Archer D F, Dorin M H, Heine W, Nanavati N, Arce J C
Clinical Research Center, Eastern Virginia Medical School, Norfolk, 23507, USA.
Obstet Gynecol. 1999 Sep;94(3):323-9. doi: 10.1016/s0029-7844(99)00358-0.
To investigate the incidence of uterine bleeding during 12 months of treatment with 17beta-estradiol (E2) 1 mg, unopposed or in combination with three doses of norethindrone acetate.
This study was a prospective, double-masked, randomized, multicenter trial. A total of 1176 healthy postmenopausal women age 45 years and older without evidence of endometrial abnormalities were randomly assigned to receive either unopposed E2 1 mg, or continuous-combined formulations of E2 1 mg and norethindrone acetate 0.1 mg, 0.25 mg, or 0.5 mg. Any spotting or bleeding episodes during the treatment period were recorded in a daily diary and reported by weekly telephone calls.
The incidence of bleeding was low in the combination groups, even during the initial 3 months of treatment (24-28%), after which it decreased with increasing doses of norethindrone acetate. Conversely, the incidence of bleeding increased over time with unopposed E2 1 mg. After the initial 3 months, the incidence of bleeding among the combination groups was lowest in the norethindrone acetate 0.5 mg group. Among women initiating therapy close to menopause, fewer reported bleeding with norethindrone acetate 0.5 mg than with the other combination groups. There was a significantly (P<.05) lower discontinuation rate due to bleeding in the norethindrone acetate 0.5 mg group compared with all other treatment groups.
Continuous-combined formulations of E2 1 mg with norethindrone acetate 0.1, 0.25, or 0.5 mg are associated with a low incidence of uterine bleeding. After the initial 3 months of treatment, bleeding profiles improved with increasing doses of norethindrone acetate.
研究1毫克17β-雌二醇（E2）单独使用或与三种剂量醋酸炔诺酮联合使用12个月期间子宫出血的发生率。
本研究为前瞻性、双盲、随机、多中心试验。共有1176名年龄在45岁及以上、无子宫内膜异常证据的健康绝经后妇女被随机分配接受1毫克单独使用的E2，或E2 1毫克与醋酸炔诺酮0.1毫克、0.25毫克或0.5毫克的连续联合制剂。治疗期间的任何点滴出血或出血事件都记录在每日日记中，并通过每周电话报告。
联合用药组的出血发生率较低，即使在治疗的最初3个月（24%-28%）也是如此，此后随着醋酸炔诺酮剂量的增加而降低。相反，单独使用1毫克E2时，出血发生率随时间增加。在最初3个月后，联合用药组中醋酸炔诺酮0.5毫克组的出血发生率最低。在接近绝经开始治疗的女性中，报告使用醋酸炔诺酮0.5毫克出血的人数少于其他联合用药组。与所有其他治疗组相比，醋酸炔诺酮0.5毫克组因出血导致的停药率显著降低（P<0.05）。
E2 1毫克与醋酸炔诺酮0.1毫克、0.25毫克或0.5毫克的连续联合制剂与子宫出血发生率低相关。治疗最初3个月后，随着醋酸炔诺酮剂量增加，出血情况改善。
