Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.796
Filtrar
1.
N Engl J Med ; 382(4): 328-340, 2020 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-31971678

RESUMO

BACKGROUND: Uterine fibroids are hormone-responsive neoplasms that are associated with heavy menstrual bleeding. Elagolix, an oral gonadotropin-releasing hormone antagonist resulting in rapid, reversible suppression of ovarian sex hormones, may reduce fibroid-associated bleeding. METHODS: We conducted two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials (Elaris Uterine Fibroids 1 and 2 [UF-1 and UF-2]) to evaluate the efficacy and safety of elagolix at a dose of 300 mg twice daily with hormonal "add-back" therapy (to replace reduced levels of endogenous hormones; in this case, estradiol, 1 mg, and norethindrone acetate, 0.5 mg, once daily) in women with fibroid-associated bleeding. An elagolix-alone group was included to assess the impact of add-back therapy on the hypoestrogenic effects of elagolix. The primary end point was menstrual blood loss of less than 80 ml during the final month of treatment and at least a 50% reduction in menstrual blood loss from baseline to the final month; missing data were imputed with the use of multiple imputation. RESULTS: A total of 412 women in UF-1 and 378 women in UF-2 underwent randomization, received elagolix or placebo, and were included in the analyses. Criteria for the primary end point were met in 68.5% of 206 women in UF-1 and in 76.5% of 189 women in UF-2 who received elagolix plus add-back therapy, as compared with 8.7% of 102 women and 10% of 94 women, respectively, who received placebo (P<0.001 for both trials). Among the women who received elagolix alone, the primary end point was met in 84.1% of 104 women in UF-1 and in 77% of 95 women in UF-2. Hot flushes (in both trials) and metrorrhagia (in UF-1) occurred significantly more commonly with elagolix plus add-back therapy than with placebo. Hypoestrogenic effects of elagolix, especially decreases in bone mineral density, were attenuated with add-back therapy. CONCLUSIONS: Elagolix with add-back therapy was effective in reducing heavy menstrual bleeding in women with uterine fibroids. (Funded by AbbVie; Elaris UF-1 and Elaris UF-2 ClinicalTrials.gov numbers, NCT02654054 and NCT02691494.).


Assuntos
Estradiol/uso terapêutico , Estrogênios/uso terapêutico , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hidrocarbonetos Fluorados/uso terapêutico , Leiomioma/complicações , Menorragia/tratamento farmacológico , Pirimidinas/uso terapêutico , Adulto , Densidade Óssea/efeitos dos fármacos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Fogachos/induzido quimicamente , Humanos , Hidrocarbonetos Fluorados/efeitos adversos , Menorragia/etiologia , Pessoa de Meia-Idade , Pirimidinas/efeitos adversos , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e Questionários
2.
J Med Case Rep ; 13(1): 321, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31665081

RESUMO

BACKGROUND: Infertility continues to be an enigmatic and emerging problem. Although in vitro fertilization has proved to be revolutionary and immensely beneficial to many people, it is far from perfect, and many women experience recurrent in vitro fertilization failures. There can be a multitude of factors involved in recurrent in vitro fertilization failures. The aim of this report was to explore the role of hysteroscopy in determining potential causes of in vitro fertilization failure and how the relevant hysteroscopic findings can address the issue of infertility in terms of a subsequent successful in vitro fertilization. CASE PRESENTATION: A 37-year-old white Arab woman with a history of eight in vitro fertilization failures and one curettage performed for a blighted ovum presented to our hospital because of inability to conceive. Her past medical history was significant for hypothyroidism and positive factor V Leiden. She underwent hystero contrast sonography, which revealed a normal uterine cavity with irregular fillings in the right corner. To explore this further, hysteroscopy was performed, which showed dense adhesions in the right upper corner and first-degree adhesions in the lower half of the uterus. After undergoing adhesiolysis and a cycle of estradiol valerate and progesterone, the patient successfully conceived twins. CONCLUSIONS: Hysteroscopy may play an important role before or in conjunction with assisted reproductive techniques to help infertile women and couples achieve their goals of pregnancy and live birth of a child.


Assuntos
Fertilização In Vitro/efeitos adversos , Histeroscopia , Gravidez de Gêmeos , Aderências Teciduais/cirurgia , Doenças Uterinas/cirurgia , Adulto , Amenorreia/complicações , Estradiol/uso terapêutico , Estrogênios/uso terapêutico , Feminino , Humanos , Infertilidade Feminina/etiologia , Infertilidade Feminina/terapia , Gravidez , Progesterona/uso terapêutico , Progestinas/uso terapêutico , Aderências Teciduais/diagnóstico por imagem , Falha de Tratamento , Doenças Uterinas/diagnóstico por imagem
3.
Lancet ; 394(10204): 1159-1168, 2019 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-31474332

RESUMO

BACKGROUND: Published findings on breast cancer risk associated with different types of menopausal hormone therapy (MHT) are inconsistent, with limited information on long-term effects. We bring together the epidemiological evidence, published and unpublished, on these associations, and review the relevant randomised evidence. METHODS: Principal analyses used individual participant data from all eligible prospective studies that had sought information on the type and timing of MHT use; the main analyses are of individuals with complete information on this. Studies were identified by searching many formal and informal sources regularly from Jan 1, 1992, to Jan 1, 2018. Current users were included up to 5 years (mean 1·4 years) after last-reported MHT use. Logistic regression yielded adjusted risk ratios (RRs) comparing particular groups of MHT users versus never users. FINDINGS: During prospective follow-up, 108 647 postmenopausal women developed breast cancer at mean age 65 years (SD 7); 55 575 (51%) had used MHT. Among women with complete information, mean MHT duration was 10 years (SD 6) in current users and 7 years (SD 6) in past users, and mean age was 50 years (SD 5) at menopause and 50 years (SD 6) at starting MHT. Every MHT type, except vaginal oestrogens, was associated with excess breast cancer risks, which increased steadily with duration of use and were greater for oestrogen-progestagen than oestrogen-only preparations. Among current users, these excess risks were definite even during years 1-4 (oestrogen-progestagen RR 1·60, 95% CI 1·52-1·69; oestrogen-only RR 1·17, 1·10-1·26), and were twice as great during years 5-14 (oestrogen-progestagen RR 2·08, 2·02-2·15; oestrogen-only RR 1·33, 1·28-1·37). The oestrogen-progestagen risks during years 5-14 were greater with daily than with less frequent progestagen use (RR 2·30, 2·21-2·40 vs 1·93, 1·84-2·01; heterogeneity p<0·0001). For a given preparation, the RRs during years 5-14 of current use were much greater for oestrogen-receptor-positive tumours than for oestrogen-receptor-negative tumours, were similar for women starting MHT at ages 40-44, 45-49, 50-54, and 55-59 years, and were attenuated by starting after age 60 years or by adiposity (with little risk from oestrogen-only MHT in women who were obese). After ceasing MHT, some excess risk persisted for more than 10 years; its magnitude depended on the duration of previous use, with little excess following less than 1 year of MHT use. INTERPRETATION: If these associations are largely causal, then for women of average weight in developed countries, 5 years of MHT, starting at age 50 years, would increase breast cancer incidence at ages 50-69 years by about one in every 50 users of oestrogen plus daily progestagen preparations; one in every 70 users of oestrogen plus intermittent progestagen preparations; and one in every 200 users of oestrogen-only preparations. The corresponding excesses from 10 years of MHT would be about twice as great. FUNDING: Cancer Research UK and the Medical Research Council.


Assuntos
Neoplasias da Mama/epidemiologia , Estrogênios/uso terapêutico , Progesterona/uso terapêutico , Progestinas/uso terapêutico , Adulto , Idoso , Quimioterapia Combinada , Terapia de Reposição de Estrogênios , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Obesidade/epidemiologia , Análise de Componente Principal , Risco , Fatores de Risco , Fatores de Tempo
4.
Pediatrics ; 144(3)2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31383814

RESUMO

BACKGROUND: Fertility preservation enables patients undergoing gonadotoxic therapies to retain the potential for biological children and now has broader implications in the care of transgender individuals. Multiple medical societies recommend counseling on fertility preservation before initiating therapy for gender dysphoria; however, outcome data pre- and posttreatment are limited in feminizing transgender adolescents and young adults. METHODS: The University of Pittsburgh Institutional Research Board approved this study. Data were collected retrospectively on transgender patients seeking fertility preservation between 2015 and 2018, including age at initial consultation and semen analysis parameters. RESULTS: Eleven feminizing transgender patients accepted a referral for fertility preservation during this time; consultation occurred at median age 19 (range 16-24 years). Ten patients attempted and completed at least 1 semen collection. Eight patients cryopreserved semen before initiating treatment. Of those patients, all exhibited low morphology with otherwise normal median semen analysis parameters. In 1 patient who discontinued leuprolide acetate to attempt fertility preservation, transient azoospermia of 5 months' duration was demonstrated with subsequent recovery of spermatogenesis. In a patient who had previously been treated with spironolactone and estradiol, semen analysis revealed persistent azoospermia for the 4 months leading up to orchiectomy after discontinuation of both medications. CONCLUSIONS: Semen cryopreservation is a viable method of fertility preservation in adolescent and young adult transgender individuals and can be considered in patients who have already initiated therapy for gender dysphoria. Further research is needed to determine the optimal length of time these therapies should be discontinued to facilitate successful semen cryopreservation.


Assuntos
Criopreservação/métodos , Preservação da Fertilidade/métodos , Disforia de Gênero/terapia , Sêmen , Adolescente , Aconselhamento , Estradiol/uso terapêutico , Estrogênios/uso terapêutico , Feminino , Disforia de Gênero/psicologia , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Masculino , Estudos Retrospectivos , Espironolactona/uso terapêutico , Adulto Jovem
5.
Ann Intern Med ; 171(1): ITC1-ITC16, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31261405

RESUMO

Transgender persons are a diverse group whose gender identity differs from their sex recorded at birth. Some choose to undergo medical treatment to align their physical appearance with their gender identity. Barriers to accessing appropriate and culturally competent care contribute to health disparities in transgender persons, such as increased rates of certain types of cancer, substance abuse, mental health conditions, infections, and chronic diseases. Thus, it is important that clinicians understand the specific medical issues that are relevant to this population.


Assuntos
Atenção Primária à Saúde/métodos , Pessoas Transgênero , Transexualismo/terapia , Confidencialidade , Aconselhamento , Estrogênios/efeitos adversos , Estrogênios/uso terapêutico , Ética Médica , Fertilidade , Infecções por HIV/prevenção & controle , Humanos , Monitorização Fisiológica , Educação de Pacientes como Assunto , Papel do Médico , Puberdade , Encaminhamento e Consulta , Procedimentos de Readequação Sexual , Terminologia como Assunto , Testosterona/efeitos adversos , Testosterona/uso terapêutico , Pessoas Transgênero/classificação , Pessoas Transgênero/legislação & jurisprudência , Pessoas Transgênero/psicologia , Transexualismo/classificação , Transexualismo/psicologia
6.
Discov Med ; 27(149): 177-188, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31361980

RESUMO

Genistein is an isoflavone derived from soy-rich products, which is known to exhibit several beneficial biological effects, such as anti-tumor activity, improvement of glucose metabolism, and reduction of the frequency of peri-menopausal hot flashes, and thus has potential for clinical application. Certain limitations and side effects, such as low bioavailability, biological estrogenic activity, and detrimental effects on thyroid function, have restricted its clinical applications to some extent. Recently, it has been reported that fermentation, use of micromicelles, and modification of its chemical structure can enhance the bioavailability of genistein. Moreover, the modification of its molecular structure may also eliminate its biological estrogenic activity and adverse effects on thyroid function. In this review, we summarize the clinical application prospects and limitations of genistein, as well as the plausible solutions to overcome its low bioavailability, phytoestrogenic activity, and adverse effects on thyroid function.


Assuntos
Antineoplásicos Fitogênicos , Estrogênios , Genisteína , Fogachos/tratamento farmacológico , Menopausa/metabolismo , Glândula Tireoide/metabolismo , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/farmacologia , Estrogênios/farmacocinética , Estrogênios/uso terapêutico , Feminino , Genisteína/farmacocinética , Genisteína/uso terapêutico , Fogachos/metabolismo , Fogachos/patologia , Humanos , Micelas
7.
Maturitas ; 126: 34-37, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31239115

RESUMO

This review discusses established transgender individuals on hormones who have reached their desired post-pubertal phenotype. Current guidelines have not clearly integrated specific considerations for the older population. This review focuses on changes in physiology with age, recommended maintenance therapy and safety evaluation to mitigate the risks of hormone therapy with a focus on the older population.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Estrogênios/uso terapêutico , Testosterona/uso terapêutico , Pessoas Transgênero , Humanos , Procedimentos de Readequação Sexual
8.
Int J Mol Sci ; 20(12)2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31242705

RESUMO

In women, oral menopausal hormonal therapy (MHT) is associated with adverse effects including an increased incidence of thromboembolic events, classically attributed to an increase in several liver-derived coagulation factors due to hepatic first pass. While platelets are central players in thrombus constitution, their implication in women treated with estrogens remains incompletely characterized. Platelets and their medullar progenitors, megakaryocytes, express estrogen receptors (ER) that may explain, at least in part, a sensitivity to hormonal changes. The purpose of this review is to summarize our current knowledge of estrogen actions on platelets and megakaryocytes in mice following in vivo administration and in women using MHT.


Assuntos
Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Estrogênios/farmacologia , Megacariócitos/efeitos dos fármacos , Megacariócitos/metabolismo , Animais , Estrogênios/uso terapêutico , Feminino , Humanos , Ativação Plaquetária/efeitos dos fármacos , Fatores Sexuais , Trombopoese/efeitos dos fármacos
9.
Biomed Pharmacother ; 117: 109114, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31207575

RESUMO

BACKGROUND: Lily bulb is often used as a dietary supplement for menopause. This study was aimed to investigate the ameliorative effects of aqueous extract of lily bulb (AELB) on the menopause-associated psychiatric disorders and the underlying mechanisms in comparison with estrogen therapy. METHODS: Ovariectomized (OVX) mice were treated with 1.8 g/kg AELB or 0.3 mg/kg estradiol for 5 weeks. Animals were tested in multiple behavioral paradigms. Serum, uterus, and brain tissues were collected for the measurement of neurotransmitters and their related biomarkers, neurotrophins, and estrogen receptor α (ERα) and ß (ERß). RESULTS: AELB and estradiol had similar anxiolytic, antidepressant, and cognition-improving effects. While estradiol limited OVX-induced weight gains and prevented uterine shrinkage and the drop of serum estrogen level, AELB had minor and even no effects on these indices. AELB, but not estradiol, reversed OVX-induced decreases in the expression levels of hippocampal nerve growth factor (NGF) and prefrontal glial cell-derived neurotrophic factor (GDNF). In addition to hypothalamic and prefrontal ERα, AELB enhanced uterine and brain regional ERß expression levels without affecting uterine ERα, NGF, and GDNF. Conversely, estradiol completely restored the expression levels of estrogen receptors and neurotrophins in uterus. CONCLUSIONS: While AELB is comparable to estradiol in alleviating menopause-like behavior, it has distinct brain-uterus mechanisms in association with the predominant protection of catecholamine synthesis, neurotrophins, and ERß receptors in brain, but with minor effects on uterus. AELB and its constituents may be novel treatments for menopause.


Assuntos
Comportamento Animal , Encéfalo/fisiologia , Estrogênios/uso terapêutico , Lilium/química , Menopausa/efeitos dos fármacos , Ovariectomia , Extratos Vegetais/farmacologia , Útero/fisiologia , Animais , Ansiedade/complicações , Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Cognição , Depressão/complicações , Dopamina/metabolismo , Estradiol/sangue , Feminino , Terapia de Reposição Hormonal , Menopausa/sangue , Metaboloma , Camundongos Endogâmicos C57BL , Fatores de Crescimento Neural/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Receptores Estrogênicos/metabolismo , Serotonina/metabolismo , Útero/efeitos dos fármacos , Água
11.
BMJ ; 365: l1652, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31088823

RESUMO

OBJECTIVE: To investigate the incidence and characteristics of breast cancer in transgender people in the Netherlands compared with the general Dutch population. DESIGN: Retrospective, nationwide cohort study. SETTING: Specialised tertiary gender clinic in Amsterdam, the Netherlands. PARTICIPANTS: 2260 adult trans women (male sex assigned at birth, female gender identity) and 1229 adult trans men (female sex assigned at birth, male gender identity) who received gender affirming hormone treatment. MAIN OUTCOME MEASURES: Incidence and characteristics (eg, histology, hormone receptor status) of breast cancer in transgender people. RESULTS: The total person time in this cohort was 33 991 years for trans women and 14 883 years for trans men. In the 2260 trans women in the cohort, 15 cases of invasive breast cancer were identified (median duration of hormone treatment 18 years, range 7-37 years). This was 46-fold higher than in cisgender men (standardised incidence ratio 46.7, 95% confidence interval 27.2 to 75.4) but lower than in cisgender women (0.3, 0.2 to 0.4). Most tumours were of ductal origin and oestrogen and progesterone receptor positive, and 8.3% were human epidermal growth factor 2 (HER2) positive. In 1229 trans men, four cases of invasive breast cancer were identified (median duration of hormone treatment 15 years, range 2-17 years). This was lower than expected compared with cisgender women (standardised incidence ratio 0.2, 95% confidence interval 0.1 to 0.5). CONCLUSIONS: This study showed an increased risk of breast cancer in trans women compared with cisgender men, and a lower risk in trans men compared with cisgender women. In trans women, the risk of breast cancer increased during a relatively short duration of hormone treatment and the characteristics of the breast cancer resembled a more female pattern. These results suggest that breast cancer screening guidelines for cisgender people are sufficient for transgender people using hormone treatment.


Assuntos
Neoplasias da Mama/epidemiologia , Estrogênios/efeitos adversos , Transexualismo/tratamento farmacológico , Adulto , Antagonistas de Androgênios/uso terapêutico , Neoplasias da Mama Masculina/epidemiologia , Estrogênios/uso terapêutico , Feminino , Humanos , Incidência , Masculino , Países Baixos/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Testosterona/uso terapêutico , Adulto Jovem
12.
Eur J Med Chem ; 177: 116-143, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31129450

RESUMO

Breast cancer, a most common malignancy in women, was known to be associated with steroid hormone estrogen. The discovery of estrogen receptor (ER) gave us not only a powerful predictive and prognostic marker, but also an efficient target for the treatment of hormone-dependent breast cancer with various estrogen ligands. ER consists of two subtypes i.e. ERα and ERß, that are mostly G-protein-coupled receptors and activated by estrogen, specially 17ß-estradiol. The activation is followed by translocation into the nucleus and binding with DNA to modulate activities of different genes. ERs can manage synthesis of RNA through genomic actions without directly binding to DNA. Receptors are tethered by protein-protein interactions to a transcription factor complex to communicate with DNA. Estrogens also exhibit nongenomic actions, a characteristic feature of steroid hormones, which are so rapid to be considered by the activation of RNA and translation. These are habitually related to stimulation of different protein kinase cascades. Majority of post-menopausal breast cancer is estrogen dependent, mostly potent biological estrogen (E2) for continuous growth and proliferation. Estrogen helps in regulating the differentiation and proliferation of normal breast epithelial cells. In this review we have investigated the important role of ER in development and progression of breast cancer, which is complicated by receptor's interaction with co-regulatory proteins, cross-talk with other signal transduction pathways and development of treatment strategies viz. selective estrogen receptor modulators (SERMs), selective estrogen receptor down regulators (SERDs), aromatase and sulphatase inhibitors.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Antagonistas de Estrogênios/uso terapêutico , Estrogênios/uso terapêutico , Receptores Estrogênicos/metabolismo , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Inibidores da Aromatase/química , Inibidores da Aromatase/farmacologia , Inibidores da Aromatase/uso terapêutico , Linhagem Celular Tumoral , Antagonistas de Estrogênios/química , Antagonistas de Estrogênios/farmacologia , Estrogênios/química , Estrogênios/farmacologia , Feminino , Humanos , Ligantes , Homens , Estrutura Molecular , Moduladores Seletivos de Receptor Estrogênico/química , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Transdução de Sinais/fisiologia , Sulfatases/antagonistas & inibidores
13.
Eur J Endocrinol ; 181(1): R23-R43, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31096185

RESUMO

Evidence has been accumulating that, in men, some of the biological actions traditionally attributed to testosterone acting via the androgen receptor may in fact be dependent on its aromatization to estradiol (E2). In men, E2 circulates at concentrations exceeding those of postmenopausal women, and estrogen receptors are expressed in many male reproductive and somatic tissues. Human studies contributing evidence for the role of E2 in men comprise rare case reports of men lacking aromatase or a functional estrogen receptor alpha, short-term experiments manipulating sex steroid milieu in healthy men, men with organic hypogonadism or men with prostate cancer treated with androgen deprivation therapy (ADT) and from observational studies in community-dwelling men. The collective evidence suggests that, in men, E2 is an important hormone for hypothalamic-pituitary-testicular axis regulation, reproductive function, growth hormone insulin-like growth factor-1 axis regulation, bone growth and maintenance of skeletal health, body composition and glucose metabolism and vasomotor stability. In other tissues, particularly brain, elucidation of the clinical relevance of E2 actions requires further research. From a clinical perspective, the current evidence supports the use of testosterone as the treatment of choice in male hypogonadism, rather than aromatase inhibitors (which raise testosterone and lower E2), selective androgen receptor modulators and selective estrogen receptor modulators (with insufficiently understood tissue-specific estrogenic effects). Finally, E2 treatment, either as add-back to conventional ADT or as sole mode of ADT could be a useful strategy for men with prostate cancer.


Assuntos
Estradiol/uso terapêutico , Estrogênios/uso terapêutico , Terapia de Reposição Hormonal/métodos , Hipogonadismo/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Androgênios/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Humanos , Masculino , Receptores Estrogênicos/metabolismo , Testosterona/uso terapêutico
14.
Int Immunopharmacol ; 72: 504-510, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31055232

RESUMO

Neuroendocrine changes are essential factors contributing to the progression and development of rheumatoid arthritis. However, the role of estrogen in the innate immunity during arthritis development is still controversial. Here, we evaluated the effect of estrous cycle, ovariectomy, estradiol replacement therapy and treatment with estrogen receptor (ER)α and ERß specific agonists on joint edema formation, neutrophil recruitment, and articular levels of cytokines/chemokines in murine zymosan-induced arthritis. Our results showed that articular inflammation of proestus/estrus was similar to metaestus/diestrus animals indicating that the inflammatory response in acute arthritis is not affected by the estrous cycle. However, ovariectomy increased joint swelling, neutrophil migration, and TNF-α level. Treatment for six consecutive days with estradiol cypionate re-established the acute inflammation in ovariectomized arthritic mice to responses similar to those in SHAM-proestrus/estrus or naive mice. Moreover, treatment with propylpyrazoletriol and diarylpropionitrile, two ERα and ERß selective agonists, respectively, inhibited both edema and neutrophil recruitment. Finally, the non-genomic properties of estradiol were analyzed with an acute treatment with ß-estradiol-water soluble, which reduced the edema only. In the present study, estradiol replacement therapy improves the innate immune responses in ovariectomized arthritic mice by activating nuclear estrogen receptors. These results suggest that estradiol can induce a protective anti-inflammatory effect in arthritis during ovaries failure, as observed in the menopause.


Assuntos
Artrite/tratamento farmacológico , Estradiol/uso terapêutico , Estrogênios/uso terapêutico , Terapia de Reposição Hormonal , Animais , Artrite/imunologia , Feminino , Imunidade Inata/efeitos dos fármacos , Camundongos , Neutrófilos/efeitos dos fármacos , Ovariectomia
17.
Front Neuroendocrinol ; 53: 100743, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30922675

RESUMO

More than thirty years have passed since sex and gender differences were noted in the age of onset, course and outcomes for schizophrenia. The 'estrogen hypothesis" was coined in the 1990's to describe neuroprotective effects of estrogen. Intervention studies in schizophrenia patients with estradiol and selective estrogen receptor modulators (SERMs) are promising but psychiatrists and other health practitioners do not generally take up this useful adjunctive treatment for their female patients with schizophrenia. The reasons for this are manifold, but overall a cultural shift in the practice of psychiatry is needed to recognise the specific needs of women with schizophrenia and tailor treatments, such as hormone adjuncts to improve the outcomes for this significant population. The two main aims of this article are to review the evidence and theory of estrogen treatments in schizophrenia and to recommend translation of adjunctive estrogen treatment into clinical practice for women with schizophrenia.


Assuntos
Estradiol/uso terapêutico , Estrogênios/uso terapêutico , Esquizofrenia/tratamento farmacológico , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Animais , Humanos , Fatores Sexuais , Resultado do Tratamento
18.
Ann Intern Med ; 170(7): 465-479, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30884526

RESUMO

Background: Urinary incontinence (UI), a common malady in women, most often is classified as stress, urgency, or mixed. Purpose: To compare the effectiveness of pharmacologic and nonpharmacologic interventions to improve or cure stress, urgency, or mixed UI in nonpregnant women. Data Sources: MEDLINE, Cochrane Central Register of Controlled Trials (Wiley), Cochrane Database of Systematic Reviews (Wiley), EMBASE (Elsevier), CINAHL (EBSCO), and PsycINFO (American Psychological Association) from inception through 10 August 2018. Study Selection: 84 randomized trials that evaluated 14 categories of interventions and reported categorical cure or improvement outcomes. Data Extraction: 1 researcher extracted study characteristics, results, and study-level risk of bias, with verification by another independent researcher. The research team collaborated to assess strength of evidence (SoE) across studies. Data Synthesis: 84 studies reported cure or improvement outcomes (32 in stress UI, 16 in urgency UI, 4 in mixed UI, and 32 in any or unspecified UI type). The most commonly evaluated active intervention types included behavioral therapies, anticholinergics, and neuromodulation. Network meta-analysis showed that all interventions, except hormones and periurethral bulking agents (variable SoE), were more effective than no treatment in achieving at least 1 favorable UI outcome. Among treatments used specifically for stress UI, behavioral therapy was more effective than either α-agonists or hormones in achieving cure or improvement (moderate SoE); α-agonists were more effective than hormones in achieving improvement (moderate SoE); and neuromodulation was more effective than no treatment for cure, improvement, and satisfaction (high SoE). Among treatments used specifically for urgency UI, behavioral therapy was statistically significantly more effective than anticholinergics in achieving cure or improvement (high SoE), both neuromodulation and onabotulinum toxin A (BTX) were more effective than no treatment (high SoE), and BTX may have been more effective than neuromodulation in achieving cure (low SoE). Limitation: Scarce direct (head-to-head trial) evidence and population heterogeneity based on UI type, UI severity, and history of prior treatment. Conclusion: Most nonpharmacologic and pharmacologic interventions are more likely than no treatment to improve UI outcomes. Behavioral therapy, alone or in combination with other interventions, is generally more effective than pharmacologic therapies alone in treating both stress and urgency UI. Primary Funding Source: Patient-Centered Outcomes Research Institute. (PROSPERO: CRD42017069903).


Assuntos
Incontinência Urinária por Estresse/terapia , Incontinência Urinária de Urgência/terapia , Terapia Comportamental , Antagonistas Colinérgicos/uso terapêutico , Terapia por Estimulação Elétrica , Estrogênios/uso terapêutico , Terapia por Exercício , Feminino , Humanos , Terapia de Campo Magnético , Meta-Análise em Rede
19.
Life Sci ; 222: 203-211, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30825546

RESUMO

AIMS: The purpose of the present study was to investigate the potential antioxidant, anti-apoptotic and sperm function-preserving effects of estrogen, estrogen receptor (ER)α and ERß agonists in a rat model of testis torsion-detorsion (T/D). MAIN METHODS: Under anesthesia, 6-8-week-old male Sprague-Dawley rats underwent sham-operation or testicular torsion by fixing left testis rotated at 720° for 2 h. After detorsion, rats were treated with ERα agonist (1 mg/kg/day, subcutaneously, sc) or ERß agonist (1 mg/kg/day, sc) or estradiol (E2, 1 mg/kg/day, in drinking water) or vehicle on the following two days. On the third day, testicular blood-flow was recorded and then left testes were extracted for molecular and histochemical analysis. KEY FINDINGS: The findings showed that reduced testicular blood-flow following torsion was partially restored on the 3rd day of detorsion, while treatments with either of the ER agonists or E2 returned blood flow fully back to the control levels. When the testis-torsioned rats were given ERß agonist during the detorsion period, tubular injury was lessened, sperm count and motility were increased, while the production of reactive oxygen metabolites and apoptosis in the testis tissues were totally suppressed. Although a down-regulated expression of androgen receptor (AR) along with a reduction in serum testosterone level was observed in the vehicle-treated T/D group, all three treatments up-regulated the expressions of AR and its mRNA, while ERα agonist and E2 suppressed the testosterone level. SIGNIFICANCE: ERß receptor activation during the post-ischemic period may be beneficial in protection against torsion-related oxidant testicular injury and infertility.


Assuntos
Receptor beta de Estrogênio/agonistas , Estrogênios/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Torção do Cordão Espermático/tratamento farmacológico , Testículo/irrigação sanguínea , Testículo/efeitos dos fármacos , Animais , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Velocidade do Fluxo Sanguíneo/fisiologia , Estrogênios/farmacologia , Masculino , Estresse Oxidativo/fisiologia , Ratos , Ratos Sprague-Dawley , Torção do Cordão Espermático/patologia , Testículo/patologia , Resultado do Tratamento
20.
Br J Cancer ; 120(7): 754-760, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30814688

RESUMO

BACKGROUND: Although the photosensitising effects of oestrogens may increase the impact of ultraviolet radiation (UVR) on melanoma risk, few prospective studies have comprehensively assessed the association between oestrogen-related factors and melanoma. METHODS: We examined the associations between reproductive factors, exogenous oestrogen use and first primary invasive melanoma among 167 503 non-Hispanic white, postmenopausal women in the NIH-AARP Diet and Health Study. Satellite-based ambient UVR estimates were linked to geocoded residential locations of participants at study baseline. RESULTS: Increased risk of melanoma was associated with early age at menarche (≤10 vs ≥15 years: HR = 1.25, 95% CI: 0.92, 1.71; P for trend = 0.04) and late age at menopause (≥50 vs <45 years: HR = 1.34, 95% CI: 1.13, 1.59; P for trend = 0.001). The relationship between ambient UVR and melanoma risk was highest among women with age at menarche ≤10 years (HR per UVR quartile increase = 1.29; 95% CI: 1.05, 1.58; P-interaction = 0.02). Melanoma risk was not associated with parity, age at first birth, use of oral contraceptives or use of menopausal hormone therapy. CONCLUSIONS: Our findings suggest that increased melanoma risk is associated with early age at menarche and late age at menopause. Effect modification findings support the hypothesis that endogenous oestrogen exposure in childhood increases photocarcinogenicity. Future studies should include information on personal UVR exposure and sun sensitivity.


Assuntos
Anticoncepcionais Orais Hormonais/uso terapêutico , Terapia de Reposição de Estrogênios/estatística & dados numéricos , Melanoma/epidemiologia , Menarca , Menopausa , Neoplasias Cutâneas/epidemiologia , Fatores Etários , Idoso , Estrogênios/uso terapêutico , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Raios Ultravioleta , Estados Unidos/epidemiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA