ORAL CONTRACEPTIVES ? Oral contraceptives are useful in some women with normal menses and no evidence of excess androgen production. The estrogen in oral contraceptives suppresses ovarian androgen production via the inhibition of gonadotropins. In addition, estrogen elevates steroid hormone binding globulin, leading to decreased levels of circulating testosterone.
Combination oral contraceptives ? Combination oral contraceptives contain progestins, many of which are known to possess intrinsic androgenic activity. Newer third generation progestins (norgestimate, desogestrel, or gestodene) are considered to be less androgenic than their precursors. However, because all low-dose combination oral contraceptives are actually estrogen-dominant (and thus, anti-androgenic), oral contraceptives containing other progestins are beneficial in acne vulgaris [4-6]. Only three oral contraceptives (Ortho Tri-Cyclen?, Estrostep?, and Yaz?) have been approved by the US Food and Drug Administration (FDA) for the treatment of acne.
The triphasic combination pill with norgestimate and ethinyl estradiol (Ortho Tri-Cyclen?) was approved to treat acne vulgaris on the basis of its success in a randomized, placebo-controlled trial of 250 women ages 15 to 49 years with moderate disease . The oral contraceptive group performed significantly better than placebo for all primary efficacy measures, including inflammatory lesions (mean reduction 51 versus 35 percent), total lesions (mean reduction 46 versus 34 percent), and the investigator's global assessment (83 versus 63 percent). The significant placebo effect was likely due, in part, to improved skin care and more frequent visits for the study population overall.
With anti-androgenic progestins ? Oral contraceptives with anti-androgenic progestins are available as therapies for women with acne. These include oral contraceptives that contain cyproterone acetate, chlormadinone acetate, or drospirenone plus an estrogen [8,9]. Oral contraceptives containing cyproterone acetate and chlormadinone acetate are not available in the United States, but are used in Europe . Yasmin? (ethinyl estradiol 30 ug/drospirenone 3 mg) and Yaz? (ethinyl estradiol 20 ug/drospirenone 3 mg) are the two drospirenone-containing oral contraceptives that are prescribed in the United States.
Examples of evidence that supports the use of oral contraceptives containing anti-androgenic progestins include:
Two large, randomized, double-blind trials involving patients with moderate acne showed greater reductions in acne lesion counts with treatment with ethinyl estradiol 20 ug/drospirenone 3 mg (Yaz?) than with placebo [10,11]. Total lesion counts were reduced 46.3% for the combination oral contraceptive group and 30.6% for placebo group in one trial .
A large, randomized, double-blind trial compared ethinyl estradiol 30 ug/drospirenone 3 mg (Yasmin?) to ethinyl estradiol 35 ug/norgestimate 0.180,0.125,0.250 mg (Ortho Tri-Cyclen?) . There was a slightly greater reduction in total lesion count with drospirenone (-3.3 percent, 95% CI -6.6 to -0.1) although inflammatory lesion counts were similar in both groups.
An investigator-blinded randomized trial of 199 women with moderate acne showed reductions in acne papules and pustules after treatment with ethinyl estradiol 30 ug/chlormadinone acetate 2 mg or ethinyl estradiol 30 ug/levonorgestrel 0.15 mg. A greater percentage of women receiving chlormadinone acetate versus women receiving levonorgestrel (59 versus 46 percent) achieved at least a 50 percent reduction in acne lesions .
These trials are not sufficient to negate the use of traditional oral contraceptives for the management of acne vulgaris. Oral contraceptives without these anti-androgenic progestins remain effective treatments for women with acne.
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