von Holst Thomas, Lang Eva, Winkler Ulrich, Keil Dieter
Ruprecht-Karls-Universität Heidelberg, Universitäts-Frauenklinik, Vossstrasse 9, 69115 Heidelberg, Germany.
Maturitas. 2002 Dec 10;43(4):265-75. doi: 10.1016/s0378-5122(02)00203-7.
The aim of this study was to compare the incidence of women presenting irregular bleeding episodes following 9 months of treatment with a low dose continuous combined hormone replacement therapy consisting of estradiol (E(2)) and norethisterone acetate (NETA) versus a sequential hormone replacement therapy consisting of conjugated equine estrogens (CEE) and medrogestone (MG). Secondary aims were to establish the relationship between menopausal age and the occurrence of irregular bleeding for both therapies and to assess the efficacy of both therapies in alleviating menopausal symptoms.
This was a stratified and randomised, open label study conducted with late peri and postmenopausal women at 35 sites in Austria and Germany. A total of 446 women were randomly allocated into two cohorts based on time since last bleeding and then stratified to either a low dose continuous combined therapy consisting of 1 mg E(2) and 0.5 mg NETA for 28 days or a sequential therapy consisting of 0.625 mg CEE for 28 days and 5 mg MG for the final 14 days. Bleeding and menopausal complaints were continuously assessed. Treatments were administered for 9 lunar months.
The incidence rate of women presenting irregular bleeding episodes including spotting during cycle 9 was 12.2% with 1mgE(2)/0.5mgNETA and 25.8% with 0.625mgCEE/5mgMG (P = 0.0014). In the group of postmenopausal women (time since last bleeding > or = 12 months) the incidence of irregular bleeding during cycle 9 was 11.0% for 1mgE(2)/0.5mgNETA and 25.0% for 0.625mgCEE/5mgMG). In the group of late perimenopausal women (time since last bleeding 6-11 months) the incidence of irregular bleeding was similar for both treatments at cycle 3, but markedly less in patients with 1mgE(2)/0.5mgNETA at cycle 6 and 9, being significantly different compared to patients with 0.625mgCEE/5mgMG at cycle 6 (P < 0.05). The cumulative rate of amenorrhea (no bleeding or spotting) achieved with 1mgE(2)/0.5mgNETA was 89% for the postmenopausal women and 83.7% for the late perimenopausal women. Both treatments relieved menopausal complaints equally effective.
Regarding the occurrence of irregular bleeding, the low dose continuous combined therapy was superior to the sequential therapy (0.625mgCEE/5mgMG). The low dose continuous combined E(2)/NETA regimen is also suitable for late perimenopausal women since more than 80% of the women had no bleeding or spotting after 9 months of treatment.
本研究旨在比较接受由雌二醇（E₂）和醋酸炔诺酮（NETA）组成的低剂量连续联合激素替代疗法治疗9个月后出现不规则出血的女性发生率，与接受由结合马雌激素（CEE）和甲地孕酮（MG）组成的序贯激素替代疗法的女性发生率。次要目的是确定两种疗法中绝经年龄与不规则出血发生之间的关系，并评估两种疗法缓解绝经症状的疗效。
这是一项在奥地利和德国35个地点对围绝经期晚期和绝经后女性进行的分层随机开放标签研究。总共446名女性根据距上次出血的时间随机分为两个队列，然后分层接受为期28天的由1mg E₂和0.5mg NETA组成的低剂量连续联合疗法，或接受为期28天的0.625mg CEE以及最后14天的5mg MG的序贯疗法。持续评估出血情况和绝经相关症状。治疗持续9个农历月。
在第9周期出现包括点滴出血在内的不规则出血的女性发生率，1mg E₂/0.5mg NETA组为12.2%，0.625mg CEE/5mg MG组为25.8%（P = 0.0014）。在绝经后女性组（距上次出血时间≥12个月）中，第9周期不规则出血的发生率，1mg E₂/0.5mg NETA组为11.0%，0.625mg CEE/5mg MG组为25.0%。在围绝经期晚期女性组（距上次出血时间6 - 11个月）中，两种治疗在第3周期的不规则出血发生率相似，但在第6周期和第9周期，1mg E₂/0.5mg NETA组患者的不规则出血明显较少，与第6周期接受0.625mg CEE/5mg MG治疗的患者相比有显著差异（P < 0.05）。1mg E₂/0.5mg NETA实现的闭经（无出血或点滴出血）累积率，绝经后女性为89%，围绝经期晚期女性为83.7%。两种治疗缓解绝经相关症状的效果相同。
关于不规则出血的发生情况，低剂量连续联合疗法优于序贯疗法（0.625mg CEE/5mg MG）。低剂量连续联合E₂/NET A方案也适用于围绝经期晚期女性，因为超过80%的女性在治疗9个月后无出血或点滴出血。
