超低剂量雌二醇阴道片的子宫内膜安全性。

Endometrial safety of ultra-low-dose estradiol vaginal tablets.

机构信息

From Women's Health & Research Consultants, Washington, DC; New York University School of Medicine, New York, New York; Copenhagen University Hospital Rigshospitalet, Department of Gynecology and Obstetrics, Copenhagen, Denmark; Novo Nordisk FemCare AG, Zurich, Switzerland; Novo Nordisk, Princeton, New Jersey.

出版信息

Obstet Gynecol. 2010 Oct;116(4):876-883. doi: 10.1097/AOG.0b013e3181f386bb.

DOI:10.1097/AOG.0b013e3181f386bb

PMID:20859151

Abstract

OBJECTIVE

To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17β-estradiol vaginal tablets in postmenopausal women with vaginal atrophy.

METHODS

Endometrial biopsy data from individuals using active treatment (n=205) in a randomized, double-blind, placebo-controlled trial were pooled with the data from an open-label endometrial safety trial (n=336). Patients received 10-microgram estradiol vaginal tablets for 52 weeks. All endometrial biopsy samples were histologically analyzed at baseline and at end of trial by the same laboratory in both trials.

RESULTS

A total of 541 women using estradiol were included in the combined analysis of endometrial safety. A total of 456 women completed the trials, and 443 women had a biopsy performed at week 52: 85.6% were categorized as "atrophic endometrium," 12.6% had nonevaluable biopsy samples, 1.1% had polyps, and 0.2% were categorized as "weakly proliferative." One case of complex hyperplasia without atypia was reported in an individual exposed to trial drug for only 9 days. One woman's biopsy sample demonstrated endometrioid adenocarcinoma, grade 2, but the lack of an evaluable screening biopsy sample makes it uncertain whether the carcinoma was preexisting. In total, two events of hyperplasia and carcinoma were reported in 386 evaluable biopsy samples (incidence rate 0.52% per year).

CONCLUSION

The reported background incidence rate of endometrial hyperplasia and carcinoma in postmenopausal women is 0% to 1%. The results of this pooled analysis therefore support the endometrial safety of unopposed ultra-low-dose vaginal estrogen. There was no increased risk of endometrial hyperplasia and carcinoma in postmenopausal women undergoing treatment with 10-microgram estradiol vaginal tablets for 1 year under study conditions.

CLINICAL TRIAL REGISTRATION

ClinicalTrials.gov, www.clinicaltrials.gov, NCT00108849 (VAG-2195) and NCT00431132 (VAG 1748).

LEVEL OF EVIDENCE

II.

摘要

目的

评估 52 周超低剂量 10 微克 17β-雌二醇阴道片治疗绝经后阴道萎缩患者的子宫内膜增生和癌发生率。

方法

对一项随机、双盲、安慰剂对照试验中接受活性治疗（n=205）的个体的子宫内膜活检数据进行汇总，并与开放标签子宫内膜安全性试验（n=336）的数据进行合并。患者接受 10 微克雌二醇阴道片治疗 52 周。两项试验均由同一实验室在基线和试验结束时对所有子宫内膜活检样本进行组织学分析。

结果

共有 541 名使用雌二醇的女性纳入子宫内膜安全性联合分析。共有 456 名女性完成了试验，443 名女性在第 52 周进行了活检：85.6%为“萎缩性子宫内膜”，12.6%活检样本不可评估，1.1%为息肉，0.2%为“弱增生性”。在仅接受试验药物治疗 9 天的个体中报告了 1 例单纯性增生伴非典型性病例。1 名女性的活检样本显示为子宫内膜样腺癌，2 级，但缺乏可评估的筛查活检样本，因此无法确定该癌是否为先前存在。在 386 例可评估活检样本中，共报告了 2 例增生和癌事件（年发生率为 0.52%）。