New evidence shows long COVID may intensify bleeding and trigger phase-specific symptom surges, revealing hidden hormonal and immune disruptions in the menstrual cycle.
Study: The potential bidirectional relationship between long COVID and menstruation. Image Credit: Halfpoint / Shutterstock
In a recent study published in the journal Nature Communications, researchers determined whether post- coronavirus disease 2019 (COVID-19) condition (long COVID) is associated with abnormal uterine bleeding (AUB), using a definition of long COVID with symptoms persisting at least 28,30 days before the survey, whether long COVID symptoms fluctuate across the menstrual cycle, and which hormonal and inflammatory pathways may underlie these patterns.
Background
One in three women reports heavy periods, hurting work, sleep, and confidence. COVID-19 brought focus to cycles as infection, vaccination, and stress coincided with unexpected changes. AUB, as defined by the International Federation of Gynecology and Obstetrics (FIGO), is a common and major cause of iron-deficiency anemia.
Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) now circulates year-round, it is essential to understand how it may impact menstruation and daily life. Clear answers help people plan care, avoid missed days, and feel in control. Further research is needed to identify risks, mechanisms, and effective treatments.
About the study
In the present study, researchers combined three approaches. First, an online survey in the United Kingdom (UK) applied FIGO criteria to compare menstrual parameters among individuals who had never been infected, those recovered from acute COVID-19, and those with long COVID. After exclusions, 12,187 remained; covariates included age, body mass index (BMI), baseline menstrual features, exogenous hormones, and reproductive diagnoses.
Groups consisted of 9,423 individuals who were never infected, 1,716 who had recovered, and 1,048 with long COVID. Second, a prospective app-based cohort tracked 29 symptoms prospectively for three months across late secretory/menstrual, proliferative, and secretory phases in menstruating adults with long COVID.
Eligible participants were 21-50 years, had regular 24-38-day cycles, and were not pregnant, breastfeeding, or using a copper intrauterine device (IUD) or hormones. Multilevel Poisson, logistic, and cumulative-link models controlled false discovery.
Third, a laboratory study collected serum and endometrial tissue samples across the various phases. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to measure steroids.
Polymerase chain reaction (PCR) and immunohistochemistry assessed progesterone receptor (PGR), androgen receptor (AR), cytokines, and immune cells. Anti-Müllerian Hormone (AMH) was used to gauge ovarian reserve. Two-way analysis of variance (ANOVA) with the Tukey adjustment was used to compare groups and phases.
Study results
In the survey, long COVID was associated with heavier flow, longer periods, and spotting compared with never-infected controls. However, menstrual frequency and regularity were similar, and any small differences were not significant after adjusting for false-discovery rates. Relative to controls, the risk of heavier versus unchanged flow was markedly higher with long COVID, and periods exceeding eight days were roughly doubled.
This analysis used the subset with available period length data (n≈1,938). Intermenstrual bleeding increased, and missed or stopped periods were more common, whereas those who had recovered from an acute infection showed minimal, mostly transient changes. In the longitudinal cohort (n = 54), the number of distinct daily symptoms did not differ by phase; however, severity increased around menstruation.
Late secretory/menstrual days were associated with more severe dizziness, fatigue, post-exertional malaise, muscle aches, headaches, and tinnitus. Proliferative days showed a greater severity of breathing issues, headaches, and post-exertional malaise.
In the biological cohort, serum levels of 17β-estradiol and progesterone did not differ between individuals with long COVID and controls across phases, suggesting preserved ovulatory function. However, secretory-phase serum 5α-dihydrotestosterone (DHT) was higher in long COVID.
Endometrial tissue showed fewer AR-positive cells and lower AR histoscores during menstruation and the proliferative phase in long COVID, and lower proliferative-phase PGR messenger ribonucleic acid (mRNA), AMH was comparable.
In serum, tumor necrosis factor (TNF) was elevated during menstruation in long COVID, while interleukin-8 (IL-8) was lower in the proliferative phase, with similar trends observed for other cytokines. Paired analyses showed menstrual rises in interleukin-10 (IL-10) and interleukin-6 (IL-6) in long COVID only.
Endometrium at menstruation displayed lower TNF and IL-10 mRNA in long COVID, alongside visible aggregates of neutrophils and macrophages within glands on cluster of differentiation 68 (CD68) and cathelicidin LL-37 (LL-37) staining, without overall differences in cell counts.
Serum cortisol and cortisone did not differ by COVID-19 status, and endometrial glucocorticoids were broadly similar, however, the cortisol-to-cortisone ratio rose at menses in controls but not clearly in long COVID.
The menstrual phase did not alter symptom counts, and survey-level frequency and regularity remained unchanged, indicating that ovulation appeared intact, while volume, duration, and intermenstrual bleeding patterns shifted.
These findings are associative and come from UK-based cohorts with limited diversity and small mechanistic sample sizes, so they warrant confirmation in larger and more diverse populations. Collectively, findings indicate a bidirectional relationship: long COVID is associated with AUB, and menstrual phases characterized by progesterone withdrawal align with worse symptom severity, potentially via altered androgen signaling and phase-specific inflammation.
Analyses were adjusted for age, BMI, menstrual history, contraceptive use, and reproductive diagnoses to minimize confounding.
Conclusions
Long COVID appears to increase AUB (heavier flow, extended duration, and spotting) without disrupting ovulation, while several symptoms intensify around menstruation. Hormonal data reveal intact estradiol-progesterone cycles, alongside higher DHT and reduced endometrial AR and PGR. Cytokine profiles indicate heightened systemic inflammation at menses and altered local immune responses.
Clinically, screening for bleeding and potential iron deficiency, timely treatment, and symptom planning by cycle phase may improve quality of life. Randomized and mechanistic studies should test targeted anti-inflammatory or hormonal strategies and include diverse populations in real-world care settings globally.
Journal reference:
- Maybin, J. A., Walker, C., Watters, M., Homer, N. Z. M., Simpson, J. P., Robb, C., Gibson, D. A., Jeanjean, L., Critchley, H. O. D., Kountourides, G., Olszewska, Z., & Alvergne, A. (2025). The potential bidirectional relationship between long COVID and menstruation. Nature Communications, 16. DOI: 10.1038/s41467-025-62965-7, https://www.nature.com/articles/s41467-025-62965-7