Acne in Adult Women Allison Arthur, MD April 2018 Disclosures • I will discuss FDA off-label use of oral contraceptive pills, spironolactone, oral antibiotics, and topical azelaic acid Objectives • Discuss the pathogenesis of acne in adult women • Discuss treatment options for acne in adult women • Discuss dietary changes that can serve as adjunctive treatments for acne in adult women • Review treatment options for acne during pregnancy Adult Female Acne • May persist into adulthood or • New onset in adulthood • Affects approx 12-22% of women in the US • Strong premenstrual flare • May flare when OCP discontinued • Associated with anxiety, depression, and reduced quality of life Pathogenesis • Sebum production/plugging • Genetics • Alteration in follicular keratinization and differentiation • P. acnes • Diet • Medications • Androgens Is “Hormonal Acne” a Misnomer? • ALL acne is hormonally mediated– including acne during puberty, when increased androgen production leads to more sebum • While some women have hormone abnormalities (i.e. PCOS), many women have hormonal levels within the normal range • Many theorize that adult female acne may be a manifestation of end-organ hypersensitivity What is in the Differential Diagnosis? • Rosacea • Perioral dermatitis • Seborrheic dermatitis • Acne cosmetica • Acne medicamentosa: testosterone, DHEA, progestin, lithium, prednisone, EGFR chemotherapy, etc. Medical Evaluation • Prior and current treatments for acne • Medical history, including medications • Menstrual history – Oligomenorrhea <8 menstrual cycles/year – Amenorrhea • Smoking history • ROS: hirsutism, androgenetic alopecia, deepening voice Polycycstic Ovarian Syndrome • Diagnostic criteria – 2 of 3 – Oligomenorrhea – Serum or clinical hyperandrogenism – Polycystic ovaries on transvaginal ultrasound • Other cutaneous manifestations – Hirsutism, acanthosis nigricans, androgenetic alopecia, seborrhea • Prevalence 5-10% of reproductive age women PCOS Sequelae • 40% insulin resistance • 10% diabetes • 40% obese • Fatty liver • Obstructive sleep apnea • Subfertility, complications of pregnancy • Increased risk of endometrial cancer Hirsutism • Affects >50% patients with PCOS • Trunk is most common site – Central chest, back • Best predictor of hyperandrogenism • Major impact on quality of life Acanthosis Nigricans • Affects >30% PCOS patients • Axillae, neck, central chest, inframammary • Can be CARP-like Crutchfield Dermatology When should I worry about a hormonal disorder? • Hirsutism • Acanthosis nigricans • <8 periods per year Labs • Endocrine evaluation – Off OCP’s, spironolactone for 4 weeks – Free testosterone, DHEA-S, LH:FSH (>3 in 95% PCOS pts) – Transvaginal ultrasound • Metabolic evaluation – BMI – Blood pressure – Fasting lips, fasting insulin, glucose, Hgb A1c, ALT Treatment of Acne in Adult Women • In one study of 200 women >25 years old: – 80% failed multiple courses of systemic antibiotics – 30% relapsed after several therapeutic cycles of isotretinoin Hormonal Treatment • Often considered in settings of: – Hyperandrogenism – Acne onset >25 years old – Jawline or “beard” acne distribution – Acne that is resistant to conventional therapies • Prior to initiation of therapy, need to discuss family planning Hormonal Treatment • How do OCP’s work? – Estrogen increases synthesis of sex hormone binding globulin (binds androgens -> decreases levels of free testosterone, DHEA-S) – Estrogen inhibits 5-alpha reductase – Decreases ovarian & adrenal androgen synthesis – Because estrogen provides the most benefit, giving patients a “low” version is a disservice Combined Oral Contraceptives • 4 are FDA approved for acne – Ortho Tri-Cyclen (norgestimate) – Estrostep (norethindrone) – YAZ (drosperinone) – BEYAZ (drosperinone) • Certain progestins have lower androgenic activity – i.e. Norgestimate, desogestrel, drosperinone Are patients required to have a PAP smear and pelvic exam before starting an OCP? NO (According to WHO, ACOG, Planned Parenthood) OCP Side effects • Headache • Unscheduled bleeding (“spotting”) • Nausea • Breast tenderness • Weight gain 1-2 kg in 30% of patients, usually due to fluid retention • Mood changes • Melasma • Thromboembolic events: DVT, MI, stroke DVT Risk • Baseline 1-3/10,000 woman/years • 1 year on OCP 7-9/10,000 • Pregnancy 29/10,000 • Post-partum 300/10,000 • Highest risk in carriers of genetic hypercoagulability • Screen/counsel for other risk factors: – Family history, obesity, age, malignancy, trauma, immobilization, smoking Breast Cancer Risk? • RR 1.20 in current or recent OCP users vs non-users • Increased risk with longer duration of use • BUT OCPs decrease risk of ovarian cancer and endometrial cancer Hormonal IUD • Some data to show that there ARE circulating levels of progestin • In a retrospective analysis of 493 patients with hormonal IUD – 36% Acne worsened – 54% Not much effect on acne – 7% acne slightly improved – 3% acne significantly improved Lortscher D et al. JDD 2016;15(6):670-674. Spironolactone • Typically start at 100 mg daily • Can take 3 months + to see results • 8 year safety study in acne, no serious complications • Common side effects: – GI upset/cramping, dizziness, headache – Menstrual irregularities (if used as monotherapy) – At higher doses, breast tenderness Spironolactone • Black box warning based on animal studies, benign tumor formation after 18 months of 50, 150, or 500 mg/kg/day • No increased risk of cancer in 2 large female cohort studies • Classified as teratogen but no reported abnormalities in pregnant women who have been exposed Spironolactone • Low usefulness of screening K+ in young, healthy women • Consider K+ screening if mid 40’s or older • Recommend K+ screening if: – Cardiac disease – Renal disease – On spironolactone and drospirenone OCP • After stable for 6 months, can often taper and maintain at lower dose Other Considerations Diet in Adult Women with Acne • Italian case-control study, 248 women 25 years older or greater with acne • Low consumption of vegetables or fruit and fish (less than 3 days/week) were associated with adult female acne Diet & Acne • Glycemic index (GI): a numeric system that measures the rise in blood sugar following consumption of a carbohydrate • Low glycemic index diet recommended Glycemic Index & Acne • High GI/GL diet leads to insulin & IGF-1 • IGF-1 stimulates: – Keratinocyte proliferation – Sebocyte proliferation/sebum production – Adrenal androgen synthesis How Can I Explain This to Patients? • Sugars and refined grains cause spikes in your blood sugar that lead to increased oil production, elevated androgen hormones, and inflammation • These things can all make acne worse! Milk and Acne • Milk also elevates insulin and IGF-1 levels • Contains bovine IGF-1 • Contains dihydroxytestosterone (DHT) precursors • 47,355 women (Nurses’ Health Study II) • History of severe acne was positively associated with frequent consumption of milk Spearment Tea & Acne? • Study on PCOS patients with hirsutism • Spearmint tea twice daily for 30 days • Androgen levels decreased (study length too short to see signif difference with hirsutism) • Conclusion: Spearmint tea has antiandrogen properties Grant P. Phytother Res 2010 Feb;24(2):186-8. Spearmint Tea & Acne? • May be an alternative to spironolactone for women with acne who are seeking a “natural” approach Supplements • Niacinamide • Probiotic Acne in Pregnancy What NOT to use for Acne in Pregnancy • Limited data on safety of topical retinoids, therefore most experts do not recommend • Isotretinoin and Tazarotene are contraindicated • Spironolactone should not be used due to risk of feminization in a male fetus • Tetracycline family antibiotics are contraindicated What Topical Meds CAN I Prescribe for Acne in Pregnancy? • Clindamycin • Azelaic acid • Glycolic acid wash • Benzoyl peroxide may be used on limited areas (I typically have patient run it by OB, have gotten OB approval 100%) What oral meds CAN I Prescribe for Acne in Pregnancy? • First line: Amoxicillin or cefadroxil for severe acne vulgaris/acne rosacea • Second line: Clindamycin Questions?.