The syndrome of polycystic ovaries (PCOS) is associated with adiposity and 
metabolic changes predisposing to insulin resistance and diabetes mellitus. 
Because the recently discovered GH secretagogue, ghrelin, is intimately involved 
in the control of appetite and weight regulation, we studied ghrelin levels in a 
group of 26 otherwise healthy women with PCOS. They were compared with 61 
healthy female control subjects and 5 gastrectomized women. Insulin sensitivity 
was assessed by homeostasis model assessment (HOMA) and continuous infusion of 
glucose with model assessment (CIGMA) in all patients. In PCOS women, serum 
ghrelin levels were significantly lower than in healthy lean or obese controls 
(P < 0.001). In insulin-sensitive PCOS women, ghrelin concentrations compared 
well with the healthy controls, whereas in insulin-resistant PCOS ghrelin levels 
were significantly lower and indistinguishable from the low levels found in the 
gastrectomized women. There was a close correlation of ghrelin to insulin 
sensitivity (HOMA, r(2) = 0.330, P < 0.002; CIGMA, r(2) = 0.568, P < 0.0001). 
Treatment of 10 insulin-resistant PCOS women with metformin significantly 
increased circulating fasting ghrelin concentrations (P < 0.02). Ghrelin levels 
did not correlate to any of the parameters of hyperandrogenemia, to the LH/FSH 
ratio, to body mass index, or to fasting insulin and glucose concentrations. In 
summary, ghrelin levels are decreased in PCOS women and are highly correlated to 
the degree of insulin resistance. This suggests that ghrelin could be linked to 
insulin resistance in PCOS women. However, whether low ghrelin in PCOS is a 
cause or the consequence of insulin resistance awaits further investigations.