Hyperandrogenism

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Hyperandrogenism

• Dr. Mona Shroff
• Diploma in Obs. Gynaec UltrasoundEMOC Clinical
  Trainer (FOGSI-GOI-ICOG)

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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

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• What are the various causes of hyperandrogenism?
• In this adolescent girl what probable cause do
  you suspect?

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Aetiology of hyperandrogenism

• FOH of puberty
• PCOS
• HAIR-AN syndrome
• Hyperprolactinemia
• Hypothyroidism
• NCAH
• TUMORS-Ovarian / Adrenal
• Cushings disease
• Drugs

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• What particular aspects of history clinical
  features would you like to look for?

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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

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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

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What is this C/F?
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• Would you like to investigate this patient at
  this juncture?

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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?

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• J Pediatr. 2004 Jan144(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.

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LIFESTYLE MODIFICATIONS

• LIFESTYLE MODIFICATIONS

LIFESTYLE MODIFICATIONS
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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. 200013 Suppl 51285-9

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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

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• Would you like to evaluate this patient now?
• What initial screening investigations would you
  like to go for why?

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INITIAL LAB SCREENING

• TESTOSTERONE
• PROACTIN
• TSH
• Evaluation for HYPERINSULINEMIA
• 17 OH PROGESTERONE

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INITIAL LAB SCREENING

• Testosterone
• total may be N in hirsute woman
• if Tgt 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

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• TSH - esp if alopecia
• PROLACTIN - DHEAS ,free T
• (SHBG
  )
• HYPERINSULINEMIA
• Fasting glucose Insulin lt 4.5
• Fasting insulin gt 20
• 2 hr GTT gt 140

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• 17 OH P
• - for NCAH , follicular ph/morning
• -routine screen in HA indicated
• (esp if sev hirsutism at younger
• age ,short stature)
• lt200 ng/dl N
• 200 800 ACTH stimulation test
• gt 800 diagnostic

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• 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 gt 200 micgm/ dl

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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?

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DHEAS ???

• Moderate elevation common in anovulatory females
• gt 700 micgm/dl v.rare
• if Tgt 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

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Lab resultsof this patient
TSH, Prolactin, 17OH P normal Total T 70
ng/mL lt72 ng/mL Fasting Insulin 22 mIU/mL
lt20 mIU/mL Fasting Glucose 92 mg/dL
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• What are the options available for treating HA?

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ANTIANDROGENS SPIRONOLACTONE FUTAMIDE FINASTERIDE
CYPROTERONE DEXAMETHASONE KETOCONAZOLE CIMETEDINE
COCPs
GnRH AGONISTS
INSULIN SENSITIZERS
MECHANICAL AGENTS(hirsutism) ANTIBIOTICS (acne)
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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?

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• Management of excess ovarian androgen production
  
• Standard therapy is combined EP OCs
• It reduces ovarian androgen production
• It increases SHBG
• It induces competition at the cellular level for
  binding to the androgen receptor

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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 Sep20(9)2457-62.
  Hum Reprod. 2002 Jul17(7)1729-37.

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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. 1999Mar71(3)445-51.
  
•  

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S/E cost of antiandrogens
drug S/E Cost/mnth(Rs)
spironolactone Metrorrhagia,K G.I,drowsiness 120-480
Finasteride mild 280-300
flutamide G.I, Liver 750
Cyproterone acetate As with COCPs 270-350
Ketoconazole G.I , Liver 180-360
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• Would you like to add a steroid (dexona) to your
  therapy in this patient?

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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)

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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. 198613429-32.
• Int J Fertil Menopausal
  Stud. 1996 Jul-Aug41(4)423-9.
• 
  Fertil Steril. 2002 May77(5)919-27.
• Eur J Contracept Reprod Health
  Care. 2001 Mar6(1)46-53.
• J Obstet Gynaecol
  Can. 2003 Dec25(12)1011-8.
• Pharmacoepidemiol Drug
  Saf. 2004 Jul13(7)427-36.
• Pharmacoepidemiol Drug Saf.
  2003 Oct-Nov12(7)541-50.

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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 ??

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Lab results

• TSH,, Prolactin normal
• 17OH P 2.5 ng/mL lt2 ng/mL
• Total T 70 ng/mL lt72 ng/mL
• Fasting Insulin 14 mIU/mL lt17 mIU/mL
• Fasting Glucose 92 mg/dL
• What would you do next?

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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?
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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

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NCAHJ Clin Endocrinol Metab. 1990
Mar70(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.

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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
  glucoseinsulin, 17 OH P
• Imaging for tumor if Tgt200 or rapid virilisation

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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.

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• THANK YOU