POLYCYSTIC OVARY SYNDROME SPOTLIGHTS

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POLYCYSTIC OVARY SYNDROMESPOTLIGHTS

• Dr. Mohammed AbdallaEgypt, Domiat Hospital

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Pathogenesis (etiology?)

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

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Prevalence

• PCO on ultrasound 20
• Oligomenorrhea 4 21
• Oligomenorrhea hyperandrogenemism 3.5
  9

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Ultrasound in vs Meglocystic ovaries
PCO

• Polycystic ovaries
• Bilateral
• Multiple cysts
• Cyst diam lt4-6 mm
• Stroma increased

• Megalocystic ovaries
• Bilateral
• Multiple cysts
• Cyst diam gt 6-10 mm
• Stroma not increased

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Long term risks in PCOS

• Definite
• Type 2 diabetes
• Dyslipidemia (Hypercholesterolemia with
  diminished HDL2 and increased LDL)
• Endometrial cancer (OR 3.1 95 CI 1.1 -7.3)

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Long term risks in PCOS

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

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OVARIAN STEROIDOGENESIS
LH
Theca cell
Cholesterol
17-20 Lyase
17 hydroxylase
Pregnenolone
17 OH-Pregnenolone
DHEA
T
17 OH-Progesterone
Androstenandion
Progesterone
Granulosa cell
Estrone
FSH
estradiol
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Abnormal hormonal feedback mechanisms
LH FSH
acyclic estrogen
follicular maturation
Chronic anovulation
Extra glandular aromatization
Stim. Of stroma and theca
Cyclic estrogen
Adipose tissue
Ovarian androgen
Androgen excess
Adrenal androgen
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Obesity and insulin resistance
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Obesity Insulin resistance Hyperinsulinemic state
Androgens
Serum insulin
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Obesity
Insulin
IGF-1
SHBG
5-alfa reductase activity is stimulated
Free testosterone
IGF insulin like growth factor
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PCOS - Pathogenesis

• Excessive ovarian stimulation caused by the
  progressively rising insulin and insulin like
  growth factor - I (IGF-I) levels during puberty
  induces a PCOS in predisposed girls
• Nobels and Devailly FertilSteril 1992
• 5-alfa reductase activity is stimulated by
  iGF-I. This intensifies the hirsute response in
  hyperandrogenic patients
• Speroff 1993

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• Insulin resistance is characterized by
  decreased sensitivity to insulin in peripheral
  tissues (muscle and adipose tissue), but not in
  hepatic tissue Franks 1995

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SHBG decrease
atresia
Wt. increase
Insulin increase
Insulin receptor disorder
IGFBP-I decrease
Free estradiol increase
Theca (IGF-I)
Free testosteron increase
High LH Low FSH
hirsutism
Androstenandion increase
Testosteron increase
Endometrial cancer
Estrone increase
IGFBP insulin like growth factor binding
protein
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Insulin effects related to ovarian function
Directly stimulates steroidogenesis Stimulates
17-hydroxylase Stimulates or inhibits
aromatase Up-regulates LH receptors Promotes
ovarian growth and cyst formation synergistically
with LH/hCG Up-regulates Type I IGF receptors
Inhibits IGFBP-1 production Inhibits SHBG
production Potentiates the effect of GnRH on
LH/FSH
Ovary Ovary Ovary and adipose Ovary Ovary Ovary
Ovary and liver Ovary Hypothalamus/pituitary
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Ratio of LH/FSH 2-3/1
LH LH pulses gt 25pulses /24h
INSULIN resistance
PUBERTY
ANDROGEN INCREASE
ANOVULATION

• HIRSUTISM
• ACNE
• ALOPECIA

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Gonadotropin Secretion in PCOS

• Increased LH secretion
• Ratio of LH/FSH 2-3/1
• Prevalence 30 to 90 !

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Treatments for PCOS

• Oral Contraceptives.
• Clomiphene.
• Ovarian diathermy/laser tx.
• ART.
• Cyproterone acetate EE, Spironolactone.
• Insulin sensitizing agents. Biguanides
  (metformin)
• Thiazolidinediones (troglitazone).
• Weight loss.

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thank you