci and its involvement in postmenopausal osteoporosis (P=0.003). We detected two digenic genotypes involving ESR2-NRIP1 and ESR2-ESR1 genes strongly associated with osteoporosis (P=0.007). Replication of multilocus studies using 437 patients confirmed the detected interactions (P0.01). We proposed a non-additive non-multiplicative oligogenic model including ESR2 AG genotype modulated by NRIP1 A+ or ESR1 TT genotypes involved in osteoporosis. Our results reaffirm the polygenic nature and the genetic complexity of osteoporosis trait adding a new candidate gene (NRIP1) for association studies of bone-related traits.

An important goal in menopause research is to develop knowledge and identify interventions that strive to promote, maintain and enhance well-being for women.To evaluate the knowledge of postmenopausal Spanish women about menopause and their knowledge of and trust in hormone replacement therapy (HRT) and to identify their sources of information and how those data are related to compliance with their prescription.A total of 270 symptomatic postmenopausal women were personally interviewed using a structured questionnaire, which was designed to collect information on their familiarity with medical menopause studies, the menopause and the effects of HRT, their knowledge of alternative therapies, and to identify their sources of information.The most well-known menopausal complaints were hot flushes, sweats, irregular menstruation, cessation of menstruation, irritability and mood changes. Following suggestions of other symptoms by the interviewer, other complaints such as vaginal dryness, insomnia and depression/anxiety were also mentioned. HRT and phytoestrogens were recognized as treatments for the climacteric by most of the women. A woman's decision to seek treatment was initiated in 77% of cases by the gynecologist, in 12% by the general practitioner, in 3% by friends/family and in 3% by books/magazines. The most frequent responses of women to the onset of menopausal symptoms were to talk with their partner (39%), to discuss it with their gynecologist (33%) or with their general practitioner (14%) and to talk with their friends/family or to read books/magazines (10%).Vasomotor symptoms are recognized as the main complaint during the climacteric and HRT and phytoestrogens as the main therapies. Gynecologists play an important role in assuring compliance with therapies related to the menopause.

To consider what a correct preventive approach for osteoporosis should be in the management of the asymptomatic post-menopausal woman. Literature review and opinions on this issue shared by a group of professionals with wide clinical experience in health care for peri- and post-menopausal women. There is agreement that osteoporosis combines most of the ideal requirements for the application of a preventive strategy. The natural evolution of this pathology leads to serious events, fractures, but it provides various opportunities for prevention. Osteoporosis can be avoided and in particular, fractures due to bone fragility and their consequences should be avoided. Nowadays, there are different courses of action (pharmacological or otherwise) with proven effectiveness for the prevention osteoporosis and osteoporotic fractures. However, long-term action is required for a broad segment of the population, so a certain strategy is necessary to guide clinical decisions for different profiles of women. There is little data in the literature to justify a different preventive approach, depending on the presence or absence of vasomotor symptoms, but clinical experience shows that their absence is not associated with a lower osteoporosis risk. Different strategies have been tried for the prevention of osteoporosis and its complications and some of them might be effective, but there is no analysis with conclusive results. A preventive strategy for osteoporosis should be included in the management of asymptomatic post-menopausal women, because this is an avoidable pathology and the absence of vasomotor symptoms does not reduce the risk of its development. Nevertheless, a well-designed cost-benefit analysis is needed to justify the implementation of any strategy at a community level, because adverse effects and economic cost could exceed the benefits obtained in low fracture risk populations.

Background: To analyze the therapeutic results of one dose of 3 million IU of recombinant interleukin-2 (rIL-2) left intracyst (group I) versus two doses with a 1-month interval (group II) after transvaginal ultrasound (US)-guided drainage of endometriomas under the effect of GnRH analogues. Methods: Prospective and randomized clinical trial (helped by a random number table) at a University Hospital. Twenty-four consecutive patients with endometriomas initially sent to us for laparotomy and conservative surgery for endometriosis were included. Interventions: Treatment with GnRH analogues every 28 days, 3 doses. Under their effect, one or two transvaginal US-guided punctures were performed in order to aspirate the endometriomas, and 3 million IU of rIL-2 were left in the aspirated cysts each time. Main outcome measures: Clinical results: two menstruations after GnRH analogues. Other secondary outcome measures were: the time until recurrence of cysts, symptoms and CA-125 >35 U/ml, and the need for further medical or surgical treatment. Results: They were moderate or good in >50% of cases with one drainage and one dose of 3 million IU of rIL-2 intracyst, but were better with a second drainage and two doses of rIL-2 (25 vs. 58.3% ‘good results’). There were fewer recurrences and the interval before recurrence was longer after two doses but differences were not significant. Six patients from group I (50%) and 3 from group II (25%) needed laparotomy and conservative surgery at 17.5 ± 8.7 months (total time of follow-up = 33 ± 8.8 months). Conclusions: Treatment of endometriomas with transvaginal US-guided drainage and rIL-2 left in the cysts under endometrial suppressive therapy with GnRH analogues has beneficial effects, improving clinical manifestationsand avoiding some surgical therapies. The use of a higher dose of rIL-2 does not produce better results, whereas drainage + rIL-2 twice does.

Resumen Objetivos Correlacionar los estadios clinico y quirurgicopatologico del cancer cervical y analizar los resultados terapeuticos tras haber realizado cirugia radical de Wertheim-Meigs en la mayoria de los mismos con estadio IIB o inferior. Sujetos y metodos Analisis retrospectivo de 115 pacientes diagnosticadas de carcinoma cervical en estadio IIB o inferior entre los anos 1984 y 1999; fueron operados 100 casos y se realizo cirugia radical en el 65% de los canceres en estadio IIB; asimismo, 58 de los casos operados recibieron radioterapia; las otras 15 pacientes no operadas se trataron con radioterapia sola. Resultados El 21% de los casos en estadio clinico IA-IB se hallaba en realidad en un estadio quirurgicopatologico mas elevado, mientras que entre aquellas pacientes operadas con un estadio clinico IIB, el 48% se encontraba realmente en un estadio mas bajo. Las tasas de supervivencia actuarial a 5 anos en los 100 casos operados fueron del 100% para el estadio IA, el 88% para el IB, el 100% para el IIA y el 59,4% para el IIB; a los 10 anos fueron del 100, el 88, el 100 y el 52%, respectivamente. En los casos de estadio IIB no operados, las tasas de supervivencia a los 5 anos fueron del 71,7 y a los 10 anos del 40%. No hubo diferencias en lo que respecta a la supervivencia o recurrencias entre las pacientes en estadio IB/IIA a las que se practico cirugia radical con o sin radioterapia posterior. Tampoco hubo diferencias en las tasas referidas al comparar la presencia o no de ganglios positivos. Sin embargo, en el estadio posquirurgico IIB, la supervivencia a los 5 anos fue del 80% si los ganglios linfaticos fueron negativos, frente al 17,8% si estos eran positivos para cancer. Conclusiones En primer lugar, en condiciones apropiadas, mediante la cirugia radical de Wertheim-Meigs se obtienen buenos resultados de supervivencia (mas del 90%) en los estadios IB-IIA, que se mantienen tras la radioterapia adicional para aquellos casos con factores pronosticos adversos. En segundo lugar, la comparacion entre cirugia y radioterapia no puede establecerse en el estadio clinico IIB puesto que entre los casos operados, el 47% se encontraba realmente en un estadio mas bajo. Por ultimo, en el estadio quirurgicopatologico IIB, si los ganglios linfaticos son negativos, la supervivencia es buena (80%) y las tasas de recurrencia, bajas. Por tanto, estos casos tambien podrian beneficiarse de la cirugia radical.

Objective: To analyze the correlations among insulin, androgens, body mass index (BMI), and other related metabolic anomalies in women with and without polycystic ovary syndrome (PCOS). Design: Retrospective study of normal and obese women with and without PCOS. Setting: Gynecologic endocrinology units of Elche, San Juan, and Alicante Hospitals and Hormone Laboratory at Alicante University Hospital ("Miguel Hernandez" University). Patient(s): A total of 212 women were studied: 137 with PCOS and 75 without PCOS. Intervention(s): BMI, gonadotropins, insulin, androgens (T, androstenedione, DHEAS), 17α-hydroxyprogesterone, sex hormone-binding globulin, and triglycerides were studied. Glycemia and insulin response to the tolerance test (GTT) with a 100-g oral glucose load were also assessed in 103 women. Result(s): A good correlation between insulin and BMI was found in normal and obese women without hormonal dysfunction and in patients with or without PCOS. Good correlations, although lower, between insulin and T, and BMI, insulin, and T with triglycerides were also found in patients with PCOS. These patients fell into clearly distinct categories: with or without insulin resistance and with or without obesity, but slim women with PCOS had insulin and metabolic variables similar to those without PCOS, and most obese women with PCOS were insulin-resistant and more hyperandrogenic and hypertriglyceridemic. Conclusion(s): Insulin, androgens, and BMI are related in women both with PCOS and without PCOS, especially in obese ones. Insulin and metabolic indices are similar in lean women with PCOS and those without PCOS, but obese women with PCOS are more insulin-resistant, hyperandrogenic, and hypertriglyceridemic. Three types of disorders can be distinguished: simple nonhyperandrogenic obesity, typical nonhyperinsulinemic PCOS, and insulin-resistant PCOS.

To determine the effect of human interferon (IFN)-alpha-2b on experimental endometriosis in rats.Experimental, controlled, double-blind randomized study.Experimental surgery laboratory in a university department.Ninety-six Wistar rats with endometriosis, induced by transplanting four endometrial fragments into the peritoneal cavity.One third of the animals served as controls (group A). The others were randomly divided into two groups and were given IFN-alpha-2b either as a single intraperitoneal dose (group B) or as three SC doses (on alternate days) (group C).Laparotomy was performed to measure the size of each implant at various times (days 0, 6, 12, 20, and 120 after treatment).There were no differences among the groups in the size of the average implants before IFN was administered (17.3+/-6.7, 19.7+/-7.8, and 18.1+/-9.2 mm for groups A, B, and C, respectively). These values were significantly smaller after treatment in group B (14.9+/-8.0 mm) and group C (14.0+/-9.5 mm) than in the control group (17.6+/-7.5 mm) (P.05). Intraperitoneal IFN produced an initial maximum decrease in the size of the implants (40% reduction on day 6), which diminished until day 20 (20%) and then was maintained on a plateau until day 120 (25%). By contrast, group C showed an initial minimal reduction (13% at day 6), which increased up to day 20 (19%), after which a plateau was reached (23% at day 120). Thus, the effects in both treatment groups were similar in the long term.Two short regimens of human IFN-alpha-2b reduced the size of experimental endometriosis in rats.

Germline mutations in different genes are associated with premature ovarian failure (POF, OMIM 311360), defined as premature menopause with amenorrhea occurring before the age of 40 years along with increased gonadotropin concentrations [follicle-stimulating hormone (FSH) >40 IU/L]. A new candidate gene, bone morphogenetic protein 15 ( BMP15 ) has been investigated in POF. In a family affected by hypergonadotropic ovarian failure, a mutation in the pro-region of the BMP15 gene (Y235C) was found in 2 affected sisters (1), and 3 linked markers within the BMP15 gene (−673C>T, −9C>G and IVS1 + 905A>G) are associated with high follicle production in women undergoing recombinant FSH stimulation (2). Several heterozygous variations affecting the pro-region and mature peptide of the BMP15 gene have been identified in women with POF (3)(4)(5), but A180T was the only variant found in all reported studies, occurring with relatively high frequency in POF women (8 of 502, 1.6%) but not at all in control groups. To clarify the role of the A180T allele in early menopause and ovarian failure, we used a pyrosequencing protocol (Biotage) to evaluate the A180T …

Pedro Acién,1–3 Clara Núñez,1 Francisco Quereda,1–3 Irene Velasco,1 Marta Valiente,1 Virginia Vidal1 1Department of Obstetrics and Gynecology, San Juan University Hospital, 2Department/Division of Gynecology, School of Medicine, Miguel Hernandez University, Campus of San Juan, 3Institute of Gynecology PAA, Alicante, Spain Background: The purpose of this paper is to report the long-term results of surgery without bowel resection in patients suffering from deep infiltrating endometriosis with rectovaginal or colorectal involvement. Methods: This retrospective observational study identified 42 patients suffering with deep infiltrating endometriosis who underwent surgery. Conservative surgery was performed in 23 women (only one of them with bowel resection), and 19 women underwent a hysterectomy and bilateral salpingo-oophorectomy (HBSO). In the conservative surgery group, a later HBSO was performed in eight patients as a second operation. Pregnancies, recurrences, reoperations, use of hormone replacement therapy, and outcomes during long-term follow-up were analyzed. Results: The average follow-up duration was 7 ± 5.7 years in conservative surgery cases. Only one patient was treated with sigmoid bowel resection in 1997 and had complications. In this conservative surgery group, 13 patients (56%) received medical treatment after surgery, 10 patients wanted to get pregnant (of whom seven [70%] were successful), and eight patients underwent a subsequent HBSO because of recurrent symptoms and/or endometrioma. Therefore, HBSO was performed in 27 patients, of whom 14 (51.8%) used hormone replacement therapy for 5.6 ± 3.6 years. No recurrences or complications were observed in patients after HBSO with or without hormone replacement therapy. Conclusion: Good clinical results can be obtained by performing only conservative surgery and/or HBSO without bowel resection, an alternative that could reduce the number of colorectal resections that are performed very frequently nowadays. After HBSO, patients may use hormone replacement therapy for several years with total satisfaction and well-being. Keywords: deep infiltrating endometriosis, rectovaginal septum, bowel resection, colorectal, endometriosis

Breast cancer is the most common female cancer in Spain. Its high prevalence, its high survival rate, and its incidence are the reasons treatment is increasingly sought for common problems by young women who have survived it. Besides the contraception and fertility issues, many breast cancer survivors develop sexual disorders and menopausal symptoms, whether as a consequence of treatment-induced menopause or side effects of treatment. For such reasons, a panel of experts from the Spanish Menopause Society has met to develop usage recommendations for the relief of vasomotor symptoms and for sexual and reproductive health in patients with breast cancer based on the best evidence available.

To evaluate the effects of triptoreline, gestrinone, and both, on experimental endometriosis in rats.Experimental endometriosis was surgically induced in 225 Wistar rats. Of these, 202 rats showed at least one grown implant, 22 of which composed the control group, while 180 were treated with triptoreline, gestrinone, or both, for 28 days. The implants were evaluated again after 25 days.There were no changes in size in the control group. About 73% of the implants treated with triptoreline showed a high reduction (50%), vs. 51% with gestrinone (P0.0005) and 65% with both (P0.005). Triptoreline caused macroscopic resolution in 40% of the implants vs. 31% for gestrinone (not significant) and 26% for both substances (P0.05). In the triptoreline group, the mean size of the implants decreased by 65% between the 25th and 28th days, 58% between the 29th and the 35th, and 39% after the 36th day. This reduction was 51%, 36%, and 33%, respectively, in gestrinone group.Triptoreline was more effective than gestrinone, but perhaps not in the long run. Their association did not improve the results.

Objectives To report a simple and safe procedure of abdominal myomectomy and our results performing this technique. Design The operative technique comprises the incision on the most prominent part of the myoma, the use of a hooked clamp to hold the tumor, and a surgical knife to peel it, without removing the apparent excess of myometrium or serosa. Setting University Medical Centers and private practice. Patients Eighty patients, 9 of whom were operated between 10 and 26weeks of pregnancy, 3 during cesarean section, and 22 others who had infertility. Results Myomectomy was performed successfully in all patients for whom it was scheduled. Eight of nine pregnant patients had successful deliveries at term. The cumulative 10-year reoccurrence and reoperation rates by life-table analysis were 38% and 18%, respectively. The cumulative conception rates were 100% for otherwise unexplained infertility at 2years, and 63% and 79% at 5years for all infertile and all patients attempting conception after myomectomy, respectively. An age>30years, infertility>3years, and multiple fibroids negatively affected these rates, whereas the use of an absorbable adhesion barrier (Interceed; Johnson & Johnson AB, Somerville, NJ) had a positive effect. Conclusions This procedure is an appropriate alternative for most women who want to preserve or enhance fertility potential, and, if necessary, for pregnant women.

To date, more than 150 candidate genes related to osteoporosis have been described, but osteoporosis has increasingly been considered a polygenic disease modulated by environmental factors. It is thought that osteoporosis predisposition, pathology, and treatment response depend on the interaction between different genes or between genes and environmental factors.The aim of this study was to evaluate the relationship between the presence of single nucleotide polymorphisms (SNPs) in the estrogen metabolic pathway and the development of osteoporosis and to determine whether this relationship is monogenic or whether interactions between genes exist.A multicentric study with 1980 postmenopausal Spanish women in five Spanish communities was conducted. The women completed a specific questionnaire that inquired about risk factors for osteoporosis. Data on participants' bone mineral density were obtained with dual-energy X-ray densitometers, and genetic data were obtained from frozen peripheral blood.The digenic protection combinations indicated involvement of the wild-type genotype (WT) of the 3'UTR marker for the CYP19A1 gene, the IVS4 marker of the same gene, and the BMP15 and FSHR genes. Among patients who carried two or more of the genotypes considered 'risky', the triple combination among markers of the ESR2 and NRIP1 genes with any of the two mutations of the analyzed markers of the BMP15 gene gave a mean T-score value of -2.32±0.91 (p = 0.02).Variants of the new candidate genes (NRIP and BMP15) can predispose patients to osteoporosis.

Aim. The purpose of this study is to confirm in our population the decreasing secular trend in the age of menarche (AAM) observed in other European countries. Another aim is to investigate the association between early menarche and breast cancer, metabolic disorders risk or early menopause. Materials and Methods We conducted a nationwide population-based study of 1980 Caucasoid Spanish postmenopausal women from 2003 to 2006 to investigate the AAM, the duration of the fertile period and the relation of early menarche with breast cancer and some metabolic disorders. Results Regression analysis of AAM demonstrates a trend towards the younger AAM in our population during the past decades ( P > 0.001). Parallel to this decrease we observe a significant increase in the fertility period and the height of our population ( P < 0.001). In the women with AAM less than 11 years, there is an increased risk of hypercholesterolaemia, being overweight and obesity. However, early menarche does not raise the risk of adult onset diabetes, hypertension or breast cancer. Conclusions These data indicate a decreasing secular trend of AAM in a Spanish population in the last decades. Furthermore, hypercholesterolaemia and obesity, but not breast cancer, appears to be influenced by younger AAM. Only women who have their menarche at the age of nine years or less are more likely to have an earlier menopause.

Objective Age at natural menopause (ANM) can be considered a complex parameter that depends on the interaction of multiple factors. In the present study, the role of interaction between genetic variants within estrogen synthesis and signalling pathways in the ANM in Spanish women is studied. Material and methods Nine single nucleotide polymorphisms (SNPs) located at different candidate genes related to the estrogen signalling pathway were analysed in 1980 Spanish postmenopausal women. Results Independently, none of the nine markers were significantly associated with early ANM. Only heterozygosis at the NRIP rs2229741 locus could be associated with early menopause; however, this marker does not maintain statistical significance. In contrast, linear regression analysis suggests several epistatic interactions including these markers in relation to ANM, especially between ESR2, NRIP1 and BMP15. The genetic variant that appears most in these interactions is that of the BMP15 rs3897937. It was observed that AA-TC combined genotype for NRIP-BMP15 (rs3897937), respectively, appears to be associated with a lower ANM than other possible combinations of these SNP (46.1±5.9 versus 50.4±3.3; P = 0.002). In the multilocus analysis, the multigenic interaction formed by ESR2 (AA), BMP15 rs3897937 (TC) and NRIP1 (AA) has the lower ANM (45.37±6.8 versus 48.69±5; P = 0.038). Conclusions The results suggest that epistatic interactions of estrogen-related alleles may contribute to variance in ANM in Spanish women. Moreover, BMP15 and NRIP1 also appear as attractive candidate genes for premature menopause but require further investigation to confirm them.

ObjectiveThe aim of this study was to evaluate the knowledge, attitudes and expectations of patients receiving treatment for postmenopausal osteoporosis, analysing the factors related to good compliance with treatment.MethodsA national, epidemiological, cross-sectional study collected information on personal medical history, family history, bone densitometry, and treatment and compliance of patients over 45 years who were receiving treatment for osteoporosis and provided their informed consent. The patients anonymously completed a questionnaire about their knowledge of osteoporosis and the Morisky and Green treatment compliance evaluation test.ResultsThree hundred and fifteen specialists in gynaecology participated, recruiting 1179 patients with postmenopausal osteoporosis. The mean age was 59.9 years (standard deviation [SD] = 7.5). Only 22.6% of the patients showed an acceptable knowledge of osteoporosis (the criterion established was correct response to 80% of the questions). Treatment compliance was evaluated using a combination of Morisky–Green and Haynes–Sackett criteria. Of the patients 39.2% were classified as compliant, 74.6% of the patients were very or quite concerned about their condition and 53.3%; described their health status as excellent or good. However, 63.6% of the patients indicated that they needed more information about osteoporosis. The factors related to good compliance were the existence of one or no concomitant disease (odds ratio [OR] = 1.38, P = 0.025) and the type of knowledge about their disease (acceptable knowledge: OR = 1.33, P = 0.043).ConclusionsCorrect knowledge about osteoporosis would increase the possibility of appropriate compliance with the prescribed treatment, thus reducing the risk of osteoporotic fractures.

Medical attention during perimenopause requires different therapeutic strategies.To define strategies for the attention of perimenopause women that can favor a healthy aging.Review of influencing factors and lifestyle modifications that can be introduced in perimenopause to prevent pathologies.Diet composition and weight control influence cardiovascular and bone risks. It is difficult to get permanent changes in diet habits and there is a lack of conclusive evidence over the results of these recommendations, however there begin to arise better works that shows cardiovascular and osseous benefits of physical activity and specific exercise schedules. Due to them higher risk, it is necessary to suppress toxic habits. Several studies suggest phytotherapeutic supplements consumption benefit, however there is a lack of well-designed clinical essays to justify them recommendation.Correct nutritional state, appropriate diet, weight control, a common exercise practice, and suppression of toxic habits are applicable measures during perimenopause transition that could influence woman's health level for them lifespan. Individualized identification of diseases risk can justify the recommendations.

Objective To investigate whether body mass index (BMI), abdominal obesity, and fat distribution in postmenopausal women influence quality of life. Design Cross-sectional survey. Setting Outpatient clinics in the hospital setting and private practices. Patient(s) 274 postmenopausal Spanish women, distributed by body phenotype, fat distribution (android or gynoid), and BMI. Intervention(s) The Cervantes scale, a specific health-related quality of life (HRQOL) questionnaire. Main Outcome Measure(s) The quality of life of the obese and overweight patients was compared by age, sex, education, marriage, and municipality with matched healthy normal-weight controls. Result(s) Women of the pyknoid phenotype have worse general HRQOL, menopausal symptoms, and psychological and sexuality scores than athletic or lean women. Android fat distribution is also related to low global Cervantes scale scores. All scores on the Cervantes scale worsened with increasing BMI (≥25). Conclusion(s) Pyknoid phenotype, android fat distribution, and a higher BMI are related to poor HRQOL.

Objective This study was designed to examine the burnout syndrome among residents in obstetrics and gynaecology in Spain, and to analyse the predisposing factors for this condition. Setting Eight Spanish University hospitals. Sample A total of 162 residents representative of all active residents in obstetrics and gynaecology in Spain with regards to age, sex and year of residency were asked to take part in this survey. Methods The Maslach Burnout Inventory was mailed to each resident of eight Spanish hospitals representative of all active residents in obstetrics and gynaecology in Spain with regards to age, sex and year of residency. Burnout was defined as a high score on the emotional exhaustion or depersonalisation subscores, according to validated standard cutoff values. The demographic and predisposing work factors were noted for each participant using a self-reported questionnaire. A binary logistic regression model was constructed from all predisposing factors as covariates for the prediction of the burnout syndrome. Results Sixty-seven percent of the 162 eligible residents returned their questionnaires within a 3-month period. Of those, 58% fulfilled the criteria for the burnout syndrome. In the multivariate analysis, marital status and workload in office practice were found to be significant predisposing factors. Single marital status increased the odds ratio for burnout by 5.2 (95% CI 1.3–21). For every extra ten patients attended in the office per week, the odds ratio for burnout increased by 1.25 (95% CI 1.0–1.5). A stratified multivariate subanalysis showed that this risk remained significant only in the group of residents without staff supervision with an odds ratio of 2.1 (95% CI 1.3–2.9). Conclusion The prevalence of the burnout syndrome during obstetrics and gynaecology residency is high. Single marital status and workload in office practice without staff supervision are significant predisposing factors.

To evaluate the effect of interleukin-2 (IL-2) on an experimental model of endometriosis.Double blind and randomized experimental prospective placebo-controlled study. Experimental endometriosis was induced in 66 three-month-old female Wistar rats, by auto-transplanting fragments of endometrium to the peritoneum. After four weeks, the size of each implant was measured in millimeters by laparotomy (L2), and animals were randomly distributed for intraperitoneal administration of human-IL-2, rat-IL-2 or placebo. Four weeks later, the implants were measured (L3) and a second dose was given. After four weeks, endometriosis size was evaluated again (L4).We found a reduction of experimental endometriosis at L3 that was only significant in IL-2 treated groups: 20.1% and 30.3% with human-IL-2 and rat-IL-2, respectively (p0.001 with respect to L2 size), versus a non-significant reduction of 9.0% found in placebo group, but the differences were not statistically significant between groups. The decrease after a second dose (L4) was: 49.8%, 41.8% and 11.4% with human-IL-2, rat-IL-2 and placebo, respectively (p0.001 in IL-2 groups versus L2 and L3, and p0.05 in both groups versus placebo at L4).Intraperitoneal administration of IL-2 reduces experimental endometriosis, and this effect is similar using rat-IL-2 or human IL-2 (non specie-specific effect).

Bilateral ovarian enlargement can be found in the course of a cesarean section. It is necessary to keep in mind that hyperreactio luteinalis is a benign condition, because the appropriate management is conservative. We present an unexpected, intraoperatively diagnosed case of bilateral ovarian cystic-solid tumours (13 cm) in a twin pregnancy.