Key points
- International Women’s Day (IWD) is both a call to accelerate progress toward gender equality and a moment to highlight discrimination based on sex, and its consequences.
- ME/CFS research has been delayed due to systemic prejudice against women, known as ‘medical misogyny’ in healthcare that leads to their concerns being dismissed or minimised.
- Studies have shown differences between men and women with ME/CFS, for example; sex-based ‘cardiometabolic’ (relating to both the heart and blood vessels, and energy production and utilisation in the body) differences.
- Differences in male and female hormones – and the onset of reproductive hormonal events – may contribute to these differences.
- In 2025, a small study in Pakistan found that ME/CFS symptom burden appears to be highest when female reproductive hormones oestrogen and progesterone are lowest: in the second half of the menstrual cycle (known as the luteal phase), in perimenopause (here oestrogen levels fluctuate), and post-menopause.
- A review published in 2023 made similar observations, stating that hormonal changes during the menstrual cycle, particularly prior to menstruation, perimenopause, menopause and post-menopause, may all exacerbate symptoms, or act as a trigger for ME/CFS.
- Delays in ME/CFS research due to medical misogyny have not only impacted women with the disease, but have delayed understanding for all.
- Much more research is needed to better understand both sex differences in ME/CFS, and the link with reproductive hormones; especially considering female hormonal events such as menstruation, pregnancy, and menopause.
Introduction
International Women’s Day (IWD) is both a call to accelerate progress toward gender equality and a moment to highlight discrimination based on sex, and its consequences.
In 2025, Professor Chris Ponting, lead of the DecodeME study and an ME Research UK-funded researcher, stated that ME/CFS research has been delayed due to “medical misogyny” — systemic prejudice against women in healthcare that leads to their concerns being dismissed or minimised.
This means that because ME/CFS is more common in women than in men (at a ratio of approximately 4:1), research into the disease — as with other illnesses that are more common in women than in men, such as endometriosis, fibromyalgia, and lupus — has not progressed as quickly as it would have done had all things been equal.
Previously highlighted by ME Research UK, the fields of medicine and medical research have been dominated by white men. Historically, the white male body was used as the default human body from which medical students learned about diseases that occur in both sexes, and across other ethnic groups. This has further delayed understanding and contributed to the stigma and bias that still exist today for diseases more common in women than men, including ME/CFS. It also means that people from black and minority ethnic groups face additional disadvantages.
Over the years, there have also been restrictions on women’s participation in research. Scientists at the time – who were predominantly white men – viewed women as more complex due to hormonal fluctuations, and were concerned about potential adverse effects on reproductive health. While there have been much needed updates to policy to ensure the inclusion of women, these changes have not been enough to undo the many years where women were not adequately represented in medical research.
Due to the fact that women’s bodies were (and regrettably still are) not as well understood as men’s, there was a widely held view that unexplained illnesses in women, such as ME/CFS, were psychiatric and often referred to as “hysteria”. One example is the 1955 outbreak of an unknown illness among predominantly female nursing staff at the Royal Free Hospital in London. Although in The Lancet in 1956 the illness was termed “benign myalgic encephalomyelitis”, in 1970 two male physicians, McEvedy and Beard, published an article in the British Medical Journal labelling the outbreak as “epidemic hysteria”. While McEvedy and Beard’s paper has since been refuted on many occasions — including in a 2020 article which found that, when re-evaluated, the results were “mathematically incorrect” — many people, sadly including some researchers and health professionals, continue to hold the erroneous view that ME/CFS is psychological in nature.
Further evidence of delays in ME/CFS research progress due to misconceptions that the disease is psychological comes from Professor Maureen Hanson, who, in an article on the viral origins of ME/CFS, recalled that in the 1980s, some outbreaks were not recorded by the Centers for Disease Control and Prevention (CDC) because they were classified as “hysteria” rather than as physical illness. Importantly, this meant that crucial information — such as potential infectious agents — was not collected, hampering advances in understanding how different microorganisms may be linked to the onset of ME/CFS.
Overall, this means that illnesses more common in women than in men have suffered delays in understanding, and chronic underfunding — something that is unfortunately still true for ME/CFS today, particularly in relation to areas of women’s health like the menstrual cycle, pregnancy, and menopause.
What does the limited evidence tell us about women’s health issues and ME/CFS?
Although women’s health and ME/CFS is a severely under-researched area, the limited studies that do exist suggest that ME/CFS symptoms and severity may fluctuate with hormonal changes during the menstrual cycle, and could even change following menopause; a natural, permanent decline in the sex hormones oestrogen and progesterone, typically resulting in symptoms like hot flashes and bone density changes.
Observations made in a review paper, published in 2023, by Dr. Beth Pollack and colleagues, identified that hormonal changes during the menstrual cycle, particularly prior to menstruation, perimenopause, menopause, and post-menopause, may all exacerbate symptoms, or could even act as a trigger for ME/CFS.
More recently, in 2025, a team of researchers in Karachi, Pakistan, conducted a study of 150 women who met the IoM diagnostic criteria for ME/CFS. Amongst the participants, 90 were pre-menopausal and still experiencing regular periods, 30 were peri-menopausal (the transitional, often 4-to-10-year, period before menopause where oestrogen levels fluctuate, typically beginning in a woman’s 40s), and 30 were post-menopausal (had permanently decreased levels of oestrogen and progesterone). Regrettably, this study did not have a healthy control group.
The researchers followed the women up between January 2024 and June 2025 to assess the relationship between ME/CFS and reproductive hormones and found that their results suggested a link between lower sex hormones and a higher ME/CFS symptom burden. Key observations were that:
- ME/CFS symptom burden appeared to be highest in the second half of the menstrual cycle – known as the luteal phase – when oestrogen and progesterone fall.
- ME/CFS symptoms were worse for those in the peri- and post-menopausal groups compared with those who were pre-menopausal.
Reflecting on their findings, the authors stated:
“These findings support the theory that changes in sex hormones throughout the menstrual cycle exert a measurable influence on symptom severity, particularly for fatigue, pain, and cognition, with the luteal phase identified as the period when pre-menopausal women with ME/CFS are most symptomatic”
Interestingly, there has also been a link identified between ME/CFS and endometriosis. A systematic review of 13 studies, published in the journal diagnostics, found that women with endometriosis were 2.79 times more likely to have ME/CFS (diagnosed using a number of different methods including self-report, Fukuda criteria for CFS (this criteria does not require post exertional malaise for a diagnosis to be made), Canadian Consensus Criteria for ME/CFS, and the Institute of Medicine Criteria for ME/CFS) compared to those without endometriosis, and women with ME/CFS were 2.52 times more likely to have a diagnosis of endometriosis. The authors of the review suggested that the link may be explained as the two illnesses are though to share disease mechanisms, specifically immune dysregulation and chronic inflammation.
It is worth noting that, in contrast with the luteal phase and post menopause, endometriosis is usually characterised by high oestrogen levels and progesterone resistance, which together fuel inflammation, pain, and tissue growth. More research is needed to establish how ME/CFS and endometriosis may be linked using ME/CFS criteria which require the presence of post exertional malaise for a diagnosis to be made. It is possible in the above study that combining people who were not all diagnosed using the same criteria may have impacted the results.
How might reproductive hormones link to ME/CFS symptoms?
In the paper by Dr Khan and colleagues, the authors explain that oestrogen promotes:
- A complex biological process, known as ‘mitochondrial biogenesis’ – which is crucial for energy production – in which new mitochondria (often referred to as the energy powerhouses of our cells) are formed from pre-existing ones.
- ‘Oxidative phosphorylation’ – the final stage of a process in the body, known as aerobic respiration, which produces the molecule – Adenosine Triphosphate (ATP) – that powers all cellular processes, including muscle contraction and nerve transmission.
- Anti-inflammatory signalling pathways.
While not discussed in the paper, progesterone is a hormone said to be crucial for energy production and utilisation (metabolism), brain function, and the generation of corticosteroids, which are involved in processes such as the stress response, immune response, and regulation of inflammation, carbohydrate metabolism, breakdown of protein molecules, and blood electrolyte levels.
Therefore, although much more research is needed, it is possible that low levels of oestrogen and progesterone could contribute to impaired energy metabolism, a dysregulated immune response, increased inflammation, altered brain function, and dysregulation of blood electrolyte levels – all of which have been linked with ME/CFS.
A further point worth considering here is that many people with Postural Orthostatic Tachycardia Syndrome (POTS), a debilitating, under-recognised condition and co-morbidity of ME/CFS, find that their symptoms worsen during their menstrual cycle. It is thought that hormonal changes, alongside blood volume fluctuations, histamine release, and temperature regulation changes, could explain the relationship between POTS and menstruation.
Where next?
A paper has been published outlining the methods for a study which aims to map the menstrual cycle – and biological process that repeats every 24 hours (diurnal rhythms), heavily influenced by environmental cues like light and darkness, such as the sleep-wake cycle and daily hormone changes – in people with ME/CFS (meeting the NICE criteria), and in those with long COVID.
Importantly, this study, entitled ‘MELLOW’, will follow the study population up over time enabling the researchers to map temporal links between hormonal, molecular, physiological, and ME/CFS symptom dynamics.
Conclusions
Research suggests that in women, ME/CFS symptoms and severity are impacted by fluctuating reproductive hormone levels – not only during the menstrual cycle, but also during peri- and post-menopause. Less is known about the impact of hormones during pregnancy and lactation, but systematic review evidence has indicated that these reproductive events may also have an impact on ME/CFS symptoms and severity.
Delays in ME/CFS research due to medical misogyny have not only impacted women with the disease, but have delayed understanding for all. Regrettably, some groups within the population – underserved groups – are impacted by a lack of research into ME/CFS generally, but also receive less than adequate access to resources, services, or representation due to factors such as ethnicity, sexuality, geographic location, or social and economic position.
Much more research is needed to better understand the links between hormone fluctuations and ME/CFS symptoms and severity, and the MELLOW study appears to be a key initial step in this journey. Importantly, when designing future studies researchers must follow participants up over time and ensure that they consider “intersectionality”, a term coined by Kimberlé W. Crenshaw in 1989 to help people understand “the ways that multiple forms of inequality or disadvantage sometimes compound themselves and create obstacles that often are not understood among conventional ways of thinking”.
