Long COVID linked to abnormal uterine bleeding and hormonal changes

Abnormal uterine bleeding (AUB) and long COVID symptom severity may be influenced by differences in peripheral and endometrial inflammation, according to a recent study published in Nature Communications.¹

Women with long-term COVID-19 symptoms have reported menstrual disturbances, but data about contributors to these associations remains limited. However, multiple studies have reported menstrual disturbances in patients with acute COVID-19 infection.² Investigators hypothesized ovarian hormone fluctuations may also impact long COVID symptoms.¹

“However, the effects of the menstrual cycle on longer-term symptoms of COVID-19 remain under-researched,” wrote investigators.

Menstrual health measures

The study was conducted to assess the link between long COVID and AUB, alongside long COVID symptom severity in patients with altered ovarian sex hormones. Information was collected through an online survey launched on March 8, 2021, based on feedback from women impacted by long COVID.

There were 105 questions included in the survey, collecting data about pre-pandemic life circumstances and health, behaviors, menstrual cycles, and COVID-19 disease and vaccination history. Respondents included patients aged over 18 years with a history of menstruation residing in the United Kingdom and providing informed consent.

A question asking how many days on average a patient’s cycle lasted in the last year was used to determine cycle frequency, with responses of 24 to 38 days, under 24 days, and over 38 days. There was also a question about the irregularity of cycles on average. Normal cycles were defined as up to 10 days, somewhat irregular 10 to 20 days, and very irregular over 20 days.

Additional questions asked patients about the duration of menstrual cycles, volume of bleeding, and intermenstrual bleeding. Covariates included sociodemographic variables, standard proxies for health, and pre-pandemic reproductive variables.

Menstrual frequency and regularity

There were 12,187 participants included in the final analysis, 77% of whom had never been diagnosed with COVID, 14% reported prior acute COVID infections, and 9% had long COVID. Median ages in these groups were 32, 31, and 36 years, respectively.

COVID vaccination was reported by 40% of participants, nulliparity by 64%, university or college degree by 47%, and 1 or more abnormal menstrual symptoms by 57%.

For menstrual frequency, 71% of participants reported normal cycles, 26% frequent cycles, and 3% infrequent cycles. No significant variations in the risk of abnormal frequency were observed based on COVID status.

Menstrual regularity rates were also similar between groups, as those with long COVID reported a 39% increased risk of reporting somewhat irregular vs regular cycles; this difference was not statistically significant. Nearly 80% of patients reported regular cycles, while approximately 20% reported somewhat or very irregular cycles.

Other menstruation characteristics and COVID symptoms

The odds of heavier vs normal flow volume were increased in patients with prior COVID-19 infection and with long COVID vs controls, with increased rates of 19% and 93%, respectively. Lighter and heavier flow vs no changes was also 57% more common in those with long COVID.

A 2-fold rise in rates of menstruation lasting over 8 days was observed in long COVID patients vs controls, while no significant increase was observed in patients with acute COVID infection. Additionally, the acute COVID group reported no changes in intermenstrual bleeding, while a 59% increase was found in long COVID patients.

No significant differences were reported in the median number of patient-defined long COVID symptoms based on a specific phase of the menstrual cycle, nor were there differences based on the phase of the menstrual cycle. However, chills and sweats, alongside vision issues, were more common in the late secretory/menstrual phase.

During testing with polymerase chain reaction, reduced progesterone receptor mRNA was reported in long COVID patients vs controls during the proliferative phase. Additionally, significantly fewer % positive cells were identified in long COVID patients during the secretory phase.

Implications

Overall, a link was identified between long COVID and AUB, potentially influenced by increased androgens and an altered endometrial inflammatory response at menstruation. Investigators noted that ovarian function is maintained in these patients.

“Based on our findings, we recommend future investigation of specific treatments for AUB in those with long COVID, consideration of the menstrual cycle in future long COVID biomarker development, and a focus on female-specific treatments for long COVID,” wrote investigators.

References

1. Maybin JA, Walker C, Watters M, et al. The potential bidirectional relationship between long COVID and menstruation. Nat Commun 2025;16. doi:10.1038/s41467-025-62965-7
2. Alvergne A, Kountourides G, Argentieri MA, et al. A retrospective case-control study on menstrual cycle changes following COVID-19 vaccination and disease. iScience. 2023;26(4):106401. doi: 10.1016/j.isci.2023.106401