Polycystic ovarian syndrome (PCOS) is the most common endocrine abnormality and cause of infertility in women of reproductive age. PCOS is characterized by oligomenorrhea/amenorrhea, hyperandrogenism, and polycystic ovaries on ultrasound. The pathophysiology involves an altered hypothalamic-pituitary feedback loop leading to excessive LH production and androgen excess from the ovaries. Insulin resistance also contributes to hyperandrogenism and anovulation. Labs used to diagnose PCOS show increased androgens, LH levels relative to FSH, and markers of insulin resistance. Differential diagnoses must be ruled out through appropriate testing.

1. Polycystic ovarian syndrome
Dr.Ghulam Murtaza
resident chemical pathology
D.I.M.C

2. Introduction
• Most common endocrine abnormality in reproductive age
• Most common cause of infertility in women
• PCOS is becoming a frequently diagnosed condition in Pakistan where the prevalence is
as high as 15.7-37%
(Prevalence and Knowledge of Polycystic Ovary Syndrome (PCOS) Among Female Science Students of Different Public Universities of Quetta, Pakistan
June 2017 )

3. Historical Perspective
Classic syndrome originally described by STIEN &
LEVANTHAL (1935)
Hyperandrogenism
Mensural irregularity
Polycystic ovaries
Central adiposity
Few of these original features are now considered
consistent finding in PCOS
Insulin resistance described by Burghen 1980

4. PCOS epidemiology
• PCOS accounts for 95% of cases of hyperandrogenism
• PCOS is responsible for over 20% of all cases of amenorrhea
• PCOS is responsible for up to 75% of all cases of anovulatory
infertility
• The name is actually misnomer that ovaries are covered with follicles
not cysts ( Tietz )

5. PCOS
Syndrome characterized by
Oligomenorrhoea /amenorrhea
Laboratory criteria
Hyperandrogenemia
Hyperinsulinemia
Polycystic ovaries on USG

6. Sign & symptoms

8. Pathophysiology
The pathophysiology of PCOS, although still not entirely clear, is mainly due to the hormone
imbalance caused by both hyperandrogenism and hyperinsulinemia, which are also effects of PCOS.
Abnormal Pituitary function – altered negative feedback loop
Hyperandrogenism
Insulin resistance

9. Abnormal Pituitary function – Altered
negative feedback loop
Increase GnRH from hypothalamus
Excessive LH secretion relative to FSH by pituitary gland
Ineffective suppression of the LH pulse frequency by estradiol &
progesterone
LH stimulated excessive androgen production , excessive
production leads to excessive growth of small follicles
Inhibition of follicular maturation leads to inovulation

10. Serum Androgens
►Testosterone (T)
• Majority made in ovary
• Most potent circulating androgen
• Biological activity determined by the amount of binding to sex hormone binding globulin
• Free testosterone is active
►Androstenedione (A)
• Immediate precursor to testosterone
• Ovary and adrenal production
►Dehydroepiandrosterone sulfate (DHEA-S)
• Majority derived from adrenal glands
• Small percentage from ovary
70 % bind to SHBG
20-30% albumin & 1% free active form

11. ►Dihydrotestosterone (DHT)
• Peripheral conversion in androgen responsive tissues
• Intracellular 5-alpha reductase converts T to DHT
• DHT binds to androgen receptor with affinity 10x greater than Testosterone
• Women with PCOS have increased 5-alpha reductase activity (converts T to DHT)
►Resulting in increased activation of the pilosebaceous unit (hair growth, sebum production)
with only modest increases in bioavailable testosterone

12. Hyperandrogenism :

13. Sources of Serum Androgens

14. Insulin resistance :
Mutation of the insulin receptor gene in the peripheral target tissue
Reduced tyrosine auto phosphorylation of the insulin receptors
Excess insulin production & insulin resistance
Favors anovulation ,reduced SHBG ,IGF-1 BP .
Metabolic syndrome
Abdominal obesity

15. Insulin resistance :

16. ►Insulin resistance – no
recommended screening test
• Insulin level assessment has not
been shown to identify women
who will respond to therapy
►Instead of IR testing, there is
increasing recognition of
metabolic syndrome
• 33% of PCOS patients

17. Differential diagnosis :

18. Labs :
Hyperandrogenism
• Elevated total testosterone
• Most values in PCOS < 150ng/dl ( > 200ng/dl consider ovarian/
adrenal tumor
• Free testosterone assays are not reliable yet
• Free androgen index > 4.5
(Total Testosterone/SHBG x 100 %) considered a better
indicator

19. • DHEA-S
►marker for adrenal
hyperandrogenemia
►If >800 mcg/dL (normal <270)
consider androgen secreting tumor
• LH/FSH Ratio
levels vary over menstrual cycle ,released in
pulsatile fashion , affected by OCPs
• LH/FSH > 2:1 0r 3:1 ( normal 1:1) may be
considered as diagnostic

20. Hyper insulinemia
►Fasting glucose
• Fasting plasma glucose
►<100 mg/dL normal
►100-125 mg/dL impaired fasting glucose/prediabetes
►>126 mg/dL DM
►2 hour glucose level after 75gm oral glucose load
• 140-199 mg/dL indicates impaired glucose tolerance
• Above 199 mg/dL is diagnostic for type diabetes
• Recheck every 2 years if IGT

22. Labs :
• One may see the following:
• Increased free testosterone/N testosterone, increased androstenedione
• Increased DHEA-S, DHEA
• Increased LH, normal FH; Inc. LH/FSH
• Increased estradiol, estrone
• Increased fasting insulin
• Increased insulin resistance
• Decreased SHBG
• Mildly elevated prolactin
• Increased AST,ALT in pts with NASH

24. • Thank you ….