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.

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。

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。

坤泰胶囊联合地屈孕酮及替勃龙治疗对更年期综合征患者睡眠质量和神经内分泌系统及子宫内膜厚度的影响

目的探讨坤泰胶囊联合地屈孕酮和替勃龙治疗对更年期综合征患者睡眠质量、神经内分泌系统及子宫内膜厚度的影响。方法选取2020年5月至2021年4月本院收治的76例更年期综合征患者作为研究对象,采用抽签法分为对照组与观察组,每组38例。对照组给予地屈孕酮+替勃龙治疗,观察组给予坤泰胶囊+地屈孕酮+替勃龙治疗,比较两组治疗前后相关神经内分泌系统指标、睡眠质量、子宫内膜厚度。结果治疗前,两组雌二醇(E_(2))、卵泡生成激素(FSH)、去甲肾上腺素(NE)和5-羟色胺(5-HT)水平比较差异无统计学意义;治疗后,两组E_(2)、5-HT和NE水平均高于治疗前,FSH水平均低于治疗前,且观察组E_(2)、5-HT和NE水平均高于对照组,FSH水平低于对照组,差异有统计学意义(P<0.05)。治疗前,两组睡眠质量评分及子宫内膜厚度比较差异无统计学意义;治疗后,两组睡眠质量评分均低于治疗前,子宫内膜厚度均厚于治疗前,且观察组睡眠质量评分低于对照组,子宫内膜厚度厚于对照组,差异有统计学意义(P<0.05)。结论坤泰胶囊联合地屈孕酮和替勃龙治疗更年期综合征患者疗效显著,有利于调节患者神经内分泌紊乱情况,改善子宫内膜厚度,提升睡眠质量,值得临床推广应用。

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

目的对比抗抑郁药以及性激素治疗围绝经期及绝经后妇女抑郁症的疗效。方法129例围绝经期及绝经后妇女抑郁症患者为研究对象,根据治疗方法的不同分为对照组(65例)及观察组(64例)。对照组予以抗抑郁药盐酸氟西汀治疗,观察组予以性激素替勃龙治疗。比较两组患者的临床疗效,用药不良反应发生率,治疗前后的汉密尔顿抑郁量表(HAMD)评分。结果观察组患者的治疗总有效率为95.31%,与对照组的92.31%比较,差异无统计学意义(P>0.05)。观察组患者的用药不良反应发生率为9.38%,与对照组的10.77%比较,差异无统计学意义(P>0.05)。观察组患者治疗前的HAMD评分为(15.65±3.06)分、治疗后为(3.36±0.66)分,对照组患者治疗前的HAMD评分为(16.11±3.07)分、治疗后为(3.50±0.67)分。治疗前,两组患者的HAMD评分比较,差异无统计学意义(P>0.05);治疗后,两组患者的HAMD评分均低于本组治疗前,差异具有统计学意义(P<0.05);但两组治疗后的HAMD评分比较,差异无统计学意义(P>0.05)。结论围绝经期及绝经后妇女抑郁症患者通过抗抑郁药和性激素进行治疗在疗效上没有明显的差异,安全性也相当,都能发挥改善抑郁症状的目的,所以可以根据医疗机构的实际情况或患者的需求,合理的选择。

替勃龙联合雌二醇片/雌二醇地屈孕酮片治疗围绝经期综合征的效果分析

目的:分析替勃龙联合雌二醇片/雌二醇地屈孕酮片治疗围绝经期综合征的效果。方法:选取2021年1—12月北京市丰台区青塔街道社区卫生服务中心与航天中心医院永定路社区卫生服务中心收治的64例围绝经期综合征患者作为研究对象,采用随机数字表法分为对照组与观察组,各32例。对照组应用雌二醇片/雌二醇地屈孕酮片治疗,观察组在对照组基础上应用替勃龙治疗。比较两组治疗效果。结果:两组治疗总有效率比较,差异无统计学意义(P>0.05)。治疗前,两组促黄体生成素(LH)、促卵泡生成素(FSH)、雌二醇(E_(2))水平比较,差异无统计学意义(P>0.05)。治疗后,两组LH、FSH水平低于治疗前,E_(2)水平高于治疗前,差异有统计学意义(P<0.05);两组间比较,差异无统计学意义(P>0.05)。治疗前,两组匹兹堡睡眠质量指数量表(PSQI)、更年期评定量表(MRS)评分比较,差异无统计学意义(P>0.05);治疗后,两组PSQI、MRS评分低于治疗前,且观察组低于对照组,差异有统计学意义(P<0.05)。两组不良反应总发生率比较,差异无统计学意义(P>0.05)。结论:替勃龙联合雌二醇片/雌二醇地屈孕酮片治疗围绝经期综合征效果较好,可提高患者睡眠质量及生活质量。