Oral contraceptives
Estrogen contained in oral contraceptives (OCs) provides the most benefit to acne patients. “It reduces sebum production, decreases free testosterone and DHEA-S by stimulating SHBG synthesis in the liver, inhibits 5-alpha-reductase, which decreases peripheral testosterone conversion, and it decreases the production of ovarian and adrenal androgens,” Dr. Murase explained. “On average, you can get about 40%-70% reduction of lesion count, which is pretty good.”
Progestins with low androgenetic activity are the most helpful for acne, including norgestimate, desogestrel, and drospirenone. FDA-approved OC options include Ortho Tri-Cyclen, EstroStep, Yaz, and Beyaz. None has data showing superior efficacy.
No Pap smear or pelvic exam is required when prescribing OCs, but the risk of clotting should be discussed with patients. According to Dr. Murase, the risk of deep vein thrombosis (DVT) at baseline is about 1 per 10,000 woman-years, while the risk of DVT after 1 year on an OC is 3.4 per 10,000 years.
Dr. Jenny E. Murase
“This is a very mild increased risk that we’re talking about, but it is relevant in smokers, in those with hypertension, and in those who are diabetic,” she said. As for the risk of cancer associated with the use of OCs, a large collaborative study found a relative risk of 1.24 for developing breast cancer (not dose or duration related), but a risk reduction for endometrial, colorectal, and ovarian cancer.
The most common side effects associated with OCs are unscheduled bleeding, nausea, breast tenderness, and possible weight gain. Concomitant antibiotics can be used, with the exception of CYP3A4 inducers, such as rifampin. “That’s the main antibiotic we have to worry about that could affect the efficacy of the birth control pill,” she said. “It accounts for about three-quarters of pregnancies on antibiotics.”
Tetracyclines do not appear to increase the rate of birth defects with incidental first-trimester exposure, and data are reassuring but “tetracycline should be stopped within the first trimester as soon as the patient discovers she is pregnant,” Dr. Murase said.
Contraindications for OCs include being pregnant or breastfeeding; history of stroke, venous thromboembolism, or MI; history of smoking and being over age 35; uncontrolled hypertension; migraines with focal symptoms/aura; current or past breast cancer; hypercholesterolemia; diabetes with end-organ damage or having diabetes over age 35; liver issues such as a tumor, viral hepatitis, or cirrhosis; and a history of major surgery with prolonged immobilization.
Spironolactone
Another treatment option is spironolactone, a potassium-sparing diuretic that blocks aldosterone at a dose of 25 mg/day. At doses of 50-100 mg/day, it blocks androgen. “It can be used in combination with an oral contraceptive, with the rates of efficacy reported to range between 33% and 85%,” Dr. Murase said.
Spironolactone can also reduce hirsutism, improve androgenetic alopecia, and lower blood pressure by about 5 mm Hg systolic and 2.5 mm Hg diastolic. Dr. Murase usually checks blood pressure in patients, and “only if they’re really low I’ll talk about the potential for postural hypotension and the fact that you can get a little bit dizzy when going from a position of lying down to standing up.” Potassium levels should be checked at baseline and 4 weeks in patients older than age 46, in those with cardiac and/or renal disease, or in those on concomitant drospirenone or a third-generation progestin.
Spironolactone is classified as a pregnancy category D drug that could compromise the genital development of a male fetus. “So the onus is on us as providers to have the conversation with our patient,” she said. “If you’re putting a patient on spironolactone and they are of child-bearing age, you need to make sure that you’ve had the conversation with them about the fact that they should not get pregnant while on the medicine.”
Spironolactone also has a boxed warning citing the development of benign tumors in animal studies. That warning is based on studies in rats at doses of 10-150 mg/kg per day, “which is an extremely high dose and would never be given in humans,” said Dr. Murase, who has coauthored CME content regarding the safety of dermatologic medications in pregnancy and lactation.
In humans, there has been no evidence of the development of benign tumors associated with spironolactone therapy, and “there has been a decreased risk of prostate cancer and no association with its use and the development of breast, ovarian, bladder, kidney, gastric, or esophageal cancer,” she said.
Dr. Murase noted that during pregnancy, first-line oral antibiotics include amoxicillin for acne rosacea and cefadroxil for acne vulgaris. Macrolides are a second-line choice because of an increase in atrial/ventricular septal defects and pyloric stenosis that have been reported with first-trimester exposure.
“Erythromycin is the preferred choice over azithromycin and clarithromycin because it has the most data, [but] erythromycin estolate has been associated with increased AST levels in the second trimester,” she said. “It occurs in about 10% of cases and is reversible. Erythromycin base and erythromycin ethylsuccinate do not have this risk, and those are preferable.”
Dr. Murase disclosed that she has been a paid speaker of unbranded medical content for Regeneron and UCB. She is also a member of the advisory board for Leo Pharma, Eli Lilly, UCB, and Genzyme/Sanofi.