In April 2020, a manager working in a big company in Kuala Lumpur was on her way to promotion, unaware that her life and career were about to be derailed by a virus still poorly understood at the time. COVID-19 struck, and what started as migraine headaches soon turned into a relentless onslaught of symptoms now recognised as long COVID—fatigue, pain, insomnia, and gastrointestinal issues. Among these, one symptom stood out for her and countless other women across the globe: unexpected and distressing changes to the menstrual cycle.

Prior to infection, her periods were textbook regular, controlled by a hormonal IUD—minimal discomfort, light bleeding, nothing out of the ordinary. Suddenly, her periods vanished. For years, there was silence. Then, just as mysteriously as they had disappeared, they returned with a vengeance: heavy, prolonged bleeding that left her drained and exacerbated her post-viral malaise. This is not a rare story. This is an anecdote that many women share.

Across continents, women report similar disruptions to their reproductive health following COVID-19. The experience has launched a new wave of scientific inquiry into why women appear more susceptible to chronic conditions like long COVID.

A landmark study published in JAMA Network Open and conducted under the National Institutes of Health’s RECOVER initiative has shed light on the scale of the problem.

Analysing data from more than 12,200 COVID-19 survivors between 2021 and 2024, researchers found that women have a strikingly higher risk of developing long COVID compared to men—between 31% and 44% more likely, even after accounting for differences in age, race, and underlying health conditions. This disparity is most pronounced among younger women who are neither pregnant nor menopausal.

These findings are significant. For years, chronic illnesses that predominantly affect women have been marginalised in medical research. Now, five years into the pandemic, the science is catching up. Researchers are beginning to map out how biological sex, pregnancy status, hormonal cycles, and life stage all interact with the risk of developing long COVID. Experts involved in the RECOVER initiative call this a novel development in understanding post-viral illnesses.

The study goes further. Pregnant women in their late teens to late thirties showed a lower risk of long COVID compared with nonpregnant women of similar age. Likewise, menopausal women between forty and fifty-four had a reduced risk compared to their nonmenopausal peers. These patterns suggest hormonal changes and shifting immune responses with age may play a crucial role.

Why does this matter? The implications reach far beyond epidemiology. Identifying which groups are at heightened risk could unlock targeted therapies and improve patient care. Yet, the complexity of long COVID means that easy answers remain elusive.

Current research highlights four main theories for its cause: persistent viral infection, reactivation of dormant viruses (like herpes), ongoing tissue and organ inflammation, and autoimmunity—when the immune system starts attacking the body itself.

Of these four, autoimmunity offers some of the most intriguing clues about why women are disproportionately affected. Scientists note that women possess two X chromosomes. While one is usually switched off in each cell, this inactivation is incomplete. Some key immune genes remain active on both chromosomes.

The result? A more robust immune response to infections and vaccines—but also a greater risk of immune overreaction and autoimmunity.

Sex hormones further complicate the picture. Testosterone tends to suppress immune activity; men may be more likely to suffer severe acute COVID infections but less likely to linger with chronic symptoms. Oestrogen, by contrast, boosts immune responses—helpful for fighting viruses but potentially fuelling persistent inflammation after the acute phase has passed. This dynamic may explain why symptoms like severe fatigue or menstrual disruptions are so prevalent among female long COVID patients.

Researchers stress that much remains unknown regarding hormone levels and immune function during different life stages. There is an urgent need for further studies examining how pregnancy and menopause influence immune responses to COVID-19 and other viruses.

Another compelling thread emerging from recent research involves the field sometimes called “menstrual science”. Long COVID is not only linked with classic symptoms like brain fog or shortness of breath; it is increasingly associated with disruptions to menstrual cycles and female reproductive health more broadly.

A review published in 2023 highlights reports from women experiencing heavier periods, missed cycles, or worsened premenstrual symptoms after contracting COVID-19.

This connection hints at a broader relationship between sex hormone fluctuations and immune dysfunction—a relationship historically overlooked by mainstream medicine. Researchers urge greater investment in studies focusing on female-specific symptoms, noting that conditions like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which shares many features with long COVID, have long been neglected despite their high disease burden.

Symptom profiles differ by sex in other ways too. Recent research points to hair loss as an overwhelmingly female-dominant symptom of long COVID, while sexual dysfunction appears more often among men. These observations underscore the importance of tailoring medical care to individual patient experiences—especially as millions now contend with lingering effects of the virus.

The story does not end with biological sex alone. Transgender individuals report higher rates of long COVID than cisgender people—a phenomenon currently under investigation. Anecdotal evidence suggests that testosterone therapy may alleviate symptoms for some female-to-male trans individuals, offering tantalising clues about the role of hormones in recovery from post-viral syndromes. However, experts caution that social factors—such as barriers to healthcare or discrimination—also contribute to heightened vulnerability in trans communities.

What could the future hold? A simple blood test diagnosing long COVID could transform care for patients while dispelling outdated misconceptions about the condition’s legitimacy. Such advances would not only validate patients’ experiences but also pave the way for treatments tailored to hormonal profiles and immune signatures at different life stages.

Medical leaders are optimistic that understanding these biological nuances will eventually lead to targeted therapies and improved outcomes for those most at risk. Until then, raising awareness is crucial—both for clinicians and for patients themselves. Women presenting with persistent symptoms after COVID-19 infection should not dismiss their experiences or hesitate to seek medical advice.

This evolving research has significant public health implications. As new findings come to light, clinics could refine their diagnostic criteria and offer more personalised care based on age, sex, pregnancy status or menopausal stage. Policymakers may be encouraged to allocate more resources toward studying complex chronic illnesses—an area historically underfunded despite its impact on millions worldwide.

The story of long COVID is still being written. Each new study adds a piece to the puzzle: Why do some recover swiftly while others endure months or years of debilitating fatigue? How do hormonal cycles amplify or mitigate these risks? What are the broader implications for our understanding of chronic illness?

For now, one message rings clear: taking sex differences in long COVID seriously is not only an issue of scientific curiosity but also one of equity in healthcare delivery. By listening to patients’ stories and investing in rigorous research, the medical community can move closer to unlocking treatments that work for everyone—regardless of sex or life stage.