Polycystic Ovary Syndrome: Current Views

Presented by:Dr. Zuhayer AhmedHonorary Medical Officer,Dept. of Endocrinology,Dhaka Medical College Hospital,Dhaka

There is no universally accepted definition for PCOS!!

A complex endocrine disorder affecting women of childbearing age characterized by increased androgen production and ovulatorydysfunction.

Commonest cause of anovulatory infertility and hirsutism.

First described by American gynecologists Irving F. Stein, Sr. and Michael L. Leventhal in 1935.

“Syndrome O” Ovarian confusion

Ovulation disruption

Over-nourishment

Overproduction of insulin

20-33% of all reproductive age group have PCO

5-10% of all reproductive age group have PCOS

87% present with oligomenorrhea

26% present with amenorrhea

50% present with infertility

50% with recurrent miscarriage

Exactly Unknown

Genetics:◦ Autosomal Dominant

Environmental Effect

Neuroendorine derangement:◦ Increased LH relative to FSH

Hyperinsulinemia:◦ Defect in insulin action or secretion

Androgen Excess: Most agree that the ovary, rather than

the adrenal is the principal source

Terminal hair in 9 androgen sensitive body areas

Determined by a visual score-◦ Modified Ferriman-Gallwey Score

Different from hypertrichosis

Amenorrhea

Oligomenorrhea

Premenstrual DysphoricSyndrome

Pelvic Pain

Subfertility

NIH (1990) Rotterdam (2003)* AES (2006)

1. MenstrualIrregularity

1. Menstrual Irregularity 1. Menstrual Irregularity+/- USG-PCO

2. Hyperandrgenism 2. Hyperandrogenism 2. Hyperandrogenism

3. Exclusion of other etiologies

3. USG-Polycystic Ovary**

3. Exclusion of other etiologies

*2 out of 3 criteria**Exclusion of other etiologies

Other etiologies to be excluded:◦Hypothyroidism

◦Hyperprolactinemia

◦Non-classical congenital adrenal hyperplasia

◦Cushing Syndrome

◦Acromegaly

◦Androgen secreting tumors

◦Other causes of amenorrhea

Biochemical Evidence:◦ S. Testosterone

◦ LH/FSH ratio

To exclude other etiologies:◦ S. Prolactin

◦ 24 hours urinary free Cortisol

◦OGTT

◦ S. TSH

◦ 17-hydroxyprogesterone

12 or more follicles in each ovary measuring 2-9 mm in diameter +/-increased ovarian volume (>10 ml)

[Rotterdam criteria]

Diet:

◦ Avoid processed & fried foods, simple carbs like rice, potatoes, white sugar & pasta.

◦ Take more complex carbs like oatmeal

◦ Fresh fruits & vegetables, whole grains and lean proteins.

Regular physical exercise:

◦ Brisk walking for at least 30-40 minutes per day

For Hirsutism:◦ Shaving

◦ Bleaching

◦ Waxing

◦ Electrolysis

◦ Laser treatment

For Hirsutism:◦ Eflornithine Cream:

Should be discontinued if no improvement after 4 months of use

Insulin Sensitizers:

◦Metformin

500 mg three times daily

◦ Pioglitazone

Androgen Receptor AntagonistsCyproterone Acetate 2, 50 or 100 mg on days

1-11 of 28-day cycle with Ethinylestradiol 30

microgram on days 1-21

Spironolactone 100-200 mg daily

Flutamide No recommended dose

5- reductase inhibitor:◦ Finasteride: 5 mg daily

Hormonal contraceptives:◦ Combined with Cyproterone acetate◦ Conventional oestrogen containing

contraceptives: Ethinyl estradiol Non-androgenic Progesterone (Desogestrel,

drospirenone)

Reverse Circadian Rhythm:

Prednisolone:

2.5 mg in the morning & 5 mg at night

Suppresses ACTH production

Clomiphene Citrate:

◦ First line therapy for infertility

◦ 50-100 mg daily on days 2-6 of the cycle

◦ Recommended not to use for more than 6 cycles

In one randomized controlled clinical trial, 626 infertile women with PCOS were randomized to receive clomifene, metformin or combination therapy. After 6 months, the live birth rates were 22.5%, 7.2% and 26.8% respectively. Multiple births occurred in 6% of women receiving clomifene and none of those receiving metformin.

“I had all the side effects…dizziness, panic attacks, blurred vision…I was determined to get the thing done. It was awful, but just thought ‘keep going’.”

Jools Oliver

Depression

Anxiety Disorder

Screen for long term complications:

◦ Endometrial cancer

◦ Mood disorders

◦ Obstructive sleep apnea

◦ Diabetes Mellitus

◦ Cardio-vascular disease

Diagnosis:◦ 3 recommendations

Associated Co-morbidities:◦ 12 recommendations

Treatment of PCOS:◦ 12 recommendations

1.3 Diagnosis in perimenopauseand menopause:

Long term history of oligomenorrhea& hyperandrogenism

Polycystic ovary: less likely

Documenting cutaneous manifestations:

◦ Hirsutism (modified Ferriman-Gallwey score)

◦ Acne

◦ Androgenic Alopecia (Ludwig’s score)

◦ Acanthosis nigricans

◦ Skin tags

Screening ovulatory status (even in eumenorrheics):

◦ Increased risk of anovulation and infertility

◦ Menstrual history

◦ Midluteal S. Progesterone

Exclude other causes of infertility:

Obesity

Male factor infertility

Tubal occlusion

Preconceptual assessment:◦ Increased risk of pregnancy complications

(GDM, preterm delivery, pre-eclampsia)

◦ BMI

◦ BP

◦ OGTT

No routine USG screening for endometrial thickness in PCOS: Poor diagnostic accuracy

Screen and manage depression & anxiety

Screen & manage Obstructive Sleep Apnea: Polysomnography

Awareness about possibility of NAFLD and NASH (No screening)

Screen for IGT and T2DM:

◦OGTT or HbA1c

◦ Re-screening every 3-5 years

At Risk High Risk

Obesity

Cigarette smoking

Hypertension

Dyslipidemia

Subclinical vascular disease

Impaired glucose tolerance

Family history of premature CVD

Metabolic syndrome T2DM Overt vascular or

renal disease CVD Obstructive Sleep

Apnea

Hormonal Contraceptives:

◦ First line for menstrual abnormalities and hirsutism/acne of PCOS

◦ Screen for contraindications of HCs

Management of overweight:

◦ Exercise:

30 mins of moderate to vigorous exercise daily

◦Calorie restricted diet

◦Metformin not recommended

Metformin:

◦ NOT first line for cutaneous manifestations, obesity or preventing pregnancy complications

◦ To be used in T2DM or IGT

◦ Menstrual irregularities present and HCs are contraindicated

◦ Adjuvant for infertility to prevent Ovarian hyperstimulation syndrome (OHSS) in women with PCOS undergoing IVF

Insulin sensitizers e.g. inositols or thiazolidinedions NOT recommended

Ovulation inducers:◦Clomiphene citrate

◦ Letrozole

Statins only recommended if indications for statins present

NO TREATMENT DURATION DETERMINED

Vocal of Spice Girl

Has four children

“The Diary of an Honest Mom”

Her struggle against the subfertility

Retaining calories and storing adipose tissue may help in famine!!

The gene responsible would be deleted from the gene pool

Pregnancy issues!! No need for ECP!!

Less likely to develop osteopenia, osteoporosis-less fractures!!