WAIKOLOA, HAWAII – The androgen receptor–blocker spironolactone is highly effective and safe but underused for the treatment of acne in women, according to Dr. Julie C. Harper.

"The longer I’ve been in practice, the wider the age range where I use spironolactone as my drug of choice," Dr. Harper said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

Spironolactone is her first-line therapy for acne in postmenopausal women and in those who have had a hysterectomy. In such patients "it’s a really great drug to use by itself" because the women can’t get pregnant; the drug has a pregnancy category C rating, with an associated risk of feminization of a male fetus exposed to the drug late in the first trimester, explained Dr. Harper, a dermatologist at the University of Alabama, Birmingham.

"I have a tendency in my practice to start with an oral contraceptive in women of child-bearing potential and then maybe add spironolactone if I need to," she said.

However, Dr. Harper said that she will turn to spironolactone in women as young as 16 years of age with a contraindication to OCs. First, however, she carefully explains that the drug is safe as long as they don’t take it when pregnant. Spironolactone also cannot be used by nursing mothers because the drug’s major metabolite, canrenone, has been detected in breast milk.

Acne is a common problem in women. A survey of 1,013 adults in which Dr. Harper was a coinvestigator concluded that the prevalence of acne was significantly greater in women than men across all age groups. For example, the prevalence was 26% among 40- to 49-year-old women, compared with 12% in men of the same age, and 15% among women age 50-plus, compared to 7% in men (J. Am. Acad. Dermatol. 2008;58:56-9).

Acne is not only more common in women than men, it also differs in its characteristic presentation, which in women is typically lower-face acne in a U-shaped distribution.

Most women with adult acne have normal levels of circulating androgens. A leading hypothesis holds that their acne is the result of end-organ hyper-responsiveness to androgens. Androgen receptors are present in the sebaceous glands and the follicular wall, where comedones develop. This would explain why spironolactone is so effective clinically; the drug not only blocks the androgen receptor, it also reduces androgen synthesis in the adrenal gland and gonads, Dr. Harper noted.

She prescribes spironolactone in lower-range doses of 25-100 mg/day. At those doses she doesn’t bother to check serum potassium levels in relatively healthy young women so long as they’re not on other medications that may cause hyperkalemia, such as ACE inhibitors or chronic NSAIDs.

"You get good efficacy with fewer side effects at a maximum dose of 100 mg," according to the dermatologist.

Concomitant use of an OC lessens the menstrual irregularities and breast tenderness that can occur as side effects of spironolactone therapy. All combination OCs are probably effective in the treatment of acne. Four are approved for this indication: Ortho Tri-Cyclen, Estrostep, YAZ, and Beyaz.

Spironolactone should be thought of as long-term therapy. When spironolactone or an OC prescribed for adult acne is stopped, it’s highly likely that the acne will return within several months.

"When I plan to use spironolactone, I tell my patients they’re going to be on this for a long time if it works," Dr. Harper said.

The Food and Drug Administration has a long-standing Black Box Warning regarding spironolactone. Such warnings can send a chill down the spine of physicians and patients alike. However, there are widespread misconceptions about what this particular warning actually says. Here it is: "Spironolactone has been shown to be a tumorigen in chronic toxicity studies in rats. Spironolactone should be used only in those conditions described under Indications and Usage. Unnecessary use of this drug should be avoided."

The dosages used in those rat studies, by the way, were 25-100 times higher than those used in patients therapeutically.

"So we’re talking about rats, we’re talking about benign tumors, and we’re talking about super-duper high doses. That’s what’s in the Black Box Warning for spironolactone," she said.

Spironolactone is off-label therapy for acne, a point that caused another speaker at the seminar to bristle.

"If we used medications only for their approved indications, we couldn’t practice two-thirds of what we do," declared Dr. Theodore Rosen, professor of dermatology at Baylor College of Medicine, Houston.

"The FDA has said they’re not in the business of dictating how you practice medicine," he added. "You can use any approved drug in any fashion if you have some reasonable justification for it. If a plaintiff’s lawyer claims ‘This doctor used spironolactone off-label,’ she could line up 100 experts who’d say this is standard-of-care, and the standard of care determines what’s right and what’s wrong."

Dr. Harper is on the speakers bureaus for Allergan, Coria, Galderma, Intendis, Medicis, and Stiefel.

SDEF and this news organization are owned by Elsevier.

Oral Spironolactone Hailed for Acne in Women