Effect of ovarian hormones on long COVID and myalgic encephalomyelitis: an analysis of prospectively collected digital health app data
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Author(s)
Type
Journal Article
Abstract
Background
Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) disproportionately affect females, suggesting modulation by sex hormones. We aimed to determine whether symptom severity is affected by changes in sex hormones over the menstrual cycle or by hormonal contraception.
Methods
We analysed data prospectively collected via the Visible app from individuals with long COVID, ME/CFS, or both (7th September 2022-6th March 2024). We examined associations between symptom severity, menstrual cycle phase and contraception type using mixed-effects models. Users of the Hertility menstrual cycle tracking app (7th September 2022-28th September 2025) formed a population comparison cohort.
Findings
948 users were included in the disease cohort, and 501 users in the population cohort, all of which were female. 92.6% (878/948) of the disease cohort and 99.6% (499/501) of the population cohort identified as women. Crashes (sudden and severe worsening of symptoms following exertion) were significantly more frequent during menstruation than other phases (odds ratio (OR) compared with the late luteal phase = 0·888, 95% confidence interval (CI): 0·838-0·941). Users of combined hormonal contraception (n=70) had reduced crash incidence (OR = 0·548, 95% CI: 0·350–0·856) and overall symptom score (incidence rate ratio = 0·827, 95% CI: 0·690–0·992) compared to those not using contraception (n=786). Fatigue, brain fog, and headache showed phase-specific variation in both disease and population cohorts, albeit that these are less frequently reported in the population cohort.
Interpretation
Our findings suggest a role for ovarian hormones in modulating symptoms. We adjusted for individual, disease type, age and gravidity, however, residual confounding accounting for differences in disease severity associated with contraceptive use cannot be excluded. Nevertheless, these findings could empower menstruating people living with long COVID and ME/CFS to plan activities around cyclical changes in symptoms and could also inform their use of contraception.
Funding
The Medical Research Council (MR/W00710X/1).
Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) disproportionately affect females, suggesting modulation by sex hormones. We aimed to determine whether symptom severity is affected by changes in sex hormones over the menstrual cycle or by hormonal contraception.
Methods
We analysed data prospectively collected via the Visible app from individuals with long COVID, ME/CFS, or both (7th September 2022-6th March 2024). We examined associations between symptom severity, menstrual cycle phase and contraception type using mixed-effects models. Users of the Hertility menstrual cycle tracking app (7th September 2022-28th September 2025) formed a population comparison cohort.
Findings
948 users were included in the disease cohort, and 501 users in the population cohort, all of which were female. 92.6% (878/948) of the disease cohort and 99.6% (499/501) of the population cohort identified as women. Crashes (sudden and severe worsening of symptoms following exertion) were significantly more frequent during menstruation than other phases (odds ratio (OR) compared with the late luteal phase = 0·888, 95% confidence interval (CI): 0·838-0·941). Users of combined hormonal contraception (n=70) had reduced crash incidence (OR = 0·548, 95% CI: 0·350–0·856) and overall symptom score (incidence rate ratio = 0·827, 95% CI: 0·690–0·992) compared to those not using contraception (n=786). Fatigue, brain fog, and headache showed phase-specific variation in both disease and population cohorts, albeit that these are less frequently reported in the population cohort.
Interpretation
Our findings suggest a role for ovarian hormones in modulating symptoms. We adjusted for individual, disease type, age and gravidity, however, residual confounding accounting for differences in disease severity associated with contraceptive use cannot be excluded. Nevertheless, these findings could empower menstruating people living with long COVID and ME/CFS to plan activities around cyclical changes in symptoms and could also inform their use of contraception.
Funding
The Medical Research Council (MR/W00710X/1).
Date Acceptance
2026-08-11
Citation
The Lancet: Digital Health
ISSN
2589-7500
Publisher
Elsevier
Journal / Book Title
The Lancet: Digital Health
Copyright Statement
Copyright This paper is embargoed until publication. Once published the Version of Record (VoR) will be available on immediate open access.
License URL
Publication Status
Accepted