Sequential management of postmenopausal health and osteoporosis: An update.

Increased life expectancy means that women are now in a hypoestrogenic state for approximately one-third of their lives. Overall health and specifically bone health during this period evolves in accordance with aging and successive exposure to various risk factors. In this review, we provide a summary of the approaches to the sequential management of osteoporosis within an integrative model of care to offer physicians a useful tool to facilitate therapeutic decision-making. Current evidence suggests that pharmacologic agents should be selected based on the risk of fractures, which does not always correlate with age. Due to their effect on bone turnover and on other hormone-regulated phenomena, such as hot flushes or breast cancer risk, we position hormone therapy and selective estrogen receptor modulators as an early postmenopause intervention for the management of postmenopausal osteoporosis. When the use of these agents is not possible, compelling evidence supports antiresorptive agents as first-line treatment of postmenopausal osteoporosis in many clinical scenarios, with digestive conditions, kidney function, readiness for compliance, or patient preferences playing a role in choosing between bisphosphonates or denosumab during this period. For patients at high risk of osteoporotic fracture, the "anabolic first" approach reduces that risk. The effect on bone health with these bone-forming agents or with denosumab should be consolidated with the subsequent use of antiresorptive agents. Regardless of the strategy, follow-up and treatment should be maintained indefinitely to help prevent fractures.

Clinical perspectives on the menstrual pictogram for the assessment of heavy menstrual bleeding.

Heavy menstrual bleeding (HMB) has an estimated prevalence of 18-32% but is known to be under-reported due to poor recognition and estimation of menstrual blood loss (MBL). HMB can negatively impact quality of life, affecting social interactions, work productivity and sexual life. Abnormal menstrual bleeding may have an underlying structural or systemic cause, such as endometrial and myometrial disorders; however, for some, there is no identified pathological cause. Several methods are available for assessing MBL, including the alkaline hematin (AH) method and the menstrual pictogram (MP). The AH method is considered to be the most accurate way to monitor MBL; however, it is associated with inconvenience and expense, therefore limiting its value outside of research. The MP requires the user to select an icon from a chart that reflects the appearance of a used sanitary product; the icon is associated with a blood volume that can be used to determine MBL. Validation studies have demonstrated that the results of the MP and AH method are well correlated, showing that the MP can measure MBL with sufficient accuracy. Additionally, the MP is more convenient for users, less expensive than the AH method, may be used in regions where the AH method is unavailable and may also be used as part of a digital application. Overall, the MP offers a convenient approach to monitor MBL both in research and clinical practice settings.

Adherence to SEGO recommendations on heavy menstrual bleeding (SMA-UR Study) / Seguimiento de las recomendaciones SEGO sobre el Sangrado Menstrual Abundante (Estudio SMA-UR)

Objective: Heavy menstrual bleeding is one of the most common frequent gynecological disorders in women of reproductive age. It affects quality of life, and in Western countries, is one of the most frequent causes of anemia. The aim of this study was to analyze adherence to the current recommendations of the Spanish Society of Gynecology and Obstetrics on the diagnosis and treatment of heavy menstrual bleeding in patients attending the emergency department. Material and methods: Observational, retrospective, and prospective study performed in routine clinical practice. The study population comprised 98 women diagnosed with heavy menstrual bleeding in the absence of any organic cause attending a gynecological visit scheduled after an emergency department visit due to abnormal menstrual bleeding. Results: Adherence to the Spanish Society of Gynecology and Obstetrics heavy menstrual bleeding recommendations was good for most factors, such as the usual/current bleeding characteristics (80.5% and 86.6%, respectively), gynecological and family history (92.7%), physical examination (92.7%), and diagnostic tests (92.7%), although less favorable for laboratory tests (58.5%) and initiation of treatment and regimen (39.0%). Conclusions: Most of the recommendations in the guidelines were applied, except for laboratory tests, initiation of treatment, and treatment regimen, which were followed to a lesser extent

Objetivo: el sangrado menstrual abundante es una de las alteraciones ginecológicas más frecuentes en las mujeres en edad reproductiva. Afecta a la calidad de vida y es, en los países occidentales, una de las causas más frecuentes de anemia. El objetivo del presente estudio es analizar el seguimiento de las recomendaciones vigentes de la Sociedad Española de Ginecología y Obstetricia en el manejo diagnóstico y terapéutico del sangrado menstrual abundante en pacientes que acuden a urgencias. Material y metodos: estudio observacional, de seguimiento retrospectivo y prospectivo según práctica clínica habitual. Se incluyeron un total de 98 mujeres diagnosticadas de sangrado menstrual abundante sin causa orgánica visitadas en una consulta ginecológica tras haber acudido a urgencias por alteraciones del sangrado. Resultados: se siguieron las recomendaciones de la Sociedad Española de Ginecología y Obstetricia en el manejo del sangrado menstrual abundante de forma mayoritaria para las evaluaciones de las características del sangrado habitual/actual (80,5% y 86,6%, respectivamente), valoración de antecedentes ginecológicos y familiares (92,7%), exploración física (92,7%) y pruebas diagnósticas (92,7%), mientras que se realizó en menor medida en lo relativo a la evaluación de pruebas de laboratorio (58,5%) e instauración de tratamiento y pauta (39,0%) de acuerdo a las guías. Conclusiones: se siguieron las recomendaciones para la mayoría de las evaluaciones, excepto en lo relativo a las pruebas de laboratorio e instauración de tratamiento y pauta de seguimiento de acuerdo a las guías, que se realizaron en menor medida

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)

Revisión: Actualización en el diagnóstico del sangrado menstrual abundante / Review: An update on the diagnosis of heavy menstrual bleeding

El sangrado menstrual abundante (SMA) se define como la pérdida excesiva de sangre menstrual que interfiere con una actividad física normal, emocional o social, empeorando la calidad de vida de la mujer. Factores como un bajo nivel socioeconómico, la obesidad y la alta paridad estarían asociados a una prevalencia superior de SMA. El diagnóstico del SMA se basa en la información proporcionada por la propia paciente acerca de los cambios experimentados en su sangrado, y se fundamenta en la realización de una correcta historia clínica y una exploración física y ginecológica destinada a identificar la fuente del sangrado y que incluya palpación abdominal, una visualización cervical con espéculo y una exploración pélvica con tacto bimanual. Estas técnicas se complementarían con otras como las pruebas de laboratorio, las técnicas de imagen y los análisis histológicos. Las causas posibles de SMA varían en función de la edad de la paciente. Descartada una causa orgánica, suele ser debido a alteraciones de la integridad fisiológica del eje hipófiso-gonadal que ocasionan anovulación. Siguiendo la clasificación PALMA-ÍNDICE, el diagnóstico diferencial del SMA se establecerá teniendo en cuenta en primer lugar las alteraciones estructurales (PALMA: pólipo, adenomiosis, leiomioma y malignidad) y posteriormente las no estructurales (INDICE: las causas inespecíficas, la disovulación, la iatrogenia, los trastornos de la coagulación y la inestabilidad endometrial)

Heavy menstrual bleeding (HMB) is a disorder with a major impact on the woman which is associated with a worsening of their quality of life. The objectives pursued with its treatment are correction of anemia, decrease of the amount of bleeding, prevention of recurrence and long-term consequences of anovulation, and improving the quality of life of women. The choice of treatment should be based on the decision of the woman after knowing the benefits and adverse effects of different options, taking into account their reproductive desires and personal preferences. Drug therapy should be considered when structural abnormalities have not been identified as the cause of HMB. Non-hormonal drug treatment is the first choice in patients with HMB with ovulatory cycles, with reproductive desires or limitations to hormone treatment; It includes non-steroidal anti-inflammatories and antifibrinolytics (especially tranexamic acid). The hormonal drug treatment is the best option in HMB caused by ovulation disorders. In Spain, the LNG-IUD has this specific indication, of first choice in women who may become pregnant, and an oral quadriphasic combined with estradiol valerate and dienogest (VE2-DNG). The HMB with organic cause require the surgical approach of the pathological processes that cause them. The treatment options that have proven efficacy are endometrial ablation and endometrial resection (minimally invasive but not always completely successful) and hysterectomy (major surgery). In this paper, we analyze all of them

Revisión: Actualización en el tratamiento del sangrado menstrual abundante / Review: An update on the treatment of heavy menstrual bleeding

El sangrado menstrual abundante (SMA) es un trastorno con un gran impacto en la mujer que conlleva un empeoramiento de su calidad de vida. Los objetivos que persigue su tratamiento incluyen la corrección de la anemia, la disminución de la cantidad de sangrado, la prevención de recurrencias y de las consecuencias a largo plazo de la anovulación, y la mejora de la calidad de vida de la mujer. La elección del tratamiento debe basarse en la decisión de la mujer tras conocer las ventajas y efectos adversos de las diferentes opciones, teniendo en cuenta sus deseos reproductivos y preferencias personales. El tratamiento farmacológico debe considerarse cuando no se hayan identificado anomalías estructurales como causa del SMA. El tratamiento farmacológico no hormonal, es de primera elección en pacientes con SMA con ciclos ovulatorios, con deseos genésicos o con limitaciones al tratamiento hormonal; incluye los aintiinflamatorios no esteroideos y los antibibrinolíticos (especialmente ácido tranexámico). El tratamiento farmacológico hormonal es la opción más adecuada ante alteraciones de la ovulación que causan SMA. En España tienen indicación específica el DIU-LNG, de primera elección en mujeres que no planean un embarazo, y un combinado cuatrifásico con valerato de estradiol y dienogest (VE2-DNG) oral. Los SMA de causa orgánica requieren el abordaje quirúrgico de los procesos patológicos que los provocan. Las opciones terapéuticas que han demostrado eficacia son la ablación endometrial y la resección endometrial (mínimamente invasivas pero no siempre completamente exitosas) y la histerectomía (cirugía mayor). En la presente revisión se analizan todas ellas

Heavy menstrual bleeding (HMB) is a disorder with a major impact on the woman which is associated with a worsening of their quality of life. The objectives pursued with its treatment are correction of anemia, decrease of the amount of bleeding, prevention of recurrence and long-term consequences of anovulation, and improving the quality of life of women. The choice of treatment should be based on the decision of the woman after knowing the benefits and adverse effects of different options, taking into account their reproductive desires and personal preferences. Drug therapy should be considered when structural abnormalities have not been identified as the cause of HMB. Non-hormonal drug treatment is the first choice in patients with HMB with ovulatory cycles, with reproductive desires or limitations to hormone treatment; It includes non-steroidal anti-inflammatories and antifibrinolytics (especially tranexamic acid). The hormonal drug treatment is the best option in HMB caused by ovulation disorders. In Spain, the LNG-IUD has this specific indication, of first choice in women who may become pregnant, and an oral quadriphasic combined with estradiol valerate and dienogest (VE2-DNG). The HMB with organic cause require the surgical approach of the pathological processes that cause them. The treatment options that have proven efficacy are endometrial ablation and endometrial resection (minimally invasive but not always completely successful) and hysterectomy (major surgery). In this paper, we analyze all of them

Medical management of heavy menstrual bleeding: a comprehensive review of the literature.

IMPORTANCE: Heavy menstrual bleeding (HMB) is a common complaint among reproductive-aged women, which negatively affects their health as well as their social, professional, and family lives. Modern medical management usually provides effective control of HMB irrespective of the underlying cause. Surgical interventions should be reserved for women with significant pelvic pathology and those unresponsive to medical therapy. OBJECTIVE: The aim of this review was to provide a comprehensive summary of the efficacy and safety of available medical treatments of HMB. EVIDENCE ACQUISITION: A comprehensive MEDLINE and EMBASE literature search was undertaken using selected terms associated with HMB to identify clinical studies published before March 20, 2013, that reported changes in menstrual blood loss in women receiving medical intervention. RESULTS: The effectiveness of treatments to reduce HMB due to endometrial dysfunction in descending order was as follows: (1) the levonorgestrel-releasing intrauterine system (LNG-IUS) (initial release rate of 20 µg of LNG per 24 hours), (2) combined hormonal contraceptives (oral or transvaginal), (3) tranexamic acid, and (4) long-course oral progestogens (≥3 weeks per cycle). The LNG-IUS was found to reduce HMB due to some structural causes (leiomyomas and adenomyosis). The reduction in menstrual blood loss achieved with nonsteroidal anti-inflammatory drugs and short-course oral progestogens (≤14 days per cycle) is less impressive but may be sufficient for women who have marginally increased blood loss. CONCLUSIONS AND RELEVANCE: For women not seeking pregnancy, the LNG-IUS is the first-line medical therapy for HMB, with combined hormonal contraceptives as second choice. For other women, fewer effective options exist.

Protocolo Sociedad Española de Ginecología y Obstetricia de diagnóstico y tratamiento de las infecciones vulvovaginales. Protocolo actualizado en 2012 / The protocol of the Spanish Society of Obstetrics and Gynecology for the diagnosis and treatment of vulvovaginal infection. Update 2012

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Beneficios extraóseos de los moduladores selectivos del receptor estrogénico de tercera generación: efectos sobre la mama / Third generation selective estrogen receptor modulators benefits beyond bone: effects on breast

Los selective estrogen receptor modulators (SERM, «moduladores selectivos del receptor estrogénico») son sustancias con efecto estrogénico/antiestrogénico que actúan de forma distinta según el tejido y su composición. Desde el descubrimiento de que tamoxifeno y raloxifeno (RLX) presentaban un efecto preventivo del cáncer mamario, se ha emprendido la búsqueda del SERM ideal. Así, aparecieron ospemifeno, arzoxifeno, lasofoxifeno y bazedoxifeno (BZA) como SERM de tercera generación. De todos ellos, tan solo BZA ha alcanzado la etapa de utilización clínica. Se dispone de datos experimentales y clínicos sobre ca´ncer de mama tanto para RLX como para BZA. RLX disminuye significativamente la incidencia de cáncer de mama con receptores estrogénicos positivos en mujeres osteoporóticas posmenopaúsicas. BZA ha demostrado actuar como un antagonista de los estrógenos en estudios experimentales, pero no un efecto protector del cáncer de mama en sus estudios de referencia (301 y extensiones). Sin embargo, en estos estudios que comparan BZA frente a RLX y placebo, RLX tampoco ha demostrado la acción preventiva del cáncer de mama esperada. Es posible que la explicación resida en que estos datos reflejen un efecto estadístico motivado porque los estudios con BZA se han diseñado en una población con baja incidencia de carcinoma mamario (AU)

The selective estrogen receptor modulators (SERMs) are substances with estrogenic/anti-estrogen effect that act differently depending on the tissue and composition. Since the discovery that tamoxifen and raloxifene (RLX) had a breast cancer preventive effect, the search for the perfect SERM has been the goal. Thus, ospemifen, arzoxifene, lasofoxifene and bazedoxifene (BZA) appeared as third-generation SERMs. Among all them, only BZA reached the stage of clinical use. BZA has been shown to have an anti-estrogen effect in experimental studies, but not a protective effect on clinical breast cancer in pivotal clinical trials (301 and extensions). However, in these studies comparing BZA versus RLX and placebo, RLX has not shown the expected preventive effect on breast cancer. This lack of effect can be the consequence of the size and characteristics of BZA’s studies in a population with low incidence of breast cancer (AU)

Beneficio extraóseo de los moduladores selectivos del receptor estrogénico de tercera generación: II, acción en el endometrio / Third generation selective estrogen receptor modulators: benefits beyond bone. II, endometrial action

Los selective estrogen receptor modulators (SERM, «moduladores selectivos del receptor estrogénico») son moléculas que se vinculan a los receptores de estrógenos ejerciendo un efecto estrogénico o antiestrogénico, según su estructura y el tipo de tejido. Desde el descubrimiento del efecto preventivo en cáncer de mama del tamoxifeno y el raloxifeno (RLX), el SERM ideal sería el que indujera efectos estrogénicos a nivel óseo o en el sistema nervioso central y antiestrogénicos en la mama y el endometrio. Sin embargo, uno de los inconvenientes más importantes para la consolidación de tamoxifeno ha sido su relación con la aparición de cáncer de endometrio. Por ello, se inicia la búsqueda de una molécula con efectos neutros o protectores a este nivel. Así aparecieron ospemifeno, arzoxifeno, lasofoxifeno (LFX) y bazedoxifeno (BZA) como SERM de tercera generación. De todos ellos, tan solo BZA ha alcanzado la etapa de utilización clínica. Los datos experimentales y clínicos tanto para RLX como para los SERM de tercera generación de los que se dispone de información (BZA y LFX) muestran neutralidad o incluso antagonismo frente a los estrógenos a nivel endometrial. El BZA ha demostrado un comportamiento equivalente al vehículo en distintas condiciones experimentales y actúa como un antagonista de los estrógenos en diseños en los que se coadministran estradiol o estrógenos equinos conjugados (EEC). En los estudios de referencia a 7 años se detectaron diferencias significativas en la incidencia de adenocarcinoma de endometrio a favor de BZA comparado con placebo. En un ensayo clínico para valorar en mujeres posmenopaúsicas el efecto de la combinación de EEC y BZA sobre la sintomatología, se comprobó la capacidad de dosis de BZA de 20 mg o superiores para evitar la presentación de hiperplasia inducida por 0,625 o 0,450 de EEC (AU)

The selective estrogen receptor modulators (SERMs) are substances with estrogenic/anti-estrogen effect that act differently depending on the tissue and composition. Since the discovery that tamoxifen and raloxifene (RLX) had a breast cancer preventive effect, the search for the perfect SERM has been the goal. The evidence that tamoxifen significantly increased the risk of endometrial cancer as compared to placebo made this tissue the center of interest in developing new SERMs. Thus, ospemifen, arzoxifene, lasofoxifene (LFX) and bazedoxifene (BZA) appeared as third-generation SERMs but only BZA reached the stage of clinical use. Both experimental and clinical data available on the effects of RLX or thirdgeneration SERMs reaching clinical stage (LFX and BZA) show either neutrality or anti-estrogenic effects at endometrial level. BZA has shown to be equivalent to vehicle in several experimental conditions and acts as anti-estrogen in models were estrogens (conjugated equine estrogens [CEE] or E2) were co-administered. In a 7 years pivotal study the incidence of endometrial adenocarcinoma has been significantly lower in the BZA than in the placebo group. Moreover, in a clinical trial to evaluate the ability of a combination of BZA and CEE to prevent hot flushes in symptomatic postmenopausal women, doses of 20 mg or higher of BZA have significantly decreased the risk of presenting endometrial hyperplasia when co-administered with either 0.650 or 0.450 mg of CEE (AU)

[Third generation selective estrogen receptor modulators: benefits beyond bone. II, endometrial action]. / Beneficio extraóseo de los moduladores selectivos del receptor estrogénico de tercera generación: II, acción en el endometrio.

The selective estrogen receptor modulators (SERMs) are substances with estrogenic/anti-estrogen effect that act differently depending on the tissue and composition. Since the discovery that tamoxifen and raloxifene (RLX) had a breast cancer preventive effect, the search for the perfect SERM has been the goal. The evidence that tamoxifen significantly increased the risk of endometrial cancer as compared to placebo made this tissue the center of interest in developing new SERMs. Thus, ospemifen, arzoxifene, lasofoxifene (LFX) and bazedoxifene (BZA) appeared as third-generation SERMs but only BZA reached the stage of clinical use. Both experimental and clinical data available on the effects of RLX or third-generation SERMs reaching clinical stage (LFX and BZA) show either neutrality or anti-estrogenic effects at endometrial level. BZA has shown to be equivalent to vehicle in several experimental conditions and acts as anti-estrogen in models were estrogens (conjugated equine estrogens [CEE] or E2) were co-administered. In a 7 years pivotal study the incidence of endometrial adenocarcinoma has been significantly lower in the BZA than in the placebo group. Moreover, in a clinical trial to evaluate the ability of a combination of BZA and CEE to prevent hot flushes in symptomatic postmenopausal women, doses of 20mg or higher of BZA have significantly decreased the risk of presenting endometrial hyperplasia when co-administered with either 0.650 or 0.450mg of CEE.

[Third generation selective estrogen receptor modulators benefits beyond bone: effects on breast]. / Beneficios extraóseos de los moduladores selectivos del receptor estrogénico de tercera generación: efectos sobre la mama.

The selective estrogen receptor modulators (SERMs) are substances with estrogenic/anti-estrogen effect that act differently depending on the tissue and composition. Since the discovery that tamoxifen and raloxifene (RLX) had a breast cancer preventive effect, the search for the perfect SERM has been the goal. Thus, ospemifen, arzoxifene, lasofoxifene and bazedoxifene (BZA) appeared as third-generation SERMs. Among all them, only BZA reached the stage of clinical use. BZA has been shown to have an anti-estrogen effect in experimental studies, but not a protective effect on clinical breast cancer in pivotal clinical trials (301 and extensions). However, in these studies comparing BZA versus RLX and placebo, RLX has not shown the expected preventive effect on breast cancer. This lack of effect can be the consequence of the size and characteristics of BZA's studies in a population with low incidence of breast cancer.