RESUMO
BACKGROUND: Progesterone receptor modulators (PRMs) delivered by contraceptive vaginal rings provide an opportunity for development of an estrogen-free contraceptive that does not require daily oral intake of steroids. The objective of this proof-of-concept study was to determine whether continuous delivery of 600-800 mcg of ulipristal acetate (UPA) from a contraceptive vaginal ring could achieve 80% to 90% inhibition of ovulation. STUDY DESIGN: This was a prospective, controlled, open-labeled, multicenter international trial to examine the effectiveness and safety of this prototype vaginal ring. Thirty-nine healthy women, 21-40 years old and not at risk of pregnancy, were enrolled at three clinic sites. Volunteers participated in a control cycle, a 12-week treatment period and a post-treatment cycle. Pharmacodynamic effects on follicular function and inhibition of ovulation, effects on endometrium, bleeding patterns and serum UPA levels were evaluated. RESULTS: Mean UPA levels during treatment were nearly constant, approximately 5.1 ng/mL throughout the study. Ovulation was documented in 32% of 111 "4-week treatment cycles." A correlation was observed between serum UPA and degree of inhibition of ovarian activity. There was no evidence of hyperplasia of endometrium, but PRM-associated endometrial changes were frequently observed (41%). CONCLUSION: In this study, the minimum effective contraceptive dose was not established. Further studies are required testing higher doses of UPA to attain ovulation suppression in a higher percentage of subjects.
Assuntos
Anticoncepcionais Femininos/farmacologia , Dispositivos Anticoncepcionais Femininos , Endométrio/efeitos dos fármacos , Menstruação/efeitos dos fármacos , Norpregnadienos/farmacologia , Inibição da Ovulação/efeitos dos fármacos , Receptores de Progesterona/antagonistas & inibidores , Adulto , Biomarcadores/metabolismo , Proliferação de Células/efeitos dos fármacos , Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Femininos/efeitos adversos , Anticoncepcionais Femininos/farmacocinética , Dispositivos Anticoncepcionais Femininos/efeitos adversos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/efeitos adversos , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Endométrio/citologia , Endométrio/metabolismo , Feminino , Antagonistas de Hormônios/administração & dosagem , Antagonistas de Hormônios/efeitos adversos , Antagonistas de Hormônios/farmacocinética , Antagonistas de Hormônios/farmacologia , Humanos , Imuno-Histoquímica , Menstruação/sangue , Menstruação/metabolismo , Norpregnadienos/administração & dosagem , Norpregnadienos/efeitos adversos , Norpregnadienos/farmacocinética , Folículo Ovariano/efeitos dos fármacos , Adulto JovemRESUMO
BACKGROUND: The Population Council studied a pre-coital contraceptive microbicide vaginal product containing levonorgestrel (LNG) as active component and Carraguard gel as a vehicle (Carra/LNG gel) for couples who engage in occasional unplanned intercourse. The objective of this study was to evaluate the effect of sexual intercourse after vaginal application of Carra/LNG gel on serum levels of LNG in women and to assess LNG absorption by the male partner. STUDY DESIGN: This was a randomized, cross-over, pharmacokinetic study including an abstinence arm and an arm in which couples engaged in sexual intercourse between 2 and 4 h after gel application. In each study arm, each woman received a single application of Carra/LNG gel (0.75 mg in 4 mL gel) followed by serial blood samples taken at 0, 1, 2, 4, 8, 24 and 48 h after gel application for LNG measurements. In the intercourse arm, LNG was measured in blood samples taken from the male partner before intercourse and at 4, 8 and 24 h after gel application in the female partner. RESULTS: Time concentration curves for serum LNG levels showed a mean C(max) of 7.8+/-5.5 and 8.3+/-5.7 nmol/L, a mean T(max) of 6.2+/-5.9 and 7.5+/-5.7, and comparable area under the curve for the intercourse and abstinence arm, respectively. Pharmacokinetic parameters presented large variability between subjects, but excellent reproducibility within each subject. LNG was undetectable in 10 out of 12 male partners. CONCLUSION: Sexual intercourse does not appear to interfere with vaginal absorption of LNG after application of a Carra/LNG gel. A vaginal pre-coital contraceptive gel is feasible.
Assuntos
Carragenina/farmacocinética , Coito/fisiologia , Anticoncepcionais Femininos/farmacocinética , Levanogestrel/farmacocinética , Cremes, Espumas e Géis Vaginais/farmacocinética , Absorção , Administração Intravaginal , Adulto , Carragenina/administração & dosagem , Carragenina/sangue , Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Femininos/sangue , Estudos Cross-Over , Feminino , Humanos , Levanogestrel/administração & dosagem , Levanogestrel/sangue , Masculino , Pessoa de Meia-Idade , Cremes, Espumas e Géis Vaginais/administração & dosagemAssuntos
Expulsão de Dispositivo Intrauterino/efeitos adversos , Dispositivos Intrauterinos de Cobre/efeitos adversos , Adulto , Feminino , Humanos , México , Dor/etiologia , Paridade , Gravidez , Gravidez não Desejada , Ensaios Clínicos Controlados Aleatórios como Assunto , Hemorragia Uterina/etiologiaRESUMO
A 2-year trial of a single Nestorone (NES) rod implant was conducted at three Latin American centers, each enrolling 100 women. We studied the safety, effectiveness and acceptability of this progestin-releasing contraceptive implant. Three pregnancies occurred, the last at 18 months of use. Because no pregnancies were expected in the first 18 months, the trial was halted. At that time, 224 women had completed at least 18 months of use, and 99 women had used the implant for more than 24 months. Few participants used adjunctive contraception between the time the study was halted and the time they had their implant removed. No additional pregnancies occurred before the removal of the last implant. The 2-year cumulative pregnancy rate was 1.7 per 100 with a Pearl index of 0.6 per 100 for the 2-year period. The 1-year and 2-year continuation rates were 80.5 and 66.7 per 100, respectively. Menstrual and medical disturbances were the principal reasons for discontinuation, followed by planned pregnancy. Headache and weight gain frequently led to discontinuation. The NES implant had little important effect on most clinical chemistry and lipid parameters. Over the study course, the mean change in hemoglobin was <1%. Slight modification of the design of this single 2-year implant, restoring features previously examined in clinical trials, is likely to improve its effectiveness. A single NES implant appears to provide acceptable contraception for women.
Assuntos
Anticoncepcionais Femininos/uso terapêutico , Norprogesteronas/uso terapêutico , Adolescente , Adulto , Análise de Variância , Brasil , Distribuição de Qui-Quadrado , Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Femininos/efeitos adversos , Implantes de Medicamento , Feminino , Seguimentos , Humanos , Distúrbios Menstruais/induzido quimicamente , Norprogesteronas/administração & dosagem , Norprogesteronas/efeitos adversos , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Gravidez , Gravidez não Desejada/estatística & dados numéricos , Resultado do TratamentoRESUMO
To study the question of whether one brand of oral contraceptives may be as acceptable as another for use in publicly-assisted family planning programs, a double blind study of two well-known brands, Ovral and Norinyl, was undertaken in Costa Rica and Trinidad. The pills were randomly assigned to 1,200 women. Common side effects - nausea, dizziness, vomiting, headaches - were associated with both Norinyl and Ovral. Differences in event rates for these conditions were much more marked by country than by pill used. Ovral was associated with increases in skin problems, notably chloasma, in Costa Rica. A higher percentage of women using Norinyl reported intermentstral bleeding and spotting in both countries. In Costa Rica continuation rated for Norinyl were adversely affected by this. With these exceptions there appear to be no important differences between the brands that would affect their use in family planning programs (AU)