RESUMO
Sex hormone binding globulin (SHBG) is a homodimeric glycoprotein and is the major carrier protein for sex steroids in plasma, regulating sex hormone availability in most vertebrate groups. Although it was initially thought that human dimeric SHBG bound a single ligand at the homodimer interface, studies demonstrated that dimeric SHBG binds a ligand to each subunit with similar affinity. In fact, the findings from recent experimental studies suggest that ligand binding to the SHBG dimer involves a complex allosteric mechanism involving conformational changes that limit observations of the presence of allosteric regulation. Therefore, we combined structural data with molecular dynamics simulations using Molecular Mechanics Generalized-Born Surface Area (MMGBSA) to dissect the structural and energetic basis for molecular recognition between five ligands whose affinities and binding positions on SHBG are known, i.e., 3ß,17α-diol; 3ß,17ß-diol; DHT; norgestrel (NOG); and estradiol (E2), and monomeric and dimeric SHBG. Protein-ligand complexes, involving dimeric SHBG saturated with two ligands on each subunit, reproduce the experimental affinity tendency and allow the observation that dimerization exerts disparate effects on binding affinity, characteristic of negative cooperativity for E2, DHT, and NOG, whereas 3ß-17α-diol and 3ß-17ß-diol lack allostery.
Assuntos
Androstenodióis/metabolismo , Di-Hidrotestosterona/metabolismo , Estradiol/metabolismo , Norgestrel/metabolismo , Globulina de Ligação a Hormônio Sexual/química , Globulina de Ligação a Hormônio Sexual/metabolismo , Androstenodióis/química , Di-Hidrotestosterona/química , Estradiol/química , Humanos , Ligantes , Modelos Moleculares , Simulação de Dinâmica Molecular , Norgestrel/química , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Multimerização ProteicaRESUMO
BACKGROUND: The contraceptive skin patch (CSP) accepted by the U.S. FDA in 2001 includes ethinylestradiol and norelgestromine, whereas the subdermal contraceptive implant (SCI) has etonogestrel and is also approved by the FDA. In Mexico, both are now widely used for contraception but their effects on Mexican population are unknown. The objective of the study was to evaluate if these treatments induce metabolic changes in a sample of indigenous and mestizo Mexican women. METHODS: An observational, prospective, longitudinal, non-randomized study of women between 18 and 35 years of age assigned to CSP or SCI. We performed several laboratory tests: clinical chemistry, lipid profile, and liver and thyroid function tests. Also, serum levels of insulin, C-peptide, IGF-1, leptin, adiponectin, and C reactive protein were assayed. RESULTS: Sixty-two women were enrolled, 25 used CSP (0 indigenous; 25 mestizos) and 37 used SCI (18 indigenous; 19 mestizos). Clinical symptoms were relatively more frequent in the SCI group. Thirty-four contraceptive users gained weight without other clinical significant changes. After 4 months of treatment, significant changes were found in some biochemical parameters in both treatment groups. Most were clinically irrelevant. Interestingly, the percentage of users with an abnormal atherogenic index diminished from 75% to 41.6% after follow-up. CONCLUSIONS: The CSP slightly modified the metabolic variables. Most changes were nonsignificant, whereas for SCI users changes were more evident and perhaps beneficial. Results of this attempt to evaluate the effects of contraceptives in mestizo and native-American populations show that clinical symptoms are frequent in Mexican users of CSP and SCI. Although these medications may affect some metabolic variables, these changes seem clinically irrelevant. Induction of abnormalities in other physiological pathways cannot be ruled out.
Assuntos
Anticoncepcionais Femininos/efeitos adversos , Desogestrel/efeitos adversos , Etinilestradiol/efeitos adversos , Norgestrel/análogos & derivados , Adiponectina/sangue , Adulto , Peptídeo C/sangue , Proteína C-Reativa/metabolismo , Anticoncepcionais Femininos/administração & dosagem , Desogestrel/administração & dosagem , Combinação de Medicamentos , Etinilestradiol/administração & dosagem , Feminino , Humanos , Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Leptina/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Testes de Função Hepática , Estudos Longitudinais , México , Norgestrel/administração & dosagem , Norgestrel/efeitos adversos , Oximas/administração & dosagem , Oximas/efeitos adversos , Testes de Função Tireóidea , Adesivo Transdérmico , Aumento de Peso/efeitos dos fármacosRESUMO
OBJECTIVE: To compare the bleeding patterns, satisfaction and tolerability of 3 different contraceptive in an extended regimens in the service of Family Planning of the North Central Hospital of PEMEX. MATERIAL AND METHODS: Healthy, adult women with desire of contraception for one year (N 120) were randomly assigned to receive oral contraceptive drospirenone/ethinyl E2 (group1), the norelgestromin/ethinyl E2 transdermal patch (group 2) and vaginal ring etonogestrel/ ethinyl E2 (group 3) in an extended regimen (42 consecutive days, 1 hormone-free week). Study assessments were conducted at scheduled visits at the time of initial screening, at baseline after 1, 3, 6, and 12 months. Subjects recorded menstrual associated symptoms bleeding data and completed satisfaction questionnaires. Subjects and investigators provided overall assessments of the regimens. RESULTS: Extended use of 3 different contraceptive resulted in fewer bleeding days in every group (66.6%, 55% and 58.3% P 0.0024), and less mastalgia and menstrual pain. Subjects were highly satisfied with three regimens (93.3%, 96.6% and 91.6% P 0.00421). Although not mayor adverse events were reported with this regimen, there was an increase in spotting days; it decreased with each successive cycle of therapy. Efficacy and safety were similar to those reported for traditional cycle. CONCLUSION: Extended-contraceptive regimen delays menses and reduces bleeding, a profile that may be preferred by women who seek flexibility with their contraceptive method.
Assuntos
Androstenos/farmacologia , Anticoncepcionais Orais Combinados/farmacologia , Anticoncepcionais Orais Hormonais/farmacologia , Desogestrel/farmacologia , Etinilestradiol/farmacologia , Ciclo Menstrual/efeitos dos fármacos , Norgestrel/análogos & derivados , Administração Cutânea , Adolescente , Adulto , Androstenos/administração & dosagem , Androstenos/efeitos adversos , Doenças Mamárias/induzido quimicamente , Dispositivos Anticoncepcionais Femininos , Anticoncepcionais Orais Combinados/administração & dosagem , Anticoncepcionais Orais Combinados/efeitos adversos , Anticoncepcionais Orais Hormonais/administração & dosagem , Anticoncepcionais Orais Hormonais/efeitos adversos , Desogestrel/administração & dosagem , Desogestrel/efeitos adversos , Combinação de Medicamentos , Dismenorreia/prevenção & controle , Etinilestradiol/administração & dosagem , Etinilestradiol/efeitos adversos , Feminino , Cefaleia/induzido quimicamente , Humanos , Norgestrel/administração & dosagem , Norgestrel/efeitos adversos , Norgestrel/farmacologia , Aceitação pelo Paciente de Cuidados de Saúde , Estudos Prospectivos , Fatores de Tempo , Hemorragia Uterina/induzido quimicamente , Adulto JovemRESUMO
The objective of the study was to analyze comparatively the jitter and shimmer values of spoken voice among women in menacme and menopausal women using or not hormonal replacement therapy (HRT). Forty-five women were studied, divided into the following groups: Control Group (CG), 15 women aged 20-40 years with regular menstrual cycles who did not take hormonal contraceptives; Treated Group (TG), 15 women aged 45-60 years with at least 2 years of menopause, under continuous HRT with 1 mg estradiol valerate + 90 microg norgestimate per day for at least 6 months; Untreated Group (UG), 15 women aged 45-60 years with at least 2 years of menopause who did not use HRT. Mean age was 30.3, 54.5, and 56.5 years for CG, TG, and UG, respectively. All subjects were submitted to acoustic analysis of jitter and shimmer for the sustained vowels /e/ and /i/. Mean jitter values were 0.56%, 0.64%, and 0.56% for the vowel /e/ and 0.88%, 0.79%, and 0.68% for the vowel /i/ for CG, TG, and UG, respectively. Mean shimmer values were 4.17%, 4.38%, and 4.77% for the vowel /e/ and 5.19%, 4.59%, and 5.37% for the vowel /i/ for CG, TG, and UG, respectively. There were no significant differences between the groups studied. The results obtained here by the methodology used suggest that there were no significant differences in jitter and shimmer when we assessed the sustained vowels /i/ and /e/ between menopausal women using or not HRT or between young and menopausal women treated or not.
Assuntos
Pós-Menopausa/fisiologia , Acústica da Fala , Fala/fisiologia , Adulto , Estradiol/análogos & derivados , Estradiol/farmacologia , Terapia de Reposição de Estrogênios , Feminino , Humanos , Pessoa de Meia-Idade , Norgestrel/análogos & derivados , Norgestrel/farmacologia , Fonética , Pós-Menopausa/efeitos dos fármacos , Fala/efeitos dos fármacos , Adulto JovemRESUMO
OBJECTIVE: To report a case of successful use of a transdermal contraceptive in a patient with hereditary angioedema. DESIGN: Case report. SETTING: University medical center. PATIENT(S): A patient who had used oral contraceptives contracted SC and submucosal tumefaction every 1 or 2 months. She was diagnosed with type I hereditary angioedema. It was determined that she was complement C4 deficient and C1-inhibitor quantitative deficient but functional C1-inhibitor normal. After she was diagnosed, the use of oral contraceptives was contraindicated. INTERVENTION(S): Oral contraceptives were suspended, and a hormonal transdermal contraceptive was started. MAIN OUTCOME MEASURE(S): The absence of symptoms after 26 months using a transdermal contraceptive. RESULT(S): After 26 months of using this treatment, the patient has not experienced any symptoms of the hereditary angioedema. CONCLUSION(S): The use of hormonal contraceptives transdermally can be an alternative in patients with hereditary angioedema.
Assuntos
Angioedemas Hereditários/etiologia , Anticoncepcionais Orais Hormonais/efeitos adversos , Etinilestradiol/administração & dosagem , Norgestrel/análogos & derivados , Administração Cutânea , Angioedemas Hereditários/induzido quimicamente , Angioedemas Hereditários/imunologia , Combinação de Medicamentos , Feminino , Humanos , Norgestrel/administração & dosagemAssuntos
Anticoncepcionais Femininos/efeitos adversos , Dermatite Alérgica de Contato/etiologia , Etinilestradiol/efeitos adversos , Norgestrel/análogos & derivados , Administração Cutânea , Adolescente , Anticoncepcionais Femininos/administração & dosagem , Dermatite Alérgica de Contato/tratamento farmacológico , Combinação de Medicamentos , Etinilestradiol/administração & dosagem , Feminino , Glucocorticoides/administração & dosagem , Humanos , Norgestrel/administração & dosagem , Norgestrel/efeitos adversosRESUMO
Se evaluó el efecto de la inyección im de 3 mg de norgestomet (NG) en la inducción de atresia del folículo dominante persistente (FDP) y la formación del cuerpo lúteo (Cl) que se desarrolla después de inducir la ovulación del FDP con hCG, en vacas sincronizadas con implantes de norgestomet. Se utilizaron 11 vaquillas y 20 vacas Holstein previamente sincronizados con doble inyección de PGF2a. El día 7 del ciclo (día 0 del experimento), se les insertó un implante sc de 3 mg de norgestomet (iNG) y recibieron PGF2a; posteriormente se asignaron al azar a los siguientes tratamientos: para el tratamiento hCG (n = 8) el día tres se aplicaron 2 500 UI de hCG im; para el tratamiento hCG + NG (n = 8) el día tres se aplicaron 2 500 UI de hCG im y el día cinco recibieron 3 mg de norgestomet im; para el tratamiento NG (n = 8) el día cinco recibieron 3 mg im de norgestomet. Al grupo testigo (n = 7) se le aplicó solución salina im el día tres y el día cinco, 5 ml de aceite vegetal. El iNG se retiró nueve días después de su inserción. Diariamente, a partir de la inserción del iNG y hasta la presentación del estro, se realizaron ultrasonografías de los ovarios y se tomaron muestras sanguíneas, en las cuales se determinaron las concentraciones de progesterona. La proporción de animales en los cuales se eliminó el FDP y se promovió un recambio folicular fue similar (0.05 < P < 0.1) entre los tratamientos hCG (5/8), hCG + NG (7/8) y NG (6/7), pero fue diferente (P < 0.05) al grupo testigo, en el cual no se eliminó ningún FDP (0/7). El porcentaje de concepción fue similar (P > 0.05) entre las vacas que ovularon un folículo nuevo (66.6 por ciento; 12/18) y aquellas que ovularon el FDP (53.8 por ciento; 7/13). En el grupo hCG + NG el tratamiento con norgestomet después de la inyección de hCG evitó el desarrollo del Cl, ya que sólo una vaca de seis que ovularon tuvo niveles > 1 ng/ml de progesterona al retirar el iNG, mientras que en el grupo hCG los cinco5 animales que ovularon tuvieron niveles > 1ng/ml de progesterona (P < 0.05). Se concluye que la inyección de 3 mg de norgestomet el día cinco posterior a la inserción del iNG provocó la atresia del FDP y evitó el desarrollo del cuerpo lúteo inducido con hCG.
Assuntos
Animais , Bovinos , Bovinos , Norgestrel , Corpo Lúteo , Sincronização do Estro , Implantes Experimentais , Atresia FolicularRESUMO
OBJETIVO: Evaluar la actividad de la enzima butirilcolinesterasa en mujeres usuarias de dos anticonceptivos hormonales, norgestrel etinilestradiol y acetato de medroxiprogesterona, utilizando como marcador hepático indirecto la fosfatasa alcalina. MATERIAL Y MÉTODOS: Mujeres que asistían al programa de Planificación Familiar del C. S. "7 de Octubre" - El Agustino, continuadoras en los métodos de anticoncepción hormonal (mayor de seis meses). Se extrajo sangre en ayunas y realizó la medición sérica de la actividad enzimática. RESULTADOS: Las usuarias de ambos tipos de anticonceptivos tuvieron aumento significativo de la actividad butirilcolinesterasa respecto al grupo control, observándose en las usuarias de medroxiprogesterona 30 por ciento más con cifras elevadas. El 12 por ciento de usuarias de norgestrel etinilestradiol y el 18 por ciento de medroxiprogesterona tuvo valores fuera del promedio ñ2 DE. La actividad de fosfatasa alcalina tuvo aumento significativo de 8 por ciento sólo en usuarias de medroxiprogesterona. CONCLUSIONES: El uso del anticonceptivo acetato de medroxiprogesterona originó mayor variación de la actividad butirilcolinesterasa y por más tiempo que el del norgestrel etinilestradiol.
Assuntos
Humanos , Feminino , Butirilcolinesterase , Anticoncepcionais Orais Hormonais , Medroxiprogesterona , Norgestrel , AnticoncepçãoRESUMO
In the following article, the most recent knowledge on emergency contraception (EC) is reviewed. EC is defined as those contraceptive methods that may be used to prevent an unwanted pregnancy up to 3 days after unprotected intercourse, contraceptive failure or rape. In case of non-hormonal methods (IUD), the time window for pregnancy prevention goes up to 5 days after intercourse. The different regimens now available, hormonal and non-hormonal methods, indications, contraceptive effectiveness, side effects and safety profile, possible mechanisms of action and counseling strategies will be reviewed. The potential benefits on reproductive health of wide-spread knowledge and easy, non-restrictive access to this methodology are emphasized. An extensive list of recent references is enclosed.