CAJ | 학술논문

目的：探讨促性腺释放激素类似物(GnRHa)联合环磷酰胺(CTX)治疗对系统性红斑狼疮(SLE)患者病情的影响，以及GnRHa作为CTX治疗的SLE患者卵巢保护剂的安全性。方法选取2013年3月~2014年12月在北京大学深圳医院风湿科确诊为SLE的育龄女性24例，根据是否使用GnRHa分为CTX+GnRHa组和CTX组，每组各12例。采用双能X线骨密度仪检测两组患者腰椎(L1~L4正位)骨密度；比较两组患者治疗前后病情、CTX的累积治疗量、骨密度及治疗后副作用。结果①SLE病情：治疗后两组SLE患者临床症状均消失，两组治疗前后系统性红斑狼疮疾病活动指数(SLEDAI)评分组内比较，差异均有高度统计学意义(t=23.534、19.187，均P=0.000)；治疗后两组SLEDAI评分比较，差异有高度统计学意义(t=3.425，P=0.002)。②CTX的累积治疗量：CTX+GnRHa组与CTX组的CTX的累积治疗量分别为(6.9±2.0)、(7.0±1.5)g，两组比较差异无统计学意义(t=0.217，均P=0.830)。③骨密度：两组SLE患者治疗前后腰椎(L1~L4正位)骨密度值比较，差异均无统计学意义(t=0.126、0.175，P=0.901、0.863)。④治疗后的副作用、围绝经期症状及月经改变：CTX+GnRHa组在使用第2次GnRHa后均出现闭经，并伴有不同程度的潮热、多汗、睡眠困难等低雌激素症状，而停用GnRHa、月经恢复后上述症状缓解消失。CTX组有7例出现月经不规则，其中3例月经淋漓不尽，4例月经稀发，但均无低雌激素症状。结论 GnRHa联合CTX治疗对SLE患者的病情无明显的负面影响，GnRHa具有保护CTX治疗中SLE患者卵巢的功能，但其作为CTX治疗的SLE患者的卵巢功能保护剂的安全性及有效性仍有待进一步证实。
목적：탐토촉성선석방격소유사물(GnRHa)연합배린선알(CTX)치료대계통성홍반랑창(SLE)환자병정적영향，이급GnRHa작위CTX치료적SLE환자란소보호제적안전성。방법선취2013년3월~2014년12월재북경대학심수의원풍습과학진위SLE적육령녀성24례，근거시부사용GnRHa분위CTX+GnRHa조화CTX조，매조각12례。채용쌍능X선골밀도의검측량조환자요추(L1~L4정위)골밀도；비교량조환자치료전후병정、CTX적루적치료량、골밀도급치료후부작용。결과①SLE병정：치료후량조SLE환자림상증상균소실，량조치료전후계통성홍반랑창질병활동지수(SLEDAI)평분조내비교，차이균유고도통계학의의(t=23.534、19.187，균P=0.000)；치료후량조SLEDAI평분비교，차이유고도통계학의의(t=3.425，P=0.002)。②CTX적루적치료량：CTX+GnRHa조여CTX조적CTX적루적치료량분별위(6.9±2.0)、(7.0±1.5)g，량조비교차이무통계학의의(t=0.217，균P=0.830)。③골밀도：량조SLE환자치료전후요추(L1~L4정위)골밀도치비교，차이균무통계학의의(t=0.126、0.175，P=0.901、0.863)。④치료후적부작용、위절경기증상급월경개변：CTX+GnRHa조재사용제2차GnRHa후균출현폐경，병반유불동정도적조열、다한、수면곤난등저자격소증상，이정용GnRHa、월경회복후상술증상완해소실。CTX조유7례출현월경불규칙，기중3례월경림리불진，4례월경희발，단균무저자격소증상。결론 GnRHa연합CTX치료대SLE환자적병정무명현적부면영향，GnRHa구유보호CTX치료중SLE환자란소적공능，단기작위CTX치료적SLE환자적란소공능보호제적안전성급유효성잉유대진일보증실。
Objective To study the effect of gonadotropin releasing hormone analogue (GnRHa) combined with Cy-clophosphamide (CTX) for patients with systemic lupus erythematosus (SLE), and the safety of GnRHa as the ovarian protective agent for CTX treatment in patients with SLE. Methods 24 female patients with SLE of childbearing age from March 2013 to December 2014 in Peking University Shenzhen Hospital were recruited and divided into the CTX+ GnRHa group (n=12) and CTX group (n=12) according to whether using GnRHa. While dual-energy X-ray absorp-tiometry was used to measure bone mineral density (BMD) of lumbar 1-4 (L1-L4 posterior-anterior position). SLE con-ditions between the two groups before and after the treatments, accumulation of CTX, BMD, as well as side effects after the treatments of two groups were compared. Results①SLE conditions:the clinical symptoms of patients in two groups were disappeared after treatments. There were significant differences in SLE disease activity index (SLEDAI) scores within the group before and after the treatments (t=23.534, 19.187;all P=0.000), while also significant differences in SLEDAI scores between the two groups after the treat-ments (t=3.425, P=0.002). ②The accumulation of CTX: the accumulation of CTX were (6.9±2.0), (7.0±1.5) g, respec-tively in the CTX + GnRHa and CTX group, with no statistically significant differences (t=0.217, P=0.830). ③BMD:there were no statistically significant differences in lumbar spine BMD before and after the treatments within two groups (t=0.126, 0.175;P=0.901, 0.863).④Side effects, perimenopausal symptoms and menstrual changes after the treatments:amenorrhoea appeared after using the second GnRHa in the CTX + GnRHa group, which accompanied by varying de-grees of low estrogen symptoms such as hot flash, sweating, sleep difficulties. While menstruation recovered and low es-trogen symptoms disappeared after stopping GnRHa. 7 cases appeared irregular menstruation, including 3 cases of menstrual dripping endless, 4 cases of oligomenorrhea, but without low estrogen symptoms in the CTX group. Conclu-sion Negative effect on SLE patients treated with GnRHa combined CTX, while GnRHa may protect the existing ovari-an function of SLE treated with CTX, and GnRHa as the ovarian protective agent for CTX treatment in SLE is whether safe or effective still need further clinical studies to confirm.