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BACKGROUND: Prolactin (PRL) has been proposed to play an important role in the pathophysiology of obesity. To further elucidate the relationship between PRL and obesity-related metabolic disturbances, we performed a large cross-sectional study and also reassessed serum PRL levels in a subsample approximately 1 year after gastric bypass surgery. METHODS: In the cross-sectional part of the study, we assessed basal serum PRL levels in 344 obese subjects (68% women; BMI mean+/-SD, 44.3+/-6.6 kg/m2; range 27.0-67.0 kg/m2) along with measurements of glucose, insulin, C-peptide, triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol, high sensitive (hs) C-reactive protein, and fat mass assessed by bioelectrical impedance analysis. In 38 patients, we reassessed PRL levels approximately 1 year after they have undergone a gastric bypass operation. RESULTS: Women displayed higher basal PRL levels than men (9.0+/-4.8 vs. 7.9+/-3.6 microg/l, P=0.03). Basal PRL levels were neither significantly correlated with the BMI of the subjects (r=-0.05, P=0.77) nor with any other of the assessed variables (all r<0.16, P>0.06) even after adjusting for the influence of sex. After massive surgically induced weight loss that on average almost approached 50 kg, basal serum PRL levels remained completely unchanged (before vs. after, 9.1+/-6.0 vs. 9.2+/-4.6 microg/l, P=0.86). However, preoperative PRL levels significantly correlated with that assessed after the operation (r=0.47; P=0.005). CONCLUSIONS: In contrast to our expectation, we could detect neither any significant association between basal PRL levels and the degree of obesity or related metabolic disturbances nor any systematic changes in basal concentrations of the hormone after massive weight loss. In sum, our data do not support the notion of a major role of PRL in the pathophysiology of obesity.