Dydrogesterone treatment for menstrual-cycle regularization in routine clinical practice: a multicenter observational study

Dydrogesterone is an oral retroprogesterone widely used to treat progesterone deficiencies, including irregular menstrual cycles (MCs). This prospective, non-interventional, single-arm, post-marketing, observational study evaluated the effects of dydrogesterone on MC regularization. Women aged 18–40 years who had been prescribed dydrogesterone to treat irregular MCs due to progesterone deficiency were enrolled across 64 centers in Russia, Ukraine, Kazakhstan and Uzbekistan. Study objectives included: patients reporting ≥1 regular MC during treatment; the number of regular MCs after the end of treatment over a 6-month follow-up (FU) period. In total, 996 women were enrolled. Of those who completed treatment, 946/955 patients (99.1%) achieved ≥1 regular MC. During FU, 680/860 patients (79.1%) maintained ≥6 regular MCs. Patient grading of menstrual pain and anxiety decreased significantly during treatment (p?≤?0.0001 versus baseline); this persisted during FU. Dydrogesterone was associated with high or very high patient satisfaction (856/955; 89.6%); the clinical response was considered good or excellent in 819/955 patients (85.8%). In total, 16/986 patients (1.6%) reported an adverse event (AE); two had serious AEs (SAEs) (unrelated to treatment) and three discontinued treatment due to non-SAEs. Dydrogesterone therapy was effective in achieving MC regularization and reducing menstrual pain and anxiety, during both treatment and 6-month FU.     

来曲唑联合地屈孕酮治疗不孕症疗效及对血清孕酮的影响

目的:研究来曲唑片和地屈孕酮片联合治疗不孕症的疗效及其对患者血清孕酮的影响。方法:选取在某院确诊为不孕症并接受治疗的患者100例作为研究对象,按照治疗方法的不同,将其均分为单一组和联合组两个组别。单一组患者在常规治疗基础上通过来曲唑片进行的单一治疗,联合组患者在对照组基础上通过地屈孕酮片进行治疗,对比两组患者治疗的效果及相关指标的变化。结果:联合组患者治疗的总有效率为90%,显著高于单一组患者的72%(P<0.05);联合组患者的排卵率、SP、E2、LH水平均有显著改善,且优于单一组患者(P<0.05)。结论:对于不孕症患者来说,相比于使用来曲唑片进行单一治疗,来曲唑片和地屈孕酮片联合治疗不仅可以有效提高治疗效果及妊娠率,而且可以更有效改善患者的血清孕酮等水平,因此值得推广。     

Effect of oral administration of dydrogestrone versus vaginal administration of natural micronized progesterone on the secretory transformation of endometrium and luteal endocrine profile in patients with premature ovarian failure: a proof of concept

BACKGROUND: We aimed to explore the endometrial histology and endocrine profiles on day 21 of an artificial cycle in patients with premature ovarian failure (POF) treated with oral dydrogesterone (DG) or vaginal micronized progesterone. METHODS: The study was designed as a prospective pilot study at an academic reproductive medicine unit. Six POF patients were included in the study. After estrogen endometrial priming, patients were randomized to receive DG or progesterone in two subsequent cycles. The main outcome measure was the endometrial histology and the endocrine profiles on day 21 of the cycle. RESULTS: Development of endometrial glands corresponded to an early secretory phase in five out of six cases supplemented with DG (out-phase). In contrast, five out of six cases treated with micronized progesterone showed an endometrium corresponding to a mid-luteal phase (in-phase) (P = 0.021 versus DG). There was a significant difference in the mean progesterone value [8.6 versus 0.3 microg l(-1) (P = 0.013)], the mean LH value [12.9 versus 22.5 IU l(-1) (P = 0.049)] and the mean FSH value [13.0 versus 23.9 IU l(-1) (P = 0.047)] between the progesterone and DG group, respectively, on day 21 of the cycle. CONCLUSIONS: After estrogen endometrial priming in POF patients, exogenous vaginal micronized progesterone is more effective than oral DG in creating an 'in-phase' secretory endometrium and induces significantly higher progesterone and lower LH and FSH serum concentrations on day 21 of the cycle.     

安胎一号穴位贴敷联合雌二醇地屈孕酮片治疗肾虚型早期先兆流产临床研究

目的:观察安胎一号穴位贴敷联合雌二醇地屈孕酮片治疗肾虚型早期先兆流产的临床疗效。方法:选取肾虚型早期先兆流产患者74例,按随机数字表法分为对照组和观察组各37例。对照组给予雌二醇地屈孕酮片治疗,观察组在对照组基础上给予安胎一号穴位贴敷。统计2组临床症状积分,检测孕激素(P)、人绒毛膜促性腺激素(β-HCG)、雌二醇(E2)水平,观察不良反应发生情况。结果:治疗前,2组各项临床症状评分比较,差异无统计学意义(P>0.05)。治疗后,2组各项临床症状评分较治疗前降低,且观察组各项临床症状评分均低于对照组,差异均有统计学意义(P<0.05)。治疗前,2组P、β-HCG、E2水平比较,差异无统计学意义(P>0.05)。治疗后,2组P、β-HCG、E2水平较治疗前升高(P<0.05),且观察组P、β-HCG、E2水平均高于对照组(P<0.05)。对照组不良反应发生率为8.11%,观察组为5.41%,2组比较,差异无统计学意义(P>0.05)。结论:安胎一号穴位贴敷联合雌二醇地屈孕酮片治疗肾虚型早期先兆流产疗效显著,能够减轻临床症状,促进性激素水平恢复,安全性高。     

低剂量结合雌激素与标准剂量CEE联合天然黄体酮或地屈孕酮对围绝经期综合征患者骨密度的影响研究

目的探讨低剂量雌激素与标准剂量雌激素联合天然黄体酮或地屈孕酮对围绝经期综合征患者骨密度的影响。方法选取2015年1月至2017年1月间我院收治的围绝经期综合征患者83例,按照随机数字表法将其分为Ⅰ组、Ⅱ组、Ⅲ组、Ⅳ组,Ⅰ组28例采用低剂量雌激素联合天然黄体酮治疗,Ⅱ组27例采用低剂量雌激素联合地屈孕酮治疗,Ⅲ组26例采用标准剂量雌激素联合天然黄体酮治疗,Ⅳ组26例采用标准剂量雌激素联合地屈孕酮治疗,对比各组治疗前后体内相关激素水平、更年期Kupperman评分结果、不良反应等。结果治疗前四组临床症状及促卵泡素(FSH)、黄体生成素(LH)、雌二醇(E2)等各项指标对比差异无统计学意义(P0. 05);治疗1个周期及3个周期后,各组Greene评分均有所降低,且各组FSH、E2、LH较治疗前有不同程度的好转,其中Ⅰ组和Ⅲ组FSH高于其他组别,E2、LH水平明显低于其他组,差异有统计学意义(P0. 05),治疗前各组L_(1～4)骨密度、股骨颈骨密度差异对比无统计学意义(P0. 05);治疗后各组L_(1～4)骨密度、股骨颈骨密度均有所提升,但相比之下,Ⅰ组和Ⅲ组的L_(1～4)骨密度、股骨颈骨密度好转情况更加显著,差异有统计学意义(P0. 05)。结论采用低剂量雌激素联合天然黄体酮既能满足患者症状缓解的需求,同时也有助于体内激素水平的改善,且不会对骨密度造成负面影响,建议采纳。     

孕激素治疗先兆流产的临床研究进展

先兆流产是女性妊娠期的常见并发症,半数左右将进展为自发流产,严重影响女性身心健康.孕激素在维持妊娠中具有重要作用,多年来作为一种经典药物被用于先兆流产患者防止妊娠丢失.常用给药途径包括口服给药、肌肉注射及经阴道给药等.尽管孕激素用于治疗先兆流产已近70年,至今仍无确凿证据支持其疗效.本文通过结合近年来国内、外相关领域研究进展,综合评价孕激素在先兆流产患者中的治疗效果,并探索不同制剂、用药途径之间是否存在差异,旨在为临床应用提供参考借鉴.     

Oral oestradiol/trimegestone replacement reduces procarboxypeptidase U (TAFI): a randomized, placebo- controlled, 12-week study in early postmenopausal women

OBJECTIVE: To investigate the effects of short-term postmenopausal oral hormone administration on plasma levels of procarboxypeptidase U (proCPU, thrombin-activatable fibrinolysis inhibitor, EC 3.4.17.20), an inhibitor of fibrinolysis, in healthy early postmenopausal women. DESIGN: A prospective, randomized, placebo-controlled study. SETTING: Outpatient clinic of the Department of Obstetrics and Gynaecology. SUBJECTS: Seventy-seven healthy early postmenopausal women were screened of whom 65 were randomized. Analyses were based on 60 participants. INTERVENTIONS: The women received oral micronized oestradiol 2 mg either alone (E2 group, n=16), or sequentially combined with dydrogesterone 10 mg (E2 + D group, n=14) or trimegestone 0.5 mg (E2 + T, n=14), or placebo (n=16) for 12 weeks. MAIN OUTCOME MEASURE: ProCPU concentrations at baseline, and at 4 and 12 weeks of treatment. RESULTS: Four weeks of E2 + T was associated with a significant decrease in the fasting proCPU concentration, which was sustained after 12 weeks [t=0: 636 +/- 57 U L(-1) (mean +/- SD); t=4: 583 +/- 63UL-1; t=12: 589 +/- 48 U L(-1); ANCOVA versus placebo: P=0.011]. The percentage change from baseline versus placebo in this group was -8.4% [95% confidence interval (CI) -15.7 to -1.1] after 4 weeks and -5.9% (95% CI -11.7 to -0.1) after 12 weeks. There were no significant changes versus placebo in the E2 group nor in the E2 + D group. CONCLUSION: Short-term treatment with E2 + T, but not E2 alone or E2 + D, lowers proCPU concentration. These findings add to accumulating evidence suggesting that different progestagens added to oestrogen replacement may differentially affect the risk of arterial and venous disease.     

红花逍遥片联合雌二醇片/雌二醇地屈孕酮片复合包装治疗围绝经期综合征的临床研究

目的探讨红花逍遥片联合雌二醇片/雌二醇地屈孕酮片复合包装治疗围绝经期综合征的临床效果。方法选取2016年7月—2019年6月新乡市中心医院收治的100例围绝经期综合征患者,使用随机数字表法将其随机分成与对照组和治疗组,每组各50例。对照组口服雌二醇片/雌二醇地屈孕酮片复合包装,1片/次,1次/d,以28 d为1个疗程,前14 d服用白色片,后14 d服用灰色片。治疗组在对照组基础上口服红花逍遥片,3片/次,3次/d。两组均连续治疗3个疗程。观察两组的临床疗效,比较两组改良Kupperman绝经指数(KMI)评分、绝经期生存质量量表(MENQOL)总分、血流变学指标[全血高、低切黏度(HBV和LBV)、红细胞沉降率(ESR)和纤维蛋白原(FIB)]及血清性激素[卵泡刺激素(FSH)、促黄体生成素(LH)和雌二醇(E_2)]、炎症因子[肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6]水平的变化情况。结果治疗后,治疗组总有效率为96.0%,显著高于对照组84.0%(P0.05)。与治疗前相比,两组治疗后改良KMI评分和MENQOL总分均显著降低(P0.05),且与对照组治疗后相比,治疗组对以上评分的改善效果更显著(P0.05)。两组治疗后HBV、LBV、ESR及FIB均显著低于本组治疗前(P0.05);治疗后,治疗组血流变学指标低于对照组(P0.05)。治疗后,两组血清FSH、LH、TNF-α和IL-6水平均较本组治疗前显著下降,但血清E_2水平均显著升高(P0.05);且治疗后治疗组血清性激素和炎症因子水平改善更明显(P0.05)。结论红花逍遥片联合雌二醇片/雌二醇地屈孕酮片复合包装治疗围绝经期综合征患者效果确切,能减轻患者围绝经期相关症状、提高生命质量,并能显著改善机体血液流变学状态、调节生殖内分泌紊乱及下调相关炎症因子表达,值得临床推广应用。     

泰山磐石散加减结合地屈孕酮对气血两虚型习惯性流产妊娠影响研究

目的探究泰山磐石散加减结合地屈孕酮对气血两虚型习惯性流产患者妊娠影响。方法研究合计纳入92例气血两虚型习惯性流产患者,均由医院2017年1月—2020年2月收治,采取随机数字表法将其分为两组,予以对照组患者(46例)地屈孕酮治疗,予以观察组患者(46例)泰山磐石散加减结合地屈孕酮治疗,比较两组患者临床疗效、治疗前后中医症状(自然流产、月经异常、精神萎靡、头晕耳鸣、畏寒肢冷、夜尿频繁等)积分变化、妊娠结局、治疗前后患者孕酮(P)、雌二醇(E₂)水平变化、治疗前后患者免疫功能指标变化以及患者治疗满意程度。结果观察组患者治疗总有效率(97.83%,45/46)高于对照组(84.78%,39/46)(P<0.05);观察组患者顺利分娩率(97.83%,45/46)高于对照组(82.61%,38/46)(P<0.05);治疗前,两组患者自然流产、月经异常、精神萎靡、头晕耳鸣、畏寒肢冷、夜尿频繁等中医症状积分、P及E₂水平、白介素-4(IL-4)、γ干扰素(IFN-γ)、IFN-γ/IL-4等免疫功能指标比较,P>0.05,治疗后各组患者自然流产、月经异常、精神萎靡、头晕耳鸣、畏寒肢冷、夜尿频繁等中医症状积分、P及E₂水平、IL-4、IFN-γ、IFN-γ/IL-4等免疫功能指标均改善,观察组患者治疗后自然流产、月经异常、精神萎靡、头晕耳鸣、畏寒肢冷、夜尿频繁等中医症状积分、P及E₂水平、IL-4、IFN-γ、IFN-γ/IL-4等免疫功能指标均优于对照组(P<0.05);观察组患者治疗后满意率(93.48%,43/46)显著高于对照组患者(78.26%,36/46)(P<0.05)。结论泰山磐石散加减结合地屈孕酮治疗气血两虚型习惯性流产效果良好,可提升患者顺利分娩率,患者恢复好,免疫力提升,患者十分满意,值得应用。