The aim of the present study was to determine if the level of plasma totalghrelin and soluble circulating RANKL (sRANKL) vary with the menopausestage, as well as assessing their relationship to each other, and to changes inbone (mineral) mass density (BMD), estradiol (E2) and follicle-stimulatinghormone (FSH). The present study included three main groups: a premenopausal(group I), a peri-menopausal (group II), and a post-menopausal(group III). After assessing the BMD, using the dual-energy-X rayabsorbitometryor DXA test, the peri- and post-menopausal groups were subclassifiedinto subgroups with normal BMD (at lumbar spine, hip and radius)and subgroups with low BMD (osteopenia and/ or osteoporosis). Plasma totalghrelin and sRANKL were estimated by ELISA technique, E2 and FSH werealso measured.The mean plasma level of ghrelin was significantly decreased in the perimenopausaland postmenopausal groups in comparison to the pre-menopausalgroup, and in the peri-menopausal and postmenopausal subjects with low BMDversus those with normal BMD. A significant positive correlation was foundbetween ghrelin and each of E2 and BMD in all subjects, as well as, in peri- andpostmenopausal women, while a significant negative correlation was foundbetween ghrelin and FSH. A regards sRANKL, non-significant decreases in itsmean plasma levels were found in the peri- and post-menopausal groups versusthe pre-menopausal group, as well as in the groups with low BMD versus thosewith normal BMD. However a significant correlation was detected betweensRANKL and each of lumbar BMD and E2, while a positive correlation wasfound with FSH.In conclusion, the positive associations between ghrelin and both ofBMD and estrogen suggest that estrogen and ghrelin may affect BMD by eitherindependent or convergent mechanisms, and may offer the potential for theinclusion of ghrelin agonists in the treatment strategies of postmenopausalosteoporosis. The non-significant changes detected in sRANKL, in spite of thesignificant negative correlation with lumbar spine BMD and E2, questions therole of sRANKL as a bone turnover marker in postmenopausal osteoporosis.