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What I Wish I’d Known in Residency: PCOS & Hirsutism

What I Wish I’d Known in Residency: PCOS & Hirsutism. Kathryn C. Calhoun, MD UNC-Chapel Hill Reproductive Endocrinology & Infertility. Objectives. Review the normal menstrual cycle Patterns suggestive of predictable ovulation Understand PCOS Metabolic implications Screening Treatment

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What I Wish I’d Known in Residency: PCOS & Hirsutism

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  1. What I Wish I’d Known in Residency:PCOS & Hirsutism Kathryn C. Calhoun, MD UNC-Chapel Hill Reproductive Endocrinology & Infertility

  2. Objectives • Review the normal menstrual cycle • Patterns suggestive of predictable ovulation • Understand PCOS • Metabolic implications • Screening • Treatment • Management of Hirsutism

  3. The Menstrual Cycle Normal Interval? 24-35 days Normal Duration? 3-7 days Molimina

  4. The Menstrual Cycle GnRH H P FSH, LH FSH - + + Prog Estrogen Inhibin B @ 200 pg/ml X 50 hrs Corpus Luteum X 14 days unless rescued by HCG

  5. Anovulatory Cycles GnRH H 1. AUB 2. Hyperplasia P FSH, LH FSH - + + Prog Estrogen Inhibin B @ 200 pg/ml X 50 hrs

  6. Anovulation: Why should I care? • Regulate bleeding patterns • Identify source of sub/infertility • Identify patients at risk for … • Endometrial Hyperplasia/Cancer • Metabolic Syndrome

  7. Diagnosing Anovulation • Unpredictable bleeding patterns • Absence of molimina BEWARE PATIENT SABATOGE Attempts to superimpose order on chaos My periods are every 37-45 days I bleed, like, every month. I just gave you my menstrual history from last year when I was on Yaz

  8. Ok, we’ve diagnosed anovulation… Now, why is it happening?

  9. DDX: Anovulation • First … • #1 reason for weird bleeding = (check UPT) • Exclude structural defects, intermenstrual bleeding

  10. Central Defects • Pituitary Tumors • Inhibit GT secretion • Cushings, Acromegaly • Hyperprolactinemia • ↑ DA impairs GnRH • Hypothyroidism, ↑ TRH, ↑ PRL • Stress/Illness • Abnormal gonadotropin secretion • i.e. GnRH pulse programmed to favor LH Check PRL & TSH !

  11. Anovulation – Central Defect GnRH H 1. AUB 2. Hyperplasia P FSH, LH FSH ? Estrogen Inhibin B @ 200 pg/ml X 50 hrs

  12. Abnormal Feedback Signals • Chronically elevated Estrogen levels • Estrogen does not fall in late LP • FSH cannot rise • New cohort cannot be recruited • Ex: pregnancy, obesity, thyroid, liver • Failure of LH surge • Fail to achieve/sustain the Estrogen level required to trigger LH surge

  13. Anovulation-Abnormal Feedback GnRH H 1. AUB 2. Hyperplasia P FSH, LH FSH - + + Estrogen Inhibin B @ 200 pg/ml X 50 hrs

  14. Local Ovarian Conditions • Premature Ovarian Failure • High FSH, low AMH, normal/low Estrogen • High Androgens impede follicular maturation LH FSH THECA: androgens GRANULOSA: Aromatized To estrogens

  15. High Androgens ?? Anovulation??

  16. Polycystic Ovarian Syndrome (PCOS) • Diagnosis • Hyperandrogenism • Anovulation/Oligo-ovulation • Multicystic ovaries on ultrasound • Absence of other causes • Nc CAH, acromegaly, Cushings • Increased risk: • Diabetes • High cholesterol

  17. Clinical Hyperandrogenism • Acne • Hirsutism/Alopecia • Virilization

  18. Laboratory Hyperandrogenism • Total testosterone (20-80 ng/ml) • DHEAS (100-350 ug/dl) --------------------------------------- • DHEA • Androstenedione • Free testosterone • DHT • peripheral conversion only

  19. PCOS: Multicystic Ovaries • End result of chronic anovulation • Many atretic follicles • Enlarged stromal component • Present in ovulatory women Not prognostic for metabolic derangement

  20. Obesity The PCOS Cycle Insulin Resistance in Muscle/Fat Brain More glucose in circulation ↑ Free Androgens, ↓ SHBG LH Pancreas + Liver More insulin made ↑ Androgens Immature follicles join ovarian stroma

  21. Obesity • Increased peripheral aromatization of androgens  chronic estrogen elevation • Decreased SHBG • Insulin resistance

  22. PCOS: Treatment • Fasting lipids and 2hr GTT Q yr • Diet/exercise • Cycle regulation (cOCP or Progesterone) or… • Ovulation induction

  23. Wait!! Can we hear more about HIRSUTISM AND HYPERANDROGENISM???

  24. Hirsutism: What is it? • Coarse, dark hairs in the midline • Ferriman Gallwey ≥ 3

  25. Hirsutism: What causes it? • Specific Disorders • Tumor • Classical CAH • Nonclassical CAH • HAIR AN • PRL directly stimulates DHEAS production • Disorders of Exclusion • PCOS • *most common cause of androgen excess • Idiopathic

  26. Hirsutism: What is your job? • Specific Disorders • Tumor • Classical CAH • Nonclassical CAH • HAIR AN • Cushings • Disorders of Exclusion • PCOS • Idiopathic Exclude the stuff that can kill your patient

  27. But … how?

  28. The history! • Symptoms suggestive of TUMOR • Pre-pubertal • Late onset (>25yo) • Unless they were on the pill until age 25 • Virilization • Voice Δ, muscle mass, breast atrophy, clitoromegaly • Rapidly-progressing symptoms

  29. The history! • Symptoms suggestive of Cushing’s • Thin skin • Easy bruising • Striae • Moon face • Buffalo hump • Testing • Overnight DST

  30. I think it’s a Tumor • Rule out exogenous • Labs • Testosterone (ovary) • DHEAS (adrenal) • Imaging • Pelvic US • Adrenal CT

  31. You don’t need to order DHEAS • -adrenal tumors co-secrete • DHEAS  T

  32. What kind of tumor? • Ovary • Sertoli Leydig • Lipid • Theca cell • Hilus cell • Adrenals

  33. I think it’s a Tumor • Elevated DHEAS (> 350ug/dl) Adrenal CT should find tumor • Elevated T (>150 ng/dl) if negative US, consider ovarian venous sampling for USO vs. BSO • Rule out pregnancy (T>100 in 1st tri, 800 3rd tri) • Re-address exogenous use • If labs normal, proceed to ….

  34. It’s not a Tumor! • Exogenous • PCOS • HAIR-AN • nc CAH • ↑ 5 alpha reductase • Idiopathic

  35. Exogenous • Steroids • Phenytoin • Danazol • Cyclosporin • Minoxidil • Supplements (DHEA, Androstenedione)

  36. What is that? • HAIR-AN • Hyperandrogenism, insulin resistance, acanthosisnigricans • Uber- PCOS • nc CAH • Elevated follicular 17-OHP (> 800ng/dl) • 5 alpha reductase • T  DHT in periphery  virilizes hair follicle • Includes many “idiopathic” hirsutism patients

  37. Treatment of (non-tumor) Hirsutism • Set realistic expectations • At least 6 months (half life of hair follicle) • Combine with permanent hair removal • Cannot reverse virilization once it’s happened

  38. Treatment of (non-tumor) Hirsutism • cOCP • Decrease LH drive of theca androgens • Increase SHBG • Decrease DHEAS production • Decrease 5 alpha reductase • Prog only • Decrease LH drive of theca androgens • Increased Testosterone clearance • Resultant decrease in SHBG ok

  39. Still not working? • Did you wait 6 months? • Add antiandrogen • Spironolactone = androgen receptor antag • Finasteride • Blocks 5 alpha reductase (TDHT) • Creams • Vaniqua

  40. For women who want to be pregnant • Most treatments contra-indicated • teratogenicity • Many experience decreased hair growth in pregnancy (elevated E, P) • Virilization during pregnancy • Luteoma • Theca-lutein cysts (multiples, moles)

  41. Questions?

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