Because the sebaceous gland is sensitive to androgens, there has been interest in developing a topical antiandrogen. Cyproterone acetate is a potent steroidal antiandrogen with progestational activity that has been used in combination with estrogen to treat women with hyperandrogenization. Cyproterone acetate competes with dihydrotestosterone for androgen receptors. Gruber and associates compared the effectiveness of topical cyproterone acetate with oral medication consisting of 0.035 mg of ethinyl estradiol and 2 mg of cyproterone acetate in women with acne.

Forty women were randomized to undergo treatment with 0.035 mg of oral ethinyl estradiol and 2 mg of cyproterone acetate, topical 20-mg cyproterone acetate lotion or placebo. The patients were assessed monthly for three months. Acne severity, lesion counts and determinations of serum cyproterone concentrations were graded clinically. Response to therapy was measured by calculating the difference between baseline measurements and measurements after three months of therapy. None of the patients received any systemic therapy for six weeks before the study began.

During the assessment period, both oral and topical cyproterone acetate were found to be significantly more effective than placebo in reducing mean facial acne grades and lesion counts. No significant differences were observed between the oral and topical cyproterone therapy groups.

After three months of topical cyproterone acetate application, lesion counts had decreased from a mean of 35.9 to a mean of 9.1. Serum cyproterone acetate concentrations were below the detection limit of 28 pg per mL before the treatment but increased to values between 119 and 311 pg per mL after topical cyproterone treatment. No adverse effects occurred in any of the groups during treatment.

Results of this study suggest that although well-established hormonal and nonhormonal treatments of acne are numerous, a topical agent can be efficacious without having adverse effects. Although other therapies such as spironolactone, flutamide, progesterone and gonadotropin-releasing agonists have been used to treat androgen symptoms in women, these medications may cause systemic side effects. Previous studies using topical cyproterone acetate have been unsuccessful because of inability to deliver the active substance to the target cell. This disadvantage was overcome by using a liposome lotion as the carrier for the active drug. Serum cyproterone acetate levels were 10 times lower after topical application than after oral use, but with a similar clinical response.

The authors conclude that topical cyproterone acetate is as effective as oral cyproterone acetate used in combination with ethinyl estradiol. This formulation represents a suitable alternative or additional topical treatment for women with acne.