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Evidence summaries

Combined Oral Contraceptive Pills (Cocs) for Treatment of Acne

Combined oral contraceptive pills appear to be effective in reducing acne lesion counts, severity grades and self-assessed acne compared with placebo. The effect may depend of the progestin used. Level of evidence: "B"

Comment: The quality of evidence is downgraded by study quality.

A Cochrane review [Abstract] 1 included 31 studies (6 placebo-controlled, 17 comparing 2 different COC regimens, 1 comparing a COC to an antibiotic), with a total of 12 579 subjects. Combination oral contraceptives (COC) reduced 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.

A randomized trial 2 compared ethinyl estradiol (EE) and chlormadinone acetate (CMA) versus COCs containing EE and drospirenone (DRSP) for the treatment of acne and dysmenorrhea.180 women were included. At month 6, acne lesions were reduced in both groups. There was a significantly greater reduction of total acne lesion in the EE/chlormadinone acetate group than EE/drospirenone (72.2% vs 64.5%; p = 0.009). As per the investigator's global assessment of acne treatment, a higher proportion of the subjects from the chlormadinone acetate group was rated "excellent" than those from the drospirenone (75.3% vs 49.4%). A higher proportion of the subjects in the chlormadinone acetate group reported a decrease in dysmenorrhoeic pain as "much decrease" and "decrease". The treatments were generally well-tolerated in both groups. There were no significant differences between both groups for adverse events.

A comparative study 3 divided women with polycystic ovary syndrome (PCOS) either to receive COC containing 3 mg drospirenone/30 mcg EE (ethinylestradiol) (DRSP group, n=60) or 2 mg chlormadinone acetate/30 mcg EE (CMA group, n=60). After 6 months of continuous treatment, a significant improvement was observed in hirsutism in both groups, the drop in Ferriman-Gallwey score was around 8 units (scale 0 to 36). also in acne lesions (scale 0-3) the imrovement was significant: with DRSP from2.32 ± 0.89to 0.31 ± 0.78 and with CMA 2.32 ± 0.89 to0.45 ± 0.98. Among glucose, insulin levels and HOMA-IR, there were statistically significant higher levels and the hormonal parameters (LH, FSH, prolactin, testosterone and DHEA-S) were statistically significant lower in both groups.

A Cochrane review [Abstract] 4 included 44 trials involving a total of 2253 women with PCOS. Metformin was less effective in improving hirsutism compared to COC in the subgroup BMI 25 kg/m² to 30 kg/m² (MD 1.92, 95% CI 1.21 to 2.64, 5 RCTs, n = 254), but there were no clear difference in the subgroup BMI under 25. Either metformin alone or COC alone may be less effective in improving hirsutism compared to metformin combined with COC. Metformin resulted in a higher incidence of gastrointestinal and a lower incidence of non-gastrointestinal severe adverse effects requiring stopping of medication.

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    References

    • Arowojolu AO, Gallo MF, Lopez LM et al. Combined oral contraceptive pills for treatment of acne. Cochrane Database Syst Rev 2012;(7):CD004425. [PubMed]
    • Jaisamrarn U, Santibenchakul S. A comparison of combined oral contraceptives containing chlormadinone acetate versus drospirenone for the treatment of acne and dysmenorrhea: a randomized trial. Contracept Reprod Med 2018;(3):5. [PubMed]
    • Podfigurna A, Meczekalski B, Petraglia F, et al. Clinical, hormonal and metabolic parameters in women with PCOS with different combined oral contraceptives (containing chlormadinone acetate versus drospirenone). J Endocrinol Invest 2020;43(4):483-492 [PubMed]
    • Fraison E, Kostova E, Moran LJ, et al. Metformin versus the combined oral contraceptive pill for hirsutism, acne, and menstrual pattern in polycystic ovary syndrome. Cochrane Database Syst Rev 2020;8(8):CD005552 [PubMed]

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