Rural and Urban Differences in Pubertal Development and Menstrual Characteristics in a Costa Rican Cohort - SUMMARY/ABSTRACT The global trend toward earlier pubertal development has extensive public health implications, particularly for low- and middle-income countries (LMICs) where age at menarche has been decreasing faster than in high- income countries (HICs). Additionally, in several LMICs, the timing of menarche has been found to vary by rural versus urban residence. As younger age at menarche is a risk factor for negative health outcomes like reproductive cancers, obesity, and cardiovascular disease, understanding the timing and determinants of pubertal development and menstrual characteristics may elucidate linkages between pubertal exposures and related health disparities. Therefore, we propose to characterize patterns in the timing, tempo, and determinants of pubertal development and menstrual characteristics in the Costa Rican study, Estudio de Comparacion de Una y Dos Dosis de Vacunas Contra el Virus de Papiloma Humano (ESCUDDO). We hypothesize that urban girls will experience earlier puberty, faster tempo, and shorter, regular menstrual cycles compared to their rural counterparts. We will leverage data from the full ESCUDDO cohort and the Immunogenicity Subcohort Group (ISG) which comprise of pubertal development and menstrual history from Costa Rican girls ages 12-21 and ages 12-14 at baseline, respectively. We will first evaluate if the timing and tempo of pubertal development and menstrual characteristics is earlier and faster in urban girls compared to rural girls (Aim 1). Using data from the full cohort (n=24,782), we will ascertain differences in pubertal development and menstrual characteristics across the rural-urban continuum in girls ages 12 to 21 using parametric survival models for pubertal timing and mixed-effects models for pubertal tempo (Aim 1a). Using longitudinal data from the ISG (n=1,408) we will update our estimates of pubertal timing and tempo (Aim 1b). We will also determine if associations between determinants of earlier and faster pubertal development and menstrual characteristics in predominantly HICs are also determinants in Costa Rica (Aim 2) by measuring the effect of early pubertal development predictors including weight, BMI, prenatal and neonatal history, smoking, and socioeconomic status on the timing and tempo of pubertal development and menstrual characteristics using parametric survival models. The proposed study will be the largest comprehensive assessment of pubertal development and menstrual characteristics in female adolescents to date and will help identify populations at high risk of earlier, faster pubertal development and shorter, regular menstrual cycles. The objectives outlined in this proposal will provide me with extensive experience in reproductive health research, while contributing to the large knowledge gap of pubertal development globally. Furthermore, the combination of rigorous training in advanced epidemiologic methods, experiential learning, and expert mentorship will ensure my transition to a successful physician-scientist.