Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Hum Reprod. 2023 Nov 2;38(11):2239-2246. doi: 10.1093/humrep/dead176.
What are the associations between female-specific reproductive factors and leukocyte telomere length (LTL)?
Early menarche, early menopause, short reproductive lifespan, early age at first birth, multiparity, and use of oral contraceptives (OCs) and hormone replacement therapy (HRT) were associated with shorter LTL.
Reproductive factors have been associated with age-related diseases, but their associations with cellular aging, as indicated by LTL, are unclear.
STUDY DESIGN, SIZE, DURATION: This population-based study included 224 965 women aged 40-69 years from the UK Biobank between 2006 and 2010.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 40-69 were included. Female-specific reproductive factors, including age at menarche, age at natural menopause, reproductive lifespan, number of live births, age at first live birth, history of stillbirth, history of miscarriage, and use of OCs and HRT were self-reported. LTL was measured using a validated polymerase chain reaction method. Multiple linear regression and restricted cubic spline models were applied to explore the association between each reproductive factor and LTL.
After adjustment for potential confounders, early menarche (<12 years; percent change, per unit change in LTL Z score: -1.29%, 95% CI: -2.32%, -0.26%), early menopause (<45 years; percent change: -7.18%, 95% CI: -8.87%, -5.45%), short reproductive lifespan (<30 years; percent change: -6.10%, 95% CI: -8.14%, -4.01%), multiparity (percent change: -3.38%, 95% CI: -4.38%, -2.37%), early age at first live birth (<20 years; percent change: -4.46%, 95% CI: -6.00%, -2.90%), and use of OCs (percent change: -1.10%, 95% CI: -2.18%, -0.02%) and HRT (percent change: -3.72%, 95% CI: -4.63%, -2.80%) were all significantly associated with shorter LTL. However, no significant association was found for history of miscarriage and stillbirth. We observed nonlinear relationships of age at menarche, age at natural menopause, reproductive lifespan, and age at first live birth with LTL (Pnonlinear < 0.05).
LIMITATIONS, REASONS FOR CAUTION: Considering that the participants were predominantly of European ethnicity, the findings may not be generalizable to women of other ethnic backgrounds.
Our findings suggest that early menarche, early menopause, short reproductive lifespan, early age at first birth, multiparity, and use of OCs and HRT were associated with shorter LTL, which has been linked to various chronic diseases. The accelerated shortening of telomeres may potentially contribute to the development of chronic diseases related to reproductive factors.
STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the National Natural Science Foundation of China (82003479, 82073660), Hubei Provincial Natural Science Foundation of China (2023AFB663), and the China Postdoctoral Science Foundation (2019M662646, 2020T130220). The authors have no competing interests to disclose.
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女性生殖因素与白细胞端粒长度（LTL）之间有何关联？
初潮年龄较早、绝经年龄较早、生殖寿命较短、首次生育年龄较早、多产以及使用口服避孕药（OCs）和激素替代疗法（HRT）与 LTL 较短有关。
生殖因素与与年龄相关的疾病有关，但它们与细胞衰老（由 LTL 表示）的关联尚不清楚。
研究设计、大小和持续时间：这项基于人群的研究包括 2006 年至 2010 年间英国生物库中 224965 名年龄在 40-69 岁的女性。
参与者/材料、设置、方法：纳入年龄在 40-69 岁的女性。包括初潮年龄、自然绝经年龄、生殖寿命、活产数、首次活产年龄、死产史、流产史以及使用 OCs 和 HRT 等女性生殖因素均为自我报告。使用经过验证的聚合酶链反应方法测量 LTL。应用多元线性回归和限制立方样条模型来探讨每个生殖因素与 LTL 之间的关联。
在调整了潜在混杂因素后，初潮年龄较早（<12 岁；LTL Z 分数每单位变化的百分比变化：-1.29%，95%CI：-2.32%，-0.26%）、绝经年龄较早（<45 岁；百分比变化：-7.18%，95%CI：-8.87%，-5.45%）、生殖寿命较短（<30 岁；百分比变化：-6.10%，95%CI：-8.14%，-4.01%）、多产（百分比变化：-3.38%，95%CI：-4.38%，-2.37%）、首次生育年龄较早（<20 岁；百分比变化：-4.46%，95%CI：-6.00%，-2.90%）以及使用 OCs（百分比变化：-1.10%，95%CI：-2.18%，-0.02%）和 HRT（百分比变化：-3.72%，95%CI：-4.63%，-2.80%）均与 LTL 较短显著相关。然而，流产史和死产史与 LTL 无显著关联。我们观察到初潮年龄、自然绝经年龄、生殖寿命和首次生育年龄与 LTL 之间存在非线性关系（Pnonlinear < 0.05）。
局限性、谨慎的原因：考虑到参与者主要为欧洲血统，研究结果可能不适用于其他族裔背景的女性。
我们的研究结果表明，初潮年龄较早、绝经年龄较早、生殖寿命较短、首次生育年龄较早、多产以及使用 OCs 和 HRT 与 LTL 较短有关，而 LTL 与各种慢性疾病有关。端粒的加速缩短可能会导致与生殖因素相关的慢性疾病的发展。
研究资金/利益冲突：本研究由国家自然科学基金（82003479、82073660）、湖北省自然科学基金（2023AFB663）和中国博士后科学基金（2019M662646、2020T130220）资助。作者没有利益冲突需要披露。
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