Decades of Missed Diagnoses Masquerading as Biology

Researchers have found that men develop Parkinson's disease at roughly 1.

The newest hypothesis targets gene expression—how genes turn on and off differently between sexes—as the biological culprit. It's a clean story, and also a trap.

In 1956, a geriatrician named George Cotzias began treating Parkinson's patients with levodopa and published results showing dramatic improvement in symptoms. His patient pool was almost entirely men. Women with Parkinson's existed. They were simply not arriving at his clinic with diagnoses because the disease in women presents differently, with rigidity instead of tremor, gait problems instead of bradykinesia. Clinicians trained on the male presentation missed them entirely.

A diagnostic bias creates a skewed data set. That skewed data set gets published. New researchers, working from published literature, design experiments around the statistical pattern they've inherited—and when they find a biological explanation for that pattern, they've actually explained the bias, not the disease. The gene expression studies emerging now are elegant work, but they're potentially measuring an artifact dressed up as discovery.

When they find a biological explanation for that pattern, they've actually explained the bias, not the disease.

The field knows this history. Parkinson's researchers have published explicitly on sex-based diagnostic disparities and know women get diagnosed later and less often. Yet the momentum of collective research—where funding follows published prevalence patterns, where experiments design around existing datasets, where peer review validates work that confirms the statistical shape already in the literature—doesn't stop. It accelerates and finds mechanisms to explain what it already expects to see.

None of this means the gene expression findings are wrong. It means they might be discovering why more men appear in the data we collected from a system that wasn't looking for women. The prevalence difference may be real. Or we may finally be watching the consequences of 1956 crystallize into biology textbooks. The only way forward is to ask which diagnosis was missed first. Was it the disease or the women carrying it?