Transcript Hyperandrogenism in the adolescent girl

Hyperandrogenism in the
adolescent girl
Dr. Mona Shroff, M.D.
Diploma in Obs. & Gynaec Ultrasound
EMOC Clinical Trainer (JHPIEGO)
Mild symptoms of hyperandrogenism are
common in adolescents
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Hirsutism – 6%
Acne – 36-98% in western countries
1. Hashemipour M. et al. Horm Res.
2004;62(6):278-82. Epub 2004 Oct
29.
2. J.J. Chan and J.B. Rohr. Australas J Dermatol 41 (2000) (Suppl), pp. S69–
S72
3. Freyre EA et al. J Adolesc Health. 1998 Jun;22(6):480-4.
• Additionally
:: These HA symptoms may
be associated with irregular menstrual
cycles.
•Three years post menarche 20 -40%
cycles are irregular (Physiological HA of
Puberty).
Hashemipour M. et al. Horm Res. 2004;62(6):278-82. Epub 2004 Oct
29.
Widholm & Kantero.. Act Obstet Gynecol Scand;1971:14:1-36
• .... In some girls These features
persist and even make worse..
Subjects with persistent symptoms of
hyperandrogenism
Most frequently associated with PCOS
But another etiologies must be ruled
out.
Clinicians main aim should be to
• Establish an early PCOS diagnosis.
• Rule out Adrenal/Ovarian Tumor & NCAH
This presentaton includes
• Aetiology of HA
• Approach to an adolescent with HA
- Important clinical features to look for
-the optimum necessary Ix
-Evidence based best possible Rx protocol
• Case studies
Adult v/s Adolescent HA
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FOH or Organic cause???
USG not reliable-ovaries may be N.
Premature adrenarche –strong predictor.
Long term Rx-choose drugs with min.
lipid & metabolic S/E.
• Lifestyle changes – biggest impactPrevention of PCOD !!!
J Pediatr Endocrinol Metab. 2000;13 Suppl 5:1285-9
Aetiology of
hyperandrogenism
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FOH of puberty
PCOS
HAIR-AN syndrome
Hyperprolactinemia
Hypothyroidism
NCAH
TUMORS-Ovarian / Adrenal
Cushings disease
Drugs
Abnormalities
Associated with
Androgen Excess
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Acne
Hirsutism
Alopecia
Android obesity
Menstrual dysfunction
Infertility
Cardiovascular disease
Dyslipidemia
Glucose intolerance/insulin
resistance/T2NIDDM
• Hypertension
Signs of
Virilization
• Acne
• Hirsutism
• Clitoromegaly
• Deepening of voice
• Increased libido
• Increased muscle mass
(primarily shoulder girdle)
• Infrequent or absent
menses
• Loss of breast tissue or
normal female body
contour
• Malodorous perspiration
• Temporal hair recession
and balding
Diagnosis of HA in Female
Adolescents
1. Clinical assessment
2. Laboratory screening
3. Further investigations
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
Age-related changes in the
PCOS phenotype
Reproductive abnormalities
Clinical hyperandrogenism
Metabolic abnormalities
Adolescence
Adult fertile age
Menopause
Postmenopause
INITIAL LAB
SCREENING
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TESTOSTERONE
PROACTIN
TSH
Evaluation for HYPERINSULINEMIA
17 OH PROGESTERONE
INITIAL LAB
SCREENING
• Testosterone
total – may be N in hirsute woman
if T> 200 screen for tumor
free – no clinical need to check
if HA effect seen then
free T must be raised
• TSH - esp if alopecia
• PROLACTIN DHEAS ,free T
(SHBG )
• HYPERINSULINEMIA
Fasting glucose : Insulin < 4.5
Fasting insulin > 20
2 hr GTT > 140
• 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
• 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
DHEAS ???
• Moderate elevation common in
anovulatory females
• > 700 micgm/dl – v.rare
• if T> 200 – screen for tumor must
• No further benefit by testing,not
cost effective
Gordon,Speroff 2002
ANTIANDROGENS
COCPs
GnRH AGONISTS
MECHANICAL AGENTS(hirsutism)
ANTIBIOTICS (acne)
SPIRONOLACTONE
FUTAMIDE
FINASTERIDE
CYPROTERONE
DEXAMETHASONE
KETOCONAZOLE
CIMETEDINE
INSULIN SENSITIZERS
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
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.
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.
S/E & cost of antiandrogens
drug
S/E
Cost/mnth(Rs)
spironolactone
120-480
Finasteride
Metrorrhagia,K
G.I,drowsiness
mild
flutamide
G.I, Liver
750
Cyproterone
acetate
Ketoconazole
As with COCPs 270-350
G.I , Liver
280-300
180-360
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):1729-
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.
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.
TUMOUR
SURGICAL REMOVAL
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
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.
Case A
16 y/o female
• Menses q 3--4 months
• Mild facial acne
• FG Score of 5 (1 lip, 1 chin, 2 lower abd,
1 back)
• BMI 33.3 kg/m2
• No galactorrhoea
How would you evaluate this patient?
Lab results
TSH, Prolactin, 17OH P : normal
Total T : 70 ng/mL [<72 ng/mL]
Fasting Insulin : 22 mIU/mL [<17 mIU/mL]
Fasting Glucose 92 mg/dL
How would you treat this patient?
Patient was treated with
metformin (consider adding COCs)
After 3 months:
Spontaneous resumption of monthly
menses
Hirsutism and acne improved
Case B
16 y/o Hispanic 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
How would you evaluate this patient?
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?
ACTH Stimulation Test
Baseline 17 OH P 2..5 ng/dL
60 min 17 OH P 18 ng/dL
How would you treat this patient?
•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
THANK YOU