Effect of Hyperinsulinemia on Leptin and Ghrelin Levels in Polycystic Ovarian Syndrome: A Meta-Analysis

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Leptin and ghrelin are important markers in PCOS due to their correlation with obesity, insulin resistance, and fertility. There is currently a debate in the literature about whether altered leptin and ghrelin levels in women with PCOS are a result of the disease itself or if they are due to factors such as the hyperinsulinemic state characteristic of PCOS. This meta-analysis aims to assess if insulin levels impact leptin and ghrelin levels in PCOS.  Eight case-control studies assessing the relationship between insulin and leptin, as well as five case-control studies assessing the relationship between insulin and ghrelin, were identified in PubMed. Pearson's correlation coefficient (PCC) and the sample size were extracted, and two meta-analyses were conducted using a random-effects model. Total heterogeneity (I2) with a confidence interval of 95% was then determined. "Leave-one out" diagnostics were calculated for each case. If a study was identified as being significantly influential, the study was removed from the data set, and the trim and fill procedure was applied. Publication bias was assessed using Egger's regression test and rank correlation test.  Our results showed a moderate positive relationship (r=0.56, 95% confidence interval (CI) (0.42, 0.71), with substantial heterogeneity I²=81.35%, 95% CI (25.2799, 88.2451)) between insulin and leptin levels, and a moderate negative relationship (r=-0.33, 95% CI (-0.43, -0.24)), with low heterogeneity (I²=0.00%, 95% CI (0.0000, 80.8159)) between insulin and ghrelin levels. Therefore, there is a significant relationship between insulin and higher leptin and lower ghrelin levels in women with PCOS. Better insulin control may have a positive effect on fertility, appetite, weight, body image, and quality of life in these women. This correlation is likely multifactorial, and further studies are needed to isolate factors influencing these hormones.