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Meta-Analysis
. 2013 Apr 30;2013(4):CD003552.
doi: 10.1002/14651858.CD003552.pub4.

Skin patch and vaginal ring versus combined oral contraceptives for contraception

Laureen M Lopez  1 , David A Grimes, Maria F Gallo, Laurie L Stockton, Kenneth F Schulz
Affiliations
Meta-Analysis

Skin patch and vaginal ring versus combined oral contraceptives for contraception

Laureen M Lopez et al. Cochrane Database Syst Rev. .

Abstract

Background: The delivery of combination contraceptive steroids from a transdermal contraceptive patch or a contraceptive vaginal ring offers potential advantages over the traditional oral route. The transdermal patch and vaginal ring could require a lower dose due to increased bioavailability and improved user compliance.

Objectives: To compare the contraceptive effectiveness, cycle control, compliance (adherence), and safety of the contraceptive patch or the vaginal ring versus combination oral contraceptives (COCs).

Search methods: Through February 2013, we searched MEDLINE, POPLINE, CENTRAL, LILACS, ClinicalTrials.gov, and ICTRP for trials of the contraceptive patch or the vaginal ring. Earlier searches also included EMBASE. For the initial review, we contacted known researchers and manufacturers to identify other trials.

Selection criteria: We considered randomized controlled trials comparing a transdermal contraceptive patch or a contraceptive vaginal ring with a COC.

Data collection and analysis: Data were abstracted by two authors and entered into RevMan. For dichotomous variables, the Peto odds ratio (OR) with 95% confidence intervals (CI) was calculated. For continuous variables, the mean difference was computed. We also assessed the quality of evidence for this review.

Main results: We found 18 trials that met our inclusion criteria. Of six patch studies, five examined the marketed patch containing norelgestromin plus ethinyl estradiol (EE); one studied a patch in development that contains levonorgestrel (LNG) plus EE. Of 12 vaginal ring trials, 11 examined the same marketing ring containing etonogestrel plus EE; one studied a ring being developed that contains nesterone plus EE.Contraceptive effectiveness was not significantly different for the patch or ring versus the comparison COC. Compliance data were limited. Patch users showed better compliance than COC users in three trials. For the norelgestromin plus EE patch, ORs were 2.05 (95% CI 1.83 to 2.29) and 2.76 (95% CI 2.35 to 3.24). In the levonorgestrel plus EE patch report, patch users were less likely to have missed days of therapy (OR 0.36; 95% CI 0.25 to 0.51). Of four vaginal ring trials, one found ring users had more noncompliance (OR 3.99; 95% CI 1.87 to 8.52), while another showed more compliance with the regimen (OR 1.67; 95% CI 1.04 to 2.68).More patch users discontinued early than COC users. ORs from two meta-analyses were 1.59 (95% CI 1.26 to 2.00) and 1.56 (95% CI 1.18 to 2.06) and another trial showed OR 2.57 (95% CI 0.99 to 6.64). Patch users also had more discontinuation due to adverse events than COC users. Users of the norelgestromin-containing patch reported more breast discomfort, dysmenorrhea, nausea, and vomiting. In the levonorgestrel-containing patch trial, patch users reported less vomiting, headaches, and fatigue.Of 11 ring trials with discontinuation data, two showed the ring group discontinued less than the COC group: OR 0.32 (95% CI 0.16 to 0.66) and OR 0.52 (95% CI 0.31 to 0.88). Ring users were less likely to discontinue due to adverse events in one study (OR 0.32; 95% CI 0.15 to 0.70). Compared to the COC users, ring users had more vaginitis and leukorrhea but less vaginal dryness. Ring users also reported less nausea, acne, irritability, depression, and emotional lability than COC users.For cycle control, only one trial study showed a significant difference. Women in the patch group were less likely to have breakthrough bleeding and spotting. Seven ring studies had bleeding data; four trials showed the ring group generally had better cycle control than the COC group.

Authors' conclusions: Effectiveness was not significantly different for the methods compared. Pregnancy data were available from half of the patch trials but two-thirds of ring trials. The patch could lead to more discontinuation than the COC. The patch group had better compliance than the COC group. Compliance data came from half of the patch studies and one-third of the ring trials. Patch users had more side effects than the COC group. Ring users generally had fewer adverse events than COC users but more vaginal irritation and discharge.The quality of the evidence for this review was considered low for the patch and moderate for the ring. The main reasons for downgrading were lack of information on the randomization sequence generation or allocation concealment, the outcome assessment methods, high losses to follow up, and exclusions after randomization.

PubMed Disclaimer

Conflict of interest statement

D Grimes has consulted with Bayer Healthcare Pharmaceuticals and Merck & Co., Inc.

Figures

1.1
1.1. Analysis
Comparison 1 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC levonorgestrel 50/75/125 µg + EE 30/40/30 µg, Outcome 1 Pregnancy per cycle.
1.3
1.3. Analysis
Comparison 1 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC levonorgestrel 50/75/125 µg + EE 30/40/30 µg, Outcome 3 Discontinuation ‐ overall (6 or 13 cycles).
1.4
1.4. Analysis
Comparison 1 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC levonorgestrel 50/75/125 µg + EE 30/40/30 µg, Outcome 4 Discontinuation ‐ adverse events (5 or 13 cycles).
1.5
1.5. Analysis
Comparison 1 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC levonorgestrel 50/75/125 µg + EE 30/40/30 µg, Outcome 5 Compliance per cycle.
1.6
1.6. Analysis
Comparison 1 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC levonorgestrel 50/75/125 µg + EE 30/40/30 µg, Outcome 6 Breakthrough bleeding or spotting (cycle 6).
1.7
1.7. Analysis
Comparison 1 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC levonorgestrel 50/75/125 µg + EE 30/40/30 µg, Outcome 7 Breakthrough bleeding or spotting (cycle 13).
1.8
1.8. Analysis
Comparison 1 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC levonorgestrel 50/75/125 µg + EE 30/40/30 µg, Outcome 8 Breast discomfort.
1.9
1.9. Analysis
Comparison 1 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC levonorgestrel 50/75/125 µg + EE 30/40/30 µg, Outcome 9 Headache.
1.10
1.10. Analysis
Comparison 1 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC levonorgestrel 50/75/125 µg + EE 30/40/30 µg, Outcome 10 Nausea.
1.11
1.11. Analysis
Comparison 1 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC levonorgestrel 50/75/125 µg + EE 30/40/30 µg, Outcome 11 Dysmenorrhea.
1.12
1.12. Analysis
Comparison 1 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC levonorgestrel 50/75/125 µg + EE 30/40/30 µg, Outcome 12 Abdominal pain.
1.13
1.13. Analysis
Comparison 1 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC levonorgestrel 50/75/125 µg + EE 30/40/30 µg, Outcome 13 Adverse events ‐ total (6 cycles).
2.1
2.1. Analysis
Comparison 2 Skin patches containing norelgestromin + EE versus COC norgestimate 250 µg + EE 35 µg, Outcome 1 Discontinuation ‐ overall (cycle 4): patch NGMN 150 µg + EE 20 µg versus OC.
2.2
2.2. Analysis
Comparison 2 Skin patches containing norelgestromin + EE versus COC norgestimate 250 µg + EE 35 µg, Outcome 2 Discontinuation ‐ overall (cycle 4): patch NGMN 112.5 µg + EE 15 µg versus OC.
2.3
2.3. Analysis
Comparison 2 Skin patches containing norelgestromin + EE versus COC norgestimate 250 µg + EE 35 µg, Outcome 3 Discontinuation ‐ overall (cycle 4): patch NGMN 75 µg + EE 10 µg versus OC.
2.4
2.4. Analysis
Comparison 2 Skin patches containing norelgestromin + EE versus COC norgestimate 250 µg + EE 35 µg, Outcome 4 Discontinuation ‐ adverse events (cycle 4): patch NGMN 150 µg + EE 20 µg versus OC.
2.5
2.5. Analysis
Comparison 2 Skin patches containing norelgestromin + EE versus COC norgestimate 250 µg + EE 35 µg, Outcome 5 Discontinuation ‐ adverse events (cycle 4): patch NGMN 112.5 µg + EE 15 µg versus OC.
2.6
2.6. Analysis
Comparison 2 Skin patches containing norelgestromin + EE versus COC norgestimate 250 µg + EE 35 µg, Outcome 6 Discontinuation ‐ adverse events (cycle 4): patch NGMN 75 µg + EE 10 µg versus OC.
2.7
2.7. Analysis
Comparison 2 Skin patches containing norelgestromin + EE versus COC norgestimate 250 µg + EE 35 µg, Outcome 7 Breakthrough bleeding or spotting (cycle 3): patch NGMN 150 µg + EE 20 µg versus OC.
2.8
2.8. Analysis
Comparison 2 Skin patches containing norelgestromin + EE versus COC norgestimate 250 µg + EE 35 µg, Outcome 8 Breakthrough bleeding or spotting (cycle 3): patch NGMN 112.5 µg + EE 15 µg versus OC.
2.9
2.9. Analysis
Comparison 2 Skin patches containing norelgestromin + EE versus COC norgestimate 250 µg + EE 35 µg, Outcome 9 Breakthrough bleeding or spotting (cycle 3): patch NGMN 75 µg + EE 10 µg versus OC.
3.1
3.1. Analysis
Comparison 3 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 1 Pregnancy per woman (3 cycles).
3.2
3.2. Analysis
Comparison 3 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 2 Spotting (3 cycles).
3.3
3.3. Analysis
Comparison 3 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 3 Amenorrhea.
3.4
3.4. Analysis
Comparison 3 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 4 Breast tenderness.
3.5
3.5. Analysis
Comparison 3 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 5 Nausea.
4.1
4.1. Analysis
Comparison 4 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC desogestrel 150 µg + EE 20 µg, Outcome 1 Pregnancy per woman.
4.3
4.3. Analysis
Comparison 4 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC desogestrel 150 µg + EE 20 µg, Outcome 3 Discontinuation ‐ overall (6 or 13 cycles).
4.4
4.4. Analysis
Comparison 4 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC desogestrel 150 µg + EE 20 µg, Outcome 4 Discontinuation ‐ adverse events (6 or 13 cycles).
4.5
4.5. Analysis
Comparison 4 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC desogestrel 150 µg + EE 20 µg, Outcome 5 Compliance per cycle.
4.6
4.6. Analysis
Comparison 4 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC desogestrel 150 µg + EE 20 µg, Outcome 6 Breakthrough bleeding and spotting (cycle 3).
4.7
4.7. Analysis
Comparison 4 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC desogestrel 150 µg + EE 20 µg, Outcome 7 Breakthrough bleeding and spotting (cycle 13).
4.8
4.8. Analysis
Comparison 4 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC desogestrel 150 µg + EE 20 µg, Outcome 8 Breast discomfort or pain.
4.9
4.9. Analysis
Comparison 4 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC desogestrel 150 µg + EE 20 µg, Outcome 9 Headache.
4.10
4.10. Analysis
Comparison 4 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC desogestrel 150 µg + EE 20 µg, Outcome 10 Nausea.
4.11
4.11. Analysis
Comparison 4 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC desogestrel 150 µg + EE 20 µg, Outcome 11 Dysmenorrhea.
4.12
4.12. Analysis
Comparison 4 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC desogestrel 150 µg + EE 20 µg, Outcome 12 Abdominal pain.
4.13
4.13. Analysis
Comparison 4 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC desogestrel 150 µg + EE 20 µg, Outcome 13 Vaginitis.
4.14
4.14. Analysis
Comparison 4 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC desogestrel 150 µg + EE 20 µg, Outcome 14 Vomiting.
4.15
4.15. Analysis
Comparison 4 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC desogestrel 150 µg + EE 20 µg, Outcome 15 Adverse events ‐ total.
4.16
4.16. Analysis
Comparison 4 Skin patch releasing norelgestromin 150 µg + EE 20 µg versus COC desogestrel 150 µg + EE 20 µg, Outcome 16 Very satisfied with method.
5.1
5.1. Analysis
Comparison 5 Skin patch containing levonorgestrel + EE versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 1 Discontinuation ‐ adverse events (cycle 6).
5.2
5.2. Analysis
Comparison 5 Skin patch containing levonorgestrel + EE versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 2 Noncompliance per cycle (cycle 6).
5.3
5.3. Analysis
Comparison 5 Skin patch containing levonorgestrel + EE versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 3 Breast tenderness (6 cycles).
5.4
5.4. Analysis
Comparison 5 Skin patch containing levonorgestrel + EE versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 4 Headache (6 cycles).
5.5
5.5. Analysis
Comparison 5 Skin patch containing levonorgestrel + EE versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 5 Migraine (6 cycles).
5.6
5.6. Analysis
Comparison 5 Skin patch containing levonorgestrel + EE versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 6 Nausea (6 cycles).
5.7
5.7. Analysis
Comparison 5 Skin patch containing levonorgestrel + EE versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 7 Dysmenorrhea (6 cycles).
5.8
5.8. Analysis
Comparison 5 Skin patch containing levonorgestrel + EE versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 8 Acne (6 cycles).
5.9
5.9. Analysis
Comparison 5 Skin patch containing levonorgestrel + EE versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 9 Vomiting (6 cycles).
5.10
5.10. Analysis
Comparison 5 Skin patch containing levonorgestrel + EE versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 10 Mood swings (6 cycles).
5.11
5.11. Analysis
Comparison 5 Skin patch containing levonorgestrel + EE versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 11 Depression (6 cycles).
5.12
5.12. Analysis
Comparison 5 Skin patch containing levonorgestrel + EE versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 12 Dizziness (6 cycles).
5.13
5.13. Analysis
Comparison 5 Skin patch containing levonorgestrel + EE versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 13 Fatigue (6 cycles).
5.14
5.14. Analysis
Comparison 5 Skin patch containing levonorgestrel + EE versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 14 Hypertension (6 cycles).
5.15
5.15. Analysis
Comparison 5 Skin patch containing levonorgestrel + EE versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 15 Libido decreased (6 cycles).
5.16
5.16. Analysis
Comparison 5 Skin patch containing levonorgestrel + EE versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 16 Weight increased (6 cycles).
6.1
6.1. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 1 Pregnancy per woman.
6.2
6.2. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 2 Discontinuation ‐ overall (3 to 12 cycles).
6.3
6.3. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 3 Discontinuation ‐ adverse events (3 or 12 cycles).
6.4
6.4. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 4 Noncompliance per woman.
6.5
6.5. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 5 Early or late withdrawal bleeding (cycle 6).
6.6
6.6. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 6 Early or late withdrawal bleeding (cycle 12).
6.7
6.7. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 7 Spotting or breakthrough bleeding (cycle 6).
6.8
6.8. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 8 Spotting or breakthrough bleeding (cycle 12).
6.9
6.9. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 9 Breakthrough bleeding (cycle 5).
6.10
6.10. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 10 Breast tenderness (cycles 5 & 6).
6.11
6.11. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 11 Breast tenderness (cycle 12).
6.12
6.12. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 12 Headache (cycle 6).
6.13
6.13. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 13 Headache (cycle 12).
6.14
6.14. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 14 Nausea (cycle 6).
6.15
6.15. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 15 Nausea (cycle 12).
6.16
6.16. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 16 Vaginal dryness (cycle 6).
6.17
6.17. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 17 Vaginal dryness (cycle 12).
6.18
6.18. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 18 Vaginal yeast infection/discomfort (cycle 5).
6.19
6.19. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 19 Irritability (cycle 6).
6.20
6.20. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 20 Irritability (cycle 12).
6.21
6.21. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 21 Mood swings (cycle 5).
6.22
6.22. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 22 Depression (cycle 6).
6.23
6.23. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 23 Depression (cycle 12).
6.24
6.24. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 24 Hot flashes (cycle 5).
6.25
6.25. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 25 Mean score for satisfaction with method.
6.26
6.26. Analysis
Comparison 6 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 100 µg + EE 20 µg, Outcome 26 Planned to use method.
7.1
7.1. Analysis
Comparison 7 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC gestodene 60 µg + EE 15 µg, Outcome 1 Pregnancy per woman.
7.2
7.2. Analysis
Comparison 7 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC gestodene 60 µg + EE 15 µg, Outcome 2 Discontinuation ‐ overall (12 cycles).
7.3
7.3. Analysis
Comparison 7 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC gestodene 60 µg + EE 15 µg, Outcome 3 Discontinuation ‐ adverse events (12 cycles).
7.4
7.4. Analysis
Comparison 7 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC gestodene 60 µg + EE 15 µg, Outcome 4 Early or late withdrawal bleeding (cycle 6).
7.5
7.5. Analysis
Comparison 7 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC gestodene 60 µg + EE 15 µg, Outcome 5 Early or late withdrawal bleeding (cycle 12).
7.6
7.6. Analysis
Comparison 7 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC gestodene 60 µg + EE 15 µg, Outcome 6 Spotting or breakthrough bleeding (cycle 6).
7.7
7.7. Analysis
Comparison 7 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC gestodene 60 µg + EE 15 µg, Outcome 7 Spotting or breakthrough bleeding (cycle 12).
7.8
7.8. Analysis
Comparison 7 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC gestodene 60 µg + EE 15 µg, Outcome 8 Breast tenderness (cycle 6).
7.9
7.9. Analysis
Comparison 7 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC gestodene 60 µg + EE 15 µg, Outcome 9 Breast tenderness (cycle 12).
7.10
7.10. Analysis
Comparison 7 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC gestodene 60 µg + EE 15 µg, Outcome 10 Headache (cycle 6).
7.11
7.11. Analysis
Comparison 7 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC gestodene 60 µg + EE 15 µg, Outcome 11 Headache (cycle 12).
7.12
7.12. Analysis
Comparison 7 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC gestodene 60 µg + EE 15 µg, Outcome 12 Nausea (cycle 6).
7.13
7.13. Analysis
Comparison 7 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC gestodene 60 µg + EE 15 µg, Outcome 13 Nausea (cycle 12).
7.14
7.14. Analysis
Comparison 7 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC gestodene 60 µg + EE 15 µg, Outcome 14 Vaginal dryness (cycle 6).
7.15
7.15. Analysis
Comparison 7 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC gestodene 60 µg + EE 15 µg, Outcome 15 Vaginal dryness (cycle 12).
7.16
7.16. Analysis
Comparison 7 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC gestodene 60 µg + EE 15 µg, Outcome 16 Irritability (cycle 6).
7.17
7.17. Analysis
Comparison 7 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC gestodene 60 µg + EE 15 µg, Outcome 17 Irritability (cycle 12).
7.18
7.18. Analysis
Comparison 7 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC gestodene 60 µg + EE 15 µg, Outcome 18 Depression (cycle 6).
7.19
7.19. Analysis
Comparison 7 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC gestodene 60 µg + EE 15 µg, Outcome 19 Depression (cycle 12).
8.1
8.1. Analysis
Comparison 8 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC desogestrel 150 µg + EE 20 µg, Outcome 1 Discontinuation ‐ overall (cycle 6).
9.1
9.1. Analysis
Comparison 9 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC drospirenone 3 mg + EE 30 µg, Outcome 1 Pregnancy per woman.
9.2
9.2. Analysis
Comparison 9 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC drospirenone 3 mg + EE 30 µg, Outcome 2 Discontinuation ‐ overall (cycle 12 or 13).
9.3
9.3. Analysis
Comparison 9 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC drospirenone 3 mg + EE 30 µg, Outcome 3 Discontinuation ‐ adverse events (cycle 12 or 13).
9.4
9.4. Analysis
Comparison 9 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC drospirenone 3 mg + EE 30 µg, Outcome 4 Mean breakthrough bleeding or spotting days (cycle 6).
9.5
9.5. Analysis
Comparison 9 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC drospirenone 3 mg + EE 30 µg, Outcome 5 Mean breakthrough bleeding or spotting days (cycle 13).
9.6
9.6. Analysis
Comparison 9 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC drospirenone 3 mg + EE 30 µg, Outcome 6 Breakthrough bleeding or spotting (12 cycles).
9.7
9.7. Analysis
Comparison 9 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC drospirenone 3 mg + EE 30 µg, Outcome 7 No withdrawal bleeding (12 cycles).
9.8
9.8. Analysis
Comparison 9 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC drospirenone 3 mg + EE 30 µg, Outcome 8 Breast pain.
9.9
9.9. Analysis
Comparison 9 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC drospirenone 3 mg + EE 30 µg, Outcome 9 Headache.
9.10
9.10. Analysis
Comparison 9 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC drospirenone 3 mg + EE 30 µg, Outcome 10 Nausea.
9.11
9.11. Analysis
Comparison 9 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC drospirenone 3 mg + EE 30 µg, Outcome 11 Dysmenorrhea.
9.12
9.12. Analysis
Comparison 9 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC drospirenone 3 mg + EE 30 µg, Outcome 12 Vaginitis.
9.13
9.13. Analysis
Comparison 9 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC drospirenone 3 mg + EE 30 µg, Outcome 13 Leukorrhea.
9.14
9.14. Analysis
Comparison 9 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC drospirenone 3 mg + EE 30 µg, Outcome 14 Acne.
9.15
9.15. Analysis
Comparison 9 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC drospirenone 3 mg + EE 30 µg, Outcome 15 Vomiting.
9.16
9.16. Analysis
Comparison 9 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC drospirenone 3 mg + EE 30 µg, Outcome 16 Emotional lability.
9.17
9.17. Analysis
Comparison 9 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC drospirenone 3 mg + EE 30 µg, Outcome 17 Decreased libido.
9.18
9.18. Analysis
Comparison 9 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC drospirenone 3 mg + EE 30 µg, Outcome 18 Weight increase.
9.19
9.19. Analysis
Comparison 9 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC drospirenone 3 mg + EE 30 µg, Outcome 19 Total number of adverse events (cycle 12).
9.20
9.20. Analysis
Comparison 9 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC drospirenone 3 mg + EE 30 µg, Outcome 20 Satisfied or very satisfied with method.
10.1
10.1. Analysis
Comparison 10 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC norgestimate 180/215/250 µg + EE 25 µg, Outcome 1 Pregnancy per woman.
10.2
10.2. Analysis
Comparison 10 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC norgestimate 180/215/250 µg + EE 25 µg, Outcome 2 Discontinuation.
10.3
10.3. Analysis
Comparison 10 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC norgestimate 180/215/250 µg + EE 25 µg, Outcome 3 Compliance: perfect use (3 months).
10.4
10.4. Analysis
Comparison 10 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC norgestimate 180/215/250 µg + EE 25 µg, Outcome 4 Frequent bleeding (> 4 episodes of bleeding or spotting).
10.5
10.5. Analysis
Comparison 10 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC norgestimate 180/215/250 µg + EE 25 µg, Outcome 5 Irregular bleeding (bleeding‐free interval > 17 days).
10.6
10.6. Analysis
Comparison 10 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC norgestimate 180/215/250 µg + EE 25 µg, Outcome 6 Prolonged bleeding (bleeding or spotting episode lasting >= 10 days).
10.7
10.7. Analysis
Comparison 10 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC norgestimate 180/215/250 µg + EE 25 µg, Outcome 7 Satisfied or very satisfied with method.
10.8
10.8. Analysis
Comparison 10 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC norgestimate 180/215/250 µg + EE 25 µg, Outcome 8 Planned to use method.
11.1
11.1. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 1 Pregnancy per woman.
11.2
11.2. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 2 Pregnancy per cycle.
11.3
11.3. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 3 Discontinuation ‐ overall (6 or 13 cycles).
11.4
11.4. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 4 Discontinuation ‐ adverse events (6 or 13 cycles).
11.5
11.5. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 5 Compliance per cycle.
11.6
11.6. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 6 Breakthrough bleeding (cycle 6).
11.7
11.7. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 7 Breakthrough spotting (cycle 6).
11.8
11.8. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 8 Breakthrough bleeding (cycle 13).
11.9
11.9. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 9 Breakthrough spotting (cycle 13).
11.10
11.10. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 10 Nausea.
11.11
11.11. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 11 Breast tenderness or pain.
11.12
11.12. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 12 Headache.
11.13
11.13. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 13 Dysmenorrhea.
11.14
11.14. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 14 Abdominal pain.
11.15
11.15. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 15 Vaginitis.
11.16
11.16. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 16 Genital pruritus.
11.17
11.17. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 17 Leukorrhea.
11.18
11.18. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 18 Urinary tract infection.
11.19
11.19. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 19 Acne.
11.20
11.20. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 20 Nervousness.
11.21
11.21. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 21 Depression.
11.22
11.22. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 22 Dizziness.
11.23
11.23. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 23 Libido decrease.
11.24
11.24. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 24 Weight increase.
11.25
11.25. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 25 Increased glucocorticoids.
11.26
11.26. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 26 Sinusitis.
11.27
11.27. Analysis
Comparison 11 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 27 Leg pain.
12.1
12.1. Analysis
Comparison 12 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC norgestimate 250 µg + EE 35 µg, Outcome 1 Pregnancy per woman (3 cycles).
12.2
12.2. Analysis
Comparison 12 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC norgestimate 250 µg + EE 35 µg, Outcome 2 Compliance per woman.
12.3
12.3. Analysis
Comparison 12 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC norgestimate 250 µg + EE 35 µg, Outcome 3 Amount of blood in period ‐ worse.
12.4
12.4. Analysis
Comparison 12 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC norgestimate 250 µg + EE 35 µg, Outcome 4 Bothersome side effects ‐ worse.
12.5
12.5. Analysis
Comparison 12 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC norgestimate 250 µg + EE 35 µg, Outcome 5 Headaches ‐ worse.
12.6
12.6. Analysis
Comparison 12 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC norgestimate 250 µg + EE 35 µg, Outcome 6 Nausea ‐ worse.
12.7
12.7. Analysis
Comparison 12 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC norgestimate 250 µg + EE 35 µg, Outcome 7 Cramping in periods ‐ worse.
12.8
12.8. Analysis
Comparison 12 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC norgestimate 250 µg + EE 35 µg, Outcome 8 PMS ‐ worse.
12.9
12.9. Analysis
Comparison 12 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC norgestimate 250 µg + EE 35 µg, Outcome 9 Discharge ‐ worse.
12.10
12.10. Analysis
Comparison 12 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC norgestimate 250 µg + EE 35 µg, Outcome 10 Acne ‐ worse.
12.11
12.11. Analysis
Comparison 12 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC norgestimate 250 µg + EE 35 µg, Outcome 11 Moodiness ‐ worse.
12.12
12.12. Analysis
Comparison 12 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC norgestimate 250 µg + EE 35 µg, Outcome 12 Depresssion ‐ worse.
12.13
12.13. Analysis
Comparison 12 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC norgestimate 250 µg + EE 35 µg, Outcome 13 Sex drive ‐ worse.
12.14
12.14. Analysis
Comparison 12 Vaginal ring releasing etonogestrel 120 µg + EE 15 µg versus COC norgestimate 250 µg + EE 35 µg, Outcome 14 Weight ‐ worse.
13.1
13.1. Analysis
Comparison 13 Vaginal ring releasing nestorone 150 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 1 Pregnancy.
13.2
13.2. Analysis
Comparison 13 Vaginal ring releasing nestorone 150 µg + EE 15 µg versus COC levonorgestrel 150 µg + EE 30 µg, Outcome 2 Discontinuation ‐ overall (cycle 3).
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Ahrendt 2006 {published data only}
    1. Ahrendt H‐J, Nisand I, Bastianelli C, Gómez AM, Gemzell‐Danielsson K, Urdl W, et al. Efficacy, acceptability and tolerability of the combined contraceptive ring, NuvaRing, compared with an oral contraceptive containing 3 µg of ethinyl estradiol and 3 mg of drospirenone. Contraception 2006;74(6):451‐7. - PubMed
    1. Milsom I, Lete I, Bjertnaes A, Rokstad K, Lindh I, Gruber CJ, et al. Effects on cycle control and bodyweight of the combined contraceptive ring, NuvaRing, versus an oral contraceptive containing 30 µg ethinyl estradiol and 3 mg drospirenone. Human Reproduction 2006;21(9):2304‐11. - PubMed
Audet 2001 {published data only}
    1. Audet MC, Moreau M, Koltun WD, Waldbaum AS, Shangold G, Fisher AC, et al. Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs an oral contraceptive: a randomized controlled trial. Journal of the American Medical Association 2001;285(18):2347‐54. - PubMed
Boonyarangkul 2007 {published data only}
    1. Boonyarangkul A, Taneepanichskul S. Comparison of cycle control and side effects between transdermal contraceptive patch and an oral contraceptive in women older than 35 years. Journal of the Medical Association of Thailand 2007;90(9):1715‐9. - PubMed
Dittrich 2002 {published data only}
    1. Dittrich R, Parker L, Rosen JB, Shangold G, Creasy GW, Fisher AC. Transdermal contraception: evaluation of three transdermal norelgestromin/ethinyl estradiol doses in a randomized, multicenter, dose‐response study. American Journal of Obstetrics and Gynecology 2002;186(1):15‐20. - PubMed
Duijkers 2004a {published and unpublished data}
    1. Duijkers I, Killick S, Bigrigg A, Dieben TO. A comparative study on the effects of a contraceptive vaginal ring NuvaRing and an oral contraceptive on carbohydrate metabolism and adrenal and thyroid function. European Journal of Contraception and Reproductive Health Care 2004;9(3):131‐40. - PubMed
Elkind‐Hirsch 2007 {published data only}
    1. Elkind‐Hirsch KE, Darensbourg C, Ogden B, Ogden LF, Hindelang P. Contraceptive vaginal ring use for women has less adverse metabolic effects than an oral contraceptive. Contraception 2007;76(5):348‐56. - PubMed
Gilliam 2010 {published data only}
    1. Gilliam M L, Neustadt A, Kozloski M, Mistretta S, Tilmon S, Godfrey E. Adherence and acceptability of the contraceptive ring compared with the pill among students: a randomized controlled trial. Obstetrics and Gynecology 2010;115(3):503‐10. - PubMed
    1. Hughey A B, Neustadt A B, Mistretta S Q, Tilmon S J, Gilliam M L. Daily context matters: predictors of missed oral contraceptive pills among college and graduate students. American Journal of Obstetrics and Gynecology 2010;203(4):323 e1‐7. - PubMed
Guida 2005 {published data only}
    1. Guida M, Spiezio Sardo A, Bramante S, Sparice S, Acunzo G, Tommaselli GA, et al. Effects of two types of hormonal contraception‐‐oral versus intravaginal‐‐on the sexual life of women and their partners. Human Reproduction 2005;20(4):1100‐6. - PubMed
Kaunitz 2012 {published data only (unpublished sought but not used)}
    1. Kaunitz A, Archer DF, Foegh M. Increased compliance with a low‐dose combination contraceptive patch (AG200‐15) compared with a low‐dose combination oral contraceptive (COC) in a Phase 3 clinical trial (abstract). Contraception 2012;86(2):178.
    1. Kaunitz A, Foegh M, Mishell D. Increased compliance independent of patient demographics with a low‐dose combination contraceptive patch (AG200‐15) compared with a low‐dose combination oral contraceptive in a Phase 3 clinical trial (abstract). Contraception 2012;86(3):314.
    1. Kaunitz AM, Mishell DR, Foegh M. Comparative Phase 3 study of AG200‐15, a low‐dose estrogen and levonorgestrel contraceptive patch. http://www.agiletherapeutics.com/Clinical_support.html (accessed 26 Sep 2012).
Kluft 2008 {published data only}
    1. Kluft C, Mayer G, Helmerhorst FM, Hall H, Creasy G. Comparison of the effects of a contraceptive patch and oral contraceptives on coagulation parameters [abstract no. FC2.30.04]. International Journal of Gynaecology and Obstetrics 2000;70(Suppl 2):B77.
    1. Kluft C, Meijer P, LaGuardia KD, Fisher AC. Comparison of a transdermal contraceptive patch vs. oral contraceptives on hemostasis variables. Contraception 2008;77(2):77‐83. - PubMed
Mohamed 2011 {published data only (unpublished sought but not used)}
    1. Mohamed A M, El‐Sherbiny W S, Mostafa W A. Combined contraceptive ring versus combined oral contraceptive (30‐mug ethinylestradiol and 3‐mg drospirenone). International Journal of Gynaecology and Obstetrics 2011;114(2):145‐8. - PubMed
Oddsson 2005 {published data only}
    1. Oddsson K, Leifels‐Fischer B, Wiel‐Masson D, Melo NR, Benedetto C, Verhoeven CHJ, et al. Superior cycle control with a contraceptive vaginal ring compared with an oral contraceptive containing 30 µg ethinylestradiol and 150 µg levonorgestrel: a randomized trial. Human Reproduction 2005;20(2):557‐62. - PubMed
    1. Oddsson K, Leifels‐Fischer B, Melo NR, Wiel‐Masson D, Benedetto C, Verhoeven CHJ, et al. Efficacy and safety of a contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive: a 1‐year randomized trial. Contraception 2005;71(3):176‐82. - PubMed
Rad 2006 {published data only}
    1. Rad M, Kluft C, Menard J, Burggraaf J, Kam ML, Meijer P, et al. Comparative effects of a contraceptive vaginal ring delivering a nonandrogenic progestin and continuous ethinyl estradiol and a combined oral contraceptive containing levonorgestrel on hemostasis variables. American Journal of Obstetrics and Gynecology 2006;195(1):72‐7. - PubMed
    1. Sitruk‐Ware RL, Menard J, Rad M, Burggraaf J, Kam ML, Tokay BA, et al. Comparison of the impact of vaginal and oral administration of combined hormonal contraceptives on hepatic proteins sensitive to estrogen. Contraception 2007;75(6):430‐7. - PubMed
Sabatini 2006 {published data only}
    1. Sabatini R, Cagiano R. Comparison profiles of cycle control, side effects and sexual satisfaction of three hormonal contraceptives. Contraception 2006;74(3):220‐3. - PubMed
Stewart 2007 {published data only}
    1. Stewart FH, Brown BA, Raine TR, Weitz TA, Harper CC. Adolescent and young women's experience with the vaginal ring and oral contraceptive pills. Journal of Pediatric and Adolescent Gynecology 2007;20(6):345‐51. - PMC - PubMed
Urdl 2005 {published data only}
    1. Hedon B, Helmerhorst FM, Cronje HS, Shangold G, Fisher A, Creasy G. Comparison of efficacy, cycle control, compliance and safety in users of a contraceptive patch vs an oral contraceptive. International Journal of Gynaecology and Obstetrics 2000;70(Suppl 2):B78.
    1. Urdl W, Apter D, Alperstein A, Koll P, Schönian S, Bringer J, et al. Contraceptive efficacy, compliance and beyond: factors related to satisfaction with once‐weekly transdermal compared with oral contraception. European Journal of Obstetrics & Gynecology and Reproductive Biology 2005;121(2):202‐10. - PubMed
Veres 2004 {published data only}
    1. Veres S, Miller L, Burington B. A comparison between the vaginal ring and oral contraceptives. Obstetrics and Gynecology 2004;104(3):555‐63. - PubMed
Westhoff 2005 {published data only}
    1. O'Connell KJ, Osborne LM, Westhoff C. Measured and reported weight change for women using a vaginal contraceptive ring vs. a low‐dose oral contraceptive. Contraception 2005;72(5):323‐7. - PubMed
    1. Schafer JE, Osborne LM, Davis AR, Westhoff C. Acceptability and satisfaction using Quick Start with the contraceptive vaginal ring versus an oral contraceptive. Contraception 2006;73(5):488‐92. - PubMed
    1. Westhoff C, Osborne LM, Schafer JE, Morroni C. Bleeding patterns after immediate initiation of an oral compared with a vaginal hormonal contraceptive. Obstetrics and Gynecology 2005;106(1):89‐96. - PubMed

References to studies excluded from this review

Archer 2002 {published data only}
    1. Archer D, Bigrigg A, Smallwood G, Shangold G, Creasy G. An integrated assessment of patient compliance with a weekly contraceptive patch (ORTHO EVRA / EVRA). Fertility and Sterility 2001; Vol. 76 (3 Suppl 1):20. - PubMed
    1. Archer DF, Bigrigg A, Smallwood GH, Shangold GA, Creasy GW, Fisher AC. Assessment of compliance with a weekly contraceptive patch (Ortho Evra™/Evra™) among North American women. Fertility and Sterility 2002;77:27‐31. - PubMed
Archer 2004 {published data only}
    1. Archer DF, Cullins V, Creasy GW, Fisher AC. The impact of improved compliance with a weekly contraceptive transdermal system (Ortho Evra) on contraceptive efficacy. Contraception 2004;69:189‐95. - PubMed
Bednarek 2008 {published data only}
    1. Bednarek PH, Nichols MD, Carlson N, Edelman AB, Creinin MD, Truitt S, et al. Effect of "observed start" vs. traditional "Sunday start" on hormonal contraceptive continuation rates after medical abortion. Contraception 2008;78(1):26‐30. - PubMed
Bjarnadottir 2002 {published data only}
    1. Bjarnadottir RI, Tuppurainen M, Killick SR. Comparison of cycle control with a combined contraceptive vaginal ring and oral levonorgestrel/ethinyl estradiol. American Journal of Obstetrics and Gynecology 2002;186:389‐95. - PubMed
Bustillos‐Alamilla 2010 {published data only}
    1. Bustillos‐Alamilla E, Zepeda‐Zaragoza J, Hernandez‐Ruiz M A, Briones‐Landa C H. Combined hormonal contraception in cycles artificially extended [Anticoncepción con hormonales combinados en ciclos extendidos artificialmente]. Ginecología de Obstetricia de México 2010;78(1):37‐45. - PubMed
Creasy 2000 {published data only}
    1. Creasy G, Hall N, Shangold G. Patient adherence with the contraceptive patch dosing schedule versus oral contraceptives. Obstetrics and Gynecology 2000; Vol. 95:S60.
Duijkers 2004b {published data only}
    1. Duijkers IJM, Klipping C, Verhoeven CHJ, Dieben TOM. Ovarian function with the contraceptive vaginal ring or an oral contraceptive: a randomized study. Human Reproduction 2004;19:2668‐73. - PubMed
    1. Duijkers IJM, Verhoeven CHJ, Dieben TOM, Klipping C. Follicular growth during contraceptive pill or vaginal ring treatment depends on the day of ovulation in the pretreatment cycle. Human Reproduction 2004;19:2674‐9. - PubMed
Guazzelli 2011 {published data only}
    1. Guazzelli CA, Barreiros FA, Barbosa R, Torloni MR, Barbieri M. Extended regimens of the contraceptive vaginal ring versus hormonal oral contraceptives: effects on lipid metabolism. Contraception 2011. - PubMed
Mulders 2001 {published data only}
    1. Mulders TM, Dieben TO. Use of the novel combined contraceptive vaginal ring NuvaRing for ovulation inhibition. Fertility and Sterility 2001;75:865‐70. - PubMed
Pierson 2000 {published data only}
    1. Pierson RA, Hess AR, Archer DF, Parsons K, Shangold G, Fisher A, et al. Effects of a contraceptive patch and 3 oral contraceptives on follicular development following incorrect dosing [abstract no. FC2.30.08]. International Journal of Gynaecology and Obstetrics 2000;70:78.
Pierson 2003 {published data only}
    1. Pierson RA, Archer DF, Moreau M, Shangold GA, Fisher AC, Creasy GW. Ortho Evra/Evra versus oral contraceptives: follicular development and ovulation in normal cycles and after an intentional dosing error. Contraception 2003;80:34‐42. - PubMed
Roumen 2006 {published data only}
    1. Roumen FJ, Dieben TO. Comparison of uterine concentrations of ethinyl estradiol and etonogestrel after use of a contraceptive vaginal ring and an oral contraceptive. Fertility and Sterility 2006;85:57‐62. - PubMed
Sibai 2002 {published data only}
    1. Sibai BM, Odlind V, Meador ML, Shangold GA, Fisher AC, Creasy GW. A comparative and pooled analysis of the safety and tolerability of the contraceptive patch (Ortho Evra™/Evra™). Fertility and Sterility 2002;77:19‐26. - PubMed
Smallwood 2001 {published data only}
    1. Smallwood GH, Meador ML, Lenihan JP, Shangold GA, Fisher AC, Creasy GW. Efficacy and safety of a transdermal contraceptive system. Obstetrics and Gynecology 2001;98(5 Pt 1):799‐805. - PubMed
Timmer 2000 {published data only}
    1. Timmer CJ, Mulders TM. Pharmacokinetics of etonogestrel and ethinylestradiol released from a combined contraceptive vaginal ring. Clinical Pharmacokinetics 2000;39:233‐42. - PubMed
Van den Heuvel 2005 {published data only}
    1. Heuvel MW, Bragt AJ, Alnabawy AK, Kaptein MC. Comparison of ethinylestradiol pharmacokinetics in three hormonal contraceptive formulations: the vaginal ring, the transdermal patch and an oral contraceptive. Contraception 2005;72:168‐74. - PubMed
White 2005 {published data only}
    1. White T, Jain JK, Stanczyk FZ. Effect of oral versus transdermal steroidal contraceptives on androgenic markers. American Journal of Obstetrics and Gynecology 2005;192:2055‐9. - PubMed
    1. White T, Özel B, Jain JK, Stanczyk FZ. Effects of transdermal and oral contraceptives on estrogen‐sensitive hepatic proteins. Contraception 2006;74:293‐6. - PubMed
Zacur 2002 {published data only}
    1. Zacur HA, Hedon B, Mansour D, Shangold GA, Fisher AC, Creasy GW. Integrated summary of Ortho Evra™/Evra™ contraceptive patch adhesion in varied climates and conditions. Fertility and Sterility 2002;77:32‐5. - PubMed
Zieman 2002 {published data only}
    1. Zieman M, Guillebaud J, Weisberg E, Shangold GA, Fisher AC, Creasy GW. Contraceptive efficacy and cycle control with the Ortho Evra™/Evra™ transdermal system. Fertility and Sterility 2002;77:13‐8. - PubMed

References to studies awaiting assessment

Agile 2011 {published data only (unpublished sought but not used)}
    1. Agile Therapeutics. Transdermal contraceptive delivery system (TCDS) of levonorgestrel and ethinyl estradiol (ATI‐CL13). http://clinicaltrials.gov/ct2/show/NCT01236768 (accessed 27 Sep 2012). [NCT01236768]
Bayer 2012b {published and unpublished data}
    1. Bayer Healthcare AG. US cycle control and blood pressure study. http://clinicaltrials.gov/ct2/show/NCT00920985 (accessed 27 Sep 2012). [NCT00920985]
Weisberg 2012 {published data only}
    1. Weisberg E. Comparative 12 month study of menstrually‐signalled use of a combined contraceptive pill versus a combined contraceptive vaginal ring. http://www.anzctr.org.au/ACTRN12609000391279.aspx (accessed 26 Jul 2012).

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Bayer 2012a
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Brache 2013
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FDA 2012
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Grimes 2009
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Heit 2005
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Hou 2010
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Lete 2008
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