What every dermatologist should know about Polycystic Ovary Syndrome (PCOS) Kanade Shinkai, MD PhD University of California, San Francisco Associate Professor of Dermatology I have no conflicts of interest to disclose. I will be discussing off-label use of medications during this lecture.
Learning objectives Describe skin signs in PCOS and their reliability as disease markers Order appropriate diagnostic evaluation for patients suspected of having PCOS Select effective treatments for cutaneous manifestations of hyperandrogenism
Part I of III: What is PCOS? What skin findings do we see in PCOS?
Polycystic Ovary Syndrome (PCOS) Stein-Leventhal Disease Rotterdam criteria (2003): 2 of 3 oligomenorrhea (< 8 per year) serum or clinical hyperandrogenism ultrasound (+) polycystic ovaries Prevalence: 5-10% Heterogeneous phenotype Stein & Leventhal (1935) Am J Obstet Gynecol, 29:181-191 Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group (2004) Human Reproduc. 19:41-47
Why is it important to recognize PCOS? 10% develop diabetes in 3 rd or 4 th decade Endocrine 40% have impaired glucose tolerance 40% are obese CV Controversial Nurses Health Study Hyperlipidemia, hypertension, fatty liver Reproductive Subfertility Complications of pregnancy Oncologic Endometrial CA Association with obesity, type 2 DM Other Sleep apnea (30x risk) Quality of life (obesity, hirsutism) Norman RJ et al (2007) Lancet 370:685-697 Ehrmann DA (2005) NEJM 352:1223-1236
Cutaneous signs of PCOS Cross-sectional study 401 women suspected of having PCOS (69% PCOS+) Comprehensive skin exam by dermatologist 92% of patients with PCOS had skin finding Schmidt T et al (2015) JAMA Derm, Dec 23:1-8 Schmidt T et al (2016) manuscript submitted
Acne affects 61% of patients with PCOS 40% in high-risk population Sites: Face Trunk No systemic associations No significant QOL impact Not reliable marker of PCOS Schmidt T et al (2015) JAMA Derm, Dec 23:1-8 Beshay A et al (2015) unpublished results
Hirsutism is specific sign in PCOS
How is hirsutism measured? 1 2 3 4 Modified Ferriman-Gallwey 9 body sites Visual scale: 0 to 4 Total score: 36 (hirsutism >7) Mild: mfg 8-15 Moderate: mfg 16-25 Severe: mfg 26-36 Ferriman D, Gallwey JD (1961) J Clin Endo, 21:1140-1447 Hatch R et al (1981) Am J Obstet Gyn, 140:815-830
Hirsutism is most reliable sign of hyperandrogenism Multiple studies: 70-80% of patients with hirsutism meet PCOS criteria Hirsutism always warrants diagnostic evaluation Caucasian, East Asian women w/ PCOS: mfg comparable Increasing rate of hirsutism in higher Fitzpatrick skin types Fauser B et al (2012) Fertil Steril, 97:28-38 Escobar-Morreale H et al (2012) Human Repro Update, 18:146-170 Wang E et al (2013) Fert Steril, 100:214-218 Afifi L et al (2017) IJWD, in press
Hirsutism affects 53% of patients with PCOS 31% in high-risk population Important systemic associations Sites: Face Trunk Shoulders Thighs Schmidt T et al (2015) JAMA Derm, Dec 23:1-8
Hirsutism: how does it affect patients? Clinicians and patients do not see the same thing Clinician rating: 8.6 (range 0 31) Patient self-rating: 13.3 (range 1 33) 4.3 Patient ratings best predict depression and QOL impact Beck Depression Index Skindex-16: patients report significant QOL impact Pasch L et al (2016) JAMA Derm, 152:783
Acanthosis nigricans is specific sign in PCOS
Cannavo SP et al (2006) JEADV 20:478-480
Serin D (2005) Ophthal Plast Recon Surg 21:403-404 Peri-ocular acanthosis nigricans
Peri-oral acanthosis nigricans Ozhan B et al (2015) J Ped 167:1453
AN affects 37% of PCOS patients 20% in high-risk population Sites: Neck Axillary Central chest Inframammary Inguinal Knuckles Knees, elbows, face Schmidt T et al (2015) JAMA Derm, Dec 23:1-8 Metabolic associations
Part II of III: When should I worry about a hormonal disorder? How/ when to evaluate?
When should I worry about a hormonal disorder? Hirsutism, acanthosis nigricans Oligomenorrhea (<8 per year) or amenorrhea Virilization: Deepening voice Clitoromegaly Increased muscle mass Decreased breast size Virilization = sign of androgen-secreting tumor Azziz R et al (2004) J Clin Endo Metab, 89:453-462 Escobar-Morreale H et al (2012) Hum Reprod Update, 18:146-170 JC Harper (2008) J Drugs Derm 7: 527-530 Lolis MS et al (2009) Med Clin N Am 93:1161-1181
Hyperandrogenism workup: results PCOS Idiopathic HA Idiopathic Hirsutism NCCAH Tumors Misc 71% 15% 10% 3% 0.3% 0.7% PCOS is #1 cause of androgen excess Tumors, hormonal disorders are very rare Escobar-Morreale H et al (2012) Human Repro Update, 18:146-170
Diagnostic workup for PCOS Step 1: Endocrine When? Step 2: Metabolic Testosterone (free, total) 17-hydroxyprogesterone trans-vaginal ultrasound DHEA-S TSH prolactin androstenedione LH: FSH (>3 in 95% PCOS) BMI Blood pressure Fasting lipid panel Fasting insulin, glucose 2 hour glucose challenge HgbA1c ALT Schmidt TH, Shinkai K (2015) JAAD 73:672-690 Dizon M, Schmidt TH, Shinkai K (2016) Cutis, 98:11-13
Part III of III: What are the best treatments for women with skin signs of hyperandrogenism?
Focus on hirsutism: best practices Most: not FDA approved for hirsutism Prolonged (>6 months) medical therapy is needed (level B) Use effective contraception with anti-androgens (level B) Drosperinone dosage in OCP is not anti-androgenic (level B) Escobar-Morreale H et al (2012) Human Repro Update, 18:146-170
Off-label systemic treatments for hirsutism OCP Spironolactone Finasteride Flutamide 2B 1B 2C 2B mild hirsutism severe hirsutism category X side effects hepatotoxicity?additional benefit? Van Zuuren E, Fedorowicz Z (2015) JAMA, 314:1863-1864 Schmidt TH, Shinkai K (2015) JAAD 73:672-690 Fauser B et al (2012) Fertil Steril, 97:28-38 Escobar-Morreale H et al (2012) Human Repro Update, 18:146-170
Additional treatments for hirsutism Laser 1B IPL Eflornithine Metformin 0B,1C Statins Pio/troglitazone 50% reduction Limited evidence Van Zuuren E, Fedorowicz Z (2015) JAMA, 314:1863-1864 Schmidt TH, Shinkai K (2015) JAAD 73:672-690 Haedersdal M, Gotzsche PC (2006) Cochrane Database Syst Rev, CD004684 Escobar-Morreale H et al (2012) Human Repro Update, 18:146-170
Conclusions PCOS is most common cause of hyperandrogenism Best skin signs for PCOS: hirsutism, acanthosis nigricans Diagnostic evaluation before treatment Management of HA: delayed response, long-term treatment Important role of dermatologists in diagnosis, management, and advancement of our understanding of PCOS
Q&A