Patients with long COVID may be more likely to report heavier menstrual bleeding, prolonged periods, and symptom flare-ups during menstruation compared with patients who never had COVID, according to a large study in the United Kingdom. The prevalence of periods lasting longer than 8 days was more than twice as high in patients with long COVID. Fatigue, headache, dizziness, and postexertional malaise worsened during the late secretory and menstrual phases. Investigators also reported higher tumor necrosis factor levels during menstruation and altered hormone receptor patterns in patients with long COVID. Ovarian reserve markers, including estradiol, progesterone, and anti-Müllerian hormone, didn't significantly differ between the groups.
The research included three approaches. An online survey of 12,187 menstruating patients assessed their menstrual changes, history of COVID-19 infections, and demographics. Among the respondents, 1,048 reported experiencing long COVID, 1,716 had a prior acute infection, and 9,423 had never been diagnosed. The median age was 36 years among the patients with long COVID and 32 years among controls.
A cycle-tracking substudy followed patients with long COVID and showed a higher risk of symptom worsening during menstruation compared with earlier phases.
A mechanistic study measured cytokines and analyzed endometrial tissue. Blood levels of the inflammatory markers tumor necrosis factor and interleukin-8 were elevated during menstruation in long COVID, whereas endometrial expression of tumor necrosis factor and interleukin-10 was lower. Neutrophil aggregates were observed in the endometrium of patients with long COVID but not in controls. Circulating 5-alpha–dihydrotestosterone was higher in the secretory phase, and androgen receptor staining was reduced during menstrual and proliferative phases.
The study had several limitations. Menstrual changes and COVID-19 status were self-reported, which may have introduced recall bias. Recruitment through social media resulted in a sample composed primarily of White, educated women, limiting generalizability. Despite efforts to stratify sampling, patients from minority and lower socioeconomic groups were underrepresented. The mechanistic substudy included small sample sizes, which may have limited conclusions about immune and hormonal findings.
“Any increase in prevalence of [abnormal uterine bleeding] due to COVID-19 [infections] has the potential to increase the gender health gap and add to the financial burden for health services and the economy,” said lead study author Jacqueline A. Maybin, PhD, of the Centre for Reproductive Health at the University of Edinburgh, and her colleagues.
The investigators concluded that long COVID was associated with abnormal uterine bleeding and symptom flare-ups during menstruation. The findings suggested that inflammatory and hormonal pathways may play a role, although ovarian function appeared preserved. Further studies are needed to clarify mechanisms and evaluate treatment strategies.
Full disclosures can be found in the study.
Source: Nature Communications
