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1.
Nutrients ; 12(12)2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33334009

RESUMO

Middle-aged and elderly women are affected by various symptoms and diseases induced by estrogen deficiency. Proanthocyanidins, widely present in many kinds of fruits and berries, have many beneficial effects, such as antioxidative, anti-inflammatory, and antimicrobial activities. We researched the effects of proanthocyanidins for middle-aged and elderly women, finding that it has been revealed in many clinical trials and cohort studies that proanthocyanidins contribute to the prevention of cardiovascular disease, hypertension, obesity, cancer, osteoporosis, and urinary tract infection, as well as the improvement of menopausal symptoms, renal function, and skin damage. Thus, proanthocyanidins can be considered one of the potent representatives of complementary alternative therapy.


Assuntos
Ingestão de Alimentos/fisiologia , Pós-Menopausa/efeitos dos fármacos , Proantocianidinas/farmacologia , Adulto , Idoso , Feminino , Análise de Alimentos , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Lancet Oncol ; 21(11): 1443-1454, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33152284

RESUMO

BACKGROUND: Preoperative and perioperative aromatase inhibitor (POAI) therapy has the potential to improve outcomes in women with operable oestrogen receptor-positive primary breast cancer. It has also been suggested that tumour Ki67 values after 2 weeks (Ki672W) of POAI predicts individual patient outcome better than baseline Ki67 (Ki67B). The POETIC trial aimed to test these two hypotheses. METHODS: POETIC was an open-label, multicentre, parallel-group, randomised, phase 3 trial (done in 130 UK hospitals) in which postmenopausal women aged at least 50 years with WHO performance status 0-1 and hormone receptor-positive, operable breast cancer were randomly assigned (2:1) to POAI (letrozole 2·5 mg per day orally or anastrozole 1 mg per day orally) for 14 days before and following surgery or no POAI (control). Adjuvant treatment was given as per UK standard local practice. Randomisation was done centrally by computer-generated permuted block method (variable block size of six or nine) and was stratified by hospital. Treatment allocation was not masked. The primary endpoint was time to recurrence. A key second objective explored association between Ki67 (dichotomised at 10%) and disease outcomes. The primary analysis for clinical endpoints was by modified intention to treat (excluding patients who withdrew consent). For Ki67 biomarker association and endpoint analysis, the evaluable population included all randomly assigned patients who had paired Ki67 values available. This study is registered with ClinicalTrials.gov, NCT02338310; the European Clinical Trials database, EudraCT2007-003877-21; and the ISRCTN registry, ISRCTN63882543. Recruitment is complete and long-term follow-up is ongoing. FINDINGS: Between Oct 13, 2008, and April 16, 2014, 4480 women were recruited and randomly assigned to POAI (n=2976) or control (n=1504). On Feb 6, 2018, median follow-up was 62·9 months (IQR 58·1-74·1). 434 (10%) of 4480 women had a breast cancer recurrence (280 [9%] POAI; 154 [10%] control), hazard ratio 0·92 (95% CI 0·75-1·12); p=0·40 with the proportion free from breast cancer recurrence at 5 years of 91·0% (95% CI 89·9-92·0) for patients in the POAI group and 90·4% (88·7-91·9) in the control group. Within the POAI-treated HER2-negative subpopulation, 5-year recurrence risk in women with low Ki67B and Ki672W (low-low) was 4·3% (95% CI 2·9-6·3), 8·4% (6·8-10·5) with high Ki67B and low Ki672W (high-low) and 21·5% (17·1-27·0) with high Ki67B and Ki672W (high-high). Within the POAI-treated HER2-positive subpopulation, 5-year recurrence risk in the low-low group was 10·1% (95% CI 3·2-31·3), 7·7% (3·4-17·5) in the high-low group, and 15·7% (10·1-24·4) in the high-high group. The most commonly reported grade 3 adverse events were hot flushes (20 [1%] of 2801 patients in the POAI group vs six [<1%] of 1400 in the control group) and musculoskeletal pain (29 [1%] vs 13 [1%]). No treatment-related deaths were reported. INTERPRETATION: POAI has not been shown to improve treatment outcome, but can be used without detriment to help select appropriate adjuvant therapy based on tumour Ki67. Most patients with low Ki67B or low POAI-induced Ki672W do well with adjuvant standard endocrine therapy (giving consideration to clinical-pathological factors), whereas those whose POAI-induced Ki672W remains high might benefit from further adjuvant treatment or trials of new therapies. FUNDING: Cancer Research UK.


Assuntos
Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Antígeno Ki-67/genética , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Idoso , Inibidores da Aromatase/efeitos adversos , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Receptor alfa de Estrogênio/genética , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Hormônio-Dependentes/genética , Neoplasias Hormônio-Dependentes/patologia , Pós-Menopausa/efeitos dos fármacos , Prognóstico , Receptor ErbB-2/genética
3.
Obstet Gynecol ; 136(4): 675-684, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32925623

RESUMO

OBJECTIVE: To identify factors associated with serum estradiol (E2) levels among healthy postmenopausal women using hormone therapy (HT). METHODS: This is an unplanned post hoc analysis of data from ELITE (Early versus Late Intervention Trial with Estradiol), a randomized controlled trial of 1 mg oral E2 with or without vaginal progesterone in healthy early compared with late (<6 years compared with 10 or more years since menopause) postmenopausal women. We included results from visits when women reported at least 80% compliance with HT. Mixed-effects linear models identified factors associated with serum E2 levels while participants were taking HT, assessed every 6 months over a median follow-up of 4.8 years and adjusted for baseline E2 level, visit, and reduced E2 dose. Possible correlates evaluated included demographics, clinical characteristics, medication use, and biomarkers of liver and kidney metabolic function. RESULTS: The analysis included 2,160 E2 measurements in 275 postmenopausal women. Mean±SD age was 55.4±3.9 vs 64.4±5.5 years, and mean±SD time since menopause was 3.6±1.8 vs 16.0±5.6 years for early vs late postmenopausal women. Adjusted for pretreatment E2 level, visit, and reduced dose indicator, higher serum E2 levels were associated with higher body mass index (BMI), higher weight, surgical menopause, alcohol use, and antihypertensive medication use. Current and past smoking and antifungal medication use were associated with lower serum E2 levels. In the multivariable model, higher BMI and alcohol use were associated with higher serum E2 levels, whereas current and past smoking were associated with lower serum E2 levels. These factors were similar between early and late postmenopausal women. CONCLUSION: Factors associated with serum E2 levels among postmenopausal women taking HT include BMI, alcohol use, and smoking. As serum E2 levels relate to HT effect, achievement of desirable E2 levels may be maximized through personalized intervention. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00114517.


Assuntos
Estradiol/sangue , Terapia de Reposição de Estrogênios/métodos , Estrogênios/administração & dosagem , Pós-Menopausa , Progesterona/administração & dosagem , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Índice de Massa Corporal , Causalidade , Vias de Administração de Medicamentos , Monitoramento de Medicamentos/métodos , Feminino , Hormônios/administração & dosagem , Humanos , Testes de Função Renal/métodos , Testes de Função Hepática/métodos , Pessoa de Meia-Idade , Pós-Menopausa/sangue , Pós-Menopausa/efeitos dos fármacos , Fumar/epidemiologia
4.
Life Sci ; 258: 118030, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32739470

RESUMO

The risk of atherosclerosis (AS) ascends among post-menopausal women, while current hormone replacement therapy exerts several adverse effects. Alisol B 23-acetate (AB23A), a tetracyclic triterpenoid isolated from the rhizome of Alisma orientale, was reported to show multiple physiological activities, including regulating lipid metabolism. According to molecular docking analysis, it was predicted to bind with estrogen receptor α (ERα). In this study, we aimed to observe the effect of AB23A on preventing post-menopausal AS and explore whether the mechanism was mediated by ERα. In vitro, free fatty acid (FFA) was applied to induce the abnormal lipid metabolism of L02 cells. In vivo, the ApoE-/- mice were ovariectomized to mimic the cessation of estrogen. The high-fat diet was also given to induce post-menopausal AS. We demonstrated AB23A attenuated the accumulation of total cholesterol and triglyceride induced by free fatty acids in hepatocytes. In high-fat diet-ovariectomy-treated ApoE-/- mice, AB23A eliminated lipids in blood and liver. AB23A not only reduced the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) through sterol-regulatory element binding proteins (SREBPs) but also suppressed the secretion of PCSK9 through silent information regulator 1 (SIRT1). Notably, AB23A promoted the expression of ERα in vivo and in vitro. The both ERα inhibitor and ERα siRNA were also applied in confirming whether the hepatic protective effect of AB23A was mediated by ERα. We found that AB23A significantly promoted the expression of ERα. AB23A could inhibit the synthesis and secretion of PCSK9 through ERα, lower the accumulation of triglyceride and cholesterol, and prevent post-menopausal AS.


Assuntos
Aterosclerose/patologia , Colestenonas/farmacologia , Receptor alfa de Estrogênio/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Pós-Menopausa/efeitos dos fármacos , Animais , Aterosclerose/genética , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Colestenonas/química , Dieta Hiperlipídica , Ácidos Graxos/metabolismo , Feminino , Lipoproteínas LDL/metabolismo , Camundongos , Ovariectomia , Regiões Promotoras Genéticas/genética , Pró-Proteína Convertase 9/genética , Pró-Proteína Convertase 9/metabolismo , Receptores de LDL/genética , Receptores de LDL/metabolismo , Sirtuína 1/metabolismo , Proteínas de Ligação a Elemento Regulador de Esterol/genética , Proteínas de Ligação a Elemento Regulador de Esterol/metabolismo , Regulação para Cima/efeitos dos fármacos
5.
Maturitas ; 139: 20-26, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32747036

RESUMO

OBJECTIVES: Various combinations of estrogens and progestogens are available for menopausal hormone therapy that differ in their efficacy and safety profile. We evaluated the efficacy and long-term safety of low-dose estradiol (0.5 mg) / dydrogesterone (2.5 mg) in subgroups of postmenopausal women with vasomotor symptoms. ANALYSIS: Efficacy analysis was performed on data from 2 previously published studies for subgroups defined by age, duration of menopause, and body mass index at baseline. The primary efficacy variable was the number of moderate to severe hot flushes from baseline to week 13. Long-term safety was evaluated in relation to age and duration of menopause. Safety variables included adverse events to week 52 and change from baseline to endpoint in laboratory and vital sign values. RESULTS: The treatment difference seen in the overall population in favour of low-dose estradiol/dydrogesterone was also observed in the subgroups of patients aged 45 to < 55 years (p < 0.01) and ≥55 years (p < 0.05), with menopause duration of >12 months to <60 months (p < 0.05) and ≥ 60 months (p < 0.005), and with a BMI at baseline of <25 kg/m2 (p < 0.05) and 25 to <30 kg/m2 (p < 0.01). Low-dose estradilol/dydrogesterone was well tolerated across the different subgroups. The incidence of breast-related adverse events was very low. No breast malignancy was reported. Only one adverse endometrial outcome of simple hyperplasia was observed. CONCLUSION: The results of our analyses confirmed the consistent treatment effect on vasomotor symptoms and the favourable safety profile of 0.5 mg 17ß estradiol and 2.5 mg dydrogesterone in different patient subgroups.


Assuntos
Didrogesterona/uso terapêutico , Estradiol/uso terapêutico , Terapia de Reposição Hormonal , Fogachos/tratamento farmacológico , Idoso , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa/efeitos dos fármacos
6.
Medicine (Baltimore) ; 99(29): e20821, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702824

RESUMO

This study was to investigate the efficacy and safety of fulvestrant 500 mg for the treatment of hormone receptor positive advanced postmenopausal women, including ovarian ablation and investigated factors associated with prolonged time-to-treatment failure.Data from 60 women with metastatic breast cancer who were treated at Zhejiang Cancer Hospital. Patients received 500 mg (n = 60) between December 2011 and November 2012 were followed until November 2017. Main outcomes were clinical responses to fulvestrant, including best response, progressive disease, partial response, and stable disease lasting 12 months or more. Time to progression and time to progression-free-survival were also analyzed.Among the included 60 patients (mean age 47.18 years), 51 (85.0%) had received prior adjuvant therapy. During follow-up after fulvestrant treatment, the median PFS for the best response was derived as 7.0 months (inter-quartile = 4, 13.8 months). The observed median progression-free-survival time for best response was represented longer when fulvestrant was first-line treatment than when patients received prior endocrine and/or chemotherapy. Univariate analysis revealed that receiving either endocrine therapy only or endocrine therapy plus chemotherapy prior to fulvestrant treatment may be associated with median progression-free survival time to best response (P = .002, .026, .007, respectively).Fulvestrant treatment is safe and well-tolerated in women with hormone-sensitive advanced breast cancer, and first-line fulvestrant therapy increases progression-free-survival time, especially in patients without prior adjuvant treatment.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Antagonistas do Receptor de Estrogênio/uso terapêutico , Fulvestranto/uso terapêutico , Metástase Neoplásica/tratamento farmacológico , Pós-Menopausa/efeitos dos fármacos , Adulto , Antineoplásicos Hormonais/uso terapêutico , Grupo com Ancestrais do Continente Asiático/etnologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/métodos , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Intervalo Livre de Progressão , Estudos Retrospectivos , Segurança , Tempo para o Tratamento , Resultado do Tratamento
7.
Eur J Endocrinol ; 183(4): 439-452, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32698159

RESUMO

Objective: Combining conjugated estrogens (CE) with the selective estrogen receptor modulator bazedoxifene (BZA) is a novel, orally administered menopausal therapy. We investigated the effect of CE/BZA on insulin sensitivity, energy metabolism, and serum metabolome in postmenopausal women with obesity. Design: Randomized, double-blind, crossover pilot trial with washout was conducted at Pennington Biomedical Research Center. Eight postmenopausal women (age 50-60 years, BMI 30-40 kg/m2) were randomized to 8 weeks CE/BZA or placebo. Primary outcome was insulin sensitivity (hyperinsulinemic-euglycemic clamp). Secondary outcomes included body composition (DXA); resting metabolic rate (RMR); substrate oxidation (indirect calorimetry); ectopic lipids (1H-MRS); fat cell size, adipose and skeletal muscle gene expression (biopsies); serum inflammatory markers; and serum metabolome (LC/MS). Results: CE/BZA treatment produced no detectable effect on insulin sensitivity, body composition, ectopic fat, fat cell size, or substrate oxidation, but resulted in a non-significant increase in RMR (basal: P = 0.06; high-dose clamp: P = 0.08) compared to placebo. CE/BZA increased serum high-density lipoprotein (HDL)-cholesterol. CE/BZA also increased serum diacylglycerol (DAG) and triacylglycerol (TAG) species containing long-chain saturated, mono- and polyunsaturated fatty acids (FAs) and decreased long-chain acylcarnitines, possibly reflecting increased hepatic de novo FA synthesis and esterification into TAGs for export into very low-density lipoproteins, as well as decreased FA oxidation, respectively (P < 0.05). CE/BZA increased serum phosphatidylcholines, phosphatidylethanolamines, ceramides, and sphingomyelins, possibly reflecting the increase in serum lipoproteins (P < 0.05). Conclusions: A short treatment of obese postmenopausal women with CE/BZA does not alter insulin action or ectopic fat but increases serum markers of hepatic de novo lipogenesis and TAG production.


Assuntos
Metabolismo dos Carboidratos/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Estrogênios Conjugados (USP)/farmacologia , Glucose/metabolismo , Indóis/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/metabolismo , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Estudos Cross-Over , Método Duplo-Cego , Estrogênios Conjugados (USP)/uso terapêutico , Feminino , Humanos , Indóis/uso terapêutico , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico , Projetos Piloto , Pós-Menopausa/efeitos dos fármacos , Pós-Menopausa/metabolismo
8.
BMC Womens Health ; 20(1): 108, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32429977

RESUMO

BACKGROUND: Around 90% of postmenopausal women are suffering from vaginal atrophy. This study aimed to evaluate the effect of oxytocin vaginal gel on vaginal atrophy among postmenopausal women. METHODS: This was a randomized controlled trial that was conducted on 96 postmenopausal women who suffered from vaginal atrophy. The inclusion criteria were: literate women, age 40-60, at least 1 year passed from their last menstrual period or the level of FSH > 40 IU, monogamous women with the sexual relationship. Women in the intervention group, requested to use one applicator of 400 IU oxytocin gel per night and women in the placebo group used placebo each night. The subjective symptoms of vaginal atrophy, vaginal PH, maturation index were measured before and after the intervention. RESULTS: The number of superficial cells was increased significantly in the oxytocin group compared to placebo (38.7 ± 7.18 vs. 3.69 ± 2.76, p = 0.0001), while the number of parabasal cells was decreased significantly in the oxytocin compared to placebo after the intervention. The improvement of the maturation index was more dominant in the oxytocin group (increased from 7.76 ± 4.68 to 52.48 ± 7.54) in comparison to the placebo group (increased from 8.58 ± 4.35 to 13.25 ± 5.06). The PH of the vagina decreased significantly in the oxytocin group in comparison to the placebo group (p = 0.0001). After 8 weeks, 88.6 and 7.1% of women in the oxytocin and placebo groups did not show the severe symptoms of vaginal atrophy (p = 0.001). CONCLUSION: The results of this study showed that eight- week intervention with oxytocin vaginal gel (400 IU) could significantly improve the vaginal maturation index, subjective symptoms of vaginal atrophy and reduce the PH of the vagina. Using this medication in women who have a contraindication for hormone therapy is recommended. TRIAL REGISTRATION: IRCT20160602028220N2.


Assuntos
Atrofia/tratamento farmacológico , Ocitocina/administração & dosagem , Pós-Menopausa/efeitos dos fármacos , Vagina/efeitos dos fármacos , Vagina/patologia , Cremes, Espumas e Géis Vaginais/administração & dosagem , Doenças Vaginais/tratamento farmacológico , Administração Intravaginal , Idoso , Método Duplo-Cego , Feminino , Humanos , Irã (Geográfico) , Pessoa de Meia-Idade , Ocitocina/uso terapêutico , Resultado do Tratamento , Cremes, Espumas e Géis Vaginais/uso terapêutico , Doenças Vaginais/patologia
9.
Internist (Berl) ; 61(6): 558-564, 2020 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-32333087

RESUMO

Peri- and postmenopausal disorders can have a significant impact on quality of life. Hormone replacement therapy (HRT) might be necessary in order to decrease women's symptoms. The German S3 guideline "Peri- and Postmenopause-Diagnostics and Therapy" (2020) provides recommendations that include the most recent evidence as well as the Women's Health Initiative (WHI) study results from 2002 and 2004. These results led to reduced prescription patterns due to a high risk of cardiovascular diseases as well as an increased risk for breast cancer if HRT had been administered. Both ongoing analyses of subgroups and other studies extenuated the WHI data, since the increased risks were neither generalizable to the typical postmenopausal patient (regarding age and risk profile) nor to the medication being used today. This article summarizes all aspects of HRT in peri- and postmenopausal women (indications, contraindications, practical approaches, risks, prevention) and provides recommendations with respect to the most recent S3 guideline.


Assuntos
Terapia de Reposição de Estrogênios/efeitos adversos , Estrogênios/efeitos adversos , Terapia de Reposição Hormonal , Perimenopausa/efeitos dos fármacos , Pós-Menopausa/efeitos dos fármacos , Pós-Menopausa/psicologia , Progesterona/efeitos adversos , Idoso , Terapia de Reposição de Estrogênios/métodos , Estrogênios/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Perimenopausa/fisiologia , Perimenopausa/psicologia , Pós-Menopausa/fisiologia , Progesterona/uso terapêutico , Qualidade de Vida , Saúde da Mulher
10.
Rev. Hosp. Ital. B. Aires (2004) ; 40(1): 34-38, mar. 2020. tab
Artigo em Espanhol | LILACS | ID: biblio-1102292

RESUMO

Las mujeres han sido tratadas por décadas con testosterona intentando aliviar una gran variedad de síntomas con riesgos y beneficios inciertos. En la mayoría de los países, la testosterona se prescribe "off-label", de modo que las mujeres están utilizando compuestos y dosis ideadas para tratamientos en hombres. En este sentido, varias sociedades médicas de distintos continentes adoptaron recientemente por consenso una toma de posición sobre los beneficios y potenciales riesgos de la terapia con testosterona en la mujer, explorar las áreas de incertidumbre e identificar prácticas de prescripción con potencial de causar daño. Las recomendaciones con respecto a los beneficios y riesgos de la terapia con testosterona se basan en los resultados de ensayos clínicos controlados con placebo de al menos 12 semanas de duración. A continuación se comentan las recomendaciones. (AU)


There are currently no clear established indications for testosterone replacement therapy for women. Nonetheless, clinicians have been treating women with testosterone to alleviate a variety of symptoms for decades with uncertainty regarding its benefits and risks. In most countries, testosterone therapy is prescribed off-label, which means that women are using testosterone formulations or compounds approved for men with a modified dose for women. Due to these issues, there was a need for a global Consensus Position Statement on testosterone therapy for women based on the available evidence from placebo randomized controlled trials (RCTs). This Position Statement was developed to inform health care professionals about the benefits and potential risks of testosterone therapy intended for women. The aim of the Consensus was to provide clear guidance as to which women might benefit from testosterone therapy; to identify symptoms, signs, and certain conditions for which the evidence does not support the prescription of testosterone; to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm. (AU)


Assuntos
Humanos , Feminino , Idoso , Testosterona/uso terapêutico , Pós-Menopausa/efeitos dos fármacos , Depressores do Apetite/efeitos adversos , Fenitoína/efeitos adversos , Placebos/administração & dosagem , Psicotrópicos/efeitos adversos , Tamoxifeno/efeitos adversos , Testosterona/administração & dosagem , Testosterona/análise , Testosterona/efeitos adversos , Testosterona/farmacologia , Fármacos Cardiovasculares/efeitos adversos , Indometacina/efeitos adversos , Hormônio Liberador de Gonadotropina/efeitos adversos , Pós-Menopausa/fisiologia , Ensaios Clínicos Controlados como Assunto , Antagonistas Colinérgicos/efeitos adversos , Anticoncepcionais Orais/efeitos adversos , Disfunções Sexuais Psicogênicas/etiologia , Disfunções Sexuais Psicogênicas/terapia , Danazol/efeitos adversos , Consenso , Inibidores da Aromatase/efeitos adversos , Uso Off-Label , Inibidores do Fator Xa/efeitos adversos , Anfetaminas/efeitos adversos , Antagonistas dos Receptores Histamínicos/efeitos adversos , Antagonistas de Androgênios/efeitos adversos , Androgênios/fisiologia , Cetoconazol/efeitos adversos , Entorpecentes/efeitos adversos
11.
Complement Ther Med ; 48: 102267, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31987231

RESUMO

OBJECTIVE: The decline and eventual cessation of estrogen production cause a variety of symptoms during menopause, affecting each woman differently. Most women reported severe hot flashes and night sweats during menopause. The present study aimed to determine and compare the efficacy of curcumin and vitamin E on hot flashes and anxiety (primary objectives), sexual function, menopausal symptoms and adverse effects (secondary objectives). MATERIALS AND METHODS: This was a triple-blind randomized controlled clinical trial. The participants consisted of 93 postmenopausal women in Ahar city-Iran. They were assigned into three groups (two intervention groups and one control group). The first intervention group received oral capsule of curcumin (500 mg), the second intervention group was given oral tablets of vitamin E (200 IU/day), and the third group (control) received placebo twice a day for eight weeks. The participants completed the hot flash checklist one week before the intervention, and 4 weeks and 8 weeks after the intervention. They also filled out the Anxiety Scale, the Female Sexual Function Index (FSFI), the Greene Climacteric Scale before the intervention, and 4 weeks and 8 weeks after the intervention. One-way ANOVA, repeated measures ANOVA and ANCOVA tests were used for data analysis. RESULTS: There was no statistically significant difference between groups in terms of demographic characteristics, mean number of hot flashes, mean score of anxiety, sexual function index and menopausal symptoms before the intervention (p > 0.05). The mean age of participants was 51.7 years. Mean number of hot flashes in the curcumin group (adjusted mean difference = -10.7, 95%confidence interval = -3.6 to -17.9, P = 0.001) and in the vitamin E group (-8.7, -0.6 to -15.0, P = 0.029) was significantly lower than the placebo group after the intervention. The first significant effect of curcumin on hot flashes was observed after four weeks (P = 0.027). However, there was no significant difference between vitamin E group and placebo four weeks after intervention (P = 0.052) and the first significant effect of vitamin E on hot flashes was observed after eight weeks (P = 0.025). There was no statistically significant difference between the groups in terms of sexual function index, anxiety and menopausal symptoms (P > 0.05). CONCLUSION: The results of this study showed that oral intake of curcumin and vitamin E significantly reduced hot flashes in postmenopausal women but had no significant effect on anxiety, sexual function and menopausal symptoms.


Assuntos
Ansiedade/terapia , Curcumina/uso terapêutico , Fogachos/terapia , Pós-Menopausa/efeitos dos fármacos , Vitamina E/uso terapêutico , Administração Oral , Cápsulas , Curcumina/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Vitamina E/administração & dosagem
13.
Pharmacogenomics ; 21(1): 43-53, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31769341

RESUMO

Aim: To assess the cost-effectiveness of CYP2D6*10 genetic testing for the management of Chinese women with hormone receptor-positive (HR+) breast cancer treated with selective estrogen receptor modulator. Methods: A Markov model was developed to evaluate a total expected cost and an incremental cost-effectiveness ratio (ICER). Robustness of the model was addressed in one-way analyses and probabilistic sensitivity analysis. Results: The cost of strategies of tamoxifen, toremifene without genotyping and the strategy base on CYP2D6*10 genotype were $63,879.19, $90,156.60 and $95,021.41, and the quality-adjusted life years gained are 8.1588, 12.89687 and 13.85911, respectively. The incremental cost-effectiveness ratio of the CYP2D6*10 testing versus toremifene were 5,055.74221/quality-adjusted life year, respectively. Conclusion: CYP2D6*10 pharmacogenetic-guided selective estrogen receptor modulator can be a cost-effective strategy in the Chinese patients with hormone receptor-positive breast cancer.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Análise Custo-Benefício , Citocromo P-450 CYP2D6/genética , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/economia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Genótipo , Humanos , Cadeias de Markov , Farmacogenética , Testes Farmacogenômicos , Pós-Menopausa/efeitos dos fármacos , Anos de Vida Ajustados por Qualidade de Vida , Receptores Estrogênicos/genética , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Tamoxifeno/efeitos adversos , Tamoxifeno/uso terapêutico , Triazóis/efeitos adversos , Triazóis/uso terapêutico
14.
J Oncol Pharm Pract ; 26(2): 492-495, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31260379

RESUMO

INTRODUCTION: Glucose 6-phosphate dehydrogenase (G6PD) is a basic antioxidant pathway for erythrocytes, being its deficiency the most common gene mutation worldwide. As breast cancer is one of the most frequent tumors, many of these patients may present with G6PD deficiency prior treatment without notice. CASE REPORT: We present the case of a woman deficient for G6PD with the diagnosis of Stage IIIB (cT4d cN1 cM0) HER2-enriched early breast cancer. MANAGEMENT AND OUTCOME: The patient underwent neoadjuvance with trastuzumab and anthracycline-free chemotherapy, based on docetaxel (75 mg/m2, 120 mg) and carboplatin (AUC 5, 560 mg). She did not present hemolytic crisis and no blood transfusions were needed. She achieved a good pathologic response and completed one-year adjuvant trastuzumab without incidences. DISCUSSION: Although the role of HER2 and trastuzumab in oxidative stress is not yet completely understood, we suggest that trastuzumab may be a suitable agent for treatment in patients with HER2-enriched breast cancer in a non-oxidative chemotherapy scheme, with acceptable responses and no triggering hemolytic crisis.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Deficiência de Glucosefosfato Desidrogenase/tratamento farmacológico , Terapia Neoadjuvante/métodos , Pós-Menopausa/efeitos dos fármacos , Receptor ErbB-2 , Trastuzumab/administração & dosagem , Idoso , Antineoplásicos Imunológicos/administração & dosagem , Neoplasias da Mama/complicações , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Feminino , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Humanos , Pós-Menopausa/genética , Receptor ErbB-2/genética , Resultado do Tratamento
15.
J Womens Health (Larchmt) ; 29(1): 57-64, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31687883

RESUMO

Androgens are believed to have an important biologic role in women, particularly in regulation of libido and sexual arousal, although much about their function on other systems in women is unknown. Testosterone, the primary ovarian androgen, has been used to treat carefully selected postmenopausal women with hypoactive sexual desire disorder (HSDD). However, testosterone use in women has not been approved by the United States Food and Drug Administration (FDA) because of uncertainties regarding the effectiveness and long-term safety of this strategy. An intravaginal form of the adrenal androgen, dehydroepiandrosterone (DHEA) has been approved by the FDA to treat genitourinary syndrome of menopause. In this article, we review the current knowledge regarding the role of androgens and their clinical use in women. We conducted a systematic search of PubMed for publications describing the role and clinical use of androgens in women. We used the search terms "HSDD," "DHEA in women," "testosterone in women," and "androgens in women," and reviewed most references from all relevant articles. Most randomized placebo-controlled trials show an improvement in sexual function with low-dose testosterone therapy in select postmenopausal women with HSDD. Although this strategy appears to be safe in the short term and no major safety concerns have emerged thus far, long-term effects on cardiovascular risk and breast cancer incidence are not known. A trial of low-dose testosterone therapy may be considered for carefully selected postmenopausal women with HSDD, as long as other contributors to sexual dysfunction have been adequately addressed. However, patients need careful counseling regarding the lack of long-term safety data, and close clinical and laboratory monitoring of these women is recommended to avoid supraphysiologic dosing.


Assuntos
Androgênios/administração & dosagem , Libido/efeitos dos fármacos , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Testosterona/administração & dosagem , Desidroepiandrosterona/administração & dosagem , Feminino , Terapia de Reposição Hormonal/métodos , Humanos , Pós-Menopausa/efeitos dos fármacos
16.
Medicina (Kaunas) ; 55(9)2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31480427

RESUMO

Background and Objectives: Hot flushes and sleep disturbances are the most common vasomotor symptoms (VMS) reported by postmenopausal women. Hormonal treatment is to date referred to as the gold standard approach but not suitable for all the patients. Alternative treatments are needed in case of a contraindication to menopausal hormone therapy (MHT), adverse side effects, and poor compliance. Paroxetine salt is the only nonhormonal medication approved by the US Food and Drug Administration for the management of VMS. Nonetheless, few trials with low consensus are available about this topic. In this review, we aimed to evaluate the efficacy of low-dose paroxetine therapy in the treatment of vasomotor hot flushes and night sleep disturbances in postmenopausal women. Materials and Methods: We performed an electronic search from the beginning of all databases to July 2019. All results were then limited to a randomized trial. Restrictions for language or geographic location were not utilized. Inclusion criteria were randomized clinical trials of physiological or surgical postmenopausal women experiencing hot flushes and sleep disturbances who were randomized to either low-dose paroxetine or placebo (i.e., formulations without active ingredients). The primary outcome evaluated was the mean weekly reduction of hot flushes. Results: Five randomized clinical trials, including 1482 postmenopausal women, were analyzed. Significant heterogeneity (I2 = 90%) between studies was noted. Hot flushes episodes were significantly reduced in the treatment arm compared to placebo (mean difference (MD) -7.97 [-10.51, -5.92] episodes/week). Results on the improvement on sleep were limited by being reported in only two studies; however, no significant reduction of night-time awakenings was observed (MD, -0.40 awakenings/night [-1.38, 0.58 CI]). Conclusions: Low-dose paroxetine is an effective treatment for vasomotor menopause symptoms, including hot flushes.


Assuntos
Fogachos/tratamento farmacológico , Paroxetina/administração & dosagem , Pós-Menopausa , Inibidores de Captação de Serotonina/administração & dosagem , Transtornos do Sono-Vigília/tratamento farmacológico , Feminino , Humanos , Ovariectomia , Pós-Menopausa/efeitos dos fármacos , Pós-Menopausa/fisiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Food Funct ; 10(8): 5228-5238, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31384878

RESUMO

Obesity leads to detrimental abnormalities of iron (Fe) metabolism. So far, studies have shown that single-strain probiotic supplementation ameliorates the gut microbiota quality disrupted in the obese and improves Fe homeostasis. The effect of multistrain probiotic supplementation and its dose-dependence in obese postmenopausal women remain unknown. The study aimed to investigate the effect of multistrain probiotic supplementation in two doses on selected parameters of Fe metabolism in obese postmenopausal female patients. Three groups of obese postmenopausal women, 30 subjects each, received nine-strain oral probiotic supplement at a daily dose of 2.5 × 109 CFU (LD group), 1 × 1010 CFU (HD group), or placebo for 12 weeks (ClinicalTrails.gov no: NCT03100162). After the intervention, the hair Fe content was lower in both supplemented groups compared to the baseline, the serum zinc (Zn) concentration was higher in the LD group and lower in the HD group vs. the baseline, and the serum erythroferrone (FAM) concentration was lower in the HD group and serum ferritin (FE) concentration was higher in the LD group vs. the baseline. In the whole study population after the completion of the intervention hair Zn correlated positively with serum HEPC and FAM and negatively with serum FE. Hair Fe correlated negatively with serum FE. It is concluded that multistrain probiotic supplementation may influence iron metabolism in obese postmenopausal female patients.


Assuntos
Ferro/metabolismo , Obesidade/tratamento farmacológico , Pós-Menopausa/efeitos dos fármacos , Probióticos/administração & dosagem , Idoso , Suplementos Nutricionais/análise , Feminino , Ferritinas/sangue , Cabelo/química , Cabelo/metabolismo , Humanos , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/microbiologia , Pós-Menopausa/sangue , Zinco/metabolismo
18.
JAMA Netw Open ; 2(8): e1910154, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-31461147

RESUMO

Importance: Hormone therapy (HT) has been suggested for protection against age-related muscle weakness in women. However, the potential for HT-associated health risks necessitates a better understanding of the direction and magnitude of the association between HT and health outcomes, such as lean body mass (LBM). Objective: To determine whether HT was associated with reduced LBM loss compared with not receiving HT among postmenopausal women aged 50 years and older. Data Sources: MEDLINE, Embase, AgeLine, CINAHL, and SportDiscus (searched from inception until April 25, 2018). Study Selection: For this systematic review and meta-analysis, randomized clinical trials including postmenopausal women undergoing HT and control groups of women not receiving HT were selected by 2 reviewers. Studies were included if LBM or fat-free mass were measured as an outcome. Studies with participants from hospitals, long-term care facilities, or with specific diseases were excluded. Data Extraction and Synthesis: Information regarding study characteristics and outcome measures were extracted by 1 reviewer and verified by another. Risk of bias was evaluated. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used to abstract data and assess data quality/validity. Data were pooled using a fixed-effects model. Main Outcomes and Measures: The primary study outcome was the overall absolute change in LBM (measured in kilograms), captured by dual-energy x-ray absorptiometry, dual-photon absorptiometry, or bioelectrical impedance analysis imaging. Results: Of 8961 studies that met selection criteria, 12 were included, with a total of 4474 recruited participants. Of the participants, mean (SD) age was 59.0 (6.1) years. Data on ethnicity were collected by 2 of the studies. Of the 22 HT intervention arms, 15 used estrogen-progesterone combination HT and 7 used estrogen-only HT. Control participants were women who received no HT at all or who received placebo. The median follow-up duration was 2 years (range, 6 months to 6 years). Seven treatment arms showed a loss of LBM, and 14 were protective. Overall, HT users lost 0.06 kg (95% CI, -0.05 to 0.18) less LBM compared with control participants, but the difference was not statistically significant (P = .26). The results were unchanged when stratified based on treatment type and dosage, duration of follow-up, time since menopause, study quality, and type of LBM measurement, with HT users losing between 0.06 kg more to 0.20 kg less LBM compared with control participants for all strata. The quality of evidence based on GRADE was low. Conclusions and Relevance: This systematic review and meta-analysis did not show a significant beneficial or detrimental association of HT with muscle mass. Although muscle retention in aging women is of crucial importance, these findings suggest that interventions other than HT should be explored.


Assuntos
Composição Corporal/efeitos dos fármacos , Terapia de Reposição de Estrogênios/efeitos adversos , Terapia de Reposição Hormonal/efeitos adversos , Debilidade Muscular/tratamento farmacológico , Músculo Esquelético/efeitos dos fármacos , Pós-Menopausa/efeitos dos fármacos , Absorciometria de Fóton/métodos , Idoso , Estudos de Casos e Controles , Impedância Elétrica , Terapia de Reposição de Estrogênios/métodos , Estrogênios/efeitos adversos , Estrogênios/uso terapêutico , Feminino , Seguimentos , Terapia de Reposição Hormonal/métodos , Humanos , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Placebos/administração & dosagem , Pós-Menopausa/etnologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Pharmacol Res ; 148: 104414, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31449974

RESUMO

Atherosclerosis (AS) is one of the major causes leading to mortality of dysfunctional cardiovascular events in the menopausal women, which has long-term deficiency of estrogen. At present, the primary treatment for postmenopausal AS is hormone replacement therapy (HRT). However, it can increase the risks of ovarian and uterine cancers with long-term therapy. So seeking for a phytoestrogen which can overcome the disadvantages of HRT is a great mission. Dioscin, a traditional Chinese medicine, extracted from the roots of dioscorea nipponica, has anti-inflammatory, anti-tumor and anti-apoptosis activities. Especially, it also has estrogenic activity. Thus, this study aims to investigate the effects of dioscin on postmenopausal AS. Currently, ovariectomy (OVX) is the accepted model for AS associated with estrogen deficiency, and it can mimic the cessation of ovarian function that occurs in postmenopausal women as well. We used the high fat diet and ovariectomy(HFD-OVX)model to induce postmenopausal AS in the low-density lipoprotein receptor- deficient (LDLR-/-) mice. (1) The levels of TG, TC, LDL-C, HDLC, MDA, GSH, MDA and GSH in serum of HFD-OVX induced LDLR-/- mice were measured by colorimetric assay. (2) The artery injury of HFD-OVX induced LDLR-/- mice was detected with Oil Red O staining. (3) The protein expressions of NOX4, P22phox, IκB, p-p65, n-p65, ICAM-1, VCAM-1, caspase-3, caspase-9, bcl-2, PGC-1α, ERα, ERß in the arterial tissue of HFD-OVX induced LDLR-/- mice were detected by Western blot analysis. In vitro, the model of human aortic endothelial cells (HAECs) induced by oxidized low-density lipoprotein (ox-LDL) (150 µg /ml) was established, and the molecular mechanism of dioscin on atherosclerosis in postmenopausal women was investigated. (1) The levels of MDA, GSH, MDA and GSH in ox-LDL induced HAECs were measured by colorimetric assay. (2) Reactive Oxygen Species (ROS) of ox-LDL induced HAEC cells was detected by fluorescence staining. (3) The protein expressions of PGC-1α, ERα, ERß, NOX4, P22phox, IκB, p-p65, n-p65, ICAM-1, VCAM-1, caspase-3, caspase-9, bcl-2 and LC3 in ox-LDL induced HAECs were detected by Western blot analysis. (4) The autophagy level of ox-LDL induced HAECs was measured by transmission electron microscopy. (5) The applications of si-RNA transfection were used to explore whether dioscin could activate PGC-1α/ERα pathway to inhibit postmenopausal atherosclerosis. In vivo, we found that dioscin decreased the level of TG, TC, LDL-C and increased the level of HDLC in serum of HFD-OVX induced LDLR-/- mice, and it has protective effects to maintain the lipid homeostasis; The Oil Red O staining study showed that dioscin could significantly inhibit the formation of atherosclerotic plaques in HFD-OVX-treated LDLR-/- mice; Dioscin decreased the levels of NOX4, P22phox, p-p65, n-p65, ICAM-1, VCAM-1, caspase-3, caspase-9, but increased the levels of HDL-C, GSH, SOD, PGC-1α, ERα, ERß, IκB, Bcl-2 and elevated the autophagy level in arterial tissues of HFD-OVX induced LDLR-/- mice. It is particularly worth mentioning that the up-regulating effect of dioscin on ERα is stronger than ERß in OVX treated mice. In vitro, the results of colorimetric assay showed that dioscin decreased the level of MDA and LDH, increased the level of SOD and GSH in ox-LDL-induced HAEC cells; Dioscin also suppressed the release of ROS in ox-LDL-induced HAECs by fluorescence staining; Dioscin decreased the levels of NOX4, P22phox, p-p65, n-p65, ICAM-1, VCAM-1, caspase-3, caspase-9, but increased the levels of PGC-1α, ERα, ERß, IκB, Bcl-2 and the ratio of LC3-II/LC3-I in ox-LDL-induced HAECs; Dioscin significantly elevated the autophagy level of ox-LDL-induced HAECs by transmission electron microscopy analysis; In addition, by si-RNA transfection, we found that the inhibitory effects of dioscin on oxidative stress, inflammatory response and apoptosis might partly through PGC-1α/ERα pathway in ox-LDL induced HAECs. The data of dual-Luciferase reporter assay revealed that dioscin activated ERα at least partly through PGC-1α pathway. Dioscin significantly inhibited oxidative stress, inflammatory response, apoptosis and increased the level of autophagy in vivo and vitro. In addition, dioscin could regulate the balance of lipid metabolism. Moreover, we proved that the effects of dioscin attenuating postmenopausal atherosclerosis by inhibiting oxidative stress, inflammation and apoptosis were partly dependent on PGC-1α/ERα pathway. Therefore, dioscin, as a phytoestrogen, might become a drug for the treatment of atherosclerosis in postmenopausal women.


Assuntos
Apoptose/efeitos dos fármacos , Aterosclerose/prevenção & controle , Autofagia/efeitos dos fármacos , Diosgenina/análogos & derivados , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Aterosclerose/metabolismo , Células Cultivadas , Diosgenina/farmacologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Inflamação/metabolismo , Medicina Tradicional Chinesa/métodos , Camundongos , Camundongos Endogâmicos C57BL , Ovariectomia/métodos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Extratos Vegetais/farmacologia , Pós-Menopausa/efeitos dos fármacos , Pós-Menopausa/metabolismo , Receptores de LDL/metabolismo
20.
Phytother Res ; 33(11): 2979-2988, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31418933

RESUMO

Menopause, which occurs following a declined ovarian activity and reduced estrogen levels, can lead to long-term changes in lipid and glycemic profiles and increases the risk of cardiovascular disease and osteoporosis. Cornelian cherry (Cornus mas) is rich in phytochemicals and antioxidants, which appears to be useful in reducing the postmenopausal complications. This interventional, double-blinded, randomized clinical trial carried out on 84 menopaused women aged 45-60 years old. They were randomly divided into two groups. The treatment group received three capsules of 300 mg of Cornus mas extract (CME), and control group received three capsules of 300 mg of starch powder per day for 8 weeks. Then, BMI, waist circumference, glycemic indices, lipid profile, serum apoproteinase, apoprotein B100, fibrinogen, and leptin were measured. The dietary intakes were evaluated using 24-hr dietary recall questionnaire. The consumption of CME in comparison with the control group resulted in a significant reduction in weight, body mass index, waist circumference, LDL to HDL ratio, total cholesterol to HDL ratio, and fibrinogen. There was also a significant increase in HDL and ApoA1 levels in the treatment group. Furthermore, there was a significant decrease in BMI, waist circumference, fasting insulin, and insulin resistance index after 8 weeks of using CME. Summing up the results, it can be concluded that CME can have possible effects on decreasing BMI, waist circumference, and improving some aspects of lipid profile and glycemic indices in postmenopausal women.


Assuntos
Glicemia/efeitos dos fármacos , Cornus/química , Leptina/sangue , Lipídeos/sangue , Extratos Vegetais/farmacologia , Pós-Menopausa , Antioxidantes/farmacologia , Glicemia/metabolismo , Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Feminino , Frutas/química , Humanos , Insulina/sangue , Resistência à Insulina/fisiologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Pessoa de Meia-Idade , Pós-Menopausa/sangue , Pós-Menopausa/efeitos dos fármacos
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