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Home , Acne medicamentosa, Azelaic acid, Glycolic acid

Acne in Adult Women

Allison Arthur, MD

April 2018 Disclosures

• I will discuss FDA off-label use of oral contraceptive pills, , oral , and topical Objectives

• Discuss the pathogenesis of 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 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?

• • • Seborrheic dermatitis • • Acne medicamentosa: , 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: , 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 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? – 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, , 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 • • 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 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 , and • 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 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 , therefore most experts do not recommend • Isotretinoin and are contraindicated • Spironolactone should not be used due to risk of feminization in a male fetus • family antibiotics are contraindicated What Topical Meds CAN I Prescribe for Acne in Pregnancy?

• • Azelaic acid • wash • 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?