Menstruation is a key indicator of female reproductive health, yet clinical features and underlying mechanisms associated with menstrual changes following the coronavirus disease 2019 (COVID-19) infection remain unclear. Here, we recruited 253 participants through questionnaires, and 73 individuals underwent metabolomic analysis of blood serum. Over 60% reported menstrual changes, primarily experiencing longer cycle and lighter bleeding, which were significantly associated with age, general medical conditions, perceived stress, anxiety scores, and depression scores, as well as COVID-19 symptoms including fatigue and headache. General medical conditions were the sole independent risk factor for any menstrual changes. Metabolomic analysis highlighted disturbances in steroid hormone biosynthesis. We identified 52 significantly differential metabolites between groups with and without any menstrual changes (AnyC vs. NoC), with high discrimination achieved by combining phenylglyoxylic acid, PC O-40, traumatic acid, and estrone sulfate. Furthermore, several significantly upregulated metabolites were closely correlated with estradiol (E₂) levels, including estrone sulfate, which was also positively correlated with T levels. Specifically, T levels decreased with recovery duration in the AnyC group (p = 0.0015). Collectively, our findings uncovered key clinical factors and metabolic disruptions in menstrual changes, underscoring potential adverse long-term effects of COVID-19 on women's health.

Keywords: COVID‐19; hormone; menstrual change; metabolomics; recovery duration.

© 2025 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.

月经是女性生殖健康的重要指标，但冠状病毒疾病2019（COVID-19）感染后与月经变化相关的临床特征和潜在机制尚不清楚。在此研究中，我们通过问卷调查招募了253名参与者，并对其中73人的血液血清进行了代谢组学分析。超过60%的受访者报告称有月经变化，主要表现为周期延长和出血量减少，这些变化与年龄、一般健康状况、感知压力、焦虑评分和抑郁评分以及包括疲劳和头痛在内的COVID-19症状显著相关。一般健康状况是任何月经变化的唯一独立风险因素。代谢组学分析突出了类固醇激素生物合成的紊乱情况。我们识别出在有无任何月经变化（AnyC vs. NoC）的人群中，共有52种代谢物存在显著差异，通过结合苯乙醛酸、PC O-40、创伤酸和雌酮硫酸这四种代谢物可实现较高的鉴别度。此外，几种上调的代谢物与雌二醇(E₂)水平密切相关，包括也正向相关的雄烯二酮(T)水平。具体而言，在AnyC组中，T水平随恢复时间的延长而下降（p = 0.0015）。总的来说，我们的研究发现揭示了月经变化的关键临床因素和代谢紊乱情况，强调了COVID-19对女性健康可能产生的潜在长期不利影响。

关键词：COVID‐19；激素；月经变化；代谢组学；恢复时间。