肉堿治療原發性弱精癥療效和安全性的系統評價_《中國循證醫學雜志》

作者：

薛瑜 ^1,2 , 張雁鋼 ^1,3 , 王莉 ⁴ ,  盧一平 ¹

1. 四川大學華西醫院泌尿外科（成都 610041）2. 四川大學華西第二醫院兒科（成都 610041）3. 山西醫科大學第一臨床醫學院泌尿外科（太原 030001）4. 四川大學華西醫院中國循證醫學中心（成都 610041）;

關鍵詞：

肉堿弱精癥不育系統評價

DOI：

10.7507/1672-2531.20090064

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目的　評價肉堿治療原發性弱精癥的療效和安全性。
方法　采用Cochrane 系統評價方法，電子檢索1995 年1 月至2006 年12 月期間MEDLINE、EMbase、Cochrane 圖書館、CNKI 等資料庫，輔以手工檢索及追查已納入文獻的參考文獻。納入肉堿治療原發性弱精癥的隨機對照試驗（RCT）。由2 名評價者共同評價納入研究的質量，對符合標準的研究采用RevMan 4.2.10 軟件進行Meta 分析。
結果　共納入5 個RCT，其中B 級2 個，C 級3 個，包括346 例患者，排除失訪人數后實際納入307 例進行Meta 分析。Meta 分析結果顯示：① 肉堿治療3 ～ 6 個月后，治療組與對照組患者配偶的自然妊娠率差異有統計學意義［RR=2.46，95%CI（1.12，5.43），P=0.03］；② 肉堿治療3個月和6 個月后治療組與對照組前向活動精子數差異均無統計學意義［WMD=9.16，95%CI（0.14，18.18），P=0.05；WMD=5.28，95%CI（– 4.45，15.01），P=0.29)］；③ 肉堿治療3 個月和6 個月后治療組與對照組前向活動精子率差異均無統計學意義［WMD=14.56，95%CI（– 4.49，33.61），P=0.13；WMD=7.34，95%CI（– 5.93, 20.61），P=0.28］；④ 肉堿治療3 個月和6 個月后治療組與對照組活動精子數差異均無統計學意義［WMD=15.32，95%CI（– 1.34，31.98），P=0.07；WMD=6.20，95%CI（– 3.00，15.39），P=0.19］；⑤ 肉堿治療3 個月和6 個月后治療組與對照組精子總活動率差異均無統計學意義［WMD=2.97，95%CI（– 5.75，11.69），P=0.50；WMD=4.48，95%CI（– 9.17，18.14），P=0.52］；⑥ 肉堿治療3 個月和6 個月后治療組和對照組精液量差異均無統計學意義［WMD= – 0.12，95%CI（– 0.55，0.30），P=0.57；WMD=0.03，95%CI（– 0.38，0.45），P=0.87］；⑦ 肉堿治療3 個月和6 個月后治療組與對照組精子密度差異均無統計學意義［WMD=7.92，95%CI（– 2.85，18.68），P=0.15；WMD=1.02，95%CI（– 5.09，7.14），P=0.74］。有3 個研究報告治療期間均無嚴重不良反應發生。
結論　現有證據顯示，肉堿治療可提高原發性弱精癥導致不育患者配偶的自然妊娠率，但不能改善精液分析的各項指標，無明顯不良反應。由于本系統評價納入文獻的數量及質量有
限，目前尚不能肯定肉堿治療能夠改善原發性弱精癥導致不育患者的預后。建議進行大樣本、設計良好、指標全面的臨床隨機對照試驗，以提供更佳證據。

引用本文： 薛瑜,張雁鋼,王莉,盧一平. 肉堿治療原發性弱精癥療效和安全性的系統評價. 中國循證醫學雜志, 2009, 09(3): 337-345. doi: 10.7507/1672-2531.20090064 復制

1.	infertility. Urol Clin North Am, 2002, 29(4): 949-963.
2.	癥. 第1版. 北京: 人民軍醫出版社, 2003. 36-39.
3.	selected cases of male factor infertility: A double-blind crossover.
4.	trial. Fertil Steril, 2003, 79(2): 292-300.
5.	randomized trial of the use of combined l-carnitine and l-acetylcarnitine.
6.	treatment in men with asthenozoospermia. Fertil Steril,.
7.	海第二醫科大學學報, 2005, 25: 292-294.
8.	弱精子癥有效性與安全性的多中心隨機對照臨床研究. 中華男.
9.	科學雜志, 2005, 11: 761-764.
10.	randomized trial on the use of L-carnitine, L-acetylcarnitine,.
11.	or combined L-carnitine and L-acetylcarnitine in men with.
12.	idiopathic asthenozoospermia. Fertil Steril, 2005, 84(3): 662-671.
13.	of idiopathic asthenospermia: a randomized, double-blind, placebocontrolled.
14.	trial. Fertil Steril, 2006, 85(5): 1409-1414.
15.	treatment of patients with asthenozoospermia or moderate.
16.	oligoasthenozoospermia with high-dose vitamin C and vitamin E: a.
17.	randomized, placebo-controlled, double-blind study. Hum Reprod,.
18.	in post-gonadal maturation of mammalian spermatozoa. Hum.
19.	Reprod Update, 1996, 2(2): 87-102.
20.	Am Heart J, 1992, 123(6): 1726-1727.
21.	infertile patients with prostato-vesiculo-epididymitis. Hum Reprod,.
22.	acetylcarnitine on NADPH-induced lipid peroxidation of cardiac.
23.	microsomes. Drugs Exp Clin Res, 1987, 13(8): 509-515.
24.	oxygen species. Hum Reprod Update, 1999, 5(5): 399-420.
25.	activity of caspases by L-carnitine and palmitoylcarnitine. FEBS Lett,.
26.	DNA damage and cell death by activation of the sphingomyelin.
27.	pathway. Proc Natl Acad Sci U S A, 1994, 91(1): 73-77.
28.	treatment for blocking apoptosis and preventing skeletal muscle.
29.	myopathy in heart failure. Am J Physiol Cell Physiol, 2002, 283(3):.
30.	C802-810.
31.	on prepubertal rat Sertoli cells. Horm Metab Res, 2000, 32(3): 87-90.
32.	cell protein metabolism. Horm Metab Res, 2004, 36(4): 221-225.
33.	in the seminal plasma of fertile and infertile men: correlation with.
34.	sperm quality. Int J Fertil Womens Med, 2000, 45(3): 236-240.
35.	quality and seminal plasma total carnitine in infertile men. J Obstet.
36.	Gynaecol, 2003, 23(6): 653-656.
37.	Evaluation of seminal carnitine as a marker of epididymal function.
38.	Actas Urol Esp, 1989, 13(3): 181-184.
39.	redox cycling chemicals. Br J Cancer Suppl, 1987, 8: 46-52.
40.	of oxygen on living organisms: the key role of superoxide dismutase.
41.	Cell Biol Int Rep, 1978, 2(2): 113-128.
42.	assay for determining oxyradical scavenging capacity of antioxidants.
43.	and biological fluids. Free Radic Biol Med, 1998, 24(3): 480-493.
44.	capacity toward different reactive oxygen species in seminal plasma.
45.	and sperm cells. Clin Chem Lab Med, 2003, 41(1): 13-19.
46.	Siddiq FM, Sigman M. A new look at the medical management of.
47.	郭應祿, 李宏軍. 男性不育癥. 見: 郭應祿, 李宏軍, 主編. 男性不育.
48.	Lenzi A, Lombardo F, Sgro P, et al. Use of carnitine therapy in.
49.	Lenzi A, Sgro P, Salacone P, et al. A placebo-controlled double-blind.
50.	李錚, 谷榮華, 劉勇, 等. 補充肉毒堿治療少弱精子癥療效觀察. 上.
51.	李錚, 陳國武, 商學軍, 等. 左旋肉堿和乙酰左旋肉堿合用治療少.
52.	Balercia G, Regoli F, Armeni T, et al. Placebo-controlled doubleblind.
53.	Sigman M, Glass S, Campagnone J, et al. Carnitine for the treatment.
54.	Ro l f C, Co o p e r TG, Y e u n g CH, e t a l . An t i o x i d a n t.
55.	Jeulin C, Lewin LM. Role of free L-carnitine and acetyl-L-carnitine.
56.	Arduini A. Carnitine and its acyl esters as secondary antioxidants?.
57.	Vicari E, Calogero AE. Effects of treatment with carnitines in.
58.	Schinetti ML, Rossini D, Greco R, et al. Protective action of.
59.	Ochsendorf FR. Infections in the male genital tract and reactive.
60.	Mutomba MC, Yuan H, Konyavko M, et al. Regulation of the.
61.	Jarvis WD, Kolesnick RN, Fornari FA, et al. Induction of apoptotic.
62.	Vescovo G, Ravara B, Gobbo V, et al. L-Carnitine: a potential.
63.	Palmero S, Bottazzi C, Costa M, et al. Metabolic effects of L-carnitine.
64.	Caviglia D, Scarabelli L, Palmero S. Effects of carnitines on rat sertoli.
65.	Matalliotakis I, Koumantaki Y, Evageliou A, et al. L-carnitine levels.
66.	Gurbuz B, Yalti S, Ficiciolu C, et al. Relationship between semen.
67.	Salinas Sanchez AS, Moreno Aviles J, Lopez Paredes A, et al.
68.	Cohen GM, d’Arcy Doherty M. Free radical mediated cell toxicity by.
69.	Halliwell B. Biochemical mechanisms accounting for the toxic action.
70.	Winston GW, Regoli F, Dugas AJ, et al. A rapid gas chromatographic.
71.	Balercia G, Armeni T, Mantero F, et al. Total oxyradical scavenging.
72.	, 14(4): 1028-1033.
73.	, 478(1-2): 19-25.
74.	, 16(11): 2338-2342.
75.	, 81(6): 1578-1584.

1. infertility. Urol Clin North Am, 2002, 29(4): 949-963.
2. 癥. 第1版. 北京: 人民軍醫出版社, 2003. 36-39.
3. selected cases of male factor infertility: A double-blind crossover.
4. trial. Fertil Steril, 2003, 79(2): 292-300.
5. randomized trial of the use of combined l-carnitine and l-acetylcarnitine.
6. treatment in men with asthenozoospermia. Fertil Steril,.
7. 海第二醫科大學學報, 2005, 25: 292-294.
8. 弱精子癥有效性與安全性的多中心隨機對照臨床研究. 中華男.
9. 科學雜志, 2005, 11: 761-764.
10. randomized trial on the use of L-carnitine, L-acetylcarnitine,.
11. or combined L-carnitine and L-acetylcarnitine in men with.
12. idiopathic asthenozoospermia. Fertil Steril, 2005, 84(3): 662-671.
13. of idiopathic asthenospermia: a randomized, double-blind, placebocontrolled.
14. trial. Fertil Steril, 2006, 85(5): 1409-1414.
15. treatment of patients with asthenozoospermia or moderate.
16. oligoasthenozoospermia with high-dose vitamin C and vitamin E: a.
17. randomized, placebo-controlled, double-blind study. Hum Reprod,.
18. in post-gonadal maturation of mammalian spermatozoa. Hum.
19. Reprod Update, 1996, 2(2): 87-102.
20. Am Heart J, 1992, 123(6): 1726-1727.
21. infertile patients with prostato-vesiculo-epididymitis. Hum Reprod,.
22. acetylcarnitine on NADPH-induced lipid peroxidation of cardiac.
23. microsomes. Drugs Exp Clin Res, 1987, 13(8): 509-515.
24. oxygen species. Hum Reprod Update, 1999, 5(5): 399-420.
25. activity of caspases by L-carnitine and palmitoylcarnitine. FEBS Lett,.
26. DNA damage and cell death by activation of the sphingomyelin.
27. pathway. Proc Natl Acad Sci U S A, 1994, 91(1): 73-77.
28. treatment for blocking apoptosis and preventing skeletal muscle.
29. myopathy in heart failure. Am J Physiol Cell Physiol, 2002, 283(3):.
30. C802-810.
31. on prepubertal rat Sertoli cells. Horm Metab Res, 2000, 32(3): 87-90.
32. cell protein metabolism. Horm Metab Res, 2004, 36(4): 221-225.
33. in the seminal plasma of fertile and infertile men: correlation with.
34. sperm quality. Int J Fertil Womens Med, 2000, 45(3): 236-240.
35. quality and seminal plasma total carnitine in infertile men. J Obstet.
36. Gynaecol, 2003, 23(6): 653-656.
37. Evaluation of seminal carnitine as a marker of epididymal function.
38. Actas Urol Esp, 1989, 13(3): 181-184.
39. redox cycling chemicals. Br J Cancer Suppl, 1987, 8: 46-52.
40. of oxygen on living organisms: the key role of superoxide dismutase.
41. Cell Biol Int Rep, 1978, 2(2): 113-128.
42. assay for determining oxyradical scavenging capacity of antioxidants.
43. and biological fluids. Free Radic Biol Med, 1998, 24(3): 480-493.
44. capacity toward different reactive oxygen species in seminal plasma.
45. and sperm cells. Clin Chem Lab Med, 2003, 41(1): 13-19.
46. Siddiq FM, Sigman M. A new look at the medical management of.
47. 郭應祿, 李宏軍. 男性不育癥. 見: 郭應祿, 李宏軍, 主編. 男性不育.
48. Lenzi A, Lombardo F, Sgro P, et al. Use of carnitine therapy in.
49. Lenzi A, Sgro P, Salacone P, et al. A placebo-controlled double-blind.
50. 李錚, 谷榮華, 劉勇, 等. 補充肉毒堿治療少弱精子癥療效觀察. 上.
51. 李錚, 陳國武, 商學軍, 等. 左旋肉堿和乙酰左旋肉堿合用治療少.
52. Balercia G, Regoli F, Armeni T, et al. Placebo-controlled doubleblind.
53. Sigman M, Glass S, Campagnone J, et al. Carnitine for the treatment.
54. Ro l f C, Co o p e r TG, Y e u n g CH, e t a l . An t i o x i d a n t.
55. Jeulin C, Lewin LM. Role of free L-carnitine and acetyl-L-carnitine.
56. Arduini A. Carnitine and its acyl esters as secondary antioxidants?.
57. Vicari E, Calogero AE. Effects of treatment with carnitines in.
58. Schinetti ML, Rossini D, Greco R, et al. Protective action of.
59. Ochsendorf FR. Infections in the male genital tract and reactive.
60. Mutomba MC, Yuan H, Konyavko M, et al. Regulation of the.
61. Jarvis WD, Kolesnick RN, Fornari FA, et al. Induction of apoptotic.
62. Vescovo G, Ravara B, Gobbo V, et al. L-Carnitine: a potential.
63. Palmero S, Bottazzi C, Costa M, et al. Metabolic effects of L-carnitine.
64. Caviglia D, Scarabelli L, Palmero S. Effects of carnitines on rat sertoli.
65. Matalliotakis I, Koumantaki Y, Evageliou A, et al. L-carnitine levels.
66. Gurbuz B, Yalti S, Ficiciolu C, et al. Relationship between semen.
67. Salinas Sanchez AS, Moreno Aviles J, Lopez Paredes A, et al.
68. Cohen GM, d’Arcy Doherty M. Free radical mediated cell toxicity by.
69. Halliwell B. Biochemical mechanisms accounting for the toxic action.
70. Winston GW, Regoli F, Dugas AJ, et al. A rapid gas chromatographic.
71. Balercia G, Armeni T, Mantero F, et al. Total oxyradical scavenging.
72. , 14(4): 1028-1033.
73. , 478(1-2): 19-25.
74. , 16(11): 2338-2342.
75. , 81(6): 1578-1584.

《中國循證醫學雜志》

肉堿治療原發性弱精癥療效和安全性的系統評價

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《中國循證醫學雜志》

肉堿治療原發性弱精癥療效和安全性的系統評價

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