RESUMO
BACKGROUND: Levonorgestrel (LNG) consistently prevents follicular rupture only when it is given before the onset of the ovulatory stimulus. As locally synthesized prostaglandin (PG) plays a crucial role in follicular rupture and cyclooxygenase-2 (cox-2) catalyses the final step of PG synthesis, we reasoned that adding a cox-2 inhibitor to LNG would prevent follicular rupture even after the ovulatory process had been triggered by the gonadotrophin surge. METHODS: Forty-one women were divided into two groups. One was treated when the size of the leading follicle was 15-17 mm (n=10) and the other when it was >or=18 mm (n=31). Each woman contributed with one cycle treated with LNG 1.5 mg single dose plus placebo and another treated with LNG + meloxicam (Melox) 15 mg, in a randomized order. Serial blood sampling for the assay of LH and follicular monitoring by transvaginal ultrasound were performed before and after treatment. RESULTS: Follicular rupture failed to occur within the 5-day period that followed treatment in 50 and 70% of cycles treated with LNG + Placebo and LNG + Melox, respectively, in the 15-17 mm group (P=0.15) and in 16 and 39% of cycles treated with LNG + Placebo and LNG + Melox, respectively, in the >or=18 mm group (P < 0.052). The overall proportion of cycles with no follicular rupture or ovulatory dysfunction increased significantly by the addition of Melox to LNG (66 versus 88%, P < 0.012; n=41-matched pairs). CONCLUSIONS: The trend towards increased incidence of no follicular rupture when Melox was combined with LNG suggests that the addition of a cox-2 inhibitor has the potential to improve the contraceptive efficacy of LNG by a pre-fertilization effect.
Assuntos
Anovulação/induzido quimicamente , Anticoncepcionais Sintéticos Pós-Coito/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Levanogestrel/farmacologia , Tiazinas/farmacologia , Tiazóis/farmacologia , Adolescente , Adulto , Chile , Anticoncepcionais Sintéticos Pós-Coito/administração & dosagem , República Dominicana , Feminino , Humanos , Meloxicam , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/fisiologiaRESUMO
The objective of this study was to evaluate the contraceptive efficacy and clinical performance of a Nestorone subdermal implant (NES) in the postpartum period. NES (n = 100) and Copper T intrauterine device (T-Cu; n = 100) acceptors initiated contraception at 8 weeks postpartum and were followed at monthly intervals during the first year and at 3-month intervals thereafter. Pregnancy rates, breastfeeding performance, infant growth, bleeding pattern, and side effects were assessed. Blood and milk NES concentration were measured. No pregnancy occurred in 2195 and 2145 woman-months of NES implant and T-Cu use, respectively. No effect of NES on lactation and infant growth and no serious adverse events were observed. Lactational amenorrhea was significantly longer in NES users (353 +/- 20 days) than in T-Cu users (201 +/- 11 days). More NES users (55.8%) experienced prolonged bleedings than did T-Cu users (36.2%). Concentrations of NES in breast milk ranged between 54-135 pmol/liter. The Nestorone implant is a highly effective contraceptive, safe for breastfed infants because the steroid is inactive by the oral route.
Assuntos
Anticoncepção , Anticoncepcionais Femininos/administração & dosagem , Lactação/efeitos dos fármacos , Norprogesteronas/administração & dosagem , Adolescente , Adulto , Amenorreia/fisiopatologia , Aleitamento Materno , Chile , Anticoncepcionais Femininos/metabolismo , Implantes de Medicamento , Feminino , Seguimentos , Humanos , Dispositivos Intrauterinos de Cobre/efeitos adversos , Leite Humano/efeitos dos fármacos , Leite Humano/metabolismo , Norprogesteronas/efeitos adversos , Norprogesteronas/metabolismo , Pacientes Desistentes do Tratamento , Período Pós-Parto/efeitos dos fármacos , Fatores de Tempo , Hemorragia Uterina/induzido quimicamente , DesmameRESUMO
The efficacy of a low dose of mifepristone, 5 mg/day for the first 15 days of the menstrual cycle, followed by medroxy-progesterone acetate (MPA), 10 mg/day for the next 13 days, for inhibiting ovulation was assessed in ten volunteers who were treated for three successive cycles. Hormonal determinations in blood and urine samples, ovarian ultrasonography and an endometrial biopsy taken on day 21-24 of the third treatment cycle were used to monitor the cycles. Ovulation was confirmed in 11 of the 30 treated cycles and, in these 11, the LH peak and follicular rupture occurred during MPA treatment periods. Out of 19 anovulatory cycles, 16 had no increase in progesterone levels and another 3 developed a luteinized unruptured follicle. Progestin administration induced secretory changes in the endometrium, but irregular or delayed development was found. Regular withdrawal bleeding occurred in all subjects. These data indicate that the sequential regimen can suppress ovulation while maintaining regular bleeding but increased efficacy is needed for phase II clinical trials.
PIP: The efficacy of a low dose of mifepristone, 5 mg/day for the first 15 days of the menstrual cycle, followed by medroxyprogesterone acetate (MPA), 10 mg/day for the next 13 days, for inhibiting ovulation was assessed in 10 Chilean volunteers who were treated for 3 successive cycles. They were healthy, surgically sterilized women with a mean age of 36.6 years and mean weight of 58.6 kg. Hormonal determinations in blood and urine samples, ovarian ultrasonography and an endometrial biopsy taken on days 21-24 of the third treatment cycle were used to monitor the cycles. Treatment inhibited ovulation during the 3 treatment cycles in 5 women. The regimen was partially effective in 3 women and totally ineffective in another 2 women. Ovulation was confirmed in 11 of the 30 treated cycles, and, in these 11, the luteinizing (LH) peak and follicular rupture occurred during MPA treatment periods. Out of 19 anovulatory cycles, 16 had no increase in progesterone levels and another 3 developed a luteinized unruptured follicle. Among the anovulatory cycles, 3 cycles presented a biphasic hormonal profile. In these 3 cycles the luteal phase progesterone level were much lower than in baseline cycles and they were associated with unruptured follicles. The other 16 cycles had a monophasic hormonal profile with no increase in progesterone levels in spite of a delayed rise in LH level. Progestin administration induced secretory changes in the endometrium, but irregular or delayed development was found. Only 9 post-treatment cycles were followed and 5 of these were ovulatory, 1 of them without a detectable LH midcycle peak. Regular withdrawal bleeding occurred in all subjects. These data indicate that the sequential regimen can suppress ovulation while maintaining regular bleeding, but increased efficacy is needed for phase II clinical trials.