Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Sciences and Moores Cancer Center, University of California, San Diego, La Jolla, California.
Division of Biostatistics and Bioinformatics, Department of Family Medicine and Public Health and Moores Cancer Center, University of California, San Diego, La Jolla, California.
J Clin Endocrinol Metab. 2020 Aug 1;105(8):2740-51. doi: 10.1210/clinem/dgaa172.
Many female survivors of adolescent and young adult cancers (AYA survivors) have shortened reproductive lifespans. However, the timing and duration of ovarian function after cancer treatment are largely unknown.
To model the trajectory of ovarian function over two decades following cancer treatment and evaluate how trajectories vary by treatment gonadotoxicity and age.
In a prospective cohort, AYA survivors aged 18-39 at variable times since cancer treatment completion provided dried blood spots (DBS) every 6 months for up to 18 months. Anti-Müllerian hormone (AMH) levels were measured using the Ansh DBS AMH enzyme-linked immunosorbent assay. The mean AMH trajectory was modeled for the entire cohort and separately by treatment gonadotoxicity and age using functional principal components analysis.
763 participants, mean (standard deviation) enrollment age 33.3 (4.7) and age at cancer diagnosis 25.9 (5.7) years, contributed 1905 DBS samples. The most common cancers were breast (26.9%), lymphoma (24.8%), and thyroid (18.0%). AMH trajectories differed among survivors by treatment gonadotoxicity (low, moderate, or high) (P < 0.001). Following low or moderately gonadotoxic treatments, AMH levels increased over 2-3 years and plateaued over 10-15 years before declining. In contrast, following highly gonadotoxic treatment, AMH levels were lower overall and declined shortly after peak at 2-3 years. Younger age at treatment was associated with higher trajectories, but a protective effect of younger age was not observed in survivors exposed to highly gonadotoxic treatments (Pinteraction < 0.001).
In this large AYA survivor cohort, timing and duration of ovarian function strongly depended on treatment gonadotoxicity and age at treatment. The findings provide novel, more precise information to guide reproductive decision-making.
许多青少年和年轻成年癌症（AYA 幸存者）的女性幸存者的生殖寿命缩短了。然而，癌症治疗后卵巢功能的时间和持续时间在很大程度上尚不清楚。
建立癌症治疗后二十年卵巢功能的轨迹模型，并评估轨迹如何因治疗性腺毒性和年龄而异。
在一项前瞻性队列研究中，18-39 岁的 AYA 幸存者在癌症治疗完成后不同时间点每隔 6 个月提供一次干血斑（DBS），最长可达 18 个月。使用 Ansh DBS AMH 酶联免疫吸附测定法测量抗缪勒管激素（AMH）水平。使用功能主成分分析对整个队列和按治疗性腺毒性和年龄分别对平均 AMH 轨迹进行建模。
763 名参与者，平均（标准差）入组年龄为 33.3（4.7）岁，癌症诊断年龄为 25.9（5.7）岁，共提供了 1905 份 DBS 样本。最常见的癌症是乳腺癌（26.9%）、淋巴瘤（24.8%）和甲状腺癌（18.0%）。AMH 轨迹因治疗性腺毒性（低、中或高）而在幸存者中有所不同（P < 0.001）。在低或中度性腺毒性治疗后，AMH 水平在 2-3 年内增加并在 10-15 年内稳定，然后下降。相比之下，在高性腺毒性治疗后，AMH 水平总体较低，在 2-3 年内达到峰值后不久下降。治疗时年龄较小与较高的轨迹相关，但在暴露于高性腺毒性治疗的幸存者中，年龄较小的保护作用不明显（P 交互 < 0.001）。
在这项大型 AYA 幸存者队列研究中，卵巢功能的时间和持续时间强烈取决于治疗性腺毒性和治疗时的年龄。这些发现为指导生殖决策提供了新的、更精确的信息。
