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Hyperandrogenism

Hyperandrogenism

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Hyperandrogenism

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  1. Hyperandrogenism Dr. Mona Shroff Diploma in Obs. & Gynaec UltrasoundEMOC Clinical Trainer (FOGSI-GOI-ICOG) Dr Mona Shroff www.obgyntoday.info

  2. Case A • 14 y/o female (menarche 1 yr back) • Menses q 3--4 months • Mild facial acne • FG Score of 5 (1 lip, 1 chin, 2 lower abd, • 1 back) • BMI 29 kg/m2 • No galactorrhoea Dr Mona Shroff www.obgyntoday.info

  3. What are the various causes of hyperandrogenism? • In this adolescent girl what probable cause do you suspect? Dr Mona Shroff www.obgyntoday.info

  4. Aetiology of hyperandrogenism • FOH of puberty • PCOS • HAIR-AN syndrome • Hyperprolactinemia • Hypothyroidism • NCAH • TUMORS-Ovarian / Adrenal • Cushings disease • Drugs Dr Mona Shroff www.obgyntoday.info

  5. What particular aspects of history & clinical features would you like to look for? Dr Mona Shroff www.obgyntoday.info

  6. Clinical assessment • History • The following items are important:: • Family History of HA/Obesity/temporal balding/infertility • Hx of Precocious adrenarche • More than 2 years of oligomenorrhea Dr Mona Shroff www.obgyntoday.info

  7. Clinical assessment.. • Physical examination • Degree of hirsutism, acne • Obesity ,increased W/H ratio Acanthosis nigricans- r/o PCOS,HAIR-AN • Rapidly growing hirsutism or • Virilizing symptoms – r/o TUMOR • Symptoms of hypercorticism –r/o CUSHING • Galactorrhea – r/o HYPERPROLACTINEMIA Dr Mona Shroff www.obgyntoday.info

  8. What is this C/F? Dr Mona Shroff www.obgyntoday.info

  9. Dr Mona Shroff www.obgyntoday.info

  10. Would you like to investigate this patient at this juncture? Dr Mona Shroff www.obgyntoday.info

  11. Would you like to start treatment at this time? • In which particular patients would you evaluate & treat at an early age? Dr Mona Shroff www.obgyntoday.info

  12. J Pediatr. 2004 Jan;144(1):23-9. Insulin sensitization early after menarche prevents progression from precocious pubarche to polycystic ovary syndromein a high-risk group of formerly LBW girls. Dr Mona Shroff www.obgyntoday.info

  13. LIFESTYLE MODIFICATIONS LIFESTYLE MODIFICATIONS LIFESTYLE MODIFICATIONS Dr Mona Shroff www.obgyntoday.info

  14. Adult v/s Adolescent HA • FOH or Organic cause??? • USG not reliable-ovaries may be N. • Premature adrenarche –strong predictor. • Lifestyle changes – biggest impact-Prevention of PCOD !!! J Pediatr Endocrinol Metab. 2000;13 Suppl 5:1285-9 Dr Mona Shroff www.obgyntoday.info

  15. Same patient comes to you after 2 yrs (age 16 yrs) - still having same clinical picture but worsened delayed periods mod. acne & hirsutism BMI 32 Dr Mona Shroff www.obgyntoday.info

  16. Would you like to evaluate this patient now? • What initial screening investigations would you like to go for & why? Dr Mona Shroff www.obgyntoday.info

  17. INITIAL LAB SCREENING • TESTOSTERONE • PROACTIN • TSH • Evaluation for HYPERINSULINEMIA • 17 OH PROGESTERONE Dr Mona Shroff www.obgyntoday.info

  18. INITIAL LAB SCREENING • Testosterone total – may be N in hirsute woman if T> 200 screen for tumor free T?? Should we ask for? – no clinical need to check - if HA effect seen then free T must be raised - does not help in D/D or treatment Dr Mona Shroff www.obgyntoday.info

  19. TSH - esp if alopecia • PROLACTIN - DHEAS ,free T (SHBG ) • HYPERINSULINEMIA Fasting glucose : Insulin < 4.5 Fasting insulin > 20 2 hr GTT > 140 Dr Mona Shroff www.obgyntoday.info

  20. 17 OH P - for NCAH , follicular ph/morning -routine screen in HA indicated (esp if sev hirsutism at younger age ,short stature) * <200 ng/dl : N * 200 – 800 : ACTH stimulation test * > 800 : diagnostic Dr Mona Shroff www.obgyntoday.info

  21. Screen for Cushings if clinical suspicion late eve. plasma cortisol single dose overnight DST • Imaging of adrenals & ovaries (USG/CT/MRI) * if rapid virilization * T > 200 micgm/ dl Dr Mona Shroff www.obgyntoday.info

  22. Audience question • Would you like to include S.DHEAS in her list of investigations? If YES - WHY? If NO – WHY NOT? Dr Mona Shroff www.obgyntoday.info

  23. DHEAS ??? • Moderate elevation common in anovulatory females • > 700 micgm/dl – v.rare • if T> 200 – screen for tumor must • Mod. elevated DHEAS does not necessitate or prove the need & benefit of treatment with dexamethasone • No further benefit by testing,not cost effective Gordon,Speroff 2002 Dr Mona Shroff www.obgyntoday.info

  24. Lab resultsof this patient TSH, Prolactin, 17OH P : normal Total T : 70 ng/mL [<72 ng/mL] Fasting Insulin : 22 mIU/mL [<20 mIU/mL] Fasting Glucose 92 mg/dL Dr Mona Shroff www.obgyntoday.info

  25. What are the options available for treating HA? Dr Mona Shroff www.obgyntoday.info

  26. ANTIANDROGENS SPIRONOLACTONE FUTAMIDE FINASTERIDE CYPROTERONE DEXAMETHASONE KETOCONAZOLE CIMETEDINE COCPs GnRH AGONISTS MECHANICAL AGENTS(hirsutism) ANTIBIOTICS (acne) INSULIN SENSITIZERS Dr Mona Shroff www.obgyntoday.info

  27. Considering our diagnosis of PCOS in this girl what are your aims of treatment • What treatment would you like to start in this patient? • How long should you continue with this treatment? Dr Mona Shroff www.obgyntoday.info

  28. Management of excess ovarian androgen production : Standard therapy is :combined E+P OCs • It reduces ovarian androgen production • It increases SHBG • It induces competition at the cellular level for binding to the androgen receptor Dr Mona Shroff www.obgyntoday.info

  29. METFORMIN • In addition to the expected improvements in insulin sensitivity and glucose metabolism • Ameliorates hyperandrogenism and menstrual irregularity. • Reduces total cholesterol, LDL and triglycerides of PCOS adolescents while increasing HDL cholesterol . • Decrease C-reactive protein and a normalization of the neutrophil/lymphocyte ratio , which are predictive of cardiovascular disease. Benefits both obese & non obese Hum Reprod. 2005 Sep;20(9):2457-62. Hum Reprod. 2002 Jul;17(7):1729-37. Dr Mona Shroff www.obgyntoday.info

  30. ANTIANDROGENS • According to currenty available evidence no antiandrogen is superior to other in terms of clinical efficacy, so choice depends upon S/E & cost.Further studies needed. Chocrane reviews, Issue 1, 2006 Fertil Steril. 1999Mar;71(3):445-51. Dr Mona Shroff www.obgyntoday.info

  31. S/E & cost of antiandrogens Dr Mona Shroff www.obgyntoday.info

  32. Would you like to add a steroid (dexona) to your therapy in this patient? Dr Mona Shroff www.obgyntoday.info

  33. AUDIENCE QUESTION WHICH PILL WOULD YOU CHOOSE FOR ADOLESCENT PCOS with HA & WHY? • LNG containing (mala-D,ovral-L,Loette) • DESOGESTREL containing (novelon,femilon) • CYPROTERONE containing (Ginette,krimson35, diane35) • DROSPIRINONE containing (yasmin) Dr Mona Shroff www.obgyntoday.info

  34. COCs LNG vs Desogestrel vs CPA • DSG & CPA pills comparable efficacy, better than LNG.(CPA slightly better for acne) • DSG & CPA pills comparable side effects ( VENOUS THROMBOEMBOLISM & LIVER ) Acta Obstet Gynecol Scand Suppl. 1986;134:29-32. Int J Fertil Menopausal Stud. 1996 Jul-Aug;41(4):423-9. Fertil Steril. 2002 May;77(5):919-27. Eur J Contracept Reprod Health Care. 2001 Mar;6(1):46-53. J Obstet Gynaecol Can. 2003 Dec;25(12):1011-8. Pharmacoepidemiol Drug Saf. 2004 Jul;13(7):427-36. Pharmacoepidemiol Drug Saf. 2003 Oct-Nov;12(7):541-50. Dr Mona Shroff www.obgyntoday.info

  35. Case B • 16 y/o female • Menses q 3-4 months • Moderate facial acne • FG Score of 5 (1 lip, 1 chin, 2 lower abd, 1 back) • Tanner Stage breast 4, pubic hair 4 • BMI 26..3 kg/m2 • No galactorrhoea • INITIAL SCREENING ?? Dr Mona Shroff www.obgyntoday.info

  36. Lab results • TSH,, Prolactin normal • 17OH P : 2.5 ng/mL [<2 ng/mL] • Total T : 70 ng/mL [<72 ng/mL] • Fasting Insulin 14 mIU/mL [<17 mIU/mL] • Fasting Glucose 92 mg/dL • What would you do next? Dr Mona Shroff www.obgyntoday.info

  37. ACTH Stimulation Test Baseline 17 OH P 2..5 ng/dL 60 min 17 OH P 18 ng/dL What is your inference? How would you treat thispatient? Dr Mona Shroff www.obgyntoday.info

  38. Treat hyperandrogenism with dexamethasone or CPA or spironolactone or flutamide • Treat irregular menses with combined oral contraceptive pills • Treat infertility when patient desires pregnancy • Consider adding dexamethasone to ovulation induction Dr Mona Shroff www.obgyntoday.info

  39. NCAHJ Clin Endocrinol Metab. 1990 Mar;70(3):642-6.Cyproterone acetate versus hydrocortisone treatment in late-onset adrenal hyperplasia. • Peripheral antiandrogen therapy may be more appropriate in late-onset adrenal hyperplasia patients than conventional adrenal inhibition using cortisone therapy. Dr Mona Shroff www.obgyntoday.info

  40. Dr Mona Shroff www.obgyntoday.info

  41. Dr Mona Shroff www.obgyntoday.info

  42. CONCLUSIONS • HA is a common adolescent probem • Our main aim is early PCOS diagnosis & ruling out tumor/NCAH. • Watch for premature pubarche. • Initial screen –T, TSH, Prolactin, fasting glucose:insulin, 17 OH P • Imaging for tumor if T>200 or rapid virilisation Dr Mona Shroff www.obgyntoday.info

  43. CONCLUSIONS (contd.) • Lifestye modification & weight reduction plays a key role. • Integrated approach – combination of drugs with best outcome & min. S/E. (COCs + IS +/- Antiandrogen). • PCOS - Candidates for long term therapy. Dr Mona Shroff www.obgyntoday.info

  44. THANK YOU Dr Mona Shroff www.obgyntoday.info