van Rooij Ilse A J, Tonkelaar Isolde den, Broekmans Frank J M, Looman Caspar W N, Scheffer Gabrielle J, de Jong Frank H, Themmen Axel P N, te Velde Egbert R
Department of Reproductive Medicine, University Medical Center, 3584 CX, The Netherlands.
Menopause. 2004 Nov-Dec;11(6 Pt 1):601-6. doi: 10.1097/01.gme.0000123642.76105.6e.
Age at menopause and age at the start of the preceding period of cycle irregularity (menopausal transition) show considerable individual variation. In this study we explored several markers for their ability to predict the occurrence of the transition to menopause.
A group of 81 normal women between 25 and 46 years of age visited the clinic two times (at T1 and T2) with an average interval of 4 years. All had a regular menstrual cycle pattern at T1. At T1, anti-mullerian hormone (AMH), follicle-stimulating hormone (FSH), inhibin B and estradiol (E2) were measured, and an antral follicle count (AFC) was made during the early follicular phase. At T2, information regarding cycle length and variability was obtained. Menopause transition was defined as a mean cycle length of less than 21 days or more than 35 days or as a mean cycle length of 21 to 35 days, but with the next cycle not predictable within 7 days during the last half year. A logistic regression analysis was performed, with the outcome measure as menopause transition. The area under the receiver operating curve (ROCAUC) was calculated as a measure of predictive accuracy.
In 14 volunteers, the cycle had become irregular at T2. Compared with women with a regular cycle at T2, these women were significantly older (median 44.7 vs 39.8 y, P < 0.001) and differed significantly in AFC, AMH, FSH, and inhibin B levels assessed at T1. All parameters with the exception of E2 were significantly associated with the occurrence of cycle irregularity; AMH, AFC, and age had the highest predictive accuracy (ROCAUC 0.87, 0.80, and 0.82, respectively). After adjusting for age, only AMH and inhibin B were significantly associated with cycle irregularity. Inclusion of inhibin B and age to AMH in a multivariable model improved the predictive accuracy (ROCAUC 0.92).
The novel marker AMH is a promising predictor for the occurrence of menopausal transition within 4 years. Adding inhibin B improved the prediction. Therefore, AMH alone or in combination with inhibin B may well prove a useful indicator for the reproductive status of an individual woman.
绝经年龄以及绝经前月经周期不规律阶段(围绝经期过渡)开始时的年龄存在显著个体差异。在本研究中,我们探究了几种标志物预测围绝经期过渡发生的能力。
一组81名年龄在25至46岁之间的正常女性到诊所就诊两次(T1和T2),平均间隔4年。所有女性在T1时月经周期规律。在T1时,测量抗苗勒管激素(AMH)、促卵泡生成素(FSH)、抑制素B和雌二醇(E2),并在卵泡早期进行窦卵泡计数(AFC)。在T2时,获取有关月经周期长度和变异性的信息。围绝经期过渡定义为平均月经周期长度小于21天或大于35天,或平均月经周期长度为21至35天,但在过去半年内下一个周期在7天内不可预测。进行逻辑回归分析,将围绝经期过渡作为结果指标。计算受试者工作特征曲线下面积(ROCAUC)作为预测准确性的指标。
在14名志愿者中,T2时月经周期变得不规律。与T2时月经周期规律的女性相比,这些女性年龄显著更大(中位数44.7岁对39.8岁,P<0.001),并且在T1时评估的AFC、AMH、FSH和抑制素B水平存在显著差异。除E2外,所有参数均与月经周期不规律的发生显著相关;AMH、AFC和年龄具有最高的预测准确性(ROCAUC分别为0.87、0.80和0.82)。在调整年龄后,只有AMH和抑制素B与月经周期不规律显著相关。在多变量模型中将抑制素B和年龄纳入AMH可提高预测准确性(ROCAUC为0.92)。
新型标志物AMH是4年内围绝经期过渡发生的有前景的预测指标。加入抑制素B可改善预测。因此,单独的AMH或与抑制素B联合使用很可能被证明是个体女性生殖状态的有用指标。