Antipsychotic-Induced Hyperprolactinemia Inhibits the Hypothalamo-Pituitary-Gonadal Axis and Reduces Bone Mineral Density in Male Patients With Schizophrenia
J Clin Psychiatry 2008;69(3):385-391
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Objective: An inhibitory effect of hyperprolactinemia on the
hypothalamo-pituitary-gonadal axis has been suggested as a mechanism of bone
loss in schizophrenia, but this has not been confirmed. In this study, which
was conducted in Tokyo, Japan, from February to May 2005, we examined the
possible causes of reduced bone mineral density (BMD) in male patients with
Method: The BMD of the radius of 74 male patients (aged
31-78 years) who met the diagnostic criteria for DSM-IV schizophrenia was
measured by dual-energy x-ray absorptiometry. Levels of prolactin (PRL),
follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone,
estradiol, and 1,25-dihydroxy vitamin D (VitD) were also measured. Pedometers
were used to measure the impact of exercise.
Results: Study subjects showed lower BMD in all age
groups compared with reference values in healthy persons. There was no
significant difference in the Z score among low, medium, and high exercise
groups. 87% of the subjects had hyperprolactinemia, and VitD levels were normal
in all subjects except 1. The high PRL group had lower levels of FSH and LH,
and significantly lower levels of estradiol (p < .05), compared with the normal
PRL group. In the high PRL group, there was a significant negative correlation
between the duration of treatment and the Z score (p < .05).
Conclusion: Male patients with schizophrenia had lower BMD
than normal individuals irrespective of the amount of exercise or the level of
VitD. The results support the hypothesis that inhibition of the
hypothalamo-pituitary-gonadal axis by hyperprolactinemia contributes to the
mechanism of the bone loss and suggest that the longer the duration of
hyperprolactinemia, the greater the reduction in BMD.