Digital health app data reveals an effect of ovarian hormones on long COVID and myalgic encephalomyelitis symptoms
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Background
Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) disproportionately affect females, suggesting modulation by sex hormones. We sought to investigate whether symptom severity is influenced by changes in sex hormones over the menstrual cycle, or by hormonal contraception.
Methods
We carried out a retrospective analysis of menstrual and symptom data, prospectively collected via the Visible app from individuals with long COVID, ME/CFS, or both, who had regular menstrual cycles, between 7th September 2022 and 6th March 2024. Mixed-effects models were used to examine associations between symptom severity, menstrual cycle phase and contraception type.
Findings
948 users were included; 100% of users were female and 92.6% identified as women. The most tracked symptoms were fatigue (99·5% of users), brain fog (88·3%), headaches (85·1%) and muscle aches (78·6%). All menstrual cycle phases showed a modest, but significant, improvement compared to the menstrual phase, most markedly the early luteal (IRR = 0·963, 95% CI: 0·958–0·968), but also the follicular (IRR = 0·985, 95% CI: 0·981–0·990) and late luteal phases (IRR = 0·980, 95% CI: 0·974– 0·985). Crashes (sudden and severe worsening of symptoms following exertion) were significantly more frequent during menstruation than in other phases. Users of combined hormonal contraception (n=70) had a statistically significant reduction in overall symptom score (OR = 0·827, 95% CI: 0·690–0·992) and crash incidence (OR = 0·548, 95% CI: 0·350–0·856) compared to those not using contraception (n=786).
Interpretation
Menstruation is associated with worsened symptoms in long COVID and ME/CFS. Users of combined hormonal contraception report a lower symptom burden than non-users, suggesting a modulatory role of ovarian hormones. These findings could empower menstruating people living with long COVID and ME/CFS to anticipate cyclical changes in symptoms and plan their activities accordingly, and could also inform their use of contraception.
Funding
UK Medical Research Council, NIHR, Community Jameel, the Eric and Wendy Schmidt Fund for Strategic Innovation, Bill & Melinda Gates Foundation, Borne, Action Medical Research, and Genesis Research Trust.
