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Polycystic ovary

syndrome

Dr. Gurpreet Kaur

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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

Polycystic ovary is sign not a disease

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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

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Oligovulation and anovulation

Anovulatory cycles
Lack of cyclical progesterone
Irregular uterine bleeding

Raised estradiol levels


Diminished FSH
Raised LH

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Hyperandrogenism
Clinical and biochemical parameters
Clinical Biochemical
Hirsutism ↑ Testosterone
Acne ↑ Free androgen index
Alopecia ↑ DHEAS
Clitoromegaly ↑ Androstenedione
17 alpha hydroxy
progesterone
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Ultrasonography
 In20 – 25% women without PCOS – USG
features of polycystic ovary are seen

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Pathophysiology
Clinical features…
Cause

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Pathophysiology

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Pathophysiology
Clinical features…
Hypothalamus
Pituitary

Ovary

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Pathophysiology
Clinical features…
Hypothalamus & pituitary

GnRH Pulsatility⇑

LH ⇑ FSH (⇓or⇔)

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Pathophysiology

 Raised E2 level causes negative feed back


 Decreased FSH

 But increased LH

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Pathophysiology
Clinical features…

Normal

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Pathophysiology
Clinical features…

ANOVULATION

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Pathophysiology & Clinical features

⇑LH

Theca cell hyperplasia

⇑Testosterone ⇑Androstenedione

⇓SHBG Estrogen

⇑free estradiol ⇑Free testosterone


Endometrial Ca
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Pathophysiology & Clinical features

Free Testosterone⇑

Hirsutism Acne Clitoromegaly Alopecia

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Pathophysiology & Clinical
features
↔↓ FSH

Follicular growth

2-9 mm follicle Infertility


No ovulation Menstrual disturbances

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Associated Factors

 Hyperinsulinemia

 Obesity

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Hyperinsulinemia
 Insulinresistance occur irrespective of BMI
 Obesity and hyperinsulinemia have
synergetic effect

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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

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Obesity
Metabolic Syndrome X
 Abdominal obesity > 88 cm

 Triglycerides ≥ 150 mg/dl

 HDL < 50 mg/dl

 B.P ≥ 130/85 mm of Hg

 Abnormal GTT

Three of the above have to be present for


diagnosis

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Metabolic syndrome X

Insulin resistance syndrome

Cardiovascular Glucose
HTN disorders Dyslipidemia
intolerance

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Infertility and PCOS
 PCOS is the cause of anovulatory infertility in 75%
Factors implicated in chronic anovulation

Factor Abnormality Consequence


FSH Relative Inadequate follicle stimulation
deficiency
LH ↑↑ Hyperandrogenemia
Follicle growth arrest
Insulin ↑↑ Hyperandrogenemia
Follicle growth arrest
Androgen ↑ ↑ Abnormal gonadotropin
release & follicle growth
arrest 22
Early pregnancy loss and PCOS

 ⇑LH
 Hyperandrogenism
 Hyperinsulinemia
 Endometrial non receptivity
 Obesity

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Clinical Manifestations

Menstrual disturbances : 70% of cases


- Oligomenorrhoea – 47%
- Amenorrhea – 19.2%
- Normal cycles – 29.7%
- Polymenorrhoea – 2.7%
- Menorrhagia – 1.4%

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Clinical Manifestations
Features of hyperandrogenism
 Hirsutism

 Acne

 Alopecia

 Clitoromegaly

Infertility
Recurrent pregnancy loss

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Clinical Manifestations
Long term consequences
 HTN

 Type 2 DM

 Cardiovascular disease

 Dyslipidemia

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Diagnostic evaluation
FSH LH
USG Prolactin

FBS Testosterone
PCOS

Insulin DHEAS

Lipid profile
cortisol
SHBG TSH

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Differential diagnosis
• Hypogonadotropic hypogonadism
• Hyperprolactinemia
• Hypothyroidism
• Hyperadrenalism
• - Cushing syndrome
• - Non classic congenital adrenal hyperplasia
• Androgen secreting tumors
• - Ovarian
• - Adrenal
• Androgenic alopecia

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Approach
History
 Menstrual history

 H/o androgenic symptoms

 Body weight changes

 Life style – eating and exercise, alcohol,

smoking
 History of infertility, recurrent miscarriages

 Family history of PCOS, diabetes, obesity,

hypertension, hyperandrogenism

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Approach…
Examination
• General Examination

- B.P
- Breast examination – galactorrhea
- Thyroid examination
• Assessment of obesity
• BMI
• Waist hip ratio - > 0.85
• Waist circumference > 88 cm

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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

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Assessment of hirsutism
Ferryman – Gallwey score - >8

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Approach…
Examination
• General Examination

- Abdominal striae – Cushing’s syndrome


- Virilization : Frontal balding, deepening of voice
broadening of shoulders, ↓ breast size
• Pelvic examination
- Clitoral inspection
- Loss of vaginal rugae
- Bimanual examination : ovarian enlargement

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Investigations
Baseline investigation
Ultrasonography - Rotterdam criteria
 Follicles > 12 in number, size: 2 – 9 mm
 Ovarian volume > 10 cm3
 Stromal hyperechogenicity
 Presence of findings in single ovary sufficient
 Endometrial thickness
 Done in early follicular phase ( D1 – D3)
 TVS – better resolution ~100% detection, TAS – 30% detection

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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/↓

Prolactin 5.4 – 22.5 N/↑


ng/dl

TSH – 0.5 – 5 IU/L


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Investigations…
Assessment of metabolic function
 Fasting glucose / insulin - < 4.5 – insulin resistance
 Glucose tolerance test: BMI > 30, ( > 25 in south
asian women)
 Lipid profile

RCOG guidelines (2003)

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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

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Management…
Menstrual disturbances and hirsutism
 Weight reduction
 Combined oral contraceptive pills:
- Estrogen - ↑SHBG
- Progestins
* Inhibit 5 α reductase
* Androgen receptor antagonist
* ↑ Clearance of androgen
Ethinyl estradiol (30 mcg) with desogestrel (.15 mg)
low androgenic potential progestins (norgestimate, gestodene)

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Management…
Menstrual disturbances
Progestins with anti-androgenic activity:
 Cyproterone acetate

 Drosperinone - 17α spironolactone derivative

 Mechanism:
 ↑ SHBG
 Androgen receptor antagonist
 Reduced androgen production
 Inhibits 5 α reductase activity
 Antidiuretic action

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Management …
Menstrual disturbances
Ethinyl estradiol 35 mcg + cyproterone acetate 2mg
Ethinyl estradiol 35 mcg + drosperinone 5mg

Progestin only therapy


 Cyclical progesterone therapy
 Depot progesterone injections
 Progesterone releasing IUCD (Mirena)

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Management …
Hirsutism
Antiandrogens
Spironolactone - 25 - 100 mg/day
Flutamide - 500 mg/day
Finasteride - 5 mg/day

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Management…
Insulin sensitizing agents

Metformin
 Oral biguanide
 ↑ peripheral glucose uptake, ↓ hepatic glucose
production and ↑ insulin sensitivity
 ↓ androgen production

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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

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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

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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

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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%)

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Management of infertility…
Gonadotropin therapy
 Following clomiphene failure

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Management of infertility…
Aromatase inhibitors (letrozole)
 Suppress estrogen production

 Does not have anti-estrogenic action on endometrium

 Useful in
 Clomifene resistant cases
 Adjunct to FSH in poor responders
 Possible teratogenicity

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Infertility
Step-wise approach
 Weight loss

 Ovulation induction with clomiphene citrate

 Metformin as single agent

 Metformin with clomiphene citrate

 Gonadotropin therapy

 Insulin sensitizers with gonadotropin therapy

 IVF

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Laparoscopic ovarian drilling
Indications
 Clomiphene resistant women with no
consistent ovulation.
 Side effects with clomiphene

 Failed gonadotropin treatment

 Women with OHSS with clomiphene citrate or


gonadotropins

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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

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Tender
loving care

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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

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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

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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

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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

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