Doppler analysis of ovarian stromal blood flow changes after treatment with metformin versus ethinyl estradiol-cyproterone acetate in women with polycystic ovarian syndrome: A randomized controlled trial.

Objectives: To evaluate the effects of oral contraceptive pill (OCP) and metformin at the end of 6 months of treatment on ovarian stromal blood flow by using pulsed and color Doppler in women with PCOS.

Methods: Women with PCOS (n=101) fulfilling the Rotterdam criteria were enrolled and randomized to receive either OCP or metformin. OCP was administered in cycles of 28 days (21 pills containing 35μg of ethinylestradiol plus 2mg of cyproterone acetate followed by 7 placebo pills) for six cycles and metformin 500mg was administered twice daily for 6 months. Clinical, anthropometric, hormonal and metabolic parameters and resistance index (RI) and pulsatility index (PI) of both ovarian stromal vessels were assessed before and after treatment.

Results: OCP resulted in a higher reduction in serum luteinizing hormone (LH) and androgens whereas metformin resulted in significant reduction in BMI, waist circumference, and insulin resistance. There was a significant increase in RI and PI of both ovarian stromal vessels with both drugs post-treatment, however, the increase was more prominent in the OCP group. There was a significant negative correlation between changes in LH and testosterone levels with changes in PI and RI in OCP group whereas changes in serum fasting insulin levels negatively correlated with changes in PI and RI values in the Metformin group.

Conclusions: Treatment with both OCP and metformin leads to a reduction in ovarian stromal vascularization in PCOS women perhaps through different mechanisms and this reduction is more prominent with OCP.