Metformin therapy increases insulin-like growth factor binding protein-1 in hyperinsulinemic women with polycystic ovary syndrome.
OBJECTIVE
Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism, insulin resistance, compensatory hyperinsulinemia, and increased levels of free insulin-like growth factor-I (IGF-I), presumably due to a decline in IGF binding protein 1 (IGFBP-1). This study was designed to evaluate effects of metformin therapy on serum levels of IGFBP-1 and IGF-I.


METHODS
Twenty-seven obese, hyperandrogenic PCOS women with elevated fasting insulin were treated for 12 weeks with metformin (500 mg p.o., t.i.d.). Serum levels of insulin, testosterone, sex hormone binding globulin (SHBG), IGF-I, and IGFBP-1 were measured before and after treatment. Body mass index (BMI) and waist-to-hip ratio (WHR) were assessed at baseline and at the end of therapy.


RESULTS
Metformin therapy significantly increased IGFBP-1 concentration by 38% (P = 0.05) but had no demonstrable effect on the total IGF-I levels. Fasting insulin levels declined by 38% (P = 0.0001) while the glucose/insulin ratio increased by 72% (P = 0.0001) and quantitative insulin sensitivity check index (QUICKI) increased by 8% (P = 0.0001). Metformin treatment also significantly decreased testosterone (by 37%, P = 0.0001) and increased SHBG concentration (by 16%, P = 0.04). Multiple linear regression analysis revealed that baseline IGFBP-1 levels correlated inversely and independently with two baseline parameters: WHR (P = 0.003) and free testosterone index (P = 0.04).


CONCLUSIONS
The present study shows that metformin therapy not only restores normal levels of insulin and testosterone, but also decreases the pool of free-bioactive IGF-I by increasing the levels of circulating IGFBP-1. We provide further arguments in favor of metformin therapy in hyperinsulinemic women with PCOS.
Pawelczyk
Leszek
L
Department of Gynecology and Obstetrics, Karol Marcinkowski University of Medical Sciences, ul. Polna 33, 60-535 Poznan, Poland. pawelczyk@gpsk.am.poznan.pl
Spaczynski
Robert Z
RZ
Banaszewska
Beata
B
Duleba
Antoni J
AJ
D000328:Adult; D001824:Body Constitution; D015992:Body Mass Index; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D016014:Linear Models; D008687:Metformin / Q000627:therapeutic use*; D011085:Polycystic Ovary Syndrome / Q000097:blood*; D011388:Prolactin / Q000097:blood; D013739:Testosterone / Q000097:blood
D007004:Hypoglycemic Agents; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D011388:Prolactin; D008687:Metformin