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Polycystic Ovary Syndrome: Dr. Gurpreet Kaur
Polycystic Ovary Syndrome: Dr. Gurpreet Kaur
syndrome
1
Introduction
Also known as Stein-Leventhal syndrome
Incidence - 1%
Age group – 15-25 years
Heterogeneous collection of signs and symptoms
Ranging from women with polycystic ovary & no
overt abnormality at one end, to those with severe
clinical and biochemical disorders at the other end
2
Definition
Rotterdam criteria(2003)
• Oligo and / or anovulation
• Clinical and / or biochemical evidence of
hyperandrogenism, excluding other etiologies
• Polycystic ovaries in USG
Presence of any 2 of the above is PCOS
3
Oligovulation and anovulation
Anovulatory cycles
Lack of cyclical progesterone
Irregular uterine bleeding
4
Hyperandrogenism
Clinical and biochemical parameters
Clinical Biochemical
Hirsutism Testosterone
Acne Free androgen index
Alopecia DHEAS
Clitoromegaly Androstenedione
17 alpha hydroxy
progesterone
5
Ultrasonography
In 20 – 25% women without PCOS – USG
features of polycystic ovary are seen
6
Pathophysiology
Clinical features…
Cause
7
Pathophysiology
8
Pathophysiology
Clinical features…
Hypothalamus
Pituitary
Ovary
9
Pathophysiology
Clinical features…
Hypothalamus & pituitary
GnRH Pulsatility
LH FSH (or)
10
Pathophysiology
11
Pathophysiology
Clinical features…
Normal
12
Pathophysiology
Clinical features…
ANOVULATION
13
Pathophysiology & Clinical features
LH
Testosterone Androstenedione
SHBG Estrogen
Free Testosterone
15
Pathophysiology & Clinical
features
FSH
Follicular growth
16
Associated Factors
Hyperinsulinemia
Obesity
17
Hyperinsulinemia
Insulin resistance occur irrespective of BMI
Obesity and hyperinsulinemia have
synergetic effect
18
Obesity
50%
Android type
BMI 25 kg/m2
Waist hip ratio > 0.85
Visceral obesity is metabolically more active
Metabolic syndrome is common in PCOS
19
Obesity
Metabolic Syndrome X
Abdominal obesity > 88 cm
B.P 130/85 mm of Hg
Abnormal GTT
Cardiovascular Glucose
HTN disorders Dyslipidemia
intolerance
21
Infertility and PCOS
PCOS is the cause of anovulatory infertility in 75%
Factors implicated in chronic anovulation
LH
Hyperandrogenism
Hyperinsulinemia
Endometrial non receptivity
Obesity
23
Clinical Manifestations
24
Clinical Manifestations
Features of hyperandrogenism
Hirsutism
Acne
Alopecia
Clitoromegaly
Infertility
Recurrent pregnancy loss
25
Clinical Manifestations
Long term consequences
HTN
Type 2 DM
Cardiovascular disease
Dyslipidemia
26
Diagnostic evaluation
FSH LH
USG Prolactin
FBS
Testosterone
PCOS
Insulin DHEAS
Lipid profile
cortisol
SHBG TSH
27
Differential diagnosis
• Hypogonadotropic hypogonadism
• Hyperprolactinemia
• Hypothyroidism
• Hyperadrenalism
• - Cushing syndrome
• - Non classic congenital adrenal hyperplasia
• Androgen secreting tumors
• - Ovarian
• - Adrenal
• Androgenic alopecia
28
Approach
History
Menstrual history
smoking
History of infertility, recurrent miscarriages
hypertension, hyperandrogenism
29
Approach…
Examination
• General Examination
- B.P
- Breast examination – galactorrhea
- Thyroid examination
• Assessment of obesity
• BMI
• Waist hip ratio - > 0.85
• Waist circumference > 88 cm
30
Approach…
Assessment of acne:
Mild - < 10 papules on one side of the face
Moderate - > 10 papules and pustules on one
side or spread to shoulders
Severe – above plus deep infiltrates
31
Assessment of hirsutism
Ferryman – Gallwey score - >8
32
Approach…
Examination
• General Examination
34
Baseline investigations…
Assessment of pituitary and ovarian hormones
Normal PCOS
LH (D1-3) 2-10 IU/L ↑
FSH (D1-3) 2-8 IU/L N/↓
36
PCOS over the life span
Prepubertal Adolescence Reproductive age Postmenopausal
Premature
pubarche
Menstrual
problems
Acne, hirsutism
Infertility
Obesity
Insulin resistance
Type II diabetes
Hypertension
Cardiovascular disease
Endometrial cancer 37
Management
Obesity
Weight reduction
Life style modifications
Dietary modification
High protein, low carbohydrate
Small frequent meals
Education and counseling
38
Management…
Menstrual disturbances and hirsutism
Weight reduction
Combined oral contraceptive pills:
- Estrogen - SHBG
- Progestins
* Inhibit 5 reductase
* Androgen receptor antagonist
* Clearance of androgen
Ethinyl estradiol (30 mcg) with desogestrel (.15 mg)
low androgenic potential progestins (norgestimate, gestodene)
39
Management…
Menstrual disturbances
Progestins with anti-androgenic activity:
Cyproterone acetate
Mechanism:
↑ SHBG
Androgen receptor antagonist
Reduced androgen production
Inhibits 5 reductase activity
Antidiuretic action
40
Management …
Menstrual disturbances
Ethinyl estradiol 35 mcg + cyproterone acetate 2mg
Ethinyl estradiol 35 mcg + drosperinone 5mg
41
Management …
Hirsutism
Antiandrogens
Spironolactone - 25 - 100 mg/day
Flutamide - 500 mg/day
Finasteride - 5 mg/day
42
Management…
Insulin sensitizing agents
Metformin
Oral biguanide
↑ peripheral glucose uptake, ↓ hepatic glucose
production and ↑ insulin sensitivity
↓ androgen production
43
Management of infertility
Directed towards establishing ovulation
Weight loss :
- Loss of 5-10% - restores reproductive function in
55-100%.
- Insulin and androgen
- SHBG
- First line of treatment in obese women with
anovulatory infertility
44
Management of infertility…
Clomiphene citrate
• First line drug therapy for ovulation induction
• Ovulation rate – 80%, pregnancy rate – 40%
• 75% of pregnancies achieved within three
cycles
45
Management of infertility…
Metformin
Indications:
No response to clomiphene citrate
Obese patients who fail to lose weight
Lean patients with hyperinsulinemia
Dose: 1500 – 2250 mg / day (incremental
doses)
Side effects – GI disturbances, lactic acidosis
46
Management of infertility…
Metformin
Advantages
Regularizes cycles in 96% women
Reduces hyperandrogenism
Ovulation rate – 87%
Metformin + clomiphene citrate
Improved ovulation and pregnancy rates (76% vs.
46%)
47
Management of infertility…
Gonadotropin therapy
Following clomiphene failure
48
Management of infertility…
Aromatase inhibitors (letrozole)
Suppress estrogen production
Gonadotropin therapy
IVF
50
Laparoscopic ovarian drilling
Indications
Clomiphene resistant women with no
consistent ovulation.
Side effects with clomiphene
51
Pregnancy and PCOS
risk of miscarriage due to hypersecretion of
LH
• Risk of recurrent miscarriage 36 – 56% (24%
in general population)
risk of GDM – GTT to be done
• Metformin therapy to lower serum insulin may
have beneficial effect on miscarriage rate and
risk of GDM
• Increased risk of preeclampsia
52
Tender loving
care
53
Summary
The cause of PCOS is not known
Multifactorial and polygenic
Rotterdam's criteria
Oligovulation and / or anovulation
Clinical and / biochemical evidence of hyperandrogenism
Polycystic ovary on USG
Defect
Central
Ovary
Feedback axis
54
Summary…
Insulin: co-gonadotropin
Hyperinsulinemia and obesity – synergetic effect →
hyperandrogenemia and anovulation
PCOS – most common cause of anovulatory
infertility ( 75%)
Long term sequelae
Hypertension
Type 2 diabetes mellitus
Cardiovascular disease
Endometrial cancer
55
Summary …
Meticulous history and examination
Appropriate selection of investigations
PCOS – different problems in different age
groups
Symptomatic approach of management
Weight loss and life style modification – first
line management for menstrual problems,
infertility and to prevent long term sequelae
56
Summary …
Combined OCPs – first line drugs for
menstrual problems and hirsutism
Step wise approach to infertility
Increased risk of miscarriage, GDM and
preeclampsia
Long term sequelae – chance to detect them
at a younger age group
57