Publication date: Jan 26, 2025
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 7 September 2022 and 6 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 compare to the menstrual phase, most markedly in 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 phase (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 hormonal contraception (=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.
| Concepts | Keywords |
|---|---|
| Arthritis | Cfs |
| Males1617 | Contraception |
| Ovarian | Covid |
| Viral | Cycle |
| Day | |
| Days | |
| Hormonal | |
| Hormones | |
| Long | |
| Menstrual | |
| Period | |
| Phase | |
| Phases | |
| Symptom | |
| Symptoms |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | long COVID |
| disease | MESH | myalgic encephalomyelitis |
| disease | IDO | symptom |
| disease | MESH | brain fog |
| disease | MESH | symptom burden |
| disease | IDO | role |
| pathway | REACTOME | Metabolism |
| pathway | REACTOME | Digestion |
| pathway | REACTOME | Reproduction |
| drug | DRUGBANK | Etodolac |
| disease | MESH | COVID 19 |
| disease | MESH | infections |
| disease | IDO | infection |
| disease | MESH | insomnia |
| disease | MESH | viral infection |
| disease | MESH | autoimmune disease |
| drug | DRUGBANK | Progesterone |
| drug | DRUGBANK | Testosterone |
| disease | MESH | rheumatoid arthritis |
| pathway | KEGG | Rheumatoid arthritis |
| disease | MESH | inflammatory bowel disease |
| pathway | KEGG | Inflammatory bowel disease |
| disease | MESH | multiple sclerosis |
| disease | MESH | asthma |
| pathway | KEGG | Asthma |
| disease | IDO | susceptibility |
| disease | MESH | chronic conditions |
| disease | MESH | death |
| disease | MESH | relapses |
| disease | MESH | symptom exacerbation |
| disease | MESH | Gravidity |