Menopause hormonal therapy in women with systemic lupus erythematosus

Abstract

Objective. To evaluate the effects of menopause hormonal therapy on disease activity in women with systemic lupus erythematosus (SLE).Methods. We conducted a double-blind, randomized clinical trial involving 106 women with SLE who were in the menopausal transition or in early or late postmenopause. Patients received a continuoussequential estrogen-progestogen regimen (n ‫؍‬ 52) or placebo (n ‫؍‬ 54). Disease activity was assessed at baseline and at 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 months, according to the SLE Disease Activity Index (SLEDAI). The primary outcome measure was global disease activity, estimated by measuring the area under the SLEDAI curve. Secondary outcome measures included maximum SLEDAI score, change in SLEDAI score, incidence of lupus flares, median time to flare, medication use, and adverse events. Results were studied using intent-totreat analysis.Results. At baseline, demographic and disease characteristics were similar in both groups. Mean ؎ SD SLEDAI scores were 3.5 ؎ 3.3 and 3.1 ؎ 3.4 in the menopause hormonal therapy and placebo groups, respectively (P ‫؍‬ 0.57). Disease activity remained mild and stable in both groups throughout the trial. There were no significant differences between the groups in global or maximum disease activity, incidence or probability of flares, or medication use. Median time to flare was 3 months in both groups. Thromboses occurred in 3 patients who received menopause hormonal therapy and in 1 patient who received placebo. One patient in each group died during the trial due to sepsis.Conclusion. Menopause hormonal therapy did not alter disease activity during 2 years of treatment. However, an apparently increased risk of thrombosis seems to be a real threat in women with SLE who receive menopausal hormone therapy.

Efficacy of estrogen plus progestin on menopausal symptoms in women with systemic lupus erythematosus: A randomized, double‐blind, controlled trial

“…Regarding safety, we and other investigators have reported that hormone therapy did not affect the course of lupus activity at a clinically significant level, but as in the general population, increased the risk of thromboses (9,31). No additional severe adverse events were found; however, the study was not adequately powered to detect differences in the incidence of cardiovascular diseases, cancer, etc., between groups.…”

“…As reported previously (9), from the 1,981 patients who underwent screening, 149 remained eligible for the study, 43 declined to participate, and 106 were randomly assigned to menopausal hormone therapy (n ϭ 52) or placebo (n ϭ 54). Women who declined to participate in the study and those who underwent randomization did not differ in most demographic and lupus characteristics, including previous use of hormone therapy.…”

“…The study was approved by the hospital's institutional review board, and all patients provided written informed consent. The methodologic details of this clinical trial have been published previously, with the results of the effects of estrogen plus progestin on lupus activity (9). Briefly, 1,981 women with a diagnosis of systemic lupus erythematosus (10) were assessed for eligibility.…”

“…Adherence to treatment was assessed primarily by self-reported medication intake, and confirmed by measurement of serum levels of estradiol at baseline and at 1, 2, 3, 6, and 15 months. Study treatment was discontinued in women who developed any severe complication or whenever they desired (9). The date and primary reason for discontinuation were coded.…”

“…Sample size calculations were based on the disease activity end point (9). Assuming that 60% of symptomatic women at baseline became asymptomatic at 3 months in the hormone-treated group, and that the corresponding figure in the placebo group was Ͻ25%, a total sample of 72 symptomatic women, one-half in the treated group and one-half in the placebo group, would be required to detect this difference as significant, with a significance level of 95% and power of 80%.…”