绝经后女性长期服用替勃龙对代谢指标的影响和安全性评价

Effect and safety evaluation of metabolic indexes in postmenopausal women with long-term use of tibolone

目的 探讨绝经后女性长期服用替勃龙对糖脂代谢的影响及长期用药的安全性。方法 回顾性分析2011年11月至2021年12月在山西医科大学第一医院就诊的符合绝经激素治疗(menopause hormone therapy,MHT)的绝经后女性,纳入68例,口服替勃龙1.25 mg/d。随访至12、24、36个月,病例数分别为68、50、32例。收集体质量指数(body mass index,BMI)、腰围、收缩压、舒张压、改良Kupperman评分、空腹血糖、总胆固醇(total cholesterol,TC)、三酰甘油(triglycerides,TG)、血清高密度脂蛋白胆固醇(high-density lipoprotein,HDL-C)及血清低密度脂蛋白胆固醇(low-density lipoprotein,LDL-C)、肝肾功能、骨密度等资料。统计学方法采用t检验、秩和检验。结果 改良Kupperman评分的基线值为(20.0±8.9)分,替勃龙治疗3个月后明显下降至(7.2±5.5)分,(t=11.967,P<0.001)。观察期内BMI、腰围、收缩压、舒张压均未出现明显的变化,差异无统计学意义(P值均>0.05)。治疗12个月后,TC、TG分别为[4.6(4.0,5.1)和0.9(0.7,1.1)mmol/L];治疗24个月后,TC、TG分别为[4.6(3.9,5.0)和0.8(0.6,1.2)mmol/L],均低于治疗前[5.0(4.4,5.4)、1.1(0.8,1.6)和4.9(4.2,5.2)、1.0(0.8,1.6)mmol/L,P值均<0.05]。HDL-C在治疗12、24、36个月分别为[1.3(1.1,1.5)、1.3(1.1,1.6)、1.2(1.0,1.6)mmol/L],均低于治疗前[1.4(1.2,1.8)、1.6(1.3,1.9)、1.5(1.3,1.8)mmol/L,P值均<0.01]。治疗不同时间段LDL-C和空腹血糖下降,但差异无统计学意义(P>0.05)。治疗36个月后,尿素(blood urea nitrogen,Urea)治疗后的数值低于治疗前[4.9(4.6,7.8)与4.6(3.9,4.9)mmol/L,P<0.05];治疗12个月后,肌酐(creatinine,CRE)治疗后的数值高于治疗前[57.0(26.4,66.6)与68.0(59.0,78.5)μmol/L,P<0.05],但在正常范围值内。治疗后左髋、右髋骨密度无明显变化,差异无统计学意义(P值均>0.05);腰椎骨密度分别为[(0.934±0.104)、(0.936±0.121)、(0.986±0.156)g/cm~2]均高于治疗前[(0.911±0.112)、(0.905±0.135)、(0.919±0.171)g/cm~2, P<0.05]。结论 替勃龙用药3个月后更年期症状明显改善甚至消失。最长用药36个月对体质量、体态以及血压影响不大,能够有效降低TC、TG水平,同时降低了HDL-C水平,对肝、肾功能无影响,提高了腰椎的骨密度,对髋部骨密度无影响。

Objective To investigate the effect and the safety on glucose and lipid metabolism in postmenopausal women with long-term use of tibolone. Method From November 2011 to December 2021, 68 postmenopausal women who had undergone menopause hormone therapy(MHT) in the First Hospital of Shanxi Medical University by retrospective analysis, who oral tibolone 1.25 mg/d. Follow-up to 12, 24 and 36 months, the number of cases were 68, 50 and 32. Body mass index(BMI),waist circumference, systolic pressure, diastolic blood pressure, modified Kupperman score, fasting blood glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol(HDL-C) and low-density lipoprotein cholesterol(LDL-C), liver and kidney function values, bone mineral density were collected. t-test and rank sum test were used for statistical analysis. Result The baseline value of the modified Kupperman score was(20.0±8.9), which was significantly decreased to(7.2±5.5) after 3 months of tibolone treatment, the difference was statistically significant(t=11.967, P<0.001). There was no statistical significance in BMI, waist circumference, systolic pressure, diastolic blood pressure, during the observation period(P>0.05). After 12 months of treatment, TC and TG were [4.6(4.0, 5.1) vs 0.9(0.7, 1.1) mmol/L], respectively;after 24 months of treatment, TC and TG were [4.6(3.9, 5.0) vs 0.8(0.6, 1.2) mmol/L], respectively, which were lower than those before treatment [5.0(4.4, 5.4), 1.1(0.8, 1.6) vs 4.9(4.2, 5.2), 1.0(0.8, 1.6) mmol/L, all P<0.05]. HDL-C at 12, 24 and 36 months of treatment were [1.3(1.1, 1.5), 1.3(1.1, 1.6), 1.2(1.0, 1.6) mmol/L], respectively, which were lower than those before treatment [1.4(1.2, 1.8), 1.6(1.3, 1.9), 1.5(1.3, 1.8) mmol/L, all P<0.01]. There was no statistical significance in LDL-C and fasting blood glucose decreased in different treatment time periods(P>0.05);After 36 months of treatment, Urea was lower than before treatment [4.9(4.6, 7.8) vs 4.6(3.9, 4.9) mmol/L], the difference was statistically significant(P<0.05). After 12 months of treatment, CRE was higher than before treatment [57.0(26.4, 66.6) vs 68.0(59.0, 78.5) μmol/L], the difference was statistically significant(P<0.05), but within the normal range. There was no significant change in the bone mineral density of the left hip and right hip at different time periods(P>0.05);the bone mineral density of the lumbar spine were [(0.934±0.104),(0.936±0.121) and(0.986±0.156) g/cm~2], higher than those before treatment [(0.911±0.112),(0.905±0.135) and(0.919±0.171) g/cm~2, P<0.05]. Conclusion After 3 months of tibolone treatment, menopausal symptoms are significantly improved or even disappeared. It has little effect on body weight, body posture and blood pressure with longest medication for 36 months, it can effectively reduce the levels of TC and TG, while reducing the level of HDL-C, it has no effect on the liver and kidney functions;the bone density of the lumbar spine is improved, and had no effect on the bone mineral density of the hip.