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.
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 )
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 â altered negative feedback loop
Hyperandrogenism
Insulin resistance
9. Abnormal Pituitary function â 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
âşTestosterone (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
âşAndrostenedione (A)
⢠Immediate precursor to testosterone
⢠Ovary and adrenal production
âşDehydroepiandrosterone sulfate (DHEA-S)
⢠Majority derived from adrenal glands
⢠Small percentage from ovary
70 % bind to SHBG
20-30% albumin & 1% free active form
11. âşDihydrotestosterone (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)
âşResulting in increased activation of the pilosebaceous unit (hair growth, sebum production)
with only modest increases in bioavailable testosterone
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
16. âşInsulin resistance â no
recommended screening test
⢠Insulin level assessment has not
been shown to identify women
who will respond to therapy
âşInstead of IR testing, there is
increasing recognition of
metabolic syndrome
⢠33% of PCOS patients
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
âşmarker for adrenal
hyperandrogenemia
âşIf >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
âşFasting glucose
⢠Fasting plasma glucose
âş<100 mg/dL normal
âş100-125 mg/dL impaired fasting glucose/prediabetes
âş>126 mg/dL DM
âş2 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
21.
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