Transcript Slide 1

Hyperandrogenism
Dr. Mona Shroff
Diploma in Obs. & Gynaec Ultrasound
EMOC Clinical Trainer (FOGSI-GOI-ICOG)
Dr Mona Shroff
www.obgyntoday.info
1
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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• 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
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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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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. 2004 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
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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 !!!
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J Pediatr Endocrinol Metab. 2000;13 Suppl 5:1285Dr 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
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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
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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 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
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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
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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)
* <200 ng/dl : N
* 200 – 800 : ACTH stimulation test
* > 800 : diagnostic
Dr Mona Shroff
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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 > 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
• > 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
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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
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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
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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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
37.
Hum Reprod. 2005 Sep;20(9):2457-62.
Hum Reprod. 2002 Jul;17(7):1729Dr Mona Shroff
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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. 1999Mar;71(3):445-51.
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S/E & cost of antiandrogens
drug
S/E
Cost/mnth(Rs)
spironolactone Metrorrhagia,K 120-480
G.I,drowsiness
Finasteride
mild
280-300
flutamide
G.I, Liver
750
Cyproterone
acetate
Ketoconazole
As with
COCPs
270-350
G.I , Liver
180-360
Dr Mona Shroff
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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. 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.
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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 ??
Dr Mona Shroff
www.obgyntoday.info
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Lab results
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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
www.obgyntoday.info
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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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NCAH
J 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
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Dr Mona Shroff
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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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