The Invisible Burden: Examining the Impact of Exposure Misclassification in Epidemiologic Analyses of Uterine Fibroids.

Abstract

Background: Uterine fibroids, a common gynaecologic condition, are often underdiagnosed, potentially biasing results in epidemiologic studies due to measurement error.

Objectives: To examine how varying sensitivity in detecting uterine fibroids impacts effect estimates, using the association with hypertension onset as an example.

Methods: Three simulation studies were conducted (N = 100,000), considering true population prevalences of uterine fibroids of 5%, 20% and 60%. The first study varied detection sensitivity between 0% and 100%. The second examined differential sensitivity by symptom status (asymptomatic vs. symptomatic). The third assessed differential sensitivity by racialised groups. Specificity remained fixed at 90%, and true risk ratios (RRs) for the association with hypertension were set at 1.3 and 1.8.

Results: Decreasing sensitivity biased results towards the null, with low-sensitivity methods (e.g., self-report) showing the largest bias and high-sensitivity methods (e.g., transvaginal ultrasonography) the least bias. At low fibroid prevalence (5%), even gold-standard ascertainment introduced bias due to imperfect specificity, whereas this concern diminished at higher prevalence. Assuming a dose-response relationship between fibroids and hypertension based on symptom status, results remained biased towards the null unless sensitivity was 100% and prevalence was high (60%); bias was most pronounced at low prevalence. When only symptomatic fibroids were associated with hypertension, increasing sensitivity biased results away from the null by capturing more asymptomatic cases. Studies using low-sensitivity methods may fail to identify a true effect among Black females while identifying it among White females, potentially exacerbating disparities. Detection bias, where those with fibroids are more likely to have hypertension detected, could result in bias away from the null.

Conclusions: Underdiagnosis of uterine fibroids can bias results towards the null, particularly with self-report or modest effect estimates, potentially obscuring true effects. When only symptomatic fibroids were associated with the outcome, the bias was away from the null. Results varied by symptom status and race, highlighting the need to prioritise sensitive ascertainment methods, employ sensitivity analyses and improve reliability across diverse gynecologic conditions and health disparities.