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Oral Anti-androgen Treatment for Acne

Androgens influence the acne development due to its stimulation of the sebaceous glands, which in turn produces excessive amounts of sebum. The reduction of androgens’ influence will increase the effectiveness of any acne treatment. One method that has seen considerable use is the employment of agents that block the androgen receptor, effectively reducing the effects of androgens on the sebaceous glands.

Oral anti Androgens

A newer concept involves impeding the activity of the androgen-metabolizing enzymes in the skin, or in the sebaceous glands themselves. These agents are known as anti-androgens.

The most commonly used anti-androgens include the following:

  • Inocoterone acetate
  • Spironolactone
  • Cyproterone acetate
  • Flutamide
  • 5-alpha reductase inhibitors

Topical inocoterone acetate: While topical anti-androgenic preparations could not match the acne-reducing efficacy of oral treatments, a recent 12-week trial of topical inocoterone acetate (a non-steroidal anti-androgen) reduced inflamed acne by a small but significant amount. It failed, however, to reduce either the number of comedonal lesions and the rate of sebum secretion.

Spironolactone

A synthetic steroid, spironolactone treats acne by blocking androgen receptors and inhibiting 5-alpha reductase enzymes in the skin. Oral doses of 50-100mg reduces sebum production by 30-50%, although healthy women (and women with inflammatory acne lesions) may lean towards a more moderate dosage of 25mg. Side effects include breast tenderness and menstrual irregularities in women, and testicular atrophy and erectile dysfunction in men. Spironolactone may induce high potassium levels, and pregnancy during spironolactone therapy should be avoided. Tests are currently being administered to compare the efficacy of topical use against oral administration.

Cyproterone Acetate

Like spironolactone, cyproterone acetate is a synthetic steroid that has shown comparable efficacy in both oral and topical administration (based on a three-month study), although topical application resulted in much lower concentrations in serum cyproterone acetate than with oral use. Cyproterone acetate inhibits ovulation when taken orally, and blocks androgen receptors in sebaceous gland cells when applied topically.

Cyproterone acetate also acts as an oral contraceptive, where a low does of the drug is combined with varying doses of ethinyl estradiol. Dosage ranges from 2-100mg daily, and has shown improvement in 75-90% of women suffering from acne. Cyproterone acetate’s main potential side effect is liver toxicity, and patients taking high doses of this anti-androgen must be regularly monitored for any changes in liver function.

Flutamide

Flutamide is a potent non-steroidal, pure anti-androgen. It is taken orally and has been shown to be effective in acne treatment. Doses of 250mg daily are taken in combination with an oral contraceptive. Flutamide is the oldest anti-androgen in use and also has the most adverse side effects—fatal hepatitis has been reported, although rarely, with flutamide use. Risk-benefit ratios and pregnancy issues should be thoroughly assessed before flutamide treatment, and liver function should be monitored during treatment. These days, flutamide has been largely replaced by bicalutamide, owing to the latter’s less serious list of side effects.

5-alpha reductase inhibitors

A recent development in anti-androgen acne treatment is the inhibition of androgen-metabolizing enzymes in the skin or in the sebaceous glands themselves. One such androgen-metabolizing enzyme is the 5-alpha reductase inhibitor finasteride, which metabolizes testosterone into 5-alpha-testosterone in androgen-regulated target tissues. This enzyme exists in its two isoforms. The Type I isoform mainly occurs in the skin, located in the sebocytes, epidermal and follicular keratinocytes. Antagonists that bind selectively to this Type I isoform includes finasteride and dutasteride, and are believed to be capable of treating acne. European dermatologists have been using finasteride (used in combination with oral contraceptives for female patients) to treat acne, and have received effective results. Such an approach is yet to be approved for use in North America.

Disadvantages

Anti-androgens cannot be taken orally by male patients, as it causes several male disorders such as the reversal of secondary male sex characteristics, reduced activity of the male organs, and reduced libido. Finasteride is instead indicated for male patients—while primarily a treatment for pattern-baldness, it has also shown considerable efficacy in treating acne.