Changes in the withdrawal bleeding pattern and endometrial histology during 17β-estradiol —dydrogesterone therapy in postmenopausal women: a 2 year prospective study

Objective: To describe changes in the withdrawal bleeding pattern and endometrial histology during a sequential 17β-estradiol —dydrogesterone regimen in postmenopausal women. Design: Open-label, non-comparative, prospective study. Setting: Gynecological outpatient department of a university hospital. Patients: Twenty-seven healthy nonhysterectomized postmenopausal women. Interventions: Continuous micronized 17β-estradiol supplementation, 2 mg daily, and cyclic administration of dydrogesterone, 10 mg daily for the first half of each 28 day treatment cycle. Main Outcome Measures: Changes in the characteristics of the withdrawal bleeding pattern and the endometrial biopsy histology during 2 years of treatment. Results: The initial withdrawal bleeding was comparable to normal menstruation with respect to amount and duration. During the 2 years of treatment the bleeding showed a significant tendency to become shorter with less blood loss. This was mainly the result of the decrease (P < 0.001) in the number of days per cycle with bleeding grade II (normal menstruation). None of the women developed endometrial hyperplasia, and in almost all women the given hormone replacement therapy regimen induced secretory or atrophic changes of the endometrium. Conclusions: This sequential 17β-estradiol —dydrogesterone regimen can be regarded as safe with respect to the prevention of endometrial disease and appeared to foster patient compliance.     

A comparative study of dydrogesterone and micronized progesterone for luteal phase support during in vitro fertilization (IVF) cycles

The aim of the present study was to compare the efficacy, tolerability and patients’ satisfaction after the use of oral dydrogesterone with vaginal micronized progesterone for luteal-phase support (LPS) among infertile women undergoing in vitro fertilization (IVF). A total of 210 women (aged 20–40 years old) with a history of infertility, who underwent controlled ovarian stimulation for fresh intra-cytoplasmic sperm injection-embryo transfer cycles, were included in the study. Consequently, they were randomized to receive LPS with dydrogesterone 20?mg twice daily (n?=?96) or micronized progesterone 400?mg twice daily at the day of oocyte retrieval (n?=?114). The clinical success rate (31% versus 33%; p?=?0.888), miscarriage rate (5.0% versus 3.0%; p?=?0.721), ongoing pregnancy rate (30.0% versus 30.0%; p?=?1.000), implantation (22.0% versus 24.0%; p?=?0.254) and multiple pregnancy rate (5.30% versus 7.20%; p?=?0.394) were comparable among the two groups. Serum progesterone levels were significantly lower among the patients receiving dydrogesterone than the control group (13.62?±?13.83?ng/ml versus 20.66?±?18.09?ng/ml; p?=?0.001). However, there was no statistically significant difference regarding the patients’ satisfaction (p?=?0.825) and tolerability (0.790) between the two groups. Our results showed that oral dydrogesterone (40?mg/day) is as effective as vaginal micronized progesterone considering its clinical outcomes and patients’ satisfaction and tolerability, for LPS among women undergoing IVF.     

戊酸雌二醇联合地屈孕酮治疗非器质性月经过多的疗效观察

目的观察戊酸雌二醇联合地屈孕酮治疗非器质性月经过多的临床疗效及安全性。方法选取86例非器质性月经过多患者,采用信封法随机分为2组,每组43例。对照组患者采用戊酸雌二醇联合安宫黄体酮治疗,观察组采用戊酸雌二醇联合地屈孕酮治疗,两组患者均给予补充铁剂、加强营养、注意休息等对症支持治疗,均连续治疗3个周期。按照月经失血图评分法(PBAC)评估两组患者经血量,评分>100分(经血量>80 mL)为月经过多。记录两组患者用药后出血控制时间、出血停止时间,并根据两组患者阴道出血情况进行疗效评定。治疗期间严密观察两组患者不良反应发生情况。结果观察组、对照组的总有效率分别为95.35%、81.40%,两组比较差异有统计学意义(P<0.05)。观察组、对照组的出血控制时间分别为(16.5±2.0)d、(25.6±3.0)d,出血停止时间分别为(23.5±3.8)d、(40.5±5.0)d,两组比较差异均有统计学意义(P<0.05)。观察组治疗1个周期、2个周期、3个周期后,PABC评分明显低于对照组(P<0.05)。观察组、对照组分别有4例(9.30%)、5例(11.63%)发生不良反应,两组比较差异无统计学意义(P>0.05)。结论采用戊酸雌二醇联合地屈孕酮治疗非器质性月经过多,可迅速控制出血,减少月经出血量,不良反应少而轻微。     

地屈孕酮治疗先兆流产的系统评价

目的:评价地屈孕酮治疗先兆流产的有效性和安全性。方法:计算机检索PubMed、Embase、Cochrane Central、中国生物医学文献数据库(CBM)、中国期刊全文数据库(CNKI)、维普中文科技期刊全文数据库(VIP)、ClinicalTrials.gov和世界卫生组织国际临床试验注册平台(WHOICTRP),获得地屈孕酮治疗先兆流产已发表和未发表的随机对照试验(RCT)。2名研究者独立筛选文献、提取资料和评估偏倚风险,采用RevMan5.0软件进行Meta分析。结果:共纳入8个RCT,包括1185名受试者。地屈孕酮vs.保守治疗:纳入4个RCT,Meta分析结果显示,地屈孕酮组流产率低于保守治疗组[RR=0.46,95%C(I0.32,0.65),P<0.0001],2组早产(P=0.77)、产前出血(P=0.57)及胎儿先天畸形(P=0.71)发生率差异均无统计学意义;地屈孕酮vs.黄体酮:纳入2个RCT,因偏倚较大未进行Meta分析,均报道2组流产率差异无统计学意义(P=1.000和P=0.630);地屈孕酮vs.人绒毛膜促性腺激素(HCG):纳入1个RCT,2组流产(P=0.711)、早产(P=0.727)和胎儿畸形(P=0.461)发生率差异均无统计学意义;地屈孕酮联合中药治疗:纳入2个RCT,地屈孕酮联合滋肾育胎丸与单服地屈孕酮组流产率分别为8%和13%,差异无统计学意义(P=0.655),地屈孕酮联合补肾活血安胎方与黄体酮组流产率分别为7.5%和15%,差异无统计学意义(P=0.390)。结论:地屈孕酮较单纯保守治疗流产率低,但现有研究方法学质量均较低,有待高质量研究验证其疗效;尚缺乏证据证明母亲或胎儿的不良结局与孕期服用地屈孕酮有关;现有研究尚不能提示地屈孕酮与黄体酮、HCG疗效有差异;现有证据尚不能提示地屈孕酮联合中药治疗有益。     

间苯三酚联合地屈孕酮治疗先兆流产的疗效观察

目的探讨间苯三酚联合地屈孕酮治疗孕12周前先兆流产的临床效果。方法将2010～2011年收治的先兆流产患者96例随机分成两组：观察组使用间苯三酚联合地屈孕酮治疗,对照组单纯使用地屈孕酮治疗。比较两组保胎成功率、临床症状缓解及消失时间、药物不良反应。结果观察组与对照组相比,临床症状缓解及消失时间短、保胎成功率高、药物不良反应少（P〈0.05）。结论间苯三酚联合地屈孕酮治疗孕12周前先兆流产疗效显著,可快速缓解流产症状,缩短治疗时间,药物不良反应少,值得临床推广应用。     

地屈孕酮对先兆流产患者Th1/Th2型细胞因子平衡的影响

目的探讨孕激素地屈孕酮对先兆流产患者Th1/Th2型细胞因子平衡的影响,分析以免疫调节治疗先兆流产的机制。方法采用酶联免疫吸附方法检测42例正常妊娠妇女和60例先兆流产妇女使用地屈孕酮治疗前后的血清中Th1型细胞因子（IL-2和TNF-α）及Th2型细胞因子（IL-4和IL-10）的表达水平。结果先兆流产组治疗后血清中IL-2和TNF-α的表达水平与治疗前相比明显降低（P值均〈0.05）,与正常妊娠组相比差异无统计学意义（P值均〉0.05）;而先兆流产组血清中IL-4和IL-10的表达水平在治疗前后差异无统计学意义（P值均〉0.05）,治疗后略有上升,达到和正常妊娠组相当的水平（P值均〉0.05）。结论孕激素治疗先兆流产的机制可能在于促进Th2型细胞因子的分泌,纠正Th1/Th2型细胞因子的病理偏移,使其向着正常妊娠时的平衡移动,即由Th1向Th2的移动。     

地屈孕酮对不明原因复发性自然流产患者外周血辅助T细胞的影响

目的探讨地屈孕酮补充治疗对不明原因复发性自然流产(URSA)患者外周血辅助性T细胞(Th)亚群Th1/Th2的影响。方法选取30例不明原因复发性自然流产患者为URSA组,另选取30例正常育龄妇女作为对照组,URSA组予以地屈孕酮治疗,对照组不采取任何治疗措施。两组均进行γ干扰素(IFN-γ)(Th1细胞因子)、白细胞介素-4(IL-4)(Th2细胞因子)的检测,观察URSA组妊娠情况,比较两组Th细胞因子变化情况、妊娠后不同时期Th1/Th2的变化,分析地屈孕酮对不同流产次数患者再次妊娠成功后Th细胞因子的影响。结果30例URSA患者妊娠28例,其中2例生化妊娠,3例妊娠40+d胚胎停育清宫,23例妊娠成功已转入产科定期产前检查。URSA组外周血Th1型细胞因子IFN-γ(26.37±3.13)pg/ml高于对照组的(17.01±3.22)pg/ml,差异有统计学意义(P<0.05)。两组Th2型细胞因子IL-4比较差异无统计学意义(P>0.05)。流产2次患者与流产>2次患者之间,IFN-γ活性出现升高趋势,Th1/Th2比值明显向Th1偏移。妊娠40 d及妊娠3个月,外周血Th1型细胞因子IFN-γ活性低于妊娠前,差异有统计学意义(P<0.05);与对照组比较差异无统计学意义(P>0.05);Th2型细胞因子IL-4活性高于妊娠前,差异有统计学意义(P<0.05)。Th1/Th2模式向后者偏移,Th1/Th2比值为4.37 vs 2.37。至孕3个月,偏移越趋于明显,5例妊娠失败患者外周血中,Th1型细胞因子IFN-γ及Th2型细胞因子IL-4与妊娠前比较,差异无统计学意义(P>0.05)。经地屈孕酮治疗后,流产2次的URSA患者Th1型细胞因子IFN-γ(16.03±5.11)pg/ml低于流产>2次的(21.48±1.83)pg/ml,差异有统计学意义(P<0.05);流产>2次的URSA患者呈现出更为明显的Th2偏移现象。结论地屈孕酮治疗可以使Th1/Th2平衡向Th2偏移,对免疫调节起重要作用,有利于妊娠成功。     

子宫内膜息肉宫腔镜电切或诊刮术后联合药物治疗的疗效分析

目的探讨子宫内膜息肉行宫腔镜电切术或行宫腔镜下诊刮术后进行联合用药或未用药的疗效,为临床有效治疗子宫内膜息肉提供依据。方法回顾性分析2018年7月至2019年6月我院的子宫内膜息肉患者的临床资料。将符合要求的患者分为4组。1组:单纯的宫腔镜下诊刮术;2组:宫腔镜下诊刮术术后地屈孕酮治疗3个月;3组:单纯的宫腔镜下子宫内膜息肉电切术;4组:宫腔镜下子宫内膜息肉电切术术后地屈孕酮治疗3个月。比较各组的月经情况、异常子宫出血改善情况、子宫内膜息肉复发情况、术后有生育要求的术后6个月内妊娠情况及子宫内膜厚度情况。结果各组的月经情况比较:4组月经情况改善率(95.42%)最高;异常子宫出血改善情况比较:4组异常子宫出血改善率(89.31%)最高;子宫内膜息肉的复发率情况比较:4组子宫内膜息肉的复发率9.92%最低;子宫内膜的厚度情况比较:4组子宫内膜厚度最薄;术后有生育要求的术后6个月内妊娠情况的比较:4组术后6个月内妊娠率10.69%最高;各组比较差异均有统计学意义(P0.05)。结论单纯的宫腔镜下子宫内膜息肉电切术比单纯宫腔镜下诊刮术疗效好,术后地屈孕酮治疗3个月组较无药物治疗组疗效好,治疗方案以宫腔镜下子宫内膜息肉电切术术后地屈孕酮治疗3个月为最佳。     

宫腔镜下子宫内膜息肉切除术联合地屈孕酮治疗子宫内膜息肉60例

目的 分析宫腔镜下子宫内膜息肉切除术(TCRP)联合地屈孕酮(达芙通)治疗子宫内膜息肉的疗效及对预后的影响.方法 选取2015年1月至2018年11月皖北煤电集团总医院接收的子宫内膜息肉病人120例,据随机数表法分为两组,每组60例,对照组单行TCRP治疗,观察组行TCRP+地屈孕酮治疗,观察两组TCRP术后第12、1...     

Oral ultra-low dose continuous combined hormone replacement therapy with 0.5 mg 17β-oestradiol and 2.5 mg dydrogesterone for the treatment of vasomotor symptoms: Results from a double-blind,controlled study

Objectives

Guidelines recommend using the lowest effective dose of oestrogen for the management of vasomotor symptoms in postmenopausal women. The primary aim of this double-blind, multi-centre, randomised study was to assess the efficacy of oral ultra-low dose continuous combined hormone replacement therapy with 17β-oestradiol and dydrogesterone.

Study design

313 women with ≥50 moderate to severe hot flushes during the previous week were randomised to 0.5 mg 17β-oestradiol/2.5 mg dydrogesterone (E 0.5 mg/D 2.5 mg), 1 mg 17β-oestradiol/5 mg dydrogesterone (E 1 mg/D 5 mg) or placebo for 13 weeks. The placebo group then switched to E 0.5 mg/D 2.5 mg for a further 39 weeks, whilst the other groups continued on the same treatment.

Results

After 13 weeks, the reduction in the number of moderate to severe hot flushes/day in the E 0.5 mg/D 2.5 mg group was greater than in the placebo group (−6.4 vs. −4.9, p < 0.001) and comparable to that in the 1/5 mg group (−6.3). E 0.5 mg/D 2.5 mg and E 1 mg/D 5 mg significantly improved the total Menopause Rating Scale score. The number of bleeding/spotting days was lower with E 0.5 mg/D 2.5 mg than with E 1 mg/D 5 mg. The overall amenorrhoea rate with E 0.5 mg/D 2.5 mg was 81%; this increased to 91% in months 10–12.

Conclusions

Continuous combined 0.5 mg 17β-oestradiol and 2.5 mg dydrogesterone was effective in alleviating vasomotor symptoms and improving quality of life, and was associated with a high amenorrhoea rate and a good tolerability profile.