In this prospective, randomized study we determined 10-d effects of medroxyprogesterone acetate (MPA) and micronized progesterone (MP) either orally or per vaginally on hormonal parameters, glucose metabolism and lipid profiles in patients with polycystic ovary syndrome (PCOS). Twenty-eight consecutive women with PCOS were randomized to receive 10-d MPA, oral MP, or vaginal MP. Hormonal parameters, insulin levels, oral glucose tolerance test, lipid profiles, and homeostasis model assessment and quantitative insulin sensitivity check indexes were assessed in all groups before and after treatment. Oral MPA and oral MP decreased LH (15.64 ± 13.17 to 7.27 ± 4.35 IU/liter, P = 0.028, and 18.85 ± 11.86 to 10.49 ± 6.48 IU/liter, P = 0.009, respectively) and total testosterone (5.85 ± 2.80 to 3.40 ± 1.72 nmol/liter, P = 0.013, and 5.29 ± 2.98 to 3.43 ± 2.10 nmol/liter, P = 0.037, respectively) levels. Hormonal parameters did not change with vaginal MP. Basal insulin (123.42 ± 97.50 to 87.38 ± 48.68 pmol/liter; P = 0.021) and homeostasis model assessment levels decreased, and quantitative insulin sensitivity check index increased significantly in the oral MPA group. Low density lipoprotein cholesterol and lipoprotein (a) levels decreased only in the MPA group. In conclusion, short-term oral MP and especially oral MPA might ameliorate insulin sensitivity in patients with PCOS. Vaginal MP has no effect on glucose metabolism and lipid profiles. LH, total testosterone, and insulin levels may be affected from the short-term progesterone treatment.