Metformin decreases BMI more than thiazolidinediones
In a meta-analysis of 10 RCTs (459 patients) comparing the effects of metformin and thiazolidinediones (TZDs), metformin reduced body mass index (BMI) more than TZDs at 3 months (weighted mean difference [WMD]=-2.5 kg/m2; 95% CI, -3.3 to -.6) and 6 months (WMD=-0.70 kg/m2; 95% CI, -0.76 to -0.65).3
In a prospective cohort dose-comparison study, 201 women with PCOS received either metformin 1000 mg or 1500 to 1700 mg daily for 6 months. Patients were asked not to modify their diet or exercise routines. In both dosage groups, patients lost weight from baseline (-3 kg; P<.01), and the number of menstrual cycles increased (0.7 per 6 months; P<.001).4 No clear dose-response relationship was observed.
Spironolactone can significantly reduce hirsutism
A systematic review identified 4 studies (132 patients) of antiandrogen therapy for hirsutism in PCOS. The 3 studies that used the FG score as an outcome all showed significant reductions in hirsutism after 6 to 12 months of treatment with spironolactone.5
Lifestyle modification and metformin both reduce body weight, but lifestyle modification may be better tolerated.
A 6-month RCT of 198 patients with PCOS compared outcomes for spironolactone (50 mg/d), metformin (1000 mg/d), or both. Combined therapy was marginally better than either agent alone for reducing the FG score (end score for combined therapy 9.1 vs 9.6 for spironolactone and 9.7 for metformin, an absolute difference for combined therapy vs spironolactone of -0.5 FG points or -1.4%; P<.05).6
OCPs normalize menstrual cycles and reduce hirsutism
A Cochrane review evaluating the effects of OCPs on patients with PCOS included 4 RCTs (104 patients) that compared OCPs with metformin (1500-2000 mg/d) and 2 RCTs (70 patients) that compared the combination of an OCP and metformin with the OCP alone. Use of an OCP was much more likely to normalize menstrual cycling than metformin alone (2 trials, N=35; odds ratio [OR]=12; 95% CI, 2.2-100). Combining an OCP with metformin resulted in slightly better FG scores than an OCP alone (1 trial, N=40; WMD=-2.8 points; 95% CI, -5.4 to -0.17).7 There was no difference in the final BMI between patients taking an OCP alone, metformin alone, or both.
An RCT of 35 patients compared the effect on insulin levels of an OCP with rosiglitazone 4 mg/d and also looked at menstrual cycling as a secondary outcome. The study found no difference in effect on insulin levels in the 2 groups. All patients taking the OCP reported regular menstrual cycles at the end of the study compared with 75% of the patients taking rosiglitazone (P=.7).8 The study was underpowered to find a difference, however.