Cutaneous manifestations of hyperandrogenic disorders (
acne,
seborrhea,
hirsutism and
androgenetic alopecia) can be caused by elevated levels of free
testosterone or
androgen precursors. In women with normal serum levels of
testosterone or
androgen precursors, enhanced local conversion to
testosterone, or to the more potent
androgen dihydrotestosterone, may lead to increased
androgen activity in the pilosebaceous unit. Large individual variations in the response to normal or elevated
androgens suggests considerable differences in local
androgen metabolism and
androgen receptor-mediated activities, which may partly be related to genetic disposition.
Androgens cause opposite effects on hair follicles in the scalp compared with the face and body, and there are large differences in the length of anagen phase.
Androgens enhance sebum production and keratinization, prolong the growth phase of face and body hair, stimulate the transformation of vellus to terminal hair, and shorten the anagen phase of scalp hair.
Estrogens may antagonize the
androgen-induced actions on sebaceous glands and hair follicles. Treatment with
oral contraceptives (OCs) reduces the production of
androgens and
androgen precursors and increases
sex hormone-binding globulin, resulting in a decrease of free
testosterone levels. According to type and dose, the
estrogen and
progestogen components of OCs may directly reduce the effect of
androgens within sebaceous glands and hair follicles. Therefore, OCs with a predominant
estrogen effect may improve mild to moderate forms of
acne and
seborrhea,
hirsutism and
androgenetic alopecia, in a time-dependent manner. In women who do not respond satisfactorily, treatment with OCs containing a
progestogen with antiandrogenic activity is recommended. In many women with severe
acne or
hirsutism, a considerable increase in the local concentration of the antiandrogenic
progestogen is required to reduce the androgenic interaction with the
androgen receptor. For this
therapy, an OC containing
cyproterone acetate can be used. If necessary, the dose of
cyproterone acetate can be increased in a stepwise manner. While
androgenetic alopecia is best treated with a low-dose OC containing
cyproterone acetate (optimal effect occurs after at least 12 months of
therapy), severe
acne and
hirsutism are significantly improved after 6-12 months of regimens containing high doses of
cyproterone acetate (25-100 mg/day). After termination of treatment the disorders may reappear, therefore treatment with suitable low-dose formulations is recommended to maintain the
therapeutic effect.