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

2. 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

3. 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

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

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

6. Dr Mona Shroff www.obgyntoday.info
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

7. Dr Mona Shroff www.obgyntoday.info
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

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

9. Dr Mona Shroff www.obgyntoday.info

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

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

12. Dr Mona Shroff www.obgyntoday.info
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

13. LIFESTYLE MODIFICATIONS
Dr Mona Shroff

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

15. Dr Mona Shroff www.obgyntoday.info
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

16. 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

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

18. 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

19. Dr Mona Shroff www.obgyntoday.info
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

20. 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

21. 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

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

23. Dr Mona Shroff www.obgyntoday.info
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

24. 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

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

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

27. Dr Mona Shroff www.obgyntoday.info
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

28. Dr Mona Shroff www.obgyntoday.info
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

29. 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

30. 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

31. 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

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

33. 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

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 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

35. 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

36. 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

37. Dr Mona Shroff www.obgyntoday.info
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

38. Dr Mona Shroff www.obgyntoday.info
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

39. 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

40. Dr Mona Shroff www.obgyntoday.info

41. Dr Mona Shroff www.obgyntoday.info

42. Dr Mona Shroff www.obgyntoday.info
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

43. Dr Mona Shroff www.obgyntoday.info
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

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