Effects of the etonogestrel-releasing implant Implanon and a nonmedicated intrauterine device on the growth of breast-fed infants.

The study objectives were to compare the effects of an etonogestrel-releasing implant (Implanon) and a nonmedicated intrauterine device (IUD) on parameters of lactation in breast-feeding women and on the growth of their breast-fed infants over a 3-year period. Healthy lactating women (28-56 days postpartum) chose either the implant (n=42) or the IUD (n=38). Infant growth during a 3-year follow-up period is reported here. Total duration of breast-feeding coinciding with the mothers' treatment was 421.0 and 423.4 days in the Implanon and IUD groups, respectively. There were no differences between the infant groups in terms of body length, biparietal head circumference and body weight. No abnormalities were reported in psychomotor development or during physical examination. No treatment-related side effects were observed in either group. In conclusion, there were no differences in the growth of breast-fed infants of women treated with Implanon or a nonmedicated IUD. Implanon, therefore, appears to be a safe contraceptive option for breast-feeding women and their infants.

The combined contraceptive vaginal ring (NuvaRing) and endometrial histology.

We investigated the effects of NuvaRing on endometrial histology in a 2-year open-label, multicenter trial in 103 premenopausal women aged 18-35 years. Subjects received 26 cycles of treatment, each comprising 3 weeks of ring use followed by a 1-week ring-free period. Endometrial biopsies were taken at baseline, and at cycles 13 (month 12) and 26 (month 24). Normal biopsy results were obtained in all subjects after 24 months of NuvaRing treatment. Atrophic or inactive endometrium and secretory changes were present in the majority of the biopsies after 1 year and 2 years of treatment with the vaginal ring. It was concluded that long-term use of NuvaRing has no adverse effects on endometrial histology.

Maintenance of ovulation inhibition with the 75-microg desogestrel-only contraceptive pill (Cerazette) after scheduled 12-h delays in tablet intake.

BACKGROUND: In contrast to traditional progestagen-only pills (POPs), the desogestrel-only pill Cerazette consistently inhibits ovulation. This study was performed to test the hypothesis that desogestrel alone will keep inhibiting ovulation even when pills are taken 12 h late, indicating that delays in tablet intake of up to 12 h do not jeopardize contraceptive efficacy. METHODS: Women aged between 19 and 40 years with confirmed ovulation were admitted to this open-label pharmacodynamic study. They were treated with Cerazette for 56 days with three tablets to be taken 12 h late, having been randomized to a regimen with scheduled late tablets on Days 39, 42 and 49 (Group A) or on Days 11, 14 and 21 (Group B). The occurrence of ovulation during treatment was determined by measuring progesterone serum levels every 2 days. RESULTS: One of the 103 treated subjects ovulated during treatment. The ovulation incidence thus amounts to 1.0% (two-sided 95% confidence interval 0.02-5.29%). There was no apparent relationship between these ovulations and scheduled late tablets. The minimum time to first posttreatment ovulation was 7 days, whereas it took 17.2 days on average from last tablet intake until ovulation. CONCLUSIONS: Ovulation inhibition with Cerazette is maintained after 12-h delays in tablet intake and return of ovulation takes at least 7 days. These properties distinguish Cerazette from all other POPs.

Efficacy and safety of a contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive: a 1-year randomized trial.

This open-label, randomized, Phase III study compared the efficacy and tolerability of and compliance with NuvaRing, a combined contraceptive vaginal ring releasing 15 microg of ethinylestradiol (EE) and 120 microg of etonogestrel daily, with those of and with a combined oral contraceptive (COC) containing 150 microg of levonorgestrel (LNG) and 30 microg of EE. Subjects received NuvaRing or a COC for 13 cycles (3 weeks of ring/pill treatment followed by a 1-week ring-/pill-free period). A total of 1030 subjects (NuvaRing, n=512; COC, n=518) was randomized and started treatment (intent-to-treat [ITT] population). The percentage of women in the ITT population who completed the trial was 70.9% for the NuvaRing group and 71.2% for the COC group. Five in-treatment pregnancies occurred in each group, giving Pearl indices of 1.23 for NuvaRing and 1.19 for the COC. Compliance with both treatments was excellent and both were well tolerated. In conclusion, NuvaRing has comparable efficacy and tolerability with a COC containing 150 microg of LNG and 30 microg of EE and does not require daily dosing.

Efficacy, cycle control, and user acceptability of a novel combined contraceptive vaginal ring.

OBJECTIVE: To assess the contraceptive efficacy, cycle control, tolerability, and user acceptability of a novel combined contraceptive vaginal ring for up to 13 cycles. METHODS: Healthy women requesting contraception were enrolled in this 1-year multicenter study. Each ring released 120 microg of etonogestrel and 15 microg of ethinylestradiol daily, and was used for 3 weeks followed by a 1-week ring-free period. RESULTS: A total of 2322 women started treatment and so formed the intent-to-treat population. Subjects were followed for 23,298 cycles, equivalent to 1786 woman-years. Compliance was good with 85.6% of cycles in full compliance with specified criteria. In the intent-to-treat population, 21 pregnancies occurred, giving a Pearl Index of 1.18 (95% confidence interval 0.73, 1.80). Eleven of the pregnancies were attributable to noncompliance; the Pearl Index for the per-protocol population was 0.77 (95% confidence interval 0.37, 1.40). The mean incidence of withdrawal bleeding was 98.5% in all cycles. Irregular bleeding occurred in 5.5% of all cycles, and in most women, early or late withdrawal bleeding was restricted to spotting. The ring was well tolerated with a low incidence of adverse events; only 2.5% of all discontinuations were device related. The ring was easy to insert and remove and did not interfere with intercourse. Eighty-five percent of women were satisfied with the ring, and 90% would recommend its use to others. CONCLUSION: The ring is an effective contraceptive with excellent cycle control that is convenient, well tolerated, and highly acceptable to users.

Comparison of uterine concentrations of ethinyl estradiol and etonogestrel after use of a contraceptive vaginal ring and an oral contraceptive.

OBJECTIVE: To compare uterine tissue concentrations of ethinyl estradiol (EE) and etonogestrel (ENG) after one cycle of use of a contraceptive vaginal ring (NuvaRing; NV Organon, Oss, The Netherlands) or a combined oral contraceptive (COC). DESIGN: Randomized, open-label, pharmacokinetic study. SETTING: Obstetrics and gynecology unit. PATIENT(S): Eight premenopausal women about to undergo hysterectomy but otherwise healthy. INTERVENTION(S): One cycle (17-21 days) of NuvaRing or COC treatment that ended with surgical hysterectomy. MAIN OUTCOME MEASURE(S): Tissue concentrations of EE and ENG in uterine tissue samples taken from the upper myometrium and mid-myometrium, the cervical region, and the endometrium. RESULT(S): In both groups, concentrations of EE and ENG were similar in uterine tissue taken from the upper myometrium and mid-myometrium and the cervical region. However, compared with the COC group, concentrations of both hormones were markedly lower in tissue samples from the endometrium of women who had been treated with NuvaRing. CONCLUSION(S): Vaginal administration of hormones with NuvaRing did not produce elevated uterine concentrations of EE and ENG, compared with an oral contraceptive.

Follicular growth during contraceptive pill or vaginal ring treatment depends on the day of ovulation in the pretreatment cycle.

BACKGROUND: The aim of this study was to investigate whether the day of ovulation and the duration of a pretreatment cycle were related to the degree of follicular growth during subsequent contraceptive treatment. METHODS: This randomized, open-label study was performed in 40 healthy female volunteers, who were randomized by a computer-generated list after stratification for the ovulation day in a pretreatment cycle. They received two cycles of NuvaRing (21 subjects) or a combined oral contraceptive (COC) containing 30 microg ethinylestradiol and 150 microg levonorgestrel (19 subjects). Follicular diameter and serum hormone concentrations (FSH, LH, 17beta-estradiol, progesterone) were measured every third day. Data from treatment day 20 onwards were used for analysis. RESULTS: In the NuvaRing users, subjects with short cycles and early ovulations in the pretreatment cycle developed larger follicles during treatment than subjects with longer cycles and late ovulations. In the COC users, subjects with early ovulations in the pretreatment cycle developed larger follicles during treatment. CONCLUSIONS: The degree of follicular growth during treatment with a combined hormonal contraceptive is influenced by the duration of the pretreatment cycle and particularly by the duration of the follicular phase.

Ovarian function with the contraceptive vaginal ring or an oral contraceptive: a randomized study.

BACKGROUND: The effects on ovarian function of the combined contraceptive vaginal ring NuvaRing and a combined oral contraceptive (COC) were compared. METHODS: This randomized, open-label study was performed in 40 healthy female volunteers, who were randomized by a computer-generated list after stratification for the ovulation day in a pretreatment cycle. They received two cycles of NuvaRing (21 subjects) or a COC (30 microg ethinylestradiol and 150 microg levonorgestrel, 19 subjects). NuvaRing was started on cycle day 5, COC on cycle day 1. Follicular diameter, endometrial thickness and FSH, LH, 17beta-estradiol (E2) and progesterone concentrations were determined. RESULTS: The median maximum follicular diameter (maxFD) was < or =11 mm during treatment. In the first treatment cycle the maxFD was lower in the COC than in the NuvaRing group, due to the different starting procedures. MaxFD were not different in the second treatment cycle. In both groups, E2 and progesterone levels remained low during treatment. Ovulations did not occur. CONCLUSIONS: In both groups, ovarian activity was adequately suppressed. Due to the different starting procedures, lower ovarian activity was observed in the COC group in the first treatment cycle. In the second cycle, ovarian suppression was comparable with NuvaRing and COC treatment.

Ovarian function with a novel combined contraceptive vaginal ring.

BACKGROUND: NuvaRing is a combined contraceptive vaginal ring designed for 3 weeks continuous use followed by a 1 week ring-free period. The present study evaluated ovarian function in women who were instructed to either adhere to, or deviate from, the recommended regimen of use. METHODS: In this open-label, randomized study, 45 women aged between 18 and 35 years used NuvaRing for one cycle in which the ring was used according to the recommended regimen. Women in group A (n = 15) then continued with a 'normal' 3 week period of ring use after which the restoration of ovarian function-i.e. the time to ovulation-for each woman was determined by daily vaginal ultrasound and serum hormone levels. For women in group B (n = 15), the second cycle consisted of only 3 consecutive days of ring use, after which each woman was monitored until ovulation. Women in group C (n = 15) were not permitted to start a second 'normal' cycle until a follicle with a diameter of 13 mm was observed by vaginal ultrasound; subsequently, the development of these follicles during the second cycle of ring use was monitored daily. RESULTS: Irrespective of the length of the second cycle, 3 weeks (group A) versus 3 days (group B), a new cohort of follicles needed to be recruited and the time to ovulation after ring removal was similar (19 versus 17 days). The median time needed to develop a follicle up to 13 mm in diameter (group C) was 11 days (range 8-21 days); none of the women ovulated after insertion of the second ring. CONCLUSION: NuvaRing is a highly effective, reversible method of hormonal contraception. Ovulation, at least until the stage of a 13 mm dominant follicle, is prevented and as little as 3 consecutive days of NuvaRing use interferes with follicle growth.