Polycystic Ovarian Syndrome

Anna Lissa J. Bernadas, M.D., F.P.O.G.S

Irving F. Stein
Michael L. Leventhal
in 1935

Amenorrhea
Hirsutism
Obesity
Enlarged ovaries
Classic definition of PCOS(2/3)

Anovulation
(irregular periods)

Hyperandrogenism
(hirsutism or elevated androgen)

Polycystic ovaries on UTZ

Ovarian morphology

Rotterdam criteria:

Presence of 12 or more
follicles in either ovary
measuring 2-9 mm in
diameter and or increased
ovarian volume ( > 10 cm3)
ESHRE/ASRM-PCOSConsensus Workshop
Group 2004
PHENOTYPE
PHENOTYPE A Hyperandrogenism
Chronic anovulation
PCO on US in ovulatory women

PHENOTYPE B Hyperandrogenism
Chronic anovulation
PHENOTYPE C Hyperandrogenism
PCO on US in ovulatory women

PHENOTYPE D Absence of hyperandrogenism

Irregular cycles (Chronic anovulation) and
PCO on US
Ovarian Morphology

Christ criteria
Ovarian Morphology
POLYCYSTIC APPEARING OVARIES (PAO)
*10-25% of normal reproductive age group may have polycystic ovaries
found on UTZ.
* The ovaries have been called polycystic-appearing ovaries
Ovarian Morphology

No signs and
symptoms of PCOS
but have PCO on
US

10-25% of normal
women have
PCOM
There is increased GnRH pulse amplitude resulting in elevated levels of LH. The high LH results to increase
production of androgen and estradiol. The increased estradiol may stimulate increased GNRH pulsatility and
produce elevated LH and anovulation. INSULIN acts with LH to enhance androgen production.
INSULIN suppresses SHBG resulting in increased free testosterone.
What is the main mechanism responsible for the
development of PCOS ?

Peripheral insulin resistance

↓
Hyperinsulinemia
Dewailly D et al. Clin Endocrinol (Oxf).1994 Nov,41(5):557-62.

10
Insulin resistance: diminished effect of insulin on
glucose metabolism

Normally in the body: With insulin resistance: glucose does not

glucose goes into cell go into cell, stored as fat
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 Insulin Resistance
Reduced glucose response to insulin or decreased ability of
insulin to stimulate glucose disposal to tissues
 What happens as insulin level increases?

1. Directly suppresses sex hormone binding globulin

↓
Increased free testosterone
Increased free estradiol

2. Decrease Insulin Growth Factor Binding Protein 1( IGFBP 1)

↓
Increased levels of Insulin growth factors
Stimulates the theca cells to produce androgens

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 The Two-Cell System

The interaction
between the
granulosa and
theca cells
results in
accelerated
estrogen
Falck B Acta Physiol Scand
production
163:1,1959

15
Interplay between PCOS and abdominal adiposity

PCOS
‘vicious
circle’

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Acanthosis Nigricans
• Found in 30% of hyperandrogenic
women

• 50% of hyperandrogenic
women who had PCOS and were
obese had AN.
Consequences of PCOS
• Weight gain/Obesity/Metabolic Syndrome
• Diabetes
• Quality-of-life Issues
• Cardiovascular concerns
• Cancers on PCOS
Consequences…
Weight gain/Obesity/Metabolic Syndrome
• Major predictor of abnormal metabolic • Driven by obesity and leads to diabetes and
findings and the emergence of CV disease CVD

• Increased abdominal and visceral fat Adult Treatment Panel III Criteria (3/5):

• Correlated with IR and metabolic Waist circumference >88cm

dysfunction HDL <50 mg/dl
TG >150 mg/dl
• Treatment: lifestyle modification BP >130/85 mmHg
FBS >110mg/dl
Consequences…
Diabetes
• Driven by IR

• Management:
• HgbA1c – lack of precision
• Diet and exercise – mainstay treatment
• Metformin 1500mg/day - significant
role
 Consequences…
Quality of Life Issues
Overweight
Irregular cycles
Decreased fertility
Acne
Hirsutism
Depression the most!
Cardiovascular Concerns

Lipid and lipoprotein

abnormalities

They should be
counseled regarding CVD
risk factors and
preventing hypertension,
dyslipidemia, diabetes
 PCOS and Endometrial Hyperplasia

Unopposed estrogen causes

endometrial growth and irregular
endometrial shedding and predisposes
to abnormal uterine bleeding,
endometrial hyperplasia and
endometrial cancer

Hardiman P et al PCOS
Lancet 2003

23
 Endometrial Cancer in PCOS
Irregular bleeding Risk of endometrial cancer due to
unopposed estrogen stimulation from
(Abnormal Uterine Bleeding)
anovulation
 Endometrial Cancers in PCOS

• Due to long-term anovulation and

unopposed estrogen stimulation of the
endometrium.
• Due to defect in progesterone signaling in
the endometrium
Treatment are directed at androgen excess
 Treatment are directed at irregular bleeding

Endometrial biopsy
Endometrial biopsy should be
done if the endometrial lining is
>10 mm thick on TVS done
between days 6-10

Any PCOS patient with AUB or who is older than 35 y.o

should have an endometrial biopsy to rule out carcinoma.
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Treatment are directed at irregular bleeding
Oral Contraceptives Progesterone therapy alone at 2-3 month
interval

Medroxyporgesterone acetate 5-10 mg OD

Norethindrone acetate 2.5-10 mg

Weight Loss
The impact of obesity in reproduction can
be attributed to increased insulin levels
and increased androgen production via
suppression of SHBG

Weight loss is the 1st line treatment for

obesity in PCOS women who desire
pregnancy because it improves ovulation
rates
Moran LJ. J Clin Endocrinol 1992;36(1):105-11

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 Treatment are directed at fertility concerns

Before Ovulation
Induction it is necessary to
normalize glucose level
and encourage weight loss.
 Treatment are directed at fertility concerns

Metformin 1500mg OD

Clomiphene Citrate 50 mg OD
 Treatment are directed at fertility concerns

When Aromatase is inhibited by the Letrozole,

Estrogen levels are suppressed. This results to
increase FSH.

In women with PCOS or anovulation the

increase FSH results in development of a
mature follicle resulting to ovulation
Treatment are directed at fertility concerns
 Treatment are directed at fertility concerns
Recommended as the final treatment
option for infertility treatment in
Dexamethasone women with PCOS
Dopamine agonists
Thiazolidinediones
 PCOS TREATMENT
COMPLAINT TREATMENT OPTIONS

Infertility Letrozole, Clomiphene, with or without metformin,

gonadotropins, ovarian cautery (“drilling”)

Skin Manifestations OCP + Antiandrogen (spironolactone, finasteride), GnRH

agonists

Abnormal Bleeding Cyclic progestogen, OCP

Weight, metabolic concerns Diet/lifestyle management, metformin