Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, MA 01003, USA.
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Hum Reprod. 2018 Jun 1;33(6):1175-1182. doi: 10.1093/humrep/dey077.
Are anti-Müllerian hormone (AMH) levels assessed in women aged 32-44 associated with risk of incident early natural menopause?
We observed strong, significant associations between lower AMH levels and higher risk of early menopause.
The ability to predict risk early menopause, defined as menopause before age 45, prior to fertility decline would improve options for family planning and cardiovascular disease prevention. Though AMH is an established marker of menopause timing in older reproductive-aged women, whether AMH is associated with risk of early menopause has not been evaluated.
STUDY DESIGN, SIZE, DURATION: We assessed these relations in a nested case-control study within the prospective Nurses' Health Study II cohort. Premenopausal blood samples were collected in 1996-1999. Participants were followed until 2011 for early natural menopause, with follow-up rates >94%.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Early menopause cases (n = 327) were women reporting natural menopause between blood collection and age 45. Controls (n = 491) experienced menopause after age 45 and included 327 cases matched to controls on the basis of age at blood draw (±4 months) and other factors. AMH levels up to 12 years before early menopause were assayed in 2016.
In multivariable conditional logistic regression models adjusting for matching factors, body mass index, smoking, parity, oral contraceptive use, and other factors, each 0.10 ng/ml decrease in AMH was associated with a 14% higher risk of early menopause (95% confidence interval (CI) 1.10 to 1.18; P < 0.001). In polynomial regression models including linear and quadratic terms for AMH, odds ratios for early menopause for women with AMH levels of 1.5, 1.0 and 0.5 ng/ml compared to 2.0 ng/ml were 2.6, 7.5 and 23 (all P < 0.001). Significant associations were observed irrespective of smoking status, adiposity, infertility history and menstrual cycle characteristics. Furthermore, models assessing the predictive ability of AMH showed high concordance, and C-statistics were high, ranging from 0.68 (age ≤35) to 0.93 (age 42).
LIMITATIONS, REASONS FOR CAUTION: Our population was relatively homogenous with respect to race/ethnicity. Further work in more ethnically diverse populations is needed.
To our knowledge, this is the first prospective study to evaluate whether AMH levels are associated with early menopause. These findings support the utility of AMH as a clinical marker of early menopause in otherwise healthy women.
STUDY FUNDING/COMPETING INTEREST(S): This project was supported by UM1CA176726, R01CA67262, and R01HD078517 from the U.S. Department of Health and Human Services, National Institutes of Health. No competing interests declared.
32-44 岁女性的抗苗勒管激素（AMH）水平是否与早发性自然绝经的风险相关？
我们观察到较低的 AMH 水平与更高的早绝经风险之间存在强烈且显著的关联。
能够预测 45 岁前的早发性绝经（定义为绝经前），这将改善生育力下降前的计划生育和心血管疾病预防选择。尽管 AMH 是老年生殖年龄女性绝经时间的既定标志物，但 AMH 是否与早发性绝经风险相关尚未得到评估。
研究设计、大小和持续时间：我们在前瞻性护士健康研究 II 队列的嵌套病例对照研究中评估了这些关系。1996-1999 年采集了绝经前的血样。参与者在随访至 2011 年，随访率>94%。
参与者/材料、地点、方法：早发性绝经病例（n=327）为在采血后至 45 岁期间报告自然绝经的女性。对照（n=491）在 45 岁后经历了绝经，其中 327 例病例按采血时的年龄（±4 个月）和其他因素与对照匹配。2016 年检测了早发性绝经前长达 12 年的 AMH 水平。
在多变量条件逻辑回归模型中，根据匹配因素、体重指数、吸烟、生育史、口服避孕药使用和其他因素进行调整，AMH 每降低 0.10ng/ml，早发性绝经的风险就会增加 14%（95%置信区间（CI）为 1.10 至 1.18；P<0.001）。在包括 AMH 线性和二次项的多项式回归模型中，与 2.0ng/ml AMH 相比，AMH 水平为 1.5、1.0 和 0.5ng/ml 的女性早发性绝经的比值比分别为 2.6、7.5 和 23（均 P<0.001）。观察到的关联与吸烟状况、肥胖、不孕史和月经周期特征无关。此外，评估 AMH 预测能力的模型显示出高度一致性，C 统计量较高，范围从 0.68（年龄≤35 岁）到 0.93（年龄 42 岁）。
局限性、谨慎的原因：我们的人群在种族/民族方面相对同质。需要在更多种族多样化的人群中开展进一步的工作。
据我们所知，这是第一项评估 AMH 水平是否与早发性绝经相关的前瞻性研究。这些发现支持 AMH 作为健康女性早发性绝经的临床标志物的效用。
研究资金/利益冲突：本项目由美国国立卫生研究院下属的 UM1CA176726、R01CA67262 和 R01HD078517 资助。无竞争利益声明。
