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Toenail metal concentrations and age at menopause: A prospective study.

ABSTRACT: Background:Menopause timing is related to cancer, cardiovascular disease, and mortality. Lead has been associated with an earlier age at menopause, but no study has considered exposure to other metals or multiple metals simultaneously. Methods:At baseline, we measured toenail concentrations of 16 metals for 903 premenopausal women in the Sister Study (2003-2009). Age at menopause was ascertained through follow-up questionnaires. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between individual metals and age at menopause. We used quantile-g-computation to examine the association between age at menopause and the joint effect of a simultaneous increase in (1) all metals and for subgroups of metals categorized as (2) essential or (3) non-essential. Results:For individual metals, we observed negligible associations except for an interquartile range increase in lead which was modestly associated with an earlier age at menopause (HR = 1.03, 95% CI = 1.01, 1.05). In the mixture analyses, a quartile increase in all metals was associated with a later age at menopause (HR = 0.81, 95% CI = 0.64, 1.02). The metals with the largest negative contributions (i.e., associated with a later age at menopause) were chromium and nickel. The joint effect for the essential metals remained inverse (HR = 0.83, 95% CI = 0.64, 1.07), but was attenuated for nonessential metals (HR = 0.98, 95% CI = 0.76, 1.24). Conclusions:Although no individual metal was strongly associated with age at menopause, our joint effect analysis suggests that having low levels of essential metals could be associated with an earlier age at menopause.

SUBMITTER: White AJ

PROVIDER: S-EPMC7423523 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Toenail metal concentrations and age at menopause: A prospective study.

White Alexandra J AJ O'Brien Katie M KM Niehoff Nicole M NM Jackson Brian P BP Karagas Margaret R MR Weinberg Clarice R CR Keil Alexander P AP

Environmental epidemiology (Philadelphia, Pa.) 20200716 4

<h4>Background</h4>Menopause timing is related to cancer, cardiovascular disease, and mortality. Lead has been associated with an earlier age at menopause, but no study has considered exposure to other metals or multiple metals simultaneously.<h4>Methods</h4>At baseline, we measured toenail concentrations of 16 metals for 903 premenopausal women in the Sister Study (2003-2009). Age at menopause was ascertained through follow-up questionnaires. Cox proportional hazard models were used to estimate ...[more]

PMID: 32832842

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Project description:BackgroundToenails are a promising matrix for chronic metal exposure assessment, but there are currently no standard methods for collection and analysis. Questions remain about sample mass requirements and the extent to which metals measured in this matrix are representative of chronic body burden.ObjectiveThis study proposes a method to maximize sample conservation for toenail metals analysis using inductively coupled plasma mass spectrometry (ICP-MS). We demonstrate the reliability of an ~25 mg toenail sample (typically 1-2 clippings) for metals analysis and evaluate the intra-individual variability of multiple metals in this matrix over time in men from the Gulf Long-term Follow-up (GuLF) Study.MethodsToenail samples from 123 GuLF Study participants were collected at two visits 3 years apart and analyzed for 18 elements using ICP-MS. Participants with samples exceeding 200 mg at the first visit (n = 29) were selected for triplicate sub-sample analysis. Kendall's coefficient of concordance (W) was used to assess sub-sample reliability and Spearman's correlation coefficients (ρ) were used to evaluate fluctuations in elemental concentrations over time.ResultsResults were not reported for Cd, Co, Mo, Sb, and V (detected in <60% of the samples). There was strong agreement among triplicate samples (Kendall's W: 0.72 (Cu)-0.90 (Cu)) across all elements evaluated, moderate correlations of elemental concentrations (Spearman's ρ: 0.21-0.42) over 3 years for As, Ca, Cr, Fe, Pb, Mn, and Zn, and strong correlations (>0.50) for Se, Cu, and Hg.Impact statementThis toenail reliability study found that a low-mass (~25 mg) toenail sample (1-2 clippings) is suitable for the determination of most elements using ICP-MS and helps to increase the analytical capacity of limited toenail biospecimens collected in cohort studies. The results highlight differences in the suitability of toenails for chronic metal exposure assessment by element and underscore the need to consider intra-person variability, especially when comparing results across studies. We also provide recommendations for analytical standardization and the partitioning of the total collected toenail sample into multiple analytic sub-samples for future studies using toenail biospecimen for multiple assays.

Dataset Information

Toenail metal concentrations and age at menopause: A prospective study.

Publications

Toenail metal concentrations and age at menopause: A prospective study.

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