20 µg versus >20 µg estrogen combined oral contraceptives for contraception
Maria F Gallo, Kavita Nanda, David A Grimes, Laureen M Lopez, Kenneth F Schulz, Maria F Gallo, Kavita Nanda, David A Grimes, Laureen M Lopez, Kenneth F Schulz
Abstract
Background: Concern about estrogen-related adverse effects has led to progressive reductions in the estrogen dose in combination oral contraceptives (COCs). However, reducing the amount of estrogen to improve safety could result in decreased contraceptive effectiveness and unacceptable changes in bleeding patterns.
Objectives: To test the hypothesis that COCs containing ≤ 20 μg ethinyl estradiol (EE) perform similarly as those containing > 20 μg in terms of contraceptive effectiveness, bleeding patterns, discontinuation, and side effects.
Search methods: In July 2013, we searched CENTRAL, MEDLINE, and POPLINE, and examined references of potentially eligible trials. We also searched for recent clinical trials using ClinicalTrials.gov and ICTRP. No new trials met the inclusion criteria. Previous searches included EMBASE. For the initial review, we wrote to oral contraceptive manufacturers to identify trials.
Selection criteria: English-language reports of randomized controlled trials were eligible that compare a COC containing ≤ 20 μg EE with a COC containing > 20 μg EE. We excluded studies where the interventions were designed to be administered for less than three consecutive cycles or to be used primarily as treatment for non-contraceptive conditions. Trials had to report on contraceptive effectiveness, bleeding patterns, trial discontinuation due to bleeding-related reasons or other side effects, or side effects to be included in the review.
Data collection and analysis: One author evaluated all titles and abstracts from literature searches to determine whether they met the inclusion criteria. Two authors independently extracted data from studies identified for inclusion. We wrote to the researchers when additional information was needed. Data were entered and analyzed with RevMan.
Main results: No differences were found in contraceptive effectiveness for the 13 COC pairs for which this outcome was reported. Compared to the higher-estrogen pills, several COCs containing 20 μg EE resulted in higher rates of early trial discontinuation (overall and due to adverse events such as irregular bleeding) as well as increased risk of bleeding disturbances (both amenorrhea or infrequent bleeding and irregular, prolonged, frequent bleeding, or breakthrough bleeding or spotting).
Authors' conclusions: While COCs containing 20 μg EE may be theoretically safer, this review did not focus on the rare events required to assess this hypothesis. Data from existing randomized controlled trials are inadequate to detect possible differences in contraceptive effectiveness. Low-dose estrogen COCs resulted in higher rates of bleeding pattern disruptions. However, most trials compared COCs containing different progestin types, and changes in bleeding patterns could be related to progestin type as well as estrogen dose. Higher follow-up rates are essential for meaningful interpretation of results.
Conflict of interest statement
DA Grimes has consulted with the pharmaceutical companies Bayer Healthcare Pharmaceuticals and Merck & Co, Inc.
Figures
Comparison 1 EE 20 µg and desogestrel 150 µg versus EE 30 µg and desogestrel 150 µg, Outcome 1 Pregnancy per woman.
Comparison 1 EE 20 µg and desogestrel 150 µg versus EE 30 µg and desogestrel 150 µg, Outcome 2 Discontinuation ‐ overall.
Comparison 1 EE 20 µg and desogestrel 150 µg versus EE 30 µg and desogestrel 150 µg, Outcome 3 Discontinuation ‐ mood changes.
Comparison 1 EE 20 µg and desogestrel 150 µg versus EE 30 µg and desogestrel 150 µg, Outcome 4 Discontinuation ‐ irregular bleeding.
Comparison 1 EE 20 µg and desogestrel 150 µg versus EE 30 µg and desogestrel 150 µg, Outcome 5 Discontinuation ‐ nausea.
Comparison 1 EE 20 µg and desogestrel 150 µg versus EE 30 µg and desogestrel 150 µg, Outcome 6 Amenorrhea ‐ cycle 3.
Comparison 1 EE 20 µg and desogestrel 150 µg versus EE 30 µg and desogestrel 150 µg, Outcome 7 Amenorrhea ‐ cycle 6.
Comparison 1 EE 20 µg and desogestrel 150 µg versus EE 30 µg and desogestrel 150 µg, Outcome 8 Irregular bleeding ‐ cycle 3.
Comparison 1 EE 20 µg and desogestrel 150 µg versus EE 30 µg and desogestrel 150 µg, Outcome 9 Duration of irregular bleeding in days ‐ cycle 3.
Comparison 1 EE 20 µg and desogestrel 150 µg versus EE 30 µg and desogestrel 150 µg, Outcome 10 Duration of irregular bleeding in days ‐ cycle 6.
Comparison 1 EE 20 µg and desogestrel 150 µg versus EE 30 µg and desogestrel 150 µg, Outcome 11 Dizziness.
Comparison 1 EE 20 µg and desogestrel 150 µg versus EE 30 µg and desogestrel 150 µg, Outcome 12 Dysmenorrhea.
Comparison 1 EE 20 µg and desogestrel 150 µg versus EE 30 µg and desogestrel 150 µg, Outcome 13 Headache.
Comparison 1 EE 20 µg and desogestrel 150 µg versus EE 30 µg and desogestrel 150 µg, Outcome 14 Increased weight.
Comparison 1 EE 20 µg and desogestrel 150 µg versus EE 30 µg and desogestrel 150 µg, Outcome 15 Irregular bleeding.
Comparison 1 EE 20 µg and desogestrel 150 µg versus EE 30 µg and desogestrel 150 µg, Outcome 16 Mood change.
Comparison 1 EE 20 µg and desogestrel 150 µg versus EE 30 µg and desogestrel 150 µg, Outcome 17 Nausea, diarrhea, vomiting.
Comparison 1 EE 20 µg and desogestrel 150 µg versus EE 30 µg and desogestrel 150 µg, Outcome 18 Prolonged withdrawal bleeding.
Comparison 2 EE 20 µg and desogestrel 150 µg versus EE 50 µg and desogestrel 125 µg, Outcome 1 Breakthough bleeding ‐ cycles 1 to 3.
Comparison 2 EE 20 µg and desogestrel 150 µg versus EE 50 µg and desogestrel 125 µg, Outcome 2 Breakthrough spotting ‐ cycles 1 to 3.
Comparison 2 EE 20 µg and desogestrel 150 µg versus EE 50 µg and desogestrel 125 µg, Outcome 3 Acne.
Comparison 2 EE 20 µg and desogestrel 150 µg versus EE 50 µg and desogestrel 125 µg, Outcome 4 Breast tenderness.
Comparison 2 EE 20 µg and desogestrel 150 µg versus EE 50 µg and desogestrel 125 µg, Outcome 5 Headache.
Comparison 2 EE 20 µg and desogestrel 150 µg versus EE 50 µg and desogestrel 125 µg, Outcome 6 Weight gain.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 1 Pregnancy per woman.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 2 Discontinuation ‐ overall.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 3 Discontinuation ‐ abdominal pain.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 4 Discontinuation ‐ adverse event.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 5 Discontinuation ‐ breast tension.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 6 Discontinuation ‐ colpitis.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 7 Discontinuation ‐ depressive mood.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 8 Discontinuation ‐ dizziness.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 9 Discontinuation ‐ headache.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 10 Discontinuation ‐ hypertension.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 11 Discontinuation ‐ hypomenorrhea.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 12 Discontinuation ‐ intermenstrual bleeding.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 13 Discontinuation ‐ menorrhagia.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 14 Discontinuation ‐ menstrual disorder.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 15 Discontinuation ‐ metrorrhagia.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 16 Discontinuation ‐ nausea.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 17 Discontinuation ‐ nervousness.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 18 Discontinuation ‐ pruritus.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 19 Discontinuation ‐ vomiting.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 20 Irregular bleeding ‐ cycle 3.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 21 Irregular bleeding ‐ cycle 6.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 22 Amenorrhea ‐ cycle 3.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 23 Amenorrhea ‐ cycle 6.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 24 Abdominal pain.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 25 Acne.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 26 Breast pain.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 27 Decreased libido.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 28 Depression.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 29 Dizziness.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 30 Dysmenorrhea.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 31 Emotional lability.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 32 Flatulence.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 33 Headache.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 34 Menstrual disorder.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 35 Metrorrhagia.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 36 Migraine.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 37 Nausea.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 38 Pain.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 39 Vaginal moniliasis.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 40 Vomiting.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 41 Weight gain.
Comparison 3 EE 20 µg and desogestrel 150 µg versus EE 30 µg and gestodene 75 µg, Outcome 42 Weight gain in kg.
Comparison 4 EE 20 µg and desogestrel 150 µg versus EE 30‐40‐30 µg and gestodene 50‐70‐100 µg, Outcome 1 Pregnancy per woman.
Comparison 4 EE 20 µg and desogestrel 150 µg versus EE 30‐40‐30 µg and gestodene 50‐70‐100 µg, Outcome 2 Discontinuation ‐ overall.
Comparison 4 EE 20 µg and desogestrel 150 µg versus EE 30‐40‐30 µg and gestodene 50‐70‐100 µg, Outcome 3 Discontinuation ‐ adverse reaction.
Comparison 4 EE 20 µg and desogestrel 150 µg versus EE 30‐40‐30 µg and gestodene 50‐70‐100 µg, Outcome 4 Discontinuation ‐ metrorrhagia.
Comparison 4 EE 20 µg and desogestrel 150 µg versus EE 30‐40‐30 µg and gestodene 50‐70‐100 µg, Outcome 5 Abdominal pain.
Comparison 4 EE 20 µg and desogestrel 150 µg versus EE 30‐40‐30 µg and gestodene 50‐70‐100 µg, Outcome 6 Acne.
Comparison 4 EE 20 µg and desogestrel 150 µg versus EE 30‐40‐30 µg and gestodene 50‐70‐100 µg, Outcome 7 Breast pain.
Comparison 4 EE 20 µg and desogestrel 150 µg versus EE 30‐40‐30 µg and gestodene 50‐70‐100 µg, Outcome 8 Decreased libido.
Comparison 4 EE 20 µg and desogestrel 150 µg versus EE 30‐40‐30 µg and gestodene 50‐70‐100 µg, Outcome 9 Depression.
Comparison 4 EE 20 µg and desogestrel 150 µg versus EE 30‐40‐30 µg and gestodene 50‐70‐100 µg, Outcome 10 Dizziness.
Comparison 4 EE 20 µg and desogestrel 150 µg versus EE 30‐40‐30 µg and gestodene 50‐70‐100 µg, Outcome 11 Dysmenorrhea.
Comparison 4 EE 20 µg and desogestrel 150 µg versus EE 30‐40‐30 µg and gestodene 50‐70‐100 µg, Outcome 12 Emotional lability.
Comparison 4 EE 20 µg and desogestrel 150 µg versus EE 30‐40‐30 µg and gestodene 50‐70‐100 µg, Outcome 13 Flatulence.
Comparison 4 EE 20 µg and desogestrel 150 µg versus EE 30‐40‐30 µg and gestodene 50‐70‐100 µg, Outcome 14 Headache.
Comparison 4 EE 20 µg and desogestrel 150 µg versus EE 30‐40‐30 µg and gestodene 50‐70‐100 µg, Outcome 15 Menstrual disorder.
Comparison 4 EE 20 µg and desogestrel 150 µg versus EE 30‐40‐30 µg and gestodene 50‐70‐100 µg, Outcome 16 Metrorrhagia.
Comparison 4 EE 20 µg and desogestrel 150 µg versus EE 30‐40‐30 µg and gestodene 50‐70‐100 µg, Outcome 17 Migraine.
Comparison 4 EE 20 µg and desogestrel 150 µg versus EE 30‐40‐30 µg and gestodene 50‐70‐100 µg, Outcome 18 Nausea.
Comparison 4 EE 20 µg and desogestrel 150 µg versus EE 30‐40‐30 µg and gestodene 50‐70‐100 µg, Outcome 19 Pain.
Comparison 4 EE 20 µg and desogestrel 150 µg versus EE 30‐40‐30 µg and gestodene 50‐70‐100 µg, Outcome 20 Vaginal moniliasis.
Comparison 4 EE 20 µg and desogestrel 150 µg versus EE 30‐40‐30 µg and gestodene 50‐70‐100 µg, Outcome 21 Vomiting.
Comparison 4 EE 20 µg and desogestrel 150 µg versus EE 30‐40‐30 µg and gestodene 50‐70‐100 µg, Outcome 22 Weight gain.
Comparison 5 EE 20 µg and desogestrel 150 µg versus EE 35 µg and norgestimate 180‐215‐250 µg, Outcome 1 Pregnancy per woman.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 1 Pregnancy per woman.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 2 Discontinuation ‐ overall.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 3 Discontinuation ‐ adverse event.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 4 Discontinuation ‐ intermenstrual bleeding.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 5 Discontinuation ‐ metrorrhagia.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 6 Breakthrough bleeding ‐ cycle 3.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 7 Breakthrough bleeding ‐ cycle 6.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 8 Spotting ‐ cycle 3.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 9 Spotting ‐ cycle 6.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 10 Acne.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 11 Breast tension or tenderness.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 12 Change in libido.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 13 Chloasma.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 14 Depressive moods.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 15 Diarrhea.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 16 Dizziness.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 17 Edema.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 18 Headache.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 19 Nausea.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 20 Nausea and vomiting.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 21 Nervousness.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 22 Varicose conditions.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 23 Vomiting.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 24 Weight gain >2 kg.
Comparison 6 EE 20 µg and gestodene 75 µg versus EE 30 µg and gestodene 75 µg, Outcome 25 Weight gain in kg.
Comparison 7 EE 20 µg and gestodene 75 µg (23‐day) versus EE 30 µg and gestodene 75 µg (21‐day), Outcome 1 Pregnancy per woman.
Comparison 7 EE 20 µg and gestodene 75 µg (23‐day) versus EE 30 µg and gestodene 75 µg (21‐day), Outcome 2 Intracyclic bleeding ‐ cycle 1 and at least once during cycles 2 to 6.
Comparison 8 EE 20 µg and levonorgestrel 100 µg versus EE 35 µg and norethindrone 500‐750‐1000 µg, Outcome 1 Pregnancy per woman.
Comparison 8 EE 20 µg and levonorgestrel 100 µg versus EE 35 µg and norethindrone 500‐750‐1000 µg, Outcome 2 Discontinuation ‐ overall.
Comparison 8 EE 20 µg and levonorgestrel 100 µg versus EE 35 µg and norethindrone 500‐750‐1000 µg, Outcome 3 Discontinuation ‐ adverse events.
Comparison 8 EE 20 µg and levonorgestrel 100 µg versus EE 35 µg and norethindrone 500‐750‐1000 µg, Outcome 4 Discontinuation ‐ breakthrough bleeding.
Comparison 8 EE 20 µg and levonorgestrel 100 µg versus EE 35 µg and norethindrone 500‐750‐1000 µg, Outcome 5 Discontinuation ‐ headache.
Comparison 8 EE 20 µg and levonorgestrel 100 µg versus EE 35 µg and norethindrone 500‐750‐1000 µg, Outcome 6 Discontinuation ‐ nausea or vomiting.
Comparison 8 EE 20 µg and levonorgestrel 100 µg versus EE 35 µg and norethindrone 500‐750‐1000 µg, Outcome 7 Intermenstrual bleeding ‐ cycle 3.
Comparison 8 EE 20 µg and levonorgestrel 100 µg versus EE 35 µg and norethindrone 500‐750‐1000 µg, Outcome 8 Amenorrhea ‐ cycle 3.
Comparison 8 EE 20 µg and levonorgestrel 100 µg versus EE 35 µg and norethindrone 500‐750‐1000 µg, Outcome 9 Breast pain.
Comparison 8 EE 20 µg and levonorgestrel 100 µg versus EE 35 µg and norethindrone 500‐750‐1000 µg, Outcome 10 Dysmenorrhea.
Comparison 8 EE 20 µg and levonorgestrel 100 µg versus EE 35 µg and norethindrone 500‐750‐1000 µg, Outcome 11 Headache.
Comparison 8 EE 20 µg and levonorgestrel 100 µg versus EE 35 µg and norethindrone 500‐750‐1000 µg, Outcome 12 Nausea.
Comparison 8 EE 20 µg and levonorgestrel 100 µg versus EE 35 µg and norethindrone 500‐750‐1000 µg, Outcome 13 Vomiting.
Comparison 9 EE 20 µg and levonorgestrel 100 µg versus EE 35 µg and norgestimate 180‐215‐250 µg, Outcome 1 Pregnancy per woman.
Comparison 10 EE 20 µg and norethindrone acetate 1 mg versus EE 30 µg and levonorgestrel 150 µg, Outcome 1 Pregnancy per woman.
Comparison 10 EE 20 µg and norethindrone acetate 1 mg versus EE 30 µg and levonorgestrel 150 µg, Outcome 2 Discontinuation ‐ bleeding.
Comparison 10 EE 20 µg and norethindrone acetate 1 mg versus EE 30 µg and levonorgestrel 150 µg, Outcome 3 Frequent bleeding ‐ cycles 1 to 3.
Comparison 10 EE 20 µg and norethindrone acetate 1 mg versus EE 30 µg and levonorgestrel 150 µg, Outcome 4 Infrequent bleeding ‐ cycles 1 to 3.
Comparison 10 EE 20 µg and norethindrone acetate 1 mg versus EE 30 µg and levonorgestrel 150 µg, Outcome 5 Irregular bleeding ‐ cycles 1 to 3.
Comparison 10 EE 20 µg and norethindrone acetate 1 mg versus EE 30 µg and levonorgestrel 150 µg, Outcome 6 Prolonged bleeding ‐ cycles 1 to 3.
Comparison 11 EE 20 µg and norethindrone acetate 1 mg versus EE 50 µg and levonorgestrel 150 µg, Outcome 1 Frequent bleeding ‐ cycles 1 to 3.
Comparison 11 EE 20 µg and norethindrone acetate 1 mg versus EE 50 µg and levonorgestrel 150 µg, Outcome 2 Infrequent bleeding ‐ cycles 1 to 3.
Comparison 11 EE 20 µg and norethindrone acetate 1 mg versus EE 50 µg and levonorgestrel 150 µg, Outcome 3 Irregular bleeding ‐ cycles 1 to 3.
Comparison 11 EE 20 µg and norethindrone acetate 1 mg versus EE 50 µg and levonorgestrel 150 µg, Outcome 4 Prolonged bleeding ‐ cycles 1 to 3.
Comparison 12 EE 20 µg and norethindrone acetate 1 mg versus EE 30 µg and norethindrone acetate 1.5 mg, Outcome 1 Duration of breakthrough bleeding or spotting in days ‐ cycle 3.
Comparison 12 EE 20 µg and norethindrone acetate 1 mg versus EE 30 µg and norethindrone acetate 1.5 mg, Outcome 2 Amenorrhea ‐ cycle 3.
Comparison 13 EE 20 µg and norethindrone acetate 1 mg versus EE 50 µg and norethindrone acetate 1 mg, Outcome 1 Duration of breakthrough bleeding or spotting in days ‐ cycle 3.
Comparison 13 EE 20 µg and norethindrone acetate 1 mg versus EE 50 µg and norethindrone acetate 1 mg, Outcome 2 Amenorrhea ‐ cycle 3.
Comparison 13 EE 20 µg and norethindrone acetate 1 mg versus EE 50 µg and norethindrone acetate 1 mg, Outcome 3 Frequent bleeding ‐ cycles 1 to 3.
Comparison 13 EE 20 µg and norethindrone acetate 1 mg versus EE 50 µg and norethindrone acetate 1 mg, Outcome 4 Infrequent bleeding ‐ cycles 1 to 3.
Comparison 13 EE 20 µg and norethindrone acetate 1 mg versus EE 50 µg and norethindrone acetate 1 mg, Outcome 5 Irregular bleeding ‐ cycles 1 to 3.
Comparison 13 EE 20 µg and norethindrone acetate 1 mg versus EE 50 µg and norethindrone acetate 1 mg, Outcome 6 Prolonged bleeding ‐ cycles 1 to 3.
Comparison 14 EE 20 µg and norethindrone acetate 1 mg versus EE 20‐30‐50 µg and norethindrone acetate 1‐1.5‐1 mg, Outcome 1 Duration of bleeding or spotting in days ‐ cycle 3.
Comparison 14 EE 20 µg and norethindrone acetate 1 mg versus EE 20‐30‐50 µg and norethindrone acetate 1‐1.5‐1 mg, Outcome 2 Amenorrhea ‐ cycle 3.
Comparison 15 EE 20 µg and norethindrone acetate 1 mg versus EE 35 µg and norethindrone acetate 400 µg, Outcome 1 Frequent bleeding ‐ cycles 1 to 3.
Comparison 15 EE 20 µg and norethindrone acetate 1 mg versus EE 35 µg and norethindrone acetate 400 µg, Outcome 2 Infrequent bleeding ‐ cycles 1 to 3.
Comparison 15 EE 20 µg and norethindrone acetate 1 mg versus EE 35 µg and norethindrone acetate 400 µg, Outcome 3 Irregular bleeding ‐ cycles 1 to 3.
Comparison 15 EE 20 µg and norethindrone acetate 1 mg versus EE 35 µg and norethindrone acetate 400 µg, Outcome 4 Prolonged bleeding ‐ cycles 1 to 3.
Comparison 16 EE 20 µg and norethindrone acetate 1 mg versus mestranol 50 µg and norethindrone 1 mg, Outcome 1 Frequent bleeding ‐ cycles 1 to 3.
Comparison 16 EE 20 µg and norethindrone acetate 1 mg versus mestranol 50 µg and norethindrone 1 mg, Outcome 2 Infrequent bleeding ‐ cycles 1 to 3.
Comparison 16 EE 20 µg and norethindrone acetate 1 mg versus mestranol 50 µg and norethindrone 1 mg, Outcome 3 Irregular bleeding ‐ cycles 1 to 3.
Comparison 16 EE 20 µg and norethindrone acetate 1 mg versus mestranol 50 µg and norethindrone 1 mg, Outcome 4 Prolonged bleeding ‐ cycles 1 to 3.
Comparison 17 EE 20 µg and norethindrone acetate 1 mg versus EE 25 µg and norgestimate 180‐215‐250 µg, Outcome 1 Pregnancy per woman.
Comparison 17 EE 20 µg and norethindrone acetate 1 mg versus EE 25 µg and norgestimate 180‐215‐250 µg, Outcome 2 Discontinuation ‐ overall.
Comparison 17 EE 20 µg and norethindrone acetate 1 mg versus EE 25 µg and norgestimate 180‐215‐250 µg, Outcome 3 Discontinuation ‐ adverse events.
Comparison 17 EE 20 µg and norethindrone acetate 1 mg versus EE 25 µg and norgestimate 180‐215‐250 µg, Outcome 4 Breakthrough bleeding ‐ cycle 3.
Comparison 17 EE 20 µg and norethindrone acetate 1 mg versus EE 25 µg and norgestimate 180‐215‐250 µg, Outcome 5 Breakthrough bleeding ‐ cycle 6.
Comparison 17 EE 20 µg and norethindrone acetate 1 mg versus EE 25 µg and norgestimate 180‐215‐250 µg, Outcome 6 Breakthrough bleeding or spotting ‐ cycle 3.
Comparison 17 EE 20 µg and norethindrone acetate 1 mg versus EE 25 µg and norgestimate 180‐215‐250 µg, Outcome 7 Breakthrough bleeding or spotting ‐ cycle 6.
Comparison 17 EE 20 µg and norethindrone acetate 1 mg versus EE 25 µg and norgestimate 180‐215‐250 µg, Outcome 8 Unscheduled bleeding ‐ cycle 3.
Comparison 17 EE 20 µg and norethindrone acetate 1 mg versus EE 25 µg and norgestimate 180‐215‐250 µg, Outcome 9 Unscheduled bleeding ‐ cycle 6.
Comparison 17 EE 20 µg and norethindrone acetate 1 mg versus EE 25 µg and norgestimate 180‐215‐250 µg, Outcome 10 Weight loss, maintenance, or gain 18.1. Analysis 19.1. Analysis 20.1. Analysis 20.2. Analysis
18.1. Analysis
Comparison 18 EE 20 µg…
18.1. Analysis
Comparison 18 EE 20 µg and drospirenone 3 mg versus EE 30 µg…
Comparison 18 EE 20 µg and drospirenone 3 mg versus EE 30 µg and drospirenone 3 mg, Outcome 1 Pregnancy per woman.
19.1. Analysis
Comparison 19 EE 20 µg…
19.1. Analysis
Comparison 19 EE 20 µg and drospirenone 3 mg versus EE 25 µg…
Comparison 19 EE 20 µg and drospirenone 3 mg versus EE 25 µg and norgestimate 180‐215‐250 µg, Outcome 1 Unscheduled bleeding days ‐ cycle 3.
20.1. Analysis
Comparison 20 EE 20 µg…
20.1. Analysis
Comparison 20 EE 20 µg and levonorgestrel 100 µg versus EE 30 µg…
Comparison 20 EE 20 µg and levonorgestrel 100 µg versus EE 30 µg and levonorgestrel 150 µg, Outcome 1 Pregnancy per woman.
20.2. Analysis
Comparison 20 EE 20 µg…
20.2. Analysis
Comparison 20 EE 20 µg and levonorgestrel 100 µg versus EE 30 µg…
Comparison 20 EE 20 µg and levonorgestrel 100 µg versus EE 30 µg and levonorgestrel 150 µg, Outcome 2 Adverse events.
All figures (172)
Comparison 18 EE 20 µg and drospirenone 3 mg versus EE 30 µg and drospirenone 3 mg, Outcome 1 Pregnancy per woman.
Comparison 19 EE 20 µg and drospirenone 3 mg versus EE 25 µg and norgestimate 180‐215‐250 µg, Outcome 1 Unscheduled bleeding days ‐ cycle 3.
Comparison 20 EE 20 µg and levonorgestrel 100 µg versus EE 30 µg and levonorgestrel 150 µg, Outcome 1 Pregnancy per woman.
Comparison 20 EE 20 µg and levonorgestrel 100 µg versus EE 30 µg and levonorgestrel 150 µg, Outcome 2 Adverse events.
Source: PubMed