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1.
Maturitas ; 146: 57-62, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33722365

RESUMO

OBJECTIVE: The study aimed to evaluate the degree of menopausal hormonal therapy (MHT) use and the related trends, as well as the characteristics of Korean women who used MHT by type of hormone therapy. METHODS: Women aged ≥40 years were selected using data from the Korea National Insurance Service-National Sample Cohort 2002-2013 database. MHT entailed either estrogen therapy or estrogen plus progestogen therapy, as categorized by the Anatomical Therapeutic Chemical system. The prevalence of MHT use was calculated as the number of women with prescriptions annually and the level of hormone consumption was calculated using the defined daily dose (DDD). RESULTS: The proportion of MHT users among women aged ≥40 years was 7.8 % in 2002, which decreased to 6.3 % in 2013. The overall MHT consumption level in 2002 was 27.5 DDDs/1000 inhabitants/day. There was a sharp decline in the first few years after 2002 and this value decreased to 12.5 DID in 2013; however, the decrease had lessened from 2006 to 2013 and differed by HT type, administration route, age, and income level. During the 11-year follow-up, over 70 % of women were prescribed MHT for less than 1 year, while only 11.8 % had a prescription for 3 years or more, and women who started treatment at age 45-59 years showed longer treatment duration. CONCLUSIONS: Since 2002, MHT use among Korean women, especially overall MHT consumption, has declined remarkably. Regarding the pattern of use among women who took hormone preparations during 2002-2013, MHT was used around menopause, over the short term only, and at low dose.


Assuntos
Estrogênios/uso terapêutico , Terapia de Reposição Hormonal , Progestinas/uso terapêutico , Adulto , Idoso , Estudos de Coortes , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , República da Coreia/epidemiologia
2.
Obstet Gynecol ; 137(1): e7-e15, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33399429

RESUMO

ABSTRACT: Obstetrician-gynecologists frequently are consulted either before the initiation of cancer treatment to request menstrual suppression or during an episode of severe heavy bleeding to stop bleeding emergently. Adolescents presenting emergently with severe uterine bleeding usually require only medical management; surgical management rarely is required. Surgical management should be considered for patients who are not clinically stable, or for those whose conditions are not suitable for medical management or have failed to respond appropriately to medical management. When used continuously, combined hormonal contraceptives are effective for producing amenorrhea, although complete amenorrhea cannot be guaranteed. The risk of venous thromboembolism in patients with cancer is compounded by multiple factors, including presence of metastatic or fast-growing, biologically aggressive cancers; hematologic cancers; treatment-related factors such as surgery or central venous catheters; and the number and type of comorbid conditions. Although as a group, patients undergoing cancer treatment are at elevated risk of venous thromboembolism compared with the general population, this risk may be extremely elevated for certain patients and existing guidance on risk stratification should be consulted. The decision to use estrogen in patients with cancer should be tailored to the individual patient after collaborative consideration of the risk-benefit ratio with the patient and the health care team; the patient should be closely monitored for known adverse effects such as liver toxicity and venous thromboembolism.


Assuntos
Menstruação/efeitos dos fármacos , Neoplasias/terapia , Hemorragia Uterina/prevenção & controle , Adolescente , Anticoncepcionais Orais Combinados/administração & dosagem , Tratamento de Emergência , Feminino , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Progestinas/farmacologia , Progestinas/uso terapêutico
3.
J Pediatr Orthop ; 41(1): e94-e97, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32991492

RESUMO

BACKGROUND: Limb deficiencies associated with amniotic bands comprise a wide range of congenital anomalies. The association of maternal medication and the risk of amniotic band sequence (ABS) has not yet been addressed. METHODS: This nationwide population-based case-control study used national registers on congenital anomalies, births and induced abortions, cross-linked with information on maternal prescription medicine use obtained from the registers on Reimbursed Drug Purchases and Medical Special Reimbursements. All cases with congenital limb deficiency associated with amniotic bands born between 1996 and 2008 were included in the study. Five controls without limb deficiency matched for residency and time of conception were randomly selected from the Medical Birth Register. RESULTS: In total, 106 children with limb deficiency associated with ABS were identified and compared with 530 matched controls. Young maternal age (less than 25 y) increased the risk of limb deficiencies [odds ratio=1.72; 95% confidence interval (CI): 1.06, 2.80]. Primiparity was also associated with increased risk [adjusted odds ratio (aOR)=2.42; 95% CI: 1.52, 3.88]. After adjusting for maternal age, pregestational diabetes, and parity, maternal use of beta-blockers (adjusted OR=24.2; 95% CI: 2.57, 228) and progestogens (adjusted OR=3.79; 95% CI: 1.38, 10.4) during the first trimester of pregnancy significantly increased the risk of limb deficiencies associated with amniotic bands. CONCLUSIONS: Primiparity significantly increased the risk of limb defects associated with amniotic bands. Also, a novel association on increased risk of ABS with maternal use of progestogens or beta-blockers during the first trimester of pregnancy was observed. LEVEL OF EVIDENCE: Level III.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Síndrome de Bandas Amnióticas , Deformidades Congênitas dos Membros , Idade Materna , Progestinas/uso terapêutico , Adulto , Síndrome de Bandas Amnióticas/complicações , Síndrome de Bandas Amnióticas/diagnóstico , Síndrome de Bandas Amnióticas/epidemiologia , Estudos de Casos e Controles , Feminino , Finlândia/epidemiologia , Humanos , Recém-Nascido , Deformidades Congênitas dos Membros/diagnóstico , Deformidades Congênitas dos Membros/epidemiologia , Deformidades Congênitas dos Membros/etiologia , Masculino , Paridade , Gravidez , Resultado da Gravidez/epidemiologia , Prevalência , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco
4.
Artigo em Inglês | MEDLINE | ID: mdl-32978069

RESUMO

Progesterone is essential for the maintenance of pregnancy, and progesterone deficiency is associated with miscarriage. The subject of whether progesterone supplementation in early pregnancy can prevent miscarriage has been a long-standing research question and has been investigated and debated in the medical literature for over 70 years. During this time, several different progestogens have been synthesised and tested for the prevention of miscarriage. In this chapter, we describe the prior evidence alongside the latest research using micronized natural progesterone as well as synthetic progestogens, which were used to treat both recurrent and threatened miscarriage. The totality of evidence indicates that women with a past history of miscarriage who present with bleeding in early pregnancy may benefit from the use of vaginal micronized progesterone. The clinical implications of the findings are discussed.


Assuntos
Aborto Habitual , Aborto Espontâneo , Ameaça de Aborto , Aborto Habitual/etiologia , Aborto Habitual/prevenção & controle , Aborto Espontâneo/prevenção & controle , Ameaça de Aborto/tratamento farmacológico , Ameaça de Aborto/prevenção & controle , Feminino , Humanos , Gravidez , Progesterona , Progestinas/uso terapêutico , Vagina
5.
Metas enferm ; 23(7): 49-59, sept. 2020. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-196460

RESUMO

OBJETIVO: conocer los métodos anticonceptivos adecuados para su uso en el periodo postparto según la evidencia científica, así como el momento idóneo para informar sobre la anticoncepción postparto. MÉTODO: se realizó una revisión narrativa, mediante localización y búsqueda bibliográfica de los artículos publicados en las siguientes bases de datos: PubMed, Cochrane Plus y Cuiden. También se consultó la base de datos Uptodate, Biblioteca de Salud Reproductiva de la Organización Mundial de la Salud (OMS) y las Guías de Práctica Clínica (GPC) del Sistema Nacional de Salud, así como los protocolos publicados en la Sociedad Española de Contracepción (SEC). La búsqueda se estableció entre los años 2010-2020, incluyéndose solo artículos en español e inglés. Los documentos encontrados fueron revisados y seleccionados en función de varios criterios de inclusión. RESULTADOS: de los 579 documentos identificados, cuatro fueron eliminados por ser duplicados, por lo que fueron revisados un total de 575 artículos. De los mismos, 524 artículos fueron eliminados por incumplir los criterios de inclusión y solo 51 fueron seleccionados para valorar la calidad de los mismos, de los cuales se incluyeron 27 en la revisión. Los resultados se organizaron según los siguientes contenidos: cuándo y cómo informar sobre los métodos anticonceptivos postparto y los métodos anticonceptivos adecuados para ese periodo. CONCLUSIONES: a pesar de la demanda poblacional existe un déficit de información y consejo sobre la planificación familiar postparto. Los profesionales de la salud han de aprovechar cada oportunidad durante el embarazo, el parto y el puerperio para proporcionar información y asesoramiento. Los métodos anticonceptivos adecuados para el postparto son variados. Sigue existiendo controversia en relación al momento de inicio de los anticonceptivos con gestágenos y sobre el momento más idóneo para la inserción del DIU


OBJECTIVE: to identify the contraceptive methods adequate for use in the post-partum period according to scientific evidence, as well as the adequate time to inform about post-partum contraception. METHOD: a narrative review was conducted, through bibliographic location and search of the articles published in the following databases: PubMed, Cochrane Plus and Cuiden. The Uptodate database was also consulted, as well as the Library of Reproductive Health by the World Health Organization (WHO) and the Clinical Practice Guidelines (CPG) by the National Health System, and the protocols published at the Spanish Society of Contraception (SEC). The search was established during the years 2010-2020, and only articles in Spanish and English were included. The documents found were reviewed and selected according to various inclusion criteria. RESULTS: of the 579 documents identified, four were eliminated because they were duplicates; therefore, 575 articles were reviewed in total. Out of these, 524 articles were eliminated because the inclusion criteria were not met, and only 51 were selected in order to assess their quality, and 27 of these were included in the review. Results were classified according to the following contents: when and how to inform about post-partum contraception methods, and the contraceptive methods adequate for said period. CONCLUSIONS: regardless of demands by the population, there is deficit of information and advice regarding post-partum family planning. Health professionals must take every opportunity during pregnancy, delivery and puerperium, in order to provide information and guidance. There is a variety of contraceptive methods adequate for the post-partum period. There is still some controversy regarding the time to initiate contraception with gestagens, and the most adequate time to insert an IUD


Assuntos
Humanos , Feminino , Planejamento Familiar , Anticoncepção/enfermagem , Enfermagem Baseada em Evidências/métodos , Período Pós-Parto , Enfermeiras Obstétricas , Cuidado Pós-Natal , Conhecimentos, Atitudes e Prática em Saúde , Progestinas/uso terapêutico , Dispositivos Anticoncepcionais Femininos
6.
Obstet Gynecol ; 136(3): 622-627, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32769653

RESUMO

U.S. Food and Drug Administration (FDA)-approved 17α-hydroxyprogesterone caproate therapy is currently available to reduce recurrent preterm birth in the United States. This commentary reviews the original landmark Meis trial ("Prevention of Recurrent Preterm Delivery by 17 Alpha-Hydroxyprogesterone Caproate"), which led to conditional approval of 17α-hydroxyprogesterone caproate by the FDA in 2011. The recent PROLONG (Progestin's Role in Optimizing Neonatal Gestation) trial failed to confirm the original findings. The Meis trial was rigorously designed and conducted, with highly statistically significant results that should not be undermined by the negative results of PROLONG. Given that the United States has among the highest preterm birth rates in the world and that the predominant enrollment in PROLONG was outside the United States, the results of the "old" Meis trial should not be summarily dismissed. It would be detrimental to high-risk pregnant patients to inappropriately prioritize results of PROLONG over the Maternal-Fetal Medicine Units Network's Meis trial (funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development). We assert PROLONG was underpowered, based on substantially lower observed preterm birth rates than anticipated, and therefore was a false-negative study, rather than the Meis trial being a false-positive study. Careful assessment of these two trials is critical as removal of 17α-hydroxyprogesterone caproate from the U.S. marketplace may have substantial effects on public health.


Assuntos
Caproato de 17 alfa-Hidroxiprogesterona/uso terapêutico , Nascimento Prematuro/prevenção & controle , Progestinas/uso terapêutico , Feminino , Humanos , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Resultado do Tratamento
7.
Revista Digital de Postgrado ; 9(2): 227, ago. 2020. tab
Artigo em Espanhol | LILACS, LIVECS | ID: biblio-1103383

RESUMO

Evaluar los efectos de la terapia hormonal (TH) con Drospírenona (DRSP)/17 ß -estradiol (E2), sobre los parámetros del Síndrome Metabólico (SM) en pacientes postmenopáusicas. Métodos: Investigación comparativa y aplicada, con diseño cuasi experimental, de casos y controles a simple ciego, prospectivo y de campo; realizada en la Consulta de Ginecología. Hospital "Dr. Manuel Noriega Trigo". San Francisco, Estado Zulia. Venezuela. Participaron 120 mujeres separadas al azar para recibir la combinación DRSP/E2 (Grupo A) o un placebo (Grupo B). Se evaluaron los componentes del SM antes y posterior a 6 meses de haber recibido la TH. Resultados: Se encontró una alta prevalencia de SM en ambos grupos antes de recibir el tratamiento (53,3% y 48%; grupo A y B respectivamente). Posterior al tratamiento, DRSP/E2 al compararse con un placebo, redujo significativamente tanto la prevalencia del SM como el riesgo de padecerlo (21,7% versus 48,3%, OR [IC95%]= 0,29 [0,13-0,65]; p < 0.001), con reducción significativa (p< 0.001) de la hipertensión arterial, glicemia basal alterada, hipertrigliceridemia y obesidad central; además de una reducción significativa de los síntomas vasomotores, síntomas psicológicos e incontinencia urinaria (p< 0.001). En el grupo B la prevalencia del SM se mantuvo sin cambios, salvo para la glicemia basal alterada y los síntomas vasomotores y psicológicos que mostraron una reducción significativa (p< 0.001). Conclusión: DRSP/E2 (2mg/1 mg) demostró ser eficaz luego de 6 meses de tratamiento tanto para el control de los parámetros que definen al SM; con pocos y leves efectos indeseados(AU)


To assess the effects of hormone therapy (HT) with drospirenone (DRSP)/17 ß -estradiol (E2) on the parameters of the metabolic syndrome (MS) in postmenopausal patients. Methods: We performed a comparative and applied research, with quasiexperimental, case-control, single-blind, prospective and field design. The study was realized in the Gynecology consultation. Hospital "Dr. Manuel Noriega Trigo". San Francisco, Estado Zulia. Venezuela. 120 women were included, they were separated to receive either the combination DRSP/E2 (Group A) or placebo (Group B). We assess MS components before and ather 6 months of receiving HT. Results: We found a high prevalence in both groups before receiving treatment (53.3% and 48%, group A and B respectively). A ther treatment, DRSP/E2 when compared to placebo, significantly reduced both the prevalence of MS as the risk of setting it (21.7% versus 48.3%, OR [95%] = 0.29 [0.13-0.65] p <0.001), with a significant reduction (p <0.001) of hypertension, impaired fasting glucose, hypertriglyceridemia, central obesity; and a significant reduction in vasomotor symptoms, psychological symptoms and urinary incontinence (p <0.001). In group B the prevalence of MS was unchanged, except for impaired fasting glycemia and vasomotor and psychological symptoms showed a significant reduction (p <0.001). Conclusion: DRSP/E2 (2mg /1mg), proved to be effective a ther 6 months of treatment both for the control of the parameters that define the SM, with few and mild side effects(AU)


Assuntos
Humanos , Feminino , Progestinas/uso terapêutico , Terapia de Reposição Hormonal , Síndrome Metabólica/fisiopatologia , Estradiol/uso terapêutico , Pós-Menopausa , Endocrinologia , Ginecologia
8.
Endocrinology ; 161(9)2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32730568

RESUMO

Severe outcomes and death from the novel coronavirus disease 2019 (COVID-19) appear to be characterized by an exaggerated immune response with hypercytokinemia leading to inflammatory infiltration of the lungs and acute respiratory distress syndrome. Risk of severe COVID-19 outcomes is consistently lower in women than men worldwide, suggesting that female biological sex is instrumental in protection. This mini-review discusses the immunomodulatory and anti-inflammatory actions of high physiological concentrations of the steroids 17ß-estradiol (E2) and progesterone (P4). We review how E2 and P4 favor a state of decreased innate immune inflammatory response while enhancing immune tolerance and antibody production. We discuss how the combination of E2 and P4 may improve the immune dysregulation that leads to the COVID-19 cytokine storm. It is intended to stimulate novel consideration of the biological forces that are protective in women compared to men, and to therapeutically harness these factors to mitigate COVID-19 morbidity and mortality.


Assuntos
Infecções por Coronavirus/imunologia , Estradiol/imunologia , Imunomodulação/imunologia , Pneumonia Viral/imunologia , Progesterona/imunologia , Formação de Anticorpos/imunologia , Betacoronavirus , Anticoncepcionais Orais Hormonais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Síndrome da Liberação de Citocina/imunologia , Reposicionamento de Medicamentos , Estradiol/uso terapêutico , Terapia de Reposição de Estrogênios , Estrogênios/uso terapêutico , Feminino , Humanos , Tolerância Imunológica/imunologia , Imunidade Inata/imunologia , Masculino , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Progesterona/uso terapêutico , Progestinas/uso terapêutico , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Índice de Gravidade de Doença , Fatores Sexuais
9.
Cochrane Database Syst Rev ; 7: CD013651, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32700364

RESUMO

BACKGROUND: Within the context of heavy menstrual bleeding, pandemics impact upon women's assessment and treatment by healthcare providers. OBJECTIVES: To summarise the evidence from Cochrane Reviews evaluating interventions for heavy menstrual bleeding that are commonly available during pandemics. METHODS: We sought published Cochrane Reviews, evaluating interventions that can continue during pandemics for women with heavy menstrual bleeding with no known underlying cause. We identified Cochrane Reviews by searching the Cochrane Database of Systematic Reviews in June 2020. The primary outcome was menstrual bleeding. Secondary outcomes included quality of life, patient satisfaction, side effects, and serious adverse events. We undertook the selection of systematic reviews, data extraction, and quality assessment in duplicate. We resolved any disagreements by discussion. We assessed review quality using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) 2 tool, and the certainty of the evidence for each outcome using GRADE methods. MAIN RESULTS: We included four Cochrane Reviews, with 11 comparisons, data from 44 randomised controlled trials (RCTs), and 3196 women. We assessed all the reviews to be high quality. Non-steroidal anti-inflammatory drugs (NSAIDs) NSAIDs may be more effective in reducing heavy menstrual bleeding than placebo (mean difference (MD) -124 mL per cycle, 95% confidence interval (CI) -186 to -62 mL per cycle; 1 RCT, 11 women; low-certainty evidence). Mefenamic acid may be similar to naproxen (MD 21 mL per cycle, 95% CI -6 to 48 mL per cycle; 2 RCTs, 61 women; low-certainty evidence), and NSAIDs may be similar to combined hormonal contraceptives for heavy menstrual bleeding (MD 25 mL per cycle, 95% CI -22 to 73 mL per cycle; 1 RCT, 26 women; low-certainty evidence). NSAIDs may be be less effective in reducing menstrual bleeding than antifibrinolytics (relative risk (RR) 0.70, 95% CI 0.58 to 0.85; 2 RCTs, 161 women; low-certainty evidence). We are uncertain whether NSAIDs reduce menstrual blood loss more than short-cycle progestogens (RR 0.80, 95% CI 0.49 to 1.32; 1 RCT 32 women; very low-certainty evidence). Antifibrinolytics Antifibrinolytics appear to be more effective in reducing heavy menstrual bleeding than placebo (MD -53 mL per cycle, 95% CI -63 to -44 mL per cycle; 4 RCTs, 565 women; moderate-certainty evidence). Antifibrinolytics may be similar to placebo on the incidence of side effects (RR 1.05, 95% CI 0.93 to 1.18; 1 RCT, 297 women; low-certainty evidence), and they are probably similar on the incidence of serious adverse events (thrombotic events; RR 0.10, 95% CI 0.00 to 2.46; 2 RCT, 468 women; moderate-certainty evidence). Antifibrinolytics may be more effective in reducing heavy menstrual bleeding than short-cycle progestogen (MD -111 mL per cycle, 95% CI -178 mL to -44 mL per cycle; 1 RCT, 46 women; low-certainty evidence). We are uncertain whether antifibrinolytics are similar to short-cycle progestogens on quality of life (RR 1.67, 95% CI 0.76 to 3.64; 1 RCT, 44 women; very low-certainty evidence), patient satisfaction (RR 0.91, 95% CI 0.59 to 1.39; 1 RCT, 42 women; very low-certainty evidence), or side effects (RR 0.85, 95% CI 0.65 to 1.12; 3 RCTs, 211 women; very low-certainty evidence). We are uncertain whether antifibrinolytics are more effective in reducing heavy menstrual bleeding when compared with long-cycle progestogen (MD -9 points per cycle, 95% CI -30 to 12 points per cycle; 2 RCTs, 184 women; low-certainty evidence). Antifibrinolytics may increase self-reported improvement in menstrual bleeding when compared with long-cycle medroxyprogesterone acetate (RR 1.32, 95% CI 1.08 to 1.61; 1 RCT, 94 women; low-certainty evidence). Antifibrinolytics may be similar to long-cycle progestogens on quality of life (MD 5, 95% CI -2.49 to 12.49; 1 RCT, 90 women; low-certainty evidence). We are uncertain whether antifibrinolytics are similar to long-cycle progestogens on side effects (RR 0.58, 95% CI 0.33 to 1.00; 2 RCTs, 184 women; very low-certainty evidence). There were no trials comparing antifibrinolytics to combined hormonal contraceptives. Combined hormonal contraceptives Combined hormonal contraceptives appear to be more effective for heavy menstrual bleeding than placebo or no treatment (RR 13.25, 95% CI 2.94 to 59.64; 2 RCTs, 363 women; moderate-certainty evidence). Combined hormonal contraceptives are probably similar to placebo on the incidence of side effects (RR 1.53, 95% CI 0.90 to 2.60; 2 RCTs, 411 women; moderate-certainty evidence). Progestogens There were no trials comparing progestogens to placebo. Limitations in the evidence included risk of bias in the primary RCTs, inconsistency between the primary RCTs, and imprecision in effect estimates. AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that antifibrinolytics and combined hormonal contraceptives reduce heavy menstrual bleeding compared with placebo. There is low-certainty evidence that NSAIDs reduce heavy menstrual bleeding compared with placebo. There is low-certainty evidence that antifibrinolytics are more effective in reducing heavy menstrual bleeding when compared with NSAIDs and short-cycle progestogens, but we are unable to draw conclusions about the effects of antifibrinolytics compared to long-cycle progestogens, on low-certainty evidence.


Assuntos
Menorragia/tratamento farmacológico , Pandemias , Anti-Inflamatórios não Esteroides/uso terapêutico , Antifibrinolíticos/uso terapêutico , Anticoncepcionais Orais Hormonais/uso terapêutico , Feminino , Humanos , Ácido Mefenâmico/uso terapêutico , Placebos/uso terapêutico , Progestinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Literatura de Revisão como Assunto
10.
PLoS Comput Biol ; 16(6): e1007848, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32598357

RESUMO

Contraceptive drugs intended for family planning are used by the majority of married or in-union women in almost all regions of the world. The two most prevalent types of hormones associated with contraception are synthetic estrogens and progestins. Hormonal based contraceptives contain a dose of a synthetic progesterone (progestin) or a combination of a progestin and a synthetic estrogen. In this study we use mathematical modeling to understand better how these contraceptive paradigms prevent ovulation, special focus is on understanding how changes in dose impact hormonal cycling. To explain this phenomenon, we added two autocrine mechanisms essential to achieve contraception within our previous menstrual cycle models. This new model predicts mean daily blood concentrations of key hormones during a contraceptive state achieved by administering progestins, synthetic estrogens, or a combined treatment. Model outputs are compared with data from two clinical trials: one for a progestin only treatment and one for a combined hormonal treatment. Results show that contraception can be achieved with synthetic estrogen, with progestin, and by combining the two hormones. An advantage of the combined treatment is that a contraceptive state can be obtained at a lower dose of each hormone. The model studied here is qualitative in nature, but can be coupled with a pharmacokinetic/pharamacodynamic (PKPD) model providing the ability to fit exogenous inputs to specific bioavailability and affinity. A model of this type may allow insight into a specific drug's effects, which has potential to be useful in the pre-clinical trial stage identifying the lowest dose required to achieve contraception.


Assuntos
Anticoncepcionais/uso terapêutico , Contracepção Hormonal , Ciclo Menstrual/efeitos dos fármacos , Progestinas/uso terapêutico , Adulto , Estrogênios/uso terapêutico , Feminino , Hormônio Foliculoestimulante/fisiologia , Humanos , Hipotálamo/efeitos dos fármacos , Hormônio Luteinizante/fisiologia , Modelos Biológicos , Ovário/efeitos dos fármacos , Hipófise/efeitos dos fármacos
11.
Drugs Today (Barc) ; 56(5): 321-328, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32406879

RESUMO

Drospirenone (DRSP) was synthesized as an analogue of spironolactone with the aim of producing a fourth-generation progestogen that differed from earlier progestogens in that it had antiandrogenic and little or no androgenic activity and lacked estrogenic effects while retaining some antimineralocorticoid activity. Since then, DRSP has been included in several oral contraceptive preparations together with an estrogen. However, increasing evidence has demonstrated that DRSP 4 mg on its own inhibits ovulation. It was thus a logical development to determine the efficacy of a tablet that only included DRSP 4 mg as an oral contraceptive. This proved successful and this product has now been approved by the Food and Drug Administration (FDA).


Assuntos
Androstenos/uso terapêutico , Anticoncepcionais Orais/uso terapêutico , Progestinas/uso terapêutico , Estrogênios , Feminino , Humanos , Estados Unidos , United States Food and Drug Administration
12.
Am J Obstet Gynecol ; 223(1): B16-B18, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32277894

RESUMO

In late 2019, results from the Progestin's Role in Optimizing Neonatal Gestation (PROLONG) trial were published showing no benefit of weekly injections of 17-alpha hydroxyprogesterone caproate (17-)HPC) from 16-20 weeks of gestation in women with a history of a singleton PTB in reducing the rates of subsequent PTB and neonatal morbidity. The Society for Maternal-Fetal Medicine believes that the differences in these results from the earlier Meis, et al trial, which did show a benefit of 17-OHPC in reducing the rate of spontaneous PTB (sPTB), may be at least partially explained by differences in study populations. SMFM concludes that it is reasonable for providers to use 17-OHPC in women with a profile more representative of the very-high-risk population reported in the Meis trial. For all women at risk of recurrent sPTB, the risk/benefit discussion should incorporate a shared decision-making approach, taking into account the lack of short-term safety concerns but uncertainty regarding benefit.


Assuntos
Caproato de 17 alfa-Hidroxiprogesterona/uso terapêutico , Nascimento Prematuro/prevenção & controle , Progestinas/uso terapêutico , Feminino , Humanos , Gravidez , Recidiva
13.
BJOG ; 127(9): 1055-1063, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32324957

RESUMO

BACKGROUND: Threatened miscarriage is a common complication of pregnancy. Results of randomised controlled trials on the efficacy of progestogen in the treatment of threatened miscarriage remain inconsistent. OBJECTIVE: To investigate whether the use of progestogen is associated with improved event rate of live birth and other benefits in women with threatened miscarriage. SEARCH STRATEGY: Ovid MEDLINE, Ovid Embase and Cochrane CENTRAL Register of Controlled Trials from their inception until 8 July 2019. SELECTION CRITERIA: Randomised controlled trials comparing progestogen with a placebo or no treatment for pregnancy outcomes in women with threatened miscarriage. DATA COLLECTION AND ANALYSIS: Two authors independently conducted data extraction and assessed study quality. We calculated risk ratios (RR) and 95% confidence intervals using the Mantel-Haenszel approach for dichotomous outcomes. MAIN RESULTS: Ten trials with a total of 5056 participants were eligible for analysis. The use of progesterone increased the incidence of live birth (RR 1.07, 95% CI 1.00-1.15; P = 0.04; I2  = 18%), with benefit only seen with the use of oral progestogen (RR 1.17, 95% CI 1.04-1.31; P = 0.008; I2  = 0%) and not with vaginal progesterone (RR 1.04, 95% CI 1.00-1.08; P = 0.07; I2  = 0%). Similarly, progestogen reduced the risk of miscarriage (RR 0.73, 95% CI 0.59-0.92), with benefit only seen with oral progestogen and not with vaginal progesterone. CONCLUSION: Progestogens may have benefits on live birth rate and miscarriage rate for women with threatened miscarriage. These benefits appear to be confined to the use of oral progestogen, and no statistically significant improvements were seen with vaginal progesterone. TWEETABLE ABSTRACT: A meta-analysis of 10 trials found that progestogens increased live birth rates and reduced miscarriage rates for women with threatened miscarriage.


Assuntos
Ameaça de Aborto/tratamento farmacológico , Nascimento Vivo , Progesterona/uso terapêutico , Progestinas/uso terapêutico , Aborto Espontâneo/prevenção & controle , Administração Intravaginal , Administração Oral , Feminino , Humanos , Gravidez , Progesterona/administração & dosagem , Progestinas/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
J Womens Health (Larchmt) ; 29(7): 937-943, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32155101

RESUMO

Contraceptives that contain estrogen and/or progestins are used by millions of women around the world to prevent pregnancy. Owing to their unique physiological mechanism of action, many of these medications can also be used to prevent cancer and treat multiple general medical conditions that are common in women. We performed a comprehensive literature search. This article will describe the specific mechanisms of action and summarize the available data documenting how hormonal contraceptives can prevent ovarian and uterine cancer and be used to treat women with a variety of gynecological and nongynecological conditions such as endometriosis, uterine fibroids, heavy menstrual bleeding, polycystic ovary syndrome, acne, and migraines. Contraceptive methods containing estrogen and progestin can be used for a wide variety of medical issues in women.


Assuntos
Anticoncepcionais Orais Hormonais/uso terapêutico , Endometriose/tratamento farmacológico , Estrogênios/uso terapêutico , Neoplasias Ovarianas/prevenção & controle , Síndrome do Ovário Policístico/tratamento farmacológico , Progestinas/uso terapêutico , Neoplasias Uterinas/prevenção & controle , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Saúde Reprodutiva
15.
Expert Opin Pharmacother ; 21(8): 893-903, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32164462

RESUMO

INTRODUCTION: Endometriosis is estimated to affect 10% of reproductive-aged women. The gold standard for treatment is surgery; however, surgery carries a significant morbidity and cost burden. There is an ongoing need for safe, effective medical therapies for endometriosis patients, both in conjunction with and independent of surgical interventions. Most conventional therapies for endometriosis work by a similar mechanism, and efficacy is variable. In recent years, there has been increased interest in the development and testing of novel pharmacotherapies for endometriosis. AREAS COVERED: This review discusses both conventional and emerging treatments for endometriosis. The authors present the application of these drugs in different presentations of endometriosis across the lifespan and discuss how emerging therapies might fit into future medical management of endometriosis. Conventional therapies include nonsteroidal anti-inflammatory drugs, combined oral contraceptives, progestins, GnRH agonists/antagonists, and aromatase inhibitors. Emerging therapies are focused on disease-specific targets such as endothelial growth factor receptors. EXPERT OPINION: The field of endometriosis therapy is moving toward modifying the immune and inflammatory milieu surrounding endometrial implants. If these drugs show efficacy in clinical trials, combining them with current medical treatment is expected to result in a profound impact on symptom and disease burden for patients who suffer from endometriosis worldwide.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Anticoncepcionais Orais Combinados/uso terapêutico , Endometriose/tratamento farmacológico , Hormônio Liberador de Gonadotropina , Antagonistas de Hormônios/uso terapêutico , Progestinas/uso terapêutico , Adulto , Endometriose/metabolismo , Feminino , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Humanos , Longevidade
18.
J Ovarian Res ; 13(1): 18, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054493

RESUMO

BACKGROUND: PPOS protocols, initially described for FP in women with cancer, have many advantages compared to antagonist protocols. PPOS protocols were not evaluated for women with endometriosis. The objective of the study was to describe fertility preservation outcomes in women with endometriosis and to compare an antagonist protocol with a Progestin-Primed Ovarian Stimulation (PPOS) protocol. METHOD: We conducted a prospective cohort study associated with a cost-effectiveness analysis in a tertiary-care university hospital. The measured outcomes included the numbers of retrieved and vitrified oocytes, and direct medical costs. In the whole population, unique and multiple linear regressions analysis were performed to search for a correlation between individual characteristics and the number of retrieved oocyte. RESULTS: We included 108 women with endometriosis who had a single stimulation cycle performed with either an antagonist or a PPOS protocol. Overall, 8.1 ± 6.6 oocytes were retrieved and 6.4 ± 5.6 oocytes vitrified per patient. In the multiple regression model, age (p = 0.001), prior ovarian surgery (p = 0.035), and anti-Mullerian hormone level (p = 0.001) were associated with the number of retrieved oocytes. Fifty-four women were stimulated with an antagonist protocol, and 54 with a PPOS protocol. A mean of 7.9 ± 7.4 oocytes were retrieved in the antagonist group and 8.2 ± 5.6 in the PPOS group (p = 0.78). A mean of 6.4 ± 6.4 oocytes were vitrified in the antagonist group and 6.4 ± 4.7 in the PPOS group (p = 1). In the cost-effectiveness analysis, the PPOS protocol was strongly dominant over the antagonist protocol. CONCLUSION: Fertility preservation procedures are feasible and effective for patients affected by endometriosis. Antagonist and PPOS protocols were associated with similar results but the medico-economic analysis was in favor of PPOS protocols.


Assuntos
Endometriose/complicações , Preservação da Fertilidade/métodos , Indução da Ovulação/métodos , Progestinas/uso terapêutico , Adulto , Estudos de Coortes , Feminino , Humanos , Progestinas/farmacologia , Estudos Prospectivos
19.
J Obstet Gynaecol Res ; 46(2): 215-222, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32017321

RESUMO

This review seeks to describe new fertility-sparing endometrial cancer (EC) treatment strategies that take into consideration the medical and general health background of patients. We particularly focus on the application of metformin, which is a biguanide widely prescribed for treatment of type 2 diabetes mellitus. Fertility-sparing treatment using progestin is considered a standard treatment option for patients with atypical endometrial hyperplasia (AEH) and EC who desire to conceive. A previous meta-analysis of fertility-sparing treatments revealed a high remission rate; however, high rates of relapse persisted. Most young patients with AEH and EC who are subjected to fertility-sparing treatment have a background of obesity, insulin resistance and abnormal glucose tolerance complicated with polycystic ovary syndrome. Recently, metformin has been attracting more attention in the field of cancer research. Several in vitro and in vivo reports regarding the efficacy of metformin in EC management have accumulated. Thus far, the efficacy of combining metformin with progestin has been revealed in a single phase II study of medroxyprogesterone acetate in combination with metformin as a fertility-sparing treatment for patients with AEH or EC. In addition to improving the metabolic profile of patients with EC having metabolic disorders, metformin supplementation may improve the long-term oncological outcome of these patients. To date, many clinical trials employing progestin and metformin as a fertility-sparing treatment of AEH and EC are ongoing. In the near future, it is expected that the clinical advantage of metformin progestin combination therapy will be clarified.


Assuntos
Neoplasias do Endométrio/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Tratamentos com Preservação do Órgão , Progestinas/uso terapêutico , Hiperplasia Endometrial/tratamento farmacológico , Feminino , Humanos
20.
Am J Obstet Gynecol ; 223(2): 167-176, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32008730

RESUMO

Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone supplementation may reduce the risk of miscarriage in women with recurrent or threatened miscarriage. Cochrane Reviews summarized the evidence and found that the trials were small with substantial methodologic weaknesses. Since then, the effects of first-trimester use of vaginal micronized progesterone have been evaluated in 2 large, high-quality, multicenter placebo-controlled trials, one targeting women with unexplained recurrent miscarriages (the PROMISE [PROgesterone in recurrent MIScarriagE] trial) and the other targeting women with early pregnancy bleeding (the PRISM [PRogesterone In Spontaneous Miscarriage] trial). The PROMISE trial studied 836 women from 45 hospitals in the United Kingdom and the Netherlands and found a 3% greater live birth rate with progesterone but with substantial statistical uncertainty. The PRISM trial studied 4153 women from 48 hospitals in the United Kingdom and found a 3% greater live birth rate with progesterone, but with a P value of .08. A key finding, first observed in the PROMISE trial, and then replicated in the PRISM trial, was that treatment with vaginal micronized progesterone 400 mg twice daily was associated with increasing live birth rates according to the number of previous miscarriages. Prespecified PRISM trial subgroup analysis in women with the dual risk factors of previous miscarriage(s) and current pregnancy bleeding fulfilled all 11 conditions for credible subgroup analysis. For the subgroup of women with a history of 1 or more miscarriage(s) and current pregnancy bleeding, the live birth rate was 75% (689/914) with progesterone vs 70% (619/886) with placebo (rate difference 5%; risk ratio, 1.09, 95% confidence interval, 1.03-1.15; P=.003). The benefit was greater for the subgroup of women with 3 or more previous miscarriages and current pregnancy bleeding; live birth rate was 72% (98/137) with progesterone vs 57% (85/148) with placebo (rate difference 15%; risk ratio, 1.28, 95% confidence interval, 1.08-1.51; P=.004). No short-term safety concerns were identified from the PROMISE and PRISM trials. Therefore, women with a history of miscarriage who present with bleeding in early pregnancy may benefit from the use of vaginal micronized progesterone 400 mg twice daily. Women and their care providers should use the findings for shared decision-making.


Assuntos
Aborto Habitual/prevenção & controle , Ameaça de Aborto/tratamento farmacológico , Progesterona/uso terapêutico , Progestinas/uso terapêutico , Administração Intravaginal , Feminino , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Progesterona/administração & dosagem , Progestinas/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
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