环磷酰胺辅助化疗后乳腺癌患者卵巢功能损伤情况及中医证候特征研究
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摘要
【目的】以月经情况及血清性激素水平动态变化为观察指标,研究环磷酰胺(CTX)辅助化疗后乳腺癌患者的卵巢功能损伤情况和中医证候特征表现,以及CTX用量与卵泡刺激素(FSH)水平的相关关系。【方法】选取136例年龄<40岁经CTX辅助化疗后的乳腺癌女性患者为研究对象,根据末次化疗后血清基础FSH水平将患者分为3组:亚临床POI组(FSH为10～25 U/L)33例、POI早期组(FSH为25～40 U/L)21例和POI晚期组(FSH>40 U/L)82例。研究3组患者的中医证候、月经状况及性激素水平等相关情况。【结果】(1)3组患者的中医证型特征比较,差异无统计学意义(P>0.05),3组患者均以肝肾阴虚证多见。(2)月经情况:组间对比,3组患者的既往月经及化疗期间月经情况比较,差异无统计学意义(P>0.05),化疗后1年月经复常情况比较,差异有统计学意义(P<0.01);组内对比,3组患者化疗前后及化疗后1年月经情况比较,差异均有统计学意义(P<0.01)。(3)性激素水平方面:组间对比,末次化疗后3组患者FSH、促黄体生成素(LH)、睾酮(T)、孕酮(P)、雌二醇(E2)及FSH/LH水平比较,差异均有统计学意义(P<0.01),化疗后1年复查FSH水平,差异也有统计学意义(P<0.05);末次化疗后与化疗后1年的组内对比,亚临床POI组FSH、E2水平,POI早期组FSH、LH、T、E2水平,POI晚期组FSH、LH、T、P、E2水平差异有统计学意义(P<0.05)。(4)末次化疗后FSH水平与CTX累计剂量呈负相关,化疗后1年FSH水平与CTX累计剂量呈正相关。【结论】CTX化疗会导致乳腺癌患者出现不同程度卵巢功能损伤,中医证型以肝肾阴虚证多见,临床表现以月经紊乱为主,内分泌表现为FSH升高,E2降低;化疗后1年发现患者卵巢功能可出现一定程度的自我修复,性激素改变在一定程度上可以逆转,恢复情况与CTX累计剂量和卵巢损伤程度有关。证明临床上检测患者性激素水平,不仅有利于评估卵巢功能损伤程度,同时可为化疗源性卵巢毒性的深入研究提供依据。
Objective With menstruation and serum sex hormone levels as the observation indexes,we investigated the ovary function injury and the characteristics of traditional Chinese medicine(TCM)syndromes in breast cancer patients after adjuvant chemotherapy with cyclophosphamide(CTX),and explored the correlation of CTX dosage with follicle-stimulating hormone(FSH) level. Methods One hundred and thirty-six breast cancer patients aged less than 40 years old after adjuvant chemotherapy with CTX were included in the trial. The patients were divided into 3 groups based on the serum basal FSH level after the last chemotherapy, namely subclinical premature ovarian insufficiency(POI)group(basal FSH level being 10-25 U/L;n = 33),early POI group(basal FSH level being 25-40 U/L; n = 21) and late POI group(basal FSH level>40 U/L; n = 82). The TCM syndromes,menstruation and serum sex hormone levels in the 3 groups were studied. Results(1)The differences of TCM syndromes among the 3 groups were insignificant(P>0.05),and the syndrome of liver-kidney yin deficiency was commonly seen in the 3 groups.(2)The intergroup comparison showed that the differences of menstruation before chemotherapy and during chemotherapy among the 3 groups were insignificant(P>0.05),but the difference of the rate for menstruation becoming normal one year after chemotherapy among the 3 groups was significant(P < 0.01).The intragroup comparison showed that the differences of menstruation before and after chemotherapy and one year after chemotherapy among the 3 groups were significant(P<0.01).(3)The intergroup comparison showed that the differences of FSH,luteinizing hormone(LH), testosterone(T),progesterone(P), estradiol(E2)and FSH/LH ratio after the last chemotherapy among the 3 groups were significant(P<0.01),and the difference of FSH level one year after chemotherapy among the 3 groups was also significant(P < 0.05). The intragroup comparison showed that the differences between the last chemotherapy and one year after chemotherapy were significant in FSH and E2 level of subclinical POI group,in FSH,LH,T and E2 level of early POI group,and in FSH,LH,T,P and E2 level of late POI group(P<0.05).(4)At the end of last chemotherapy,serum FSH level was negatively correlated with the accumulative dosage of CTX,but one year after chemotherapy,serum FSH level was positively correlated with the accummulative dosage of CTX. Conclusion CTX chemotherapy causes the injury of ovary function of breast cancer patients to various degrees,and the patients after CTX chemotherapy are characterized by the syndrome of liver-kidney yin deficiency,manifested as disordered menstruation,increase of serum FSH level and decrease of serum E2. One year after chemotherapy, the ovary function of breast cancer patients can be recovered and sex hormone level can be inverted automatically to some extent,and the recovery is correlated with the accumulative dosage of CTX and the degree of ovary function injury. It is indicated that the detection of sex hormones will not only be helpful for the estimation of the degree of ovary function injury,but also can supply evidence for the further research of chemotherapy-induced ovary toxicity.
Objective With menstruation and serum sex hormone levels as the observation indexes,we investigated the ovary function injury and the characteristics of traditional Chinese medicine(TCM)syndromes in breast cancer patients after adjuvant chemotherapy with cyclophosphamide(CTX),and explored the correlation of CTX dosage with follicle-stimulating hormone(FSH) level. Methods One hundred and thirty-six breast cancer patients aged less than 40 years old after adjuvant chemotherapy with CTX were included in the trial. The patients were divided into 3 groups based on the serum basal FSH level after the last chemotherapy, namely subclinical premature ovarian insufficiency(POI)group(basal FSH level being 10-25 U/L;n = 33),early POI group(basal FSH level being 25-40 U/L; n = 21) and late POI group(basal FSH level>40 U/L; n = 82). The TCM syndromes,menstruation and serum sex hormone levels in the 3 groups were studied. Results(1)The differences of TCM syndromes among the 3 groups were insignificant(P>0.05),and the syndrome of liver-kidney yin deficiency was commonly seen in the 3 groups.(2)The intergroup comparison showed that the differences of menstruation before chemotherapy and during chemotherapy among the 3 groups were insignificant(P>0.05),but the difference of the rate for menstruation becoming normal one year after chemotherapy among the 3 groups was significant(P < 0.01).The intragroup comparison showed that the differences of menstruation before and after chemotherapy and one year after chemotherapy among the 3 groups were significant(P<0.01).(3)The intergroup comparison showed that the differences of FSH,luteinizing hormone(LH), testosterone(T),progesterone(P), estradiol(E2)and FSH/LH ratio after the last chemotherapy among the 3 groups were significant(P<0.01),and the difference of FSH level one year after chemotherapy among the 3 groups was also significant(P < 0.05). The intragroup comparison showed that the differences between the last chemotherapy and one year after chemotherapy were significant in FSH and E2 level of subclinical POI group,in FSH,LH,T and E2 level of early POI group,and in FSH,LH,T,P and E2 level of late POI group(P<0.05).(4)At the end of last chemotherapy,serum FSH level was negatively correlated with the accumulative dosage of CTX,but one year after chemotherapy,serum FSH level was positively correlated with the accummulative dosage of CTX. Conclusion CTX chemotherapy causes the injury of ovary function of breast cancer patients to various degrees,and the patients after CTX chemotherapy are characterized by the syndrome of liver-kidney yin deficiency,manifested as disordered menstruation,increase of serum FSH level and decrease of serum E2. One year after chemotherapy, the ovary function of breast cancer patients can be recovered and sex hormone level can be inverted automatically to some extent,and the recovery is correlated with the accumulative dosage of CTX and the degree of ovary function injury. It is indicated that the detection of sex hormones will not only be helpful for the estimation of the degree of ovary function injury,but also can supply evidence for the further research of chemotherapy-induced ovary toxicity.
引文
[1]陈万青,郑荣寿.中国女性乳腺癌发病死亡和生存状况[J].中国肿瘤临床,2015,42(13):668.
[2]张熙,黄欧,沈坤炜.年轻女性乳腺癌病人生育能力保存研究进展[J].中国实用外科杂志,2011,31(10):964.
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[5]吴丽婷,石玥,刘雁峰.肖承悰治疗卵巢早衰经验[J].中医杂志,2017,58(2):108.
[6]廖慧慧,赵颖,史云.张玉珍教授治疗卵巢早衰的思路与方法[J].环球中医药,2015,8(7):780.
[7]陈静,王春艳.胡国华教授治疗卵巢早衰及卵巢储备功能低下的经验[J].世界中西医结合杂志,2013,8(10):988.
[8]朱玲,罗颂平.卵巢早衰病因病机再认识[J].新中医,2015,47(4):327.
[9]徐碧红,李茂清,熊思艺,等.补肾调经膏方对肾虚型卵巢早衰患者性激素水平的影响[J].广州中医药大学学报,2017,34(2):167.
[10] Meirow D, Schiff E. Appraisal of chemotherapy effects on reproductive outcome according to animal studies and clinical data[J]. J Natl Cancer Inst Monogr,2005,34:21.
[11] Lee S J,Schover L R,Partridge A H,et al. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients[J]. J Clin Oncol,2006,24(18):2917.
[2]张熙,黄欧,沈坤炜.年轻女性乳腺癌病人生育能力保存研究进展[J].中国实用外科杂志,2011,31(10):964.
[3]罗颂平.中医妇科学[M].北京:高等教育出版社,2008:61-90.
[4]中华中医药学会.中医妇科常见病诊疗指南[M].北京:中国中医药出版社,2012.
[5]吴丽婷,石玥,刘雁峰.肖承悰治疗卵巢早衰经验[J].中医杂志,2017,58(2):108.
[6]廖慧慧,赵颖,史云.张玉珍教授治疗卵巢早衰的思路与方法[J].环球中医药,2015,8(7):780.
[7]陈静,王春艳.胡国华教授治疗卵巢早衰及卵巢储备功能低下的经验[J].世界中西医结合杂志,2013,8(10):988.
[8]朱玲,罗颂平.卵巢早衰病因病机再认识[J].新中医,2015,47(4):327.
[9]徐碧红,李茂清,熊思艺,等.补肾调经膏方对肾虚型卵巢早衰患者性激素水平的影响[J].广州中医药大学学报,2017,34(2):167.
[10] Meirow D, Schiff E. Appraisal of chemotherapy effects on reproductive outcome according to animal studies and clinical data[J]. J Natl Cancer Inst Monogr,2005,34:21.
[11] Lee S J,Schover L R,Partridge A H,et al. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients[J]. J Clin Oncol,2006,24(18):2917.