RESUMO
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy specific liver disease characterized by pruritus, elevated serum bile acids and abnormal liver function that may be associated with severe adverse pregnancy outcomes. We previously reported that plasma coenzyme Q10 (CoQ10) is decreased in women with ICP as it is its analogue coenzyme Q9 (CoQ9) in rats with ethinyl estradiol (EE)-induced cholestasis. The aim of the present study was to evaluate the possible therapeutic role of CoQ10 in experimental hepatocellular cholestasis and to compare it with ursodeoxycholic acid (UDCA) supplementation. Bile acids, CoQ9, CoQ10, transaminases, alkaline phosphatase, retinol, α-tocopherol, ascorbic acid, thiobarbituric acid reactive substances, carbonyls, glutathione, superoxide dismutase and catalase were assessed in plasma, liver and/or hepatic mitochondria in control and cholestatic rats supplemented with CoQ10 (250 mg/kg) administered alone or combined with UDCA (25 mg/kg). CoQ10 supplementation prevented bile flow decline (P < 0.05) and the increase in serum alkaline phosphatase and bile acids, particularly lithocholic acid (P < 0.05) in cholestatic rats. Furthermore, it also improved oxidative stress parameters in the liver, increased both CoQ10 and CoQ9 plasma levels and partially prevented the fall in α-tocopherol (P < 0.05). UDCA also prevented cholestasis, but it was less efficient than CoQ10 to improve the liver redox environment. Combined administration of CoQ10 and UDCA resulted in additive effects. In conclusion, present findings show that CoQ10 supplementation attenuated EE-induced cholestasis by promoting a favorable redox environment in the liver, and further suggest that it may represent an alternative therapeutic option for ICP.
Assuntos
Colestase Intra-Hepática/tratamento farmacológico , Suplementos Nutricionais , Complicações na Gravidez/tratamento farmacológico , Ubiquinona/análogos & derivados , Animais , Catalase/metabolismo , Colestase Intra-Hepática/metabolismo , Feminino , Glutationa/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Gravidez , Complicações na Gravidez/metabolismo , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Ubiquinona/farmacologia , Ubiquinona/uso terapêutico , Ácido Ursodesoxicólico/uso terapêuticoRESUMO
Hypertriglyceridemia is the third most common cause of acute pancreatitis. Among the causes that lead to secondary hypertriglyceridemia, the use of contraceptive agents is the main reason to be assessed in young women. We report a case of a 31-year-old woman who had suffered two acute pancreatitis episodes secondary to hypertriglyceridemia. In the investigation, the previous medical team indicated a genetic screening before ruling out all secondary causes. LPL, apo CII and apo AV genes were negative for mutations. In the first appointment with us, the patient reported the use of a contraceptive agent for about 2 years. She was instructed to discontinue the drug. After one year of follow-up, her serum triglycerides are within the normal range and a copper intrauterine device was the method chosen by the patient for contraception.
Assuntos
Anticoncepcionais Orais Sintéticos/efeitos adversos , Estrogênios/efeitos adversos , Etinilestradiol/efeitos adversos , Hipertrigliceridemia/complicações , Norpregnenos/efeitos adversos , Pancreatite/etiologia , Adulto , Humanos , Hipertrigliceridemia/induzido quimicamenteRESUMO
The 1 H and 13 C NMR spectra of 17-α-ethinylestradiol (EE2), a well-known contraceptive, including diastereotopic methylene groups, were fully assigned with the help of residual dipolar couplings (RDC) measured in the recently developed grafted graphene oxide orienting medium. RDC analysis, which included all 1 DCH couplings and the long-range 2 DCH1 H-C≡13 C coupling, also pointed to the presence of a minor conformation arising from pseudo-rotation of the steroid B ring. Saturation-transfer difference (STD) measurements revealed that the most likely interaction between EE2 and orienting medium occurred on the C and D ring. Copyright © 2016 John Wiley & Sons, Ltd.
Assuntos
Etinilestradiol/química , Grafite/química , Espectroscopia de Ressonância Magnética/métodos , Óxidos/química , Isótopos de Carbono/química , Modelos Moleculares , Conformação Molecular , Simulação de Dinâmica Molecular , PrótonsRESUMO
Hydroxypropyl methylcellulose (HPMC) E4M chains are crosslinked with citric acid and ethylenediaminetetraacetic acid (EDTA), resulting in adsorbent sponges (SpE4M), which are impregnated with magnetic nanoparticles (SpE4M-mag) for the adsorption of 17 α-ethinyl estradiol (EE). The characterization of SpE4M and SpE4M-mag characterization includes X-ray microcomputer tomography (Micro-CT), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) vibrational spectroscopy, elemental analysis, inductively coupled plasma optical emission spectrometry (ICP-OES), and X-ray diffraction (XRD). SpE4M and SpE4M-mag present porosities of 72±6 % and 80±7 %, respectively, and outstanding stability in water, in the pH range 4 to 8, and in alcohols, alkanes, and acetone. The compressive moduli of SpE4M and SpE4M-mag amount to 2.75 and 4.37â MPa, respectively. The adsorption of 17 α-ethinyl estradiol (EE), an estrogenic pollutant, on SpE4M and SpE4M-mag follows the pseudo-first-order kinetic model. The EE removal capacity by SpE4M is 78±5 %, which is twice that presented by SpE4M-mag. The new sponges are recovered successfully either by flotation or by an external magnet, and can be recycled five times keeping 80 % of their initial removal capacity after the fifth cycle, disclosing their potential for environmental remediation.
RESUMO
O estrogênio sintético 17α-etinilestradiol, principal componente utilizado em formulações de contraceptivos orais, tem sido apontado como um dos principais compostos responsáveis por provocar efeitos adversos no sistema endócrino de várias espécies. O objetivo deste estudo foi analisar o estado da arte dos dispositivos legais e normativos referentes ao controle desse estrogênio sintético nas águas da Europa e dos Estados Unidos, e traçar um paralelo com a realidade brasileira. No geral, os países têm buscado ampliar a regulamentação e monitoramento de alguns micropoluentes emergentes que antes não eram objeto de atenção por parte dos dispositivos legais. A Europa está mais avançada no que tange à qualidade dos corpos hídricos, enquanto que nos Estados Unidos esta substância é alvo de regulamentação apenas para a água destinada ao consumo humano. No Brasil, ainda não há nenhum dispositivo legal ou normativo que aborde esse estrogênio, o que pode ser associado a uma baixa maturidade do sistema brasileiro quanto ao controle de poluentes hídricos.
El estrógeno sintético 17α-etinilestradiol, principal componente utilizado en fórmulas de contraceptivos orales, ha sido apuntado como uno de los principales compuestos responsables por provocar efectos adversos en el sistema endócrino de varias especies. El objetivo de este estudio fue analizar el estado de la cuestión de los dispositivos legales y normativos referentes al control de este estrógeno sintético en las aguas de Europa y de los Estados Unidos, y trazar un paralelo con la realidad brasileña. En general, los países han buscado ampliar la regulación y el monitoreo de algunos microcontaminantes emergentes que antes no eran objeto de atención por parte de los dispositivos legales. Europa está más avanzada en lo que se refiere a la calidad de los cuerpos hídricos, mientras que en los Estados Unidos esta substancia es objeto de regulación solamente para el agua destinada al consumo humano. En Brasil todavía no existe ningún dispositivo legal o normativo que aborde este estrógeno, lo que puede ser asociado a una inmadurez del sistema brasileño respecto al control de contaminantes hídricos.
The synthetic estrogen 17α-ethinylestradiol, the principal component of oral contraceptives, has been identified as one of the main compounds accounting for adverse effects on the endocrine system in various species. This study aimed to analyze the state-of-the-art in legislation and guidelines for the control of this synthetic estrogen in water bodies in Europe and the United States and to draw a parallel with the Brazilian reality. Countries have generally attempted to expand the regulation and monitoring of certain emerging micropollutants not previously covered by legislation. Europe is more advanced in terms of water quality, while in the United States this estrogen is only regulated in water for human consumption. Brazil still lacks legal provisions or standards for this estrogen, which can be explained by the relatively limited maturity of the country's system for controlling water pollutants.
Assuntos
Humanos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/efeitos adversos , Poluição da Água/legislação & jurisprudência , Congêneres do Estradiol/análise , Congêneres do Estradiol/efeitos adversos , Etinilestradiol/análise , Etinilestradiol/efeitos adversos , Estados Unidos , Brasil , Estrogênios , Disruptores Endócrinos/análise , Disruptores Endócrinos/efeitos adversos , Europa (Continente) , Água Doce/análise , Água Doce/químicaRESUMO
Several studies have reported an increase in the prevalence of adult female acne. This subtype of acne presents particular characteristics, and can be triggered by several factors such as smoking, stress, the use of oily cosmetics and even by poor sleep. Sleep quality is related to well-being and the maintenance of body homeostasis. In addition, several skin diseases present a bidirectional relationship with sleep, demonstrating an important connection between skin and the central nervous system. With this in mind, we aimed to compare the effect of two types of treatment for adult female acne (azelaic acid or a combined oral contraceptive) on sleep quality and on concentrations of stress hormones. Also, we proposed to assess the correlation of sleep and hormonal parameters with acne severity. In order to do this, 32 women underwent a clinical evaluation, completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire and had their blood collected for hormone assays. These procedures were performed at baseline and after 6 months of treatment. At baseline there were no differences between the groups in terms of body mass index, age, acne severity and hormone concentrations. Results showed that both treatments demonstrated effectiveness but that women treated with azelaic acid presented a better sleep quality after the treatment compared to baseline and to the group treated with the combined oral contraceptive. The combined oral contraceptive group presented an increase in cortisol and a decrease in free testosterone concentration in relation to baseline. These data suggest that both azelaic acid and combined oral contraceptive are effective in the treatment of adult female acne but, azelaic acid seems to be a more suitable option for those women who may benefit from a better subjective sleep quality.
Assuntos
Acne Vulgar/tratamento farmacológico , Anticoncepcionais Orais Combinados/uso terapêutico , Anticoncepcionais Orais Hormonais/uso terapêutico , Ácidos Dicarboxílicos/uso terapêutico , Medicamentos Indutores do Sono/uso terapêutico , Sono/efeitos dos fármacos , Hormônio Adrenocorticotrópico/sangue , Adulto , Sistema Nervoso Central/fisiologia , Feminino , Humanos , Hidrocortisona/sangue , Fenômenos Fisiológicos da Pele , Inquéritos e Questionários , Testosterona/sangueRESUMO
This Phase III, uncontrolled, open-label, multicenter study was conducted to investigate the contraceptive efficacy, bleeding pattern, and cycle control of a novel once-a-week contraceptive patch, delivering low-dose ethinyl estradiol (EE) and gestodene (GSD) at the same systemic exposure seen after oral administration of a combined oral contraceptive containing 0.02 mg EE/0.06 mg GSD. Participants were women aged 18 to 35 years, all of whom received the EE/GSD patch for 13 cycles each of 21 treatment days (one patch per week for 3 weeks) followed by a 7-day, patch-free interval. The primary efficacy variable was the occurrence of unintended pregnancies during the study period as assessed by life table analysis and the Pearl Index. Secondary efficacy variables were days with bleeding during four 90-day reference periods and during 1 treatment year, bleeding pattern, and cycle control. The Kaplan-Meier probability of contraceptive protection after 364 treatment days was 98.8% and the adjusted Pearl Index was 0.81. The percentage of participants with intracyclic bleeding/spotting decreased over time, from 11.4% to 6.8% in cycles 1 and 12, respectively. Almost all participants (range: 90.8%-97.6%) experienced withdrawal bleeding across the study period. Compliance was very high (mean: 97.9%; median: 100%). The most frequent adverse events were headache (9.5%) and application site reaction (8.5%); no clinically significant safety concerns were observed. Results suggest the EE/GSD patch is highly effective in preventing pregnancy. Menstrual bleeding pattern was favorable and within the ranges expected of a healthy female population. The patch was well tolerated and treatment compliance was high.
Assuntos
Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Orais Combinados/administração & dosagem , Etinilestradiol/administração & dosagem , Menstruação/efeitos dos fármacos , Norpregnenos/administração & dosagem , Administração Cutânea , Administração Oral , Adolescente , Adulto , Austrália , Chile , Anticoncepcionais Femininos/efeitos adversos , Anticoncepcionais Orais Combinados/efeitos adversos , Esquema de Medicação , Etinilestradiol/efeitos adversos , Europa (Continente) , Feminino , Humanos , Adesão à Medicação , México , Norpregnenos/efeitos adversos , Gravidez , Gravidez não Planejada , Gravidez não Desejada , Fatores de Tempo , Adesivo Transdérmico , Adulto JovemRESUMO
A simple, rapid, economical and reliable high performance liquid chromatographic method has been developed and successfully applied in simultaneous determination of ethinyl estradiol and drospirenone in coated tablets. The HPLC method was performed on a LiChroCART® 100RP column (125x4 mm i.d., 5 µm) with acetonitrile:water 50:50 (v/v) as mobile phase, pumped at a flow rate of 1.0 mL.min-1. The fluorescence detection for ethinyl estradiol was made at λex= 280 nm and λem= 310 nm and a UV detection for drospirenone was made at 200 nm. The elution time for ethinyl estradiol and drospirenone were 4.0 and 5.7 min, respectively. The method was validated in accordance to USP 34 guidelines. The proposed HPLC method presented advantages over reported methods and is suitable for quality control assays of ethinyl estradiol and drospirenone in coated tablets.
Um método simples, rápido, econômico e confiável foi desenvolvido empregando a cromatografia líquida de alta eficiência para a determinação simultânea de etinilestradiol e drospirenona em comprimidos revestidos. O método foi realizado utilizando coluna LiChroCART® 100RP (125 x 4 mm d.i., 5 µm), a fase móvel constituída de acetonitrila:água, 50:50 (v/v) com vazão de 1,0 mL.min-1. A detecção foi realizada empregando fluorescência em λex= 280 nm e λem= 310 nm para o etinilestradiol e na região de UV em 200 nm para a drospirenona. O etinilestradiol e a drospirenona tiveram tempo de retenção de 4,0 e 5,7 min, respectivamente. O método foi validado de acordo com as diretrizes da USP 34. O método proposto apresentou vantagens sobre os relatados na literatura e pode ser considerado adequado para o controle de qualidade do etinilestradiol e da drospirenona em comprimidos revestidos.
Assuntos
Cromatografia Líquida de Alta Pressão , Anticoncepcionais Orais/análise , Etinilestradiol/farmacocinética , Comprimidos com Revestimento Entérico , FluorescênciaRESUMO
OBJECTIVE: To determine the effects of oral contraceptive (OC) treatment on maternal iron and copper metabolism during lactation. DESIGN: Observational study. SETTING: Private and public clinics in Brazil. PATIENT(S): Lactating mothers attending the family planning clinic of the University of Brasilia. INTERVENTION(S): The OCs used were a combination pill (0.15 mg of levonorgestrel and 0.03 mg of ethinyl estradiol) and a minipill (0.35 mg of norethidrone). Blood and breast milk samples were collected before and after a measured period of OC treatment. MAIN OUTCOME MEASURE(S): Iron and copper concentrations were studied in the serum and breast milk of 54 breast-feeding mothers who had been advised by their physicians to use an OC, and in a control group. RESULT(S): Regression analysis was performed using a model that took into consideration socioeconomic status, number of children, duration of previous lactation, type of OC, length of treatment, and age. Repeated measurements (before and after OC treatment) showed that only copper concentrations in breast milk were significantly affected by stage of lactation. During the study period, which varied from 2-15 weeks, the decline in iron concentrations in breast milk was negligible, whereas copper concentrations decreased by 50%. CONCLUSION(S): The use of OCs does not appear to affect significantly the secretion of iron and copper in breast milk during the first 6 months of lactation.
PIP: This study examines the effects of oral contraceptive (OC) treatment on maternal iron and copper metabolism during lactation. The sample included lactating mothers attending the family planning clinic at the University of Brasilia. Participants were divided into 3 groups: 1) mothers who were taking combination pills (0.15 mg levonorgestrel and 0.03 mg ethinyl estradiol); 2) those who were taking minipills (0.35 mg norethindrone); and 3) a control group. Blood and breast milk samples were collected before and after a measured period of OC treatment. Results showed no significant effects of OC use on either iron or copper concentrations in serum during lactation. However, copper concentrations were significantly affected with the stage of lactation (iron, P = 0.9619; copper, P = 0.0002) as reflected in the multivariate model analysis. Therefore, the use of OCs does not appear to affect significantly the secretion of iron and copper in breast milk during the first 6 months of lactation.
Assuntos
Anticoncepcionais Orais , Cobre/análise , Ferro/análise , Leite Humano/química , Adolescente , Adulto , Anticoncepcionais Orais Combinados , Cobre/sangue , Feminino , Humanos , Ferro/sangue , LactaçãoRESUMO
OBJECTIVE: Our purpose was to evaluate whether prolonged or irregular bleeding during Norplant implant use could be alleviated with the use of oral hormonal medication. STUDY DESIGN: One hundred fifty users of the Norplant levonorgestrel contraceptive implant with prolonged or frequent bleeding were enrolled in this prospective, randomized, comparative study and assigned to one of three treatment groups for 20 days: ethinyl estradiol 50 microg, an oral contraceptive (50 microg ethinyl estradiol and 250 microg levonogestrel), and placebo. Total days of bleeding during treatment and length of the bleeding-free interval were analyzed. RESULTS: Women treated with the levonorgestrel-ethinyl estradiol pill bled an average of 2.6 days during treatment compared with 5.4 and 12.3 days in the ethinyl estradiol and placebo groups, respectively. Differences between both hormonal groups and placebo were significant (p <0.00001); moreover, the combined pill was more effective than ethinyl estradiol along (p <0.0001). CONCLUSION: The combined pill proved to be an excellent palliative treatment and is a more practical approach because of availability at all clinic sites.
PIP: In the Dominican Republic, clinical researchers randomly assigned 150 users of the contraceptive implant Norplant who came to Profamilia's Family Planning Clinic in Santo Domingo complaining of bleeding irregularities to one of three treatment groups. They aimed to evaluate the effectiveness of a combined oral contraceptive (OC) with 250 mcg levonorgestrel and 50 mcg ethinyl estradiol (EE) and of 50 mcg EE alone in treating bleeding irregularities. Bleeding irregularities were defined as prolonged bleeding (i.e., 8 or more continuous days of bleeding or spotting) or irregular bleeding (i.e., current bleeding episode initiated after a bleeding-free interval of less than 15 days). Age, parity, duration of Norplant use, and length of bleeding episode before treatment were similar in all three groups (i.e., OC, EE, and placebo). The OC group was significantly more likely to experience ceased bleeding within three days than the two other groups (91% vs. 67% for EE group [p 0.01 from OC group] and 15% for placebo group [p 0.0005 from both treatments]). Bleeding lasting for at least one week occurred less often in the OC group than the two other groups (2% vs. 14% for EE group and 50% for placebo group [p 0.0005 for both treatments]). Duration of bleeding was significantly lower in the OC group than the other two groups (2.6 days vs. 5.4 days for EE group and 12.3 days for placebo group; p 0.0001). Even though women in both hormonal treatment groups were more likely to experience gastralgia or nausea than the placebo group (33-40% vs. 4%; p 0.005), the side effects rarely interrupted treatment. These findings suggested that the OC is a very good effective treatment for bleeding irregularities and is a practical treatment since it is available at all Profamilia clinic sites.
Assuntos
Anticoncepcionais Femininos/efeitos adversos , Anticoncepcionais Orais Combinados/uso terapêutico , Congêneres do Estradiol/uso terapêutico , Etinilestradiol/uso terapêutico , Levanogestrel/efeitos adversos , Hemorragia Uterina/tratamento farmacológico , Adulto , Análise de Variância , Distribuição de Qui-Quadrado , Implantes de Medicamento , Feminino , Humanos , Levanogestrel/uso terapêutico , Estudos Prospectivos , Hemorragia Uterina/induzido quimicamenteRESUMO
A multicenter, international, randomized, comparative trial was conducted to assess the acceptability, efficacy and safety of two different schedules of a contraceptive pill, containing 250 micrograms levonorgestrel and 50 micrograms ethinyl estradiol, administered by the vaginal route. One schedule of daily administration for 21 days with a seven-day interruption to allow withdrawal bleeding was compared to daily administration without interruption for bleeding. A total of 900 women were recruited in three countries, Brazil, Egypt and China; 7,090 women-months of vaginal pill use were recorded (3,364 using the pills intermittently and 3,726 continuously). Four undesired pregnancies occurred, one in Egypt and three in China, all four in women using the pills intermittently. There was a statistically significant difference (p = 0.486) in pregnancy rate between the two groups. There were no other significant differences in discontinuation rates despite marked differences in bleeding patterns, amenorrhea predominating in the continuous use group. Hemoglobin levels increased significantly in the two groups but hematocrit was significantly higher in the continuous use group.
PIP: 900 healthy women 16-42 years old were recruited in Brazil, China, and Egypt for a multicenter, randomized, comparative clinical trial to determine the acceptability, efficacy, and safety of two different schedules of a contraceptive pill with 250 mcg levonorgestrel and 50 mcg ethinyl estradiol administered vaginally. The two schedules were: 1) daily vaginal use of the pill for 21 days, followed by withdrawal for regular bleeding, and restarted 7 days later, and 2) use of the pill by the vaginal route nonstop for one year. There were no significant difference in cumulative discontinuation rates between the two groups (total, 15.5 for intermittent group and 14.64 for continuous group), except for unwanted pregnancy. The only unwanted pregnancies occurred to 4 women in the intermittent group (1.04%) (p = 0.0486). Women in the continuous use group were more likely than those in the intermittent group to have spotting at least once (20.6% vs. 4.4%; p 0.001). Women in the continuous group were more likely than those in the intermittent group to have amenorrhea. For example, the mean number of bleeding/spotting days during all time intervals was lower for the continuous group than for the intermittent group (p 0.001; last interval, 0.97 vs. 12.83). Hemoglobin levels increased considerably in both groups between baseline and one year of use (11.61 vs. 11.9 g/dl for intermittent group and 11.54 vs. 11.81 g/dl for continuous use; p 0.001). The mean value of hematocrit at 12 months for the continuous group was higher than that at baseline (38.8% vs. 38.2%; p = 0.011). It did not increase in the intermittent group, however. Women in both groups gained weight during the 12 months of pill use. The weight gain was significant for the continuous group only. These findings suggest that continuous use of vaginal contraceptive pills may be more advantageous than intermittent use oral contraceptives and may benefit anemic women and those who bleed heavily during menstruation.
Assuntos
Anticoncepcionais Femininos/administração & dosagem , Congêneres do Estradiol/administração & dosagem , Etinilestradiol/administração & dosagem , Levanogestrel/administração & dosagem , Administração Intravaginal , Adolescente , Adulto , Brasil , China , Anticoncepcionais Femininos/efeitos adversos , Anticoncepcionais Femininos/normas , Formas de Dosagem , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Egito , Contagem de Eritrócitos , Congêneres do Estradiol/efeitos adversos , Congêneres do Estradiol/normas , Etinilestradiol/efeitos adversos , Etinilestradiol/normas , Feminino , Hematócrito , Hemoglobinas/análise , Humanos , Cooperação Internacional , Levanogestrel/efeitos adversos , Levanogestrel/normas , Fatores de TempoRESUMO
To evaluate the competitive molecular phenomenon of Ethynyl-Estradiol (EE-2) from contraceptive formulations against the endogenous Estradiol (E-2) at the intra and the extracellular compartments, plasma and endometrial samples were simultaneously obtained on different days of the pseudomenstrual cycle from oral contraceptive users under EE-2+ Norgestrel (30 micrograms/+ 500 micrograms) and EE-2+ Norethindrone (50 micrograms + 1.0 mg) in order to quantify EE-2 & E-2. When measuring both molecules it was shown that the chronic administration of steroids regardless of the pharmacological action of the progestin component the lower content of EE-2 (30 micrograms) does not compete substantially at the circulating level permitting the cyclic fashion of the natural estradiol while at the endometrial compartment such phenomenon is not seen thus, a local infertility effect should be reconsidered to anticipate a different approach in the future of contraception.
PIP: 27 women participated in a study of systemic and endometrial estradiol concentrations in oral contraceptive (OC) users. 13 women aged 15-22 used OCs containing ethinyl estradiol 30 mcg and norgestrel 500 mg for 4-24 months, and 14 women aged 18-28 used OCs containing 50 mcg ethinyl estradiol and 1.0 mg norethindrone for 1-28 months. A peripheral blood sample and an endometrial biopsy were obtained at random from each woman on different cycle days to measure the concentration of endogenous estradiol. The ovarian response defined by endogenous plasma and endometrial estrogen levels differed greatly in the two groups. In the 30 mcg group, plasma estrogen levels were similar to those described in an ovulatory menstrual cycle, while this profile was not observed in the 50 mcg group. The endometrial estrogen profile described for women not using hormonal contraception was not observed in either of the two dose groups.
Assuntos
Anticoncepcionais Orais/análise , Etinilestradiol/análise , Noretindrona/análise , Norgestrel/análise , Adolescente , Adulto , Anticoncepcionais Orais/sangue , Endométrio/química , Etinilestradiol/sangue , Feminino , Humanos , Noretindrona/sangue , Norgestrel/sangueRESUMO
The objective of this multicenter randomized clinical trial was to compare the efficacy, acceptability, and occurrence of side effects associated with the oral versus vaginal route of administration of contraceptive pills. Eight hundred nineteen healthy, parous women of reproductive age were recruited at family planning clinics and research centers, members of the South to South Cooperation in Reproductive Health, in seven countries of the developing world. These women were randomly assigned to use either oral or vaginal administration of the same contraceptive pill, which contained 250 micrograms levonorgestrel and 50 micrograms ethinyl estradiol. No statistically significant differences were found in discontinuation rates between the two groups after 1 year. Involuntary pregnancy rates after 1 year were not statistically significantly different between the two groups. The vaginal route of administration appears to be as acceptable and efficacious as the oral route.
PIP: The objective of this multicenter randomized clinical trail was to compare the efficacy, acceptability, and occurrence of side effects associated with the oral versus vaginal route of administration of contraceptive pills. This study started in June, 1987, and data collection extended up to April, 1992, at family planning clinics and research centers, members of the South to South Cooperation in Reproductive Health, in seven countries of the developing world. The 819 subjects were from 17 to 39 years of age, had already had at least one pregnancy, had had regular menstrual cycles for 3 months before, were exposed to the risk of pregnancy, and were not using any other method of contraception. 424 were randomly assigned to use the pills orally (which contained 250 mcg levonorgestrel and 50 mcg ethinyl estradiol), whereas 395 inserted the pills vaginally. 625 subjects completed at least 6 months of use, 326 used the pills orally and 299 used the pills vaginally. 385 subjects completed 1 year of pills use, 201 in the oral group and 184 in the vaginal group. The 1-year discontinuation rate per 100 subjects per year for the oral group was 34.71 +or- 2.42, while it was 36.35 +or- 2.53 for the vaginal group. This difference was not statistically significant. The only single reason of statistically significant difference for discontinuation was "desire for pregnancy" (p = 0.444). Paired value analysis of subjects completing 12 months of study showed that women in the oral group had a statistically significant increase in weight, from a mean of 55.8 kg at admission to a mean of 56.9 kg at 6 months (p 0.05) and 57.3 kg at 1 year (p = 0.05). The mean weight of the vaginal group increased from 56.52 kg to 57.22 kg (p = 0.036) at 12 months. Significantly more complaints of vaginal discharge were recorded in women using the pills by the vaginal route (p = 0.001). However, only one subject discontinued the pills because of vaginal discharge.
Assuntos
Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Orais Hormonais , Administração Intravaginal , Adolescente , Adulto , Anticoncepcionais Femininos/efeitos adversos , Anticoncepcionais Orais Hormonais/efeitos adversos , Países em Desenvolvimento , Feminino , Humanos , Cooperação do PacienteRESUMO
The efficacy and acceptability of two widely used oral contraceptive tablets, one containing 250 mg levonorgestrel and 50 micrograms ethinyl estradiol and the other containing 150 micrograms desogestrel and 30 micrograms ethinyl estradiol, administered by the vaginal route were compared in 1055 women studied over 12,630 woman-months of vaginal contraceptive pill use. This multicenter clinical trial was performed in nine countries of the developing world by the "South to South Cooperation in Reproductive Health," an organization founded by scientists from the Third World working in the area of reproductive health, and the study was developed and coordinated by one of these centers. The findings of this study confirm the efficacy of both these tablets when administered by the vaginal route. Involuntary pregnancy rates at 1 year of 2.78 for subjects in the levonorgestrel group and 4.54 for subjects the desogestrel group showed no statistically significant difference between the two groups. However, total discontinuation rates of 47.01 for subjects in the levonorgestrel group and 56.33 for subjects in the desogestrel group showed a statistically significant difference between the two groups, and discontinuation rates attributable to prolonged bleeding of 0.6 for subjects in the levonorgestrel group and 3.2 for subjects in the desogestrel group were also significantly higher in the group of subjects using the desogestrel vaginal contraceptive pill. Blood pressure remained at admission values throughout treatment. A statistically significant weight increase from admission values occurred in both groups of subjects.
PIP: Efficacy and acceptability of 2 combined oral contraceptive pills administered vaginally are summarized. This is the 1st collaborative trial published by the South to South Cooperation in Reproductive Health. 1055 women participated in 12,630 cycles, in 9 countries, from June 1988 to May 1991. The pills were commercially available tablets containing 50 mcg ethinyl estradiol and 250 mg levonorgestrel (Schering AG, Sao Paulo, Brazil), or 30 mcg ethinyl estradiol and 15 mcg desogestrel (Organon, Sao Paulo, Brazil). Subjects were aged 17-39 younger and of lower parity from Mexico and Dominican Republic and older from Egypt and China. All had at least 1 pregnancy. 675 participated for 6 months, 470 for 1 year, 364 for 18 months, and 210 for 2 years. The 1-year discontinuation rate averaged 47.01% for the levonorgestrel group and 56.33% for the desogestrel group (p = 0.0061); 2-year discontinuation rates were 48.01% and 69.36, respectively, explained in part by higher involuntary pregnancy rates and prolonged bleeding rates in the desogestrel group. The most common medical reasons for stopping contraception were unplanned pregnancy, vaginal or vulval irritation, nausea, vaginal discharge and headache. Vaginal irritation was reported by 1%, 9 in each group. There were 32 pregnancies, 14 in the levonorgestrel and 18 in the desogestrel group. 17 were in missed pill cycles and the rest were method failures, 6 in the levonorgestrel group and 9 in the desogestrel group. The Pearl index varied from 0 in Nigeria to 12.24 in Mexico, and was 2.45 for levonorgestrel vs. 3.74 for desogestrel. There was a wide variation in discontinuation rates by center: Brazil and China had few, while many women from Dominican Republic, Mexico and Zambia left the study. Bleeding problems were common complaints, more so in the desogestrel group. There were 363 women with intermenstrual bleeding (only once in 80%), 148 with spotting (only twice in 65%). Bleeding duration was significantly less in pill cycles than baseline, pressure. Women gained an average of 1 kg over 2 years, more in the desogestrel group. The pregnancy rate of 2.78 is within the range reported for levonorgestrel rings.
Assuntos
Desogestrel/administração & dosagem , Etinilestradiol/administração & dosagem , Levanogestrel/administração & dosagem , Administração Intravaginal , Adolescente , Adulto , Desogestrel/efeitos adversos , Países em Desenvolvimento , Combinação de Medicamentos , Etinilestradiol/efeitos adversos , Feminino , Humanos , Levanogestrel/efeitos adversos , Estudos Multicêntricos como Assunto , Aceitação pelo Paciente de Cuidados de Saúde , Gravidez , Distribuição Aleatória , VaginaRESUMO
Four different models of contraceptive vaginal rings were tested during three cycles for luteal activity, bleeding control, plasma lipoproteins and serum levels of the contraceptive steroids. Two progestins, levonorgestrel acetate (LNGA) and ST 1435, alone or in combination with ethynyl-estradiol (EE) were tested. The rings released 100 ug/day of the progestins and 30 ug/day of EE. Luteal activity was detected among users of the progestin-only rings: 4 of 8 cycles with ST 1435 and 2 of 10 with LNGA. Only one of the 18 cycles studied with the two combined rings showed luteal activity, but the measurement of contraceptive steroid in plasma suggested that this subject delayed reinsertion of the ring for about one week in that particular cycle. Breakthrough bleeding was observed in 12 of 30 cycles of use of the progestin-only rings, and in only 2 of 27 cycles with the combined models. No significant changes in total cholesterol or its HDL-fraction were observed. However, the only reduction observed in HDL-cholesterol was among users of the LNGA-only ring. It is concluded that the two combined CVR models offer good possibilities of high effectiveness and bleeding control and merit further development.
PIP: Researchers analyzed data on 20 18-38 year old volunteers from the family planning clinic of PROFAMILIA in Santo Domingo, Dominican Republic, who had earlier undergone female sterilization to evaluate 4 different models of contraceptive vaginal rings during 3 cycles so as to identify which models would be the most likely to be an acceptable, safe, and effective family planning method. Women who used either of the 2 combined rings (ethinyl estradiol [EE] and either levonorgestrel acetate [LNGA] or ST 1435) had higher mean total serum levonorgestrel levels than those using the progestin-only rings (LNGA or ST 1435) (most were significant at .005). Luteal activity which marked ovulation was basically limited to users of the progestin-only rings (50% of cycles with ST 1435 and 20% of LNGA). It occurred in 1 of 18 cycles (5.6%) of users of combined rings (LNGA + EE). It probably occurred because of delayed insertion. The combined rings caused fewer incidents of breakthrough bleeding than did the progestin-only rings (7.4% vs. 40%). Neither the progestin-only nor the combined vaginal rings significantly altered total cholesterol or high density lipoprotein (HDL) levels. Users of the LNGA-only ring did experience an insignificant reduction in HDL, however. Further, triglycerides increased among users of the combined vaginal rings, but the increase was only significant with the LNGA + EE ring (25.4 mg/dl increase; p .05). Moreover, they fell significantly among users of the LNGA only ring (45.5 mg/dl decrease; p .05). The researchers concluded that the 2 combined rings hold the most promise due to good bleeding control and high effectiveness and therefore deserve further development.
Assuntos
Dispositivos Anticoncepcionais Femininos , Hormônios Esteroides Gonadais/sangue , Lipoproteínas/sangue , Ciclo Menstrual/efeitos dos fármacos , Menstruação/efeitos dos fármacos , Administração Intravaginal , Adolescente , Adulto , Anticoncepcionais Femininos/sangue , Anticoncepcionais Femininos/farmacologia , Dispositivos Anticoncepcionais Femininos/efeitos adversos , Estrogênios/sangue , Etinilestradiol/sangue , Etinilestradiol/farmacologia , Estudos de Avaliação como Assunto , Feminino , Humanos , Levanogestrel/sangue , Levanogestrel/farmacologia , Norprogesteronas/sangue , Norprogesteronas/farmacologia , Progesterona/sangue , RadioimunoensaioRESUMO
A comparative study of 5 years' duration using desogestrel (DSG), levonorgestrel (LN), and norethindrone (NET), combined with ethinyl estradiol (EE), was conducted. A total of 4499 cycles on DSG-EE, 3691 on LN-EE (1980 on triphasic and 1711 on monophasic schemes) and 1680 on NET-EE was evaluated. A contraceptive efficacy of 100% was obtained in all the groups. Minimal side effects were observed. In particular, body weight in those women on DSG-EE did not show noticeable changes and headaches were minimal. No alterations on blood pressure readings or on the routine laboratory tests were noticed in any of the groups. There was a significant increase in high-density lipoprotein-c (HDL-c) in women on DSG-EE. There was no change in NET-EE, and a significant decrease in women on LN-EE in both schemes. Changes in LDL-C, very low density lipoproteins, triglycerides, total lipids, total cholesterol, and glucose were not significant, although there was some increase at 60 cycles on triglycerides on those women on DSG-EE and on NET-EE. At the end of 5 years, 76% of women continued on DSG-EE. They indicated their satisfaction with this method.
Assuntos
Pressão Sanguínea , Peso Corporal , Técnicas de Laboratório Clínico , Ensaios Clínicos como Assunto , Anticoncepção , Anticoncepcionais Orais Combinados , Etinilestradiol , Estudos de Avaliação como Assunto , Levanogestrel , Lipídeos , Ciclo Menstrual , Metrorragia , Noretindrona , Aceitação pelo Paciente de Cuidados de Saúde , América , Biologia , Sangue , Comportamento Contraceptivo , Anticoncepcionais , Anticoncepcionais Femininos , Anticoncepcionais Orais , Anticoncepcionais Orais Hormonais , Países em Desenvolvimento , Diagnóstico , Doença , Serviços de Planejamento Familiar , Hemorragia , América Latina , Menstruação , México , América do Norte , Fisiologia , Reprodução , Pesquisa , Sinais e SintomasRESUMO
Some details about the function of natural and synthetical hormonas are reviewed, particularly estrogens as ethynyl estradiol and its 3, Methyl ether (mestranol); its peripheral concentration vs tissular hormonal contents, a relationship of biological importance as the first step in its hormonal action and the cummulative local effects that could explain some intra and extracellular phenomena.
PIP: Some studies of the peripheral concentration and concentration in reproductive tissues of ethinyl estradiol (EE) and mestranol are reviewed. Orally administered EE is observable in the peripheral circulation within 30-60 minutes. A 1970 study of radioactive EE demonstrated that the endometrium and ovaries captured most of the EE, with levels in the uterus and serum much lower. Adipose tissue was found to be important in storing the hormones. Other studies of radioactive mestranol and EE demonstrated that the compounds were deposited in other organs in significant quantities and that the deposits were perhaps irreversible or of very slow release. The ability of estrogens to remain concentrated at the systemic level and not just in reproductive organs may be related to some adverse effects reported in women using oral contraceptives (OCs). Advances in radiochemistry and immunology in the 1960s made it possible to measure steroid hormone levels in different tissues. The capacity of the endometrium to concentrate natural steroids such as 17-beta estradiol and progesterone during the ovulatory menstrual cycle was demonstrated in 1978. A subsequent study showed that the endometrium captured and stored the synthetic estrogen EE in even greater concentrations than the natural estrogen estradiol. A study of the pharmacodynamics of EE in hysterectomized women showed that 24 hours after the 1st dose of 30 mcg the EE was not detected in the peripheral circulation. But the peripheral concentration increased with continuous daily administration of 30 mcg of EE. 27 days after suppression of treatment it was still detectable in the peripheral circulation. Another experiment was designed to measure simultaneously the concentrations of EE in the peripheral circulation and in the endometrial tissue of 36 women terminating use of OCs containing norgestrel and EE after 2-36 months of treatment. The study showed that synthetic estrogen was still observable in the endometrial tissue 1 month after discontinuing OC use. Inexplicably, levels of EE were higher in the circulation in the cycle after treatment than in the final treatment cycle. 5 of the women participated in the study for 3 posttreatment cycles. EE was observed in the circulation 1 month after termination of OC use in 5 women, 2 months after termination in 4 women, and 3 months after termination in 3 women. The persistence of EE in the tissue months after termination of treatment suggests the need for further research and assessment of possible resulting risks.
Assuntos
Anticoncepcionais Orais Sintéticos/farmacocinética , Congêneres do Estradiol/farmacocinética , Tecido Adiposo/metabolismo , Adulto , Etinilestradiol/farmacocinética , Feminino , Genitália Feminina/metabolismo , Humanos , Distribuição TecidualRESUMO
In three ongoing open studies conducted by 50 investigators in Europe, South America, and New Zealand, 639 subjects followed a new triphasic regimen of gestodene (GTD) and ethinyl estradiol (EE) for 3,020 cycles. One study used GTD + EE only, but in each of the other two studies a comparator oral contraceptive (OC) also was given: norethisterone (NET) + EE in one and desogestrel (DSG) + EE in the other. The objective of all three studies was to assess the efficacy, cycle control, and safety of the triphasic GTD + EE. The following is a report of the interim results. Statistical analysis was performed only on differences between groups in the incidences of bleeding irregularities. During six treatment cycles, subjects either followed the GTD + EE regimen (50 micrograms GTD + 30 micrograms EE for 6 days, 70 micrograms GTD + 40 micrograms EE for 5 days, and 100 micrograms GTD + 30 micrograms EE for 10 days) or took triphasic NET + EE or monophasic DSG + EE. Each cycle concluded with a seven-day hiatus in study medication. No pregnancies occurred with any of the contraceptive preparations (Pearl Index = 0). Compliance was good in all studies and a majority of subjects were still participants at cycle 6. Normal bleeding was reported during 92% of the total evaluable cycles of GTD + EE use. Cycle control with GTD + EE was superior to that with NET + EE or DSG + EE: Breakthrough bleeding occurred in 1.5% of the pooled GTD + EE cycles versus 6.6% of the NET + EE cycles and 2.6% of the DSG + EE cycles; spotting occurred in 4.5% of the GTD + EE cycles versus 9.7% of the NET + EE cycles and 10.3% of the DSG + EE cycles; and breakthrough bleeding plus spotting occurred in 2.1% of the GTD + EE cycles versus 8.1% of the NET + EE cycles and 4.6% of the DSG + EE cycles. Amenorrhea occurred in 2.0% of the cycles with NET + EE, but was reported by only 0.3% of all the subjects given GTD + EE and 0.7% of those given DSG + EE. Cycle length and intensity of bleeding changed little during the use of any of the study preparations. Mean length of withdrawal bleeding during the GTD + EE regimen shortened from 4.5 days (prestudy) to 4.0 days. With each OC, the subjects' mean weight during cycles 3 and 6 differed less than 0.5 kg from baseline values.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Anticoncepcionais Orais Combinados/farmacologia , Etinilestradiol/farmacologia , Ciclo Menstrual/efeitos dos fármacos , Norpregnenos/farmacologia , Adulto , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Anticoncepcionais Orais Combinados/efeitos adversos , Desogestrel , Etinilestradiol/efeitos adversos , Europa (Continente) , Feminino , Humanos , Estudos Multicêntricos como Assunto , Nova Zelândia , Noretindrona/efeitos adversos , Noretindrona/farmacologia , Norpregnenos/efeitos adversos , Cooperação do Paciente , América do SulRESUMO
Four-hundred-twenty-six women, aged 18 to 36, completed a four-cycle comparative, randomized, single-blind (observer blind), multicenter study of a new graduated estrogen formulation with three constant-dosed combination oral contraceptives containing the same synthetic steroid compounds. The products studied were Loestrin 1/20, Loestrin 1.5/30, Norlestrin 1/50, and a new graduated estrogen product, Estrostep. A total of 1,850 cycles were completed and analyzed for efficacy, side effects, metabolic changes, and cycle control. Four pregnancies occurred during the course of the study. None of the pregnancies occurred in the group receiving Estrostep. The new formulation produced the lowest rate of breakthrough bleeding (BTB) compared with the other three products. All four combination oral contraceptives resulted in an increase in high-density lipoprotein cholesterol (HDL-C). The levels of HDL-C were greatest with Estrostep.
Assuntos
Etinilestradiol/farmacologia , Noretindrona/análogos & derivados , Noretindrona/farmacologia , Adolescente , Adulto , Amenorreia/induzido quimicamente , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Ensaios Clínicos como Assunto , Anticoncepcionais Orais Combinados/efeitos adversos , Anticoncepcionais Orais Combinados/farmacologia , Combinação de Medicamentos , Etinilestradiol/efeitos adversos , Feminino , Humanos , Noretindrona/efeitos adversos , Gravidez , Hemorragia Uterina/induzido quimicamenteRESUMO
PIP: Cyproterone acetate (Androcur), a potent progestagin and antigonadotropin, has been widely used in Europe in treatment of hirsutism, seborrhea, and alopecia. A formulation combining an estrogen, ethinyl estradiol (EE), to neutralize the progestational action and consequent amenorrhea of Androcur is marketed under the name of DIANE. 3 different treatment protocols were tested: 1) continuous administration of Androcur at doses varying from 25-150 mgr with rests every 3 months 2) high dose combination of 50 mgr Androcur and .05 mgr of EE in 21 day cycles and 3) low dose combinations of 2 mgr Androcur and .05 mgr of EE in 21-day cycles (DIANE). 54 patients who received the DIANE combined low dose treatment were compared. 7 of them had previously received the cyproterone acetate in variable doses of 25-150 mgr/day for 3-10 cycles, 16 had previously taken cyproterone acetate in variable doses of 50-150 mgr/day for 3-14 cycles, followed by the high dose combined method for 3-12 cycles and DIANE for 1-7 cycles, and 15 patients had previously received the high dose combined method for 2-22 cycles followed by DIANE for 3-7 cycles. Among the 54 patients there were 10 cases of idiopathic hirsutism, 11 of suprarenal hirsutism, 25 of ovarian hirsutism, 2 of iatrogenic hirsutism, 24 of acne, 37 of seborrhea, and 10 of alopecia. No pregnancies were reported in patients exposed to risk of pregnancy who took a total of 96 cycles of DIANE or 55 cycles of the high dose combination. Continuous dose cyproterone acetate is usually associated with amenorrhea. The high dose combination induces amenorrhea in up to 20% of cases, while with DIANE the principal change is a diminution in the amount of bleeding. Cyproterone acetate alone or associated with androgens is the preferred treatment for androgenic manifestations. The therapeutic regimen should be adapted to the predominance, time of evolution and severity of symptoms. For moderate or serious hirsutism, the treatment should be continuous administration of high doses of cyproterone acetate for 6 months followed by the combined method at high doses according to the type of initial response. When acne and seborrhea predominate, the combined low-dose method is used, because even though the high dose continuous method gives better results, the secondary effects do not justify its use. The high dose continuous method can be chosen if the low dose combined method fails. The high dose combined method is preferred for alopecia, with the low dose combined method used for maintenance.^ieng