Feasibility study of Nestorone-ethinylestradiol vaginal contraceptive ring for emergency contraception.

OBJECTIVE: The Nestorone/ethinylestradiol (NES/EE) vaginal ring is being developed as a regular contraceptive method by the Population Council. This ring is designed to release NES 150 microg/day and EE 15 microg/day during 1 year. Here, we report a Phase I clinical trial to determine the usefulness of this ring for emergency contraception. To that end, we tested the ability of this ring to interfere with ovulation when it is inserted during the follicular phase. METHOD: Forty-eight women protected from the risk of pregnancy by nonhormonal methods were divided into three groups, which differed by the size of the dominant follicle at the time of ring insertion: 12-14 mm (n = 16), 15-17 mm (n = 18) and >or=18 mm (n = 14) diameter. The NES/EE ring was left in the vagina for 7 consecutive days, after which it was removed. The growth of the leading follicle and plasma levels of estradiol, progesterone (P), luteinizing hormone (LH) and follicle stimulating hormone (FSH) in the ensuing 5 days after ring insertion were determined. Afterwards, steroid hormones were measured twice a week, until menses took place. All women had a control cycle before the ring cycle, and the range of maximum follicular diameter assigned to each volunteer was the same for the control and the ring cycle at the time when placebo was ingested or the ring inserted. RESULTS: During the 5-day period after ring insertion with follicles 12-17 mm, ovulation was absent in 25 of 34 cycles (p < .01 vs. control), and ovulatory dysfunction (absent, blunted or mistimed LH peak) occurred in 8 of the 9 remaining cycles (33/34 ovulatory processes altered; p < .005 vs. control). After ring insertion with follicles >or=18 mm in diameter, ovulation did not occur in 2 of 14 cycles or was dysfunctional in 7 of the 12 remaining cycles (9/14 ovulatory processes altered; p<.025 vs. control). Altogether, 87.5% of ring cycles (42/48) had either no ovulation or ovulatory dysfunction in the 5-day study period, in contrast to 39.6% (19/48 cycles) in control cycles (p < .001). Among follicles that failed to rupture within the 5-day study period, none ruptured later on in the ring-treated cycles, while 9 of 16 did so in control cycles. Sixty-two percent of ring-treated cycles were shorter than 24 days. Nausea, vaginal discharge and abdominal pain were the most frequently reported adverse events during ring use. CONCLUSION: Interference with 87.5% of ovulatory processes, without ovulation occurring later in the cycle and shortening of cycle length, suggests the NES/EE ring may be used as an emergency contraceptive method, with the potential advantage of providing continuing contraception after it has performed its emergency function.

Effect of intermittent treatment with mifepristone on bleeding patterns in Norplant implant users.

A double-blind, placebo-controlled, randomized trial, was carried out in 120 Norplant users to evaluate the effect of mifepristone, 100 mg/day administered for 2 consecutive days every 30 days, on the vaginal bleeding pattern. Treatment was given from months 2-7 of implant use. Volunteers recorded bleeding and spotting days, during treatment and for the ensuing 6-month period. During treatment, women on mifepristone recorded the same frequency of bleeding/spotting episodes but significantly less prolonged bleeding episodes than placebo controls (mean +/- SD: 11 +/- 3 vs. 22 +/- 23 days) and their total number of bleeding days was 35% lower than in the placebo group. After the end of mifepristone use, bleeding patterns were similar in both groups. One pregnancy occurred in the mifepristone-treated group, in month 6 of treatment, the outcome was a healthy male baby. We conclude that intermittent administration of mifepristone can offer a clinically significant improvement of the vaginal bleeding pattern in Norplant users.

Patología anexial no inflamatoria durante el uso de implantes de levonorgestrel (Norplant) o dispositivos intrauterinos / Annexial pathology non inflammatory during levonorgestrel implant use (Norplant) or intrauterine devices

Se revisan las fichas clínicas de 477 mujeres usuarias de Norplant y 200 portadoras de T-Cobre que reúnen 28548 y 9752 meses de exposición, respectivamente. Se evaluó la presencia de masas anexiales no inflamatorias iguales o mayores de 5 cm, analizando su frecuencia, evolución natural y terminaciones. En 54 usuarias de Norplant (11,3%) se diagnosticaron 62 episodios de masas anexiales que corresponden a 2,6 episodios por 1.200 meses de uso. En 7 usuarias de T-Cobre (3,5%) se diagnosticaron 8 episodios, con una tasa de 1,0 episodios por 1.200 meses de uso. Las masas fueron casi siempre ováricas y unilaterales y se interpretaron en su mayoría como quístes ováricos funcionales por sus características clínicas y ecográficas y por su evolución. En 2 mujeres de cada grupo la masa se ubicó en la trompa y correspondió a embarazos tubarios. La incidencia de embarazo tubario en el grupo Norplant fue de 1 por 100 años mujer, inferior a lo ocurrido en el grupo T-Cobre y a lo referido con otras progestinas. En la mayoría de los casos (72,6% en el grupo Norplant y 62,5% en el grupo T-Cobre) la masa anexial era asintomática y se detectó en un control ginecológico de rutina. Los motivos de consulta en los otros casos fueron algia pelviana y sangrado anormal. Los episodios regresaron espontáneamente en el 90,4% de las usuarias de Norplant y en el 62,5% del grupo T-Cobre, la mayoría de ellos en los 60 días que siguieron al diagnóstico. Las indicaciones quirúrgicas en usuarias de Norplant fueron 2 embarazos tubarios, 2 quistes foliculares y 2 tumores neoplásicos. En el grupo T-Cobre las indicaciones quirúrgicas fueron 2 embarazos ectópicos y un quiste ovárico simple. Se concluye que los quistes funcionales ováricos son más frecuentes en mujeres portadoras de implantes Norplant que en los controles, que generalmente son asintomáticos y regresan espontáneamente. Deben ser vigilados hasta su desaparición por la posibilidad que se trate de una masa anexial de otra etiología que requiera tratamiento quirúrgico