GAtherton

Debate: Gender Bias in Science and Clinical Trials & Why It Matters to Patients

Introduction: A History of Exclusion For decades, medical research and clinical trials were built around a default male body. Women were routinely excluded from studies out of concern for hormonal variation, pregnancy risks, or assumptions that female responses would mirror male ones. The consequences? Misdiagnoses, incorrect dosing, side effects overlooked in women, and entire conditions dismissed as psychological.

This pattern of systemic gender bias has had real-life consequences for millions of women, especially those living with chronic or misunderstood illnesses like ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome), long COVID, autoimmune diseases — and potentially, aspergillosis.

Section 1: Real Consequences of Exclusion

Why Gender Bias Matters in Asthma and Aspergillosis
Both asthma and aspergillosis are diseases where gender can influence immune response, disease progression, and side effects of treatment. Women are more likely to develop certain asthma subtypes (e.g., late-onset eosinophilic asthma), which overlap with allergic fungal conditions like ABPA. They may also experience more frequent exacerbations and are more vulnerable to long-term steroid side effects such as adrenal insufficiency and bone loss. Despite this, sex-specific analysis is rare in fungal disease trials, and asthma research has only recently begun to explore these differences.

Is Gender Relevant in Aspergillosis? While aspergillosis affects people of all sexes, some patterns suggest potential sex differences in prevalence, diagnosis, immune response, and treatment side effects:

• Chronic Pulmonary Aspergillosis (CPA) appears more common in men, especially in post-TB or COPD populations, but women may experience more severe fatigue or be underdiagnosed.
• In ABPA (Allergic Bronchopulmonary Aspergillosis), hormonal differences may influence disease severity, and women often report more exacerbations or sensitivity to long-term steroid treatment.
• Invasive aspergillosis is less well studied for sex differences, though some research in animal models suggests hormonal influences on fungal immunity.
• Women may also be more vulnerable to side effects of antifungals and corticosteroids, such as adrenal suppression, hearing loss, or osteoporosis.

Despite these observations, most clinical studies do not stratify by sex or explore gender-specific differences, leaving important questions unanswered.

A Message to Women Living with Aspergillosis
If you're reading this as a woman affected by aspergillosis, please don’t feel discouraged. While we highlight gaps in past research, the goal is to push for better inclusion, not to suggest you're being overlooked in care. You are not alone. Clinicians are becoming more aware of these issues, and researchers — especially in the UK — are actively working to close the gender gap. Patient groups and specialist centres like the NAC are also strong advocates for fair, personalised treatment. Your voice matters, and being informed is a powerful step in making future care better for everyone.

Clinical trials that exclude or underrepresent women have led to:

• Drugs that stay longer in women's bodies (e.g., Zolpidem) causing next-day drowsiness and driving risk
• Heart medications being under-prescribed to women, because early trials only studied men
• Misunderstanding of how autoimmune diseases develop and respond to treatment
• Failure to understand symptoms unique to women, such as how heart attacks present differently

Historically, women were also more likely to have their physical symptoms dismissed as anxiety or "hysteria." ME/CFS, a condition affecting mostly women, was dismissed for decades as psychological. When patients with ME later caught COVID-19, many were again left behind as new post-viral syndromes took priority.

For patients with aspergillosis, particularly chronic forms like CPA or ABPA, the relevance is clear. These conditions are under-researched and under-recognised, and early studies may not fully reflect how they impact women. Steroid-related side effects like osteoporosis, adrenal suppression, and hearing loss may differ by sex — yet sex-stratified data is rarely available.

Section 2: Has Anything Changed?

Yes. In the UK, the National Institute for Health and Care Research (NIHR) and the Medical Research Council (MRC) have taken steps to improve inclusion:

• NIHR-funded studies are expected to include representative populations and report on diversity
• UK Research and Innovation (UKRI) promotes equality in trial design, including sex and gender analysis
• The DecodeME study (the world’s largest ME/CFS genetics study, based in the UK) is actively engaging with female participants

But gaps remain — especially in rare diseases, chronic illnesses, and reproductive health. For fungal disease and aspergillosis specifically, many trials still do not analyse sex-specific outcomes, despite women forming a significant proportion of the affected population.

Section 3: Are Women Now Being Protected Too Much? Some worry that extra precautions — like excluding women from early-phase trials — may backfire:

• Delaying access to life-changing drugs
• Forcing women to wait until post-marketing surveillance to be included
• Excluding pregnant and breastfeeding women entirely, even when they are at high risk (e.g., in pandemics)

This creates a paradox: either women are harmed by being ignored, or excluded "for their safety."

The solution is not to avoid studying women — but to design smarter, safer, inclusive trials from the beginning.

Section 4: Will We Need Two Trials — One for Men, One for Women? This concern is understandable. Stratifying data by sex, running subgroup analyses, and including both pre- and post-menopausal women does cost more.

But it's not about running two separate trials. It's about:

• Recruiting balanced numbers of men and women
• Analysing sex-specific outcomes from one trial
• Designing adaptive trials or pooled data studies

Neglecting sex differences costs more in the long run — through failed drugs, recalls, and harm to patients.

Section 5: Positive Examples of Progress

• UK heart disease research now includes female-specific risk factors and symptom profiles in NICE guidance
• Autoimmune research increasingly uses female animal models and stratifies analysis by sex
• Endometriosis, menopause, and menstrual health are finally getting targeted research funding in the UK
• DecodeME is helping uncover the genetic basis of ME/CFS with full inclusion of women
• Long COVID clinics in the NHS are building on lessons from women-led ME/CFS research
• New studies on asthma and fungal allergy (e.g., ABPA) are beginning to explore hormonal and immunological factors that may differ by sex

Section 6: Where Patients Fit In Patients have led many of these changes:

• Women with ME, long COVID, POTS, or fibromyalgia have insisted their experiences are real
• Advocacy groups in the UK (e.g. Action for M.E., LongCovidSOS, National Aspergillosis Centre support groups) have pushed for sex-specific research
• Patient-led data collection and patient involvement in trial design are now expected in NIHR-funded studies
• In rare fungal diseases like CPA, SAFS, and ABPA, patients can support research by contributing to trials that welcome women and report on sex-specific outcomes

Conclusion: A Call to Patients This isn’t just a scientific issue — it’s a patient rights issue. Without full inclusion of women in research, we can't expect safe, effective, and equitable treatments.

Ask questions. Share your stories. Advocate for better science. And when possible, participate in trials that commit to transparency and inclusivity.

For patients with aspergillosis, the message is clear: We need sex-aware, inclusive research to understand this complex disease in all its forms — and that means including and reporting on women properly.

Medicine must work for everyone — not just the default male.

by GAtherton