pcos(polycystic ovarian syndrome)

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Dr. Gurpreet Kaur

Polycystic ovary syndrome

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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 levelsDiminished FSHRaised LH

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HyperandrogenismClinical and biochemical parameters

Clinical Biochemical

Hirsutism Testosterone

Acne Free androgen index

Alopecia DHEAS

Clitoromegaly Androstenedione

17 alpha hydroxy

progesterone

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Ultrasonography

In 20 – 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…

HypothalamusPituitary

Ovary

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Pathophysiology Clinical features…

GnRH Pulsatility

LH FSH (or)

Hypothalamus & pituitary

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Pathophysiology

Raised E2 level causes negative feed back Decreased FSH But increased LH

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PathophysiologyClinical features…

Normal

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PathophysiologyClinical features…

ANOVULATION

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Pathophysiology & Clinical features

LH

Theca cell hyperplasia

Testosterone Androstenedione

SHBG

free estradiol

Estrogen

Free testosterone Endometrial Ca

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Pathophysiology & Clinical features

Free Testosterone

Hirsutism Clitoromegaly AlopeciaAcne

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Pathophysiology & Clinical features

Follicular growth

FSH

2-9 mm follicleNo ovulation

InfertilityMenstrual disturbances

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Associated Factors

Hyperinsulinemia

Obesity

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Hyperinsulinemia

Insulin resistance 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

HTNGlucose

intolerance DyslipidemiaCardiovascular

disorders

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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 deficiency

Inadequate follicle stimulation

LH Hyperandrogenemia

Follicle growth arrest

Insulin Hyperandrogenemia

Follicle growth arrest

Androgen Abnormal gonadotropin release & follicle growth arrest

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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

USG

LH

FBS

Prolactin

FSH

DHEAS

Testosterone

SHBG

Insulin

Lipid profile

PCOS

TSH

cortisol

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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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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

Approach

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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

TSH – 0.5 – 5 IU/L

Normal PCOS

LH (D1-3) 2-10 IU/L ↑

FSH (D1-3) 2-8 IU/L N / ↓

Prolactin 5.4 – 22.5 ng/dl

N / ↑

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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

Obesity

Insulin resistance

Infertility

Type II diabetesHypertension Cardiovascular diseaseEndometrial cancer

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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 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 - 17 spironolactone derivative Mechanism:

↑ SHBG Androgen receptor antagonist Reduced androgen production Inhibits 5 reductase activity Antidiuretic action

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Management …

Menstrual disturbancesEthinyl 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 …

HirsutismAntiandrogens

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 drillingIndications 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