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
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.