Anti-androgens in acne treatment

Androgens are the main cause in the development of acne. While sebum is a more direct cause, the stimulation provided by androgens produces the excess sebum, which in turn produces acne. Therefore, for effective acne treatment, the influence of androgens must be reduced.

One available option is to use agents which block the androgen receptor, thus blocking the effect of androgens on the sebaceous glands. A newer concept is the blocking of the activity of the androgen metabolizing enzymes in the skin or in the sebaceous glands themselves. Such agents are called anti androgens.


The more common types of anti-androgens in use are inocoterone acetate, spironolactone, cyproterone acetate, flutamide and the newer 5 alpha reductase inhibitors.

Topical inocoterone acetate: Although oral contraceptives have been used to successfully treat acne for decades, topical antiandrogenic preparations initially could not be shown to be successful against acne. However, more recently a 12 week trial of the topical inocoterone acetate, a non-steroidal antiandrogen, produced a small but significant reduction of inflamed acne but was not able to reduce the number of comedonal acne lesions and the rate of sebum secretion.

Spironolactone: This compound is a synthetic steroid, which decreases sebum secretion by 30 to 50%. It blocks the androgen receptor and inhibits the enzyme 5 alpha reductase in the skin. Recommended doses are 50 – 100mg. Healthy women and women with inflammatory acne lesions respond and tolerate well to a 25mg. dose. Breast tenderness, menstrual irregularities, testicular atrophy and erectile dysfunction are some of the side effects. Pregnancy during spironolactone therapy should be avoided. Spironolactone may induce high potassium levels. While it is mostly used orally, some studies have looked at its use topically, though not enough to make a conclusion on how effective it might be topically for acne.

Cyproterone acetate, another synthetic steroidal antiandrogen, used orally but applied topically in some research studies, had a comparable effect as the oral application after three months of therapy. The serum cyproterone acetate concentrations were 10 times lower after topical application than those found after oral treatment. However, a possibility of systemic effect cannot be ruled out. Cyproterone acetate works systemically by inhibiting ovulation and topically by blocking the androgen receptors on cells in sebaceous glands.

Cyproterone acetate exhibits dual activity. Firstly it serves a use in oral contraceptives and secondly it also directly blocks the androgen receptors. Given in doses of 2mg. to 100mg per day it has shown improvement in 75 – 90% women with acne. It is most commonly used in the form of an oral contraceptive where a low dose of the drug is combined with ethinyl estradiol in varying doses. Numerous studies have confirmed the effectiveness of such contraceptive preparations in treating women with acne.

The most serious potential side effect is liver toxicity. Patients should be regularly monitored for changes in liver functions, especially if they are taking high doses.

Flutamide: It is a potent non-steroidal pure antiandrogen, orally taken, and has been shown to be effective in acne treatment. In its class it is the oldest antiandrogen in use and also has the most adverse side effects. It is administered in doses of 250mg daily in combination with an oral contraceptive. Fatal hepatitis has rarely been reported with flutamide use. Liver function tests should be monitored during treatment. Being an antiandrogen there are also pregnancy issues involved. Before using flutamide the risk – benefit ratio should be well assessed. Flutamide has been largely replaced by bicalutamide, a new member of this class, due to less serious side effects.

5-alpha reductase inhibitors: A promising new concept is the inhibition of the activity of the androgen metabolizing enzymes in the skin or in the sebaceous glands itself. One such enzyme is the 5-alpha reductase inhibitor finasteride. % alpha reductase metabolises testosterone into 5-alpha-testosterone in androgen regulated target tissues. This enzyme exists in its two isoforms. The type I isoform occurs mainly in the skin, located mainly in the sebocytes, epidermal and follicular keratinocytes. The antagonists that bind selectively to this type-I isoform, like finasteride and dutasteride, are believed to be capable of treating acne. Some small studies in Europe suggest finasteride can be quite effective for acne and some European dermatologists are using finasteride in men and a combination of finasteride and contraceptives in women to treat acne. However, such an approach is not approved for use in North America.


The main disadvantage of antiandrogens is that they cannot be used in male patients orally. In males, androgens cause several male disorders such as reversal of secondary male sex characteristics, reduced activity of the male organs and reduced sexual desire. For men the only practical option is finasteride. While officially used to treat pattern-baldness, some dermatologists use it to treat acne as well.