Polycystic ovarian syndrome

Amila Weerasinghe21st Batch

Faculty of Medical SciencesUniversity of Sri Jayewardenepura

Sri Lanka

05/04/2016

Objectives

1. Introduction

2. Aetiology

3. Clinical features

4. Diagnosis

5. Management

6. Outcomes

1. Introduction• A syndrome of ovarian dysfunction

withcardinal features of hyperandrogenismpolycystic ovary morphology

• Often complicated by chronic anovulatory infertility

• Clinical manifestations include oligomenorrhoea, hirsutism and acne

• Many women are obese and have a higher prevalence of

impaired glucose tolerance, type 2 diabetes and sleep apnoea

• They exhibit an adverse cardiovascular risk profile.

• Cardiometabolic syndrome as suggested by a

higher reported incidence of ,

hypertension

dyslipidaemia

visceral obesity

insulin resistance

hyperinsulinaemia

• Prevalence - 5 – 10 % of women of reproductive age

• The commonest cause for anovulation (80%)

• USS evidence of polycystic ovaries in 20-30 % of women

• The most common endocrine disorder in women

High risk groups

• Women with oligo ovulatory infertility 

• Obesity and/or insulin resistance

• Type 1 , type 2 or gestational diabetes mellitus

• A history of premature adrenarche

• First-degree relatives with PCOS

• Women using antiepileptic drugs (valproate)

2. Aetiology

• Not fully known• No gene or specific environmental substance has been identified.• Genetic studies showed a link between PCOS and

metabolic disturbances such as disordered insulin metabolism.

• Hence it may be a manifestation of a complex genetic disorder.

• Selective insulin resistance may be central to the aetiology of PCOS.

• Compensatory hyperinsulinaemia• Decreased levels of serum hormone binding

globulin (SHBG)• Trophic stimulus to androgen production in the

adrenals and ovaries• Direct effect on the hypothalamus causing

abnormally stimulated appetite and increased gonadotropin secretion

• Hypersecretion of LH

Stimulation of androgen secretion from ovarian thecal cells

• Elevated LH : FSH ratio

3.Clinical features

• Oligomenorrhoea / amenorrhoea - 75%• Hirsutism • Subfertility 75%• Obesity 40%• Recurrent miscarriage 50 – 60%• Acanthosis nigricans • Asymptomatic

4.Diagnosis 2 out of 3 features of Rotterdam criteria

• Amenorrhoea/oligomenorrhoea (cycle >42 days)

• Clinical or biochemical hyperandrogenism

( acne, hirsutism,alopecia )

• Polycystic ovaries on ultrasound( 8 or more subcapsular follicular cysts <10mm in diameter and increased ovarian stroma)

USS • Bilateral enlargement of the ovaries > 8.0 cm. Increased ovarian volume ( >10ml ).• Thickened tunica albugenea• Multiple small cysts (12 foliclles or lesser) of

0.2-0.9 cms in each ovary• Absence of dominant follicle• Thickened stroma (hyperthecosis)• Resting or follicular endometrium

Laboratory investigations:

• Demonstration of biochemical hyperandrogenaemia.– Total testosterone (>200ng/dL)/ Free testosterone > 2.2pg/mL.

• S. Estradiol and FSH estimations.– Exclude hypogonadotropic hypogonadism ( E2, FSH).– Exclude premature ovarian failure ( E2, FSH).

• S. Dehydroepiandrosterone sulfate.– Not of value if S. Testosterone is normal– Values > 430μg/dL significant. It is indicative

of adrenal source of androgens.– Levels > 700 μg/mL suggestive of androgen

producing adrenal tumour.• 24 hours urinary cortisol– Cortisil < 50 μg/24 hours– Exclude Cushing’s syndrome if patient is

hypertensive.

Exclusion of other causes of hyperandrogenism.

– Estimation of TSH to exclude thyroid dysfunction

– Estimation of serum prolactin to exclude

hyperprolactinemia

– Estimation of 17α hydroxyprogesterone.

Non classical congenital adrenal hyperplasia caused by

21-hydoxylase deficiency.

– Consider screening for Cushing’s syndrome,

and

– Rare conditions like acromegaly.

– Evaluation for metabolic syndrome X.

5. Management

Treatment goals of polycystic ovary syndrome:

– Prevent endometrial hyperplasia, atypia/ cancer

– Restore normal ovulation / fertility

– Restore normal menstruation

– Correct hirsutism

Aspects of management

1. Lifestyle modification2. Improving menstrual regularity3. Controlling symptoms of hyperandrogenism4. Subfertility5. Insulin sensitizers6. Psychological issues

1.Lifestyle modification

• Weight reduction through exercise and diet – the most important step in managing overweight women.

• Even a modest weight loss (5%) can improve symptoms.

• Effective in restoring ovulatory cycles and achieving pregnancy.

2. Improving menstrual regularity

• Weight loss• Combine oral contraceptive pills (COCP)

inhibits LHReduces circulating androgensincreases circulating SHBG

Low dose combination pill containing low dose of synthetic estrogen in combination with a low-androgenic progestin

• Metformin Benificial in patients with hyperinsulinaemia

and CVS risk factors.Improves peripheral insulin sensitivity;

improve ovulation rates improve glucose tolerance increased SHBG leading to reduced

bioavailability of androgens

3. Controlling symptoms of hyperandrogenism

• Mainly hirsutism

1st line treatment

Weight reductionCOCPMedroxyprogesterone acetate

2nd line treatment

SpironolactoneCyproterone acetateFinasterideFlutamideEflornithine hydrochlorideGnRH agonists

Last resort

Ketoconazole

Cosmetic approaches

PermenentLaserElectrolysis

Non-permanentLocal chemical depilatoriesBleachingWaxingTweezingMechanical epilators

4. Subfertility

• Weight loss• Ovulation induction with antioestrogens or

gonadotrophinsClomiphene citrateIs a selective estrogen receptor modulator1st line treatment in women with PCOS and anovulatory infertilityOvulation rate 70-80 %Pregnancy rate 30-40 % over 6 cycles

• Laparoscopic ovarian diathermy

Effective in patients who are resistant to clomiphine.

• In vitro fertilization ( IVF ) when ovulation can’t be achieved; or doesn’t

succeed in pregnancy.

5. Insulin sensitizers

Metformin

• Metformin combined with clomiphene citrate increases ovulation and pregnancy rates.

• No significant increase in birth rate.• No significant improvement in acne or

hirsutism.• Lowers androgen levels.

6. Psychological issues

• Symptoms can be distressing and resulting lower self esteem.

• Holistic approach

Definite / common consequences of PCOS

• Insulin resistance: Type-II diabetes

• Endometrial hyperplasia / atypia

• Gestational diabetes

• Sleep apnoea

Possible consequences of PCOS

• Hypertension

• Coronary heart disease

• Dyslipidemia

• ? Risk of ovarian cancer

• ? Risk of abortion

Summary