Multicenter study of the efficacy, cycle control and tolerability of a phasic desogestrel-containing oral contraceptive.

OBJECTIVE: To investigate the efficacy, cycle control and tolerability of a phasic oral contraceptive containing ethinylestradiol 35/30/30 microg and desogestrel 50/100/150 microg. METHODS: A multicenter study was conducted involving 2070 healthy, fertile women, who received study treatment for six treatment cycles. RESULTS: Most of the participants (79%) had previously been using an alternative oral contraceptive. In 10,408 treatment cycles, two women became pregnant while on treatment (Pearl index, 0.25). The incidence of irregular bleeding was 10% before treatment, rising to 27% at cycle 1, and decreasing to 11% by cycle 6. Irregular bleeding was mainly due to spotting rather than breakthrough bleeding and the incidence of breakthrough bleeding remained below 2.2% for most of the study period. Only 1.8% of women withdrew due to bleeding irregularities. First-time oral contraceptive users initially experienced more irregular bleeding than switchers but these differences lessened over time. The most common adverse events during treatment were headache, breast tenderness and nausea. The incidence of these adverse events fell to below pretreatment levels with continued use. CONCLUSION: The phasic preparation was effective and well tolerated.     

Multicenter study of the efficacy,cycle control and tolerability of a phasic desogestrel-containing oral contraceptive

Objective To investigate the efficacy, cycle control and tolerability of a phasic oral contraceptive containing ethinylestradiol 35/30/30 μg and desogestrel 50/100/150 μg.

Methods A multicenter study was conducted involving 2070 healthy, fertile women, who received study treatment for six treatment cycles.

Results Most of the participants (79%) had previously been using an alternative oral contraceptive. In 10 408 treatment cycles, two women became pregnant while on treatment (Pearl index, 0.25). The incidence of irregular bleeding was 10% before treatment, rising to 27% at cycle 1, and decreasing to 11% by cycle 6. Irregular bleeding was mainly due to spotting rather than breakthrough bleeding and the incidence of breakthrough bleeding remained below 2.2% for most of the study period. Only 1.8% of women withdrew due to bleeding irregularities. First-time oral contraceptive users initially experienced more irregular bleeding than switchers but these differences lessened over time. The most common adverse events during treatment were headache, breast tenderness and nausea. The incidence of these adverse events fell to below pretreatment levels with continued use.

Conclusion The phasic preparation was effective and well tolerated.     

Five-year, multicenter study of a triphasic, low-dose, combination oral contraceptive

A total of 4,342 women received a triphasic oral contraceptive combination containing levonorgestrel and ethinyl estradiol (Triphasil in the United States, Trinordiol in Europe) over a 5-year period, for a total of 70,282 cycles. Medication was begun on day 1 in the first cycle, with no backup contraception, and consisted of levonorgestrel (LNg) 50 micrograms + ethinyl estradiol (EE2) 30 micrograms for 6 days, LNg 75 micrograms + EE2 40 micrograms for 5 days, and LNg 125 micrograms + EE2 30 micrograms for 10 days. Twelve pregnancies occurred during the study, resulting in a Pearl Index of 0.22. Medication was missed in an overall total of 5,067 cycles (7.2%), and 9 of the 12 pregnancies were attributed by the investigators to misuse of the drug, resulting in a corrected Pearl Index of 0.06. Cycle control was excellent, bleeding irregularities were minimal, and the incidence of adverse experiences was low (generally less than 1% of total cycles). The results indicate that this triphasic combination, given in pharmacologic doses that are patterned after normal cycles, is a predictable, efficacious, well-tolerated, and accepted means of oral contraception.     

A comparison of the cycle control and tolerability of two ultra low-dose oral contraceptives containing 20 micrograms ethinylestradiol and either 150 micrograms desogestrel or 75 micrograms gestodene.

OBJECTIVE: To compare the cycle control and tolerability of two oral contraceptives containing 20 micrograms ethinylestradiol and either 150 micrograms desogestrel or 75 micrograms gestodene. METHODS: A randomized, multicenter study was conducted in which 1016 healthy adult women received the desogestrel (n = 509) or the gestodene (n = 507) preparation for six treatment cycles. RESULTS: No significant differences in bleeding patterns were detected between the two treatments. The incidence and duration of irregular bleeding decreased markedly, and to a similar extent, during each treatment. The occurrence of irregular bleeding per cycle decreased from 24.6 to 9.4% in the desogestrel group and from 19.7 to 8.6% in the gestodene group. Its duration fell from 1.1 to 0.2 days and from 0.9 to 0.3 days, respectively. There was a consistently low incidence of amenorrhea (1.0-2.8%). There were no significant differences between treatments for the incidence, intensity or emergence of dysmenorrhea. During both treatments, the incidence of premenstrual syndrome and complaints such as breast tenderness, nausea and headache dropped markedly. CONCLUSION: Ultra low-dose oral contraceptives containing desogestrel or gestodene offer equivalent, good cycle control and improvements in dysmenorrhea and premenstrual syndrome and have similar, excellent tolerability profiles.     

Comparison of cycle control with a combined contraceptive vaginal ring and oral levonorgestrel/ethinyl estradiol

OBJECTIVE: The purpose of this study was to compare cycle control and tolerability of the NuvaRing (NV Organon, Oss, The Netherlands), a novel combined contraceptive vaginal ring, with a standard combined oral contraceptive pill. STUDY DESIGN: Healthy women aged 18 to 40 years who requested contraception received either NuvaRing or a combined oral contraceptive containing 30 microg ethinyl estradiol and 150 microg levonorgestrel for 6 cycles in 3 similarly designed studies. Each cycle comprised 3 weeks of ring or pill use, followed by 1 ring- or pill-free week. RESULTS: Two hundred forty-seven women began the studies, 121 women with NuvaRing and 126 women with the combined oral contraceptive. Withdrawal bleeding occurred in virtually all cycles in both groups. In the NuvaRing groups, the incidence of irregular bleeding was < or =5% in all cycles; this was lower than the combined oral contraceptive groups (5.4%-38.8%). Furthermore, the incidence of a normal intended bleeding pattern was significantly higher in the NuvaRing groups than in the combined oral contraceptive groups (P <.01). Both contraceptives were well tolerated. CONCLUSION: NuvaRing has excellent cycle control and is well tolerated.     

A comparison of cycle control with monophasic levonorgestrel/ethinylestradiol 100 micrograms/20 micrograms versus triphasic norethindrone/ethinylestradiol 500-750-1000 micrograms/35 micrograms: a multicenter, randomized, open-label study.

OBJECTIVES: This multicenter, randomized, open-label study was undertaken to compare the effects on menstrual cycle control of two oral contraceptive regimens: monophasic levonorgestrel (LNG) 100 micrograms/ethinylestradiol (EE) 20 micrograms (Alesse or Loette) and triphasic norethindrone (NET) 500-750-1000 micrograms/EE 35 micrograms (OrthoNovum 7/7/7). METHODS: Healthy women with normal menstrual cycles were enrolled and completed up to four cycles of study medication. A total of 384 cycles in the LNG/EE group and 400 cycles in the NET/EE group were evaluable for analysis of cycle control. RESULTS: For all treatment cycles, the percentage of cycles classified as normal was consistently higher in the LNG/EE group than in the NET/EE group. By cycle 4, 69.9% of cycles with LNG/EE and 54.4% with NET/EE (p < 0.05) were normal. In individual cycles, consistently lower occurrences of intermenstrual bleeding (total bleeding and/or spotting) were seen for the LNG/EE group, although these differences were not statistically significant. Withdrawal bleeding characteristics were comparable between the two groups, except for the length of the latent period, which was significantly longer in the LNG/EE group. The incidence of treatment-emergent adverse events was similar in the two groups. CONCLUSION: This study indicates that the monophasic LNG/EE 100 micrograms/20 micrograms provides better cycle control than the multiphasic NET/EE product, despite its lower EE dose.     

Plasma concentrations of endogenous hormones during one regular treatment cycle with a low-dose oral contraceptive and during two cycles with deliberate omission of two tablets.

In this open, prospective, phase-I study we closely monitored levels of endogenous progesterone, 17beta-estradiol, luteinizing hormone (LH) and follicle stimulating hormone in six healthy women. We determined plasma concentrations every 1-3 days during one untreated baseline cycle and during the first treatment cycle with regular pill intake of an oral contraceptive containing 30 microg ethinylestradiol plus 75 microg gestodene. During the following two treatment cycles, two tablets were deliberately omitted (in cycle 2 on days 6/7 and in cycle 3 on days 11/12). All but possibly one volunteer ovulated in the untreated pre-cycle, as concluded from LH peaks followed by marked increases of progesterone. During the regular first treatment cycle and even after deliberate omission of two tables in treatment cycles 2 and 3, the progesterone and estradiol levels remained low, so that we concluded that no ovulation took place. However, two volunteers showed some sort of LH peak in the first regular treatment cycle and all women showed LH increases of > 40 microg/ml in at least one omission cycle. In ten out of 12 cycles, omissions of pill intake were followed by an episode of intermenstrual bleeding. In conclusion, we have shown that, after omission of two consecutive oral contraceptive tables, the endogenous hormone parameters did not provide evidence for ovulation. Although this provides confirmation of the robustness of this oral contraceptive towards non-compliance, the widely published practical recommendations should be followed.     

Plasma concentrations of endogenous hormones during one regular treatment cycle with a low-dose oral contraceptive and during two cycles with deliberate omission of two tablets

In this open, prospective, phase-I study we closely monitored levels of endogenous progesterone, 17β-estradiol, luteinizing hormone (LH) and follicle stimulating hormone in six healthy women. We determined plasma concentrations every 1–3 days during one untreated baseline cycle and during the first treatment cycle with regular pill intake of an oral contraceptive containing 30?μg ethinylestradiol plus 75?μg gestodene. During the following two treatment cycles, two tablets were deliberately omitted (in cycle 2 on days 6/7 and in cycle 3 on days 11/12). All but possibly one volunteer ovulated in the untreated pre-cycle, as concluded from LH peaks followed by marked increases of progesterone. During the regular first treatment cycle and even after deliberate omission of two tables in treatment cycles 2 and 3, the progesterone and estradiol levels remained low, so that we concluded that no ovulation took place. However, two volunteers showed some sort of LH peak in the first regular treatment cycle and all women showed LH increases of >?40?μg/ml in at least one omission cycle. In ten out of 12 cycles, omissions of pill intake were followed by an episode of intermenstrual bleeding. In conclusion, we have shown that, after omission of two consecutive oral contraceptive tables, the endogenous hormone parameters did not provide evidence for ovulation. Although this provides confirmation of the robustness of this oral contraceptive towards non-compliance, the widely published practical recommendations should be followed.     

Phase III clinical trial with a new oral contraceptive containing 150 micrograms desogestrel and 20 micrograms ethinylestradiol.

Results are presented of a Phase III international multicentre trial to study the effect of a new low-dose oral contraceptive (OC) containing 20 micrograms ethinylestradiol and 150 micrograms desogestrel (Mercilon) regarding efficacy, cycle control, blood pressure, and acceptability. Altogether 1,684 women from 12 European countries were included in the study. Four pregnancies occurred, 3 of them patient failures, one tablet failure. The overall Pearl Index was 0.20. The frequency of irregular bleeding was comparable to that recorded with other commonly used low-dose OCs. No serious side effects occurred. The incidence of the most frequently reported subjective side effects--headache, nausea and breast tension--was already low after the first cycle of treatment and decreased to below pretreatment levels with continued use. There was a small increase in mean body weight, which was confined essentially to young women. The preparation did not affect the mean systolic or diastolic blood pressure. This new preparation has thus proved to be an effective, safe and well-accepted ultra low-dose oral contraceptive.     

Efficacy, User Acceptability, Tolerability, and Cycle Control of a Combined Contraceptive Vaginal Ring: The Indian Perspective

Objective

To assess the contraceptive efficacy, user acceptability, cycle control, and tolerability of a combined contraceptive vaginal ring for up to 13 cycles.

Materials and Methods

Healthy women coming to the OPD for contraceptive advice were enrolled in this one-year study. Each ring was used for three weeks followed by a one-week ring-free period.

Results

A total of 184 women started treatment forming the intent to treat population. Subjects were followed for 13 cycles. Compliance was good with 99 % of cycles in full compliance with specified criteria. In the intent to treat population, no pregnancies occurred giving a Pearl Index of 0. The mean incidence of withdrawal bleeding was 99 % in all cycles. There was 0.16 % incidence of intermenstrual bleeding and 2 % incidence of early withdrawal bleeding. The ring was well tolerated with a low incidence of adverse events.

Conclusion

The ring is an effective contraceptive that is convenient, well tolerated with excellent cycle control, and highly acceptable to users.     

Efficacy and tolerability of a monophasic oral contraceptive containing ethinylestradiol and drospirenone.

OBJECTIVE: To assess the contraceptive reliability, cycle control and tolerability of a new monophasic oral contraceptive containing 30 g ethinylestradiol plus 3 mg drospirenone (Yasmin, Schering AG, Berlin, Germany), it was compared with an established oral contraceptive containing 30 g ethinylestradiol plus 150 g desogestrel (Marvelon, NV Organon, Oss, The Netherlands). METHODS: A randomized, open-label, 13-cycle study was performed at 80 European centers. Contraceptive reliability, cycle control, blood pressure, body weight, the incidence of adverse events and skin condition were assessed during 13 cycles of oral contraceptive use, and at follow-up. Subjects recorded body weight on three consecutive days pretreatment and weekly thereafter. RESULTS: Of 2069 women who started the study and received the trial preparations in a ratio of 4:1 (ethinylestradiol/drospirenone, n = 1657; ethinylestradiol/desogestrel, n = 412), 1615 completed the 13 cycles plus follow-up, providing data for over 23,000 evaluable cycles. Eleven pregnancies occurred during treatment, only one of which (in the ethinylestradiol/drospirenone group) could not be ascribed to user failure or interaction with other factors. Both preparations provided effective contraception and cycle control. Pre-existing acne and seborrhea were improved and blood pressure was essentially unchanged. The two treatments differed in their effect on body weight, the difference being statistically significant. In the ethinylestradiol/drospirenone group, there was a distinct decrease over the whole treatment phase, while a subtle and less distinct decrease was documented in the ethinylestradiol/desogestrel group. CONCLUSIONS: The combination of 30 g ethinylestradiol/3 mg drospirenone provides effective oral contraception, excellent cycle control, good tolerability and a level of weight loss that may have a significant beneficial effect on compliance in women with a tendency to weight gain due to water retention.     

Final Canadian Report of a Clinical Trial Evaluating the Safety and Efficacy of a New,Low-Dose Oral Contraceptive,Alesse™

The efficacy and safety of a new, low-dose, 21-day combination oral contraceptive containing 100 μg of levonorgestrel and 20 μg of ethinyl estradiol were evaluated in an open-label, multicentre trial. A total of 254 Canadian subjects were enrolled and received 4,564 cycles of exposure over the three-year course of the study. Of these, 137 completed 18 cycles of treatment. During the total 4,482 evaluable cycles of treatment, one pregnancy occurred, for a Pearl Index of 0.29 (82 cycles were excluded from this calculation due to protocol violations, including use of a second form of contraception or missing three or more consecutive pills in a cycle). Over the course of the study, 129 subjects withdrew for any reason, including 43 (17%) due to adverse events. The cumulative failure rate by life table analysis was 0.0048 per woman entering the 14th cycle. Breakthrough bleeding alone occurred in 3.9 percent of the cycles and breakthrough bleeding and spotting occurred together in 9.6 percent of the cycles. Of evaluable cycles, 1.3 percent were amenorrhoeic. The most commonly reported adverse events in this trial considered to be at least possibly due to the test drug were headache (36%) and metrorrhagia (36%). This formulation provides contraceptive efficacy similar to higher-dose oral contraceptives, while maintaining a safety and common OC side-effect profile that is consistent with prior years of reported use with kvonmgestrel-containing products.     

A low-dose triphasic oral contraceptive

Controlled clinical investigations of a three-phase, low-dose oral contraceptive combination of levonorgestrel and ethinyl estradiol were conducted at 17 sites in the United States and 60 sites in the United Kingdom. A day 1 start in cycle one with no backup contraception was used. A total of 3546 female volunteers participated in 35,036 cycles. Medication was missed in 2688 (7.7%) cycles. Nine pregnancies were reported for an uncorrected use-effectiveness rate of 0.33 per 100 woman-years. Cycle control was excellent, bleeding irregularities were minimal, and the incidence of side effects was very low. No clinically significant variations in blood pressure means or weight means were observed. Carbohydrate and lipid metabolism studies were limited to 6 months and showed minimal alterations. Subject compliance with the preparation was excellent. It is concluded that this triphasic oral contraceptive with its varying ratios of levonorgestrel and ethinyl estradiol is an effective, predictable, and well-tolerated combination oral contraceptive.     

Continuous combination oral contraceptive pills to eliminate withdrawal bleeding: a randomized trial

OBJECTIVE: To compare bleeding profiles of a traditional 28-day oral contraceptive pill cycle with continuous administration. METHODS: After a 28-day run-in cycle, women were randomized to either 28-day cycles (21 active pills and a pill-free week) or continuous use of the same 20 microg ethinyl estradiol/100 microg levonorgestrel formulation for 12 study cycles (336 days). The number of bleeding and spotting days were measured by daily diary. A subset underwent cycle 1 (n = 16), and nine (n = 14) pelvic ultrasound and endometrial histology sampling. Blood pressure, weight, hemoglobin, and adverse events were measured at revisit. The sample size with 80% power to detect a 67% reduction in bleeding days required 27 subjects in each arm. RESULTS: Of the 79 subjects randomized, 28 (70%) of the 28-day cycle and 32 (82%) of the continuous-use subjects completed the entire study (P =.6). With continuous use, 49%, 68%, and 88% of women reported no bleeding during cycles 2, 6, and 12, respectively. Amenorrhea or infrequent bleeding was present in 68% of continuous users during cycles 1-3 and increased to 88% during cycles 10-12. Spotting during cycle days 1-21 increased initially with continuous use but reduced over time, and by 9 months was less than the spotting reported by cyclic users. Adverse events, blood pressure, weight, and hemoglobin findings were similar between groups. CONCLUSION: Extension of the 28-day oral contraceptive cycle to continuous use with a low-estrogen dose combination oral birth control pill resulted in significantly fewer bleeding days.     

An open-label, multicentre trial to evaluate the vaginal bleeding pattern of the combined contraceptive vaginal ring NuvaRing

Objective

The objective of this multicentre, non-controlled, open-label study is the evaluation of the bleeding patterns during the use of a vaginal combined contraceptive, its safety in relation to occurrence of adverse effects, its efficacy as a contraceptive method and user compliance.

Study design

Healthy female volunteers (N = 165), asking for contraception, were enrolled to participate in the study. Each subject was given seven vaginal rings, releasing an average amount of 120 μg etonogestrel (ENG) and 15 μg ethinylestradiol (EE) per day. Study period was 7 cycles. A total of 878 cycles was valid for statistical analysis. The primary parameter, (breakthrough bleeding and/or spotting), was recorded for each cycle. The subjects were asked to report any adverse effect experienced during the treatment period, general physical and gynaecological examinations were performed and haematological blood tests were taken.

Results

Breakthrough bleeding/spotting occurred in 5.01% cycles (44 out of 878 cycles, of whom 37 were breakthrough spotting only). Absence of withdrawal bleeding during the ring-free period was reported in 1.94% cycles (17 out of 878). Forty-one subjects (24.8%) reported 66 events that were potentially drug-related. The most frequently drug-related events were weight increase (10 cases), headache (9 cases), nausea (4 cases). No pregnancy was reported during the study period. Haematology and chemical chemistry tests showed no clinically significant abnormality.

Conclusions

In the present study, NuvaRing^® has shown to be a valid contraceptive method to ensure optimal cycle control with low incidence of irregular bleeding and altered withdrawal bleeding. The low incidence of gastrointestinal side effects (nausea, vomiting) may be related the low hormonal dose and to the vaginal delivery of hormones which avoids the gastrointestinal tract.     

Efficacy of low-dose oral contraceptives containing levonorgestrel, gestoden and cyproterone acetate

The efficacy of low-dose oral contraceptives containing 30 micrograms or 35 micrograms ethinyl estradiol in combination with Levonorgestrel, gestoden (delta 15-Levonorgestrel) and cyproterone acetate was studied. Borderline doses for inhibition of ovulation were found to be approximately 50 micrograms for Levonorgestrel, 40 micrograms for gestoden and 1 mg for cyproterone acetate. These results were derived from the assay of luteinizing hormone, follicle-stimulating hormone, 17 beta-estradiol and progesterone serum levels during the daily treatment of a total of 47 female volunteers from day 5 through day 25 of their cycles. A combination of 30 micrograms ethinyl estradiol plus 75 micrograms Levonorgestrel or 75 micrograms gestoden resulted in complete inhibition of ovulation in each of the 20 subjects studied. Monitoring of hormone serum levels in 6 female volunteers with normal cycles during the administration of 35 micrograms ethinyl estradiol plus 2 mg cyproterone acetate showed inhibition of ovulation in all subjects studied during the first and third therapy cycle. One subject exhibited follicular maturation during the third treatment cycle as judged from the patterns of 17 beta-estradiol serum levels. Present data suggest that low-dose oral contraceptives containing Levonorgestrel, gestoden and cyproterone acetate are highly efficient in providing great contraceptive safety and do not support the previous notion that the kind of progestagen used is relevant for the degree of central inhibition.     

Sequential oral contraception using DMAP

A synthetic steroid, 3-desoxy-6-alpha-methyl-17-alpha-acetoxy progesterone (DMAP), was used as the progestin in a program of sequential oral administration of contraceptive tablets; indigent patients attending the postpartum clinic at the Medical College of Virginia were studied. No pregnancies occurred in 561 cycles of use. Withdrawal bleeding incidences usually occurred every 27 days, lasted 5 days, and were associated with moderate flow. The incidence of breakthrough bleeding was 3%; intermenstrual spotting, 2.4%; and nausea or vomiting, 9.5%. The endometrial changes more closely resembled those in a normal ovulatory cycle than those associated with oral contraceptive methods which utilize an estrogen-progestin mixture started on Cycle Day 5.     

Efficacy and tolerability of a monophasic oral contraceptive containing ethinylestradiol and drospirenone

Objective To assess the contraceptive reliability, cycle control and tolerability of a new monophasic oral contraceptive containing 30 g ethinylestradiol plus 3 mg drospirenone (Yasmin, Schering AG, Berlin, Germany), it was compared with an established oral contraceptive containing 30 g ethinylestradiol plus 150 g desogestrel (Marvelon, NV Organon, Oss, The Netherlands).

Methods A randomized, open-label, 13–cycle study was performed at 80 European centers. Contraceptive reliability, cycle control, blood pressure, body weight, the incidence of adverse events and skin condition were assessed during 13 cycles of oral contraceptive use, and at follow-up. Subjects recorded body weight on three consecutive days pretreatment and weekly thereafter.

Results Of 2069 women who started the study and received the trial preparations in a ratio of 4:1 (ethinylestradiol/drospirenone, n = 1657; ethinylestradiol/desogestrel, n = 412), 1615 completed the 13 cycles plus follow-up, providing data for over 23 000 evaluable cycles. Eleven pregnancies occurred during treatment, only one of which (in the ethinylestradiol/ drospirenone group) could not be ascribed to user failure or interaction with other factors. Both preparations provided effective contraception and cycle control. Pre-existing acne and seborrhea were improved and blood pressure was essentially unchanged. The two treatments differed in their effect on body weight, the difference being statistically significant. In the ethinylestradiol/drospirenone group, there was a distinct decrease over the whole treatment phase, while a subtle and less distinct decrease was documented in the ethinylestradiol/desogestrel group.

Conclusions The combination of 30 g ethinylestradiol/3 mg drospirenone provides effective oral contraception, excellent cycle control, good tolerability and a level of weight loss that may have a significant beneficial effect on compliance in women with a tendency to weight gain due to water retention.     

Nervousness and depression attributed to oral contraceptives: A double-blind,placebo-controlled study

In a placebo-controlled, double-blind trial of 4 oral contraceptive agents, 398 women were observed over 1,523 cycles and were questioned each cycle regarding certain subjective and objective symptoms including nervousness, depression, and weight gain. The frequency of nervousness and depression in the pretreatment cycle was considerably higher than in the first cycle of treatment with either active agents or placebo. The data fail to show any statistically significant increase over the placebo level in the incidence of depression among oral contraceptive users. There was a somewhat ambiguous increase in nervousness during the first treatment cycle with the 2 high-estrogen preparations. Thirty per cent of the placebo-treated group reported a weight gain of 5 pounds or more during the 4 months of observation in comparison to 19, 20, 28, and 31 per cent of the subjects using the 4 active agents. It would seem that the majority of nervousness, depression, and weight gain noted in oral contraceptive users is either coincidental or associated with the psychological impact of taking these agents, rather than with any pharmacologic effect.     

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.