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1.
Presse Med ; 48(11 Pt 1): 1295-1300, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31735524

RESUMO

Can menopausal hormone therapy (HT) be used in hypertensive women? The group of experts of the French Society of Hypertension has carried out a review of the recent literature in order to answer this question, based on the most recent scientific publications. If use of oral HT is associated with a discreet increase in blood pressure, the transdermal route seems to be safer. The first results of major randomized trials of HT had alerted to an increase in cardiovascular events and breast cancer with the use of oral HT, generally, tipping the benefit-risk balance of the deleterious side. Complementary analyzes have shown the importance of the window of intervention (less than 10 years after the menopause) and the age of the woman to start the HT. On the contrary, they have shown a significant decrease of the coronary events. For woman suffering from hypertension and important climacteric symptoms, it is important to evaluate the whole cardiovascular risk in order to decide the possibility of prescribing a HT. Thus, the group of experts proposes a prescription assistance algorithm based on the stratification of cardiovascular risk, always favoring, when it is authorized, HT by transdermal route of administration.


Assuntos
Neoplasias da Mama/induzido quimicamente , Doenças Cardiovasculares/induzido quimicamente , Terapia de Reposição de Estrogênios/métodos , Hipertensão , Menopausa , Administração Cutânea , Administração Oral , Fatores Etários , Algoritmos , Pressão Sanguínea/efeitos dos fármacos , Contraindicações de Medicamentos , Terapia de Reposição de Estrogênios/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Fatores de Tempo
2.
Acta Clin Croat ; 58(1): 167-172, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31363339

RESUMO

Although the use of commercially manufactured hormone therapy (HT) to treat menopausal symptoms has declined during the past 12 years, the use of custom compounded HT seems to have increased. A 39-year-old woman with refractory anemia sustained premature ovarian insufficiency following allogeneic stem cell transplantation. After systemic biologic treatment (azacitidine) and corticosteroid therapy, besides extreme climacteric symptoms (Green Climacteric Scale, 59) and impaired quality of life, she also had elevated liver enzymes. Therefore, she was not a candidate for oral HT. Treatment was started with 17-beta estradiol patch 0.5 mg (Climara) together with micronized progesterone intravaginally, 2x100 mg (Utrogestan) for 3 months. She was not satisfied, so the custom compound HT started with 17-beta estradiol 0.5 mg gel 2x/day and micronized progesterone in liposomal gel 100 mg/daily. She was much better but she complained of low libido, decreased sex drive and emotional instability, so 1% testosterone gel was added. Now she was completely satisfied, Green Climacteric Scale was 8 and liver enzymes were normal. In conclusion, custom compound HT has the possibility of tailoring and adjusting therapy to the individual need, which has been the everlasting goal in menopause medicine and should be a good option for special clinical cases.


Assuntos
Terapia de Reposição de Estrogênios/métodos , Estrogênios/administração & dosagem , Insuficiência Ovariana Primária/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Composição de Medicamentos , Feminino , Humanos , Insuficiência Ovariana Primária/induzido quimicamente , Progesterona/administração & dosagem , Progesterona/análogos & derivados , Qualidade de Vida
3.
Ren Fail ; 41(1): 507-520, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31216906

RESUMO

Menopause is an important physiological event associated with structural and functional changes in the kidneys. An animal model of bilateral ovariectomy was used to study the effects of estrogen depletion, replacement and antiestrogen on renal structure and endocrine function. Sixty female rats were divided into six groups; group I was the control group, the remaining five groups underwent ovariectomy: group II received no treatment. The other groups received estradiol in group III, tamoxifen in group IV, estradiol followed by tamoxifen in group V and tamoxifen followed by estradiol in group VI. Serum creatinine, blood urea nitrogen, and endocrine functions of kidney were measured. Tissue samples were examined both microscopically for beta estrogen receptors and ultrastructurally for cell changes. Groups II, IV & VI showed a significant increase in creatinine, blood urea nitrogen, renal malondialdehyde, renal erythropoietin, plasma renin and plasma prostaglandin E2 and a significant decrease in renal antioxidants and serum vitamin D3. Groups III &V had a significant decrease in creatinine, blood urea nitrogen, renal malondialdehyde and renal erythropoietin with an increase in renal antioxidants, plasma prostaglandin E2 and serum vitamin D3. Histopathological and ultrastructural examinations revealed atrophic tubular changes in group II. The changes were less marked in groups III &V and more extensive in groups IV & VI. Estrogen receptor beta staining showed progressively increased expression in the absence of estrogen. Structural and most endocrine functions of the kidney were significantly affected by estradiol deficiency. Estradiol replacement exhibited a protective effect on renal tissue and endocrine functions.


Assuntos
Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios/métodos , Rim/metabolismo , Menopausa/efeitos dos fármacos , Animais , Antagonistas de Estrogênios/administração & dosagem , Feminino , Rim/efeitos dos fármacos , Rim/patologia , Menopausa/metabolismo , Modelos Animais , Ovariectomia/efeitos adversos , Ratos , Tamoxifeno/administração & dosagem
4.
Medicine (Baltimore) ; 98(18): e15444, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045813

RESUMO

BACKGROUND: Premature ovarian insufficiency (POI) is a difficult-to-treat gynecological disorder with complex etiologies. Although acupuncture has gained increased popularity for the management of POI, evidence regarding its efficacy is lacking. This systematic review protocol aims to describe a meta-analysis to assess the effectiveness and safety of acupuncture for patients with POI. METHODS: The following 10 databases will be searched from the publishment to July 2019: PubMed, Embase, the Web of Science, the Cochrane Central Register of Controlled Trials, 4 Chinese databases (China National Knowledge Infrastructure, Wanfang Digital Periodicals, Chinese Biomedical Literature Database, Chinese Scientific Journal Database database), 1 Korean medical database (KoreaMed), 1 Japanese medical database (National Institute of Informatics). The primary outcomes will be the resumption of menstruation and the serum FSH levels, and the secondary outcomes include the serum Estradiol levels, anti-Mullerian hormone levels, antral follicle count, follicular growth, endometrial thickness, and adverse events. We will use RevMan V.5.3 to conduct the meta-analysis, if possible. If it is not allowed, a descriptive analysis or a subgroup analysis will be conducted. Risk ratio for dichotomous data and mean differences or standardized mean differences for continuous data will be calculated with 95% confidence intervals using a random effects model or a fixed effects model. RESULTS: This study will provide the latest analysis of the currently available evidence for the efficacy of acupuncture in treating POI. PROSPERO REGISTRATION NUMBER: CRD42019125996.


Assuntos
Terapia por Acupuntura/métodos , Insuficiência Ovariana Primária/terapia , Terapia por Acupuntura/efeitos adversos , China , Endométrio/patologia , Estradiol/sangue , Terapia de Reposição de Estrogênios/métodos , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
5.
Acta Oncol ; 58(8): 1107-1115, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30957588

RESUMO

Background: Sex steroid hormones and their receptors are important in female sexual function. The aim of this study was to investigate the expression and distribution of estrogen receptor (ER)α, ERß, G-protein-coupled ER-1 (GPER), androgen receptor (AR), progesterone receptor (PR)A, PRB and connective tissue growth factor (CTGF) in the vaginal wall among women who had been treated for cervical cancer with radiotherapy. Material and methods: We included cervical cancer survivors treated with radiotherapy and premenopausal control women of the same age scheduled for benign gynecological surgery. We analyzed the expression and distribution of sex steroid hormone receptors and CTGF in biopsies from the vaginal wall, by real-time PCR and immunohistochemistry (IHC). Serum samples were analyzed for hormone levels and radiation dose at biopsy site were calculated and correlated to levels of the sex steroid hormone receptors. Results: In the cervical cancer survivors (n = 34), we found a lower expression of ERα at both mRNA and protein levels, compared to the control women (n = 37). In the survivors with high radiation dose at biopsy site, the immunostaining of ERα and AR was lower in the epithelium and the stroma, compared to survivors with minimal radiation dose. The later group showed expression of ERα comparable to the control women. The cancer survivors were sufficiently substituted with systemic estradiol with no difference in the serum estradiol levels compared to control women. Conclusions: We found that external radiation reduces the ERα and AR protein expression in the vaginal mucosa, indicating that the vaginal changes in irradiated cervical cancer survivors and the lack of response to hormonal treatment could be due to the decreases in sex steroid hormone receptor expression.


Assuntos
Receptor alfa de Estrogênio/metabolismo , Receptores Androgênicos/metabolismo , Neoplasias do Colo do Útero/terapia , Vagina/patologia , Doenças Vaginais/patologia , Adulto , Biópsia , Sobreviventes de Câncer/estatística & dados numéricos , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Relação Dose-Resposta à Radiação , Resistência a Medicamentos , Estradiol/farmacologia , Estradiol/uso terapêutico , Terapia de Reposição de Estrogênios/métodos , Feminino , Humanos , Histerectomia , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Progestinas/farmacologia , Progestinas/uso terapêutico , Dosagem Radioterapêutica , Resultado do Tratamento , Vagina/efeitos da radiação , Doenças Vaginais/etiologia , Doenças Vaginais/terapia
6.
J Nat Med ; 73(3): 577-583, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30976950

RESUMO

Pueraria candollei (P. candollei) is a traditional Thai herb widely used for estrogen replacement therapy because it contains many unique chromenes that possess potent estrogenic activity, one of which is known as isomiroestrol. Since isomiroestrol is a promising compound that is solely present in P. candollei, it can be used as an identifying marker for standardization of P. candollei. Here, we developed a lateral-flow immunochromatographic strip (ICS) test using a colloidal gold nanoparticle-conjugated anti-isomiroestrol monoclonal antibody (12C1-mAb) for the detection of isomiroestrol in plant samples and products of P. candollei. The advantages of the developed ICS over an enzyme-linked immunosorbent assay are its simplicity and rapidity, as the ICS test can be completed 15 min after dipping the strip into the analyte solution. The detectable concentration of isomiroestrol was 7.0 µg/mL. Considering the demand for the standardization of P. candollei due to concerns regarding its quality, our ICS test using isomiroestrol as an identifying marker would be effective and useful to assess the presence of isomiroestrol.


Assuntos
Ensaio de Imunoadsorção Enzimática/métodos , Fitoestrógenos/análise , Pueraria/química , Esteroides/análise , Anticorpos Monoclonais/imunologia , Biomarcadores , Terapia de Reposição de Estrogênios/métodos , Coloide de Ouro/química , Nanopartículas Metálicas/química , Fitoestrógenos/química , Fitoestrógenos/imunologia , Esteroides/química , Esteroides/imunologia , Tailândia
7.
Maturitas ; 123: 55-60, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31027678

RESUMO

OBJECTIVES: To assess how women in Sweden with breast cancer (BC), endometrial cancer (EC), and/or pulmonary embolism (PE) were dispensed menopausal hormone therapy (HT). STUDY DESIGN: A retrospective study of Swedish women aged 40 years or more on 31 December 2005 (n = 2,863,643), followed through to December 2011. The study analysed three mandatory national healthcare registries: the Swedish Prescribed Drug Register, the National Inpatient Register and the Cancer Register. New users were defined as having a first dispensation after at least a 9-month break, and thus were possible to identify from April 2006. New users with at least one of the diagnoses BC, EC or PE before the first dispensation were classified as having a relative or absolute contraindication for HT. MAIN OUTCOME MEASURES: The relative risks of having HT dispensed after being diagnosed with BC, EC and/or PE. RESULTS: In total, 171,714 women had at least one of the diagnoses BC, EC or PE. The relative risk of having hormone therapy dispensed (current and new users) after being diagnosed with any of the diagnoses was significantly lower (PE, IRR 0.11, 95% CI 0.10-0.12;/ BC, IRR 0.12, 95% CI 0.11-0.13; EC, IRR 0.43, CI 0.40-0.46) than for women without these diagnoses. CONCLUSIONS: One in about 250 women started treatment with HT after being diagnosed with BC, PE or EC. Swedish prescribers seem to be well aware of the recommendations for HT use in women with contraindications. A few women, however, are prescribed HT despite having BC, EC or PE, possibly after careful evaluation of the risks and benefits and giving informed consent. Women with a history of PE were prescribed transdermal HT to a larger extent than women in general, in line with results from observational studies.


Assuntos
Neoplasias da Mama/epidemiologia , Contraindicações de Medicamentos , Neoplasias do Endométrio/epidemiologia , Terapia de Reposição de Estrogênios/estatística & dados numéricos , Embolia Pulmonar/epidemiologia , Sistema de Registros , Idoso , Estudos de Coortes , Terapia de Reposição de Estrogênios/métodos , Feminino , Ginecologia , Humanos , Pessoa de Meia-Idade , Farmacoepidemiologia , Estudos Retrospectivos , Suécia/epidemiologia , Adesivo Transdérmico
8.
Dermatol Online J ; 25(1)2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30710894

RESUMO

Hormone replacement therapy has been shown to be effective in alleviating menopausal symptoms. However, its use is controversial owing to potential health risks, such as thromboembolism and cancer. Bioidentical hormone therapy has recently become popular as an alternative to conventional hormone replacement therapy. These bioidentical hormones have a molecular structure identical to endogenous hormones found in a woman's body. A claimed advantage of bioidentical hormone therapy is the compounding practice in order to individualize therapy depending on patient's own hormone levels and symptoms. However, there is no scientific evidence to assess the validity of these claims. Bioidentical hormone therapy has also been used by dermatologists for its anti-aging effects on the skin, but little is known about efficacy and side effects of bioidentical hormones in this field. This review illustrates the main purpose of bioidentical hormone therapy for dermatological uses and its potential side effects, serving as a tool for dermatologists when facing these patients.


Assuntos
Terapia de Reposição de Estrogênios/métodos , Menopausa , Envelhecimento da Pele , Dermatologia , Composição de Medicamentos , Estradiol/uso terapêutico , Estrogênios/uso terapêutico , Feminino , Terapia de Reposição Hormonal/métodos , Humanos , Progesterona/uso terapêutico , Progestinas/uso terapêutico , Equivalência Terapêutica
9.
Endocrinology ; 160(4): 899-914, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30753523

RESUMO

Whether hormone replacement therapy has beneficial metabolic effects in postmenopausal women remains controversial because of between-study differences in menopausal duration, estrogen formulations, and diet. Additionally, animal studies have not reflected the typical human obesogenic, Western-style diet (WSD). In this study, we determined the effects of immediate 17ß-estradiol (ImE) or delayed 17ß-estradiol treatment on weight and metabolism parameters in old ovo-hysterectomized rhesus macaques consuming a WSD over a 30-month period. The placebo and ImE groups exhibited progressive gains in weight and fat mass, which ImE initially attenuated but did not prevent. Progression of insulin resistance (IR) was lessened by ImE compared with placebo under both fasting and IV glucose-stimulated conditions, plateauing in all groups between 24 and 30 months. Consequently, relative euglycemia was maintained through lower stimulated insulin levels with ImE than with placebo. Bone mineral density decreased in the placebo group but was maintained in the ImE group, whereas bone mineral content was unaffected by placebo and increased with ImE. Daily activity was reduced while macaques consumed a WSD and was not affected by ImE. Over time, total cholesterol, triglyceride, very-low-density cholesterol, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and IL-8 levels increased or trended upward in all animals, with only the change in HDL-C affected by ImE. Delayed estrogen treatment (months 24 to 30) had no significant impact on body composition or glucometabolic parameters. In summary, detrimental WSD-induced changes in body composition and metabolism were only temporarily ameliorated by ImE, with the important exception of glucose homeostasis, which benefited from E replacement even as body composition worsened.


Assuntos
Composição Corporal/fisiologia , Metabolismo Energético/fisiologia , Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios/métodos , Pós-Menopausa/metabolismo , Animais , Glicemia/metabolismo , Composição Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Densidade Óssea/efeitos dos fármacos , Dieta , Dieta Ocidental , Metabolismo Energético/efeitos dos fármacos , Feminino , Insulina/sangue , Resistência à Insulina/fisiologia , Macaca , Pós-Menopausa/efeitos dos fármacos
11.
Expert Opin Investig Drugs ; 28(3): 235-247, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30677323

RESUMO

INTRODUCTION: Menopausal symptoms have a substantial effect on the quality of life of many women; hence, investigations for the amelioration of menopausal symptoms continue to be necessary. The two main approaches to the amelioration of symptoms are hormone therapy (HT) and non-hormonal therapy. AREAS COVERED: This review provides a background for understanding the types of menopausal symptoms and their underlying physiology. The early clinical development of natural estrogen (estetrol, E4), neurokinin 3 receptor (NK3R) antagonists, and other non-hormonal therapies are covered. The status and outcome of these novel treatment modalities are also discussed. EXPERT OPINION: The recent observation in the Women's Health Initiative (WHI) trials that HT was not associated in the long-term with all-cause mortality, brings renewed interest in the development of new treatment modalities in postmenopausal women. Estetrol (E4), a native estrogen with selective action in tissues, is a potential next-generation HT with improved cardiovascular and breast safety. NK3R antagonists may become an interesting new modality for the amelioration of hot flushes in women with contraindications to estrogens.


Assuntos
Desenvolvimento de Medicamentos/métodos , Drogas em Investigação/administração & dosagem , Menopausa , Administração Oral , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Drogas em Investigação/farmacologia , Terapia de Reposição de Estrogênios/métodos , Feminino , Fogachos/tratamento farmacológico , Fogachos/etiologia , Humanos , Qualidade de Vida
12.
Menopause ; 26(6): 637-642, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30601452

RESUMO

OBJECTIVE: To characterize the impact of TX-001HR on the relationship between vasomotor symptom (VMS) improvement and quality of life and sleep. METHODS: REPLENISH (NCT01942668) was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial, which evaluated four daily doses of 17ß-estradiol and progesterone (E2/P4) combined in a single, oral, softgel capsule in postmenopausal women (40-65 years) with a uterus and moderate to severe VMS (≥7/day or ≥50/week). In post hoc analyses, growth models were used to examine relationships between linear changes in VMS frequency and severity over 12 weeks and changes from baseline in the Menopause-Specific Quality of Life (MENQOL; total score and VMS domain) and the Medical Outcomes Study-Sleep (total score, sleep problems indices I and II) questionnaire outcomes at 12 weeks with treatment compared with placebo. RESULTS: Outcomes with all four E2/P4 doses were combined (n = 591) and compared with placebo (n = 135). In all 5 growth models, the effects of TX-001HR on MENQOL total score and vasomotor domain were significantly associated with changes in VMS frequency and severity observed over 12 weeks (all, P < 0.001). Treatment-mediated effects on MENQOL via VMS frequency and severity models were significant. Similar results were found with Medical Outcomes Study-Sleep total score and sleep problems indices. CONCLUSIONS: TX-001HR improvements in quality of life and sleep outcomes are associated with and may be mediated through improvements in VMS frequency and severity.


Assuntos
Estradiol/administração & dosagem , Estradiol/uso terapêutico , Terapia de Reposição de Estrogênios/métodos , Fogachos/tratamento farmacológico , Pós-Menopausa , Progesterona/administração & dosagem , Progesterona/uso terapêutico , Qualidade de Vida , Sono/efeitos dos fármacos , Administração Oral , Adulto , Idoso , Método Duplo-Cego , Hiperplasia Endometrial , Feminino , Humanos , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do Tratamento , Útero/fisiologia
13.
Technol Health Care ; 27(1): 49-59, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30475776

RESUMO

BACKGROUND: The diversity of the results of different hormone replacement therapy (HRT) protocols and the fuzziness of the conclusions have caused problems in routine clinical practice. OBJECTIVE: To develop an intelligent decision-making system for HRT specifically is appropriate as we use the abbrevation HRT in the background section in menopausal women in order to assist physicians. METHODS: This study consisted of 179 peri- and post-menopausal patients who were admitted to Hacettepe University Hospital (between 1996 and 2001) with various menopausal complaints. Database variables used in this study were age, height, weight, menopause duration, clinical condition, HRT duration, and the laboratory test results. Our newly developed multiple-centered fuzzy clustering (MCFC) algorithm was applied to the medical data set to differentiate patient groups. Finally, a hybrid intelligent decision-making system was developed by combining knowledge-based algorithms and the MCFC algorithm results. RESULTS: We have used Fuzzy C-means, K-means, Hard C-means, similarity based clustering, and MCFC algorithms on the medical data set and have determined that the MCFC algorithm is the most appropriate algorithm for our medical model. We have defined 5 clusters and 16 cluster centers. A diagnostic phrase was assigned to each cluster center by the physician and these clusters together with knowledge-based algorithms were used for the decision-making system. CONCLUSIONS: We have developed a computerized hybrid decision-making system recommending HRT to peri- and post-menopausal women in order to assist and protect physicians.


Assuntos
Quimioterapia Assistida por Computador/métodos , Terapia de Reposição de Estrogênios/métodos , Algoritmos , Estradiol/administração & dosagem , Estradiol/uso terapêutico , Estrogênios Conjugados (USP)/uso terapêutico , Feminino , Lógica Fuzzy , Humanos , Pessoa de Meia-Idade , Adesivo Transdérmico
14.
Blood Coagul Fibrinolysis ; 30(1): 17-23, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30507711

RESUMO

: Postmenopausal hormone therapy increases the risk of venous thrombosis. Sex hormone binding globulin (SHBG) is a suggested marker of 'total estrogenicity'. The study objective was to evaluate the impact of hormone therapy on SHBG and the association with coagulation variables. The study populations comprised 202 healthy postmenopausal women randomized to treatment with low-dose or conventional-dose hormone therapy, tibolone or raloxifene (RET-study) and 140 women with a history of venous thrombosis randomized to conventional-dose hormone therapy or placebo (EVTET-study). SHBG was determined in serum collected at baseline and after 12 weeks. In healthy women, conventional-dose hormone therapy increased SHBG with mean 9.7 (95% confidence interval 4.8-14.5) nmol/l, low-dose hormone therapy by mean 5.9 (0.4-11.5) nmol/l, raloxifene by mean 7.2 (3.9-10.4) nmol/l, while tibolone reduced SHBG with mean -25.1 (-29.9 to -20.4) nmol/l. SHBG correlated with protein S, tissue factor pathway inhibitor (TFPI) and protein C at baseline, and with protein S and TFPI after 12 weeks, but the change in SHBG from baseline to 12 weeks was only associated with the change in activated protein C (APC) resistance. In women with a history of venous thrombosis, the mean increase in SHBG was 13.6 (8.4-18.9) nmol/l in the conventional-dose hormone therapy group, with no change in the placebo group. Baseline SHBG was higher among women who developed recurrent venous thrombosis on conventional-dose hormone therapy. SHBG correlated with several coagulation inhibitors, but the change in SHBG induced by postmenopausal hormone therapy was only associated with the change in APC resistance.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Terapia de Reposição de Estrogênios/métodos , Globulina de Ligação a Hormônio Sexual/efeitos dos fármacos , Trombose Venosa/tratamento farmacológico , Resistência à Proteína C Ativada/sangue , Moduladores de Receptor Estrogênico/farmacologia , Moduladores de Receptor Estrogênico/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Norpregnenos , Pós-Menopausa/sangue , Cloridrato de Raloxifeno , Globulina de Ligação a Hormônio Sexual/análise
15.
J Clin Endocrinol Metab ; 104(2): 293-300, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30272234

RESUMO

Context: The Early vs Late Intervention Trial with Estradiol showed that hormone therapy (HT) reduced progression of atherosclerosis when initiated in early but not in late postmenopause. Objective: This posttrial analysis examined the association between plasma estradiol (E2) levels and atherosclerosis determined by rate of change in carotid artery intima-media thickness (CIMT) and tested whether this association is equally evident in early (<6 years) vs late (≥10 years) postmenopause. Design: Randomized controlled trial stratified by time since menopause (ClinicalTrials.gov no. NCT00114517). Mixed-effects linear models tested the association of E2 levels with CIMT rate of change. Setting: Los Angeles, California. Participants: Healthy women in postmenopause. Intervention: Oral E2 with/without cyclic vaginal progesterone. Main Outcome Measures: Plasma E2 levels and CIMT assessed every 6 months over an average of 4.8 years. Results: Among 596 women in postmenopause, higher E2 level was inversely associated with CIMT progression in those in early postmenopause (P = 0.041) and positively associated with CIMT progression in those in late postmenopause (P = 0.006) (P for interaction <0.001). CIMT progression rates for the lowest vs highest quartile of E2 levels among women in early postmenopause were 8.5 and 7.2 µm/y, respectively , whereas among women in late postmenopause they were 9.8 and 11.7 µm/y, respectively. Conclusion: E2 levels were differentially associated with atherosclerosis progression according to timing of HT initiation. With higher E2 levels, CIMT progression rate was decreased among women in early postmenopause but increased among women in late postmenopause. These results support the timing hypothesis of HT initiation on cardiovascular benefit, with reduced atherosclerosis progression for initiation during early postmenopause.


Assuntos
Aterosclerose/sangue , Aterosclerose/prevenção & controle , Estradiol/sangue , Terapia de Reposição de Estrogênios/métodos , Idoso , Espessura Intima-Media Carotídea , Progressão da Doença , Método Duplo-Cego , Esquema de Medicação , Estradiol/administração & dosagem , Estradiol/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa/sangue , Fatores de Tempo
16.
Int J Cancer ; 144(4): 730-740, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30183089

RESUMO

The WHI found an unexpected reduced breast cancer risk in women using CEE alone. We hypothesized CEE alone induces estrogen hydroxylation along the 2-pathway rather than the competing 16-pathway, a pattern linked to reduced postmenopausal breast cancer risk. One thousand eight hundred and sixty-four women in a WHIOS case-control study of estrogen metabolism and ovarian and endometrial cancer were studied of whom 609 were current E + P users (351 used CEE + MPA), while 272 used E alone (162 used CEE). Fifteen EM were measured, and analyses were conducted for each metabolite, hydroxylation pathway (2-, 4-, or 16-pathway) and ratios of pathway concentrations using inverse probability weighted linear regression. Compared to E + P users, all EM were higher in E alone users (significant for unconjugated estrone, total/conjugated estradiol, total/unconjugated 2-methoxyestrone, 4-methoxyestrone and unconjugated estriol). The relative concentrations of 2- and 4-pathway EM did not differ between the MHT users (2-pathway EM comprised 15% and 4-pathway EM <2% of the total), but 16-pathway EM were lower in E alone users (p = 0.036). Ratios of 2- and 4-pathway EM compared to 16-pathway EM were significantly higher in E alone compared to E + P users. Similar but not significant patterns were observed in CEE-alone and CEE + MPA users. Our data suggest that compared to E + P users, women using E alone have more extensive metabolism via the 2- vs. the competing 16-pathway. This is consistent with epidemiologic evidence of reduced postmenopausal breast cancer risk associated with this metabolic profile and may provide a clue to the breast cancer risk reduction in CEE alone users during the WHI.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Terapia de Reposição de Estrogênios/métodos , Estrogênios/administração & dosagem , Pós-Menopausa , Progestinas/administração & dosagem , Idoso , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Quimioterapia Combinada , Estrogênios/metabolismo , Estrogênios Conjugados (USP)/administração & dosagem , Feminino , Humanos , Acetato de Medroxiprogesterona/administração & dosagem , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento
17.
Int Urogynecol J ; 30(2): 251-256, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29946829

RESUMO

INTRODUCTION AND HYPOTHESIS: The impact of estradiol-based hormone therapy (HT) on the incidence of stress urinary incontinence (SUI) is unknown. Therefore, we compared the use of such HT regimens and tibolone in women with and without SUI. METHODS: The women with a history of SUI operation (N = 15,002) were identified from the Finnish National Hospital Discharge Register, and the control women without such an operation (N = 44,389) from the Finnish Central Population Register. The use of HT was traced from the National Drug Reimbursement Register, and the odd ratios (ORs) with 95% confidence intervals (95% CIs) for SUI were calculated by using the conditional logistic regression analysis. RESULTS: The cases had used any HT more often than the controls. The use of systemic estradiol-only or estradiol-progestin therapy was accompanied by an increased SUI risk (OR 3.8, 95% CI: 3.6-4.0 and OR 2.7, 95% CI: 2.6-2.9 respectively). The use of estradiol with noretisterone acetate showed a higher risk of increase than that with medroxyprogesterone acetate. Age over 55 years at the initiation of systemic HT was accompanied by a higher SUI risk increase than that under 55 years of age. The use of tibolone, an estradiol + levonorgestrel-releasing intrauterine device, or vaginal estradiol also increased the risk. CONCLUSIONS: The use of HT regimens may predispose to the de novo development or worsening of pre-existing SUI. Thus, caution is needed when these regimens are prescribed to women with mild stress-related urine leakage or with established SUI risk factors.


Assuntos
Estradiol/efeitos adversos , Terapia de Reposição de Estrogênios/efeitos adversos , Estrogênios/efeitos adversos , Norpregnenos/efeitos adversos , Incontinência Urinária por Estresse/epidemiologia , Terapia de Reposição de Estrogênios/métodos , Feminino , Finlândia/epidemiologia , Humanos , Pessoa de Meia-Idade , Pós-Menopausa/efeitos dos fármacos , Sistema de Registros , Fatores de Risco , Incontinência Urinária por Estresse/induzido quimicamente
18.
Prim Care ; 45(4): 625-641, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30401346

RESUMO

The menopausal transition is a time when many physical and psychological changes are occurring for women. Women may experience irregular menses, vasomotor symptoms, sleep disruption, mood disorders as well as genitourinary symptoms. Despite irregular menstrual cycles, some women can still conceive. It is important to understand what is within normal physiologic changes and what may represent pathologic changes and how to further evaluate this. There are many options available to manage menopausal symptoms when they are impacting quality of life.


Assuntos
Menopausa/fisiologia , Atenção Primária à Saúde/organização & administração , Saúde da Mulher , Anticoncepção/métodos , Neoplasias do Endométrio/fisiopatologia , Terapia de Reposição de Estrogênios/métodos , Feminino , Gabapentina/uso terapêutico , Fogachos/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Transtornos do Humor/tratamento farmacológico , Gravidez , Gravidez não Planejada , Qualidade de Vida , Fatores de Risco , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/terapia
19.
Int J Pharm Compd ; 22(6): 504-511, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30384351

RESUMO

Estrogen replacement therapy is often recommended when female patients present with lower than normal physiologic levels, such as patients going through menopause. The physical and chemical stability of estriol 0.25 mg/g and 10 mg/g vaginal creams (VersaBase) was tested over a period of 182 days, at room temperature and refrigerated conditions, in order to determine the corresponding beyond-use date. The physical characterization consisted in observing all samples for color/appearance and odor, and testing for pH, whereas the chemical characterization consisted in ultra-performance liquid chromatography assay testing. Both vaginal creams were proven physically and chemically stable, and the ultra-performance liquid chromatography method was proven stability indicating. As a result, the beyond-use date of the estriol 0.025% to 1% vaginal creams (VersaBase), in electronic mortar and pestle plastic jars, is six months at both room temperature and refrigerated conditions.


Assuntos
Estriol/química , Terapia de Reposição de Estrogênios/métodos , Bases para Pomadas/química , Administração Intravaginal , Composição de Medicamentos , Estabilidade de Medicamentos , Estriol/administração & dosagem , Feminino , Humanos , Temperatura , Fatores de Tempo
20.
Curr Atheroscler Rep ; 20(12): 57, 2018 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-30350133

RESUMO

PURPOSE OF REVIEW: Cardiovascular disease (CVD) is known to be an increasing cause of mortality among women, particularly postmenopausal women. Hormone replacement therapy (HRT) is a topic that has been investigated over the past decade for its known impact on the cardiovascular system. This review summarizes the evidence and current opinion on the associations between HRT and CVD, evidence both supporting and against HRT use as a prevention to the development of coronary heart disease (CHD). RECENT FINDINGS: The majority of the new data available suggests the use of HRT has the potential to be more beneficial in the prevention of CVD if started in women at younger ages. Current studies also suggest that while starting HRT in older postmenopausal women may be associated with an initial slight increase in CVD, the overall lifetime occurrence rate is not increased. Several studies have also started to use the "timing hypothesis" to suggest that HRT initiated soon after menopause has the potential of being the greatest cardiovascular benefit to the patient. Overall, the data support the finding that HRT should be used only for symptomatic treatment, not in an attempt to slow progression of CVD. Current evidence does not support the use of HRT for either primary or secondary prevention of CHD. HRT has different implications based on the temporal relationship in which it is initiated in relation to the onset of menopause. Overall, the use of HRT should be an individualized decision with each patient on the basis of the individual's symptoms and overall risk profile.


Assuntos
Doença das Coronárias/prevenção & controle , Terapia de Reposição de Estrogênios , Menopausa , Terapia de Reposição de Estrogênios/efeitos adversos , Terapia de Reposição de Estrogênios/métodos , Feminino , Humanos , Medição de Risco
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