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Dr Mona Shroff www.obgyntoday.info
Hyperandrogenism Dr. Mona Shroff Diploma in Obs. & Gynaec Ultrasound EMOC Clinical Trainer (FOGSI-GOI-ICOG) Dr Mona Shroff
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Dr Mona Shroff www.obgyntoday.info
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
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Dr Mona Shroff www.obgyntoday.info
What are the various causes of hyperandrogenism? In this adolescent girl what probable cause do you suspect? Dr Mona Shroff
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Aetiology of hyperandrogenism
FOH of puberty PCOS HAIR-AN syndrome Hyperprolactinemia Hypothyroidism NCAH TUMORS-Ovarian / Adrenal Cushings disease Drugs Dr Mona Shroff
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What particular aspects of history & clinical features would you like to look for? Dr Mona Shroff
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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
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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
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What is this C/F? Dr Mona Shroff
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Would you like to investigate this patient at this juncture? Dr Mona Shroff
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Would you like to start treatment at this time? In which particular patients would you evaluate & treat at an early age? Dr Mona Shroff
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J Pediatr Jan;144(1):23-9. Insulin sensitization early after menarche prevents progression from precocious pubarche to polycystic ovary syndrome in a high-risk group of formerly LBW girls. Dr Mona Shroff
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LIFESTYLE MODIFICATIONS
Dr Mona Shroff
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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
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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
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Dr Mona Shroff www.obgyntoday.info
Would you like to evaluate this patient now? What initial screening investigations would you like to go for & why? Dr Mona Shroff
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INITIAL LAB SCREENING TESTOSTERONE PROACTIN TSH Evaluation for HYPERINSULINEMIA 17 OH PROGESTERONE Dr Mona Shroff
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Dr Mona Shroff www.obgyntoday.info
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
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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
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Dr Mona Shroff www.obgyntoday.info
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
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Dr Mona Shroff www.obgyntoday.info
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
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Audience question Would you like to include S.DHEAS in her list of investigations? If YES - WHY? If NO – WHY NOT? Dr Mona Shroff
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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
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Lab results of 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
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What are the options available for treating HA? Dr Mona Shroff
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MECHANICAL AGENTS(hirsutism)
ANTIANDROGENS SPIRONOLACTONE FUTAMIDE FINASTERIDE CYPROTERONE DEXAMETHASONE KETOCONAZOLE CIMETEDINE COCPs GnRH AGONISTS MECHANICAL AGENTS(hirsutism) ANTIBIOTICS (acne) INSULIN SENSITIZERS Dr Mona Shroff
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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
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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
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Dr Mona Shroff www.obgyntoday.info
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 Sep;20(9): Hum Reprod Jul;17(7): Dr Mona Shroff
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Dr Mona Shroff www.obgyntoday.info
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): Dr Mona Shroff
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S/E & cost of antiandrogens
drug S/E Cost/mnth(Rs) spironolactone Metrorrhagia,K G.I,drowsiness Finasteride mild flutamide G.I, Liver 750 Cyproterone acetate As with COCPs Ketoconazole G.I , Liver Dr Mona Shroff
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Dr Mona Shroff www.obgyntoday.info
Would you like to add a steroid (dexona) to your therapy in this patient? Dr Mona Shroff
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Dr Mona Shroff www.obgyntoday.info
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
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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 Jul-Aug;41(4):423-9. Fertil Steril May;77(5): Eur J Contracept Reprod Health Care Mar;6(1):46-53. J Obstet Gynaecol Can Dec;25(12): Pharmacoepidemiol Drug Saf Jul;13(7): Pharmacoepidemiol Drug Saf Oct-Nov;12(7): Dr Mona Shroff
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Dr Mona Shroff www.obgyntoday.info
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 kg/m2 No galactorrhoea INITIAL SCREENING ?? Dr Mona Shroff
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Dr Mona Shroff www.obgyntoday.info
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
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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 this patient? Dr Mona Shroff
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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
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Dr Mona Shroff www.obgyntoday.info
NCAH J Clin Endocrinol Metab Mar;70(3): 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
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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
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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
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THANK YOU Dr Mona Shroff
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