腹腔镜联合促性腺激素释放激素激动剂治疗中重度子宫内膜异位症的疗效分析

目的观察中重度子宫内膜异位症患者采用腹腔镜联合促性腺激素释放激素激动剂治疗的疗效。方法选取2013年8月~2015年6月我院收治的中重度子宫内膜异位症患者102例,随机将其分成A1组以及A2组,各51例。A1组:选择腹腔镜联合促性腺激素释放激素激动剂进行治疗;A2组:单纯选择腹腔镜手术的方法进行治疗;比较中重度子宫内膜异位症患者在术后复发率以及疼痛缓解率等方面表现出的差异。结果治疗后,A1组在复发率、远期疼痛发生率、盆腔疼痛缓解率以及痛经缓解率等方面,显著优于A2组,差异有统计学意义(P0.05)。结论针对子宫内膜异位症患者,临床选择腹腔镜联合促性腺激素释放激素激动剂进行治疗,可以有效降低术后疾病复发率,提高术后疼痛缓解率,最终显著提高子宫内膜异位症患者的生活质量。     

GnRHR与ER在子宫腺肌病在位及异位内膜的表达及意义

目的探讨促性腺激素释放激素受体（GnRHR）和雌激素受体（ER）在子宫腺肌病在位内膜与异位内膜的表达、相关性及意义。方法收集51例行全子宫切除手术的子宫腺肌病患者，取其在位内膜为研究组A，异位内膜为研究组B，同期30份正常子宫内膜作为对照组。采用免疫组织化学方法测定各组内膜腺细胞中GnRHR与ER的表达，根据阳性率和表达强度进行量化评分（免疫组化评分），并做相关性分析。结果①研究组AGnRHR与ER的表达均显著高于研究组B和对照组，差异有统计学意义（P〈0.05）；②研究组A及正常子宫内膜中，GnRHR表达有周期性，分泌期显著高于增生期，差异有统计学意义（P〈0.01），而在研究组B中增生期与分泌期相比较差异无统计学意义；③GnRHR与ER在各组内膜的表达水平无相关性（P〉0.05）。结论GnRHR在子宫腺肌病在位内膜、异位内膜及正常子宫内膜中均有不同程度的表达；GnRHR在子宫腺肌病在位内膜及正常子宫内膜中分泌期表达显著高于增生期；推测促性腺激素释放激素（GnRH）可能通过其受体介导，对异位内膜细胞的种植和生长直接产生作用，在正常子宫内膜，则可能与受精卵着床及胚胎早期发育有关。     

复发性卵巢子宫内膜异位症的管理

子宫内膜异位症（内异症）是慢性复发性疾病,年复发率约10%。复发性卵巢子宫内膜异位症一般指卵巢子宫内膜异位囊肿复发,是内异症最常见的复发类型,也是导致再次手术的主要原因。治疗原则基本遵循初始治疗,但应个体化。治疗包括药物治疗和手术治疗。常用药物有孕激素类、促性腺激素释放激素激动剂（GnRH-a）、复方口服避孕药物及中医中药等。有些药物比如地诺孕素可以使复发的卵巢子宫内膜异位囊肿明显变小甚至消失,从而免去了患者承受再次手术的风险,近年来广泛推荐使用。再次手术对卵巢储备功能影响更大,术后仍易复发,部分患者也可选择超声引导穿刺治疗。对合并不孕者首先推荐辅助生殖技术。药物维持治疗及长期管理是减少卵巢子宫内膜异位囊肿复发的关键。业已证明,长期使用孕激素类、GnRH-a和复方口服避孕药等均可预防卵巢子宫内膜异位囊肿复发。     

口服避孕药治疗子宫内膜异位症疼痛的研究进展

疼痛是子宫内膜异位症最常见和最重要的临床表现。口服避孕药治疗原发性痛经和子宫内膜异位症疼痛,预防和治疗子宫内膜异位症术后疼痛及病灶复发均有显著疗效,与促性腺激素释放激素激动剂效果相当。口服避孕药的连续用药或长周期用药模式的效果优于短期用药。突破性出血是连续用药最常见的不良反应,严重不良反应罕见。     

腹腔镜手术联合促性腺激素释放激素激动剂治疗子宫内膜异位症的临床效果

目的探讨腹腔镜手术联合促性腺激素释放激素激动剂治疗子宫内膜异位症的临床。方法对108例子宫内膜异位症患者基础资料收集整合并纳入研究对象,参照区组随机设计原则划分本组患者为两组,即参照组54例、研究组54例。前组患者给予腹腔镜手术治疗,后组患者给予腹腔镜手术联合促性腺激素释放激素激动剂进行治疗,统计整合两组与治疗的相关数据指标情况并进行比较。结果研究组经治疗后FSH、LH、E2指标数值明显优于参照组,P<0.05;研究组PRL指标数值与参照组无明显差异,P>0.05;研究组受孕率明显高于参照组,P<0.05;研究组复发率明显低于参照组,P<0.05。结论针对子宫内膜异位症患者采取腹腔镜手术联合促性腺激素释放激素激动剂治疗方法,治疗效果佳,复发率低,患者在治疗后受孕率有所提升,值得推广。     

子宫内膜息肉的药物治疗

子宫内膜息肉是妇科常见疾病，宫腔镜下子宫内膜息肉切除术是首选治疗方法，但药物治疗的重要性也不容忽视。临床常用的药物包括：孕激素、复方口服避孕药、促性腺激素释放激素激动剂、止血药物等。左炔诺孕酮宫内缓释系统在子宫内膜息肉的药物治疗中占据重要地位。文章综述了各药物的临床应用与研究情况。     

宫腹腔镜术后联合GnRH—a治疗轻中度内异症性不孕的疗效分析

目的：探讨宫腹腔镜术后联合不同药物对轻、中度子宫内膜异位症（EMs）性不孕患者妊娠率的影响。方法：回顾分析2008年9月至2011年12月在我院就诊的82例Ⅱ～Ⅲ期EMs性不孕患者的临床资料，患者均行宫腹腔镜联合保留生育功能的手术。按照严格的纳入和剔除标准，筛选出有自然受孕能力的患者，术后按个人意愿用药。按患者术后用药情况分为对照组（18例）、促性腺激素释放激素激动剂组（GnRH．a，博恩诺康）（31例）和口服避孕药组（去氧孕烯炔雌醇片，妈富隆）（33例），比较3组患者在术后不同时期的妊娠率及异位妊娠的发生率。结果：博恩诺康组、妈富隆组和对照组患者术后1年内的妊娠率分别为77．42％（24／31）、51．52％（17／33）和33．33％（6／18），博恩诺康组显著高于对照组及妈富隆组（P〈0．05），而后两组则无显著差异（P〉0．05）。3组患者的异位妊娠率分别为3．23％（1／31）、6．06％（2／33）和5．56％（1／18），均无显著差异（P均〉0．05）。术后1年内，Ⅱ期EMs患者中，3组妊娠率差异显著（P=0．020）；Ⅲ期EMs患者中，3组妊娠率无显著差异（P=0．297）。II、HI期患者中，3组的异位妊娠率均无显著差异（P〉0．05）。结论：宫腹腔镜术后联合博恩诺康有利于改善轻、中度EMs性不孕患者的生育能力。     

促性腺激素释放激素激动剂治疗与骨量丢失

促性腺激素释放激素激动剂（GnRH-a）已广泛应用于妇科子宫内膜异位症、子宫肌瘤、性早熟等雌激素依赖性疾病的治疗。但其导致的低雌激素血症与骨丢失也愈来愈引起人们的认识和重视。GnRH-a与HRT反向添加疗法可以降低骨丢失、改善生活质量，从而延长GnRH-a治疗时间。     

促性腺激素释放激素激动剂对子宫内膜癌neu基因蛋白表达的调控

促性腺激素释放激素激动剂对子宫内膜癌ｎｅｕ基因蛋白表达的调控张玉泉曹斌融郑颂国张惜阴张泰明冯炜炜据文献报道，促性腺激素释放激素激动剂（ＧｎＲＨ－ａ）对激素依赖性肿瘤，如乳腺癌、卵巢癌及前列腺癌有一定疗效［１～３］，对子宫内膜癌也有治疗作用［４，５］。...     

不同方案超排卵对金黄地鼠子宫内膜组织学和超微结？…

目的 比较促性腺激素释放激素激动剂辅助超排卵和单纯促性腺激素（ＰＭＳＧ）超排对金黄地鼠子宫内膜的影响。方法 模仿人类长周期,对金黄地鼠进行ＧｎＲＨ－ａ预处理后,用ＰＭＳＧ超排卵（１０只,ＬＡ＋ＰＭＳＧ组）,并以１０只单用ＰＭＳＧ超排卵（ＰＭＳＧ组）和１０只自然周期金黄地鼠（对照组）为对照,对子宫内膜进行组织学和超微结构分析。结果 组织学检查显示：ＬＡ＋ＰＭＳＧ组子宫内膜成熟度与对照组相比,差异无显     

黑升麻在中重度子宫内膜异位症GnRH-a反加治疗中的疗效评估

目的:比较黑升麻和替勃龙在中重度子宫内膜异位症腹腔镜术后GnRH-a反加治疗中的疗效。方法:前瞻性随机对照比较中重度子宫内膜异位症腹腔镜术后患者90例,分为戈舍瑞林+黑升麻组、戈舍瑞林+替勃龙组、戈舍瑞林组,各30例,分析各组用药3个月后血清雌二醇(E2)、促卵泡激素(FSH)水平;子宫内膜厚度;Kupperman(KMI)评分;视觉疼痛症状评分法(VAS)评分;血清骨钙素(BGP);CA125、肝肾功能、血脂等变化。结果:戈舍瑞林+替勃龙组血清E2水平显著高于戈舍瑞林+黑升麻组及戈舍瑞林组(P均<0.05),FSH显著低于戈舍瑞林+黑升麻组及戈舍瑞林组(P均<0.05),戈舍瑞林+黑升麻组和戈舍瑞林组间无差异(P>0.05);戈舍瑞林组KMI评分明显高于戈舍瑞林+替勃龙组和戈舍瑞林+黑升麻组(P<0.05),而戈舍瑞林+替勃龙组和戈舍瑞林+黑升麻组间无差异(P>0.05);戈舍瑞林+替勃龙组血清BGP浓度显著低于戈舍瑞林组和戈舍瑞林+黑升麻组(P均<0.05),而戈舍瑞林组和戈舍瑞林+黑升麻组间无差异(P>0.05)。各组间EM、VAS评分、CA125、肝肾功能及血脂等均无明显差异(P>0.05)。结论:黑升麻是中重度子宫内膜异位症腹腔镜术后GnRH-a反加治疗安全有效的选择之一。     

促性腺激素释放激素激动剂联合戊酸雌二醇及地屈孕酮治疗子宫内膜异位症的临床疗效与安全性

目的 比较促性腺激素释放激素激动剂(GnRH-a)联合地屈孕酮和戊酸雌二醇(反向添加疗法)及单用GnRH-a对子宫内膜异位症(内异症)患者生殖激素水平、低雌激素症状、生活质量及骨密度等的影响.方法 选择经腹腔镜或开腹手术确诊并治疗两个月内的Ⅲ～Ⅳ期内异症患者70例,随机分为GnRH-a组和反加组各35例,GnRH-a组单用戈舍瑞林3.6 mg皮下注射,每28天注射1次,共3次,反加组在应用戈舍瑞林的同时,每天口服戊酸雌二醇0.5 mg及地屈孕酮5 mg.于治疗前后测定两组患者的疼痛症状视觉模拟评分(VAS)、简明健康量表(SF-36)得分、改良Kupperman评分、骨密度、外固血卵泡刺激素(FSH)、雌二醇及血清骨钙素(BGP)水平,并随访治疗结束后第1次月经复潮情况及VAS评分.结果 两组各有3例患者未完成随访.(1)生殖激素水平:治疗末反加组雌二醇水平为(94±71)pmol/L,明显高于GnRH-a组的(54±52)pmol/L,两组比较,差异有统计学意义(P<0.01);反加组FSH水平为(3.0±1.9)U/L,低于GnRH-a组的(5.7±2.9)U/L,两组比较,差异也有统计学意义(P<0.05);(2)VAS评分:两组治疗末VAS评分均较治疗前显著下降(P<0.05),并保持至治疗后第1次月经来潮;(3)Kupperman评分:治疗未反加组Kupperman评分为(10±8)分,明显低于GnRH-a组的(14±6)分,差异有统计学意义(P<0.05);(4)骨密度:GnRH-a组治疗末较治疗前骨密度显著下降,差异有统计学意义(P<0.05),反加组治疗前后骨密度比较,差异无统计学意义(P>0.05);治疗前两组外周血BGP水平比较,差异无统计学意义(P>0.05),治疗末GnRH-a组外周血BGP水平为(7932±5206)ng/L显著高于反加组的(5419±2917)ng/L,差异有统计学意义(P<0.05).结论 GnRH-a联合地屈孕酮及戊酸雌二醇能有效缓解内异症患者的疼痛症状,并可减轻GnRH-a引起的低雌激素症状,减少骨质丢失,是一种有效、安全的治疗方法.     

Update on the medical treatment of endometriosis

The treatment of women with endometriosis can be a challenge. Therapeutic strategies must be tailored to the individual symptoms, age, and desire for fertility. Medical therapy continues to be based on endocrine treatment, such as oral contraceptives, progestins, danazol, and GnRH agonists. Unfortunately, recurrence rates are high after discontinuation of therapy. Recent clinical research on GnRH analogues plus add-back therapy has produced favorable results. Long-term treatment of patients using this approach has successfully reduced pain while minimizing symptoms of hypoestrogenism and adverse metabolic effects, such as loss of bone mineral density. Currently, GnRH analogues given with add-back therapy seems to be the most effective long-term approach to the treatment of symptomatic endometriosis. In the future, other modalities, such as medicated vaginal rings, inhibitors of steroidogenic enzymes, and GnRH antagonists, will most likely be options.     

Add-back therapy and gonadotropin-releasing hormone agonists in the treatment of patients with endometriosis: can a consensus be reached? Add-Back Consensus Working Group

OBJECTIVE: To reach a consensus on the role of add-back therapy for patients with endometriosis administered GnRH agonists (GnRH-a). DESIGN: Results of consensus conference reviewing MEDLINE search of English language abstracts of both prospective and retrospective series. SETTING: Consensus conference of 31 specialists in gynecologic surgery and reproductive endocrinology. PATIENT(S): Patients with symptomatic endometriosis who were candidates for GnRH-a therapy in treatment courses ranging in duration from 6 to 12 months. INTERVENTION(S): Oral steroidal and nonsteroidal add-back regimens. MAIN OUTCOME MEASURE(S): Alteration in painful symptoms, extent of disease, vasomotor symptoms, bone mineral density, and serum lipid profile. RESULT(S): When added to GnRH-a for 6 months, both 2.5 mg of norethindrone and 0.625 mg of conjugated equine estrogens with 5 mg/d of medroxyprogesterone acetate provide effective relief of vasomotor symptoms and decrease but do not eliminate bone mineral density loss. During 12 months of GnRH-a therapy, bone mineral density loss is eliminated effectively with an add-back of 5 mg of norethindrone acetate alone or in conjunction with low-dose conjugated equine estrogens. Organic bisphosphonates also may play a role. CONCLUSION(S): In patients with symptomatic endometriosis, the efficacy of GnRH agonists may be preserved and therapy prolonged while overcoming hypoestrogenic side effects with the use of appropriate add-back regimens.     

Use of a progestogen only preparation containing desogestrel in the treatment of recurrent pelvic pain after conservative surgery for endometriosis

OBJECTIVE: To assess the effect of a new progestin progestogen only pill (desogestrel) versus an oral contraceptive in the treatment of recurrent endometriosis. STUDY DESIGN: A randomized prospective clinical study. A group of women with endometriosis (n=40) who showed recurrent dysmenorrhea and/or pelvic pain after conservative surgery, and did not desire a pregnancy. Continuous treatment for 6 months with desogestrel (75 microg/d) (n=20) versus a combined oral contraceptive (ethinyl estradiol 20 microg plus desogestrel 150 microg) (n=20) was performed. RESULTS: A significant improvement of both pelvic pain and dysmenorrhea was observed following each type of treatment (P<0.001). The use of desogestrel progestogen only pill was associated with a breakthrough bleeding in 20% patients, while a significant body weight increase was observed in 15% after oral contraceptive. CONCLUSIONS: Both desogestrel and an oral estro-progestinic were effective, safe and low cost therapy of pain symptoms after endoscopic surgery for endometriosis, the former showing an impact on breakthrough bleeding, the later an incidence on body weight increase.     

Add-back therapy in the treatment of endometriosis-associated pain

OBJECTIVE: To determine the efficacy of GnRH analogue plus add-back therapy compared with GnRH analogue alone and estroprogestin in patients with relapse of endometriosis-associated pain. DESIGN: Randomized, controlled study. SETTING: University hospital. PATIENT(S): One hundred thirty-three women with relapse of endometriosis-related pain after previous endometriosis surgery. INTERVENTION(S): Forty-six women were treated with GnRH analogue plus add-back therapy, 44 women were given GnRH analogue alone, and 43 women received estroprogestin, for 12 months. MAIN OUTCOME MEASURE(S): Pain evaluation by a visual analogue scale, quality of life in treated patients according to the SF-36 questionnaire, and occurrence of adverse effects, including bone mass density loss, at pretreatment, after 6 months of treatment, at the end of treatment (12 months), and 6 months after discontinuation of treatment. RESULT(S): Patients treated either with GnRH analogue alone or GnRH analogue plus add-back therapy showed a higher reduction of pelvic pain, dysmenorrhea, and dyspareunia than patients treated with oral contraceptive, whereas patients treated with add-back therapy showed a better quality of life, as assessed with the SF-36 questionnaire, and adverse effects rate than the other two groups. CONCLUSION(S): Add-back therapy allows the treatment of women with relapse of endometriosis-associated pain for a longer period, with reduced bone mineral density loss, good control of pain symptoms, and better patient quality of life compared with GnRH analogue alone or oral contraceptive.     

Efficacy of every-other-day administration of conjugated equine estrogen and medroxyprogesterone acetate on gonadotropin-releasing hormone agonists treatment in women with endometriosis.

We performed a randomized controlled study to determine the efficacy of add-backed therapy by every-other-day administration of 0.625 mg conjugated equine estrogen (CEE) and 2.5 mg medroxyprogesterone acetate (MPA) on GnRH agonists (GnRH-a) treatment in Japanese women with symptomatic endometriosis. At the end of treatment, serum estrone and estradiol levels in the add-back group (n = 11) were significantly higher than those in the control group (n = 10). The assessment of Beecham classification by bimanual examination, serum CA-125 levels, and the frequency of genital bleeding revealed no significant differences between the two groups. The add-back group showed reduced Kupperman indices relative to those of the control group, and could prevent the loss of bone density. These findings led to a conclusion that GnRH-a therapy added back by every-other-day administration of 0.625 mg CEE and 2.5 mg MPA was a safe and effective treatment for Japanese women with endometriosis.     

来曲唑对子宫内膜异位症大鼠TNF-α、IL-6、NF-κB表达的影响

目的:研究不同剂量来曲唑对大鼠子宫内膜异位症(EMs)模型的治疗作用及其对异位病灶中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、核转录因子-κB(NF-κB)表达的影响。方法:将建模成功的大鼠随机分为来曲唑组(低、中、高剂量组)、米非司酮组及生理盐水空白对照组。灌胃4周后采用自定义疼痛评分及阴道痛觉过敏实验评价大鼠疼痛情况;观察异位内膜生长情况;放射免疫法测定血清E2、P、T水平;应用免疫组化法检测TNF-α、IL-6、NF-κB蛋白表达;用逆转录聚合酶链反应(RT-PCR)技术检测TNF-α mRNA、IL-6 mRNA、NF-κB mRNA的含量。结果:来曲唑各组异位病灶体积明显缩小或萎缩,与空白对照组比较差异均有统计学意义(P<0.05);来曲唑中、高剂量组与低剂量组、米非司酮组相比较,异位病灶体积缩小更明显(P<0.05)。治疗后各组大鼠血清E2、P水平均无显著差异(P>0.05),但来曲唑组大鼠血清T水平升高,且呈剂量依赖性(P<0.05)。来曲唑治疗后模型鼠疼痛评分降低,与对照组比较差异有统计学意义(P<0.05),且高剂量来曲唑组较米非司酮组疼痛减轻更明显(P<0.05)。在20、30、40mmHg阴道压力的刺激下,米非司酮组和来曲唑组大鼠的逃避率较空白组显著降低(P<0.05),较少发生痛觉过敏,而在压力为5、10mmHg时,各组间逃避率的差异无统计学意义(P>0.05)。各治疗组异位内膜中TNF-α、IL-6、NF-κB蛋白和mRNA的表达,均较空白组显著降低(P<0.05),尤以高剂量来曲唑组蛋白表达最低。NF-κB与TNF-α、IL-6的表达均呈正相关(P<0.05)。结论:来曲唑对大鼠异位病灶体积影响明显,可缓解EMs引起的疼痛。这可能是通过降低异位病灶局部雌激素水平,降调TNF-α、IL-6、NF-κB在异位内膜组织中的表达而发挥治疗作用的。     

保守性手术联合长效醋酸甲羟孕酮治疗中重度子宫内膜异位症的临床观察

目的　探讨长效醋酸甲羟孕酮 (DMPA)用于中重度子宫内膜异位症患者保守性手术后巩固治疗的临床效果及副反应。方法　将资料完整的中重度子宫内膜异位症行保守性手术治疗的患者 94例 ,分为DMPA组、促性腺激素释放激素激动剂 (GnRH a)组及对照组。DMPA组 34例 ,术后月经来潮 5d内 ,深部肌内注射DMPA 15 0mg ,2 8～ 30d注射 1次 ,共 6次 ;GnRH a组 30例 ,术后月经来潮 5d内 ,皮下注射亮丙瑞林 3 75mg ,2 8～ 30d注射 1次 ,共 6次 ;对照组 30例 ,术后未用药物治疗。观察治疗前后患者疼痛症状和体征的临床缓解情况、月经变化、体重改变、肝肾功能及性激素水平变化。结果　DMPA组及GnRH a组患者疼痛症状和体征完全缓解率分别为 88%及 93% ,显著高于对照组的 5 3% ,差异有统计学意义 (χ2 =12 2 73,P <0 0 1;χ2 =9 6 0 4 ,P <0 0 1) ,DMPA组及GnRH a组患者累积复发率分别为 6 %及 7% ,显著低于对照组的 2 7% (χ2 =5 2 2 2 ,P <0 0 5 ;χ2 =4 32 0 ,P <0 0 5 ) ,而DMPA组与GnRH a组比较 ,差异无统计学意义 (χ2 =0 4 88,P >0 0 5 ;χ2 =0 0 17,P >0 0 5 )。DMPA组用药前雌二醇水平为 (2 0 0± 15 ) pmol/L ,用药后雌二醇水平显著下降至(12 0± 9) pmol/L ,但仍维持在卵泡早期水平。GnRH a组用药前     

The efficacy and tolerability of short-term low-dose estrogen-only add-back therapy during post-operative GnRH agonist treatment for endometriosis

Objective

To evaluate the efficacy and tolerability of a low-dose estrogen-only regimen as a short-term add-back therapy during post-operative GnRH agonist (GnRHa) treatment of patients with endometriosis.

Study design

Retrospective cohort study. One hundred seventeen women of reproductive age who were treated with post-operative GnRHa after conservative laparoscopic surgery for endometrioma were eligible for this study. The patients were divided into two groups: group A (n = 56) received tibolone (2.5 mg) between 2002 and 2004 and group B (n = 61) received estradiol valerate (1 mg) between 2005 and 2007 as an add-back therapy for five months, beginning at the time of the second injection of a GnRHa. The incidence of hypoestrogenic symptoms and the degree of pelvic pain according to a verbal rating scale (VRS) scoring system, the incidence and patterns of uterine bleeding during add-back therapy, the endometrial thickness by ultrasonography two months after the last GnRHa treatment, and the serum CA-125 level were evaluated.

Results

The incidence of uterine bleeding, hypoestrogenic symptoms such as hot flashes and sweating, and pelvic pain did not differ significantly between the two treatment groups. However, the endometrium was thicker in group A than group B (p = 0.022). In group B, the frequency of uterine bleeding was lower from the second month after starting add-back therapy than in group A, but without statistical significance (at the sixth month, p = 0.086).

Conclusion

The low-dose estrogen-only regimen was efficacious and tolerable as a short-term add-back therapy during post-operative GnRHa treatment after surgery for endometriosis.