EXPERT ANALYSIS FROM THE SPD ANNUAL MEETING
MINNEAPOLIS (FRONTLINE MEDICAL NEWS) – Whether a young female patient has a refractory flare of inflammatory acne, or has a condition that can predispose to androgen excess, using a hormonal approach can be an effective management tool for controlling adolescent acne.
During a presentation at the annual meeting of the Society for Pediatric Dermatology, Dr. Diane Thiboutot outlined tips and tricks for optimizing hormonal therapy for acne in teens, and referred to the new acne treatment guidelines from the American Academy of Dermatology, which clarify when to treat with hormones, which to choose, and when further testing might be indicated.
The full range of hormonal therapy options for acne can include oral contraceptives, which block ovarian hormone production; antiandrogens such as spironolactone, and the less commonly used flutamide, which blocks the effects of androgen on the skin; and glucocorticoids, which block adrenal production.
The 2016 guidelines recommend oral contraceptives as an effective treatment for inflammatory acne in females (J Am Acad Dermatol. 2016 May;74; 945-973.e33). Combined oral contraceptives (COCs) reduce serum androgens, and reduce free testosterone by increasing sex hormone binding globulin production, thus reducing sebum production. “The only things that really decrease sebum are oral contraceptives in women, and isotretinoin,” said Dr. Thiboutot , professor of dermatology at Penn State University, Hershey.
For most female adolescents with acne, hormonal testing is not indicated. The AAD guidelines recommend laboratory evaluation for younger patients with acne who have clinical signs of androgen excess, such as early onset body odor and axillary and/or pubic hair, accelerated growth, advanced bone age, or early genital maturation. Just obtaining a hand film for bone age and mapping growth against a growth chart can be a good initial screening tool when considering whether to perform hormonal testing, she noted.
For postpubertal females in whom polycystic ovary syndrome (PCOS) or other hyperandrogenic states are suspected, hormonal testing is indicated in the presence of the clinical signs of infrequent menses and infertility, hirsutism, truncal obesity, androgenetic alopecia, polycystic ovaries, or clitoromegaly.
In searching for an endocrine disorder, Dr. Thiboutot recommends checking total and free testosterone, luteinizing hormone/follicle stimulating hormone ratio, 17-hydroxyprogesterone levels, and dehydroepiandrosterone (DHEA-S) levels. These tests should be performed at least 6 weeks after the patient has been off hormonal contraception, and should be done during the menstrual period, or during the week prior to menses, in order to avoid ovulation-related hormonal changes.
Lab findings consistent with congenital adrenal hyperplasia include elevated serum DHEA-S, together with elevated 17-hydroxyprogesterone or testosterone. A PCOS diagnosis can be made in adolescent females if there is clinical or laboratory evidence of hyperandrogenism with concomitant persistent oligomenorrhea.
Acne related to hyperandrogenism may respond well to oral contraceptives, but COCs can also be an effective alternative to repeated courses of isotretinoin and antibiotics, as well as an effective adjunct to topical therapy, Dr. Thiboutot said.
When beginning a patient on oral contraceptives, it’s not necessary to perform a pelvic exam or obtain a Pap smear before initiating the COC, but it is important to obtain a thorough medical history and an accurate blood pressure measurement at the outset, she noted. The World Health Organization (WHO) has established recommendations outlining contraindications to COC use, also identifying populations in whom COCs should be used with caution, and who should be monitored.
Headaches are a condition frequently seen among healthy teens and young women, and one for which the WHO advises caution. There are concerns that women with migraines may be at increased risk of stroke if they take COCs, but the overall risk is low, and the American College of Obstetricians and Gynecologists (ACOG) advises that COCs can be considered for women younger than 35 with migraines if they have no focal neurologic signs, are nonsmokers, and are otherwise healthy, Dr. Thiboutot added.
A large Food and Drug Administration–sponsored retrospective cohort study examined the risk of venous thromboembolism in contraceptive users. In April 2012, the FDA concluded that though the risk of blood clots may be higher for those on hormonal contraception methods than for those who are not using them, the risk of blood clots during pregnancy and the postpartum period is higher than the thromboembolism risk for contraceptive users.
Regarding the potential for antibiotics to reduce contraceptive efficacy, Dr. Thiboutot said,“it’s okay to use oral contraceptives with antibiotics. There’s a lot of misunderstanding about antibiotics and combined oral contraceptives.” She cited an ACOG practice bulletin that reported that only rifampin has been shown to reduce serum steroid levels when taken with oral contraceptives ( Obstet Gynecol. 2006 Jun;107:1453-72 ).
According to the 2016 AAD guidelines, the use of oral glucocorticoids may be appropriate over the short term when initiating therapy for severe inflammatory acne. “Pharmacokinetic studies have not demonstrated decreased oral contraceptive levels with common antibiotics,” Dr. Thiboutot said.
Spironolactone, according to the new guidelines, is useful for acne in select females. Spironolactone is an androgen receptor and 5a-reductase blocker, and its antiandrogen effects can improve acne. Many patients do well with 25-50 mg twice daily, though breast tenderness and menstrual irregularities are commonly seen side effects, she noted. If a woman taking spironolactone becomes pregnant, there’s a risk of hypospadias for a male fetus.
Though spironolactone carries a boxed warning because of tumorigenicity observed in animal studies, Dr. Thiboutot said that a large Danish study searched for any association between breast, uterine, or ovarian cancers and spironolactone use. Among the 2.3 million women studied, no increased association was seen ( Cancer Epidemiol. 2013 Dec;37:870-5 ).
She also noted that there’s “low usefulness in monitoring potassium levels in young healthy women on spironolactone.” She cited a study that compared 974 healthy young women taking spironolactone with 1,165 women who were not on spironolactone, which found that the hyperkalemia rate of 0.72% among those on spironolactone was equivalent to the 0.76% baseline rate of hyperkalemia in the young, healthy female population ( JAMA Dermatol. 2015;151;941-944 ).
Oral corticosteroids for acne, Dr. Thiboutot said, should be reserved to quiet a severe bout of inflammatory acne while standard therapies are being initiated.
She reported being an investigator or a consultant for a number of pharmaceutical companies.
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