Long COVID associated with abnormal uterine bleeding and cycle-phase symptom variation

The Center for Reproductive Health, University of Edinburgh reports that long COVID was associated with abnormal uterine bleeding in a UK population, with increased menstrual volume, longer duration and more intermenstrual bleeding with no impaired ovarian function, alongside differences in peripheral and endometrial inflammation.

Pre-pandemic abnormal uterine bleeding was already considered common and burdensome. One in three women reported excessive menstrual loss, rising to one in two near menopause. Over 800,000 women seek treatment for heavy menstrual bleeding each year in the UK, and annual indirect costs of menstrual bleeding disorders in the US have reached $12 billion.

Pandemic-era reports describe cycle changes after infection, vaccination or stress-related shifts with small, transient changes in menstrual frequency after vaccination and larger associations reported after SARS-CoV-2 infection. Long COVID has affected more women than men and details on the specific types of menstrual disturbance remain sparse with undefined mechanisms.

In the study, “The potential bidirectional relationship between long COVID and menstruation,” published in Nature Communications, researchers combined a UK survey, a prospective symptom-tracking cohort and timed serum and endometrial sampling to test whether long COVID is associated with abnormal uterine bleeding, whether symptom severity varies by menstrual phase and which endocrine or inflammatory mechanisms may be involved.

A UK online survey enrolled 12,187 participants after exclusions, including 9,423 with no COVID diagnosis, 1,716 with previous acute COVID and 1,048 with long COVID. An app-based cohort contributed daily symptom entries from 54 regularly cycling women with long COVID.

Timed biological sampling drew serum from 10 women with long COVID at NHS Lothian in Scotland, with comparisons to pre-pandemic controls comprising 40 women with 54 serum samples and 32 endometrial samples; seven long COVID participants provided endometrial biopsies. An additional COVID-recovered serum cohort included 10 women.

Survey data linked long COVID with heavier menstrual flow compared with no COVID, a higher prevalence of periods lasting longer than eight days, more intermenstrual bleeding, and more missed or stopped periods. Menstrual frequency and regularity did not differ meaningfully across groups.

Symptom severity peaked during the late secretory or menstrual phase and during the proliferative phase. Secretory-phase serum 5α-dihydrotestosterone was higher in long COVID.

Estradiol, progesterone and Anti-Müllerian hormone showed no group differences. Endometrium showed fewer androgen receptor–positive cells at menstruation and lower androgen receptor histoscores during menstruation and the proliferative phase. Serum tumor necrosis factor was higher during menstruation in long COVID, and immune cell aggregates appeared within menstrual endometrium.

Authors conclude that long COVID is associated with abnormal uterine bleeding while ovarian function appears preserved with androgen regulation and inflammatory differences the likely cause. The team recommends investigation of targeted treatments in those with long COVID, with attention to the menstrual phase in biomarker development.

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