•DR. RABI NARAYAN SATAPATHY•ASST.PROFESSOR•DEPT. OF OBST.& GYNAECOLOGY•SCB MEDICAL COLLEGE, CUTTACK•MOB-09861281510•EMAIL-drrabisatpathy@gmail.com

PCOS-PRACTICAL APPROACH TO DIAGNOSIS

• Dr. V.K.PODDAR

DGO, FICOG, MD (Gold Medalist)• CHAIRMAN, REPRODUCTIVE ENDOCRINOLOGY

COMMITTEE, FOGSI• CHAIRMAN, IMA-AMS(NORTH-WEST),

KOLKATA

• SENIOR VICE PRESIDENT, BOGS , KOLKATA• CONSULTANT- OBSTETRICIAN AND

GYNAECOLOGIST, ADVANCED MEDICAL RESEARCH INSTITUTE, KOLKATA.

Presentation

• Patients with PCOS present with various symptoms including the following:

• *Amenorrhea• *Oligomenorrhea• *Infertility• *Hirsutism• *Obesity• *Acne Vulgaris• *Asymptomatic

Physical Signs

• *Hirsutism• Patients may have excess body

hair in male distribution pattern and acne.

• *Obesity: approximately 50% of patients are obese

• *Acanthosis Nigricans• This is thought to be the result

of insulin resistance in these patients

Clinical features of 1557 patients with PCOS

Acanthosis nigricans 3.1%

Hirsutism 13.9%

Acne 31.1%

Infertility 24.8%

Menstrual cycle status

Regular 25.0%

Oligo. 51.5%

Amen. 23.0%

Balen et al. Hum Report 1995

Diagnosis• In the past (before 2003) Necessary Lab

Tests or sonar

• Recently ( after 2003)…clinically.

• PCOS could be defined when at least two of the following three features are present, after exclusion of other etiologies :

(i) Oligomenorrhea and or Anovulation

(ii) Clinical and/or biochemical Hyperandrogenism.

(iii) Polycystic ovaries (sonar).

Rotterdam , May Rotterdam , May 2003 Definition2003 Definition

Pitfalls Rotterdam Definition

1. doubts still exist regarding borderline groups of patients ,such as hirsute ovulatory Normoandrogenic women with PCO???.

2. Neglected the role of IR

• Chronic anovulation & hyperandrogenism in absence of other endocrine disorders

• January issue of Fertility & Sterility J, 2004

•3

• Polycystic ovaries (PCO), observed on ultrasound are a sign of PCOS and not by themselves diagnostic of the syndrome.

PCO & PCOS

Ultrasonic Criteria of PCOUltrasonic Criteria of PCO

• At least one of the following: 12 or more follicles measuring 2–9 mm in diameter, increased ovarian volume (>10 cm3).

• If there is a follicle >10 mm in diameter, the scan should be repeated at a time of ovarian quiescence in order to calculate volume and area.

• The presence of a single PCO is sufficient to provide the diagnosis.

• The distribution of follicles and a description of the stroma are not required for diagnosis.

Imaging studies

• However, there is significant intra-observer and inter-observer variability and ultrasonography alone may not be a reliable method of diagnosis or excluding PCOS

What is The significance of What is The significance of polycystic-appearing ovaries versus polycystic-appearing ovaries versus normal appearing ovaries in patients normal appearing ovaries in patients

with PCOS??with PCOS??

The presence of polycystic-appearing ovaries correlates with the presence of

insulin resistance (Richard J 2002).

USG- Only Evidence of PCO PREDICTS

• *Fertility outcome with specific regime . *The risk of OHSS. The presence of many antral follicles may assist to decide collection of immature oocytes for in vitro maturation. *PCO with increased vol.& more than12-15 follicles(>2-9mm) are less likely to respond to CC singly. They may require gonadotrophin ,ovarian drilling or IVF.

Prevalence • About 20% of reproductive age women demonstrate

the ultrasound picture of polycystic ovaries. Oligomenorrhia-4-21% AND oligomenorrhia+hyperandrogenism-3.5-9%

• About 5- 10 % have clinical or biochemical signs of anovulation and androgen excess (dunaif 1995 , Norman etal 2002)

• Estimation of 'true' prevalence PCOS must be made with caution since there is no overall consensus on the diagnostic criteria that must be satisfied to make a diagnosis (Ledger and Clark 2003).

Laboratory studies

• Increased androgen levels in blood (testosterone and androstendione)

• Increased LH, exaggerated surge• Increased fasting insulin• Increased prolactin• Increased estradiol and estrone levels

• Decreased SHBG levels

•LH levels are elevated in 10% women with PCOS.LH/FSH ratios can be elevated in up to 95% of women with PCOS if women with recent ovulation are excluded. •LH levels are not necessary for clinical diagnosis of PCOS.

1.The clinical implications of this abnormality are unclear. Although some research has suggested lower fertility rates and higher miscarriage rates for women with high LH levels, other studies have contradicted this data. 2. LH levels or the administration of exogenous LH do not affect much in the chances of ovulation or pregnancy rates using CC or HMG.

Clinical

Biochemical

Hirsutism is the best clinical marker of hyperandrogenism. Acne is a more variable marker of hyperandrogenism.

Hirsutism

• Defined as the growth of pigmented coarse hair in androgen- dependent areas such as the face, chest, back, and lower abdomen • The most common manifestations of hyperandrogenism & PCOS

The Ferriman- Gallway (FG) scale

• To assess the degree of hirsutism in 11 areas of the body• Ranges from 0 – 44 & higher the score, more severe hirsutism • A typical score for someone with hirsutism is between 8 and 29 • Though subjective, it allows the physician to monitor the improvement in hair growth.

•The best biochemical markers of hyperandrogenism are free testosterone levels or free testosterone index. However, not all patients with PCOS have elevated circulating androgen levels.•Routine measurement of androstenedione cannot be recommended. •DHEAS is raised in small fraction of patient with PCOS .

DHEAS

• Assessment ascertains Adernal Androgen. In elevated DHEAS treatment with Insulin sensitizing agent more rewarding than Dexamathsone. As this Androgen is due to Hyperinsulinemia & Long contiued use of Dexamathasone causes adverse side effects.

• Women with regular cycles but with hyperandrogenism & PCO may have the PCOS.

•Women without hyperandrogenism, but with PCO & ovarian dysfunction may have PCOS.

•PCOS should be excluded from other disorders in which hirsutism and menstrual irregularities are prominent, such as Congenital adrenal hyperplasia, Cushing's syndrome, and Androgen-secreting tumors. •In oilgo/anovulation: E2 & FSH to exclude hypogonadotrophic hypogonadism (central origin of ovarian dysfunction)

• Late onset congenital adrenal hyperplasiaDHEAS > 18mmol/l17 OH Prog > 1 mmol/l

• Ovarian + adrenal androgen secreting tumoursV. high testosterone > 1mmol/l

• Cushings Syndrome- Dexamethsone suppression test- 24 hours urinary cortisol- DHEAS > 13 mmol/l

Anovulation & HyperandrogenismAnovulation & Hyperandrogenism

What is DDWhat is DD??

•In hyperandrogenic females: prolactin to exclude hyperprolactinaemia. •Thyroid disorders in PCOS patients are not more common than in other young women- TSH

Studies indicate that insulin resistance may be an important marker of a poor outcome and of patients at high risk for ovarian hyperstimulation.

How IR Can Be Assessed ??

• OGTT ( the best ).

• Fasting glucose (mmol/ L) to fasting insulin (mul/L) ( Hyperinsulinemic – euglycemic).Normal Value -< 4.5

• Clamp technique ( Gold standard) , too expensive time consuming

Insulin resistance: decreased insulin-mediated glucose utilization.occur in up to 50% of patients with PCOS, so the consensus group recommends it for PCOS patients. 1. Evaluation for metabolic syndrome2. Oral glucose tolerance tests

Metabolic syndrome

3 of 5 of the following

1. Waist circumference >88cm

2. Triglycerides >150 mg/dl

3. HDL <50 mg/dl

4. Blood pressure > 130/85

5. Fasting Blood glucose 110-121 &/or 2-h glucose 140-199 mg/dl.

2) PCOS Without IR:What are characteristics?

• Lean.• Euinsulinemic/ Euglycemic• Enhanced Ovarian Sensitivity

to insulin (although no

Hyperinsulinemia).

• PCOS + IR ( 50-70 % ).• PCOS without IR (Legro etal 2004).

Phenotypes According to IR

1) IR Phenotype of PCOS: What are the characteristics ? Obese ( may be lean) Acanthosis Nigerians. Hirsutism. Resistance to CC,

• The central paradox regarding the role of insulin in PCOS:– Is the high ovarian response to insulin,

as opposed by the the whole body resistance.

The Central Player ( Insulin The Central Player ( Insulin Resistance )Resistance )

Obesity plays a central role in the development of PCOS leading to

hyperinsulinemia in susceptible individuals.

This hyperinsulinemia may alter androgen metabolism via a variety of mechanisms, the net result of which is

hyperandrogenism.

Elevated DHEASElevated DHEAS Elevated AndrogensElevated Androgens

PancreasPancreasPancreasPancreas

Insulin Receptor Dysfunction

Hyperinsulinaemia

LHRH

HypothalamusHypothalamusHypothalamusHypothalamus

PituitaryPituitaryPituitaryPituitary

AdrenalAdrenalAdrenalAdrenal StromaStromaStromaStroma FollicleFollicleFollicleFollicle

↑ LH FSH

LiverLiverLiverLiver

Reduced SHBGReduced SHBG

Free androgens Free androgens

Hyperinsulinaemia & Hyperandrogenaemia

• Patients with anovulatory PCOS and normal menses seemed to be leaner and have lower insulin and gonadotropin levels than those with irregular menses (Carmina 2000).

Anovulation + PCO + Normoandrogenemia

What is The difference bet. Regular and irregular menst ?

IR

• Treatment of PCOS should be directed towards causative rather than symptomatic especially if IR is proved as the central player !!!!

•IR

1) Symptomatic PCOS : What is the most important

parameter ?• Increased BMI is associated with increased severity of the PCOS.

• No differences in basic , clinical and biochemical parameters between eumenorrhoic and oligomenorrhoic PCOS (Vanky etal 2004).

2) Asymptomatic PCOS• Very lean• Athletic women• May be underweight.• This may mask the

PCOS.

The less symptoms, the better response to

medication and treatment.

Asymptomatic PCO (Ovulatory + Normoandrogenic )

• There is significantly lower levels of progesterone in the early Luteal phase.

• This may contribute to the delay in conception in these patients.

• May be the starting cascade of Pcos!!!!!!!!!

Is Fertility Normal in patients Is Fertility Normal in patients With Ovulatory PCOS? With Ovulatory PCOS?

• These patients should be regarded as fertile but many studies have shown that women with ovulatory PCOS have luteal phase defect (Joseph H etal 2002).

PCOS, starts in adolescence.

But

Unfortunately, not always

diagnosed at that age.

At The End

We Can Say That PCOS is A never – ended story.