The Changes in Plasma Serotonin Levels after Hormone Therapy and Their Relationship with Estrogen Responsiveness on Bone in Postmenopausal Women

CONTEXT: Selective serotonin reuptake inhibitors have shown to be associated with an increased risk of fractures. It has been suggested that circulating serotonin is an important regulatory factor and that estrogen may regulate bone metabolism through the serotonin pathway. OBJECTIVE: Our objective was to determine the association between plasma serotonin level and bone turnover before and after hormone therapy (HT) in postmenopausal women. PARTICIPANTS AND DESIGN: In this parallel comparative study using age-matched controls, 80 postmenopausal women (21 control, 59 receiving HT) aged 46-64 yr were assessed. The plasma levels of serotonin, serum concentrations of osteocalcin and carboxyterminal telopeptides, and bone mineral density (BMD) were measured at baseline and after 3 months and 1 yr of HT. RESULTS: The plasma serotonin level was significantly correlated with serum total alkaline phosphatase level at baseline (r = -0.223, P = 0.048) but not with serum osteocalcin (r = -0.217, P = 0.056) or carboxyterminal telopeptides (r = -0.217, P = 0.054). There was no significant association between baseline serotonin and BMD measured at the spine or femur. The median decrements of circulating serotonin from baseline were -9.3% (interquartile range -34.0 to 53.6%) and -7.2% (-25.5 to 64.5%) at 3 months and 1 yr of HT, respectively. These changes were not significantly different from those in the control group. The short-term changes of circulating serotonin at 3 months after HT did not show significant association with the changes in BMD measured at the lumbar spine or proximal femur 1 year after HT. CONCLUSIONS: Our results suggest that circulating serotonin may reflect bone turnover status, but it is not a strong enough predictor of bone loss to use as a bone marker. Moreover, serial measurements of plasma serotonin after short-term treatment with estrogen cannot predict the long-term responsiveness of bone to estrogen, suggesting that the bone-preserving effect of estrogen is independent of the peripheral action of serotonin on bone.