on demand , i am uploading the full presentation on management of PCOS.....previous was only adolescent management................

1. NARENDRA MALHOTRA
M.D., F.I.C.O.G., F.I.C.M.C.H
• Prof Intermedical International University,Croatia
• President FOGSI (2008)
• Dean of I.C.M.U. (2008)
• Director Ian Donald School of Ultrasound
• National Tech. Advisor for FOGSI-G.O.I.—Mc Arthur Foundation EOC Course
• Hon Prof Ob Gyn at DMIMS,Sawangi,Advisor ART unit at MAMC & SMS Jaipur
• Practicing Obstetrician Gynecologist at Agra. Special Interest in High Risk Obs., Ultrasound,
Laparoscopy and Infertility, ART & Genetics
• Member and Fellow of many Indian and international organisations
• FOGSI Imaging Science Chairman (1996-2000)
• Awarded best paper and best poster at FOGSI : 5 times, Ethicon fellowship, AOFOG young gyn.
award, Corion award, Man of the year award, Best Citizens of India award
• Over 30 published and 100 presented papers
• Over 50 guest lectures given in India & Abroad.Presented 15 orations.
• Organised many workshops, training programmes, travel seminars and conferences
• Editor 8 books, many chapters, on editorial board of many journals
• Editor of series of STEP by STEP books
• Revising editor for Jeatcoate’s Textbook of Gynaecology (2007)
• Very active Sports man, Rotarian and Social worker
MALHOTRA HOSPITALS
84, M.G. Road, Agra-282 010
Phone : (O) 0562-2260275/2260276/2260277, (R) 0562-2260279, (M) 98370-33335; Fax : 0562-2265194
E-mail : mnmhagra10@dataone.in / mnmhagra3@gmail.com
Website : www.malhotrahospitals.com
Rainbow Hospitals, Agra
Consultant for IVF at jalandhar,ludhiana,ambala,bhiwani,gwalior,allahabad,gorakhpur,bariely,jaipur,delhi,sirsa,varanasi
Neapal & Bangladesh
NOW AT KANPUR AMBA HOSPITAL

2. MANAGEMENT OF PCOS IN VARIOUS
AGE GROUPS :ADOLESCENT TO
PERIMENOPAUSE
narendra malhotra
jaideep malhotra
neharika malhotra
www.malhotrahospitals.com
www.rainbowhospitals.org

3. Polycystic Ovarian Syndrome (PCOS)
• PCOS is a complex endocrine disorder affecting women
of childbearing age characterized by increased androgen
production and ovulatory dysfunction
• PCOS is the leading cause of anovulatory infertility and
hirsutism
• Women with PCOS have an increased risk of miscarriage,
insulin resistance, hyperlipidemia, type 2 diabetes,
cardiovascular disease, and endometrial cancer
Bauer J, et al. Epilepsy Res. 2000;41:163-167.
Dunaif A, et al. Annu Rev Med. 2001;52:401-419.
Franks S. N Engl J Med. 1995;333:853-861.

4. EPIDEMOLOGY
• 20-33% of all reproductive age group have
PCO
• 5-10% of all reproductive age group have
PCOS
• 87% of women with oligomennorhea
• 26% of women with ammenorhoea
• 50% of them presenting with infertility
• 50% women with recurrent miscarriages

5. DIAGNOSTIC CRITERIA
ASRM/EHSRE( Rotterdam
consensus 2003) defined PCOS
as the presence of 2 out of the
following 3 criteria:
– Oligo and/or Anovulation, USG Clinical
appearance features
– Hyperandrogenism
– Polycystic ovaries on USG Biochemical
(with the exclusion of other etiologies of parameters
hyperandrogenism)

6. CLINICAL MANIFESTATIONS
SYMPTOMS ASSOCIATED POSSIBLE LATE
ENDOCRINE SEQUALE
MANIFETATIONS
Obesity(38%) Androgens(29%) Diabetes mellitus(29%)
Menstrual disturbance(66%) LH(40%) Cardiovascular disease
Hyperandrogenism(48%) LH:FSH ratio Hyperinsulinemia
Infertility (73% of Free estradiol Low LDL
anovulatory infertility)
Asymptomatic(20%) Fasting insulin Endometrial carcinoma
Prolactin(27%) hypertension
Sex hormone binding
globulin

7. PCOS-A DISEASE WITH A SPECTRUM OF
CLINICAL PRESENTATIONS
MENSTRUAL IRREGULARITY.
PCO INFERTILITY,OBESITY
OVULATORY HIRSUTISM
NO HIRSUTISM ACNE,
NO DERMATOLOGICAL INSULIN RESISTANCE
ATHEROSCLEROSIS
GENETICS
BMI
LIFESTYLE

8. Genetic basis
• No clear cut mode of inheritance
• Initial studies suggest x-linked dominant
transmission but recent says autosomal
dominant inheritance
• Risk of developing PCOS is
40% if sister is affected
10%if mother is affected

9. LAB EVALUATION
• SR.TESTOSTERONE/17-OHP/DHEAS
• LH/FSH
• PROLACTIN No Biochemical test is
required for diagnosis
• 24HR FREE CORTISOL
• SHBG
• TESTS FOR INSULIN RESISTANCE

10. CRITERIA FOR METABOLIC SYNDROME
• ABDOMINAL OBESITY >88CMS/35”
• TRIGYCERIDES ≥ 150mg/dl
• HDL-C < 50Mg/dl
• BP ≥130/≥85MM hg
• FASTING/2HR ≥ 110-126
• PGBS 140-199MG/DL

11. We have to be more careful…
• South Asians
• Insulin
• BMI > 25
• More vulnerable

14. SPECTRUM OF CLINICAL CONDITIONS
ASSOCIATED WITH PCOS
PCOS
ENDOMETRIAL AN
CA OVULATION
HYPERTENSION DIABETES
INSULIN
HIRTUTISM
HIRSUTISM RESISTANCE
ATHEROSCLEROSIS

15. MANAGING PCOS: Goals
• Identify patients with risks for or with
diagnosis of PCOS
• Assess patients appropriately for PCOS and
associated disease states
• Prescribe therapy to treat complaints and
prevent sequelae

16. COUNSELING OF A PCOS PATIENT
Endocrine problems
Metabolic problems
Infertility
Risk of OHSS and multiple pregnancy
Pregnancy complications
Long term sequel
MOST IMP- Importance of life style modification

17. Any treatment for PCOS
should optimally address not only
the ovulatory dysfunction and
hyperandrogenism, but also the
dysmetabolic features such as
hyperinsulinemic insulin resistance,
obesity, dyslipidemia and abnormal
clotting mechanism.
Hence the treatment should
be for all age groups .

18. Management
• Adolescents
• Newly married conception not intended
• Married wanting conception
• Married has one child wanting spacing
• Secondary infertility
• Mature woman with completed family
• Perimenopausal
• Menopausal

19. HERE IS MISS POLY PCOS
CONCERNS are:
• Menstrual irregularities
• Obesity
• Hirsutism
• Acne

20. PROTOCOLS OF MANAGEMENT
IN ADOLESCENTS
• Counselling for weight reduction and life style
modification.
• Carbohydrate and fat restricted diet.
• Diet restriction and exercise is the sheet anchor
of
treatment for overweight.
• Low glycemic index diet upto 85% will improve
menstrual cycle regularity and ovulation in about
six months.

21. • Even 7% weight reduction may lead to
spontaneous resumption of menses.
• Moderate physical activity, 30-60 minutes per day
should be goal of all patient with adolescent PCOS.
M.O.A:-
• lowers circulating free androgen and insulin levels.
• Increases SHBG, thereby decreases level of free
testosterone.

25. Menstrual Irregularities

26. MENSTRUAL IRREGULARITIES
• Mostly managed by OCP
• MPA 10 mg/day or micronized progesterone 300 mg at
bedtime for 10 - 14 days effective in Rx of abnormal
bleeding.
• If oligomenorrhoea and amenorrhoea does not respond to
oral contraceptives and antiandrogen combinations, insulin
sensitizing agents have to be added.
• A lean PCOS may also have insulin resistance and therefore if
they do not respond to oral contraceptive dose, insulin
sensitizing drug has to be added.

27. WHY ORAL CONTRACEPTIVE PILLS ?
 Estrogenic component of the oral contraceptive
suppresses luteinising hormone and thus reduces
ovarian androgen production.
 Estrogen also enhances hepatic production of
SHBG ,thereby the level of free testosterone
declines.
 Cyproterone acetate, Drospirenone and
desogestrel can be used in combination with
ethinyl estradiol.

28. Cyproterone acetate
Competitively inhibits the binding of testosterone
and also 5α-dihydrotestosterone to the androgen
receptor.
• Ideal for Hirsut
Combination of ethinyl estradiol (0.35 µg) and
cyproterone acetate (2mg) PCOS. scientific in
is most
treating hyperandrogenicity as well as
maintaining the menstrual cyclicity.
Dose 1 tab. daily from D1 to D21 which has to be
repeated cyclically for a period of six months.

29. DROSPIRENONE
• Combination of ethinyl estradiol (30 µg) with
Drospirenone (3mg), an analogue of
spironolactone with unique antimineralocorticoid
and antiandrogenic action has also been used.
Ideal for Obese PCOS
• Combination of ethinyl estradiol (30 µg) with
Desogestrel (20 µg) can also be used.

30. IMPROVEMENT OF HYPERINSULINEMIA BY
INSULIN SENSITIZERS
 Directly sensitizing insulin receptors.
 Preventing neoglucogenesis.
 Reducing absorption of glucose from intestine.
 Increasing hepatic synthesis of SHBG level thereby
reducing the level of bioactive free testosterone.

31. Metformin
Decreases basal hepatic glucose output in patients
and lowers fasting plasma glucose concentration.
 It increases the uptake and oxidation of glucose by
adipose tissue as well as lipogenesis.
 S/E- diarrhoea, nausea, vomiting ,specially
initially.
To avoid them metformin should be taken
with meals and the dose increased gradually. Or SR
release formulations are used once a day 1000 mg
SR or 500mg SR twice a day

33. OTHER DRUGS WHICH CAN BE USED
• Rosiglitazone ,
• Pioglitazone,
• D chiro inositol,
• Myoinositol
• N acetyl cysteine.
• Micronutrients

34. OTHER DRUGS WHICH CAN BE
USED IN ADDITION TO O.C.P.
• In cases of failure or where there is clinical or
biochemical evidence of gross hyperandrogenicity
or hyperinsulinemia, addition of metformin is
recommended.
• Spironolactone- it has antiandrogenic effects in
doses 100-200 mg daily.
• Finasteride - a competitive inhibitor of Type-2 5a
reductase to treat hirsutism. Dose 1-5 mg/day.

36. COSMETIC TREATMENT
• Antiandrogens used in PCOS will prevent further
hair growth but the hair which have already grown
have to be treated by epilation, waxing, by
electrolysis or laser treatments.
• Acne may require oral antibiotics like
erythromycin and isotretinoin ointment.
• Acne also gets cleared in 6-9 months by use of oral
contraceptive pills containing cyproterone acetate.

37. Excessive Hair
Mechanical method
Laser Waxing
Shaving

38. RESPONSE TO TREATMENT IS ASSESSED
BY
• Resumption of menstrual cyclicity.
• Reduction in features of hyperandrogenicity.
• Improvement of biochemical parameters like
reduction of free serum testosterone and
normalization of fasting glucose insulin ratio.

39. MISS POLY PCOS IS NOW
MRS POLY PCOS SHE IS 24 YRS OLD
• Newly married not wanting conception
• Married wanting conception
• Married has one child wants spacing
• Secondary infertility
Newer concepts in medical management

40. HER CONCERNS:
•High BMI
•Hirsutism
•Oligo/amenorrhoea
MOST IMPORTANT : DOESN’T WANT A
PREGNANCY NOW

41. Best treatment option- After lifestyle modification
ORAL CONTRACEPTIVE PILLS
Prefer third generation pills like
•Drosperinone containing pills
•Cyproterone acetate containing pills
•Low dose estrogen newer progesterone pills
Advantages:
•Cycle regularisation
•Effective contraception
•No weight gain
•Control androgenic symptoms

42. MRS POLY PCOS wants to concieve now
• CC
• LETRAZOLE/ANASTRAZOLE
• LOW DOSE FSH/REC FSH
• LAPAROSCOPY-LEOS
• IVF

43. PCOS – Treatment Algorithm
ESHRE/ASRM consensus workshop
Preconception counseling*on life style modification
1st line Clomiphene Citrate(CC) Ovulation
Ovulation
2nd line Gonadotropin or LOS
Ovulation
3rd line IVF
Success rates: •Metformin- only in cases with
LOS alone effective in <50% cases glucose intolerance
CC-Gonadotropin paradigm – 70% •Aromatase inhibitors- insufficient
evidence to be recommended
*(wt reduction and exercise)
Fertil Steril 2008;89:505-22

44. 1
CC binds to ER and depletes
receptor concentrations  Depletion of ER in pituitary
Hypothalamus and hypothalamus due to
Pituitary
3 prolonged stimulation
FSH stimulation continues 2
estrogen –ve feedback  Estrogen feedback loop gets
interrupted
interrupted
 FSH secretion increased
leading to multiple follicle
growth
4 More smaller follicles are rescued
 Peripheral anti estrogenic
effect
5 Multiple follicles develop  Longer half life

45. 3 Releases off -ve feedback  Inhibits aromatase in ovaries and
stimulation peripheral tissues reducing estrogen
4 GnRH released Hypothalamus levels
Pituitary
 Negative feed back being active
released, stimulates hypothalamus-
FSH stimulation pituitary axis
5  GnRH release produces FSH
Falling FSH estrogen –ve feedback  FSH-mediated stimulation of follicle
2
 Rising estrogen level from follicle
suppresses FSH leaving a single
dominant-follicle
Smaller follicles undergo
atresia
1
6 Single follicle develop androstenedione  estrogen
aromatase inhibition

46. PCOS
• Stimulation in PCOs is a problem
• Response is not predictable
• Dose is not predictable
• Number of days of stimulation is not predictable.
• Control over the cycle is difficult.
• OHSS is a real problem.

47. Laparoscopic Ovarian Drilling
WHO BENEFITS FROM
Mechanism LEOS
• ?Removalresistant,
CC androgen-producing tissue
Problems Slim,
Anovulatory ,
• Hazards of laparoscopic surgery & GA (although rare)
raised S.LH
• Temporary
Efficacy
• <50% clomiphene-resistant women conceive (ovulation rate
80%+)
• Hormone profile returns to normal
• ?Fewer miscarriages compared to gonadotrophin injection
treatment

48. 33-50% OF PATIENTS REFERRED FOR
IVF HAVE PCOS

49. IVF STIMULATION PROTOCOLS
IN PCOS PATIENT

50. OVULATION INDUCTION REGIME IN PCOS
• OC Pill pretreatment (1-2 cycle)
• Long protocol
• Antagonist protocol
• Lower than usual starting dose
• FSH preferable to hMG
• Close follicular monitoring
• Serum estradiol whenever required
• Close vigilance for OHSS

51. RESPONSE OF PCOS TO
STIMULATION
• Poor responders/ hyper-responders
• Decreased fertilization rate
• Cleavage rate same
• Pregnancy rate same
• Live birth rate same
• OHSS risk increased
• High order multiple increased

52. GnRH Agonist with low dose
gonadotropin in
• High serum LH
•Repeated premature
leutinisation
•Do not conceive with
gonadotropin alone
•Early miscarriage on more
than one occasion

53. The ideal Indian protocol
5000 hCG
0.25 mg antagonist/day
75 / 150 IU rec FSH
100 mg CC / day
Letrozole 5mg
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

54. MRS POLY PCOS IS PREGNANT

55. DURING PREGNANCY
• RECURRENT MISCARRIAGES 50%
• GESTATIONAL DIABETES
• PREGNANCY INDUCED
HYPERTENSION
• INTRAUTERINE GROWTH
RETARDATION

56. Should we continue Metformin?
• In women with PCOS, continuous use of metformin during
pregnancy significantly reduced the rate of miscarriage, gestational
diabetes requiring insulin treatment and fetal growth restriction.
No congenital anomaly, intrauterine death or stillbirth was reported
in this study.
Aga Khan Publication 2010
There is a statistically significant reduction in the incidence of GDM in
favor of metformin group (OR: 0.17, 95% CI: 0.07-0.37). There is a
statistically significant reduction in the incidence of pre-eclampsia in
favor of metformin group (OR: 0.35, 95% CI: 0.13-0.94).
Conclusion. Metformin is a promising medication for the prevention
or reduction of the incidence of GDM and pre-eclampsia in PCOS
Khattab etal Gynec endoocrinol 2011

57. Screening for gestational diabetes when?
At first prenatal visit, women at high risk of GDM (severe obesity,
personal history of GDM or previous delivery of large-for-gestational
age infant, glycosuria, PCOS or a strong family history of diabetes)
should undergo standard diagnostic testing for diabetes. If abnormal,
consider these individuals to have "overt" (not gestational) diabetes. If
normal, retest between 24 - 28 weeks (ADA Standards of Medical Care
2010). 75 gms OGCT as per latest DIPSI/IDA guidelines in every
trimester
• Women seeking ART and being treated with metformin still show a
very high rate of GD or IGT after achieving pregnancy by ART.
Therefore in women undergoing ART screening for GD should be
performed as soon as pregnancy is confirmed to avoid miscarriages
due to overlooked uncontrolled glucose metabolism
Bals-Pratsch M, Großer B Clinical endocrinol 2011

58. Monitoring of pregnancies as any other high
risk pregnancy
Antenatal checks
RBT and GDM screening first visit
,if negative,repeat at 24 wks 75g
OGTT
Early USG scan
11-14 wks scan
Uterine artery notch
Two weekly checks after 24wks
Color Doppler if IUGR

59. MRS POLY PCOS
has one child & wants spacing

60. Oral contraceptive pills are the
best option for them but if wish
to use other contraceptive then
ensure 2 monthly withdrawal to
avoid the long term
complications of unopposed
estrogen action on the
endometrium

61. MRS POLY PCOS
HAS ABORTIONS/CHILD
AND NOW WANT ANOTHER ONE
AND IS NOT CONCIEVING
Secondary infertility

62. Diet / exercise/ weight reduction
If ovulating search for other causes-tubal or uterine
factor,male factor,
If anovulatory– ovulation induction
If recurrent pregnancy loss with no other causes- suppress
LH-DEW/ insulin sensitizers/GNRH agonist

63. MRS POLY PCOS HAS COMPLETED FAMILY
• IRREGULAR PERIODS
• PERIODS OF AMEN OF 2-6 MONTHS
• OBESITY
• LETHARGY
• ACNE AGAIN
• SLIGHT EXCESS BODY HAIR

64. PCOS coming again is a management
challange

65. Importance of Diagnosis - Mature PCOs.
• A firm & convincing diagnosis
will allow us to offer strong
base for counselling about
prognosis & definitive line of
treatment to prevent
dangerous sequele.
Diagnostic Criteria are same as suggested by ESHRE/ ASRM.

66. Mature PCOs – Therapeutic Goals.
IN WOMEN WHO HAVE COMPLETED THEIR
FAMILIES
NOW PCOS MANAGEMENT HAVE TO BE
THOUGHT IN TERMS OF :
• MENSTRUAL IRREGULARITIES
• CARDIOVASCULAR DISEASES
• DIABETES
• MALIGNANCY
• SEIZURE DISORDER

67. Mature PCOs
Some Common Features.
• This predisposes to : METABOLIC SYNDROME
– Type 2 Diabetes.
– Atheroscelerosis. Hyper tension.
– Coronary Artery Disesase.
– Severe Oligo menohrea / Amenohrea.
– Increases Incidence of Endo Cancer. ( 5.3 times ↑).
– No significant change in the incidence of breast cancer.
– Epilepsy.
– Sleep Apnea.
Franklin C 2008.

68. PCOS MONITORING
• Yearly testing
• Complete history
• Thorough physical exam
• B P assessment
• FBS &OGTT periodically
• Lipid profile
• Homocysteine levels
• Other cardiac risk factors

69. MANAGEMENT
• life style and excercises
• diet
• insulin sensitisers
• ocp’s
• progesterone for bleed
• statins/diabetes /antihypertensives if needed
• omega 3 and micronutrients(inositol or
myoinositol or n-actyl cysteine or alternative
medicines

70. MRS POLY PCOS
IS PERIMENOPAUSAL 44 YRS
• irregular cycles
• androgen excess
• diabetes x 7
• hypertension x 4
• lipid profile
• cardivascular ds and accidents
• endometrial cancer
• Metabolic Syndrome

71. MRS POLY PCOS IS MENOPAUSAL
HAS DEVELOPED ALL LONG TERM
COMPLICATIONS:METABOLIC SYNDROME

72. The Metabolic Syndrome:
WHO criteria
IGT/IFG or
type 2 diabetes
Central Obesity Insulin resistance
BMI > 30 kg/m² (glucose uptake below
lowest quartile)
METABOLIC SYNDROME
Microalbuminuria Blood pressure
UAE  20 µg min  160/90 mmHg
Triglycerides > 150 mg/dl
&  HDL-Ch < 35 mg/dl
Alberti & Zimmet WHO 1998 Diabetic Medicine.

73. Adult Treatment Panel III
Risk Factor Level
– Waist Circumference – >40 in (m) >35 in (f)
– Triglycerides – >150 mg/dl
– HDL Cholesterol – <40 (m) <50 (f)
– Blood Pressure – >130/85
– Fasting Blood Glucose – >110
Dysmetabolic Syndrome = 3 out of 5
ATP III, Nat. Chol. Ed. Program, NIH

74. Treatment of Metabolic Syndrome
Risk Factor Treatment
Central Obesity Lifestyle Modification
Dyslipidemia Statins and/or Fibrates
Hypertension (and/or ACE I or ARBs
endothelial dysfunction)
Prothrombotic State
ASA, Quit smoking
Insulin Resistance If T2DM: TZDs with or
And Hyperglycemia without metformin

75. CONCLUSION
• PCOS is Enigmatic,still lesser understood
• Diagnosis can be tricky
• Management is age and need oriented
• Lifestyle modification is the crux.
• Fertility can be difficult.
• Prevention of longterm implications should
be kept in mind(prevent MS)

76. Take home message
• When evaluating women with PCOS,
including younger adolescents, physicians
should assess for the presence of components
of metabolic syndrome. Therefore, clinical
evaluation should include assessments of
blood pressure, waist circumference
and/or BMI, fasting lipid profile, and glucose
tolerance by a 2-hour oral glucose
tolerance test.

77. Take home message
• Combination therapies ,most effective
• Diet control and lifestyle modification only
may not be adequate
• Pharmacotherapy is required
• Insulin sensitizers before development of
overt diabetes controversial,but increasingly
used.
• As PCOS is the “thief of womanhood” it must
be treated at all ages

78. THANKYOU