雷洛昔芬对子宫内膜异位症患者骨代谢的影响
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摘要
目的评价雷洛昔芬对长期应用促性腺激素释放激素类似物(gonadotropin-releasing hormone analogues,GnRH-a)治疗子宫内膜异位症引起的骨质丢失的影响。方法选择38例中重度子宫内膜异位症术后患者,给予亮丙瑞林(3.75 mg/4周)+雷洛昔芬(60 mg/d),治疗持续48周,治疗前后检测骨密度(bone mineral density,BMD)、血清骨钙素、碱性磷酸酶、尿吡啶啉/肌酐水平。结果与治疗前比较,治疗48周后患者腰椎2-4的BMD[(1.193±0.079)vs.(1.187±0.069)g/m2]和股骨颈BMD[(0.908±0.074)vs.(0.896±0.084)g/m2]轻度下降,血清骨钙素[13.42(9.45,18.96)vs.13.46(10.41,17.41)ng/m L]、碱性磷酸酶[79.61(56.24,109.47)vs.91.27(66.34,110.50)U/L]、尿吡啶啉/肌酐[22.31(20.63,23.66)vs.22.77(20.93,26.13)nmol/mmol]轻度升高,但治疗前后差异均无统计学意义(P>0.05)。结论雷洛昔芬联合GnRH-a可延长中重度子宫内膜异位症的疗程,并不增加骨质疏松的风险。
Objective To evaluate the efficacy of raloxifene in preventing bone loss induced by long term gonadotropin-releasing hormone analogues(GnRH-a) administration. Methods Thirty-eight women with severe endometriosis were treated with leuprolide acetate depot at a dosage of 3. 75 mg/4 weeks and raloxifene 60 mg/d,for 48 weeks after the operations. Bone mineral density(BMD),serum osteocalcin,alkaline phosphatase,and urinary pyridinoline/creatinine were measured at admission,and after treatment. Results After 48 weeks of GnRH-a plus raloxifene,L2-4 and femoral neck's BMD decreased slightly,respectively [(1. 193 ± 0. 079) vs.(1. 187 ± 0. 069) g/m2],and[(0. 908±0. 074) vs.(0. 896±0. 084) g/m2]. Serum osteocalcin,alkaline phosphatase,and urinary pyridinoline/creatinine increased slightly,respectively [13. 42(9. 45,18. 96) vs. 13. 46(10. 41,17. 41) ng/m L],[79. 61(56. 24,109. 47) vs. 91. 27(66. 34,110. 50) U/L],and[22. 31(20. 63,23. 66) vs. 22. 77(20. 93,26. 13)nmol/mmol]. All differences were not significant(all P> 0. 05). Conclusion Our study shows that the administration of GnRH-a plus raloxifene in women with severe endometriosis is an effective long-term treatment and does not increase the risk of osteoporosis.
Objective To evaluate the efficacy of raloxifene in preventing bone loss induced by long term gonadotropin-releasing hormone analogues(GnRH-a) administration. Methods Thirty-eight women with severe endometriosis were treated with leuprolide acetate depot at a dosage of 3. 75 mg/4 weeks and raloxifene 60 mg/d,for 48 weeks after the operations. Bone mineral density(BMD),serum osteocalcin,alkaline phosphatase,and urinary pyridinoline/creatinine were measured at admission,and after treatment. Results After 48 weeks of GnRH-a plus raloxifene,L2-4 and femoral neck's BMD decreased slightly,respectively [(1. 193 ± 0. 079) vs.(1. 187 ± 0. 069) g/m2],and[(0. 908±0. 074) vs.(0. 896±0. 084) g/m2]. Serum osteocalcin,alkaline phosphatase,and urinary pyridinoline/creatinine increased slightly,respectively [13. 42(9. 45,18. 96) vs. 13. 46(10. 41,17. 41) ng/m L],[79. 61(56. 24,109. 47) vs. 91. 27(66. 34,110. 50) U/L],and[22. 31(20. 63,23. 66) vs. 22. 77(20. 93,26. 13)nmol/mmol]. All differences were not significant(all P> 0. 05). Conclusion Our study shows that the administration of GnRH-a plus raloxifene in women with severe endometriosis is an effective long-term treatment and does not increase the risk of osteoporosis.
引文
[1]中华医学会妇产科学分会子宫内膜异位症协作组.子宫内膜异位症的诊治指南[J].中华妇产科杂志,2015,50:161-169.
[2]周龙书,戚潜辉,彭菊兰.GnRHa治疗子宫内膜异位症对患者血清激素及骨密度的影响[J].广东医学,2006,27:915-916.
[3]Crosignani P,Olive D,Bergqvist A,et al.Advances in the management of endometriosis:an update for clinicians[J].Hum Reprod Update,2006,12:179-189.
[4]胡钟元,马彬,杨克虎,等.促性腺激素释放激素激动剂治疗保守手术后子宫内膜异位症的Meta分析[J].实用妇产科杂志,2010,26:389-392.
[5]Cummings SR,Eckert S,Krueger KA,et al.The effect of raloxifene on risk of breast cancer in postmenopausal women:results from the MORE randomized trial.Multiple Outcomes of Raloxifene Evaluation[J].JAMA,1999,281:2189-2197.
[6]Cohen FJ,Watts S,Shah A,et al.Uterine effects of 3-year raloxifene therapy in postmenopausal women younger than age 60[J].Obstet Gynecol,2000,95:104-110.
[7]Goldstein SR,Scheele WH,Rajagopalan SK,et al.A12-month comparative study of raloxifene,estrogen,and placebo on the postmenopausal endometrium[J].Obstet Gynecol,2000,95:95-103.
[8]黄涛,刘世清,张弩,等.雷洛昔芬治疗绝经后妇女骨质疏松症的系统评价[J].中国骨质疏松杂志,2013,19:391-397.
[9]Palomba S,Orio F Jr,Morelli M,et al.Raloxifene administration in women treated with gonadotropin-releasing hormone agonist for uterine leiomyomas:effects on bone metabolism[J].J Clin Endocrinol Metab,2002,87:4476-4481.
[10]Cho YH,Um MJ,Kim SJ,et al.Raloxifene Administration in Women Treated with Long Term Gonadotropin-releasing Hormone Agonist for Severe Endometriosis:Effects on Bone Mineral Density[J].J Menopausal Med,2016,22:174-179.
[11]张萌萌.中国老年学学会骨质疏松委员会骨代谢生化指标临床应用专家共识[J].中国骨质疏松杂志,2014,20:1263-1272.
[12]Civitelli R,Armamento-Villareal R,Napoli N.Bone turnover markers:understanding their value in clinical trials and clinical practice[J].Osteoporos Int,2009,20:843-851.
[2]周龙书,戚潜辉,彭菊兰.GnRHa治疗子宫内膜异位症对患者血清激素及骨密度的影响[J].广东医学,2006,27:915-916.
[3]Crosignani P,Olive D,Bergqvist A,et al.Advances in the management of endometriosis:an update for clinicians[J].Hum Reprod Update,2006,12:179-189.
[4]胡钟元,马彬,杨克虎,等.促性腺激素释放激素激动剂治疗保守手术后子宫内膜异位症的Meta分析[J].实用妇产科杂志,2010,26:389-392.
[5]Cummings SR,Eckert S,Krueger KA,et al.The effect of raloxifene on risk of breast cancer in postmenopausal women:results from the MORE randomized trial.Multiple Outcomes of Raloxifene Evaluation[J].JAMA,1999,281:2189-2197.
[6]Cohen FJ,Watts S,Shah A,et al.Uterine effects of 3-year raloxifene therapy in postmenopausal women younger than age 60[J].Obstet Gynecol,2000,95:104-110.
[7]Goldstein SR,Scheele WH,Rajagopalan SK,et al.A12-month comparative study of raloxifene,estrogen,and placebo on the postmenopausal endometrium[J].Obstet Gynecol,2000,95:95-103.
[8]黄涛,刘世清,张弩,等.雷洛昔芬治疗绝经后妇女骨质疏松症的系统评价[J].中国骨质疏松杂志,2013,19:391-397.
[9]Palomba S,Orio F Jr,Morelli M,et al.Raloxifene administration in women treated with gonadotropin-releasing hormone agonist for uterine leiomyomas:effects on bone metabolism[J].J Clin Endocrinol Metab,2002,87:4476-4481.
[10]Cho YH,Um MJ,Kim SJ,et al.Raloxifene Administration in Women Treated with Long Term Gonadotropin-releasing Hormone Agonist for Severe Endometriosis:Effects on Bone Mineral Density[J].J Menopausal Med,2016,22:174-179.
[11]张萌萌.中国老年学学会骨质疏松委员会骨代谢生化指标临床应用专家共识[J].中国骨质疏松杂志,2014,20:1263-1272.
[12]Civitelli R,Armamento-Villareal R,Napoli N.Bone turnover markers:understanding their value in clinical trials and clinical practice[J].Osteoporos Int,2009,20:843-851.