Dermatology Online Journal

The efficacy of topical cyproterone acetate alcohol lotion versus placebo in the treatment of the mild to moderate acne vulgaris: a double blind study
Fariba Iraji MD¹, Ali Momeni MD², Seyed Morteza Naji MD², Amir Hossein Siadat MD³
Dermatology Online Journal 12 (3): 26

1. Dermatology Department, Isfahan University of Medical Sciences, Isfahan, Iran. iraji@med.mui.ac.ir
2. Isfahan University of Medical Sciences, Isfahan ,Iran
3. Skin Diseases and Leishmaniasis Research Center, Isfahan university of Medical Sciences , Isfahan, Iran

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Abstract

Acne is an inflammatory condition of the pilosebaceous unit. One of the essential factors for development of acne lesions is increased sebum excretion that is promoted by androgen. It is shown that oral cyproterone acetate significantly reduces the sebum excretion. In this study we evaluated the efficacy of cyproterone acetate alcohol lotion (CAAL) in the treatment of the mild to moderate acne vulgaris. This was a randomized double-blind clinical trial performed on 86 female patients with mild to moderate acne. They were randomly divided into 3 groups and were treated with 0.5 percent CAAL (n = 30), 1 percent CAAL (n = 13) and placebo (n = 43). They were followed every 15 days for a period of 45 days. Response to treatment was evaluated by the total acne lesions counting (TLC) and acne severity index (ASI) and was analyzed statistically by SPSS program. The efficacy of treatment on TLC was maximum for 1 percent CAAL (90 % reduction in TLC)(P value = 0.000). CAAL at 0.5 percent was able to reduce TLC as high as 80.8 percent during 6 weeks followup. The efficacy of placebo was determined to be 38.5 percent. Regarding TLC, 1 percent CAAL was 2.33 times more effective than placebo. CAAL at 0.5 percent was 2.09 times more effective than placebo in this respect. The efficacy of treatment on ASI was maximum for 1 percent CAAL (88 % reduction in ASI)(P value = 0.000). CAAL at 0.5 percent reduced ASI as much as 79.5 percent during 6 weeks of followup. The efficacy of placebo was calculated to be 9.8 percent in reduction of ASI . Regarding ASI, 1 percent CAAL was 8.97 times more effective than placebo. CAAL at 0.5 percent was 8.06 times more effective than placebo. Regarding the results of this study, we suggest the use of cyproterone acetate alcohol lotion as one of the main treatments for mild-moderate acne in female patients and as an adjuvant treatment for moderate to severe acne vulgaris.

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Acne vulgaris remains one of the commonest diseases to afflict humanity. An analysis of the 1996 Census data in the United States of America indicated that the prevalence of acne in the age group 12-24 was 85 percent [1]. Even in its mild form, acne can have lingering impacts on mental health (e.g., anxiety and depression), as well as on social interactions, self-confidence, self-esteem, and employment opportunities [2]. On the other hand, antibiotics, which suppress Propionibacterium acnes, are the standard treatment for acne but are becoming less effective probably because of the emergence of antibiotic-resistant strains [3, 4, 5, 6].

One of the suggested treatments for acne vulgaris is use of antiandrogens, including oral cyproterone acetate, that can decrease lipid secretion from the sebaceous glands. Unfortunately, oral cyproterone acetate has many side effects including fatigue, spontaneous milk secretion, development of the benign breast nodules, weight gain, and rarely anemia [7].

Application of topical microsomal form of cyproterone acetate has been suggested for treatment of this condition [8]. Regarding the price and difficulty in preparation of microsomal lotion of cyproterone acetate, we conducted a study to evaluate the efficacy of alcoholic lotion of cyproterone acetate for treatment of the mild to moderate acne vulgaris in females.

Methods

This was a double-blind clinical trial. We selected randomly 86 female patients with mild to moderate from patients presenting to Skin Disease and Leishmaniasis Research Center and Isfahan University of Medical Sciences clinics. Patients who were pregnant, breast feeding, or who had acne attributed to internal diseases were excluded. Patients who had a history of drug use for treatment of acne vulgaris in the preceding month were also excluded. Informed consent was obtained from all patients.

Patients were randomized to three groups. Group A included 30 patients treated with 0.5 percent cyproterone acetate alcohol lotion (CAAL). Group B included 13 patients treated with 1 percent CAAL. Group C included 43 patients treated with placebo. (Placebo included 70 % ethyl alcohol, 10 % propylene glycol, and talc.) Patients were instructed to apply the drug twice daily for 45 days. The patients were seen every 15 days for evaluation of the lesions and relevant side effects. At the end of study, labels were unblinded and the collected date were analyzed by using SPSS program.

To determine the efficacy of treatments on acne severity we used absolute lesion count for each type of acne lesion end acne severity index. Acne severity was calculated as follows: Acne severity index= Papules + (2 × pustules ) + (comedones) [9]. For comparison of efficacy of these treatments, statistical student t test was used. In the first visit, the total number of lesions was considered to be 100 percent and any decrease in lesions was calculated accordingly and regarded as improvement percent. The mean of these improvement percents were calculated in each group of patients and were used for statistical analysis.

Results

Demographic results

The mean age of patients in the 0.5 percent cyproterone-acetate-treated group was 19.7 years. The mean age of patients was 17.9 for 1 percent CAAL and 19.6 percent for placebo. There was no significant difference regarding the age in these three groups. The efficacy of 0.5 percent CAAL and 1 percent CAAL was significantly more there placebo.

Efficacy on total lesions counting (TLC)

The efficacy of treatment on TLC was maximum for 1 percent CAAL (90 % reduction in TLC) (p = 0.000). CAAL at 0.5 percent was able to reduce TLC as high as 80.8 percent during 6 weeks followup. The efficacy of placebo was determined to be 38.5 percent (Graph 1).

For TLC, 1 percent CAAL was 2.33 times more effective than placebo, 0.5 percent CAAL was 2.09 times more effective than placebo.

Efficacy on acne severity index (ASI)

The ASI was maximum for 1 percent CAAL (88 % reduction in ASI)(p = 0.000). CAAL at 0.5 percent reduced ASI as much as 79.5 percent during 6 weeks followup. The efficacy of placebo was calculated to be 38.5 percent in reduction of ASI (Graph 2). In terms of ASI, 1 percent CAAL was 8.97 times more effective than placebo and 0.5 percent CAAL was 8.06 times more effective than placebo.

Efficacy on number of closed comedones (CCN)

CAAL at 1 percent was shown to decrease CCN as high as 91 percent (p = 0.006), 0.5 percent CAAL reduced CCN as much as 82.5 percent during 6 weeks of followup. The efficacy of placebo was calculated to be 51.9 percent in reduction of CCN.

Efficacy on number of open comedones (OCN)

1% CAAL was shown to decrease OCN as high as 92 percent (p = 0.002), and at 0.5 %, CAAL reduced OCN as much as 82.6 percent during 6 weeks of followup. The efficacy of placebo was calculated to be 62 percent in reduction of OCN.

Efficacy on number of papules (PPN)

CAAL at 1 percent was shown to decrease PPN as high as 91 percent (p = 0.000), and at 0.5 percent CAAL reduced PPN as much as 78 percent during 6 weeks of follow up. The efficacy of placebo was calculated to be as low as 9.4 percent in reduction of PPN.

Efficacy on number of pustules (PUN)

CAAL at 1 percent was shown to decrease PUN as high as 92 percent (p = 0.000), and at 0.5 percent CAAL reduced PUN as much as 86.1 percent during 6 weeks of followup. The placebo worsened PUN (74.5 % increase in PUN).

Safety of treatment

We did not measure serum level of cyproterone acetate but none of the patients complained of any local side effcts related to drugs or placebo.

In comparison with placebo, CAAL was most effective on inflammatory lesions (papules & pustules) and least effective on non-inflammatory lesions (comedones). The effect of 1 percent CAAL was greater than 0.5 CAAL in all courses of treatment and in all types of lesions (p < 0.05) except on closed comedones. There was no significant difference between 0.5 percent and 1 percent CAAL in the treatment of the closed comedones (p > 0.05).

Discussion

The first use of antiandrogens for treatment of acne vulgaris goes back to year 1969. In that study 12 patients were evaluated but there was no significant results regarding the efficacy of this treatment [10]. Some 7 years later, this drug was used in the Cetomarogel Cream BPC, but none of the patients showed significant results [11]. Inocoterone acetate was used later but it also showed poor results [12].

In 1998 40 patients were evaluated for the efficacy of cyproterone acetate in the liposomal form. All patients were female and were allocated to receive liposomal cyproterone acetate, placebo or oral cyproterone acetate. They were treated and followed for 3 months. Doris and his colleagues concluded from this study that topical cyproterone acetate was equally effective as oral cyproterone acetate and was at least 40 percent more effective that placebo for treatment of acne vulgaris. The serum level of topical cyproterone acetate was 10 percent of oral cyproterone acetate [8].

Preparation of the drug in the liposome form is expensive and difficult. Because of this fact, we used the alcoholic formulation of cyproterone acetate. Our results showed that in all patients 1 percent CAAL was more effective than 0.5 percent CAAL and both of these formulations were significantly more effective than placebo in the treatment of the acne vulgaris. Also, in term of acne severity index, our results showed the results similar to Doris M et al. study [8]. In the Doris et al. study, liposomal formulation of the drug was approximately 40 percent more effective than placebo in the treatment of acne vulgaris. Our study showed that CAAL was 40-50 percent more effective than placebo for treatment of the mild to moderate acne vulgaris. The therapeutic effect became more prominent with continued use of the treatment.

In addition to regular lesion counting, we used acne severity index (ASI) to evaluate response to treatment. In this method, every type of lesion has different value and is calculated with different coefficient. By using this method, we can have better judgment about acne improvement during treatment [5]. Our results showed that CAAL was significantly more effective than placebo in improving acne severity index.

Black and white comedones are non-inflammatory acne lesions. CAAL was more effective in improvement of inflammatory lesions than noninflammatory lesions. This finding may be attributed to the fact that noninflammatory lesions are the results of the sebaceous gland duct obstruction and hyper cornification of the pilosebaceous ducts and these obstructions usually respond better to keratolytics. More studies are recommended in this respect.

Conclusions

Regarding the results of this study, we suggest the use of cyproterone acetate alcohol lotion as one of the main treatments for mild-moderate acne in female patients and as an adjuvant treatment for moderate to severe acne vulgaris.

Acknowledgments: We thank Dr. Meghdadi, Dr. Asilian, Dr. Shariati, Dr. Enshaieh, and Dr. Fatemi for their help to perform this research.

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