Association between urinary polycyclic aromatic hydrocarbon metabolites and premature menopause: a nationally representative cross-sectional study in the United States

Premature menopause, defined as natural menopause before age 40, is associated with diminished ovarian reserve. Despite growing concerns regarding environmental pollutants, no large-scale population-based studies have systematically examined the association between urinary polycyclic aromatic hydrocarbon metabolites (UPAHMs) and premature menopause.

This cross-sectional study analyzed 2001-2020 NHANES data, including urinary levels of six PAH metabolites: 1-naphthol (1-NAP), 2-naphthol (2-NAP), 3-fluorene (3-FLU), 2-fluorene (2-FLU), 1-phenanthrene (1-PHE), and 1-pyrene (1-PYR). Premature menopause was self-reported as natural menopause occurring before age 40. Multivariable logistic regression assessed UPAHMs' association with premature menopause, with restricted cubic splines (RCS) evaluating nonlinear trends. Subgroup analyses examined demographic interactions.

Among 2,565 participants, 662 reported premature menopause. Multivariable logistic regression showed significant associations between elevated urinary levels of 1-NAP (OR: 1.01, 95% CI: 1.00-1.02, P = 0.02), 2-NAP (OR: 1.01, 95% CI: 1.00-1.02, P = 0.02), and 3-FLU (OR: 1.03, 95% CI: 1.01-1.05, P = 0.01) and increased risk of premature menopause. RCS analysis revealed significant nonlinear relationships for 2-NAP, 3-FLU, 2-FLU, 1-PHE, and 1-PYR with premature menopause risk. White participants showed greater susceptibility to UPAHMs.

Elevated UPAHMs, particularly 1-NAP, 2-NAP, and 3-FLU, were linked to higher premature menopause risk, with nonlinear trends observed. White individuals demonstrated greater vulnerability, emphasizing the need for targeted interventions to reduce PAH exposure.