妇科恶性肿瘤术后骨质疏松症的防治

为探讨妇科恶性肿瘤术后骨质疏松症的预防措施,采用补充紫竹爱维和乐力胶囊来预防骨质疏松的发生,分别与未服药的妇科恶性肿瘤及良性肿瘤术后作对照,并对其对骨代谢指标血清骨性碱性磷酸酶(BALP)及血清抗酒石酸酸性磷酸酶(TRAP)的影响进行了临床观察.结果发现恶性肿瘤术后较良性肿瘤术后患者的BALP降低,TRAP增高,服用紫竹爱维与乐力胶囊的患者TRAP均低于未服药的恶性肿瘤术后患者,P＜0.05,均有显著性差异.表明妇科恶性肿瘤术后患者较良性肿瘤更易患骨质疏松症,服用紫竹爱维与乐力胶囊均能有效防治骨质疏松症,前者效果更佳,但应掌握性激素补充治疗(HRT)的应用指征.     

阿拉瑞林与小剂量利维爱联合应用治疗子宫内膜异位症合并不孕症的研究

目的:探讨阿拉瑞林与小剂量利维爱(替勃龙)联合应用治疗子宫内膜异位症合并不孕症的疗效及其耐受性。方法:研究对象为1998年1月～2001年6月期间在我院诊治的40例子宫内膜异位症合并不孕症患者。实验组给以阿拉瑞林及利维爱,对照组单用阿拉瑞林。结果:用药后两组患者血清E2、P、FSH、LH水平及AEMAb、CA125阳性率均明显下降;症状体征明显改善;在治疗结束后6个月,实验组中55％、对照组中45％患者妊娠,两组间差异无统计学意义(P>0.05)。实验组未出现低雌激素症候群,而对照组中85％患者出现该症候群,两组差异有统计学意义(P<0.05)。结论:阿拉瑞林与小剂量利维爱联合应用不仅疗效好,而且副作用小。     

替勃龙改善绝经期功能性消化不良症状

目的 :探讨替勃龙能否改善绝经期功能性消化不良患者临床症状及其相关机制。方法 :14 3例绝经期功能性消化不良患者随机分成 3组 ,分别给予替勃龙、西沙必利及替勃龙 +西沙必利 ,治疗 4周 ,观察治疗前后各组患者上腹胀痛、餐后胀满、早饱、暖气等临床症状积分的变化。在随机分成的 3组中再随机各抽出 2 0例患者治疗前后测定胃 30min排空率及胃半排空时间 ,观察治疗前后胃动力的变化。结果 :3组药物治疗后 2周和 4周上腹胀痛、餐后胀满症状积分均明显下降。西沙必利治疗后 2周和 4周对早饱、暖气症状无明显缓解 ,替勃龙及替勃龙 +西沙必利则对所观察的所有症状均有明显缓解 ,替勃龙改善早饱和嗳气症状优于西沙必利 ,但与西沙必利合用无增强效应。 3种药物治疗后 ,胃 30min排空率均明显增加、胃半排空时间缩短 ,与治疗前比较有显著差异 (P <0 .0 5 ) ,但 3种治疗方案之间无显著性差异 (P >0 .0 5 )。结论 :替勃龙能通过增强胃动力 ,明显改善部分绝经期功能性消化不良患者的临床症状 ,疗效优于促动力药。     

Bleeding patterns in recent postmenopausal outpatients with uterine myomas: comparison between two regimens of HRT

Objectives: To evaluate and to compare the bleeding patterns obtained with two regimens of hormone replacement therapy given to early postmenopausal women with asymptomatic uterine leiomyomas. Methods: In this randomised prospective 1-year study 50 early postmenopausal women with one to four asymptomatic uterine leiomyomas were enrolled into two study-groups to take two regimens of hormone replacement therapy for 12 28-day cycles: (A) Tibolone, 2.5 mg/day; (B) conjugated equine estrogens (CEE), 0.625 mg/day plus medroxyprogesterone acetate (MPA), 5 mg/day. The bleeding patterns and the changes in uterine volume of the 47 outpatients who completed the study were evaluated and compared. Results: Amenorrhea incidence was higher in group A (75.0% of the cycles) than in group B (65.6% of the cycles), while irregular bleeding and irregular spotting incidences were higher in group B (29.7 and 4.7% of the cycles, respectively) compared to group A (22.6 and 2.4% of the cycles, respectively). The mean bleeding and spotting lengths were not statistically different between patients in group A and those in group B. Finally, at the end of the study period transvaginal ultrasonography showed no significant change in leiomyoma size. Conclusions: The results demonstrate that, in early postmenopausal patients with asymptomatic uterine leiomyomas, Tibolone treatment seems to be preferable compared to CEE–MPA continuous combined treatment in relation to the lesser occurrence of irregular bleeding. Furthermore, neither Tibolone nor CEE–MPA therapy, at the doses used here, promote fibroid growth.     

Effects of tibolone on body composition in postmenopausal women: a 1-year follow up study

Objective: We investigated the effects of 1-year tibolone treatment on body weight, body composition and indices of android obesity in postmenopausal women.

Methods: Forty-four postmenopausal women participated in this open-label controlled study; mean age was 51.8 ± 2.21 years and all women were menopausal for 3.8 ± 1.40 years. Twenty-two of them started taking 2.5 mg tibolone (TIB) daily for 1 year, whereas the remaining 22 served as age-matched controls. All subjects underwent a structured interview, physical examination, body composition measurements performed by dual-energy X-ray absorptiometry (DXA) — Hologic QDR 4500 A, as well as bioelectrical body impedance analysis (BI) — Tanita TBF-215, Japan.

Results: The TIB group did not significantly increase their weight (+0.4 kg), while the non-treated controls increased their mean weight by 1.4 kg (p = 0.046). In the TIB group, DXA showed a non-significant body fat decrease by a mean of 0.5 kg and a non-significant lean mass increase by 0.8 kg, while in the control group, fat mass increased by 1.7 kg (p = 0.032) and lean mass did not change. BI revealed that the TIB group had lost some fat (≈0.6 kg, n.s.) and put some free-fat mass (≈1.0 kg, p = 0.048) without changes in total body water. The control group put on some fat (≈1.1 kg, p = 0.042) and lost some body water (≈0.4 kg, n.s.).

Conclusion: Results from both methods of measuring body composition show a similar trend: a decrease in fat mass and an increase in lean mass in TIB treated subjects. From the body composition perspective, tibolone may be regarded as a preferential alternative to conventional hormonal therapy (HT) in postmenopausal women.     

Effects of tibolone on lipoprotein(a) and HDL subfractions

Objective: To determine the effects of tibolone, a synthetic steroid used to alleviate climacteric symptoms and prevent osteoporosis, on lipoprotein metabolism, with particular reference to lipoprotein(a) levels and HDL subfraction profiles.Design: Thirty nine postmenopausal women were treated with tibolone (Livial) 2.5 mg/day for 6 months and fasting serum lipoprotein levels were estimated at 0, 2, 4 and 6 months. Results: Lipoprotein(a) levels were reduced significantly over the 6 months from a median level of 245 (range <60–780) mg/I to 152 (range <60–530) mg/l, a reduction of 39% in the median level. A decrease was observed in approximately two thirds of the women. Reductions were noted in all 6 subjects whose pretreatment levels were high, although concentrations remained at a level associated with increased risk in all but one. There were significant decreases in triglycerides and VLDL cholesterol and no significant change in LDL cholesterol. There was a significant reduction of 18% in HDL cholesterol and a 26% reduction in the HDL₂:HDL₃ ratio. Conclusion: The reduction in lipoprotein(a) levels may have a beneficial effect on cardiovascular risk, which could go some way towards balancing the potentially adverse effect on the cardiovascular system caused by the reduction in HDL cholesterol.     

国产替勃龙的激素活性及药效研究

为在国内开发治疗妇女更年期与手术后绝经症的新药 ,对国产替勃龙进行了多项生殖内分泌生物实验 ,结果表明该药兼具雌激素、孕激素及雄激素活性 ,并有延迟排卵作用 ,对大鼠雌激素缺乏性阴道炎也有治疗作用。其药理特性符合临床治疗女性更年期综合症要求。     

Efficacy and Safety Investigation of Kuntai Capsule for the Add-back Therapy of Gonadotropin Releasing Hormone Agonist Administration to Endometriosis Patients: A Randomized,Double-blind,Blank- and Tibolone-controlled Study

Background:

As a Chinese Traditional Medicine product, Kuntai capsule could improve the peri-menopausal symptoms in postmenopausal women. But it is still not clear whether Kuntai capsule has a good effect on alleviating peri-menopausal symptoms induced by gonadotropin releasing hormone agonist (GnRH-a) treatment. The purpose of this study was to investigate the clinical effectiveness and safety of Kuntai capsule, on peri-menopausal symptoms in endometriosis (EMS) patients, with postoperative GnRH-a treatment.

Methods:

Ninety EMS ovarian cyst women with postoperative GnRH-a administration were enrolled in the study, and were randomly divided into Kuntai group, Tibolone group, or blank Control group. The therapeutic strategy in Kuntai group was 4 Kuntai capsules tid,po for 12 weeks after the first GnRH-a injection, while Tibolone 2.5 mg qd, po for 12 weeks in Tibolone group. There was no drug addition in Control group. Climacteric complaints were evaluated by Kupperman menopausal index (KMI) and hot flash/sweating score. Liver and renal functions, lipid profile, serum sex hormone levels and endometrial thickness were measured, and the frequency of adverse events in Kuntai and Tibolone groups was recorded.

Results:

(1) Before GnRH-a therapy, the baseline parameter results were comparable in the three groups (P > 0.05). (2) After GnRH-a therapy, KMI and hot flash/sweating scores in all the three groups increased significantly (P < 0.05). At the 4^th week after GnRH-a therapy, KMI and hot flash/sweating score results were as follows: Control group > Kuntai group > Tibolone group (P < 0.05); at the 8^th and 12^th week after GnRH-a therapy, KMI and hot flash/sweating score in Control group were significantly higher than the other two groups (P < 0.05), and no significant difference was identified between Kuntai and Tibolone group (P > 0.05). (3) No statistical change took place in the liver and renal functions and lipid profile in all the three groups after the treatment (P > 0.05). (4) The posttherapeutic serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) level and endometrial thickness decreased significantly in all the three groups (P < 0.05). After therapy, serum E2 level in Tibolone group was obviously higher than the other two groups (P < 0.05), while FSH and LH levels were obviously lower (P < 0.05). (5) The incidence of vaginal bleeding, breast distending pain in Tibolne group was obviously higher than Kuntai group (P < 0. 05).

Conclusions:

Kuntai capsule is effective on the peri-menopausal symptoms induced by postoperative GnRH-a administration to EMS patients, although its clinical effect might be a few weeks later than Tibolone. Kuntai capsule might be a little safer than Tibolone tablet.     

唑来膦酸与替勃龙治疗绝经后骨质疏松疗效比较及对骨折的预防作用

目的比较唑来膦酸与替勃龙治疗绝经后骨质疏松的临床疗效及对骨折的预防作用。方法将本院诊治的128例绝经后骨质疏松患者随机分入唑来膦酸组与替勃龙组,两组患者均接受骨化三醇、钙剂治疗,唑来膦酸组患者同时接受唑来膦酸5 mg/年静脉注射,替勃龙组患者接受替勃龙2.5 mg/d,口服。用药后2年比较两组髋部及腰椎骨密度变化、血清Ⅰ型前胶原肽（CTX）、骨碱性磷酸酶（BALP）及不良反应发生情况。结果两组治疗后2年腰椎L1-L4和髋部区、股骨颈、大转子骨密度均显著增加（P〈0.05）,唑来膦酸组L1-L4骨密度增加显著优于替勃龙组（P〈0.05）;治疗后两组CTX及BALP均显著下降,唑来膦酸组CTX显著低于替勃龙组（P〈0.05）;唑来膦酸组与替勃龙组新发骨折发生率分别为4.5%和8.1%,两组比较差异无统计学意义（P〉0.05）;唑来膦酸组不良反应发生率为19.7%,替勃龙组为11.3%,两组均未发生严重不良反应。结论唑来膦酸与替勃龙治疗绝经后骨质疏松均可获得理想的临床疗效,唑来膦酸组腰椎骨质密度增加更为显著,患者治疗依从性好。     

抗抑郁药及性激素治疗围绝经期及绝经后妇女抑郁症的疗效比较

目的 比较抗抑郁药及性激素治疗围绝经期及绝经后妇女抑郁症的临床疗效.方法 将120例围绝经期及绝经后抑郁症女性按入组顺序分为A、B、C3组(每组40例),采用24项汉密尔顿抑郁量表(HAMD24)对其进行抑郁程度评价,然后根据HAMD评分每组再分为轻中度组及重度组2个亚组.A组应用抗抑郁药盐酸氟西汀(20 mg/d)+性激素替勃龙(1.25 mg/d)治疗,B组应用盐酸氟西汀( 20 mg/d)治疗,C组应用替勃龙(1.25 mg/d)治疗;连续服药2个月后进行HAMD24评定,同时计算治疗总有效率.结果 (1)临床疗效比较:A、B、C3组的轻中度亚组治疗总有效率分别为96％、95％、93％,差异无统计学意义(P＞0.05);重度亚组治疗总有效率分别为93％、83％、46％,A、B2组的重度亚组治疗总有效率明显高于C组(P＜0.05),且A组的重度亚组治疗总有效率高于B组(P＜0.05).(2)治疗前后HAMD24评分比较:治疗后3组的轻中度亚组HAMD24评分比较差异无统计学意义(P＞0.05),但治疗后HAMD24评分均明显低于治疗前基线水平[治疗前分别为(29.0±4.8)、(27.4±5.3)、(27.9±4.2)分,治疗后分别为(3.9±3.2)、(4.2±3.6)、(4.4±3.0)分;P＜0.05];治疗后,A、B2组重度亚组的HAMD24评分明显低于C组[治疗前分别为(38.2±5.4)、(37.8±4.9)、(37.3±5.3)分,治疗后分别为(5.7±2.5)、(8.4±2.8)、(20.8±5.2)分; P＜0.05],且A组重度亚组的HAMD24评分低于B组(P＜0.05).结论 围绝经期及绝经后合并轻中度抑郁症妇女抗抑郁药治疗及激素替代治疗效果相当,重度抑郁症女性则两药联用效果更佳.