Polycystic Ovary Syndrome Jamal Zaidi Consultant Obstetrician & Gynaecologist East Sussex Healthcare NHS Trust.

Polycystic Ovary Syndrome

Jamal Zaidi

Consultant Obstetrician & GynaecologistEast Sussex Healthcare NHS Trust

Objectives

• Definition & Prevalence• Pathogenesis• Diagnosis• Clinical Features• Management• Long term consequences

DefinitionASRM/ ESHRE

• Rotterdam: May 2003• Two of three: Oligomenorrhoea & or anovulation Hyperandrogenism; Clinical/biochemical PCO on USG; 12 or more follicles in each ovary, 2-

9mm,and/ or increased ovarian volume to over 10cm3

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

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

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

Ultrasound Ultrasound

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

Prevalence

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

• PCOS – approx 18% (community-based prevalence study based on Rotterdam criteria). Importantly, 70% of women in this recent study were undiagnosed

Pathogenesis

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

mode of inheritance?• A multifactorial genetic disorder?

Obesity

Insulin

Free testosterone

SHBG IGF-1

5-alfa reductase activity is stimulated

IGF*** insulin like growth factor

Hyperinsulinaemia

↑Pulse Freq

↑Thecal cell & adrenal androgens

↑Free IGF-1

Hepatic SHBG production

LH production FSH production

IGF-BP-1; insulin growth factor binding protein: IGF-1; insulin growth factor 1: SHBG; Sex hormone binding globulin: LH; Luteinising Hormone: FSH; Follicle Stimulating Hormone.

-

-

-

+

+

+

+

+

+

+

↑ Oestrogens

↑ Free testosterone

↑Adipose tissue leptin

Hepatic IGF-BP-1 production

Insulin Resistance

AtresiaHirsutism

Diagnosis

History Taking

• Menarche

• Menstrual pattern

• Weight issues

• Hirsutism

• Other aspects of gynae history

The best biochemical markers of hyperandrogenism are Increased free testosterone levels or free androgen index;Reduced SHBG levels

Not all patients with PCOS have elevated circulating androgen levels

DHEAS is raised in small fraction of patient with PCOS levels (measured to exclude adrenal causes)

Diagnosis

Biochemical tests

DiagnosisBiochemical Tests

•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

• May have increased Prolactin levels

• Increased oestradiol/oestrone levels

• Normal TFTs

• Increased fasting insulin

•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)

Diagnosis

Pelvic Ultrasound

Small ovarian follicles; result of disturbed ovarian function

In PCOS, there is a so called "follicular arrest", i.e., several follicles develop to a size of 5–7 mm, but not further.

According to the Rotterdam criteria, 12 or more small follicles should be seen in an ovary on ultrasound examination. The follicles may be oriented in the periphery, giving the appearance of a ‘string of pearls’

Clinical Features

• Amenorrhoea• Oligomenorrhoea• Irregular periods• Infertility• Hirsutism• Obesity• Acne Vulgaris• Asymptomatic

Management

• Symptom control• Diet & exercise • Wt. loss• Improves both symptoms & endocrine profile• Aim for BMI < 30kg/ m2

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

Contd

Menstrual irregularities• OCP- COCP, Yasmin, Dianette• Withdrawal bleed – regular bleed with

progestagen• Consider Endometrial sampling

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

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

2. Clomiphene citrate

3. CC +/- Metformin

4. Low dose step up protocol - FSH injection

5. Ovarian drilling

8. IVF

Mx of Hirsutism

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

Reproductive Endocrinologist /Gynaecologist

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

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

Unlikely

• Breast cancer

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])

Thank you