Obel E B, Munk-Jensen N, Svenstrup B, Bennett P, Micic S, Henrik-Nielsen R, Nielsen S P, Gydesen H, Jensen B M
Department of Surgery, Hørsholm Hospital, Denmark.
Maturitas. 1993 Jan;16(1):13-21. doi: 10.1016/0378-5122(93)90129-6.
A total of 151 postmenopausal women were randomly allocated to 3 groups for treatment with hormone replacement therapy. One group received combined therapy (2 mg oestradiol (E2) and 1 mg norethisterone acetate (NETA) daily), the second group was placed on sequential therapy (2 mg E2 for 12 days, 2 mgE2 and 1 mg NETA for 10 days and 1 mg E2 for 6 days), while the third was given placebo. Treatment was administered over 24 cycles of 28 days. The two active treatments were equally effective in relieving climacteric symptoms. In the combined therapy group, 62% of the women experienced spotting and/or breakthrough bleeding during the first 3 cycles; thereafter this proportion decreased to between 3 and 18% in each of the following three-cycle periods. Sixty-four percent (64%) of these women had no more bleeding after the first 3 cycles. Endometrial atrophy was detected in 93% of the women in this group after 24 cycles of therapy. Bleeding irregularities occurred during the first 3 cycles in 27% of the patients treated with sequential therapy and in 21% of those receiving placebo. In the subsequent 3-cycle periods these figures fell to below 10% in the 2 groups. In all 3 groups weight remained stable but blood pressure increased equally in the actively treated groups and the placebo group. The levels of follicle-stimulating hormone (FSH), sex-hormone-binding globulin (SHBG) and the free fraction of E2 in serum were significantly lower in the combined therapy group than in the sequential therapy group. The higher level of free E2 in the latter group may have been caused by a decrease in metabolism associated with the increased SHBG concentration. It was concluded that combined treatment with E2 and NETA might provide an alternative to sequential treatment in postmenopausal women willing to tolerate the initial high risk of breakthrough bleeding/spotting in order to avoid subsequent regular bleeding. In the subgroup of women in whom bleeding irregularities continue, sequential treatment should be considered.
共有151名绝经后女性被随机分为3组接受激素替代疗法治疗。一组接受联合治疗（每日2毫克雌二醇（E2）和1毫克醋酸炔诺酮（NETA）），第二组接受序贯治疗（2毫克E2治疗12天，2毫克E2和1毫克NETA治疗10天，1毫克E2治疗6天），而第三组给予安慰剂。治疗持续24个周期，每个周期28天。两种活性治疗在缓解更年期症状方面同样有效。在联合治疗组中，62%的女性在前3个周期出现点滴出血和/或突破性出血；此后，在接下来的每三个周期中，这一比例降至3%至18%之间。这些女性中有64%在最初3个周期后不再出血。在24个周期的治疗后，该组93%的女性检测到子宫内膜萎缩。接受序贯治疗的患者中有27%在最初3个周期出现出血不规律，接受安慰剂治疗的患者中有21%出现出血不规律。在随后的3个周期中，这两组的这一数字降至10%以下。在所有3组中体重保持稳定，但积极治疗组和安慰剂组的血压均有同等程度的升高。联合治疗组血清中促卵泡生成素（FSH）、性激素结合球蛋白（SHBG）和E2的游离部分水平显著低于序贯治疗组。后一组中游离E2水平较高可能是由于与SHBG浓度升高相关的代谢降低所致。得出的结论是，对于愿意忍受最初突破性出血/点滴出血高风险以避免随后规律性出血的绝经后女性，E2和NETA联合治疗可能是序贯治疗的一种替代方法。对于出血不规律持续存在的女性亚组，应考虑序贯治疗。
