Tibolone对去势裸鼠人子宫内膜癌皮下移植瘤生长及转移的影响

目的研究Tibolone对去势裸鼠人子宫内膜癌皮下移植瘤生长及转移的影响,探讨Tibolone治疗子宫内膜癌的安全性.方法建立去势裸鼠人子宫内膜癌皮下移植瘤模型,比较Tibolone灌胃组和对照组给药前后肿瘤体积变化和转移状况.结果Tibolone灌胃组和安慰剂组裸鼠子宫内膜癌皮下移植瘤体积增加值相同(1.976±1.350)mm3和(2.217±1.071)mm3,P=0.879;Tibolone灌胃组(35 d)后,没有引起肿瘤转移.

Tibolone modulates neuronal plasticity through regulating Tau, GSK3β/Akt/PI3K pathway and CDK5 p35/p25 complexes in the hippocampus of aged male mice

Aging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid hormones may have a negative impact on the formation of neurofibrillary tangles （NFTs）; these hormones can regulate Tau phosphorylation and the principal kinase GSK3β involved in this process. Hormone replacement therapy decreases NFTs, but it increases the risk of some types of cancer. However, other synthetic hormones such as tibolone （TIB） have been used for hormone replacement therapy. The aim of this work was to evaluate the long-term effects of TIB （0.01 mg/kg and 1mg/kg, intragastrically for 12 weeks） on the content of total and hyperphosphorylated Tau （PHF-1） proteins and the regulation of GSK3β/Akt/PI3K pathway and CDK5/p35/p25 complexes in the hippocampus of aged male mice. We observed that the content of PHF-1 decreased with TIB administration. In contrast, no changes were observed in the active form of GSK3β or PI3K. TIB decreased the expression of the total and phosphorylated form of Akt while increased that of p110 and p85. The content of CDK5 was differentially modified with TIB： it was increased at low doses and decreased at high doses. When we analyzed the content of CDK5 activators, an increase was found on p35; however, the content of p25 decreased with administration of low dose of TIB. Our results suggest a possible mechanism of action of TIB in the hippocampus of aged male mice. Through the regulation of Tau and GSK3β/Akt/PI3K pathway, and CDK5/p35/p25 complexes, TIB may modulate neuronal plasticity and regulate learning and memory processes.

Application of UPLC-MS/MS for separation and quantification of 3α-Hydroxy Tibolone and comparative bioavailability of two Tibolone formulations in healthy volunteers

A novel, fast, sensitive and robust method based on ultra-performance liquid chromatography coupled to atmospheric pressure electrospray ionization tandem mass spectrometry （UPLC-ESI-MS/MS） has been developed to separate two Tibolone stereoisomers i.e., 3α-Hydroxy Tibolone and 3β-Hydroxy Tibolone and to quantify 3α-Hydroxy Tibolone using p-toulenesulfonyl isocyanate （PTSI） as a derivatizing reagent in human plasma. 3α-Hydroxy Tibolone-13CD3 was used as an internal standard （IS）. The analyte and IS were extracted from human plasma by liquid-liquid extraction using ethyl acetate. Extracted samples were analyzed by UPLC-ESI-MS/MS. Chromatography was performed using binary gradient on UPLC analytical column. A linear calibration curve over the range of 0.100-35.000 ng/ mL was obtained and lower limit of quantification （LLOQ） was 0.100 ng/mL demonstrating acceptable accuracy and precision. This method was successfully applied to a pharmacokinetic study in order to compare a test Tibolone 2.5 mg formulation vs. a reference 2.5 mg Tibolone tablet formulation in 50 post-menopausal/surgical menopause female human volunteers under fasting conditions. It is concluded that test formulation of Tibolone is bioequivalent to reference formulation of Tibolone.

Low dose and short-term therapy of tibolone reduces the cardiovascular disease risk in postmenopausal women

Objective:To investigate the effects of low dose tibolone short-term therapy on clinic, endocrine and markers of cardiovascular disease in healthy postmenopausal women.Methods: A prospective study involved a total of 42 eligible postmenopausal women. 22 cases as group A and 20 cases as group B. Complete baseline work-up including Kupperman score,body mass index (BMI), gonadotropin (FSH, LH), estrogen (E2), testosterone (T), sex hormone binding globulin (SHBG), plasminogen activator inhibitor type 1 (PAI-1), tissue plasminogen activator (tPA), high-sensitivity C-response protein (hs-CRP), nitrogen oxide (NO)and fasting lipid, glucose(FPG), insulin(FINS) were performed in all subjects. Postmenopausal women in group A were treated with 1.25 mg tibolone daily. Women in group B were treated with 0. 625 mg tibolone daily. Women both in group A and group B were given calcium 600 mg with vitamin D 125IU per day. At the end of the 12-weeks therapy, subjects were re-evaluated and above parameters were measured.Results:No significant differences between group A and group B were found at baseline.Twenty-eight cases (fourteen cases in each group) completed the study. Kupperman score decreased from (22.1±8.0) and (25.4±7.5) to (7.7±4.5) and (5.2±4.5) and plasminogen activator inhibitor type 1 decreased from (95.8±32.4)μg/L and (102.9±42.6)μg/L to (72.2±39.6)μg/L and (79.9±30. 1) μg/L significantly in group A and group B respectively after treatment. In group A, Blood pressure decreased significantly from (120 ± 10)/(83 ± 6) mmHg to (110±14)/(77± 9) mmHg (P＜0.05), testosterone increased significantly from (0. 6 ±0. 4)nmol/L to (1.3 ± 1.1) nmol/L (P＜0. 05), free testosterone increased from (0. 001 ±0. 002)nmol/L to (0. 003±0. 003) nmol/L significantly (P＜0.01), SHBG decreased from (7.6±4. 9)nmol/L to (4. 3±2.9) nmol/L significantly (P＜0.05), total cholesterol decreased from (5.4±0. 8) mmol/L to (5.0±0.8) mmol/L significantly (P＜0.01), ApoA decreased from (1.8±0.3)mg/dl to (1.7±0. 3) mg/dl significantly (P＜0.05), fasting glucose decreased from (5. 6±0.8)mmol/L to (3.9±1.1) mmol/L significantly (P＜0.01) and no significant differences in BMI,FSH, LH, E2, tPA, hs-CRP, NO, TG, HDL-C, LDL-C, apoB were found after treatment. In group B, there were no significant differences in other parameters found after treatment except Kupperman score and PAI-1.Conclusions: 1.25 mg/d tibolone short-term therapy was associated with improved fibrinolytic factors and decreased Kupperman score, blood pressure, total cholesterol and fasting blood glucose level. 0. 625 mg/d tibolone therapy resulted in decrease Kupperman score and improvement of fibrinolytic factors. These changes relieve climacteric symptoms and may have some benefits on preventing the development of cardiovascular disease. An increased testosterone and free testosterone levels in 1.25 mg dose of tibolone therapy may increase energy level, general wellbeing and sexual desire in postmenopausal women. Low dose tibolone replacement therapy is a convenient effective HRT for postmenopausal

Effect of tibolone pretreatment on kinases and phosphatases that regulate the expression and phosphorylation of Tau in the hippocampus of rats exposed to ozone

Oxidative stress （OS） is a key process in the development of many neurodegenerative diseases, memory disorders, and other pathological processes related to aging. Tibolone （TIB）, a synthetic hormone used as a treatment for menopausal ymptoms, decreases lipoperoxidation levels, prevents memory impairment and learning disability caused by ozone （O3） exposure. However, it is not clear if TIB could prevent the increase in phosphorylation induced by oxidative stress of the microtubule-associated protein Tau. In this study, the effects of TIB at different times of administration on the phosphorylation of Tau, the activation of glycogen synthase kinase-3β （GSK3β）, and the inactivation of Akt and phosphatases PP2A and PTEN induced by O3 exposure were assessed in adult male Wistar rats. Rats were divided into 10 groups： control group （ozone-free air plus vehicle [C]）, control ＋ TIB group （ozone-free air plus TIB 1 mg/kg [C ＋ TIB]）; 7,15, 30, and 60 days of ozone exposure groups [O3] and 7, 15, 30, and 60 days of TIB 1 mg/kg before ozone exposure groups [O3 ＋ TIB]. The effects of O3 exposure and TIB administration were assessed by western blot analysis of total and phosphorylated Tau, GSK3β, Akt, PP2A, and PTEN proteins and oxidative stress marker nitrotyrosine, and superoxide dismutase activity and lipid peroxidation of malondialdehyde by two different spectrophotometric methods （Marklund and TBARS, respectively）. We observed that O3 exposure increases Tau phosphorylation, which is correlated with decreased PP2A and PTEN protein levels, diminished Akt protein levels, and increased GSK3β protein levels in the hippocampus of adult male rats. The effects of O3 exposure were prevented by the long-term treatment （over 15 days） with TIB. Malondialdehyde and nitrotyrosine levels increased from 15 to 60 days of exposure to O3 in comparison to C group, and superoxide dismutase activity decreased. Furthermore, TIB administration limited the changes induced by O3 exposure. Our results suggest a beneficial use of hormone replacement therapy with TIB to prevent neurodegeneration caused by O3 exposure in rats.

Beneficial Effects of Tibolone on Sexual Dys-function in Women with Premature Ovarian Failure (POF)

Introduction: Premature Ovarian Failure (POF) is cessation of ovarian functions before the age of 40 years old with consequent cessation of menstruation. Objective of study: The aim of this study was to evaluate the association between Premature Ovarian Failure and sexual dysfunctions and outcome of management with tibolone. Patients and Methods: Thirty-one women with Premature Ovarian Failure seen at the outpatient clinic of Maternity Hospital were enrolled into the study with 31 healthy women as control group. The instrument of data collection included two types of questionnaires to assess the effect of Premature Ovarian Failure on sexuality. All the women with POF had oral tibolone 2.5 mg for at least one year and the second questionnaire and the profiles were repeated. Results: Of the 31 women with POF that presented with sexual dysfunction (SD), 27 (87.1%) complained of one or more SD domains such as reduced frequency of coitus, dyspareunia, vaginal dryness, reduced libido and general sexual satisfaction (P < 0.01), amenorrhea (P < 0.01) and hot flashes compared to 5 (16.1%) control women (P < 0.01). Administration of tibolone was associated with significant increase in frequency of coitus, reduced dyspareunia and vaginal dryness, increase libido and general satisfaction and happiness. Reduction of sexual dysfunction was predicated on the estrogenic, progestogenic and androgenic metabolite of tibolone through the reduction of serum level of FSH and LH and increased levels of estrogen and testosterone (P < 0.01). Tibolone had no adverse effect on serum lipid profile. Conclusion: Premature Ovarian Failure is associated with sexual dysfunction. Tibolone provides an effective means of treating sexual dysfunction caused by Premature Ovarian Failure.

Tibolone Reverses NAFLD in Ovariectomised Rats by Reducing Adiposity and Insulin Resistance

This study aimed to investigate the effects of tibolone,a synthetic steroid,on several metabolic dysfunctions induced by oestrogen deficiency,in rats.Ovariectomised(OVX)rats were used as animal model of postmenopausal metabolic syndrome.The OVX rats were treated with daily doses of tibolone(0.16 mg/kg)and the results were compared with control(sham-operated)and OVX untreated rats.Tibolone reduced the adiposity and the visceral adipocyte size in OVX rats.The insulin sensitivity was also improved,and a decrease in the activity of the adipose tissue hormone-sensitive lipase enzyme was recorded.The lower lipolysis by visceral adipocytes,associated with the recovery of peroxisomalβ-oxidation by tibolone may have contributed to the reversion of NAFLD in treated OVX rats.The reduction of liver lipid contents resulted in a general improvement in the liver redox state.In addition,tibolone reduced the mitochondrial ROS generation and restored the activity of glucose-6-phosphate dehydrogenase.Tibolone also exerted antioxidant effects on inguinal adipose tissue.Tibolone exerted several beneficial effects on cellular and metabolic dysfunctions induced by ovariectomy in rats.One important mode of action of tibolone was the reduction of the visceral adipocyte size,corroborating the relationship between this one and the development and progression of several comorbidities associated with metabolic syndrome.

Effect of tibolone as well as Estradiol and Drospirenone replacement therapy on the neurohumoral indexes and immune function in perimenopausal women

Objective: To explore the effect of tibolone as well as Estradiol and Drospirenone replacement therapy on the neurohumoral indexes and immune function in perimenopausal women. Methods: A total of 180 perimenopausal women who were treated in our hospital between December 2014 and December 2016 were collected and divided into the tibolone group (n=90) as well as Estradiol and Drospirenone group (n=90) by random number table, they received tibolone as well as Estradiol and Drospirenone replacement therapy respectively, and both therapies lasted for 6 months. The differences in serum levels of neurohumoral indexes and immune function indexes were compared between the two groups. Results:Before treatment, differences in serum levels of neurohumoral indexes and immune function indexes were not statistically significant between the two groups. After 6 months of treatment, serum E2, IL-4 and IL-13 levels of both groups of patients were significantly higher than those before treatment while P, T, FSH, LH, PRL, IFN-γ and IL-2 levels were significantly lower than those before treatment, and serum E2, IL-4 and IL-13 levels of observation group were significantly higher than those of control group while P, T, FSH, LH, PRL, IFN-γ and IL-2 levels were significantly lower than those of control group. Conclusion: Both tibolone and Estradiol and Drospirenone can be used in the treatment of women with perimenopausal syndrome, but tibolone is more effective in optimizing hormone levels and equalizing immune function.

尿中7-甲基异炔诺酮(Tibolone)代谢物的气相色谱-质谱研究

应用气相色谱-质谱(GC/MS)选择离子监测(SIM)方式探讨甾体类药物7-甲基异炔诺酮(Tibolone)的检测方法。根据Tibolone的代谢规律,对受试者的阳性尿和空白尿检测结果进行比较。研究发现:在阳性尿中检出△4双键异构体、3α羟基和3β羟基等三种代谢物,6位、16位的羟基化代谢物没有检出。测定了3α羟基代谢物的浓度-时间关系曲线,表明Tibolone口服后吸收迅速,9小时后即可达到峰值浓度。可为该类药物的检测提供科学依据。

首批异替勃龙国家对照品的标定研究

目的制备并标定首批异替勃龙国家对照品,以有效控制替勃龙及其制剂产品质量。方法应用红外光谱、质谱、核磁共振谱对异替勃龙进行结构确证,采用反相高效液相色谱(HPLC)法测定待标品纯度,采用质量平衡法对待标品进行赋值,并对待标品的均一性和稳定性进行考察。结果异替勃龙待标品经标定,以C_(21)H_(28)O_(2)计,含量为99.6%;均一性考察符合要求,25℃±2℃、RH 75%±5%条件,40℃±2℃、RH 75%±5%条件,光照4500 lx±500 lx条件下放置10 d,纯度略有下降。结论本批待标品确认为异替勃龙,可作为第一批异替勃龙国家对照品,以供异替勃龙HPLC法鉴别和含量测定用,以C_(21)H_(28)O_(2)计,本批待标品含量为99.6%。

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：（l） 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 4th 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 8th and 12th 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.

Effects of estrogen and tibolone on bladder histology and estrogen receptors in rats

Background Estrogen deficiency causes atrophic changes within the urogenital tract, and is associated with urinary symptoms. The purpose of this study was to investigate the effects of estrogen and tibolone on bladder histology, and the changes of estrogen receptor a and β （ERα and β） protein expression in the detrusor muscle.Methods Forty female rats were separated into four groups of ten each. They received a sham operation （Sham）, ovariectomy （Ovx）, ovariectomy plus estrogen replacement （Ovx＋E）, or ovariectomy plus tibolone treatment （Ovx＋T）. After 12 weeks each rat was anesthetized and the bladders were removed. The bladders＇ ultra structure, collagen fiber （CF） to smooth muscle（SM） ratio and ER subtypes were studied. Statistical analyses were performed using the one-way analysis of variance test. Results Ovx resulted in significant degeneration in bladder ultra structure; however, estrogen and tibolone reversed those changes. Ovx increased the CF/SM ratio, estrogen and tibolone resulted in an increase. Two estrogen receptors （ERs） were expressed in the bladder detrusor, with ERβ the main subtype. Ovx resulted in up-regulation of ERα and down-regulation of ERβ. With estrogen and tibolone treatment, ERβ showed a significant increase but ERα showed no significant difference compared with Ovx. Conclusions Estrogen deficiency deteriorates bladder ultra structure and histology. Supplementary estrogen can improve bladder function which may be due to inhibition of collagen hyperplasia and increased SM density. ERβ has an important role in mediating estrogen function in the bladder. Tibolone has a mild estrogenic action and has an effect on bladder function and structure to some degree.

Study on drug retention in menopausal women with sequential hormone therapy and tibolone

In the present study, we aimed to retrospectively analyze the medication prescriptions of menopausal women diagnosed with menopausal syndrome in our hospital from 2015 to 2018, and compare the retention rate of estrogen and progesterone sequential therapy and hormone continuous therapy in menopausal women. The rational drug management system of Ningbo Women and Children’s hospital was used to screen the prescriptions of menopausal syndrome in 4 years. After the age, year included in the study, and prescription cost were adjusted, Kaplan-Meier regression analysis was performed to compare the prescription retention rates of the two drug regimens. The distribution of the two HRT regimens in the 4 years showed an increasing trend year by year, and the age groups of the two HRT regimens were mainly distributed between 41 and 60 years old, accounting for 97.1% and 87.06%, respectively. The cost distribution for the other two HRT regimens was approximately the same. Compared with the two HRT regimens, the drug retention rate of hormone continuous regimens was higher than that of hormone sequential regimens within 4 years. Kaplan-Meier regression analysis showed that the trend was significant(Tarone-Ware, Chi-square value = 3.857, P = 0.050). This study found that the median retention time of HRT therapy in menopausal women in our hospital was about half a year, which was significantly lower than that reported in previous studies of 1 year or longer. In addition, the present study found that compared with Femoston, the tibolone regimen significantly increased retention time in the treatment of menopausal syndrome.

定坤丹联合替勃龙治疗更年期综合征对性激素水平和子宫内膜的影响

目的:探究定坤丹联合替勃龙治疗更年期综合征对性激素水平和子宫内膜的影响。方法:选取2021年9月—2022年9月仙桃市妇幼保健院妇科收治的更年期综合征患者98例,按随机数字表法分为对照组和观察组,各49例。对照组予以替勃龙治疗,观察组行定坤丹联合替勃龙治疗,对比两组的临床疗效、性激素[雌二醇(E2)、卵泡刺激素(FSH)、黄体生成素(LH)]水平、子宫内膜厚度及不良反应。结果:观察组总有效率为93.88%,高于对照组的79.59%(P<0.05);治疗后观察组的E2水平高于对照组,FSH与LH水平均低于对照组(P<0.05);治疗后观察组子宫内膜厚度大于对照组(P<0.05);观察组不良反应发生率为6.12%,对照组为10.20%,两组比较差异无统计学意义(P>0.05)。结论:定坤丹联合替勃龙治疗更年期综合征,可以有效促进性激素水平与子宫内膜恢复,临床疗效显著且安全性高。

替勃龙治疗绝经后女性耳鸣的疗效及对其神经递质水平和睡眠质量的影响

目的探讨替勃龙对绝经后女性耳鸣患者的疗效及对神经递质水平和睡眠质量的影响。方法将106例收治的绝经后耳鸣患者随机分为对照组和观察组各53例。两组均接受围绝经期综合管理,对照组口服谷维素片,观察组口服替勃龙片+谷维素片。比较两组临床疗效及治疗前后改良Kupperman指数(KMI)、耳鸣障碍指标评估量表(THI)、匹兹堡睡眠质量指数(PSQI)评分,并对患者血清雌二醇(E 2)、卵泡刺激素(FSH)、黄体生成素(LH)、5-羟色胺(5-HT)、去甲肾上腺素(NE)水平进行检测。结果观察组临床总有效率高于对照组(P<0.05)。治疗后,两组KMI、THI及PSQI评分均降低,且观察低于对照组;两组血清E 2水平及5-HT水平均升高,且观察组高于对照组,FSH水平、LH水平及NE水平均降低,且观察组低于对照组(P<0.05)。结论替勃龙可明显缓解绝经后女性耳鸣症状,改善其睡眠质量,对性激素和神经递质的调节可能是其作用机制。

醋酸曲普瑞林联合小剂量替勃龙用于卵巢子宫内膜异位症术后43例的回顾性研究

目的 探讨醋酸曲普瑞林联合小剂量替勃龙治疗卵巢子宫内膜异位症的有效性。方法 以信阳职业技术学院附属医院2020年1月至2021年12月收治的卵巢子宫内膜异位症患者86例为研究对象,根据治疗方式不同分为两组,每组各43例。两组均行腹腔镜手术治疗,对照组皮下注射醋酸曲普瑞林,观察组在此基础上口服小剂量替勃龙。比较两组临床疗效,骨密度(腰椎及股骨粗隆骨骨密度),性激素水平[黄体生成素(LH)、卵泡刺激素(FSH)、雌二醇(E2)],血管内皮功能相关指标[血管内皮生长因子(VEGF)、基质金属蛋白酶-2(MMP-2)、MMP-9、多配体蛋白多糖-1(Syndecan-1)],不良反应。结果 观察组总有效率95.35%高于对照组81.40%(P<0.05);观察组术后6个月、术后12个月腰椎骨密度高于对照组(P<0.05);术后6个月、术后12个月,两组股骨粗隆骨密度比较,差异无统计学意义(P>0.05);观察组术后6个月血清E2、FSH水平高于对照组,LH水平低于对照组(P<0.05);观察组术后6个月血清VEGF、MMP-2、MMP-9、Syndecan-1水平均明显低于对照组(P<0.05);治疗期间,观察组不良反应发生率6.98%与对照组11.63%相比,差异无统计学意义(P<0.05)。结论 醋酸曲普瑞林联合小剂量替勃龙能有效地减少子宫内膜异位症患者术后的骨密度流失,调节性激素水平,改善血管内皮功能,效果确切,安全可靠。

芬吗通和替勃龙对绝经综合征患者血糖、血脂和不良反应的影响研究

目的:探究芬吗通和替勃龙在治疗绝经综合征中的效果及其对患者血糖、血脂和不良反应的影响。方法:2023年1月—2024年3月因绝经综合征在启东市人民医院妇科门诊治疗的患者共60例,简单随机抽样分成芬吗通组(口服芬吗通)和替勃龙组(口服替勃龙),各30例。比较两组患者血糖、血脂、BMI、血压、症状改善量表、不良反应发生情况,分析两种药物的运用价值及对血糖、血脂的影响和不良反应。结果:两组患者治疗后空腹血糖(fasting plasma glucose,FPG)、糖化血红蛋白(glycosylated hemoglobin,HbA1c)指标水平均低于治疗前(均P<0.05),两组患者BMI和SBP、DBP水平比治疗前更好(P<0.05),但组间差异无统计学意义(P>0.05);治疗后两组血脂指标胆固醇、三酰甘油、低密度脂蛋白、高密度脂蛋白水平均优于治疗前(均P<0.05),但组间差异无统计学意义(P>0.05);两组治疗后1、3、6个月随访Kupperman评分均低于治疗前(均P<0.05),而组间差异无统计学意义(P>0.05);两组不良反应发生率差异无统计学意义(P>0.05)。结论:芬吗通和替勃龙均可明显改善绝经综合征患者临床症状,改善患者糖脂代谢指标,且安全性较高。

替勃龙治疗绝经后更年期综合征患者的有效性

目的探讨绝经后更年期综合征患者应用替勃龙治疗的有效性。方法随机选取在濮阳油田总医院2021年2月至2023年2月接受治疗的绝经后更年期综合征患者87例,按照治疗药物的不同将所有患者分为对照组(n=43,坤泰胶囊治疗)及观察组(n=44,替勃龙治疗)。评估两组患者治疗效果、激素水平、免疫功能、生活质量及药物不良反应发生率。结果观察组患者绝经后更年期综合征症状评分低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者雌二醇水平增加、黄体生成素与血清卵泡激素水平下降,且观察组雌二醇水平高于对照组,黄体生成素与血清卵泡激素水平低于对照组,差异有统计学意义(P<0.05)。治疗后两组CD3^(+)、CD4^(+)与CD4^(+)/CD8^(+)指标高于治疗前,CD8^(+)指标低于治疗前,且观察组CD3^(+)、CD4^(+)与CD4^(+)/CD8^(+)指标高于对照组,CD8^(+)指标低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者生活质量评分均提高,且观察组患者生活质量评分高于对照组,差异有统计学意义(P<0.05)。观察组发生阴道出血、乳房胀痛、胃肠道不适、头晕的药物不良反应发生率为6.83%,对照组为11.83%,观察组药物不良反应发生率与对照组相比,差异无统计学意义(P>0.05)。结论替勃龙能有效减轻绝经后更年期综合征患者因激素失衡引起的不适症状,有助于增强免疫功能,且用药不良反应相对较少,帮助患者抵抗疾病,进而使得患者能够更好地应对日常生活。

地诺孕素与促性腺激素释放激素激动剂联合替勃龙反向添加在子宫腺肌病保守手术后的应用效果比较

目的比较地诺孕素(DNG)与促性腺激素释放激素激动剂(GnRH-a)联合替勃龙反向添加在子宫腺肌病保守手术后的应用效果。方法选择2020年3月至2021年3月于新乡医学院第一附属医院行腹腔镜下子宫腺肌病病灶切除术的100例患者为研究对象,根据术后应用的药物将患者分为观察组和对照组,每组50例。2组患者均于静脉复合全身麻醉下行腹腔镜下子宫腺肌病病灶切除术。对照组患者于术后2 d内给予GnRH-a制剂亮丙瑞林缓释微球3.75 mg,皮下注射,28 d注射1次,共注射6次;于GnRH-a第2次注射日开始,给予替勃龙片2.5 mg,口服,每日1次,连续用药至最后1次注射亮丙瑞林缓释微球后28 d停药。观察组患者于术后2 d内开始给予DNG 2.0 mg,每日1次,口服,连续用药6个月。分别于治疗前、后,采用疼痛视觉模拟评分表(VAS)评估2组患者痛经的疼痛程度;采集患者空腹肘静脉血,使用全自动电化学发光免疫分析仪检测血清糖类抗原125(CA125)、雌二醇(E_(2))水平;采用月经失血图评分法(PBAC)评估2组患者月经量。观察2组患者治疗期间潮热出汗、不规则阴道流血、失眠烦躁、肌肉骨关节疼痛等药物相关不良反应的发生情况,评估2组患者治疗后的临床治疗效果。结果对照组患者显效30例,有效18例,无效2例,总有效率为96.0%(48/50);观察组患者显效27例,有效19例,无效4例,总有效率为92.0%(46/50);2组患者总有效率比较差异无统计学意义(χ^(2)=0.709,P>0.05)。治疗前、后,2组患者的VAS、PBAC评分及血清E_(2)、CA125水平比较差异无统计学意义(P>0.05)。2组患者治疗后的VAS、PBAC评分及血清E_(2)、CA125水平显著低于治疗前(P<0.01)。治疗期间,对照组患者发生潮热出汗8例(16.0%),不规则阴道流血2例(4.0%),失眠烦躁6例(12.0%),肌肉骨关节疼痛5例(10.0%);观察组患者发生潮热出汗6例(12.0%),不规则阴道流血13例(26.0%),失眠烦躁7例(14.0%),肌肉骨关节疼痛6例(12.0%);观察组患者不规则阴道流血发生率显著高于对照组(χ^(2)=0.002,P<0.05);2组患者潮热出汗、失眠烦躁、肌肉骨关节疼痛发生率比较差异无统计学意义(χ^(2)=0.564、0.766、0.749,P>0.05)。结论子宫腺肌病患者保守手术后,应用DNG与GnRH-a联合替勃龙反向添加疗法的临床效果相当,DNG治疗便捷性更高,更有利于提高患者的治疗依从性,可作为子宫腺肌病患者保守手术后的良好选择。