Metformin, an
insulin-sensitizing
drug, has been shown to improve ovarian function and
glucose metabolism in obese women with
polycystic ovary syndrome (PCOS), but its effects and possible benefits in nonobese PCOS subjects are not well known. Seventeen nonobese (body mass index < 25 kg/m(2)) women with PCOS were randomized to receive either
metformin (500 mg twice daily for 3 months, then 1000 mg twice daily for 3 months; n = 8) or
ethinyl estradiol (EE, 35 microg)-
cyproterone acetate (CA, 2 mg)
oral contraceptive pills (EE-CA; n = 9). Waist to hip ratio; serum concentrations of sex
steroids,
glucose, and
insulin during a 75-g oral
glucose tolerance test; early phase
insulin and
C-peptide secretion; and
insulin sensitivity using a euglycemic hyperinsulinemic clamp were assessed at baseline and at 3 and 6 months of treatment.
Metformin did not have any effect on
glucose tolerance or
insulin sensitivity, but fasting
insulin concentrations decreased from 44.4 +/- 5.1 (SE) to 29.8 +/- 4.3 pmol/liter (P = 0.03), the waist to hip ratio decreased from 0.78 +/- 0.01 to 0.75 +/- 0.01 (P = 0.01), and hepatic
insulin clearance increased during the treatment. Furthermore,
metformin decreased serum
testosterone levels from 2.7 +/- 0.3 to 2.0 +/- 0.2 nmol/liter (P = 0.01) and improved menstrual cyclicity. EE-CA did not have any significant effect on
glucose tolerance, serum
insulin levels, or
insulin sensitivity, but it increased slightly the body mass index (P = 0.09) and significantly serum
leptin concentrations (P < 0.001) and decreased serum
testosterone levels from 2.1 +/- 0.2 to 1.4 +/- 0.2 nmol/liter (P = 0.03). In conclusion, EE-CA seems to be an efficient mode of
therapy for hyperandrogenic symptoms associated with PCOS, but its possible negative effects on
insulin and
glucose metabolism also have to be taken into consideration in nonobese subjects.
Metformin improved
hyperandrogenism,
hyperinsulinemia, and menstrual cyclicity, most likely through its positive effect on
insulin clearance and abdominal adiposity. Thus, similarly to obese PCOS women, nonobese PCOS subjects with
anovulation may also benefit from
metformin treatment.