Brief report
A systemic type i 5 α-reductase inhibitor is ineffective in the treatment of acne vulgaris

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Abstract

Excessive sebum production is a central aspect of the pathophysiology of acne vulgaris. Sebaceous gland function is under androgen control and it is hypothesized that dihydrotestosterone is formed by the action of 5 α-reductase. Type I is the controlling isoenzyme. This study describes a 3-month, multicenter, randomized, placebo-controlled clinical trial with a potent, selective inhibitor of type I 5 α-reductase used alone and in combination with systemic minocycline. Inhibition of type I 5 α-reductase was not associated with clinical improvement of acne when used alone and did not enhance the clinical benefit of systemic minocycline. These results indicate the need for further work at the molecular level to better understand the action of androgens on sebaceous gland function.

Section snippets

Test agent, dosage selection, and duration of trial

Compound A is a selective and potent inhibitor of type I 5 α-reductase. Data from healthy volunteers demonstrated dose-dependent decreases in serum and sebum DHT levels at doses ranging from 5 to 25 mg/d.10 Pharmacokinetic studies of doses above 25 mg/d were nonlinear and did not result in a significant increase in plasma area under the curve. For these reasons 25 mg/d was the chosen test dose. In a pilot study for patients with mild to moderately severe acne, 25 mg/d produced a significant

Results

A total of 182 evaluable patients received 3 months of therapy. In all, 37 received 3 months of therapy with Compound A, 34 received 100 mg of minocycline twice a day, 74 received a combination of minocycline (100 mg twice a day) and 25 mg of Compound A daily, and 37 were treated with placebo. Table II, Table III

Between group differenceDifference95% Confidence intervalsP value
Compound A (25 mg) vs placebo−0.4−5.3,4.4.862
Compound A (25 mg) vs minocycline5.10.2, 10.0.045
Compound A (25 mg) vs

Discussion

In this trial, a potent and selective type I 5 α-reductase inhibitor was not significantly different from placebo in the treatment of moderately severe inflammatory acne. Significant improvement was seen in those treated with minocycline (100 mg twice a day) and those treated with the combination of this antibiotic and the type I 5 α-reductase inhibitor. However, no increment in improvement was seen for patients treated with the combination. These negative results raise important questions

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Supported by Merck Research Laboratories.

Disclosure: Several authors have consultancy agreements with, are members of the Speakers Bureau at, or are employees of the sponsoring company.

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