Duke University Medical Center, Durham, North Carolina, USA.
Arthritis Care Res (Hoboken). 2011 Dec;63(12):1777-81. doi: 10.1002/acr.20605.
Standard treatment for severe granulomatosis with polyangiitis (Wegener's) (GPA) is daily oral cyclophosphamide (CYC), a cytotoxic agent associated with ovarian failure. In this study, we assessed the rate of diminished ovarian reserve in women with GPA who received CYC versus methotrexate (MTX).
Patients in the Wegener's Granulomatosis Etanercept Trial received either daily CYC or weekly MTX and were randomized to etanercept or placebo. For all women ages <50 years, plasma samples taken at baseline or early in the study were evaluated against samples taken later in the study to compare levels of anti-Müllerian hormone (AMH) and follicle-stimulating hormone (FSH), endocrine markers of remaining egg supply. Diminished ovarian reserve was defined as an AMH level of <1.0 ng/ml.
Of 42 women in this analysis (mean age 35 years), 24 had CYC exposure prior to enrollment and 28 received the drug during the study. At study entry, women with prior CYC exposure had significantly lower AMH, higher FSH, and a higher rate of early menstruation cessation. For women with normal baseline ovarian function, 6 of 8 who received CYC during the trial developed diminished ovarian reserve, compared to 0 of 4 who did not receive CYC (P < 0.05). Changes in AMH correlated inversely with cumulative CYC dose (P < 0.01), with a 0.74 ng/ml decline in AMH level for each 10 gm of CYC.
Daily oral CYC, even when administered for less than 6 months, causes diminished ovarian reserve, as indicated by low AMH levels. These data highlight the need for alternative treatments for GPA in women of childbearing age.
重症肉芽肿性多血管炎（韦格纳氏）（GPA）的标准治疗方法是每日口服环磷酰胺（CYC），这是一种与卵巢衰竭有关的细胞毒性药物。在这项研究中，我们评估了接受 CYC 治疗的 GPA 女性与接受甲氨蝶呤（MTX）治疗的女性之间卵巢储备减少的发生率。
韦格纳氏肉芽肿依那西普试验中的患者接受每日 CYC 或每周 MTX 治疗，并随机接受依那西普或安慰剂。对于所有年龄<50 岁的女性，在基线或研究早期采集的血浆样本与研究后期采集的样本进行比较，以比较抗苗勒管激素（AMH）和卵泡刺激素（FSH）的水平，这是剩余卵子供应的内分泌标志物。卵巢储备减少定义为 AMH 水平<1.0ng/ml。
在这项分析中，有 42 名女性（平均年龄 35 岁），24 名在入组前有 CYC 暴露史，28 名在研究期间接受了该药物。在研究入组时，有 CYC 暴露史的女性 AMH 明显较低，FSH 较高，月经早期停止的比例较高。对于基线卵巢功能正常的女性，在试验期间接受 CYC 的 8 人中，有 6 人出现卵巢储备减少，而未接受 CYC 的 4 人无一例发生（P<0.05）。AMH 的变化与 CYC 累积剂量呈负相关（P<0.01），每 10g CYC 导致 AMH 水平下降 0.74ng/ml。
即使 CYC 治疗时间不到 6 个月，每日口服 CYC 也会导致卵巢储备减少，表现为 AMH 水平降低。这些数据突出了在生育年龄的 GPA 女性中需要替代治疗方法的必要性。
