The effect of air pollution exposure on menstrual cycle health using self-reported data from a mobile health app: a prospective, observational study

Background: Toxicological evidence suggests that ambient air pollution has endocrine-disrupting properties that can affect menstrual cycle functioning, which represents an important marker of women's reproductive health. We aimed to estimate the effect of short-term and long-term PM2<middle dot>5 exposure on menstrual cycle outcomes across the USA, Brazil, and Mexico using self-reported data from a mobile health app. Methods: For this prospective observational study, we collected de-identified self-reported data from the Clue mobile health app, in which users self-tracked menstruation cycles. For the current study, eligible participants were aged 18-44 years, were not using hormonal birth control, and lived in one of 230 cities in the USA, Mexico, or Brazil. The primary outcome of interest at the city level was the proportion of menstrual cycles with abnormally short length (<24 days) and long length (>38 days) of all cycles recorded. The primary outcome at the cycle level was a binary indicator: abnormal cycle length (<24 days or >38 days) or not (normal cycle length). We used regression analyses to evaluate associations between long-term PM2<middle dot>5 concentrations (mean concentration between 2016 and 2020) and the city-level outcomes after controlling for potential confounders. Conditional logistic regression models were used to evaluate associations between cycle-specific PM2<middle dot>5 and if a cycle was of abnormal length within an individual in the dataset, after controlling for time-varying factors. Findings: Between Jan 1, 2016 and Dec 31, 2020, 92 550 app users residing in 230 cities across the USA, Brazil, and Mexico provided data corresponding to 2 220 281 menstrual cycles, and were included in our main cohort. A significant association was observed between long-term PM2<middle dot>5 exposure and the proportion of menstrual cycles of abnormally long or short duration (odds ratio [OR] 1<middle dot>023 [95% CI 1<middle dot>013-1<middle dot>033]) and the proportion of cycles that were specifically abnormally long (OR 1<middle dot>036 [1<middle dot>023-1<middle dot>049]) for every 10 mu g/m(3) increase in PM2<middle dot>5. No associations were identified between short-term PM2<middle dot>5 concentrations and abnormal cycle length. Interpretation: These findings suggest that PM2<middle dot>5 exposure affects menstrual cycle outcomes. More research is needed to better elucidate the biological mechanisms through which PM2<middle dot>5 affects the menstrual cycle.