POLYCYSTIC OVARY SYNDROMESPOTLIGHTS : POLYCYSTIC OVARY SYNDROMESPOTLIGHTS Dr. Mohammed AbdallaEgypt, Domiat Hospital
Pathogenesis (etiology?) : Pathogenesis (etiology?) Hypersecretion of adrenal androgens?
Hypersecretion of ovarian androgens?
A genetic disorder with an autosomal dominant mode of inheritance?
A multifactorial genetic disorder?
Prevalence : Prevalence PCO on ultrasound 20%
Oligomenorrhea 4 – 21 %
Oligomenorrhea + hyperandrogenemism 3.5 – 9 %
Ultrasound in vs Meglocystic ovaries PCO : Ultrasound in vs Meglocystic ovaries PCO Polycystic ovaries
Bilateral
Multiple cysts
Cyst diam <4-6 mm
Stroma increased Megalocystic ovaries
Bilateral
Multiple cysts
Cyst diam > 6-10 mm
Stroma not increased
Long term risks in PCOS : 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)
Long term risks in PCOS : Possible
Hypertension
Cardiovascular disease
Gestational diabetes mellitus
Pregnancy-induced hypertension
Ovarian cancer
Unlikely
Breast cancer Long term risks in PCOS
Slide 7: Cholesterol Pregnenolone Progesterone 17 OH-Pregnenolone 17 OH-Progesterone DHEA Androstenandion 17-20 Lyase 17 hydroxylase Theca cell Estrone estradiol Granulosa cell FSH LH OVARIAN STEROIDOGENESIS T
Slide 8: LH FSH follicular
maturation Androgen
excess Extra glandular
aromatization Stim. Of stroma
and theca Chronic
anovulation Adipose tissue acyclic estrogen Adrenal androgen Cyclic estrogen Ovarian androgen Abnormal hormonal feedback mechanisms
Obesity and insulin resistance : Obesity and insulin resistance
Slide 10: Obesity
Insulin resistance
Hyperinsulinemic state Androgens Serum insulin
Slide 11: Obesity Insulin Free testosterone SHBG IGF-1 5-alfa reductase activity is stimulated IGF*** insulin like growth factor
PCOS - Pathogenesis : 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
Slide 13: “Insulin resistance” is characterized by decreased sensitivity to insulin in peripheral tissues (muscle and adipose tissue), but not in hepatic tissue Franks 1995
Slide 14: Wt. increase Insulin receptor
disorder Insulin increase Free estradiol
increase High LH
Low FSH Free testosteron
increase Androstenandion
increase SHBG
decrease atresia Theca (IGF-I) Endometrial
cancer Testosteron
increase Estrone
increase hirsutism IGFBP-I ****
decrease IGFBP*** insulin like growth factor binding protein
Slide 15: 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
Slide 16: PUBERTY LH
LH pulses > 25pulses /24h INSULIN
resistance ANDROGEN
INCREASE HIRSUTISM
ACNE
ALOPECIA ANOVULATION Ratio of LH/FSH: 2-3/1
Gonadotropin Secretion in PCOS : Gonadotropin Secretion in PCOS Increased LH secretion:
•Ratio of LH/FSH: 2-3/1
•Prevalence: 30 to 90% !
Treatments for PCOS : Treatments for PCOS Oral Contraceptives.
Clomiphene.
Ovarian diathermy/laser tx.
ART.
Cyproterone acetate+ EE, Spironolactone.
Insulin sensitizing agents. Biguanides (metformin)
Thiazolidinediones (troglitazone).
Weight loss.
Slide 19: thank you