From the Departments of Neurology (J.S.G., R.G.H., B.A.C.C., E.W., A.Z., S.L.H., J.R.O.), Pharmacology (R.M.G.), Obstetrics, Gynecology and Reproductive Sciences (M.I.C.), and Epidemiology and Biostatistics (P.B.), University of California, San Francisco; and Women and Infants Hospital and the Alpert Medical School at Brown University (G.L.-M.), Providence, RI.
Neurology. 2018 Jan 16;90(3):e254-e260. doi: 10.1212/WNL.0000000000004843. Epub 2017 Dec 22.
To determine if ovarian aging as measured by levels of anti-Müllerian hormone (AMH) is associated with pattern of multiple sclerosis (MS) progression in women.
Women with MS and healthy controls were included from a longitudinal research cohort with up to 10 years follow-up. Plasma AMH levels were measured by ELISA for baseline and years 3, 5, and 8-10. Mixed effects logistic and linear regression models were employed, with adjustments for age, disease duration, and other covariables as appropriate.
AMH levels were similar (0.98-fold difference, 95% confidence interval [CI] 0.69-1.37, = 0.87) in women with MS (n = 412, mean age 42.6 years) and healthy controls (n = 180, mean age 44 years). In a multivariable model of women with MS, including adjustments for age, body mass index, and disease duration, 10-fold lower AMH level was associated with 0.43-higher Expanded Disability Status Scale (EDSS) score (95% CI 0.15-0.70, = 0.003), 0.25-unit worse MS Functional Composite score (95% CI -0.40 to -0.10, = 0.0015), and 7.44 mm lower cortical gray matter volume (95% CI -14.6 to -0.30; = 0.041) at baseline. In a multivariable random-intercept-random-slope model using all observations over time, 10-fold decrease in AMH was associated with a 0.27 increase in EDSS (95% CI 0.11-0.43, = 0.006) and 5.48 mm (95% CI 11.3-0.33, = 0.065) and 4.55 mm (95% CI 9.33-0.23, = 0.062) decreases in total gray and cortical gray matter, respectively.
As a marker of ovarian aging, lower AMH levels were associated with greater disability and gray matter loss in women with MS independent of chronological age and disease duration.
确定抗苗勒管激素(AMH)水平所衡量的卵巢衰老是否与女性多发性硬化症(MS)的进展模式相关。
本研究纳入了一项具有长达 10 年随访的纵向研究队列中的 MS 女性患者和健康对照者。通过 ELISA 法测定基线和第 3、5、8-10 年时的血浆 AMH 水平。采用混合效应逻辑和线性回归模型进行分析,并根据年龄、疾病持续时间和其他合适的协变量进行调整。
MS 女性(n = 412,平均年龄 42.6 岁)和健康对照者(n = 180,平均年龄 44 岁)的 AMH 水平相似(差异为 0.98 倍,95%置信区间 [CI] 0.69-1.37, = 0.87)。在包括年龄、体重指数和疾病持续时间调整的 MS 女性多变量模型中,AMH 水平降低 10 倍与扩展残疾状况量表(EDSS)评分升高 0.43 分(95%CI 0.15-0.70, = 0.003)、MS 功能综合评分降低 0.25 分(95%CI -0.40 至 -0.10, = 0.0015)和皮质灰质体积降低 7.44mm(95%CI -14.6 至 -0.30; = 0.041)相关。在使用随时间变化的所有观测值的多变量随机截距-随机斜率模型中,AMH 降低 10 倍与 EDSS 增加 0.27 分(95%CI 0.11-0.43, = 0.006)以及灰质总容积降低 5.48mm(95%CI 11.3-0.33, = 0.065)和皮质灰质容积降低 4.55mm(95%CI 9.33-0.23, = 0.062)相关。
作为卵巢衰老的标志物,AMH 水平降低与 MS 女性的残疾程度和灰质丢失增加相关,与实际年龄和疾病持续时间无关。