Hormonal therapy plays role as adjunct in acne therapy

"Hormonal therapy is obviously needed in patients whose acne is associated with an endocrine abnormality leading to excess androgen production by the adrenals or ovaries, but it can also be a useful adjuvant in women with normal serum androgen and sometimes as an alternative to repeat courses of isotretinoin. However, conventional modalities, including a combination of retinoids, benzoyl peroxide and antibiotics, remain the foundation of acne treatment for all patients," says Dr. Thiboutot, professor of dermatology, Penn State University College of Medicine, Hershey, Pa.

ASSESSING RED FLAGS Red flags that should lead clinicians to suspect there is an underlying endocrine component to a woman's acne include a history of sudden onset of severe acne and signs of hyperandrogenism, including hirsutism, irregular menstrual periods or voice changes.

"However, be sure that a woman having these tests performed has been off any existing oral contraceptive for at least a month. Otherwise, the androgen levels will come back normal," Dr. Thiboutot tells Dermatology Times.

HORMONAL THERAPY OPTIONS Options for hormonal therapy include a low-dose estrogen-progestin oral contraceptive (oc), which blocks androgen production by the ovaries and adrenals as well as increases levels of sex hormone binding globulin; glucocorticoids, which affect adrenal gland androgen synthesis; and off-label use of the anti-androgen spironolactone, which blocks androgen binding to receptors in the skin.

"The main mechanism by which androgens cause acne is through their effects on sebaceous gland size and activity, and aside from these hormonal therapy options, isotretinoin is the only other acne treatment that targets the sebaceous gland," Dr. Thiboutot notes.

Currently, Estrostep (norethindrone acetate/ethinyl estradiol, Pfizer) and Ortho Tri-Cyclen (norgestimate/ethinyl estradiol, Ortho McNeil) are the only low-dose OCs that are approved for the treatment of acne. Phase III studies investigating Yasmin (ethinyl estradiol/drosperinone, Berlex) have recently been completed. That agent is unique as its progestin component is an analogue of spironolactone and provides antiandrogenic activity. Alesse (levonorgestrel/ethinyl estradiol, Wyeth), Mircette (desogestrel/ethinyl estradiol, INFAR) and LoEstrin (norethindrone/ ethinyl estradiol, Parke-Davis) are other low-dose OCs. Of these, Alesse has been formally studied for the treatment of acne, but the others may be expected to have a beneficial effect.

Dr. Thiboutot notes there are several newer forms of estrogen-progestin contraceptives that dermatologists should know about since patients may be using them. Those include Ortho Evra (norelgestromin /ethinyl estradiol, Ortho McNeil), a patch that is worn weekly every week for three weeks with one week off and NuvaRing (etonogestrel/ ethinyl estradiol, Organon), a vaginal ring worn for three weeks with one week off.

OTHER HORMONAL OPTIONS The addition of spironolactone may be considered in a woman whose acne has not responded to an adequate trial of oc therapy.

When used for the treatment of acne, spironolactone can be prescribed at a low dose of just 25 mg once or twice daily.

"Low dose spironolactone will minimize the occurrence of adverse events, which most commonly include breast tenderness and menstrual irregularities. Importantly, women must avoid becoming pregnant while on spironolactone, and so this medication is often used in combination with an OC," Dr. Thiboutot says.

Glucocorticoid therapy is also prescribed at a low dose when excess androgens are from the adrenal. Prednisone 2.5 to 5 mg daily is preferred over dexamethasone in order to minimize the risk of adrenal suppression.

However, patients should still be referred to an endocrinologist who can monitor them for adrenal suppression.