Overview of elagolix for the treatment of endometriosis

Introduction: Suppression of sex-steroid secretion is required in a variety of gynecological conditions. This can be achieved using gonadotropin releasing hormone (GnRH) agonists that bind pituitary gonadotropin receptors and antagonize the link-receptor of endogenous GnRH, inhibiting the mechanism of GnRH pulsatility. On the other hand, GnRH antagonists immediately reduce gonadal steroid levels, avoiding the initial stimulatory phase of the agonists. Potential benefits of GnRH antagonists over GnRH agonists include a rapid onset and reversibility of action. Older GnRH antagonists are synthetic peptides, obtained by modifications of certain amino acids in the native GnRH sequence. They require subcutaneous injections, implantation of long-acting depots. The peptide structure is responsible for histamine-related adverse events and the tendency to elicit hypersensitivity reactions.

Areas covered: Research has worked towards the development of non-peptidic molecules exerting antagonist action on GnRH. They are available for oral administration and may have a more beneficial safety profile in comparison with peptide GnRH antagonists. This article focuses on the data of the literature about elagolix, a novel non-peptidic GnRHantagonist, in the treatment of endometriosis.

Expert opinion: Elagolix demonstrated efficacy in the management of endometriosis-associated pain and had an acceptable safety and tolerability profile. However, further studies are necessary to evaluate its non-inferiority in comparison with other endometriosis’s treatments.     

175例子宫内膜异位症药物治疗临床观察

目的 探讨孕三烯酮、口服避孕药敏定偶、中药丹莪妇康煎膏治疗内异症的疗效和安全性差异,指导临床用药.方法 从本院妇科患者中选取有子宫内膜异位症典型症状的患者,回顾分析了175例子宫内膜异位症患者的药物治疗随访资料,比较疗效及副作用发生率.结果 3组药物疗效无明显差异(P＞0.05),孕三烯酮引起的闭经、体重增加、潮热、多毛、痤疮发生率高于敏定偶和丹莪妇康煎膏(P＜0.05).丹莪妇康煎膏引起的肝功能损害仅占1.47%.结论 3种药物治疗内异症疗效无明显差异,敏定偶耐受性好,更容易被患者接受,对肝病患者丹莪妇康煎膏应为首选.     

子宫内膜不典型增生的药物转化治疗

目的 探讨醋酸甲羟孕酮治疗子宫内膜不典型增生的效果.方法 选择本院2012年5月～2013年8月收治的子宫内膜不典型增生患者56例,随机分为研究组和对照组,每组各28例,研究组患者给予醋酸甲羟孕酮治疗,2 mg/d,2次/d;对照组患者口服戊酸雌二醇片,1 mg/d;两组患者均治疗3个月,观察两组患者的治疗效果,采用PBAC评分观察治疗前后月经或阴道出血情况.结果 治疗后研究组总有效率明显低于对照组,两组差异有统计学意义.治疗后研究组阴道出血情况明显改善,PBAC评分明显高于对照组,两组差异有统计学意义.结论 醋酸甲羟孕酮治疗子宫内膜不典型增生疗效显著,可有效改善患者的出血症状,费用较低,适合患者长期治疗.     

Challenges in the development of novel therapeutic strategies for treatment of endometriosis

Introduction: Endometriosis is an estrogen-dependent disease that results in pelvic pain and infertility. Its treatment is often frustrating due to limited medical treatment options, complex surgical treatment and high recurrence rates. Despite the advances in our understanding of the pathogenesis over the last decades and the consequent novel therapeutic strategies, no new drugs have been introduced in daily clinical practice.

Areas covered: In the first part we present an overview of the pathogenesis of endometriosis. In the second part we discuss how new insights have led to the development of novel nonhormonal strategies for the treatment of endometriosis, focusing on anti-inflammatory and anti-angiogenic agents. In the third part we describe the problems encountered in the translation from experimental drugs to routine medicine for the treatment of endometriosis.

Expert Opinion: Despite the multitude of agents that have been tested in preclinical trials, only few drugs have passed to the stage of clinical testing and none have been introduced into clinical practice. It is our opinion that the major challenges in the translation from novel agents for endometriosis is due to the use of inadequate rodent models and a lack of standardization in the design and reporting of preclinical endometriosis models.     

New drugs in development for the treatment of endometriosis

Endometriosis is a common and enigmatic disease causing pelvic pain and infertility. Current treatment is mainly based on the use of surgery and ovarian suppressive agents. There is in particular the need for new therapeutic options able to allow a normal menstrual cycle to occur and also consent pregnancy. In the present review, we aimed to give a concise and practical overview in order to allow the clinician to clearly understand the level of development of these drugs. We have presented only treatments supported by in vivo researches with a special attention to studies in humans. Results show appealing new possibilities are emerging from agents counteracting the endometriosis-associated inflammation. Recent data also suggests that there is still the opportunity to refine the use of already available agents.     

盆腔子宫内膜异位症手术辅以药物治疗64例分析

目的探讨盆腔子宫内膜异位症的临床特点以及手术辅以药物治疗疗效。方法选择我院2005年1月~2009年5月收治的64例患者。结合临床症状以及术中探查情况,采取不同手术方式,术后并给予药物治疗,分析治疗效果。结果 1年后的随访发现64例患者中完全缓解率为67.2%,部分缓解率为29.7%,复发率仅为4.7%。结论根据不同临床特点采取相应手术,术后辅以药物治疗是当前治疗盆腔子宫内膜异位症比较合理的方法 。     

子宫内膜异位症合并腺肌病的诊治进展

子宫内膜异位症和子宫腺肌病是一种严重影响患者生活质量的慢性进展性良性疾病,是导致女性盆腔疼痛和生育能力低下的主要原因。随着近年来研究的深入,其发病机制以及诊断治疗有了很大的进展,但仍然存在诸多争议。本文就子宫内膜异位症合并腺肌病的发病机制、临床表现、诊断和治疗等方面进行综述,以供临床参考,但是仍有许多问题尚未明确,相信...     

子宫内膜异位症术后不同激素替代疗法的效果比较

目的探讨手术联合激素替代治疗子宫内膜异位症(endometriosis,EMs)患者的临床价值。方法综合分析2003-01～2009-11笔者所在医院手术联合激素替代治疗87例EMs患者的临床和随访资料,并行统计学分析。结果患者术后分别应用米非司酮、孕三烯酮及醋酸曲普瑞林连续治疗6个月,月经量和痛经症状均得到不同程度缓解,尤其以醋酸曲普瑞林的治疗效果为明显(P<0.05)。结论手术是EMs的主要治疗手段,术后应用米非司酮、孕三烯酮及醋酸曲普瑞林等药物巩固治疗可明显改善症状、降低复发率、提高妊娠率。三种药物中,醋酸曲普瑞林因其疗效肯定,不良反应小,耐受性好的优点,可做巩固治疗,为EMs术后治疗的首选药物。     

Emerging drugs in endometriosis

Endometriosis is a common, estrogen-dependent, gynaecological disease, defined as the presence of endometrial-like tissue outside the uterus. Although several medications are used for treatment of the disease, they are associated with high recurrence rates, considerable side effects and limited duration of application. Due to these limitations and to the impact of endometriosis on the quality of life of affected women, their environment and the society, there is a great need for new drugs able to abolish endometriosis and its symptoms. Studies in recent years investigating the (patho)physiological mechanisms involved in disease aetiology have fostered the development of novel therapeutic concepts for endometriosis, by targeting the hypothalamic–pituitary–gonadal axis, by selective modulation of estrogenic and progestogenic pathways, by inhibiting angiogenesis or by interfering with inflammatory and immunological factors. This article presents a brief summary of the currently available medications and an overview regarding the development of some of the most interesting and/or most promising novel drug candidates for endometriosis.     

子宫内膜异位症临床诊治探讨

目的：对子宫内膜异位症的临床诊治进行探讨。方法：以2009年1～6月来本院进行治疗的46例子宫内膜异位症患者作为分析和研究对象,根据患者所接受药物治疗的不同,将患者分为治疗组和对照组,对照组患者通过服用短效口服避孕药、经脉滴注孕激素、促性腺激素等传统药物治疗方式进行治疗,治疗组患者均通过口服米非司酮片的方法对子宫内膜异位症进行治疗。结果：无论是在治疗的总有效率还是在复发率方面,治疗组患者都要优于对照组患者,且P〈0.05,差异具有统计学意义。结论：米非司酮不仅治疗效果较为明显,并且无不良反应,患者的耐受性和复发率均较为满意,为子宫内膜异位症患者的临床治疗提供了一种新的选择,可以在临床中进行进一步的推广和应用。     

子宫内膜异位症腹腔镜术后应用诺雷得治疗的不良反应与对策

目的总结子宫内膜异位症术后应用诺雷得治疗的不良反应及护理措施。方法观察69例子宫内膜异位症患者腹腔镜术后应用诺雷得治疗的不良反应,并采取相应的治疗及护理措施。结果 53.62%(37/69)的患者出现不良反应,包括出血、皮疹、潮热、关节痛和围绝经期综合征。经综合治疗与护理,所有患者的不良反应均得到缓解。结论子宫内膜异位症术后应用诺雷得治疗的不良反应发生率较高,积极采取适当的措施可以有效缓解不良反应的发生。     

Advances in orally administered pharmacotherapy for the treatment of migraine

Introduction: Migraine is a common and highly disabling neurological disorder whose acute treatment remains problematic and unsatisfactory in a high percentage of cases. Consequently, there remains a need for new symptomatic therapies that can be easily handled by patients (i.e. by oral administration).

Area covered: This review reports on compounds currently under development for the oral treatment of acute migraine attacks, focusing on Calcitonin-Gene-Related-Peptide receptor antagonists, specifically ubrogepant and rimegepant. This article is based on literature obtained from PubMed and publicly available clinical trial data.

Expert opinion: Both reviewed compounds meet the need for rapid and effective pain control, combined with the control of associated bothersome symptoms while also lacking significant adverse events and safety concerns. Though further studies should assess the profile of these compounds comparatively with existing and available treatments (namely triptans), the currently available data points to these new therapies as being very promising new symptomatic oral treatments of migraines.     

New treatment strategies and emerging drugs in endometriosis

Introduction: Endometriosis, histologically defined as the presence of endometrium-like tissue – glands and stroma – that develops outside of the uterine cavity, is still an enigmatic disease responsible for pelvic pain and infertility. The current treatments of endometriosis are surgery and hormonal therapies that act by suppressing ovulation and/or directly on steroid receptors located in endometriotic lesions.

Areas covered: New hormonal and non-hormonal therapies are being developed for the treatment of endometriosis-related pain. The authors review the state of advancement and the results of novel treatments studied in registered trials (www.ClinicalTrials.gov). Cellular signaling pathways activated in endometriotic cells, which constitute potential targets for future treatments, are also described.

Expert opinion: Therapeutic research efforts should focus on identifying and testing substances capable of acting locally on the lesions themselves, without interfering with ovulation, in order to be efficacious on both pain symptoms and infertility.     

安宫黄体酮治疗药物流产后阴道出血32例临床分析

目的：探讨安宫黄体酮治疗药物流产后阴道出血的临床疗效。方法选取我院收治的64例药物流产后阴道出血患者,随机均分为对照组和观察组,对照组患者给予益母草颗粒口服,观察组患者给予安宫黄体酮片口服。比较两组患者的阴道出血持续时间、出血量和治疗总有效率的差异。结果观察组患者阴道出血持续时间和出血量均显著少于对照组（P＜0.05）;观察组治疗总有效率为90.6%,高于对照组的56.3%,两组比较差异有统计学意义（P＜0.05）。结论安宫黄体酮治疗药物流产效果确切,可显著缩短阴道出血持续时间和出血量。     

Therapeutic potential of GnRH antagonists in the treatment of precocious puberty

Pituitary-gonadal axis activation depends upon pulsatile hypothalamic gonadotropin-releasing hormone (GnRH) secretion. This phenomenon has led to clinical use of GnRH agonists in the treatment of central precocious puberty. GnRH analogues contain substitutions of the native decapeptide. Depending upon the substitutions, the analogues have GnRH agonistic or antagonistic properties. The pharmacokinetics of GnRH agonists, the established treatment of precocious puberty, includes an initial ‘flare-up’ of the pituitary-gonadal axis, followed by a reduced luteinising hormone secretion by desensitisation of pituitary GnRH receptors. Antagonistic GnRH analogues act by competitive binding to the pituitary GnRH receptors, thereby preventing the action of endogenous GnRH – theoretically offering a more direct and dose-dependent treatment alternative. The antagonist available today in Germany is a concomitant in assisted reproduction with only 1 – 3 days duration. However, long-acting depot preparations of other GnRH antagonists are in primate-testing phase. Our animal tests indicate strong potential for the development and testing of long-acting depot preparations of GnRH antagonists in treating precocious puberty.     

输尿管子宫内膜异位症5例临床分析

目的 探讨输尿管子宫内膜异位症的诊断与治疗。方法 分析复旦大学附属金山医院近7年确诊的5例输尿管子宫内膜异位症病例。结果 5例患者均进行手术治疗．术后病理证实为子宫内膜异位症，术后1周随访B超肾盂积水均得到有效恢复，输尿管梗阻消失。结论 注意与月经有关的泌尿系统症状并进行B超、静脉肾盂造影等影像学检查，有助于输尿管子宫内膜异位症的诊断。采用手术为主的治疗可以有效缓解输尿管梗阻症状。     

腹腔镜手术联合药物治疗子宫内膜异位症的疗效观察

目的 分析子宫内膜异位症疾病特点,评价腹腔镜手术与药物联合治疗的临床情况.方法 86例子宫内膜异位症患者,采取1︰1比例法分为观察组与对照组,各43例.对照组采取腹腔镜手术治疗,观察组在对照组基础上联合亮丙瑞林药物治疗.比较两组临床疗效、治疗前后相关指标.结果 观察组临床总有效率95.34％高于对照组的79.06％,差...     

腹腔镜手术联合复方醋酸棉酚片治疗中重度子宫内膜异位症的临床疗效观察

目的 观察复方醋酸棉酚片辅助腹腔镜手术治疗子宫内膜异位症的临床疗效.方法 选择经腹腔镜治疗并确诊为子宫内膜异位症的患者93例,按术后用药情况随机分为A、B两组,A组48例患者于术后应用复方醋酸棉酚片6个月,B组45例患者于术后应用达菲林6个月.比较两组的疼痛缓解率、复发率及药物不良反应发生率.结果 A、B两组疼痛缓解率分别为93.75%,95.56%,复发率分别为6.25%,4.44%,不良反应发生率分别为4.17%,13.33%,两组比较差异无统计学意义.结论 复方醋酸棉酚片辅助腹腔镜治疗子宫内膜异位症安全有效,复发率低,不良反应少,且费用低廉,值得在临床推广使用.     

Emerging drugs for endometriosis

Background: Endometriosis is a benign, common gynecological disorder affecting mostly women of reproductive age. It is associated with dysmenorrhea, pelvic pain, and subfertility. The current non-surgical medical treatment is not satisfactory and there is a pressing need for novel therapeutics with better efficacy, tolerability and safety profiles. Objective: To investigate the development of new therapies for endometriosis. Methods: The PubMed database has been extensively searched for all compounds tested preclinically and clinically. Results/conclusion: Besides the three main classes of drugs, i.e., GnRH agonists, progestins, and androgenic agents, there are several classes of compounds that have been tested preclinically and clinically. Surprisingly, a considerable proportion of officially registered Phase II/III clinical trials are listed as completed yet no information on their outcomes is available. Three completed and published Phase II trials found the tested compound disappointing. Another two Phase II clinical trials have been suspended. This apparent gap between the generally promising preclinical findings and the clinical trial outcomes reflects our current woefully inadequate understanding of the mechanisms underlying endometriosis-associated pain and subferitility and recurrence of endometriosis; questions the adequacy and value of animal models of endometriosis that are still in use; highlights the difficulty in developing new therapeutics for endometriosis; and calls for more research in the mechanisms underlying endometriosis-associated pain and subferitility and recurrence of endometriosis.