PCOS

Dr. Mridula A BenjaminDept of Obs and Gyn

RIPAS Hospital, Brunei

Introduction

• Heterogenous problem• Commonest hormonal disturbance• Ovarian expression of metabolic syndrome• Long term consequences - strategies to screen• Stein Leventhal syndrome

ASRM/ ESHRE

• Rotterdam: May 2003• Two of three: Oligomenorrhoea & or anovulation Hyperandrogenism; Clinical/biochemical PCO on USG; 12 or more, 2-9mm,10cm3

• Single PCO• The follicle distribution & increase in stromal echogenecity &

volume should be omitted• Chronic anovulation & hyperandrogenism in absence of other

endocrine disorders• January issue of Fertility & Sterility J, 2004

Ultrasound Ultrasound

• Polycystic ovaries

– Bilateral – Multiple cysts– Cyst diam <2-9mm– Stroma increased

• Multicystic ovaries

– Bilateral– Multiple cysts– Cyst diam > 6-10 mm– Stroma not increased

Gross appearance of ovaries

• Enlarged bilaterally and have a smooth thickened avascular capsule

• On cut section, subcapsular follicles in various stages of atresia are seen

• Microscopically luteinizing theca cells are seen

The best biochemical markers of hyperandrogenism are free testosterone levels or free androgen index

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 levels

LH levels are elevated in 60% women with PCOSLH/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

Implications?? High miscarriage / low fertility

The chances of ovulation or pregnancy rates using CC or HMG are unaffected

•PCOS should be excluded from other disorders in which hirsutism and menstrual irregularities are prominentCongenital adrenal hyperplasiaCushing's syndrome Androgen-secreting tumors

•In oligo/anovulation: E2 & FSH to exclude hypogonadotrophic hypogonadism (central origin of ovarian dysfunction)

•Thyroid disorders in PCOS patients are not more common than in other young women, and TSH is unnecessary

•In hyperandrogenic females: Prolactin

Metabolic syndrome

3 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 110-126 &/or 2-h glucose 140-199 mg/dl

Prevalence

• PCO on ultrasound - 20%-33%• Oligomenorrhea - 4 – 21 %• Oligomenorrhea + hyperandrogenism - 3.5 – 9 %

Pathogenesis (etiology?)

• Hypersecretion of adrenal androgens?• Hypersecretion of ovarian androgens?• A genetic disorder with an autosomal dominant

mode of inheritance?• A multifactorial genetic disorder?

Cholesterol

Pregnenolone

Progesterone

17 OH-Pregnenolone

17 OH-Progesterone

DHEA

Androstenandion

17-20 Lyase

17 hydroxylaseTheca cell

Estrone

estradiol

Granulosa cell

FSH

LH

OVARIAN STEROIDOGENESIS

T

Obesity

Insulin

Free testosterone

SHBG IGF-1

5-alfa reductase activity is stimulated

IGF*** insulin like growth factor

Obesity and insulin resistance

• Diminished biological response to insulin• In both obese and non obese• In 40%• More in obese and oligomenorrhoeic• Euglycaemia at expense of hyperinsulinaemia• Obesity more of central -35-60%

Wt. increase

Insulin receptor disorder

Insulin increase

Free estradiolincrease

High LHLow FSH

Free testosteroneincrease

Androstenandione increase

SHBG decrease

atresia

Theca (IGF-I)

Endometrial cancer

Testosteroneincrease

Estroneincrease

hirsutism

IGFBP-I**** decrease

IGFBP*** insulin like growth factor binding protein

Presentation

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

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

Long term risks in PCOS

Definite • Type 2 diabetes(15%), IGT( 18-20%) • Dyslipidemia (Hypercholesterolemia with diminished HDL2 and

increased LDL)

• Endometrial cancer (OR 3.1 95% CI 1.1 -7.3)

Possible

• Hypertension• Cardiovascular disease• Gestational diabetes mellitus• Pregnancy-induced hypertension• Ovarian cancer

Unlikely

• Breast cancer

Long term consequences

Management

• Symptom oriented• Diet & exercise • Wt. loss• Improves both symptoms & endocrine profile• BMI >30kg/ m2

• Keep CHO content down, avoid fatty food• Obesity clinics

Contd

• Menstrual irregularities• OCP- Yasmin, Dianette• ET >10mm(oligo), >15mm(amen)-Withdrawal

bleed• Fails - Endometrial sampling

STEPWISE APPROACH FOR OVULATION INDUCTION IN PCOS (ACOG,2002)

1. Weight loss: If BMI >30 K/m2

2. Clomiphene citrate

3. CC + corticosteroids if DHES > 2ug/ml

4. CC + Metformin

5. Low dose FSH injection

6. Low dose FSH injection + Metformin

7. Ovarian drilling

8. IVF

Mx of Hirsutism

• Cosmetic• Medical- 6-7 months• Cyproterone acetate+ EE, Spironolactone• Reliable contraception• Flutamide & Finasteride - Rare

Reproductive Endocrinologist

• S.testosterone > 5nmol/L• Rapid onset hirsutism• IGT/ Type2 DM• Refractory symptoms• Amen. > 6 months• Subfertility

Guidelines (RCOG, May 2003)

• 1-Patients presenting with PCOS particularly if they are obese, should be offered measurement of fasting blood glucose and urine analysis for glycosuria. Abnormal results should be investigated by a glucose tolerance test

• Such patients are at increased risk of developing type II diabetes (Evidence level IIb[C])

• 2- Women diagnosed as having PCOS before pregnancy should be screened for gestational diabetes in early pregnancy

• Refer to specialized obstetric diabetic service if abnormalities detected (evidence level IIb[B])

Guidelines (RCOG, May 2003)

• 3-Measurement of fasting cholesterol, lipids and triglycerides should be offered to patients with PCOS, since early detection of abnormal levels might encourage improvement in diet and exercise (Evidence level III[C])

• 4- Olig- and amenorrhoeic women with PCOS may develop endometrial hyperplasia and later carcinoma. It is good practice to recommend treatment with progestogens to induce withdrawal bleed at least every 3-4 months (Evidence level IIa[B])

Guidelines (RCOG, May 2003)

• 5- Evidence has accumulated demonstrating safety and efficacy of insulin-sensitizing agents in the management of short-term complications of PCOS, particularly anovulation. Long-term use of these agents for avoidance of metabolic complications of PCOS cannot as yet be recommended (Evidence level IV[B])

• 6- No clear consensus regarding regular screening of women with PCOS for later development of diabetes and dyslipidemia

• Obese women with strong family history of cardiac disease or diabetes should be assessed regularly in a general practice or hospital outpatient setting. Local protocols should be developed and adapted (Evidence level IV[C])

Guidelines (RCOG, May 2003)

• Young women diagnosed with PCOS should be informed of the possible long-term risks to health that are associated with their condition. They should be advised regarding weight and exercise (Evidence level III[C])