Luteinizing hormone-releasing hormon (LHRH) agonist induces severe bone loss in rats

• Published in: Japanese Journal of Pharmacology 2000, Vol.82 (suppl.1), p.47-47
• Main Authors: Hara, Kuniko, Akiyama, Yasuhiro, Kobayashi, Masatoshi, Tomiuga, Takashi, Kawashima, Hidetoshi
• Format: Article
• Language: eng ; jpn
• ISSN: 0021-5198
• DOI: 10.1016/S0021-5198(19)47654-3

LHRH agonists suppress ovarian sex steroid production and are used for therapy of endometriosis. However, this property also leads to bone loss. We investigated the time-course and dose-dependency of LHRH agonist on bone loss in rats. Exp.1：One mg/kg of leuprorelin (Leu, Takeda) was given to female rats every 4 weeks for 16 weeks. Uterus weight and bone mineral density (BMD) by pQCT (Stratec) were observed every 4 weeks. Uterus weight and BMD of the femoral metaphysis in the Leu-treated groups were reduced to 30% and 84% of those in the intact group, respectively, at week 4 and were maintained at the same levels thereafter. Exp.2：Leu (0.03, 0.1, 0.3, or 1.0 mg/kg s.c. ) was given to rats. At 4 weeks after treatment, the 17β-estradiol level was reduced dose-dependently from the dose at 0.03 mg/kg. However, Leu of 0.03 and 0.1 mg/kg did not affect uterus weight and that of 0.3 and 1.0 mg/kg reduced it to 65 and 41% of that in the intact group, respectively. BMD of the femoral metaphysis in the Leu 0.03, 0.1, 0.3, and 1.0 mg/kg groups were reduced to 96, 93, 85, and 87% of that in the intact group, respectively. These findings suggest that the decrease in blood estradiol by LHRH agonists affects bone to the same degree or more as uterus weight. Therefore, it is important to observe BMD in LHRH therapy.