In a previous study we were the first to describe a negative correlation between circulating
ghrelin concentrations and
androgen levels in human plasma, suggesting an interaction between
ghrelin and the endocrine regulation of reproductive physiology. We now investigated a potential direct regulatory influence of circulating
androgens on plasma
ghrelin levels. Fourteen obese women with
polycystic ovary syndrome (PCOS) on a hypocaloric diet were randomly assigned to treatment groups (open-labeled design), receiving either placebo (no.=7) or the
antiandrogen flutamide (no.=7) for 6 months. Anthropometry, visceral (VAT) and subcutaneous (SAT) adipose tissue (quantified by computerized tomography), plasma
hormone levels,
insulin sensitivity indexes (Quantitative
Insulin-Sensitivity Check Index-QUICKI) and Homeostatic Model Assessment applied to the oral
glucose tolerance test (HOMA(OGTT)) were evaluated at baseline and at the end of the study.
Body weight decreased and
insulin resistance indexes improved in both groups. A tendency toward a greater loss of VAT was observed in the
flutamide group. Only in the
flutamide group was a significant reduction of
androgens levels observed. Plasma
ghrelin levels significantly increased following treatment with
flutamide, while
ghrelin remained unchanged in the placebo group. We observed a negative correlation between changes of
ghrelin levels and changes of
androgen plasma concentration in the
flutamide-treated group. In the same group a positive correlation was found between plasma
ghrelin changes and
insulin sensitivity as expressed by HOMA(OGTT). Analysis in a multiple regression model, however, showed that plasma
ghrelin changes were mainly due to changes of
androgen levels rather than improved
insulin sensitivity. We, therefore, conclude that
androgens are independent modulators of circulating
ghrelin concentrations.