促性腺激素释放激素类似物对环磷酰胺治疗红斑狼疮患者卵巢的保护作用
Role of gonadotropin releasing hormone analogues for ovarian protection in systemic lupus erythematosus patients treated with cyclophosphamide
目的 初步探讨促性腺激素释放激素类似物(GnRH-a)对环磷酰胺引起卵巢功能衰竭的防治作用.方法 28例使用环磷酰胺治疗的红斑狼疮女性患者,平均年龄(35.3±2.4)岁(30~39岁).治疗方案:(1)每日口服泼尼松1 mg/kg体重,疗程8周后以每10日减少初始10%的速度缓慢减药;(2)环磷酰胺疗程4个月,用法为生理盐水20 ml+环磷酰胺200 mg静脉注射,隔日1次,每周查血常规1次,当血白细胞计数<3.5 × 109 /L时,暂停环磷酰胺,待血白细胞恢复正常后改为生理盐水40 ml+环磷酰胺400 mg静脉注射,每周1次;(3)在开始使用环磷酰胺时,同步使用GnRH-a 3.75mg皮下注射,每月1次,共3次.注射结束后随访6个月.结果 (1)月经恢复情况:在28例患者中25例在末次注射GnRH-a后的第69~82天(中位数73天)恢复月经,其中1例在恢复2次月经后再次出现闭经超过6个月,另外3例治疗结束后6个月未恢复月经.(2)血浆雌二醇水平的变化:治疗前雌二醇水平为(998±308)pmol/L,在注射GnRH-a后1、2和3个月,患者血浆雌二醇均显著下降[分别为(132±44),(88±37)和(81±29)pmol/L],与治疗前对比均P<0.05.(3)在末次注射GnRH-a后2个月,25例月经恢复者血浆雌二醇水平恢复到非绝经期的参考值范围;在末次注射GnRH-a后6个月,24例患者的性激素水平恢复到注射GnRH-a前的基础水平.结论 环磷酰胺治疗SLE患者时,GnRH-a可能具有保护卵巢功能的作用,但不能完全避免卵巢衰竭的发生.
更多Objective To evaluate the effectiveness of gonadotropin releasing hormone analogues (GnRH-a)in protection against premature ovarian failure during cyclophosphamide(CTX)therapy for systemic lupus erythromatosus(SLE).Methods 28 female patients with SLE,aged 35.3 ±2.4(30-39)were treated with prednisone orally 1 mg/kg daily for 8 weeks,and then the dose was decreased by 10%evcry 10 days.CTX 200 mg with normal saline 200 ml was intravenously injection every other day for 4months.Peripheral white blood cell ( WBC)count was made every week.If the WBC count was less than 3.5×109/L,the use of CTX should be stopped temporarily until the WBC count became normal.And then,the CTX administration should be adjusted to 400 mg intravenously every week.All patients were offered treatment with Hypodermic injection of GnRH-a 3.75 mg was given monthly just at the beginning of the standard CTX regimen for 3 months.Follow-up was conducted for 6 months after the last prescription of GnRH-a.Results All patients developed amenorrhea after treated by GnRH-a.Menstruation recovered 73days(69-82 days)after the last subcutaneous injection in 25 patients.Among these 25 patients,one developed amenorrhea again after two normal menses periods.The other 3 patients were in persistent amenorrhea during the following 6 months after the GnRH-a treatment.The levels of plasma estradiol(E2)was 998 ±308 pmol/Lbefore GnRH-a treatment,and decreased significantly 1,2,and 3 months after the last injection of GnRH-a(132±44 pmol/L,88 ±37 pmol/L and 81 ±29 pmol/L respectively,all P<0.05).The level of plasma E2 inereased 2 months after the last injection of GnRH-a in the 25 patients with return of menses,and the level of plasma E2 returned to the normal baseline level after 6 months in 24patients.Conclusion Treatment with GnRH-a during CTX therapy is associated with a significant reduction of premature ovarian failure in most women with SLE.
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