RESUMO
OBJECTIVE: To compare the growth and development of children born to mothers with gestational diabetes mellitus (GDM) requiring pharmacological treatment, and randomised to treatment with metformin or insulin. DESIGN: Follow-up of a randomised controlled trial (RCT) comparing metformin and insulin treatment of GDM. SETTING: Data were gathered during routine visits to child welfare clinics at the ages of 6, 12, and 18 months, including weight and height measurements, and assessment of motor, social, and linguistic development. SAMPLE: The children of mothers with GDM randomised to metformin (n = 47) or insulin (n = 50) treatment during pregnancy. METHODS: Data were collected from the structured questionnaire filled in at the child welfare clinics. MAIN OUTCOME MEASURES: The growth and development of the children until the age of 18 months. RESULTS: Children exposed to metformin were significantly heavier (10.47 versus 9.85 kg, 95% CI 0.04-1.20) at the age of 12 months and taller and heavier (83.9 vs 82.2 cm, 95% CI 0.23-3.03, 12.05 vs 11.32 kg, 95% CI 0.04-1.43) at the age of 18 months. The mean ponderal index (PI) did not differ significantly. The motor, social, or linguistic development evaluated at the age of 18 months did not differ between the groups. CONCLUSIONS: Children prenatally exposed to metformin were heavier at the 12 months measurements and taller and heavier at the 18 months measurements than those exposed to insulin, but their body composition defined by PI did not differ. Over the short term, metformin does not seem to be harmful with regards to early motor, linguistic, or social development.
Assuntos
Estatura/fisiologia , Peso Corporal/fisiologia , Desenvolvimento Infantil/fisiologia , Diabetes Gestacional/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Adulto , Feminino , Seguimentos , Humanos , Lactente , Insulina/uso terapêutico , Masculino , Metformina/uso terapêutico , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To examine if oral metformin is as effective as insulin in the prevention of fetal macrosomy in pregnancies complicated with gestational diabetes mellitus (GDM). DESIGN: Open-label prospective randomised controlled study. SETTING: Maternity outpatient clinics in a secondary and tertiary level hospital in Finland. SAMPLE: One hundred women with GDM who did not attain euglycaemia with diet. METHODS: Women were randomised to therapy with insulin (n = 50) or oral metformin (n = 50). MAIN OUTCOME MEASURES: Incidence of large-for-gestational-age (LGA) infants and neonatal morbidity. RESULTS: There were no statistically significant differences in the incidence of LGA (8.5 versus 10.0%, P = 0.97), mean birthweight, mean cord artery pH or neonatal morbidity between the insulin and metformin groups. Fifteen (31.9%) of the 47 women randomised to metformin needed supplemental insulin. They were more obese (with a body mass index of 36 versus 30 kg/m(2), P = 0.002), had higher fasting blood glucose levels in an oral glucose tolerance test (6.1 versus 5.0 mmol/l, P = 0.001) and needed medical treatment for GDM earlier (26 versus 31 gestational weeks, P = 0.002) than women who were normoglycemic with metformin. There was a tendency to a higher rate of caesarean sections in the metformin group than in the insulin group (RR 1.9; 95% CI 0.99-3.71). CONCLUSIONS: Metformin seems to be suitable for the prevention of fetal macrosomy, especially in lean or moderately overweight women developing GDM in late gestation. Women with considerable obesity, high fasting blood glucose and an early need for pharmacological treatment may be more suitable for insulin therapy.
Assuntos
Diabetes Gestacional/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Metformina/uso terapêutico , Adulto , Índice de Massa Corporal , Feminino , Macrossomia Fetal/prevenção & controle , Humanos , Obesidade/complicações , Pacientes Ambulatoriais , Gravidez , Estudos Prospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Remifentanil labour analgesia is superior to nitrous oxide but less potent than epidural analgesia. The short onset and offset times of effect suggest that the timing of the bolus in the contraction cycle could have importance. We hypothesised that administering a remifentanil bolus during contraction pause would improve analgesia in early labour. METHODS: With permission from the ethical committee and the National Authority of Medicines, 50 parturients with uncomplicated singleton pregnancies and informed consent participated in a double blind cross-over study. Intravenous doses of 0.4 µg/kg remifentanil with 1-min infusion times were used during two study periods lasting six to eight contractions. Remifentanil and saline syringes were attached to two patient-controlled devices, one of which administered the bolus immediately after a trigger and the other targeted to start 140 s before the next contraction. The parturients assessed contraction pain, pain relief, sedation and nausea. Oxygen saturation (SaO(2)) pulse and blood pressure were recorded. SaO(2)<95% was the indication for oxygen supplement. RESULTS: Forty-one parturients were included in the analyses. Because of the period effect, pain and pain relief scores were analysed separately for each of the study periods. The mean pain and pain relief scores were similar during the two different dosing regimens. Side effects, the need for supplemental oxygen, SaO(2) and haemodynamics were similar. In a subgroup with long and regular contractions, however, delayed boluses were associated with lower pain scores. CONCLUSIONS: Administering a remifentanil bolus during the uterine contraction pause does not improve pain relief.
Assuntos
Analgesia Obstétrica/métodos , Analgesia Controlada pelo Paciente , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Piperidinas/administração & dosagem , Piperidinas/uso terapêutico , Adolescente , Adulto , Índice de Apgar , Estudos Cross-Over , Interpretação Estatística de Dados , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca Fetal/efeitos dos fármacos , Hemoglobinas/metabolismo , Humanos , Bombas de Infusão , Infusões Intravenosas , Pessoa de Meia-Idade , Oxigênio/sangue , Medição da Dor , Gravidez , Remifentanil , Contração Uterina , Adulto JovemRESUMO
Gene expression studies have demonstrated the altered expression level of placental angiogenesis related genes in severe pre-eclampsia (PE). In cord compression, the transportation of oxygen from the placenta to the fetus is blocked, and it is speculated that during blockade the originally hypoxic placenta may become hyperoxic. We compared the placental gene expression profiles of one pre-eclamptic patient with cord compression (the index patient) to the profiles of patients with PE and those of normal pregnancy controls (including one woman with cord compression). The gene expression of the cord compression PE patient resembled that observed in the normal pregnancies. We hypothesize that umbilical blockade may in a short period of time lead to placental hyperoxia, which in turn has an effect on angiogenic gene expression profile.
Assuntos
Neovascularização Fisiológica/genética , Placenta/metabolismo , Pré-Eclâmpsia/genética , Complicações Hematológicas na Gravidez/patologia , Cordão Umbilical/patologia , Adulto , Estudos de Casos e Controles , Feminino , Regulação da Expressão Gênica , Humanos , Cordão Nucal/genética , Circulação Placentária/genética , Circulação Placentária/fisiologia , Gravidez , Complicações Hematológicas na Gravidez/genéticaRESUMO
BACKGROUND: We hypothesised that intravenous patient-controlled analgesia (IV PCA) with remifentanil could provide as satisfactory pain relief for labour as epidural analgesia. METHODS: Fifty-two parturients with singleton uncomplicated pregnancies were randomised to receive either IV PCA with remifentanil or epidural analgesia with 20 ml levobupivacaine 0.625 mg/ml and fentanyl 2 microg/ml in saline. The PCA dose of remifentanil was given over 1 min with a lockout time of 1 min. The dose was increased starting from the bolus of 0.1 microg/kg and following a dose escalation scheme up until the individual-effective dose was reached. The parturients assessed contraction pain (0-10), pain relief (0-4), sedation and nausea during 60 min. RESULTS: Forty-five parturients were included in the analysis. The median cervical opening was 4 cm before the study and 7 cm after the study. The median pain scores were 7.3 and 5.2 during remifentanil and epidural analgesia, respectively (P=0.009). The median pain relief scores were 2.5 and 2.8 (P=0.17). There was no difference between the groups in the proportion of parturients who discontinued due to ineffective analgesia, nor in the proportion of parturients who would have liked to continue the given medication at the end of the study. Sedation and low haemoglobin oxygen saturation were observed more often during remifentanil analgesia. Foetal heart rate tracing abnormalities were as common in both groups. CONCLUSIONS: In terms of pain scores, epidural analgesia is superior to that provided by IV remifentanil. However, there was no difference in the pain relief scores between the treatments.
Assuntos
Anestesia Epidural/métodos , Anestesia Intravenosa/métodos , Fentanila/uso terapêutico , Dor do Parto/tratamento farmacológico , Piperidinas/uso terapêutico , Adulto , Analgesia Obstétrica/métodos , Analgesia Controlada pelo Paciente/métodos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Anestésicos Combinados/administração & dosagem , Anestésicos Combinados/uso terapêutico , Anestésicos Locais/administração & dosagem , Anestésicos Locais/uso terapêutico , Bupivacaína/administração & dosagem , Bupivacaína/análogos & derivados , Bupivacaína/uso terapêutico , Método Duplo-Cego , Feminino , Fentanila/administração & dosagem , Humanos , Levobupivacaína , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Medição da Dor/estatística & dados numéricos , Satisfação do Paciente , Piperidinas/administração & dosagem , Gravidez , Remifentanil , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: This study evaluated efficacy, safety and patient satisfaction with incisional analgesia with a subfascial catheter compared to epidural analgesia for pain relief following caesarean section. METHODS: Forty patients were randomised after elective caesarean section to receive either intermittent 10-mL boluses of 0.125% levobupivacaine into the epidural space and physiologic saline into the surgical wound or intermittent 10-mL boluses of 0.25% levobupivacaine into the wound and epidural saline with a repeated 10-dose regimen. Analgesic efficacy was evaluated by numerical pain scores (0-10, 0=no pain, 10=worst pain) and based on the consumption of supplemental opioid. Side effects, patient satisfaction and plasma concentrations of levobupivacaine were recorded. RESULTS: In the epidural group average pain scores were lower (1.8 vs. 3, P=0.006) and the consumption of local anaesthetic (29 mL vs. 38 mL, P=0.01) was smaller during the first four postoperative hours, after which both groups had pain scores of 3 or less at rest. All parturients were able to walk after the 24-h study period. The total consumption of rescue opioid oxycodone (32 vs. 37 mg, P=0.6) during the whole 72-h study period was low in both study groups. Side effects were mild and rare. Satisfaction scores were equally high in the two groups. Peak plasma concentrations of levobupivacaine were below the toxic range. CONCLUSION: Incisional local analgesia via a subfascial catheter provided satisfactory pain relief with patient satisfaction comparable to that seen with epidural analgesia. This technique may be a good alternative to the more invasive epidural technique following caesarean section as a component of multimodal pain management.
Assuntos
Analgesia Epidural/métodos , Analgesia Obstétrica/métodos , Anestesia Local/métodos , Cesárea , Dor Pós-Operatória/prevenção & controle , Adulto , Analgesia Epidural/efeitos adversos , Analgesia Obstétrica/efeitos adversos , Analgesia Controlada pelo Paciente/efeitos adversos , Anestesia Local/efeitos adversos , Anestésicos Locais/administração & dosagem , Bupivacaína/administração & dosagem , Bupivacaína/análogos & derivados , Terapia Combinada , Método Duplo-Cego , Feminino , Humanos , Levobupivacaína , Medição da Dor , Dor Pós-Operatória/tratamento farmacológico , Gravidez , Estudos Prospectivos , Fatores de TempoRESUMO
OBJECTIVE AND METHODS: To study the effects of hormone replacement therapy on glucose metabolism, 31 obese (body mass index > or =27 kg/m(2)) postmenopausal women were randomized to treatment with tibolone (2.5 mg once daily; TIB; n=16) or to oestradiol valerate (2 mg daily)-dydrogesterone (20 mg daily for 2 weeks every 3 months; ED; n=15) for 12 months. Oral (OGTTs) and intravenous glucose tolerance tests (IVGTTs) and a euglycaemic hyperinsulinaemic clamp were performed before and at 6 and 12 months of treatment. RESULTS: TIB decreased the rates of whole body glucose uptake (WBGU) at 6 (P=0.04) and 12 months (P<0.001), but it did not have a significant effect on glucose tolerance. In OGTTs, serum insulin and C-peptide concentrations 2 h after the oral glucose load were increased (P<0.001 and P=0.05 respectively) at 12 months of treatment with TIB, but no changes in the areas under the curve (AUC) of insulin or C-peptide were observed. Furthermore, TIB did not have a significant effect on insulin secretion, the metabolic clearance rate (MCR) of insulin or hepatic insulin extraction. Treatment with ED did not modify the rates of WBGU, but it increased the MCR of insulin (P=0.017) and hepatic insulin extraction (P<0.001) and tended to decrease the insulin AUC (P=0.07). Moreover, glucose tolerance slightly deteriorated during this treatment (P=0.02). Although early phase insulin secretion evaluated by the serum C-peptide response at 30 min in the OGTT increased (P=0.046), the first-phase insulin response during the IVGTT decreased (P=0.05) during ED treatment. CONCLUSIONS: Despite the impairment in peripheral insulin sensitivity, TIB treatment had a neutral effect on glucose tolerance, possibly due to a compensatory decrease in endogenous glucose production. The increased demand on insulin induced by ED, due to both a stimulatory effect on pancreatic beta cells and increased insulin metabolism, may explain the slightly detrimental effect on glucose tolerance with this treatment.
Assuntos
Moduladores de Receptor Estrogênico/uso terapêutico , Terapia de Reposição de Estrogênios , Glucose/metabolismo , Norpregnenos/uso terapêutico , Obesidade/metabolismo , Pós-Menopausa , Área Sob a Curva , Glicemia/análise , Quimioterapia Combinada , Didrogesterona/uso terapêutico , Estradiol/uso terapêutico , Ácidos Graxos não Esterificados/sangue , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/metabolismo , Secreção de Insulina , Modelos Lineares , Metabolismo dos Lipídeos , Pessoa de Meia-Idade , OxirreduçãoRESUMO
OBJECTIVE: We determined the effects of continuous combined nonoral and oral estrogen-progestin therapy on plasma levels of insulin-like growth factor-I (IGF-I) and its binding proteins 1 (IGFBP-1) and 3 (IGFBP-3). DESIGN: Forty women complaining of climacteric symptoms were randomized to receive either transdermal estradiol patches (50 microg daily) in combination with an intrauterine system releasing 20 microg of levonorgestrel daily or an established regimen of an oral dose of 2 mg of estradiol and 1 mg of norethisterone acetate daily for 1 year. Fifteen women in the nonoral therapy group and 17 in the oral therapy group completed the 1-year prospective study. RESULTS: Plasma levels of IGF-I decreased significantly in the oral therapy group, but no changes were observed in the plasma levels of its binding proteins. Transdermal estrogen in combination with intrauterine levonorgestrel did not induce any change in plasma IGF-I, whereas the plasma levels of IGFBP-3 decreased. IGFBP-1 concentrations increased, which may be related to the induction of this protein into the endometrium by the intrauterine levonorgestrel delivery. CONCLUSIONS: Both the nonoral and oral continuous combined estrogen-progestin therapies used in this study produced only minor changes in the circulating concentrations of IGF-I and its binding proteins.
Assuntos
Estradiol/farmacologia , Terapia de Reposição de Estrogênios/métodos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/efeitos dos fármacos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/metabolismo , Dispositivos Intrauterinos Medicados , Levanogestrel/farmacologia , Noretindrona/farmacologia , Congêneres da Progesterona/farmacologia , Administração Cutânea , Administração Oral , Adulto , Monitoramento de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJECTIVES: Nonoral administration of hormone replacement therapy avoids the first pass metabolism of steroids in the liver. We wanted to determine to what extent it has an effect on the serum concentrations of sex-hormone binding globulin and the free testosterone index. METHODS: Postmenopausal women received 50 microg per day transdermal estradiol associated with the use of a levonorgestrel-releasing intrauterine device (20 women) or a daily oral dose of 2 mg of estradiol and 1 mg of norethisterone acetate (20 women) for 1 year. Eight women, five in the nonoral and three in the oral therapy group discontinued the study. RESULTS: Although serum sex-hormone binding globulin concentrations decreased in women receiving transdermal estradiol in combination with a levonorgestrel-releasing intrauterine device, the free testosterone index did not change significantly. In the continuous oral regimen, no significant changes in serum sex-hormone binding globulin or free testosterone index were observed. The free testosterone index, however, was significantly higher in the nonoral therapy group after 6 and 12 months of treatment than in the oral therapy group. CONCLUSIONS: Continuous progestin combined with continuous estrogen in oral and nonoral replacement therapy does not lead to a substantial androgenic excess in postmenopausal women. The intrauterine administration of levonorgestrel appears to have some hepatic effect.
Assuntos
Biomarcadores/sangue , Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios , Levanogestrel/administração & dosagem , Pós-Menopausa/efeitos dos fármacos , Globulina de Ligação a Hormônio Sexual/metabolismo , Testosterona/sangue , Administração Cutânea , Administração Oral , Adulto , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: To study the effect of postmenopause and postmenopausal hormone replacement therapy (HRT) on the measured fundamental frequency (F0) and sound pressure level (SPL) of sustained phonation and speaking voice samples and on subjective vocal/laryngeal symptoms. METHODS: Forty-three postmenopausal women (mean age 51.6) were divided into three groups: a group with no HRT, an estrogen group (daily oral dose of 2 mg of estradiol valerate), and an estrogen-progestin group (daily oral dose of 2 mg of 17-B-estradiol and 1 mg of northisterone acetate). Voice measurements were made before and after 1 year of treatment. Subjective symptoms were registered using a questionnaire. RESULTS: The mean F0 and SPL decreased significantly in the group with no HRT in spontaneous speech and reading samples as did SPL in the normal phonation sample. In both groups with HRT, the mean F0 decreased significantly only in the spontaneous speech sample and the decrease was smaller than in the group with no HRT. The mean SPL decrease in the estrogen group was significant in the normal phonation sample while in the estrogen-progestin group it was significant in both the normal phonation and the reading sample. The number of subjective symptoms was smallest in the estrogen group. CONCLUSIONS: The changes in the measured voice values and the subjective symptoms experienced suggest that at least the early postmenopausal years are associated with vocal changes and that HRT counteracts this phenomenon. This seems to be more pronounced with estrogen than with a combination of estrogen and progestin.
Assuntos
Terapia de Reposição de Estrogênios , Estrogênios/uso terapêutico , Pós-Menopausa/efeitos dos fármacos , Progestinas/uso terapêutico , Qualidade da Voz/efeitos dos fármacos , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa/fisiologia , Valores de Referência , Inquéritos e Questionários , Qualidade da Voz/fisiologiaRESUMO
OBJECTIVES: To compare the effects of a non-oral combination of a transdermal oestradiol patch (50 micrograms daily) and an intrauterine device (IUD) releasing 20 micrograms of levonorgestrel daily on the serum pattern of lipids and lipoproteins with an established oral regimen of a daily dose of 2 mg of estradiol and 1 mg of noretisterone acetate. METHODS: An open, randomized study comprised of 40 healthy, early postmenopausal women. RESULTS: During 1 year the concentration of total cholesterol decreased 5.0% in the LNg-IUD group and 10.6% in the oral therapy group; HDL cholesterol decreased 10.9% and 12.8%, respectively, and HDL2 cholesterol decreased 18.1% and 26.9%, respectively. LDL cholesterol values did not change in the LNg-IUD group, whereas a 10.3% decrease was observed in the oral therapy group. Triglyceride values did not change in either group. There were no significant differences in the serum lipoprotein changes between the groups during the treatment. CONCLUSIONS: The use of a non-oral regimen of hormone replacement therapy has been advocated to minimize the effect of steroids on the liver. Its effects on the serum pattern of lipids and lipoproteins, however, did not differ significantly from those induced by a continuous oral treatment regimen.
Assuntos
Climatério/efeitos dos fármacos , Terapia de Reposição de Estrogênios , Dispositivos Intrauterinos Medicados , Levanogestrel/administração & dosagem , Lipídeos/sangue , Lipoproteínas/sangue , Administração Cutânea , Administração Oral , Adulto , Colesterol/sangue , Climatério/sangue , Estradiol/administração & dosagem , Estradiol/efeitos adversos , Feminino , Seguimentos , Humanos , Levanogestrel/efeitos adversos , Pessoa de Meia-Idade , Noretindrona/administração & dosagem , Noretindrona/análogos & derivados , Acetato de Noretindrona , Triglicerídeos/sangueRESUMO
In an open, multicentre study, transdermal administration of oestradiol (E2) by means of skin patches was investigated in a Finnish patient population suffering from typical post-menopausal symptoms. A total of 249 women applied a patch twice weekly for 6 months. Whereas 85% of the subjects were experiencing hot flushes and 83.5% sweating before therapy, only 5.7% and 11.8%, respectively, reported these symptoms at the end of the trial. Furthermore, 97.6%, 95.7% and 94.8% of the subjects reported that depression, headache and sleep disturbances, respectively, had disappeared during therapy. Skin irritation occurred in 18.2% of these predominantly fair-skinned women. Frequent sauna bathing did not interfere with the patch therapy. General acceptance of the treatment was excellent, 84.8% of the patients completing the treatment, of whom 78% were willing to continue the treatment after the trial. These results show that transdermal administration of E2 is effective in relieving post-menopausal symptoms. Local tolerability was good and the majority of the patients considered the transdermal treatment to be superior to their previous oral replacement therapy.
Assuntos
Terapia de Reposição de Estrogênios/métodos , Administração Cutânea , Terapia de Reposição de Estrogênios/efeitos adversos , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: To investigate the effect of estrogen alone or combined with progestin on the amount and synthesis of skin collagen in postmenopausal women. METHODS: Forty-three early postmenopausal women were enrolled into this open, non-randomized parallel-groups study. Fifteen women received a continuous oral dose of 2 mg of 17 beta-estradiol and 1 mg of norethisterone acetate daily and 14 women an oral dose of 2 mg estradiol valerate daily. Fourteen subjects served as controls. The histology and type I and III procollagen immunohistochemistry of the skin, skin thickness, the amount of total collagen determined by a colorimetric method and the synthesis of type I and III collagens determined by analysing procollagen propeptides in the suction blister fluid were studied before the treatment and at 6 and 12 months. The proportional area of elastic fibers and the thickness of the epidermis were assessed from the sections obtained before the treatment and at 12 months, with computerized image analysis. RESULTS: Skin thickness, the amount and rate of collagen synthesis, the proportional area of elastic fibers and the thickness of the epidermis were not affected by either 17 beta-estradiol and 1 mg of norethisterone acetate or 2 mg of estradiol valerate. No histological or immunohistological changes were detected in the skin specimens during the 12-month treatment period compared to the baseline or to the skin specimens of the control group. CONCLUSIONS: A 1-year treatment with systemic estrogen alone or combined with progestin does not change the amount of collagen or the rate of collagen synthesis in postmenopausal women.
Assuntos
Colágeno/efeitos dos fármacos , Estradiol/farmacologia , Terapia de Reposição de Estrogênios , Noretindrona/farmacologia , Pós-Menopausa/fisiologia , Congêneres da Progesterona/farmacologia , Pele/efeitos dos fármacos , Administração Oral , Biópsia , Estudos de Coortes , Colágeno/análise , Colágeno/biossíntese , Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios/métodos , Feminino , Humanos , Hidroxiprolina/análise , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Pessoa de Meia-Idade , Noretindrona/administração & dosagem , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/imunologia , Pós-Menopausa/efeitos dos fármacos , Pró-Colágeno/análise , Pró-Colágeno/imunologia , Congêneres da Progesterona/administração & dosagem , Pele/anatomia & histologia , Pele/metabolismo , Fatores de TempoRESUMO
OBJECTIVE: Gestational diabetes mellitus (GDM) is associated with an increased risk of subsequent diabetes and metabolic syndrome (MS). The independent significance of overweight, often associated with GDM, is controversial. This study was aimed to investigate the prevalence of MS and carotid intima-media thickness (CIMT) values in normal and overweight women with previous insulin-treated GDM and control without GDM 19 years after the index pregnancy. METHODS: The study group consisted of 61 women with prior GDM and 55 controls who gave birth in Oulu University Hospital between 1988 and 1993. These women were further divided into subgroups according to pre-pregnancy BMI (<25 or ≥25âkg/m(2)). In 2008-2010, anthropometrics and blood pressure were measured, blood samples were taken, and an oral glucose tolerance test was performed to investigate the components of MS. CIMT was measured by Doppler ultrasound. RESULTS: Total prevalence of MS was 62% in the GDM group and 31% in the control group (P=0.001); it was highest (86%) in GDM women with pre-pregnancy overweight. CIMT was significantly thicker (0.67 vs 0.56âmm, P=0.007) and more often abnormal (71.7 vs 45.3%, P=0.004) in the GDM group compared with the controls. In logistic regression analysis, the strongest factor predicting MS in the whole study population was pre-pregnancy overweight. CONCLUSIONS: Pre-pregnancy overweight was the strongest predictive factor for later MS, whereas GDM indicated increased risk of subsequent diabetes and subclinical atherosclerosis. The risk of MS was highest when both of these factors were present.
Assuntos
Complicações do Diabetes/epidemiologia , Diabetes Gestacional/epidemiologia , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Adulto , Antropometria , Aterosclerose/complicações , Aterosclerose/epidemiologia , Glicemia/metabolismo , Pressão Sanguínea/fisiologia , Espessura Intima-Media Carotídea , Diabetes Mellitus Tipo 2/epidemiologia , Dislipidemias/epidemiologia , Feminino , Finlândia/epidemiologia , Seguimentos , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Modelos Logísticos , Pessoa de Meia-Idade , Paridade , Gravidez , Fatores de RiscoRESUMO
BACKGROUND: Epidural and spinal analgesia may be contraindicated or unavailable in labour. This randomised controlled study examined the suitability of paracervical block as an alternative method of labour analgesia. METHODS: Multiparous women in labour were randomised to receive either paracervical block or single-shot spinal analgesia. Pain was quantified using a numerical rating scale. Subsequent analgesia, progress of labour, and mode of delivery were noted. Fetal heart rate patterns were reviewed. Apgar scores and umbilical artery pH measurements were collected. Parturients' satisfaction and willingness to have the same method of labour analgesia again were recorded. RESULTS: 122 parturients were randomised with data available on 104. Median pain scores decreased significantly in both groups; this was greater with single-shot spinal analgesia (difference between means 2.7; 95% CI 1.9-3.5; P(g)<0.001). Parturients receiving paracervical block received subsequent analgesia more often (23/56 vs. 3/48, P<0.001). Progress of labour, instrumental delivery rates, detected abnormal decelerations in cardiotocography and neonatal outcome were similar between groups. Shivering (P<0.04) and pruritus (P<0.001) were more common with single-shot spinal analgesia. Parturients in the paracervical block group were less satisfied (median 7.0, IQR 3.0-8.0 vs. median 9.0, IQR 8.0-10.0; P<0.001) and less willing (28/55 vs. 39/48, P=0.002) to have the same labour analgesia again. CONCLUSIONS: Paracervical block was less effective than single-shot spinal analgesia. Both methods were associated with a low incidence of fetal bradycardia but maternal side effects were more common with single-shot spinal analgesia.
Assuntos
Analgesia Obstétrica , Anestesia Obstétrica , Paridade , Satisfação do Paciente , Adulto , Analgesia Obstétrica/métodos , Analgesia Obstétrica/psicologia , Analgesia Obstétrica/estatística & dados numéricos , Anestesia Obstétrica/efeitos adversos , Anestesia Obstétrica/psicologia , Anestesia Obstétrica/estatística & dados numéricos , Raquianestesia/efeitos adversos , Raquianestesia/métodos , Anestésicos Locais , Bupivacaína , Feminino , Finlândia , Frequência Cardíaca Fetal/efeitos dos fármacos , Humanos , Medição da Dor , Gravidez , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: We compared the efficacy and side-effects of remifentanil with those of nitrous oxide during the first stage of labour. METHODS: Twenty parturients participated in a randomized, double-blind, cross-over study. Intravenous remifentanil in 0.4 microg kg(-1) PCA doses with 1-min infusion and lock-out times and intermittent inhaled 50% nitrous oxide were compared during 20-min study periods with a 20-min wash-out sequence after each period. The parturients assessed the intensity of contraction pain (verbal numerical score 0-10), pain relief (score 0-4) and side-effects every 10 min. Noninvasive blood pressure, heart rate (HR), oxyhaemoglobin saturation (SaO2), end-tidal carbon dioxide, fractions of inhaled and exhaled oxygen and nitrous oxide and foetal heart rate (FHR) were recorded. Hypoxaemia and bradycardia were defined as SaO2<90% and HR<50, respectively. RESULTS: Fifteen parturients completed the study. There was no period effect or treatment-period interaction. The median decrease in pain score for remifentanil was 1.5 and that for nitrous oxide 0.5 (P=0.01). The parturients gave better pain relief scores with remifentanil than with nitrous oxide (median 2.5 vs. 0.5, respectively, P<0.001). Sedation was reported more often, and SaO2 was slightly lower during remifentanil administration. No episodes of hypoxaemia occurred. There was no difference in maternal blood pressure and HR or the incidence of abnormal FHR during remifentanil compared to nitrous oxide. Most parturients preferred remifentanil to nitrous oxide (14 vs. 1, P<0.001). CONCLUSIONS: This study suggests that IVPCA remifentanil provides better labour analgesia than intermittently inhaled nitrous oxide.
Assuntos
Analgesia Obstétrica , Analgésicos Opioides , Anestésicos Inalatórios , Óxido Nitroso , Piperidinas , Administração por Inalação , Adolescente , Adulto , Analgesia Obstétrica/efeitos adversos , Analgesia Controlada pelo Paciente , Analgésicos Opioides/efeitos adversos , Anestésicos Inalatórios/efeitos adversos , Feminino , Frequência Cardíaca Fetal/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Humanos , Injeções Intravenosas , Óxido Nitroso/efeitos adversos , Medição da Dor/efeitos dos fármacos , Piperidinas/efeitos adversos , Gravidez , RemifentanilRESUMO
OBJECTIVE: To compare the risk for congenital malformations in offspring between women with epilepsy being treated with antiepileptic drugs (AEDs) during pregnancy and those who discontinued their antiepileptic medication before pregnancy in a population-based cohort of female patients with epilepsy. METHODS: All patients with epilepsy (n = 20,101) eligible for AED reimbursement for the first time during 1985 to 1994 were identified from the Social Insurance Institution of Finland. Information on births during 1991 to 2000 was obtained from the National Medical Birth Registry. Information on AED use during pregnancy and on pregnancy outcomes was abstracted from medical records. RESULTS: Congenital malformations were more common among offspring of women on antiepileptic medication (65/1,411; 4.6%) than among offspring of untreated patients (26/939; 2.8%) (p = 0.02). The risk of malformations was substantially higher in the offspring of patients using valproate as monotherapy (OR = 4.18; 95% CI: 2.31, 7.57) or valproate as polytherapy (OR = 3.54; 95% CI: 1.42, 8.11) than of untreated patients. Polytherapy without valproate was not associated with increased risk of malformations. CONCLUSION: Excess risk was confined to patients using valproate during pregnancy. The risk for malformations was not elevated in offspring of mothers using carbamazepine, oxcarbazepine, or phenytoin (as monotherapy or polytherapy without valproate).
Assuntos
Anormalidades Induzidas por Medicamentos/epidemiologia , Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Anormalidades Induzidas por Medicamentos/patologia , Anormalidades Induzidas por Medicamentos/fisiopatologia , Adulto , Anormalidades Cardiovasculares/induzido quimicamente , Anormalidades Cardiovasculares/epidemiologia , Fissura Palatina/induzido quimicamente , Fissura Palatina/epidemiologia , Estudos de Coortes , Quimioterapia Combinada , Feminino , Finlândia/epidemiologia , Genitália/anormalidades , Humanos , Anormalidades Musculoesqueléticas/induzido quimicamente , Anormalidades Musculoesqueléticas/epidemiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Fatores de Risco , Disrafismo Espinal/induzido quimicamente , Disrafismo Espinal/epidemiologia , Ácido Valproico/efeitos adversosRESUMO
BACKGROUND: The study was devised to measure the effect of intrauterinely delivered levonorgestrel and transdermal estradiol on insulin sensitivity in postmenopausal women and compare this effect with that induced by transdermal estradiol alone. METHODS: An open, prospective, comparative study of healthy postmenopausal women without earlier use of hormone replacement therapy. The estrogen therapy group consisted of eight hysterectomized women, who used a transdermal patch delivering a daily dose of 50 microg of estradiol continuously for 6 months. The estrogen-progestin therapy group consisted of 13 women with an intact uterus, who received a simultaneous combination of a transdermal patch and a levonorgestrel (20 microg/day) intrauterine system for the same length of time. Fasting plasma concentrations of glucose, insulin and C-peptide and an insulin tolerance test were used to measure glucose metabolism and insulin sensitivity. RESULTS: Neither therapy changed the fasting plasma levels of glucose, insulin or C-peptide. Transdermal estrogen improved insulin sensitivity by 22%, as measured by an insulin tolerance test, while a small increase of 3.6% was observed using the combination therapy. CONCLUSIONS: Transdermal estradiol improves insulin sensitivity in healthy postmenopausal women. Combining intrauterine levonorgestrel to transdermal estradiol reverses this effect. This combination does not, however, seem to induce insulin resistance.
Assuntos
Estradiol/administração & dosagem , Terapia de Reposição Hormonal , Resistência à Insulina , Levanogestrel/administração & dosagem , Pós-Menopausa , Congêneres da Progesterona/administração & dosagem , Administração Cutânea , Glicemia/análise , Peptídeo C/sangue , Estradiol/sangue , Feminino , Humanos , Histerectomia , Insulina/sangue , Pessoa de Meia-IdadeRESUMO
The aim of this study was to determine the effect of continuous intrauterine release of progestin on the uterine artery pulsatility index (PI) in women on postmenopausal hormone replacement therapy (HRT). The voluntary participants, 13 symptomatic postmenopausal women received transdermal estradiol (50 micrograms/day) for 1 month before combining the levonorgestrel-releasing (20 micrograms/day) intrauterine system (LNG-IUS) with estrogen replacement therapy. The PI of uterine artery blood flow was measured by transvaginal color Doppler ultrasonography before the onset of HRT, 1 month after the treatment with estradiol (estradiol-only phase) and 1, 3 and 6 months after insertion of the LNG-IUS. The mean uterine artery PI decreased significantly from its pretreatment level after 1 month of transdermal estradiol treatment (p < 0.05), but the LNG-IUS induced an increase in PI, and 6 months after its insertion the PI did not differ significantly from the pretreatment level (p > 0.05). Compared with the estradiol-only phase, the last measurement of the PI was significantly increased (p < 0.05). The results suggest that continuous intrauterine release of levonorgestrel abolishes the vasodilatory effect on the uterine arteries accomplished by postmenopausal estradiol treatment.
Assuntos
Sistemas de Liberação de Medicamentos , Terapia de Reposição de Estrogênios , Progestinas/administração & dosagem , Útero/irrigação sanguínea , Estradiol/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Fluxo Sanguíneo Regional , Ultrassonografia Doppler , Útero/diagnóstico por imagem , Vasodilatação/efeitos dos fármacosRESUMO
OBJECTIVE: Our purpose was to study the effects of intrauterine release of a daily dose of 20 micrograms levonorgestrel by an intrauterine device on climacteric symptoms, bleeding pattern, and endometrial histologic features in postmenopausal women receiving transdermal estrogen replacement therapy. STUDY DESIGN: Forty parous postmenopausal women were randomly allocated into two groups for 1 year: 20 women receiving a continuous transdermal daily dose of 50 micrograms of estradiol had a levonorgestrel-releasing intrauterine contraceptive device inserted, and the control group of 20 women received a continuous oral dose of 2 mg of estradiol valerate and 1 mg of norethisterone acetate daily. The climacteric symptoms, bleeding patterns, endometrial thickness, and endometrial changes in biopsy samples were analyzed. Serum levels of estradiol in both groups and levonorgestrel levels in the intrauterine device group were also determined. RESULTS: Both treatment regimens effectively relieved climacteric symptoms. Spotting was more common in the intrauterine contraceptive device group than in the oral therapy group for the first 3 months. After that, the proportion of women without any bleeding was similar in both groups. Two patients in each group dropped out because of bleeding. CONCLUSION: These preliminary findings suggest that the levonorgestrel-releasing intrauterine contraceptive device is a useful alternative mode of progestin administration for certain selected women receiving estrogen replacement therapy.
PIP: The purpose was to study the effects of intrauterine release of a daily dose of 20 mcg levonorgestrel by an IUD on climacteric symptoms, bleeding pattern, and endometrial histologic features in postmenopausal women receiving transdermal estrogen replacement therapy. 40 parous postmenopausal women were randomly allocated into 2 groups for 1 year. They were required to be parous, to have an intact uterus, and to have had amenorrhea for at least 6 months but less than 5 years. 20 women received a combination of 50 mcg of estradiol per 24 hours delivered transdermally from a patch, and received estrogen pretreatment for 1 month to make insertion of a levonorgestrel-releasing IUD (Levonova), which was installed a month later, easier. This combination was continued for 1 year. The control group of 20 women received an established form of continuous oral estrogen and progestin with a daily dose of 2 mg of estradiol, and 1 mg of norethindrone acetate also administered for 1 year. Checkup visits were scheduled at 3, 6, and 12 months. The climacteric symptoms, bleeding patterns, endometrial thickness, and endometrial changes in biopsy samples were analyzed. The increase in estradiol concentration was similar in both groups, and the mean concentrations of levonorgestrel in the IUD group were 216 +or- 25 pg/ml at 3 months, 209 +or- 11 pg/ml at 6 months, and 212 + 10.5 pg/ml at 12 months. Both treatment regimens effectively relieved climacteric symptoms. The IUD group experienced more days of bleeding, primarily spotting, during the first 3 months than did the oral therapy group but the differences between the groups had disappeared by 6 months. Both treatments resulted in an atrophic endometrium developing from a proliferative one. Two patients in each group dropped out because of bleeding. The levonorgestrel-releasing IUD is a useful alternative mode of progestin administration for certain selected women receiving estrogen replacement therapy.