Buyon Jill P, Petri Michelle A, Kim Mimi Y, Kalunian Kenneth C, Grossman Jennifer, Hahn Bevra H, Merrill Joan T, Sammaritano Lisa, Lockshin Michael, Alarcón Graciela S, Manzi Susan, Belmont H Michael, Askanase Anca D, Sigler Lisa, Dooley Mary Anne, Von Feldt Joan, McCune W Joseph, Friedman Alan, Wachs Jane, Cronin Mary, Hearth-Holmes Michelene, Tan Mark, Licciardi Frederick
Hospital for Joint Diseases, New York University School of Medicine, New York, New York, USA.
Ann Intern Med. 2005 Jun 21;142(12 Pt 1):953-62. doi: 10.7326/0003-4819-142-12_part_1-200506210-00004.
There is concern that exogenous female hormones may worsen disease activity in women with systemic lupus erythematosus (SLE).
To evaluate the effect of hormone replacement therapy (HRT) on disease activity in postmenopausal women with SLE.
Randomized, double-blind, placebo-controlled noninferiority trial conducted from March 1996 to June 2002.
16 university-affiliated rheumatology clinics or practices in 11 U.S. states.
351 menopausal patients (mean age, 50 years) with inactive (81.5%) or stable-active (18.5%) SLE.
12 months of treatment with active drug (0.625 mg of conjugated estrogen daily, plus 5 mg of medroxyprogesterone for 12 days per month) or placebo. The 12-month follow-up rate was 82% for the HRT group and 87% for the placebo group.
The primary end point was occurrence of a severe flare as defined by Safety of Estrogens in Lupus Erythematosus, National Assessment-Systemic Lupus Erythematosus Disease Activity Index composite.
Severe flare was rare in both treatment groups: The 12-month severe flare rate was 0.081 for the HRT group and 0.049 for the placebo group, yielding an estimated difference of 0.033 (P = 0.23). The upper limit of the 1-sided 95% CI for the treatment difference was 0.078, within the prespecified margin of 9% for noninferiority. Mild to moderate flares were significantly increased in the HRT group: 1.14 flares/person-year for HRT and 0.86 flare/person-year for placebo (relative risk, 1.34; P = 0.01). The probability of any type of flare by 12 months was 0.64 for the HRT group and 0.51 for the placebo group (P = 0.01). In the HRT group, there were 1 death, 1 stroke, 2 cases of deep venous thrombosis, and 1 case of thrombosis in an arteriovenous graft; in the placebo group, 1 patient developed deep venous thrombosis.
Findings are not generalizable to women with high-titer anticardiolipin antibodies, lupus anticoagulant, or previous thrombosis.
Adding a short course of HRT is associated with a small risk for increasing the natural flare rate of lupus. Most of these flares are mild to moderate. The benefits of HRT can be balanced against the risk for flare because HRT did not significantly increase the risk for severe flare compared with placebo.
人们担心外源性女性激素可能会使系统性红斑狼疮（SLE）女性患者的疾病活动度恶化。
评估激素替代疗法（HRT）对绝经后SLE女性患者疾病活动度的影响。
1996年3月至2002年6月进行的随机、双盲、安慰剂对照的非劣效性试验。
美国11个州的16家大学附属医院的风湿病诊所或科室。
351名绝经患者（平均年龄50岁），患有非活动期（81.5%）或稳定活动期（18.5%）的SLE。
使用活性药物（每日0.625mg结合雌激素，加每月12天每日5mg甲羟孕酮）或安慰剂治疗12个月。HRT组的12个月随访率为82%，安慰剂组为87%。
主要终点是由红斑狼疮中雌激素安全性、国家评估 - 系统性红斑狼疮疾病活动指数综合定义的严重病情复发。
两个治疗组中严重病情复发均罕见：HRT组12个月严重病情复发率为0.081，安慰剂组为0.049，估计差异为0.033（P = 0.23）。治疗差异的单侧95%CI上限为0.078，在预先设定的非劣效性边际9%之内。HRT组轻度至中度病情复发显著增加：HRT组为1.14次病情复发/人年，安慰剂组为0.86次病情复发/人年（相对风险，1.34；P = 0.01）。12个月时任何类型病情复发的概率，HRT组为0.64，安慰剂组为0.51（P = 0.01）。HRT组有1例死亡、1例中风、2例深静脉血栓形成和1例动静脉移植物血栓形成；安慰剂组有1例患者发生深静脉血栓形成。
研究结果不适用于高滴度抗心磷脂抗体、狼疮抗凝物或既往有血栓形成的女性。
短期添加HRT与狼疮自然病情复发率增加的小风险相关。这些病情复发大多为轻度至中度。HRT的益处可与病情复发风险相权衡，因为与安慰剂相比，HRT未显著增加严重病情复发的风险。
