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Background: Cadmium, lead and mercury have been identified in human follicular fluid and ovarian tissue, and have been associated with adverse reproductive outcomes in epidemiologic studies; however, few studies have examined the relationship between blood metal levels and reproductive hormones.Methods: Among 252 premenopausal women aged 18-44 years, we examined the association between blood metal levels (cadmium, lead and mercury), cycle length, and reproductive hormones [FSH, LH, estradiol (E(2)) and progesterone] measured at clinically relevant time points in the menstrual cycle. The association between metal levels (continuous) and hormone levels was assessed using linear regression with hormone levels (natural) log transformed and the results interpreted as the percentage difference in hormone level per unit increase in metal level.Results: Median (interquartile range) cadmium, lead and mercury levels were 0.30 µg/l (0.19, 0.43), 0.87 µg/dl (0.68, 1.20) and 1.10 µg/l (0.58, 2.10), respectively. Each 1 µg/l increase in cadmium levels was associated with a 21% [95% confidence interval (CI): -2.9, 49.9] increase in early follicular phase E(2) levels after adjusting for age, race/ethnicity, lead and mercury. This association decreased when restricted to never smokers (10%; 95% CI: -19.5, 51.3). Cadmium was also associated with a non-significant 9% (95% CI: -0.2, 19.9), or 2.7 day, increase in cycle length among never smokers. No associations were observed between lead or mercury and the outcomes in adjusted analyses.Conclusions: Further evaluation of the association between cadmium, E(2) and cycle length is warranted, taking into consideration cigarette smoke and its multiple components. [ABSTRACT FROM AUTHOR]