Circulating Ghrelin Levels in Patients with Polycystic Ovary Syndrome

Abstract

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.

Ghrelin in Type 2 diabetes mellitus and metabolic syndrome

“…Low ghrelin concentrations were shown to associate independently with Type 2 diabetes and insulin resistance (Pöykkö et al, 2003). A strong inverse correlation between ghrelin concentrations and insulin resistance measured by homeostasis model of insulin resistance (HOMA-IR) and/or insulin concentrations has been observed also in other studies, for example among women with polycystic ovary syndrome (Schöfl et al, 2002) and in obese middle-aged subjects (McLaughlin et al, 2004). A recent study that aimed to clarify the relationships between total, acylated and des-acylated ghrelin molecules specifically with insulin resistance showed that these molecules might be involved in glucose and insulin metabolism in different ways.…”

“…One such molecule is ghrelin, a blood-borne orexigenic signal from gut to brain (Kojima et al, 1999), with multiple hormonal, metabolic, and cardiovascular activities (Kojima et al, 2005). Low ghrelin concentrations have been associated with the components of the MS, like obesity (Tschöp et Page 3 of 13 A c c e p t e d M a n u s c r i p t 3 al., 2001), insulin resistance (Bacha and Arslanian, 2005;Pöykkö et al, 2003;Schöfl et al, 2002), and blood pressure (Fagerberg et al, 2003;Pöykkö et al, 2003). The negative association between ghrelin and waist circumference, a prerequisite for the MS, has also been reported (Fagerberg et al, 2003).…”

Ghrelin levels are suppressed and show a blunted response to oral glucose in women with polycystic ovary syndrome.

“…There have been few studies of ghrelin in PCOS, and most have focused on fasting (total) ghrelin levels (9)(10)(11)(12)(13). These have yielded inconsistent and conflicting data to support both normal (14) and abnormal (significantly lower) fasting serum ghrelin levels in women with PCOS versus controls (9)(10)(11).…”

“…These have yielded inconsistent and conflicting data to support both normal (14) and abnormal (significantly lower) fasting serum ghrelin levels in women with PCOS versus controls (9)(10)(11). In a couple of studies, a significant negative correlation between fasting serum ghrelin and homeostasis model assessment of insulin resistance (HOMA2 IR; a measure of insulin sensitivity) has been demonstrated (9,11). However, only one previous study has assessed postprandial serum ghrelin levels in PCOS (15), and the lack of equivalent postprandial data in other studies represents a significant limitation of the current literature.…”

Ghrelin and reproductive disorders

“…Several studies have shown that ghrelin levels in obese PCOS were lower than in weightmatched control subjects without PCOS, and an inverse correlation between androgen (particularly androstenedione) blood levels has been found (Barber et al, 2008;Bideci et al, 2008;Glintborg et al, 2006;Moran et al, 2004;Pagotto et al 2002;Panidis et al, 2005;Panidis et al, 2010;Sağsöz et al, 2009;Schöfl et al, 2002;Zwirska-Korczala et al, 2008), although some studies could not confirm these findings (Orio et al, 2003;Wasko et al, 2004). In one study, an inverse correlation has been reported between the hirsutism score and ghrelin concentrations (Panidis et al, 2010).…”