Diagnosis of PCOS MCMCTACONSESSION4.pptx

DIAGNOSIS AND MANAGEMENT
OF ADOLESCENT PCOS

1. Prof. Rokeya Begum Director Surgiscope fertility center & Adviser USTC Bangladesh.

2. Adolescent PCOS Di DIAGNOSIS AND MANAGEMENT OF ADOLESCENT PCOS

3. Polycystic ovarian syndrome is most common endocrine disorder of reproductive aged women (15-45 yrs ).

4. The classic syndrome originally was described by stein and leventhal as the association of amenorrhoea with polycystic ovaries and variably hirsutism and obesity. ( J.obstet gynecol 1935)

5. It is now recognized that PCOS represents a spectrum of disease characterized primarily by the following features.  

6. Etiology Multifactorial disease with full clinical expression being the result of synergistic pathological interaction of : 1. G enetic, 2. E pigenetic 3. E nvironmental factor.

7. Genetic link Familial genetic disorder related to a single gene defect. 16 loci for PCOS (Jones and Goodarzi Fertil steril 2016) Gene polymorphism Familial clustering of PCOS common. First degree relatives of patients with PCOS may be at high risk for diabetes and glucose intolerance. Inherited cell dysfunction Mother and sister of PCOS  

8. Criteria for Diagnosis of PCOS PCOS definition NIH 1990 Patient demonstrates both: 1. Clinical and/or biochemical signs of hyperandrogenism 2. Oligo- or chronic anovulation Rotterdam criteria 2003 ( E S H R E / A S R M ) Two of the following three manifestations: 1.Irregular or absent ovulation 2.Hyperandrogenism (clinical or biochemical) 3 PCO on USG AES Criteria 2006 Patient demonstrates both: 1. Hirsutism and/or hyperandrogenemia 2. Oligo-anovulation and/or polycystic ovaries Azziz et al. JCEM 2006; 91: 4237-45 Exclude other etiologies of androgen excess – Late onset congenital adrenal hyperplasia, Androgen secreting tumours, Cushing’s syndrome

9. Can we use these criteria to diagnose PCOS in Adolescence? Normal Adolescents - O l ig om e n o rr h o e a - Amenorrhoea - Acne - Multicystic ” ovaries NO

10. Adolescence F rom Latin adolescere meaning to grow up Transitional stage of physical and psychological development from puberty to adult hood. Adolescent young people between the age of 10 -19 years.

11. DIAGNOSTIC APPROACH Unexplained clinical and /or biochemical hyperandrogenism Ovarian dysfunction

12. PCOS patient presents during adolescents 30% menstrual irregularities 60% adrogen excess 84% over weight 9% IGT or T2 DM

13. Obesity Typical obesity of PCOS is described as centripetal or apple type of fat distributions center of body as apposed to thighs and legs.   Waist circumference > 88cm marker of central / visceral obesity   Body weight primary factor affecting quality of life.  

14. Why adult criteria not applicable to young PCOS .   Anovulation 85% of cycles anovulatory in first year of menstruation. 59% of cycle anovulatory in third year. 25% of the cycle still anovulatory by the 6 th year.  

15. Abnormal menstrual patterns painting out anovulation in adolescents.   Secondary amenorrhea > 90 days   Oligomenorrhoea Postmenercheal 1 st year > 90 days < 4 periods/ yr 2 nd year > 60 days < 6 periods/ yr 3-5 yrs > 45 days < 8 periods/ yr >6yrs > 35-40 days < 9 periods/ yr Menorrhagia bleeding <21 days or> 7 days and one pad per 1-2 hours.

16. Adolescent have functional ovarian cysts High ovarian volume occurs in adolescence. Transabdominal sonography is inaccurate C linical evidence of androgen excess (especially acne) is common during puberty as resolves over time.

17. Metabolic features Insulin resistance Increase insulin level due to high growth hormone leading to obesities BMI > 24. Hyperpulsatile GnRh secretion. Decrease SHBG increase the androgen level.  Return to normal at the end of normal puberty but remain elevated in PCOS.

18. How to evaluate hyper androgenemia in the adolescent girl. Hirsutism – good marker Alopecia – from the bolding and a nterior hair line recession seen only in more severe cases of androgen excess. Acne and seborrhea. Sexual hair growth is commonly graded by semiquantitative Ferriman-Gallway (F-G score)

19. Ferriman-Gallway (F-G score)

20. Recommendation: Clinical: Isolated mild hirsutism – in early post menarched year may be development. Moderate to severe hirsutism constitutes clinical evidence of hirsutism. Girls with acne that is persistent and poorly responsive to topical dermatologic therapy should be evaluated for the presence of hyper androgenaemia before initiation of any medical therapy. Biochemical hyperandrogenic: Measurement of total and free testosterone.

21. Precaution Best assessed in early morning. Early follicular phase. Oral pill interface with the assessment of androgen. After discontinuation wait for 6 weeks.  

22. Total testosterone level The normal upper limit for semen total testosterone in woman is approximately 60ngm/dl (2.0nmol/L). Free testosterone level an elevation in serum or plasma free testosterone is the single most sensitive test to establish the presence of hyper androgenemia .

23. Evidence of Oligo anovulation It is difficult to differentiation of adolescent with physiological anovulation from those with true ovulatory dysfunction in PCOS.  

24. Recommendation Menstrual interval persistently shorter than 20 days or greater than 45 days in individuals two or more years after menerche are evidence of oligo-anovulation. A menstrual interval greater than 90 days is unusual even in first year after menerche – Require further investigations. Lack of onset of menes by the age of 15 years or by more than 2-3 years after thelarche regardless of chronological age.

25. Evaluation of polycystic ovarian morphology in an adolescent (PCOM) No compelling criteria to define PCOM have been established for adolescent - ovarian volume - follicle count 2. Multifollicular pattern which is defined by the presence of large follicle distributed throughout the ovary does not have relation with hyper androgenaemia is more common in adolescent and should not considered a pathological finding. 3. Regular menstruation with hyper androgenaemia – may show PCOM. 4. Abdominal US is Adolescent particularly obese girl may yield inadequate information. 5. AMH should not be used as diagnostic criteria for PCOS in adolescent. 6. Till now ovarian image can be deferred during the diagnostic evaluation of PCOS.

26. What are the other disease mimcs PCOS Hypothyroidism Hyper prolactineamia Nonclassical CAH Androgen secreting neoplasm - ovary - Adrenal Cushing’s syndrome Acromegaly Gluco corticoid resistance Drug – sodium valproate   The incidence is less

27. Hypothyroidism Primary – increase TRH Increase FSH/LH Increase prolactin   Secondary  PCOS – obesity – Leptin Increase TRH level

28. Hyper prolactinaemia causes PCOS phenotype Hyper prolactinaemia Central neurotransmitter dysregulation. Positive feed back of e strogen Drug OCPS, Antipsychotic 4 Other Pituitary cause Hypothyroidism Physiological PCOS – causes mild hyper prolactnaemia

29. Congenita l Adrenal Hyperplasia(CAH) Mainly nonclassical form – phenotypical like PCOS Premature pubarche Peripubertal onset Consanguinity Virilisation Total testosterone > 1.5ngm/L

30. 17 OH progesterone measurement in follicular phase Due to 21 hydroxylase deficiency. Less than 2ngm/ml - No NC CAH More than 10ngm/ml- NC CAH 2-8 ngm /ml – ACTH stimulation test < 10ngm/ nl – rule out >15ngm/ nl – NC CAH

31. Androgen secreting tumour – Malignant potential Rapid onset hirsutism Virilisation Total testosterone > 2ngm/ml DHEAS – Adrenocortical carcinoma. Imaging – USG, CT/MRI

32. Cushing syndrome Acromegaly IGF- 1 Post glucose growth hormone suppression test  

33. Following investigations has to be done. TSH and prolactin Serum 17OH progesterone Serum testosterone more than 2ngm/ml DHEA Imaging of abdomen to rule out Androgenic tumour .

34. Once the diagnosis of PCOS has been established identify the other risk factors. Early development of type-2 DM Metabolic syndrome Sleep disordered Breathing difficulty Cardiovascular risk sequence Endometrial carcinoma  

35. Family evaluation There is a high frequency of PCOS and metabolic syndrome among immediate relatives of individual with PCOS.  

36. Management of adolescent girls with PCOS Psychological support Life style change - W eight loss and exercise - Healthy approach to eat Symptom oriented treatment Anti androgens and Insulin sensitizing agent

37. Psychological intervention 1. Counselling Individual Group 2. Behavioral problem Abnormal eating patterns (21% vs 2.5%) 3 .Damaged self confidence Acne hirsutism obesity   Increased level of anxiety and depression.

38. Weight loss of only 5% of total body weight is associated with Decreased insulin and LH level Increased SHBG and decreased free androgen Improved menstrual function Reduced hirsutism and acne Lower testosterone level

39. Metformin Reduced insulin level by direct inhibition of hepatic glucose output. Suppress appetite and enhance weight reduction. Metformin is used as an adjuvant to - Management of obesity - Insulin resistant metabolic abnormalities  

40. Dose lean – 850mg/daily over weight and obese 1.5-2.5gm daily

41. Menstrual irregularity Chronic anovulation – Oligomenorrhoea Abnormal bleeding - Anaemia

42. Combination OCPS First line treatment OCP induced menstrual period with a higher degree of reliability than other form of treatment.

43. Combinations of OCPS Progesterone Inhibits endometrial proliferation Prevent hyperplasia Estrogen Inhibits the activity of the H-P-O. axis Reducing ovarian androgen production Increase level of SHBG Decrease gene of unbound testosterone OCP will normalize androgen level within 18-21 days

44. Combinations OCPS After three months – The efficacy of treatment is assessed by evaluation - clinical symptoms - Androgen level How long Till patient is gynecologically nature – 5 years post menercheal . or loss of substantial amount of excess weight   At that point withholding treatment for a few months -To allow recovery of suppression of H-P-O -Persistent of abnormalities  

45. Limitation of OCP Weight loss difficult Epiphyseal closure Post pill amenorrhoea

46. Progesterone Menstrual irregularity can be controlled with cycle progesterone alone GnRh agonist Cannot tolerate OCP Progesterone not sufficient Not use before the case of 16 yrs Pt receive GnRn agonist therapy also should be treated with low dose estradiol and progesterone add back therapy Bone mineral density should be monitored during therapy  

47. Hyper adrogenism   This is manifested in 2/5 of cases by Hirsutism Equivalent cutaneous findings Acene vulgaris Alopecia Seborrhoea Hyperhidrosis Hidradenitis suppurative

48. Hirsutism treated Cosmetic and dermatological measure Medical endocrine therapy   Cosmetic and physical measures Shaving Eflornithine cream ( vanique ) is a tropical agent that is FDA approved for the removed of unwanted facial hair in women.  

49. Laser therapy Removes hair permanently by thermal destruction of dermal papilla. Reduce hair density by 30% or move with 3-4 treatment cycle Medical therapy Reduced productions of androgen Increase SHBG Block androgen action at largest organs.

50. OCP Suppress ovarian androgen production Increase sex hormone binding globulin (SHBG) level Decrease DHEA sulfate. Transformation of vellus to terminal- reduced .   OCP Arrest progression of hirsutism Reduced the shaving by about half Improve acne – with in 3 months  

51. Androgen level has to be checked after 3 months of therapy. Anti androgen Suboptimal response after 6 months Inhibits the androgen induced transformation of vellus to terminal hair. Individual variation antiandrogen therapy reduces hirsutism by one third on average.   Antiandrogen should be prescribed with an OCP Cause menstrual disturbance Potential teratogen for fetus.

52. Anti androgen Cyproterone acetate -progesterone with anti androgenic effect. Spironolactone – Safe and potent Starting with l00mg twice day until maximum effect than reduce the dose to 50mg twice day Causes fatigue and hyper kalamia Laboratory test Electrolytes Liver function one to two week after initiation of Spironolactone  Flutamide 250mg TDS for 3 months Gradually lowering the dose Hepatocellular toxicity

53. Flutamide 250mg TDS for 3 months Gradually lowering the dose Hepatocellular toxicity Finasteride 5  reductase inhibitor

54. Acne Antibiotics and topical therapies Tetracycline, erythromycin and minocycline Used in conjunction with anti androgen treatment Topical non steroidal anti androgen Oncogenomic acetate Benzoyl peroxide. Alopecia 2% minoxidil BD with anti androgen treatment

55. Over diagnosis of PCOS Unnecessary psychological distress of having a diagnosis associated with future subfertility.

56. Under diagnosis Transition to adult hood and suffer the long term consequence of PCOS.  

57. Long term health hazard Infertility Metabolic syndrome Obesity Diabetes Heart disease

58. Take home message The overlap between normal pubertal development and characteristic features of PCOS. Other diagnosis associated with irregular menses hyper adrogenaemia need to excluded from diagnosis. Even in the absence of definitive diagnosis Alleviation of current symptoms Decrease the risk for subsequent associated co-morbidities

59. Thank You