Premenopausal women with macroprolactinemia are characterized by increased cardiometabolic risk. No previous study has investigated the impact of any lipid-lowering agent on circulating levels of cardiometabolic risk factors in patients with elevated macroprolactin content. We studied 2 groups of women matched for age, body mass index, plasma lipids, and blood pressure: 12 women with macroprolactinemia and 14 women with prolactin levels within the reference range. Because of coexistent isolated hypercholesterolemia, all subjects were then treated with atorvastatin (20 mg daily). Glucose homeostasis markers, plasma lipids, as well as circulating levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and 25-hydroxyvitamin D were measured before entering the study and 6 months later. The treatment arms differed in baseline values of hsCRP and 25-hydroxyvitamin D, as well as in insulin sensitivity. Atorvastatin decreased total and low-density lipoprotein cholesterol levels stronger in women without than in women with macroprolactinemia. In normoprolactinemic women, atorvastatin decreased circulating levels of uric acid, hsCRP, fibrinogen, homocysteine, and increased concentrations of 25-hydroxyvitamin D, whereas in women with macroprolactinemia the drug decreased levels of hsCRP and homocysteine, as well as impaired insulin sensitivity. Both study groups differed in post-treatment insulin sensitivity and post-treatment values of prolactin before polyethylene glycol precipitation, macroprolactin, total cholesterol, low-density lipoprotein cholesterol, glycated hemoglobin, uric acid, hsCRP, fibrinogen, homocysteine, and 25-hydroxyvitamin D. In conclusion, the obtained results suggest that macroprolactinemia may attenuate cardiometabolic effects of atorvastatin.