黑升麻异丙醇提取物防治GnRHa疗程中低雌激素症状疗效分析

目的研究黑升麻异丙醇提取物改善GnRHa治疗子宫内膜异位症疗程中低雌激素症状的疗效。方法选择2009年3月至2011年8月于中山大学孙逸仙纪念医院手术后应用GnRHa治疗的子宫内膜异位症患者125例,分入4组:研究组口服黑升麻异丙醇提取物,研究1组49例,从注射GnRHa第一针起开始服用,20mg/次,2次/d;研究2组45例,从注射GnRHa第二针开始口服,20mg/次,2次/d;反加疗法组21例,从使用GnRHa第二针开始口服利维爱,2.5mg/d;对照组10例,不使用研究药物或反加治疗药物。比较各组间及组内从使用GnRHa第一针起每4周Kupperman评分及各单项评分之间的差异及各组间用药前后FSH,LH,E2之间的差异。结果注射GnRHa第一针时,各组Kupperman评分差异无统计学意义(P>0.05),注射GnRHa第一针后4周,研究1组Kupperman评分,潮热出汗评分显著低于其他各组同期评分,差异有统计学意义(P<0.05)。注射GnRHa第一针后8周和12周,研究1和2组,反加疗法组Kupperman评分,潮热出汗评分均低于同期对照组,差异有统计学意义(P<0.05)。和反加疗法组比较,研究1和研究2组潮热出汗评分差异无统计学意义(P>0.05)。治疗后研究1和研究2组FSH、LH、E2与对照组相比差异无统计学意义(P>0.05)。结论 GnRHa治疗子宫内膜异位症疗程中,黑升麻异丙醇提取物从注射第一支GnRHa就开始使用,可以预防出现明显的潮热出汗症状。     

用减量的GnRHa(nafarelin)治疗子宫内膜异位症:用低剂量显效剂治疗(反减治疗)的一项试验性研究

为评价用低剂量GnRHa(显效剂)治疗子宫内膜异位症(内异症)的效果和副反应,选择有症状而经腹腔镜检查和开腹术证实为内异症,月经规则(25～28天),肝肾功能正常,无慢性病,最近未进行药物治疗和未用过已知影响骨代谢的药物者的内异症患者15例为研究对象,接受6个月GnRHa治疗。7例接受全量nafarelin200μg2次/d鼻内治疗共24周为     

GnRHa联合反加疗法用于腹腔镜术后子宫内膜异位症的临床观察

目的:探讨促性腺激素释放激素激动剂(GnRHa)联合结合型雌激素(CEE)及醋酸甲羟孕酮(MPA)用于子宫内膜异位症手术后巩固治疗的临床效果及安全性。方法:将96例腹腔镜术后子宫内膜异位症患者随机分成3组:单药组(33例):于术后皮下注射曲普瑞林3.75 mg,每28 d 1次,连用6个周期;反加组(32例)于术后皮下注射曲普瑞林3.75 mg,每28 d 1次,连用6个周期,自用药第4个周期起开始反加疗法,即加用结合型雌激素0.625 mg/d,醋酸甲羟孕酮5 mg/d,连用3个周期;对照组(31例):术后拒用药物治疗(因价格昂贵)。结果:单药组、反加组临床症状完全缓解率分别为90.9%和93.8%,均高于对照组(48.4%,P<0.01);单药组、反加组累计复发率分别为3.0%和6.2%,均低于对照组的(33.3%,P<0.01);治疗后单药组与反加组患者的血清雌二醇(E2)、卵泡刺激素(FSH)、黄体生成激素(LH)均低于对照组,差异有统计学意义(P<0.05),治疗后单药组患者的E2水平明显低于反加组(P<0.05),差异有统计学意义。结论:GnRHa联合结合型雌激素及醋酸甲羟孕酮反加疗法对控制低雌激素症状安全有效。反加疗法能减少GnRHa的不良反应且不影响其疗效。     

促性腺激素释放激素激动剂联合反加疗法治疗子宫内膜异位症的临床观察

近年来研究表明 ,应用促性腺激素释放激素激动剂(ＧｎＲＨ ａ)可有效地治疗子宫内膜异位症 (内异症 ) ,但其低雌激素状态引起潮热、阴道干燥及骨密度下降等限制了其长期使用。本研究观察应用ＧｎＲＨ ａ联合结合雌激素、安宫黄体酮反加疗法治疗内异症的疗效及对骨密度的影响。一、资料和方法1.一般资料 :1997年 4月至 2 0 0 0年 10月在我院就诊的内异症患者 3 0例 ,年龄 2 9～ 41岁 ,平均 (3 6± 4)岁 ,随机分成Ａ、Ｂ两组 (各 15例 )。内异症术后复发者 ,Ａ组 4例、Ｂ组 6例 ;内异症术后仍有残留病灶于术后继续药物治疗者 ,Ａ组11例、Ｂ组 …     

重度子宫内膜异位症腹腔镜术后联合GnRHa治疗效果及反加疗法的影响

目的:分析重度子宫内膜异位症患者腹腔镜术后联合GnRHa治疗中,应用反加疗法与否对临床疗效及副反应的影响,探讨短期应用GnRHa联合反加治疗的必要性和时机。方法:回顾分析2003年3月至2006年6月行保守性腹腔镜手术且手术证实为盆腔子宫内膜异位症,部分合并子宫腺肌症、术后应用GnRHa治疗3个月87例患者的临床资料,包括患者疼痛症状、不孕情况、体征、血清CA125、临床病理类型、手术过程、术后用药及随诊情况,根据是否应用反加疗法分成两组。统计分析用药疗效、月经恢复状态、副反应及复发情况。停药后定期随诊,随诊时间为12～28个月,平均18.25个月。结果:34例患者出现明显低雌症状,予以反加治疗(倍美力0.3mg+安宫黄体酮2mg)/d。两组治疗后疼痛VAS评分、体征改善、血清CA125均较治疗前有统计学差异(P<0.05);治疗后两组疗效及月经恢复间隔无统计学差异(P>0.05)。49例不孕患者手术用药后自然妊娠12例,辅助生殖妊娠6例,妊娠率36.74%;自然妊娠时间为停药后2～22个月,平均9.5±5.5个月,自然妊娠率为24.48%。复发平均时间为末次GnRHa用药后12.81±5.5个月;复发23例,1年内复发13例(14.94%),2年累计复发率26.43%。疼痛复发率8/87(9.2%),体征复发率20/87(22.99%)。两组复发率,复发类型及复发间隔无统计学差异(13.8%vs12.6%,P=0.133;12.13±6.15个月vs12.75±5.60个月,P=0.881)。结论:腹腔镜术后辅以GnRHa治疗重度子宫内膜异位症提高了手术成功率,有效抑制了疼痛复发。适时反向添加治疗可缓解用药副反应,不影响疗效及复发。     

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。     

GnRHa治疗子宫内膜异位症的研究进展

促性腺激素释放激素类似物(GnRHa)是子宫内膜异位症(EMs)药物治疗的一个重要方面,随着对EMs本身及GnRHa治疗EMs认识的加深,许多学者对GnRHa发挥作用的机制从蛋白、RNA水平以及腹膜腔免疫微环境等方面进行了研究,对传统治疗方法进行改进,特别在防止副作用方面提出反加疗法和反减疗法等.就GnRHa在治疗EMs中的机制和临床应用的新进展进行.     

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.     

腹腔镜手术联合促性腺激素释放激素激动剂治疗内异症的临床研究

目的 探讨腹腔镜手术联合促性腺激素释放激素激动剂(GnRH-a)治疗内异症的临床疗效和安全性.方法 选取北京安贞医院2010年1-12月收治的198例内异症患者,分成3组,腹腔镜组52例,单纯行腹腔镜手术治疗；亮丙瑞林组76例,腹腔镜手术后加用国产醋酸亮丙瑞林(其他名称:贝依)3.75 mg/28 d × 3；戈舍瑞林组70例,腹腔镜手术后加用进口醋酸戈舍瑞林(其他名称:诺雷德)3.6 mg/28 d×3.比较3组的临床疗效、妊娠率及药物不良反应.结果 198例患者中13例失访,其中腹腔镜组3例,亮丙瑞林组6例,戈舍瑞林组4例.(1)有效率:临床有效率腹腔镜组为47％(23/49)、亮丙瑞林组为77％ (54/70)、戈舍瑞林组为74％ (49/66),亮丙瑞林组和戈舍瑞林组临床有效率均明显高于腹腔镜组,差异有统计学意义(P＜0.05)；亮丙瑞林组和戈舍瑞林组间临床有效率比较,差异无统计学意义(P＞0.05).(2)复发率:复发率腹腔镜组33％ (16/49)、亮丙瑞林组为13％(9/70)、戈舍瑞林组为12％ (8/66),亮丙瑞林组和戈舍瑞林组复发率均明显低于腹腔镜组,差异有统计学意义(P＜0.05)；亮丙瑞林组和戈舍瑞林组间复发率比较,差异无统计学意义(P＞0.05).(3)妊娠率:腹腔镜组、亮丙瑞林组、戈舍瑞林组中有生育要求者分别为28例、39例和35例.术后随访2年,亮丙瑞林组、戈舍瑞林组的总妊娠率高于腹腔镜组[分别为62％(24/39)、60％ (21/35)、39％(11/28)],但3组间比较,差异无统计学意义(P＞0.05).(4)药物不良反应:药物不良反应主要为低雌激素症状及初始效应(阴道不规则出血),发生率亮丙瑞林组为21％ (15/70)、戈舍瑞林组为20％(13/66),两组比较,差异无统计学意义(P＞0.05).结论 与单纯腹腔镜手术相比,腹腔镜手术联合GnRH-a治疗内异症能提高总的临床有效率和妊娠率,降低复发率；药物不良反应发生率低；国产醋酸亮丙瑞林治疗内异症安全、有效,与进口制剂相比疗效无明显差异.     

阴道子宫内膜异位症18例临床分析

目的:探讨阴道子宫内膜异位症(内异症)的临床特点和治疗效果。方法:回顾性分析我院2003年1月至2005年10月收治的18例经病理证实为阴道内异症患者的临床资料。结果:阴道内异症独立存在者13例(72.2%),合并盆腔内异症者5例(27.8%)。前组性交痛及合并妇科良、恶性肿瘤的比例高于后组,而合并不孕的比例较后组低。所有患者中8例行保守性手术治疗,其中4例术后加用GnRHa治疗3个月;其余10例均行根治性手术治疗。平均随访18.6月,共有2例复发(11.1%),均见于肿块直径≥3 cm、行阴道局部切除未用药物治疗者。总共半年累积复发率13.3%(2/15),保守性手术复发为25%(2/8),其半年累积复发率40.0%(2/5);保守性手术术后加用药物治疗者及行根治性手术者无复发。各种术式之间比较,无明显统计学差异(P>0.05)。结论:阴道子宫内膜异位症与常见的盆腔内异症相比较,有其特殊之处。其发生机制可能与盆腔内异症不同,尚有待进一步研究。     

Estriol add-back therapy in the long-acting gonadotropin-releasing hormone agonist treatment of uterine leiomyomata.

The hypoestrogenic state induced by gonadotropin-releasing hormone agonists (GnRHa) has been shown to be effective in the treatment of uterine leiomyomas but to induce bone loss. Estriol has been described to be a weak and short-acting estrogen without an increased risk of endometrial proliferation and hyperplasia. The purpose of this study was to evaluate whether treatment of uterine leiomyomata with GnRHa plus oral estriol add-back therapy could prevent bone loss, without deteriorating the therapeutic effect of GnRHa. Twelve premenopausal women with symptomatic uterine leiomyomas were randomized to receive either leuprolide acetate depot alone at a dose of 3.75 mg s.c. every month for 6 months (non add-back group; n = 6), or GnRHa for 6 months plus oral estriol 4 mg/day for 4 months commencing with the third GnRHa injection (add-back group; n = 6). In the add-back group, leiomyoma volume, as measured by transvaginal ultrasound, decreased to 59.1% of baseline at 2 months of GnRHa therapy with no significant change in size during the remaining treatment period. In contrast, it decreased to 31.3% of pretreatment size at the end of treatment in the non add-back group. The levels of bone metabolic markers such as CrossLaps, deoxypyridinoline, osteocalcin and bone-specific alkaline phosphatase, increased significantly throughout the treatment in the non add-back group, whereas they were suppressed by the add-back therapy. The bone mineral density of lumbar spine (L2-L4) as measured by dual-energy X-ray absorptiometry decreased significantly by 7.5% at the end of treatment in the non add-back group, but did not change significantly in the add-back group. In conclusion, GnRHa plus estriol add-back therapy might be considered for long-term treatment of uterine leiomyomata.     

Estriol add-back therapy in the long-acting gonadotropin-releasing hormone agonist treatment of uterine leiomyomata

The hypoestrogenic state induced by gonadotropin-releasing hormone agonists (GnRHa) has been shown to be effective in the treatment of uterine leiomyomas but to induce bone loss. Estriol has been described to be a weak and short-acting estrogen without an increased risk of endometrial proliferation and hyperplasia. The purpose of this study was to evaluate whether treatment of uterine leiomyomata with GnRHa plus oral estriol add-back therapy could prevent bone loss, without deteriorating the therapeutic effect of GnRHa.

Twelve premenopausal women with symptomatic uterine leiomyomas were randomized to receive either leuprolide acetate depot alone at a dose of 3.75 mg sc every month for 6 months (non add-back group; n = 6), or GnRHa for 6 months plus oral estriol 4 mg/day for 4 months commencing with the third GnRHa injection (add-back group; n = 6). In the add-back group, leiomyoma volume, as measured by transvaginal ultrasound, decreased to 59.1% of baseline at 2 months of GnRHa therapy with no significant change in size during the remaining treatment period. In contrast, it decreased to 31.3% of pretreatment size at the end of treatment in the non add-back group. The levels of bone metabolic markers such as CrossLaps, deoxypyridinoline, osteocalcin and bone-specific alkaline phosphatase, increased significantly throughout the treatment in the non add-back group, whereas they were suppressed by the add-back therapy. The bone mineral density of lumbar spine (L2-L4) as measured by dual-energy X-ray absorptiometry decreased significantly by 7.5% at the end of treatment in the non add-back group, but did not change significantly in the add-back group.

In conclusion, GnRHa plus estriol add-back therapy might be considered for long-term treatment of uterine leiomyomata.     

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.     

Dose effects of progesterone in add-back therapy during GnRHa treatment

OBJECTIVE: To compare 1 mg norethisterone acetate with 5 mg norethindrone when used in conjunction with 2 mg estradiol given as add-back therapy during treatment with a gonadotropin-releasing hormone agonist (GnRHa). STUDY DESIGN: A prospective, double-blind, randomized study was conducted in a university-based teaching hospital. Forty-seven patients with pelvic endometriosis were recruited. Subcutaneous GnRHa was administered at 6-week intervals, and add-back therapy was commenced with the second dose of GnRHa. Group A patients received 2 mg estradiol and 1 mg norethisterone acetate, while group B patients received 2 mg estradiol and 5 mg norethindrone daily. Changes in bone mineral density, menopausal symptoms, lipid profile and occurrence of breakthrough bleeding were assessed before and after treatment. RESULTS: Patients in group A had no significant bone loss and satisfactory control of menopausal symptoms. The additional dose of progestogen in group B had a deleterious effect on the lipid profile and increased the frequency of breakthrough bleeding. CONCLUSION: In this study, the benefits of add-back therapy during GnRHa treatment were not enhanced, and a deleterious effect upon the lipid profile was seen when using a constant dosage of 2 mg estradiol and 5 mg norethindrone as compared to 1 mg norethisterone acetate.     

The incidence and characteristics of uterine bleeding during postoperative GnRH agonist treatment combined with tibolone add-back therapy in endometriosis patients of reproductive age

OBJECTIVES: This study was undertaken to evaluate the incidence and the factors associated with uterine bleeding while taking GnRH agonist treatment combined with tibolone add-back therapy in endometriosis patients of reproductive age. STUDY DESIGN: The medical records of 188 endometriosis (stages III-IV) patients of reproductive age receiving postoperative GnRH agonist treatment combined with tibolone add-back therapy for 6 months were reviewed. Clinical features were analyzed and compared between the two groups: Group A, patients without an episode of uterine bleeding (n=137) and Group B, patients that had experienced uterine bleeding (n=51). RESULTS: Demographic profiles were not different in the two groups. The incidence of uterine bleeding was 27.1% and irregular spotting was the most frequent bleeding pattern. The proportion of patients who received ovarian surgery during pelviscopy was higher in Group B (p<0.05), but other clinical characteristics were not different between two groups. CONCLUSIONS: The incidence of uterine bleeding was 27.1%. And, the proportion of patients who received ovarian surgery was higher in patients with uterine bleeding.     

The hormonal profile of norethindrone acetate: rationale for add-back therapy with gonadotropin-releasing hormone agonists in women with endometriosis

Gonadotropin-releasing hormone agonists (GnRHa) are an effective treatment of endometriosis-associated pelvic pain. The use of hormonal add-back therapy can alleviate the hypoestrogenic symptoms associated with GnRHa therapy, while preserving therapeutic efficacy. Norethindrone acetate (NETA) is a unique progestin that has both estrogenic and androgenic properties and is effective as an add-back regimen without estrogen supplementation. Through its estrogenic activity, NETA exerts beneficial effects on bone mineral density and vasomotor symptoms in women treated with GnRHa. In addition, NETA exhibits strong endometrial antiproliferative effects, which may result in further benefits for the endometriosis patient population. However, NETA add-back may be associated with progestogenic side effects and may lower high-density lipoprotein due to androgenic activity. These effects must be balanced with the overall benefits of NETA add-back therapy.     

GnRH agonist and add back therapy--indications, results and problems in the treatment of genital endometriosis

It was the aim of this paper to assess whether GnRH agonist and add-back therapy is an important post operative and long-term therapeutical supplement in the treatment of genital endometriosis, especially in cases of chronic pain. Although its effectiveness with regard to the relief of pain is not better than other therapeutical options, the spectrum of side effects is acceptable. Un-desired side effects of GnRH agonists are reversible and can be minimised under the synchronised application of an add-back therapy. In patients with symptomatic endometriosis the effectiveness of GnRH agonist therapy can remain and simultaneously the hypoestrogenic side-effects can be covered by the appropriate add-back therapy. In our investigations a useful combination treatment of leuprolide acetate depot (3.75 mg per month) and tibolone (2.5 mg per day) over a period of 3-6 months was found.The analyses of Hornstein et al. 1998 and Surrey et al. 2002 clearly demonstrate that a significant reduction in pain with few side effects results when from the first day of treatment with leuprolide acetate depot an add-back scheme of 5 mg norethindrone acetate per day is applied.     

An evidence-based approach to hormonal therapies for premenopausal women with fibroids

Ovarian steroids, particularly oestrogen, are important factors for fibroid growth. This has provided a rationale for the investigation of hormonal therapies for women with fibroids. This chapter will assess the role of hormonal therapies for pre-menopausal women with fibroids. A comprehensive search of MEDLINE and EMBASE was undertaken in December 2006. Twenty-nine relevant randomized controlled trials and two systematic reviews were found. The included studies assessed gonadotrophin-releasing hormone analogues (GnRHa) alone, GnRHa plus add-back (with either progestagen, tibolone, combined oestrogen and progestagen, or raloxifene) and GnRHa given for at least 3 months prior to surgery for fibroids. Two trials assessed the effects of raloxifene alone. One trial assessed the effects of low-dose mifepristone, and a pilot study assessed the role of the selective progesterone receptor modulator, asoprisinil. GnRHa reduce fibroid and uterine volume and heavy bleeding but are associated with menopausal symptoms and bone loss, which limit long-term use. There is some evidence that add-back therapy, either progestagen, tibolone, combined oestrogen and progestagen, or raloxifene, can reduce the menopausal symptoms associated with GnRHa and/or loss of bone density, but there is insufficient good-quality research to make definitive conclusions. GnRHa given for at least 3 months before fibroid surgery improve pre-operative haemoglobin concentration and haematocrit, reduce uterine and pelvic symptoms, and reduce the rate of vertical incisions during laparotomy. Women undergoing hysterectomy are more likely to have a vaginal than an abdominal procedure. Limited evidence suggests that raloxifene may be useful in older premenopausal women with lower concentrations of background oestradiol. Limited short-term evidence of two progestogenic therapies indicates that low-dose mifepristone may improve quality of life and bleeding in the short term, and asoprisinil may improve bleeding and fibroid-related symptoms. In conclusion, more research is required on the role of hormonal therapies for women with fibroids, particularly add-back options and selective oestrogen and progesterone receptor modulators. No definitive conclusions can be reached on the basis of the limited evidence found.     

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.