Diagnosis of polycystic ovarian

syndrome.
August 2006
Prof Jane Norman
Division of Developmental Medicine
University of Glasgow
Stein & Leventhal (1935)
Seven women with amenorrhoea, hirsutism,
obesity and enlarged ovaries who
underwent ovarian wedge resection
all seven resumed regular menstruation
two conceived
Ehrmann DA et al 2005 N Engl J Med 352: 1223
Rotterdam Consensus workshop
PCOS is syndrome of ovarian dysfunction along
with the cardinal features hyperandrogenism and
polycystic ovary morphology
No single diagnostic criterion is sufficient
The diagnosis of PCOS can be made on the basis
of two out of the three of the following
Oligo- or anovulation
Clinical or biochemical signs of hyperandrogenism
Polycystic ovaries on ultrasound or direct inspection
Other causes of hyperandrogenism should be
excluded
Human Reproduction (2004) 19: 1
Fertility Sterility (2004) 81:19
The polycystic ovary
PCO : ultrasound
Ultrasound criteria for diagnosis of PCO
twelve or more subcapsular follicular cysts
2 9 mm in diameter
and / or
Increase in ovarian volume up to 10ml
3
(determined by transvaginal ultrasound)
Prevalence of PCO / PCOS
Setting n PCO %
Polson et al
1988
Volunteers
257 23
Clayton et al
1992
GP practice
190 22
Farquhar et al
1994
Electoral roll
183 21
Michelmore et al
1999
GP practice
224 34
Clinical symptoms of women with PCO
Conway et al
1989
Balen et al
1995
Eden et al
1999
(n = 556) (n = 1741) (n=1019)
Amenorrhoeic
/ oligo
71% 66% 75%
Hirsutism 61% 66% 34%
Obesity 35% 38% 31%
Infertility 29% 75%* 14%
Acanthosis 2% 2.5% 0.5%
CAH 1.9%
Prevalence of PCO in symptomatic
women
Condition Proportion with PCO
Oligomenorrhoea 87 %
Amenorrhoea 26 %
Hirsutism 92 %
Adams et al, 1986
Spectrum of PCOS
Ultrasound
features
Clinical / biochemical
features of hyperandrogenism
Oligomenorrhoea /
amenorrhoea
Biochemical features of PCOS
testosterone / FAI elevated
(> 3nmol/ml or > 7)
insulin resistance
LH elevated
Clinical features of PCOS
Oligo / anovulation
Clinical signs of androgen excess
Hirsutism / (acne) / rarely clitoromegaly
Obesity
Acanthosis nigricans
Enlarged ovaries on inspection
Hirsutism - definition
Presence of terminal
(coarse) hairs in females
in a male-like pattern
Prevalence 5 15% of
women
Modified Ferriman Gallwey score
Hatch et al, 1981 Am J Obstet Gynecol 140: 815-30
Acanthosis nigricans
Rotterdam Consensus workshop
PCOS is syndrome of ovarian dysfunction along
with the cardinal features hyperandrogenism and
polycystic ovary morphology
No single diagnostic criterion is sufficient
The diagnosis of PCOS can be made on the basis
of two out of the three of the following
Oligo- or anovulation
Clinical or biochemical signs of hyperandrogenism
Polycystic ovaries on ultrasound or direct inspection
Other causes of hyperandrogenism should be
excluded
Human Reproduction (2004) 19: 1
Fertility Sterility (2004) 81:19
How to diagnose PCOS
1. Consider other possible diagnoses
Congenital adrenal hyperplasia
Defect of 21-hydroxylase enzyme
17-OHP accumulates
Steroid biosynthetic pathway
www.angelfire.com
21 hydroxylase deficiency
www.angelfire.com
How to diagnose PCOS
2. Consider other possible diagnoses
Congenital adrenal hyperplasia
Defect of 21-hydroxylase enzyme
17-OHP accumulates
Cushings syndrome
Cushings syndrome
How to diagnose PCOS
2. Consider other possible diagnoses
Congenital adrenal hyperplasia
Defect of 21-hydroxylase enzyme
17-OHP accumulates
Cushings syndrome
Androgen secreting tumour
How to diagnose PCOS
2. Do laboratory evaluation
Minimum
Serum testosterone
DHEA sulphate
17 OHP
Dynamic testing for 17 OHP
Indicated only if random test is abnormal
Laboratory evaluation
Minimum
Serum testosterone
DHEA sulphate
17 OHP
Optional
24 hr urinary free cortisol
Prolactin
Sex hormone binding globulin / free androgen index
LH / FSH
Lipids and insulin resistance?
How to diagnose PCOS
3. If uncertain after doing the preceeding,
ultrasound of ovaries is helpful
Diagnostic criteria:
twelve or more subcapsular follicular cysts 2
9 mm in diameter
and / or
Increase in ovarian volume up to 10ml
Ehrmann DA 2005 New Engl J Med 352: 1223
Suggested diagnostic algorithm
Rotterdam Consensus workshop
PCOS is syndrome of ovarian dysfunction along
with the cardinal features hyperandrogenism and
polycystic ovary morphology
No single diagnostic criterion is sufficient
The diagnosis of PCOS can be made on the basis
of two out of the three of the following
Oligo- or anovulation
Clinical or biochemical signs of hyperandrogenism
Polycystic ovaries on ultrasound or direct inspection
Other causes of hyperandrogenism should be
excluded
Human Reproduction (2004) 19: 1
Fertility Sterility (2004) 81:19
NICHD 1990 diagnostic criteria
PCOS is clinical or biochemical evidence of
hyperandrogenism and chronic anovulation
after exclusion of other disorders
USS criteria not relevant
Controversies in Rotterdam criteria
Broader criteria than NICHD
New criteria also include:
Women with hirsutism and
hyperandrogenemia, PCOS on scan but regular
cycles
Women with PCOS and oligomenorrhoea but
without androgen excess
US Viewpoint
Widespread adoption of the diagnostic criteria
suggested in Rotterdam should be considered
premature
Women with hirsutism and hyperandrogenemia,
PCOS on scan but regular cycles
Insulin disturbance and ovarian dysfunction only mild
(Carmina 2001)
Women with PCOS and oligomenorrhoea but
without androgen excess
Women with non androgenic disorders including prolactinoma, and transiently
in physiological conditions such as puberty have PCOS
Azziz R 2005 Fertil Steril 83: 1343
UK viewpoint
Expanded diagnostic criteria helpful
Women with hirsutism and hyperandrogenemia,
PCOS on scan but regular cycles
Share many of the biochemical features of classic PCOS
Carmina 2001, although insulin resistance tends to be less
Women with PCOS and oligomenorrhoea but
without androgen excess
Other disorders should be excluded no risk of
misdiagnosing POF
Uncommon (3%)
Most have disorders of androgen production on dynamic
testing
Testosterone levels dont affect response to O.I
Franks S (2006) J Clin Endocrinol Metab 91:786
Screening for metabolic disorders in PCOS 2003
conference consensus
1. No tests of insulin resistance are necessary to
make the diagnosis of PCOS, nor are they needed
to select treatments.
2. Obese women with PCOS should be screened for
the metabolic syndrome, including glucose
intolerance with an oral glucose tolerance test.
3. Further studies are necessary in non-obese
women with PCOS to determine the utility of these
tests, athough they may be considered if additional
risk factors for insulin resistance, such as a family
history of diabetes, are present.
Fertility Sterility (2004) 81:19
Criteria for the metabolic syndrome in PCOS.
110 126 mg /dL and
/or 2-h glucose 140
199 mg/dL.
5. Fasting and 2-h glucose from
oral GTT
130 / 85 4. Blood pressure
< 50mg / dL 3. HDL-C
150mg / dL 2. Triglycerides
> 88 mm (> 35 inch) 1. Abdominal obesity (waist
circumference)
Cut off Risk factor
Fertility Sterility (2004) 81:19
Conclusions
PCOS multisystem disorder
No single diagnostic criterion
Rotterdam consensus criteria helpful
Diagnose more women than NICHD
criteria, but probably more appropriate in
determining treatment
Diagnosis likely to be important in future
because of long term health risks