A Cochrane review included 531 studies (6 placebo-controlled, 17 comparing 2 different COC regimens, 1 comparing a COC to an antibiotic), with a total of 8 05112 579 subjects. Combination oral contraceptives (COC) in 6 of the 7 trials that included a placebo group and 1 did not provide sufficient data for analysisreduced acne lesion counts, severity grades and self-assessed acne compared to placebo. Levonorgestrel (LNG) 100 μg / ethinyl estradiol (EE) 20 μg (2 trials) reduced the total lesion counts (WMD –9.98; 95% CI –16.51 to –3.45), both inflammatory and non-inflammatory, compared with the placebo. Similarly with norethindrone acetate (NA) 1 mg / EE 20–30–35 μg (1 trial) the clinician global assessment of no, minimal, or mild acne was better than with placebo (OR 1.86; 95% CI 1.32 to 2.62). Norgestimate (NGM) 180–215–250 μg / EE 35 μg (2 trials) reduced the total lesion counts (WMD –9.32; 95% CI –14.19 to –4.45), inflammatory lesion counts and comedones counts. Women in the NGM/EE group also were more likely to have improved acne compared to the placebo group for clinician global assessment (OR 3.86; 95% CI 2.31 to 6.44) and for participant self-assessment (OR 4.50; 95% CI 2.37 to 8.56). Two trials examined a COC with drospirenone 3 mg plus EE 20 µg versus a placebo, and both reported the mean percentage reduction in lesion count was significantly greater in the COC group compared to the placebo (reported P < 0.0001 and < 0.001, respectively).
Comparisons of COCs containing varying progestin types produced less clear and partly conflicting results. Potential differences may have been obscured by limited number of eligible trials, comparisons made and data reported. There is little evidence on the superiority of cyproterone acetate (CPA) over other progestins. A COC with CPA showed better acne outcomes than one with desogestrel, but the studies produced conflicting results. Likewise, LNG showed a slight improvement over desogestrel in acne outcomes, but results were not consistent. A drospirenone COC appeared to be more effective than NGM or nomegestrol acetate plus 17β-estradiol but less effective than CPA.
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