Antipsychotic-induced hyperprolactinemia inhibits the hypothalamo-pituitary-gonadal axis and reduces bone mineral density in male patients with schizophrenia.
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 schizophrenia.


METHODS
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).


CONCLUSIONS
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.
Kishimoto
Taishiro
T
Oizumi Hospital, Tokyo, Japan. taishiro-k@mti.biglobe.ne.jp
Watanabe
Koichiro
K
Shimada
Naoki
N
Makita
Kazuya
K
Yagi
Gohei
G
Kashima
Haruo
H
D015502:Absorptiometry, Photon; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects*; D015519:Bone Density / Q000187:drug effects*; D004958:Estradiol / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood; D006066:Gonads / Q000187:drug effects*; D006801:Humans; D006966:Hyperprolactinemia / Q000139:chemically induced* / Q000503:physiopathology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000503:physiopathology*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000139:chemically induced / Q000453:epidemiology; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000503:physiopathology*; D011388:Prolactin / Q000097:blood; D012559:Schizophrenia / Q000188:drug therapy*; D013739:Testosterone / Q000097:blood
D014150:Antipsychotic Agents; D013739:Testosterone; D004958:Estradiol; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone