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

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

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

Terapia Estrogénica y Prevención Cardiovascular Primaria / Estrogen Therapy and Primary Cardiovascular Prevention

Antecedentes La terapia hormonal de la menopausia (THM) corresponde a la administración de hormonas exógenas para el tratamiento de síntomas asociados a climaterio y menopausia. Objetivo Analizar los estudios que dicen relación a THM y riesgo cardiovascular (CV) para entender el concepto de ventana de oportunidad cardiovascular, además analizar la fisiología de los estrógenos en el aparato CV es fundamental para una adecuada comprensión de su rol protector. Método revisión de la literatura disponible en PubMed durante octubre de 2018, utilizando los términos "menopausal hormone therapy'' y ''cardiovascular disease'.Además se revisó base de datos Scielo con los términos "terapia hormonal'', ''menopausia'' y ''cardiovascular''; se escogieron artículos entre 2000 y 2018 con los términos utilizados en el título o resumen. También se realizó búsqueda dirigida de estudios relevantes, guías clínicas, un metanálisis, una revisión sistemática relacionada y las últimas publicaciones de sociedades científicas dela especialidad. Resultados Desde los inicios de la THM se observó en distintos estudios observacionales un papel en la protección CV. Los últimos años se ha ido demostrando a través de diversos estudios aleatorizados, a raíz de las dudas que dejó el WHI de 2002, los beneficios de esta. Conclusión La THM mejora la calidad de vida de las mujeres en climaterio y menopausia. Los estrógenos tienen mejor beneficio sobre enfermedad CV al administrar terapia precozmente luego de la menopausia (ventana de oportunidad) y mantenerla durante un tiempo prolongado de acuerdo a estudios observacionales y aleatorizados. Dado el aumento de la esperanza de vida de la mujer y múltiples FR CV, es que el manejo clínico de la postmenopausia es un relevante problema de salud pública.

SUMMARY Background Menopausal hormone therapy (MHT) is the exogenous administration for climacteric and menopausal treatment. Objective To analyze studies in relation to THM and cardiovascular (CV) risk, to understand the ''cardiovascular window of opportunity'' concept, also, to analyze the physiology of estrogens into cardiovascular system is fundamental for a suitable comprehension of its protective role. Method Review of literature available on PubMed during October 2018, using the terms "menopausal hormone therapy" and "cardiovascular disease." In addition, Scielo database with the terms ''hormone therapy'', ''menopause'' and '' cardiovascular'' was reviewed; Articles were chosen between 2000 and 2018 with the terms used in the title or summary. A directed search of relevant studies, clinical guides, one meta-analysis, one related systematic review and the latest publications of scientific societies of the specialty was also conducted. Results Since beginning of MHT, a role in CV protection has been observed in different observational studies. Recent years have been demonstrated through various randomized studies, following the doubts left by the WHI of 2002, the benefits of MHT. Conclusion MHT improves the quality of life of women in climacteric and menopausal. Estrogen have better benefit on CV disease, by administering early therapy after menopausal and maintaining it for a long time. Given the women increase in life expectancy and multiple CV risk factors, clinical management of postmenopausal is a relevant public health problem.

Risks and benefits of menopausal hormone therapy

Menopausal hormone therapy (MHT) was widely used to improve quality of life by controlling menopausal symptoms, including vasomotor symptoms and urogenital atrophy. Furthermore, observational studies consistently reported beneficial effects of MHT on late problems of menopause, such as osteoporosis, coronary heart disease (CHD), and possibly dementia. However, circumstances changed abruptly after the 2002 publication of the first findings from the Women's Health Initiative (WHI) study, which was conducted in postmenopausal women (average age, 63 years) using conventional doses of conjugated equine estrogen (CEE) and medroxyprogesterone acetate. CEE with medroxyprogesterone acetate increased the risk of breast cancer and did not prevent CHD. However, CEE alone showed a tendency to decrease the risk of both breast cancer and CHD, with significant differences between the two therapies. A subgroup analysis by age and years since menopause led to a timing hypothesis regarding the effects of MHT on CHD. Indeed, CEE alone in women aged 50 to 59 significantly reduced CHD risk by 35% after 13 years of follow-up. In 2015, a Cochrane meta-analysis of MHT trials reported a 48% reduction in CHD, no change in stroke, and most importantly, a 30% decrease in total mortality in women with less than 10 years since menopause. Long-term follow-up of WHI participants confirmed beneficial impacts of CEE on breast cancer incidence and mortality. Further, fracture reduction in women with osteopenia was observed during the intervention phase of the WHI study. If initiated early after menopause, MHT could again be considered to improve menopause-related quality of life and decrease all-cause mortality.

Menopausal hormone therapy on breast lesions in perimenopausal women / 预防医学

Objective@#To explore the correlation between menopausal hormone therapy（MHT）and breast lesions in perimenopausal women,and to provide evidence for safe use of MHT. @*Methods@#The 40-60 year-old women who visited Hangzhou Women's Hospital and met the diagnostic criteria for perimenopausal syndrome were recruited. The intervention group received MHT and was divided into three subgroups according to the MHT regimen：estrogen-progesterone cycle therapy（A）,estrogen-progesterone continuous therapy（B）,estrogen therapy（C）. The control group did not receive MHT. All the patients received regular mammography to quantify and evaluate breast lesions. The generalized estimating equation was used to analyze the changes of breast lesions between different groups.@*Results@#There were 80 cases in the intervention group,with 49 in group A,26 in group B,5 in group C,and 80 cases in the control group. After two years of follow-up,there was no statistically significant differences of time,group and interaction in breast density,volume of breast fibrous tissue and the volume of breast between three intervention groups and the control group（P>0.05）; there was no statistically significant differences of group and interaction in positive rate of calcification and breast mass between the intervention group and the control group（P>0.05）. @*Conclusion@#Receiving MHT intervention for two years did not increase the risk of breast lesions.

Investigation of awareness of menopausal hormone therapy among medical staff in Zhujiang Hospital of Southern Medical University / 解放军医学杂志

Objective To investigate the awareness and attitude towards menopause and menopausal hormone therapy (MHT) among the medical staff of Zhujiang Hospital of Southern Medical University.Methods A self-designed questionnaire related to menopause and MHT was conducted among 1143 medical staffs in Zhujiang Hospital of Southern Medical University.Results The best-known symptoms,in sequences,were dysphoria and depression (90.6％),sleep disorders (81.5％),hot flashes and night sweating (69.4％),dizziness and palpitation (59.3％),and paresthesia (50.3％).Of 1143 respondents,42.1％(481) knew about MHT,and 62％(709) considered that MHT is necessary for symptomatic menopausal women.Significant differences existed in attitudes towards MHT between different titles and departments (P=0.027,P=0.000).Fifty-seven percent (651) of medical staff expressed concern about the side effects of MHT and had scruples about its use,73.1％(836) believed that MHT can improve menopausal symptoms,while 54.5％(623) believed MHT can prevent and treat osteoporosis.Conclusions The awareness rate on menopause and MHT is relatively low among the medical personnel of Zhujiang Hospital of Southern Medical University.There exist differences in attitudes towards menopause and MHT among different departments,doctors and nurses,and different titles.

Update on the diagnosis and treatment of menopause syndrome / 中国基层医药

With the advance of medicine and the extension of life expectancy,the proportion of elderly people is increasing around the world,so is the postmenopausal women in the world~ population.More and more women will be bothered by various perimenopausal problems.Vasomotor symptoms(VMS) and the genitourinary syndrome of menopause(GSM) are recognized as the most frequent symptoms associated with menopause.Menopausal hormone therapy (MHT) is the most effective intervention for management of these symptoms.However,the role of MHT in the prevention of cardiovascular disease,skeleton,urogenital systems remains controversial.New drugs such as selective estrogen receptor modulators are equivalent to MHT on the relief of VMS.In addition,it can also prevent bone loss,becoming a new research highlights.Nonhormonal management is an important consideration when hormone therapy is not an option because of medical contraindications or a woman's personal choice,like lifestyle changes,selective serotonin reuptake inhibitors,serotonin-norepinephrine reuptake inhibitors,vaginal laser and etc.

A survey and analysis on symptoms of menopausal women: 583 cases / 中华内分泌外科杂志

Objective To investigate the main symptoms and the health care consciousness of the menopausal women.Methods From Jul.2013 to Oct.2014,a one-on-one,face-to-face questionnaire was conducted in selected menopausal women in Gynecology Clinic of the Second Affiliated Hospital of Chongqing Medical University.Results There were 583 valid questionnaires overall.349 women had natural menopause,and the average age was(48.7±3.4) years.66.72％ women appeared menstrual disorders in premenopausal stage,presenting longer cycle and fewer menstrual quantity.82.50％ (481/583) women had menopausal symptoms,with hot flashes (57.46％,335/583) as the most,followed by insomnia (50.60％,295/583).Kupperman score showed 7.03％ (41/583)patients were the severe degree.Among the patients with menopausal symptoms,234 cases went to menopause clinics on their own initiative and 36 cases visited other department first and then transferred to menopause clinics.Among patients with college or above degree,51.27％ (101/197)received menopausal hormone therapy (MHT),significantly higher than those with poor educational background.Conclusion Vasomotor symptoms such as hot flashes were still the main symptoms of menopausal syndrome.Although some menopausal patients had intentions to seek medical care by themselves,there sre still some patients lacking health care consciousness,which is more commonly seen in patients with lower level of education.Menopausal education promotion is needed.

Impact of Oral Levonorgestrel for 1 Year on Mammographic Density in Menopausal Hormone Therapy / 대한폐경학회지

OBJECTIVES: We evaluated changes in mammographic density (MMGD) after hormone therapy (HT) using levonorgestrel (LNG) in Korean postmenopausal women. METHODS: In this retrospective study, 58 healthy postmenopausal women with no history of prior HT were included. Twenty-three women were given a cyclic regimen of estradiol valerate (E) 2 mg/day + LNG 0.075 mg/day and 25 untreated women served as a negative control and 10 women treated with continuous combined regimen of conjugated equine estrogen (CEE) 0.625 mg/day + medroxyprogesterone acetate (MPA) 2.5 mg/day as a positive control. Mammography was obtained at baseline and 1 year later, and MMGD was assessed. In addition, the change in the proportion of the dense area after HT was assessed using the J-image program. Data were analyzed with analysis of variance and chi-square or Fisher's exact test. RESULTS: There were no significant differences in baseline characteristics among three groups. After 1 year of HT, increase of BI-RADS grade in CEE + MPA group (7/9, 77.8%) was higher than in E + LNG group (2/16, 12.5%; P = 0.001). But there was no difference between untreated group (1/19, 5.3%) and E + LNG group (2/16, 12.5%; P = 0.446). In subgroup analysis of women with BI-RADS grade 3 at baseline, no significant difference. Changes in the proportion of dense areas assessed by the J-image program showed similar results. Regression analysis revealed that there was no correlation between baseline dense area and changes after HT in E + LNG group. CONCLUSION: HT using LNG did not influence MMGD in Korean postmenopausal women. Further study on breast cancer risk may be needed.

Impact of Oral Levonorgestrel for 1 Year on Mammographic Density in Menopausal Hormone Therapy / 대한폐경학회지

OBJECTIVES: We evaluated changes in mammographic density (MMGD) after hormone therapy (HT) using levonorgestrel (LNG) in Korean postmenopausal women. METHODS: In this retrospective study, 58 healthy postmenopausal women with no history of prior HT were included. Twenty-three women were given a cyclic regimen of estradiol valerate (E) 2 mg/day + LNG 0.075 mg/day and 25 untreated women served as a negative control and 10 women treated with continuous combined regimen of conjugated equine estrogen (CEE) 0.625 mg/day + medroxyprogesterone acetate (MPA) 2.5 mg/day as a positive control. Mammography was obtained at baseline and 1 year later, and MMGD was assessed. In addition, the change in the proportion of the dense area after HT was assessed using the J-image program. Data were analyzed with analysis of variance and chi-square or Fisher's exact test. RESULTS: There were no significant differences in baseline characteristics among three groups. After 1 year of HT, increase of BI-RADS grade in CEE + MPA group (7/9, 77.8%) was higher than in E + LNG group (2/16, 12.5%; P = 0.001). But there was no difference between untreated group (1/19, 5.3%) and E + LNG group (2/16, 12.5%; P = 0.446). In subgroup analysis of women with BI-RADS grade 3 at baseline, no significant difference. Changes in the proportion of dense areas assessed by the J-image program showed similar results. Regression analysis revealed that there was no correlation between baseline dense area and changes after HT in E + LNG group. CONCLUSION: HT using LNG did not influence MMGD in Korean postmenopausal women. Further study on breast cancer risk may be needed.