PCOS is a heterogeneous complex genetic trait of multifactorial nature, and it is one of the most common metabolic and reproductive disorders affecting women during their reproductive period . Obesity is an upcoming health hazard affecting the whole world and it is one of the most important and concerning predisposing factor of development of PCOS, since about 35-80% of PCOS women are overweight or obese [17, 18]. Weight loss and exercise as part of lifestyle modification could be the cornerstone in the management of PCOS .
A preponderance of evidence suggests that ghrelin stimulates growth hormone secretion, regulates glucose metabolism, appetite, body weight, endocrine pancreatic, and ovarian functions [20, 21].
Despite many supporting pieces of evidence about the impact of weight loss on obesity and PCOS characteristics, conflicting data have been reported regarding the impact of weight loss on ghrelin level. Therefore, we think that this is the first research that evaluates the influence of weight loss after 12 weeks of following a Mediterranean diet-based weight loss program on plasma ghrelin level and clinical phenotype of PCOS.
The results of the current study showed statistically significant elevations of obesity measures: BMI, WHR, FMI%, FFMI%, metabolic characteristics, and phenotype characteristic of PCOS compared to controls. The finding of our present study consistent with our previous studies [22,23,24,25,26].
The main finding of the present study is that, after 12 weeks of the MD weight loss programmed, there was a significant weight reduction within both groups when compared to baseline. In PCOS group, there was a statistically significant improvement of anthropometric measures, glycemic, and lipid profile, and the phenotype characteristics of PCOS obese women were also improved in particularly, hirsutism score, ovarian volume, AFC, FSH, DHEA-S, T testosterone, and androstenedione.
In accordance to our results, a study conducted by Tolino et al. showed after 4 weeks of weight loss program, there was a reduction of free testosterone and fasting insulin levels as well as improvement in menstruation .
In agreement with our results, Van Dam et al. observed that after achieving 10% weight loss via a VLCD, the estradiol-dependent negative feedback on LH was normalized and led to the resumption of ovulation .
We in this study attempted to pierce out the levels of plasma ghrelin in both obesity and PCOS, and we found that there were significantly lower levels of plasma ghrelin in PCOS women compared to obese women without PCOS and controls.
Our findings are in concordance with Houjeghani et al. meta-analysis study, and they observed that ghrelin levels were significantly lower in PCOS patients than in controls .
Our results are in consistence with those reporting the low levels of ghrelin in PCOS patients compared to the control group [29, 30]. However, an interesting study by Orio et al. identified has shown no difference in ghrelin levels among PCOS and healthy controls .
Against our results, Wasko and colleagues demonstrated that high ghrelin levels in PCOS patients compared to the control group .
Considering the association between plasma ghrelin and clinical and laboratory findings among obese women. In the obese non-PCOS group, plasma ghrelin levels were significantly negatively correlated with anthropometric measures, glycemic, lipid profile, and the phenotype characteristics of PCOS.
These results are parallel to those of Kamal et al. who stated that obese PCOS patients confirmed significantly lower ghrelin levels than controls and was negatively correlated with cardiometabolic risk factors .
Although there are many laboratory markers that could be used in the diagnosis of PCOS, we noticed neither specific nor sensitive markers of PCOS. Accordingly, we analyzed our data by ROC to estimate the sensitivity and specificity of plasma ghrelin for diagnosis of obesity by ROC analysis, the sensitivity was 96.4%, and the specificity was 96%. The power of plasma ghrelin to diagnose PCOS among obese women, the sensitivity was 88%, and specificity was 97.5%. Regarding the finding of the ROC curve, Kamal et al. detected that the sensitivity of plasma ghrelin to diagnose PCOS was 70% and specificity was 86% .
The results presented herein are innovative; as this study performs a robust evaluation of the role of weight loss on plasma ghrelin levels, we detected in both studied obese groups significant higher levels of plasma ghrelin after weight loss for 12 weeks compared to baseline levels.
Similarly, to our finding, different studies confirmed the higher levels of plasma ghrelin after weight reduction .
In addition, studies based on intensive energy restriction (very low caloric diet) showed increasing ghrelin concentrations were reported [34, 35], while other studies found that the levels of plasma ghrelin were stable after weight loss .
By contrast to our results, Cummings et al. detected decreasing ghrelin levels after weight reduction . The contrast in results may be due to differences in study design, follow-up periods, measurement techniques, surgical intervention, and circadian rhythm. Meanwhile, ghrelin is produced predominately in the stomach, and it is difficult to distinguish the effect of surgery and reduction of overweight in these studies, while the results reported by previous studies using dietary approaches for weight loss observed different results. A study conducted by Reinehr et al. found that there was no significant difference in ghrelin levels after weight loss program for a long-term period of 1 year due to a high-carbohydrate low-fat diet .
The weight loss program we used in our study was guided by MD which is characterized by a high consumption of vegetables, legumes, fruits and nuts, cereals, and olive oil with a moderate high uptake of fish, a low-to-moderate intake of dairy products, and a low intake of meat and poultry . Thus, our findings were different from Reinehr et al. results , as diet components greatly affect the gastrointestinal hormones like ghrelin, while the other hormones are not directly influenced by diet.
Some limitations should be considered. The sample size was small and non-randomization of the study, and further larger studies should be performed in the future to validate the results and take into consideration the impact of weight loss on fertility