? By Shelley Ferrell Advisor: Eileen VanDyke, PA-C PAS Spring 2006.
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Transcript of ? By Shelley Ferrell Advisor: Eileen VanDyke, PA-C PAS Spring 2006.
Behind door #1…
• 20 yo white female
• CC: menstrual irregularity over past year, no period in 5 months
• PE: obesity, acne, hirsutism
• Labs: (-) HCG, (+) hyperandrogenemia, (+) insulin resistance
• Diagnosis: ?
Behind door #2
• 21 yo white female
• CC: menstrual irregularity over past year, no period in 5 months
• PE: thin, mild acne, unremarkable
• Labs: (-) HCG, (+) hyperandrogenemia, (-) insulin resistance
• Diagnosis: ?
The Use of Metformin in Non-obese Women with
Polycystic Ovarian Syndrome
By Shelley Ferrell
Advisor: Eileen VanDyke, PA-C
PAS Spring 2006
Why care about PCOS?
• Its common
• It causes other health problems
• It is emotionally painful for women
Making the diagnosis
• Two out of three
– Oligo and/or an-ovulation
– Clinical and/or biochemical hyperandrogenemia
– Polycystic ovaries on ultrasound
• Diagnosis of exculsion
Clinical Presentation• Is there a stereotypical PCOS patient?
Sign PrevalencePolycystic Ovaries 80-100%Oligo- or amenorrhea 70%Hyperandrogenism 20-80%Hirsutism 70%Obesity 50%Increased LH 30-90% Insulin Resistance 20-50%Acne 33%
• Other symptoms occur more rarely• Obesity makes a difference
Pathophysiology
• Three Theories:– Ovarian hypothesis
– Central hypothesis
– Insulin hypothesis
• Role of obesity in pathogenesis
• Obesity status/ IR status makes difference
Treatment Options
• Obese- weight loss!
• Non-obese- OCPs, anti-androgens, insulin-sensitizers
• Drawbacks to each
• Benefits of metformin
• Remember the initial question for Patient #2:– Do non-obese pts benefit from metformin? What if they
are not insulin resistant?
Lean Women with Polycystic Ovary Syndrome Respond to Insulin Reduction with Decreases in
Ovarian P450c17{alpha} Activity and Serum Androgens
• Nestler et al, 1997
• 31 normal weight women
• 1500 mg day metformin vs placebo, 4-6 wks
• Drop in serum sex steroids – (total T ↓48%, free T ↓70% and androstenedione ↓ 36%)
• Conclusions: Non-obese PCOS patients benefit from metformin treatment
Non-obese women with polycystic ovary syndrome respond better than obese women to
treatment with metformin
• Maciel et al, 2004
• 29 women in 2 groups: obese and non-obese
• Metformin 1500 g/day vs placebo, 6 months
• Results– Non-obese: ↑menstrual cyclicity, total T↓ 38%, free T
↓58%, androstendione↓30%
– Obese: total T ↓48%, otherwise no change
• Conclusions: Non-obese women experience more benefit than obese women with metformin txt
Effects of metformin and rosiglitazone, alone and in combination, in non-obese women with
polycystic ovary syndrome and normal indices of insulin sensitivity
• Baillargeon et al, 2004
• 100 non-obese women with normal insulin sens
• 1700 mg of metformin, 8 mg of rosiglitazone, a combination of both drugs or placebo daily for 6 months
• Results (met vs placebo): ovulation 6x more common, 100% ovulating monthly by study end- vs 10% placebo, sex steroids ↓67%
• Conclusions: Metformin benefits non-obese pts without IR
Metformin-diet benefits in women with polycystic ovary syndrome in the bottom and top quintiles for
insulin resistance
• Goldenberg et al, 2005
• 67 women in top and bottom quintiles for IR out of screening of 898 PCOS pts (all weights!)
• 2550 mg/day of metformin for 1 year + diet
• Results: menstruation doubled in non-IR
• Conclusion: metformin benefits non-IR
(many non-obese are also non-IR)
Predictive value of glucose-insulin ratio in PCOS and profile of women who will benefit from metformin therapy: Obese, lean, hyper or
normoinsulinemic?
• Onalan et al, 2005• 169 women into 6 groups based on glucose-insulin ratio
(normoinsulinemic and hyperinsulinemic) and BMI (lean, overweight and obese)
• 1700- 2550 mg/day of metformin (based on BMI) or placebo for 6 months
• Results: – IR/Lean group: ↑ ovulation, ↓ hirsutism– Both Lean groups, IR/obese group: ↓ Total T– No other significant results
• Conclusion: Pts who are both lean and IR benefit most from metformin therapy
Inconsistancy?
• Onalan did not show benefit to overweight women (still
considered non-obese)
Author Group Name Inclusion Criteria Average BMINestler Lean <23.7 21.6Maciel Non-obese <30 25.2 Baillargeon Non-obese <27 24.5 Onalan Lean <25 21.3
Overweight <30 28.2
• No inconsistancy- there may be an inverse relationship between BMI and response to metformin, even within non-obese or normal weight populations
Conclusion
• OCPs very effective
• Metformin should be considered also
• Talk to your patient- see what her goals are
just try something else!
Find a treatment that the patient is satisfied with
Be sensitive to the effects that PCOS can have on self esteem
Let the patient know that there are websites and online groups for “cysters”
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• Baillargeon, J.P. and J. E. Nestler (2006). "Polycystic Ovary Syndrome: A Syndrome of Ovarian Hypersensitivity to Insulin?" J Clin Endocrinol Metab 91(1): 22-24.
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