PCOS

1. Moderator:
Prof. Dr. Sunil Mani Pokheral
HOD( Gynae and OBS)
Presenter:
Dr Lokendra Bata
2rd year resident
PCOS

2. OBJECTIVES
 To define and know Diagnostic criteria of PCOS
 To know the Pathophysiology and clinical
features of PCOS .
 To know its management and complication.

3. Introduction and Definition
• Most common Endrocrinological Disorder
• Incidence 5 to 10%.
• First described by Steven and Leventhal in 1935
•Is a syndrome of Ovarian dysfunction along
with cardinal features of hyperandrogenism
and polycystic ovary.

4. Diagnostic Criteria for PCOS
National Institute of Health
(1990)
ESHRE/ASRM (Rotterdam)
Consensus Criteria (2003)
ANDROGEN EXCESS AND
PCOS Society 2006
MUST include ALL of the
following:
- Clinical and/or biochemical
signs of Hyperandrogenism
- Chronic anovulation
- Exclusion of possible
related disorders
MUST include TWO of the
following:
- Anovulation / oligo-
ovulation
- Clinical or biochemical
signs of Hyperandrogenism
- Polycystic Ovaries
MUST include ALL of the
following:
- Hyperandrogenism-
hirsutism
- Ovarian dysfunction -oligo-
anovulation and or
polycystic ovaries
- Exclusion of possible
related disorders
* Presence of polycystic
ovaries is NOT necessary for
diagnosis
* All possible related disorders
MUST BE RULE OUT

5. Rotterdam , 2003
 diagnosis of exclusion.
 Cushings syndrome – physical findings -- moon facies,
buffalo hump, abdominal striae, and truncal obesity.
Increased 24-hour urinary excretion of free cortisol .
 Androgen secreting tumours - Palpation of an adnexal
mass , rapid virulization, DHEAS – 1000mcg/dl.
 Congenital adrenal hyperplasia - 17 OHP measurment
early morning . Level more than 200ng/dl.
 Hypogonadotropic hypogonadism
 Hyperprolactinaemia
 Syndrome of severe insulin resistance

6. Etiology
• Remains unclear
• Multifactorial
• Genetic Basis--
– Single or several genes may be involved
– autosomal dominant phenotype
– genes involved in carbohydrate , steroid hormones
and gonadotropin actions involved
– genes involved as
• CYP11A androgen receptor
• CYP17 SHBG gene
• CYP21 Insuline receptor gene

7. PATHOPHYSIOLOGY
• Hyperandrogenism and anovulation that
accompany PCOS may be caused by
abnormalities in four endocrinologically active
compartments:
(i) the ovaries,
(ii) the adrenal glands
(iii) the periphery (fat), and
(iv) the hypothalamus–pituitary compartment

8. theca
AROMATASE
Theca cells
Ant.pit
uitary
GnRH
LH
FSH
ANDROGEN(ANDROSTENRDIONE)
DESMOLASE
ESTRADIOL
GRANULOSA CELLS

9. Impaired development of follicles
extraglandular aromatization

13. CLINICAL FEATURES
Signs and symptoms
 Anovulation
– Oligomenorrhea (70-75%), Amenorrhea (20%)
– Menstrual irregularities
 Infertility (30-70%)
 Obesity (80% of PCOS women)

14. Effects of Androgen Excess
 Hyperandrogenism
• Hirsutism (70% of PCOS women)
Modified Ferriman Callwey score
• Severe acne/ acne after
adolescence
• Androgenic alopecia

15. Effects of Hyperinsulinemia
 Insulin resistence
• Acanthosis nigricans
• Skin tags
• Impaired glucose
tolerance
• Type II DM
• Obesity
• Decreased SHBG
• Increased unbound
androgens
• Reduced HDL

16. Menstrual dysfunction
– Amenorrhoea
– Oligomenorrhoea
– Menometrorrhagia
Obstructive sleep apnea
–30-40 fold
increase in PCOS
–Related to central
obesity and insulin
resistance

17. Metabolic syndrome
and cardiovascular
disease---
• Insuline resistance,
• obesity
• dyslipidemia and
• Hypertension
– approximately 45% in
women with PCOS
– endothelial dysfunction
Endometrial Neoplasia -
• Risk of endometrial
cancer x3
• Chronic anovulation 
chronic unopposed
action of estrogen
Endometrial
hyperplasia 
Endometrial cancer

18. • INFERTILITY
– Due to anovulatory
cycle
– PCOS is most
common cause 80-
90% cases
• PREGNANCY LOSS
– 30-50% incidence of
early miscarriage
– Proposed theory
• LH level and
androgen
• Insuline resistance

19. Pregnancy complications:
– Risk GDM
– PIH
– Preterm birth
– perinatal mortality x 2-3
– Treatment as ovulation induction medications 
multifetal gestation

20. Psychologic health:
–Anxiety,
–Depression
– low self esteem ,
– reduced quality of life.

21. PCOS Evaluation
• HISTORY:
- Menstrual history
. Anovulation / oligo-ovulation ( < 8 menses per year)
- Reproductive history ( Infertility)
- Weight gain ( difficulty losing weight)
- Hirsutism, acne

22. PCOS Evaluation
• PHYSICAL
• Blood Pressure
• BMI [( weight in kg / height in m)2]
■ 25–30 = overweight, greater than 30 = obese
• Waist circumference to determine body fat distribution
■ Value greater than 35 inches = abnormal
• hyperandrogenism and insulin resistance
■ Acne, hirsutism, androgenic alopecia, acanthosis nigricans

23. PCOS Evaluation
•LABORATORY TESTS:
–FSH , LH, [LH/ FSH ratio >3:1 ( 1.5: 1 normal)]
–SHBG
–TSH ,
–Prolactin – r/o Hyperprolactinemia
–Total or free testosterone levels: if above 6 nmol/L than check
to r/o androgen-secreting tumor of the adrenal gland
–DHEAS: levels above 18 nmol/L necessitate exclusion of
Cushing’s syndrome
–17-hydroxyprogesterone - if morning level is <5.5nmol/L, if the
levels are raised, check for congenital adrenal hyperplasia
–Evaluation for metabolic abnormalities - 2hr – GTT , Lipid
profile

24. PCOS Evaluation….. USG
 Ultrasonography (Abd. USG and TVS) –
- History and symptoms suggestive  USG
* at early follicular phase (3-5th day of regular cycles), between
day 3-5 after progestin induced withdrawal bleeding.
 To check for PCO
 Screen for endometrial hyperplasia

25. PCOS Evaluation….. USG
 >12 follicle of diameter 2-9mm in ovary
 Ovarian size >10ml
 Peripheral location of cysts – “Pearl necklace “
 Similar size of cysts
 Hyper-echoic central stroma

26. PCOS Evaluation….. USG
* Positive for PCO – Confirms diagnosis
* If Negative for PCO  Biochemical examinations.
(increased S. Testosterone, LH, elevated free androgen indix,
fasting glucose:Insulin <4.5) –confirms diagnosis.
If USG findings Negative and biochemical not supportive then
need to rule out other conditions.

27. Diagnostic algorithm for polycystic ovary syndrome.

28. MANAGEMENT
-Treatment is goal specific
- Management is dictated by the clinical presentation
(e.g. menstrual changes, hirsutism and/or infertility).

29. Management goals
• Identify patient with risk for or with diagnosis
of PCOS
• Assess patient appropriately for PCOS and
associated disease states
• Prescribe therapy to treat symptoms and
prevent sequelae.

30. Management Plan
1. Identify the symptoms
2. Counselling
1. Endocrine problems
2. Metabolic problems
3. Infertility
4. Pregnancy complications
5. Long term sequelae

31. • Managements depends upon:
– Reproductive age group
– Presenting Symptoms
– Maritial status
– Desire of fertility
• Any treatment for PCOS should optimally address
not only the ovulatory dysfunction and
hyperandrogenism, but also the metabolic
features like hyperinsulinemic insulin resistance,
obesity and dyslipidemia.

32. Protocols of management in
Adolescence
• 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
the menstrual cycle regularity and ovulation in
about 6 months.

33. Management
• Management of PCOS is symptoms oriented.
• Central role of insulin resistance and obesity
as an aetiology.
• Life style modification along with certain
pharmacological agents

34. Lifestyle Modification
• lifestyle changes: the most important
intervention
• weight reduction - 5% to 7% in 6-month
period ,restore ovulation and fertility >75% of
women and also improves features of
Hyperandrogenism.

35. • Dietary modifications
– Low calorie diet in obese PCOS have significant weight loss,
decrease in testosterone level and improve in insulin
sensitivity.
– Reduced energy diets(500-1000 kcal/day reduction) are
effective options for weight loss and can reduce body
weight by 7% to 10% over the period of 6-12 months.
• Moderate exercise:
– Improved ovulation, fertility and insulin sensitivity were
found.
– Structured exercise is an important component of a weight
loss regime; aim for > 30 min/day.
• Cessation of smoking

36. Metformin
• inhibits the production of hepatic glucose and
enhance the sensitivity of peripheral tissue to
insulin, thereby decrease insulin secretion.
• Improves menstrual cyclicity and ovulation in
PCOS
• Effects on live birth rate, hirsutism, acne and
obesity are unclear.

37. • Dose: 500mg PO TDS before food gradually
increament of 500mg weekly.
• continued for 6-12 months, if regular ovulation
documented, however if it has not been effective
after 3-6 months treatment, clomiphene should be
added for further 6 months.
• Where no pregnancy even after one year of
monotherapy or the combination, alternative
treatment should be considered.

38. Obesity
– 10-65% with PCOS are obese
– Weight loss recommended with BMI>30kg/m2
– Central obesity with greater truncal abdominal fat
distribution, causing higher waist:hip ratio.
– Independent of BMI and associated with higher plasma
insulin and triglycerides concentrations and reduced HDL
cholesterol concentrations.
– Correlation exist between obesity and infertility and
obesity and miscarriage. Mechanism not completely
elucidated.

39. Menstrual irregularities
– Weight loss
– Use of low dose combined oral contraceptive preparations,
resulting in artificial cycle with regular shedding of
endometrium.
– Alternative: Progesterone for 12 days every 1-3 months to
induce withdrawal bleeding.
– An USG assessment of Endometrial thickness.
– Endometrial thickness of >15mm is an indication for
withdrawal bleeding, if fail to shed, biopsy should be done
to rule out endometrial hyperplasia or malignancy.

40. COCP
- 1st line treatment.
- decrease adrenal and ovarian androgen
production and reduce hair growth in nearly 2/3 of
hirsute patients.

41. Advantages:
1. The progestin component suppresses LH, resulting in
diminished ovarian androgen production.
2. The estrogen component increases hepatic production
of SHBG, resulting in decreased free testosterone
concentration.
3. Circulating androgen levels are reduced, including
those of DHEAS, which to some extent is independent of
the effects of both LH and SHBG.
4. Estrogens decrease conversion of testosterone to DHT
in the skin by inhibition of 5α-reductase.

42. Progesterone (cyclical oral or depot
medroxyprogesterone acetate (DMPA))
• negative feedback decreases GnRH production,
resulting in decreased oestrogen and androgen
Cyclic progestin: progesterone withdrawal bleed is
recommended 1 to 3 months.
- 5 to 10 mg orally daily for 12 days.

43. Medical treatment of hirsutism
• Weight reduction
• Hormonal supression:
– Oral contraceptive pills
– Medroxyprogesterone
– Gonadotropin releasing harmone analogues
– Glucocorticoids
• Steroidogenic enzyme inhibitors: Ketoconazole.
• 5-alpha reductase inhibitors: Finasteride
• Antiandrogens:
– Cyproterone acetate
– Spironolactone
– Flutamide
• Insulin sensitizer: Metformin
• Mechanical : temporary, permanent.

44. Treatment for Hirsutism : Hormonal
supression
– 1st line therapy COC pills (the 2008 Endocrine Society
Guidelines)
– estrogen lowers circulating androgen by
1. slight inhibition of gonadotropin secretion and
gonadotropin sensitive ovarian steroid production
2. by production of SHBG by liver resulting lower free
testosterone.
– estrogens: is the mainstay, who wishes hormonal treatment
and do not wish to become pregnant.

45. Treatment for Hirsutism : Hormonal
supression
GnRH Agonists:
• Not a preferred long-term treatment
• associated bone loss, high cost, and
menopausal side effects.

46. Steroidogenic enzyme inhibitors:
Ketoconazole.
• Administered at a low dose (200 mg per day),
it can significantly reduce the levels of
androstenedione, testosterone.

47. 5 alpha reductase inhibitor
Finasteride:
• inhibits conversion of testosterone to
more active 5 alpha hydroxy testosterone.
• Dosage- 5 mg daily

48. Treatment for Hirsutism : Antiandrogen
Cyperoterone acetate:
• A progestin that has strong antiandrogenic action.
• Inhibits gonadotrophin secretion and interferes with
androgen action on target organs by competing for androgen
receptors
• Dosage- 100mg from D5-D15 with ethinyloestradiol 30-50 µg,
from D 5 to D26
• Side effects: Nausea, fatique, weight gain, loss of libido,
mastalgia

49. Treatment for Hirsutism : Antiandrogen
Spironolactone: (Antialdosterone antiandrogenic compound)
• Inhibits ovarian and adrenal androgen biosynthesis
• Competes for androgen receptors in hair follicle
• Inhibits 5 alpha reductase activity
• Dosage -100-200mg daily, maintenance dose is 25-50 mg daily
• Side effects- fatigue,menstrual irregularities, hyperkalaemia

50. Treatment for Hirsutism : Antiandrogen
Flutamide: Androgen receptor antagonist
• Dosage – 100-200mg daily
• Side effects - hepatotoxic , Dry skin
• Should be combined with a contraceptive
• Marked beneficial effect in 6 months

51. Mechanical Treatment : hirsutism
– Temporary
• Cosmetics - waxing, bleaching
• medical therapy - Eflornithine Hydrochloride
-- antimetabolite topical cream (irreversible inhibitor of
ornithine decarboxylase) applied twice daily to areas of
facial hirsutism .
• Physical treatment: Hair removal ( depilation /
epilation) / thermal destruction
– Medical treatment takes 6-9 months or longer.
– Permanent
Electrolysis (galvanic current) and laser hair removal

52. PCOS and Infertility
–ASRM/ESHRE recommend that before any
intervention is initiated, preconception
counseling should emphasize importance of
- Weight reduction and exercise in obese
- Smoking cessation
- Reducing alcohol consumption

53. Infertility
• First line of treatment:
– Oral anti-oestrogen as clomiphene citrate
– Success rate of induction 80% and
– pregnancy occurs in 40%.
• USG monitoring:
– mandatory to rule out 10 % risk of multiple
pregnancy and to ensure the ovulation.

54. ↓
↓
↓ ↓
→
↓
History /examination/ lab test
Life style advice/ folic acid/ diet/ exercise
Metformin 6-12 months.( RFT/LFT)
Not pregnant
CC for 6 cycles
Pregnant , stop
med .
Not pregnant
GNRH, Ovarian drill,
IUI, IVF Rx of infertility with PCOS

55. Infertility
• Gonadotropins : Second line
– Resistant to anti-estrogens,
– start with a very low dose
– Follicular monitoring by USG
– Treatment should be suspended if 2 or more
mature follicles develop

56. Surgical management
• Ovarian wedge resection
• Laparoscopic ovarian diathermy -
– Type I: Clomiphene resistance
– Type II: Clomiphene failure
– Type III: Clomiphene pregnancy failure

57. Ovarian Wedge Resection
• Is associated with only a transient reduction in
androstenedione levels and a prolonged minimal
decrease in plasma testosterone .
• In patients with hirsutism and PCOS hair growth was
reduced by approximately 16% .
• reports show lower pregnancy rates and a concerning
incidence of periovarian adhesions .
• premature ovarian failure and infertility were reported .
• extensive ovarian and peritubal adhesion.

58. Laparoscopic ovarian diathermy
• as an alternative to wedge resection with severe
PCOS whose condition is resistant to clomiphene
citrate.
• In each ovary, 10 to 15 punctures were created.
• led to spontaneous ovulation in 73% of patients, with
72% conceiving within 2 years.
• decrease in both androgen and LH concentrations and
an increase in FSH concentrations .

59. Laparoscopic ovarian diathermy
• Effective as gonadotropins in treatment of
clomiphene insensitive PCOS.
• Wthout the risk of hyperstimulation and multiple
pregnancy
• beneficial endocrinological effects and the
improvement in hirsutism were sustained for up to 9
years.
• Unilateral diathermy results in bilateral ovarian
activity .

60. Long term Sequelae
• Malignancy:
– Endometrial cancer
– Breast cancer
– Ovarian cancer
• Hypertension
• Diabetes
• Atherosclerosis
• Dyslipidemia
• Metabolic Syndrome

61. Endometrial Cancer
• 4% in general women <40 yrs.
• Prolonged anovulation with consequent
continued unopposed estrogen.
– Other risk factor: obesity, nullipara, infertility
– True risk of Endometrial Cancer in women with
PCOS: difficult to ascertain.
• Induction of artificial withdrawal bleed to
prevent endometrial hyperplasia is prudent
management

62. Ovarian Cancer
• Women with PCOS have relative risk of
ovarian tumor of 4.1 in compared to controls.
• However, infertility on its own increases the
risk of borderline and invasive ovarian tumors.

63. Breast cancer
• Obesity, hyperandrogenism and infertility
occur in PCOS, are also features associated
with development of breast cancer.
• Did not show any increase incidence over
controls.

64. Impaired glucose tolerance and DM
• WHO criteria, after 75gm glucose load
– Impaired glucose tolerance: 2hr glucose >=140 but
<=190
– Overt type II DM: Any glucose level >200mg/dl
Obese women with PCOS: 18-20% have IGT.
Prevalence of DM in PCOS: 15% compared to 2% in
general populations.
Insulin resistance with abdominal obesity: higher
prevalence of type 2 DM in PCOS with concomitant
increase risk for GDM.

65. Metabolic syndrome
• Diagnostic criteria:
– Female waist: >35 inches
– Triglycerides: >150 mg/dl
– HDL: <50 mg/dl
– Blood pressure: >130/85 mmHg
– Fasting glucose: 110-126 mg/dl
– 2 hr glucose(75gm OGTT): 140-199 mg/dl

66. Dyslipidemia
• Dyslipidemia is the most common metabolic disorder
seen in PCOS patient.
• Women with PCOS, higher concentration of serum
triglycerides and suppressed HDL.
• Insulin resistance, central obesity and
hyperandrogenemia, are the surrogate risk factor for
cardiovascular disease and diabetes in later life in
women with PCOS.

67. AE-PCOS recommendation
• To assess cardiovascular risk and prevention
– Waist circumference and BMI measurement every
visit, using National health and Nutrition examination
survey method.
– A complete lipid profile based on AHA guidelines. If
fasting serum lipid profile is normal, it should be
reassessed every 2 years or sooner if weight gain
occurs.
– 2-hr post 75gm oral glucose challenge measurement
in PCOS women with BMI >30kg/m2 or alternatively in
lean PCOS women with advanced age(40 years),
personal history of GDM, or family history of type 2
DM

68. • Blood pressure measurement at each visit.
The ideal BP is 120/80 mmHg or lower.
Prehypertensive should be treated because
blood pressure control has the largest benefit
in reducing cardiovascular disease.
• Regular assessment for depression, anxiety
and quality of life.

69. References
1. Berek and Novak’s Gynecology, 15th edition. United States.
LIPPINCOTT WILLIAMS & WILKINS. 2012.
2. Malhotra N, Kumar R, et al. Jeffcoates’s Principles of
GYnaecology, 18th edition, 2014.
3. Hoffman B L, Schorge J O, Schaffer J I, Halvorson L M, et al.
Williams Gynaecology, 3rd edition.United States. The
McGraw-Hill Companies, Inc. 2016.
4. Munshi A, C B Nagori, et al. Current concepts in Obstetrics,
Gynaecology and Infertility Update 2017. AICOG.

70. THANK YOU.