PCOS LECTURE PRESENTATION

1. POLYCYSTIC OVARIAN SYNDROME
(PCOS) OVERVIEW
 PCOS is a complex endocrine disorder affecting mostly
women of childbearing age
 Etiology of PCOS is largely unknown & multifactorial
 Prevalence 6-8% of general population
 30-40%% of infertile women
 PCOS is a Leading cause of anovulatory infertility and
hirsutism
 Women with PCOS have an increased risk of
miscarriage, insulin resistance, hyperlipidemia, type 2
diabetes, cardiovascular disease, and endometrial
hyperplasia & cancer

2. Stein-Leventhal Syndrome
o PCOS was first identified by German
gynecologists Stein and Leventhal in 1935
o They described a group of women : obese ,
infertile, & enlarged ovaries with multiple
cysts

3. DIAGNOSTIC CRITERIA
AND
CLINICAL
MANIFESTATIONS

4. ASRM & ESHRE joint meeting
Rotterdam(2003)
The presence of at least
• 2 out of 3 criteria to diagnose PCOS ,after Exclusion of
other causes of hyperandogenism : (congenital adrenal
hyperplasias, androgen-secreting tumors, Cushing's
syndrome)
 Clinical :Menstrual irregularity due to anovulation &/ or
oligo-ovulation .
 Evidence of hyperandrogenism : clinical or hormonal
 Polycystic ovaries by US
 presence of 10-12 follicles measuring 2 - 9 mm in diameter and/or
increased ovarian volume

5. PATHOPHISIOLOGY

6. Recently Insulin Resistance seems to be an important
factor in the syndrome :
 Several studies reported that IR is common in PCOS
regardless of BMI . 80% of women with PCOS & central
obesity as well as 25-30% of lean women diagnosed with
PCOS
 Fanser et al Fertil Steril 97 : 28-38.
 Campelli et al Metabolism 48: 167-172

7.  The cause of IR in PCOS is not clear esp. in lean
women , but a post-receptor defect that could
affect glucose transport has been proposed .
 Genazzani et al -Women Health (London Eng ) 6: 577-593
 Baillargeor et al – Diabetic care 29: 300-305
Obesity exacerbate IR & it is a
fundamental factor in the pathogenesis of
hyperandogenesim .

8. Inositol isoform(it is a vitamin factor
belonging to B-comples ) ( myo-inositol & D-
chiro – inositol ) & Alpha-lipoic acid are
effective in lowering IR in PCOS .
 Inositol involved in post-receptor transduction of
signals induced by linkage of insulin to its
receptors .

9.  ALA has been demonstrated to increase
glucose utilization by increasing AMP-
activated protein kinase in the skeletal
muscles . Metformin also seems to activate
AMPK .
 Combination of inositol & ALA improves
insulin sensitivity in overweight / obese PCOS
.
 Genazzani et al - Endocrinology & Metabolic syndrome
2014 ; 3:3

10. NORMAL INSULIN SENSITIVITY
Insulin
Liver Muscle
Pancreas
Hepatic
Glucose
Output
Glucose
Utilization

11. INSULIN RESISTANCE
Insulin
Liver Muscle
Pancreas
 Hepatic
Glucose
Output
 Glucose
Utilization
Increased

12. 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Hormone
Level
Estradiol
Progesterone
FSH
LH
Menstrual Cycle Day
Ovulation
Endometrial
Thickness
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Normal
Menstru
al Cycle

13. MENSTRUAL DYSFUNCTION
 Oligo or amenorrhea
 Menstrual irregularity typically begins in the
peripubertal period
 Delayed menarche
 Reduction in ovulatory events leads to
deficient progesterone secretion
 Chronic estrogen stimulation of the
endometrium with no progesterone for
differentiation—intermittent
breakthrough bleeding or dysfunctional
uterine bleeding
 Increased risk for endometrial
hyperplasia and/or endometrial CA

14. Hormone
Level
Estradiol
Progesterone
Endometrial
Thickness
0 2 4 6 8 10 12 14 16 18
20
0 2 4 6 8 10 12 14 16 18
20 Weeks
Breakthrough
Withdrawal
Anovulatory
Bleeding in
PCOS
Lower limit
of normal

15. HYPERANDROGENISM
 Hirsutism, acne, male pattern balding, alopecia
 50-90% patients have elevated serum androgen
levels,but level not very high ,but increased
sensitivity to testosterone at hair follicles
 Rare: increased muscle mass, deepening
voice, hypertrophy of clitoris (should prompt
search for underlying androgen producing
neoplasm)

16. OVARIAN ABNORMALITIES IN PCOS
 Thickened sclerotic cortex
 Increased ov volume
 Multiple follicles subcapsular (10-12
follicles ) less than 10 mm diameter
 80% of women with PCOS have classic
cysts

18. Polycystic
Ovaries
Cystic
Follicles
Uterus
Tube
Anatomic Features of
the Polycystic Ovary

19. OBESITY IN PCOS
 Prevalence of obesity varies from 30-75%
 2/3 of patients with PCOS who are not
obese have excessive body fat and
central adiposity
 Obese patients can be hirsute and/or
have menstrual irregularities without
having PCOS

20. OBESITY AND INSULIN RESISTANCE
 50% of PCOS patients are obese &
 > 80% are hyperinsulinemic and have
insulin resistance (independent of
obesity)
 Hyperinsulinemia contributes to
hyperandrogenism through increase
production of androgen in the theca
cells , and through its suppressive
effects on sex hormone binding globulin
production by the liver

21. 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

22. DIFFERENTIAL DIAGNOSIS
1. Hyperprolactinemia
 Prominent menstrual dysfunction esp.
amenorrhea
 Little hyperandrogenism
2. Congenital Adrenal Hyperplasia
 morning serum 17-hydroxyprogesterone
concentration greater than 200 ng/dL in the
early follicular phase strongly suggests the
diagnosis
 confirmed by a high dose (250 mcg) ACTH
stimulation test: post-ACTH serum 17-
hydroxyprogesterone value less than 1000
ng/dL

23. 3. Ovarian and adrenal tumors
 serum testosterone concentrations are always
higher than 150 ng/dL
 adrenal tumors: serum DHEA-S concentrations
higher than 800 mcg/dL
 LOW serum LH concentrations
4. Cushing’s syndrome
Elevated S cortisol level
5 .Drugs:
danazol , androgenic OC

24. INVESTIGATIONS
I .Hormonal Assay :
FSH normal
LH elevated
Serum prolactin - slightly elevated
Testosterone -slightly elevated
Thyroid function test- normal
Serum estradiol—normal
Serum estrone—elevated
DHEA-S - normal
17- OH progesterone - normal

25. II .General
 Fasting glucose: elevated
 2 hour OGTT: elevated
 Fasting insulin: elevated
 Lipids
III .Pelvic US
Characteristic features of PCOS
Peripheral 10-12 follicles (2-9 mm in diameter )
,increase ovarian vol.

26. Total Testosterone (T)
DHEA-S (DS)
17-hyroxyprogesterone (17-OHP)
T > 200 ng/dl
DS > 700 μg/dl
Suspect Tumor
17-OHP > 2 ng/ml
Suspect CAH
T Elevated
+
LH Elevated
DS Elevated
T & DS Normal
PCOS
Adrenal
Idiopathic
LABORATORY EVALUATION