Estrogen deficiency is thought to be the main factor leading to postmenopausal osteoporosis (PMO). A role for calcitonin (CT) has been proposed as mediator of estrogen action on bone, and therefore, as pathogenetic factor of PMO. However, this hypothesis is still controversial. To further analyze the relationships between estrogens and CT in PMO, we studied the effects of one-year estro/progesterone therapy on CT secretory reserve, evaluated by a calcium infusion test in 12 postmenopausal women, as compared to 12 placebo treated subjects. In the hormone treated group, blood levels of CT showed a progressive increase during the study and a plateau was reached at 9 months, indicating that CT production achieved a new steady state. Hormonal therapy also significantly improved the CT response to calcium stimulation test. A concomitant increase of vertebral bone mass was observed in the hormone treated women, who also maintained initial bone density of femoral dyaphyses. On the contrary, the placebo treated group continued to lose bone mineral at both sites. Our study demonstrates that estrogens regulate CT secretion in postmenopausal women; thus, CT may be considered a mediator of estrogen action on bone.