Reviewed by Dr Chris Armstrong, senior author and director of the Melbourne ME/CFS Collaboration, University of Melbourne.
For decades, hormone studies in ME/CFS and Long COVID have produced conflicting results. A 2026 review led from the University of Melbourne offers a possible explanation: researchers may have been measuring the right system, but in the wrong way.
Key points
- A 2026 review in Frontiers in Neuroendocrinology, led by Dr Natalie Thomas in Dr Chris Armstrong’s group at the University of Melbourne, argues that hormone research in ME/CFS and Long COVID has been inconsistent because hormones were measured as single, static snapshots rather than across their natural rhythms.
- The review proposes a “chronobiological framework”: measuring hormones across the body’s daily (circadian) and menstrual rhythms and integrating that with other biological data, so that disruptions in the timing of hormone signals, not just their levels, can be detected.
- Because ME/CFS and Long COVID affect women at far higher rates, the review identifies sex hormone signalling as a central line of inquiry rather than a variable to control for.
- The paper was authored by researchers at OMF’s Melbourne ME/CFS Collaboration at the University of Melbourne, MIT, Monash University, Stellenbosch University and OMF’s Collaborative Research Centre at Uppsala University, reflecting Open Medicine Foundation’s globally coordinated research model.
Why have hormone studies in ME/CFS been so inconsistent?
Hormones have often been measured as single, static snapshots: one sample, at one time of day, without accounting for sleep, the menstrual cycle, or sex. But the neuroendocrine system is not static. It runs on rhythms across the day, across the menstrual cycle, and in response to exertion, so measuring a hormone once can miss the very thing that is disrupted: its timing. That helps explain why a hormone such as cortisol, which regulates energy, immunity and the stress response, may look low in one study and normal in the next.
What is a chronobiological framework for studying hormones?
The chronobiological framework proposed by Dr Natalie Thomas and colleagues means measuring hormones across their natural circadian (daily) and menstrual rhythms, integrating that with other biological data, and building the timing of each measurement into the study design rather than treating it as an afterthought. The goal is to detect disruptions in the timing, coupling and responsiveness of hormone signals, not just their concentration.
What could this mean for patients?
If hormone signalling is disrupted mainly through its timing rather than through absolute hormone levels, then future diagnostic tests and treatments may need to focus on restoring the body’s natural rhythms rather than simply measuring hormone levels or attempting to correct them directly. The review is a framework for research rather than a treatment, but it points future work toward the questions most likely to help patients.
Why do the menstrual cycle and sex matter in this research?
Both ME/CFS and Long COVID affect women at far higher rates than men. The review by Dr Natalie Thomas and Dr Chris Armstrong’s group treats sex hormone signalling, reproductive stage and menstrual-cycle dynamics as a central line of inquiry rather than a variable to control for, while noting that men and gender-diverse patients remain under-studied and should be included more deliberately.
Who led the study, and where was it done?
The review was led by Dr Natalie Thomas, a post-doctoral researcher and the endocrinology lead in Dr Chris Armstrong’s group at the University of Melbourne, who is first and corresponding author. Dr Chris Armstrong is senior author. The work was co-authored by researchers at OMF’s Melbourne ME/CFS Collaboration at the University of Melbourne, MIT, Monash University, Stellenbosch University and the OMF Collaborative Research Centre at Uppsala University. It reflects the growing contribution of Dr Natalie Thomas, Dr Chris Armstrong and their colleagues to the international conversation about hormones in ME/CFS and Long COVID.
There is still a long way to go. Neither illness has a diagnostic test or an approved treatment, and for many patients that wait has been far too long. But the direction is clearer than it has been in years, and Australian researchers are helping shape that direction as part of a global effort. That progress is what your support helps build.
Open Medicine Foundation Australia funds and supports ME/CFS and Long COVID research as part of Open Medicine Foundation’s global network of Collaborative Research Centres. The Melbourne ME/CFS Collaboration, led by Dr Chris Armstrong at the University of Melbourne, is the Australian research engine within that network.