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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
