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Polycystic Ovary
Syndrome & Metformin
November 19, 2008
Polycystic Ovary Syndrome
 Epidemiology
 Clinical
manifestations
 Diagnostic
criteria
 Metformin
and other medical treatments
EPIDEMIOLOGY

Very prevalent disease affecting between 6.5
and 8 percent of women overall.
 Prevalence much higher in obese women (28%
versus 5.5%)
 Prevalence between racial groups in
Southeastern US not significantly different
 Genetic factors – genes involved in insulin
secretion and action, gonadotropin secretion
and action, and androgen biosynthesis,
secretion, transport, and metabolism
CLINICAL MANIFESTATIONS
Obesity
 Up
to one half of women
with PCOS are obese,
with an increased
prevalence of abdominal
or central obesity
 Most women with PCOS
are hyperinsulinemic and
insulin resistant
Oligomenorrhea
 Classically
have a peripubertal onset
 May have apparently regular cycles at first,
followed by irregularity and weight gain
Normal
PCOS
Hirsutism and Virilization
 Excess
body hair in a male distribution
 Male pattern balding
 Deeper voice, muscle mass, clitoromegaly
Infertility
 Female
infertility occurs when the woman
does not conceive after one year of
attempting to become pregnant
DIAGNOSTIC CRITERIA
vs.
Rotterdam
NIH Criteria
 1990



Consensus
Menstrual irregularity due to oligo/anovulation
Evidence of hyperandrogenism
Exclusion of other causes of the above two
Rotterdam Criteria
 Oligo-
and/or
anovulation
 Clinical and/or
biochemical signs of
hyperandrogenism
 POLYCYSTIC
OVARIES by
ultrasound!!!
Transvaginal Ultrasound
 12
or more follicles in each ovary
 Each follicle measuring 2-9 mm diameter
 Increased ovarian volume (>10 mL)
MEDICAL TREATMENT
 Weight
loss
 Hyperandrogenism
 Endometrial protection
 Insulin resistance
 Ovulation induction
Weight Loss
 Weight
loss alone is
associated with a
reduction in
testosterone, leading
to resumption of
ovulation and often
pregnancy.
Hyperandrogensim
 Many
women shave, wax, use Nair or get
electrolysis
 Combination oral contraceptives
 Spirinolactone – antiandrogen properties
Endometrial Protection
of unopposed estrogen 
endometrial hyperplasia
 Combination OCPs vs. Intermittent
progestin therapy
 Risk
Metformin
Metformin
– most widely used drug
worldwide for the treatment of type 2
diabetes.
 Primary action – inhibits hepatic glucose
production
 Secondarily increases peripheral
sensitivity to insulin
 A biguanide
Clinical Evidence for PCOS
 1996
study by Nestler demonstrated
reduced circulating insulin levels and
decreased ovarian secretion of androgens
Studies demonstrating decreased clinical
signs of androgen excess are limited
 2003 Meta-analysis showed PCOS
women on Metformin 3.88 times more
likely to ovulate
Clinical Evidence cont’d
 Indian
Diabetes Prevention Programme
and U.S. Diabetes Prevention Program
have shown that metformin decreases the
relative risk of progression to type 2
diabetes by 26% and 31% respectively
 Limited evidence suggests that OCPs
alone can aggravate insulin resistance and
glucose intolerance.
Recommendations
 Androgen
Excess Society recommends
that all women with PCOS be screened for
glucose intolerance at initial presentation
and every 2 years thereafter.
 AES does not mandate use of metformin
until more studies can demonstrate
efficacy.
 Metformin use should be considered in all
patients with PCOS and glucose
intolerance.
Recommendations cont’d
 American Association
of Clinical
Endocrinologists recommends that
metformin be considered the initial
intervention in most women with PCOS,
particularly those who are overweight or
obese.
Adverse Effects
acidosis – rare complication (0.3
episode per 10,000 patient-years).
 GI distress – nausea and diarrhea in 1025% of patients
 B12 Malabsorption.
 Category B drug – no teratogenic effects
in animal models and limited human
anecdotal evidence
 Lactic
Thank you!
Tyler Hansborough and Barack Obama
Taquito, 4 years old
RESOURCES
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Alvarez-Blasco, F., et al. “Prevalence and characteristics of the polycystic ovary syndrome in
overweight and obese women.” Arch Intern Med. 2006 October.
“Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic
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Adams, J, Polson, DW, Franks, S. “Prevalence of polycystic ovaries in women with anovulation
and idiopathic hirsutism.” BMJ 1996; 293:355.
Legro, RS, Barnhart, HX, Schlaff, WD, et al. “Clomiphene, metformin, or both for infertility in the
polycystic ovary syndrome.” N Engl J Med 2007; 356:551.
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of hirsutism in polycystic ovary syndrome. J Clin Endocrinol Metab 2003;88:4116-23
Nestler JE, Jakubowicz DJ. Decreases in ovarian cytochrome P450c17alpha activity and serum
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