Xin Xin, Guan Lu, Li Jiaxi, Zhang Jinfu, Wu Haicui
Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200052, People's Republic of China.
Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.
Int J Womens Health. 2025 Sep 2;17:2833-2844. doi: 10.2147/IJWH.S534178. eCollection 2025.
Female reproductive disorders (FRDs) are common diseases among women of childbearing age, affecting their reproductive health. Age at first sexual intercourse (AFS) is potentially linked to FRDs, and this study aims to investigate these associations and underlying mechanisms, to offer new insights and guidance for sex education in adolescent women and reproductive health management.
Mendelian randomization (MR) analysis was performed using summary data from genome-wide association studies (GWASs). The AFS summary data were sourced from 397,338 European participants, and the outcome data were obtained from the FinnGen consortium. Additionally, multivariate MR (MVMR) and mediation analyses were also adopted to explore more detailed association. The MR results were rigorously validated, with the inverse variance weighted (IVW) method employed as the primary approach to assess causal relationships.
There is a significant causal relationship between AFS and ovarian dysfunction (OD), polycystic ovarian syndrome (PCOS), and spontaneous abortion (0.45 [0.25-0.81], p=0.008; 0.35 [0.17-0.74], p=0.006; 0.76 [0.63-0.92], p=0.006). Among them, the genetic association between AFS and spontaneous abortion remained significant even after adjusting for more confounding variables (0.73 [0.55-0.95], p=0.020; 0.76 [0.61-0.95], p=0.015), and Body mass index (BMI) may be an important mediating factor in the association between AFS and PCOS (38.41%, p=7.17e-6) or OD (35.64%, p= 1.51e-6).
Our research suggested that early AFS is closely associated with a higher risk of reproductive disorders, and timely interventions targeting BMI may partially alleviate the adverse effects of early sexual activity on reproductive health. The analysis based on genetic data emphasizes the importance of early sex education for adolescents, while weight management can to some extent avoid the occurrence of reproductive disorders during childbearing age, which also provide scientific basis for understanding the pathogenesis of FRDs and formulating appropriate reproductive health education strategies.
女性生殖系统疾病（FRDs）是育龄期女性的常见疾病，影响她们的生殖健康。首次性交年龄（AFS）可能与FRDs有关，本研究旨在调查这些关联及其潜在机制，为青春期女性的性教育和生殖健康管理提供新的见解和指导。
使用全基因组关联研究（GWASs）的汇总数据进行孟德尔随机化（MR）分析。AFS汇总数据来自397,338名欧洲参与者，结局数据来自芬兰基因组联盟。此外，还采用了多变量MR（MVMR）和中介分析来探索更详细的关联。MR结果经过严格验证，采用逆方差加权（IVW）方法作为评估因果关系的主要方法。
AFS与卵巢功能障碍（OD）、多囊卵巢综合征（PCOS）和自然流产之间存在显著的因果关系（0.45 [0.25 - 0.81]，p = 0.008；0.35 [0.17 - 0.74]，p = 0.006；0.76 [0.63 - 0.92]，p = 0.006）。其中，即使在调整了更多混杂变量后，AFS与自然流产之间的遗传关联仍然显著（0.73 [0.55 - 0.95]，p = 0.020；0.76 [0.61 - 0.95]，p = 0.015），体重指数（BMI）可能是AFS与PCOS（38.41%，p = 7.17e - 6）或OD（35.64%，p = 1.51e - 6）之间关联的重要中介因素。
我们的研究表明，较早的AFS与较高的生殖系统疾病风险密切相关，针对BMI的及时干预可能部分减轻早期性活动对生殖健康的不利影响。基于遗传数据的分析强调了青少年早期性教育的重要性，而体重管理在一定程度上可以避免育龄期生殖系统疾病的发生，这也为理解FRDs的发病机制和制定适当的生殖健康教育策略提供了科学依据。
