BioMed CentralBMC Public Health
ssOpen AcceResearch article
The association of urinary cadmium with sex steroid hormone 
concentrations in a general population sample of US adult men
Andy Menke1, Eliseo Guallar*1,2, Meredith S Shiels1, Sabine Rohrmann3, 
Shehzad Basaria4, Nader Rifai5, William G Nelson4,6,7,8,9,10,11 and 
Elizabeth A Platz1,10,11
Address: 1Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA, 2Department of Cardiovascular 
Epidemiology and Population Genetics, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain, 3Division of Cancer 
Epidemiology, German Cancer Research Center, Heidelberg, Germany, 4Department of Medicine, Johns Hopkins School of Medicine, Baltimore, 
USA, 5Department of Laboratory Medicine, Children's Hospital Boston, Boston, USA, 6Department of Oncology, Johns Hopkins School of 
Medicine, Baltimore, USA, 7Department of Pathology, Johns Hopkins School of Medicine, Baltimore, USA, 8Department of Pharmacology and 
Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, USA, 9Department of Urology, Johns Hopkins School of Medicine, Baltimore, 
USA, 10The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, USA and 11The James Buchanan Brady 
Urological Institute, Johns Hopkins Medical Institutions, Baltimore, USA
Email: Andy Menke - amenke@jhsph.edu; Eliseo Guallar* - eguallar@jhsph.edu; Meredith S Shiels - mshiels@jhsph.edu; 
Sabine Rohrmann - s.rohrmann@dkfz-heidelberg.de; Shehzad Basaria - sbasari1@jhmi.edu; Nader Rifai - Nader.Rifai@childrens.harvard.edu; 
William G Nelson - bnelson@jhmi.edu; Elizabeth A Platz - eplatz@jhsph.edu
* Corresponding author    
Abstract
Background: Studies investigating the association of cadmium and sex steroid hormones in men
have been inconsistent, but previous studies were relatively small.
Methods: In a nationally representative sample of 1,262 men participating in the morning
examination session of phase I (1998–1991) of the third National Health and Nutrition Examination
Survey, creatinine corrected urinary cadmium and serum concentrations of sex steroid hormones
were measured following a standardized protocol.
Results: After adjustment for age and race-ethnicity, higher cadmium levels were associated with
higher levels of total testosterone, total estradiol, sex hormone-binding globulin, estimated free
testosterone, and estimated free estradiol (each p-trend < 0.05). After additionally adjusting for
smoking status and serum cotinine, none of the hormones maintained an association with urinary
cadmium (each p-trend > 0.05).
Conclusion: Urinary cadmium levels were not associated with sex steroid hormone
concentrations in a large nationally representative sample of US men.
Background
Cadmium is a widespread toxic and carcinogenic metal
with numerous adverse health effects in humans [1]. In
the general population, environmental exposure to cad-
mium occurs primarily through smoking, the consump-
tion of contaminated food and water, and inhalation of
contaminated air [2,3].
Published: 23 February 2008
BMC Public Health 2008, 8:72 doi:10.1186/1471-2458-8-72
Received: 29 October 2007
Accepted: 23 February 2008
This article is available from: http://www.biomedcentral.com/1471-2458/8/72
© 2008 Menke et al; licensee BioMed Central Ltd. 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), 
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 7
(page number not for citation purposes)
BMC Public Health 2008, 8:72 http://www.biomedcentral.com/1471-2458/8/72Cadmium shows androgen and estrogen-like activities in
vitro and in vivo, and it disrupts the male endocrine sys-
tem in animal models. There is conflicting evidence
regarding whether cadmium increases or decreases testo-
sterone production in experimental models [4-6], with
decreases more commonly seen after a single, large dose
injection of cadmium and increases more commonly seen
after chronic oral cadmium exposure [7]. Studies investi-
gating the association of cadmium and sex steroid hor-
mones in men have been inconsistent, finding either no
association [8-10], or a positive association between cad-
mium and testosterone levels [11-13]. Inconsistencies in
these studies may be due to small sample sizes, to differ-
ences in study design, or to inadequate control of con-
founders such as tobacco use, a major source of cadmium
[14] that is also associated with higher testosterone levels
in men [15,16].
The purpose of the current analysis was to evaluate the
association of urinary cadmium levels, a biomarker of
long term and ongoing cadmium exposure, with serum
concentrations of sex steroid hormones (total testoster-
one, total estradiol, androstanediol glucuronide [AAG],
estimated free testosterone, and estimated free estradiol)
and sex hormone-binding globulin (SHBG) in the Third
National Health and Nutrition Examination Survey
(NHANES III).
Methods
Study Population
NHANES III was a stratified, multistage probability survey
designed to select a representative sample of the civilian
non-institutionalized US population [17]. NHANES III
included two phases (phase I: October 1988 – October
1991 and phase II: September 1991 – October 1994),
each capable of independently producing unbiased
national estimates. Within each phase, participants were
randomly assigned to either a morning or afternoon/
evening examination. The present study was conducted
among men aged ≥ 20 years participating in the morning
examination session of phase I (N = 1,967). The study was
restricted to participants in the morning session to reduce
extraneous variation due to diurnal production of sex hor-
mones. Serum for hormone assays was available for 1,470
participants (75%). After excluding 25 participants miss-
ing data for urinary cadmium, 11 participants missing
data for urinary creatinine, 7 participants missing data for
serum testosterone, 5 participants missing data for serum
SHBG, 9 participants missing data for serum albumin, 11
participants missing data for serum cotinine, and 140 par-
ticipants missing data for other covariates, the final sam-
ple included 1,262 men. The protocol for NHANES III was
approved by the National Center for Health Statistics of
the Center for Disease Control and Prevention Institu-
tional Review Board. All participants gave written
informed consent. The assay of stored serum specimens
for the Hormone Demonstration Program was approved
by the Institutional Review Boards at the Johns Hopkins
Bloomberg School of Public Health and the National
Center for Health Statistics, Centers for Disease Control
and Prevention.
Data Collection
Demographic, household income, physical activity, ciga-
rette smoking, and alcohol consumption data were col-
lected using standardized questionnaires during an in-
home interview [17]. Whole body electrical resistance was
measured using a Valhalla Scientific Body Composition
Analyzer (model 1990B; Valhalla Scientific, Inc., San
Diego, CA) and prediction equations were used to predict
percent body fat [18]. Serum cotinine was measured using
liquid chromatography/atmospheric pressure ionization
tandem mass spectrometry [19]. Atomic absorption spec-
trometry was used to measure blood lead as described by
Sassa and colleagues [20] and serum selenium as
described by Lewis and colleagues [21].
All materials used for collecting and processing urinary
cadmium specimens were screened for possible cadmium
contamination [22]. A spot urine specimen was collected
and shipped at -20°C to the NHANES laboratory at the
National Centers for Environmental Health at the Centers
for Disease Control and Prevention in Atlanta, GA. Uri-
nary cadmium was measured by graphite furnace atomic
absorption with Zeeman background correction, using
the CDC modification of the method of Pruszkowska and
colleagues [23]. Since NHANES III only collected spot
urine samples, all analyses were performed using creati-
nine corrected urinary cadmium values (urinary cadmium
divided by urinary creatinine concentrations, expressed as
µg/g) to account for between participant differences in
urine dilution. Urinary creatinine was measured using the
method of Jaffe with a Beckman ASTRA automated ana-
lyzer [24].
Sex Steroid Hormones
Participants in the morning examination session fasted
overnight before having blood drawn. After centrifuga-
tion, serum was aliquotted and stored at -70°C. Serum
concentrations of testosterone, estradiol, AAG (a metabo-
lite of dihydrotestosterone), and SHBG were measured in
2005 at the laboratory of Dr. Nader Rifai at Children's
Hospital in Boston, MA. Sex steroid hormone levels and
SHBG are stable after multiple freeze-thaw cycles [25,26].
Testosterone, estradiol, and SHBG levels were quantified
using competitive electrochemiluminescence immu-
noassays on the 2010 Elecsys autoanalyzer (Roche Diag-
nostics, Indianapolis, IN). AAG was measured by an
enzyme immunoassay (Diagnostics Systems Laboratories,
Webster, TX). The detection limits of the assays were 0.02Page 2 of 7
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BMC Public Health 2008, 8:72 http://www.biomedcentral.com/1471-2458/8/72ng/mL for testosterone, 5 pg/mL for estradiol, 0.33 ng/mL
for AAG, and 3 nmol/L for SHBG. The coefficients of var-
iation (CV%) for quality control specimens included dur-
ing the analyses of the NHANES III samples ranged from
5.8 to 5.9% for testosterone, 2.5 to 6.7% for estradiol, 5.0
to 9.5% for AAG, and 5.3 to 5.9% for SHBG. Free testo-
sterone concentrations were estimated from measured tes-
tosterone, SHBG, and albumin, while free estradiol
concentrations were estimated from measured estradiol,
SHBG, and albumin [27,28].
Statistical Analysis
Participants were categorized into quartiles of urinary cad-
mium based on the weighted population distribution.
Age and race-ethnicity adjusted means and percentages
were calculated by linear regression for continuous covari-
ates and logistic regression for dichotomous covariates.
Due to skewed distributions of sex steroid hormones, we
calculated adjusted geometric means by quartile of cad-
mium using multiple linear regression on log-trans-
formed hormone levels. We also present analyses for
molar ratios of estradiol to testosterone, testosterone to
SHBG, and estradiol to SHBG. Initial models adjusted for
age and race-ethnicity. Subsequent models further
adjusted for smoking status and serum cotinine. Addi-
tional models further adjusted for household income,
physical activity, alcohol consumption, percent body fat,
blood lead, and serum selenium. Tests for linear trend
across quartiles of cadmium were computed by including
an ordinal variable with the median of each quartile of
cadmium in the linear regression models. Due to the
importance of smoking in determining cadmium levels
and the possibility of overadjustment, we additionally
present models separately for never, former, and current
smokers.
Data were analyzed using SUDAAN (version 9.0; Research
Triangle Institute, Research Triangle Park, NC) to account
for the complex NHANES sampling design, including
unequal probabilities of selection, over-sampling, and
non-response.
Results
The median level (range) of urinary cadmium in the study
sample was 0.34 µg/g creatinine (0.003–4.22 µg/g). Par-
ticipants with higher cadmium levels were more likely to
be older, to be non-Hispanic black, to be current smokers,
to have household incomes < $20,000, not to exercise,
and to have higher blood lead levels (Table 1). The
median levels (range) of urinary cadmium among never
(n = 436), former (n = 416), and current (n = 410) smok-
ers were 0.21 µg/g (0.003–4.22 µg/g), 0.42 µg/g (0.004–
2.32 µg/g), and 0.56 µg/g (0.004–4.02 µg/g), respectively.
After adjustment for age and race-ethnicity, higher cad-
mium levels were associated with higher levels of total tes-
tosterone, total estradiol, SHBG, estimated free
testosterone, and estimated free estradiol (each p-trend <
0.05), but not with AAG or any of the molar ratios (Table
2). After additionally adjusting for smoking status and
serum cotinine, the associations of urinary cadmium lev-
els with sex steroid hormones and their molar ratios were
small and not statistically significant (each p-trend >
0.05). After stratifying by smoking status, the associations
of urinary cadmium levels with sex steroid hormones and
their molar ratios were small and not statistically signifi-
cant for never, former, and current smokers (each p-trend
> 0.05; Table 3). However, among never smokers there
was a marginally significant, negative association between
urinary cadmium and total testosterone (p-trend = 0.06)
and among current smokers there was a marginally signif-
Table 1: Age and race-ethnicity adjusted participant characteristics* by quartile of creatinine corrected urinary cadmium
Quartile 1 < 0.18 µg/g Quartile 2 0.18–0.33 µg/g Quartile 3 0.34–0.62 µg/g Quartile 4 ≥ 0.63 µg/g p-trend
Age, years 31.7 (0.8) 37.1 (0.7) 44.6 (1.3) 54.3 (1.2) < 0.001
Non-Hispanic white, % 83.9 (2.9) 80.3 (3.4) 74.5 (5.6) 74.3 (5.2) 0.07
Non-Hispanic black, % 6.5 (1.5) 10.9 (2.2) 8.1 (1.1) 11.1 (1.7) 0.03
Mexican-American, % 4.2 (1.0) 5.6 (1.0) 4.5 (0.9) 4.7 (0.8) 0.99
Current smokers, % 11.2 (2.1) 20.4 (3.7) 42.9 (4.2) 73.6 (2.4) < 0.001
Former smokers, % 29.3 (4.3) 33.9 (4.2) 35.8 (3.7) 25.7 (3.2) 0.06
Serum cotinine, ng/mL 26.4 (8.4) 39.6 (8.4) 107.2 (12.9) 231.0 (12.1) < 0.001
Low income, % 24.1 (3.0) 20.4 (2.7) 31.0 (2.9) 42.1 (4.0) < 0.001
Consume alcohol, % 75.6 (4.1) 71.5 (3.4) 74.8 (3.2) 72.7 (3.8) 0.76
No exercise, % 40.6 (6.1) 30.1 (3.5) 41.0 (4.4) 55.2 (4.2) 0.005
Percent body fat, mean percent 25.8 (0.5) 26.1 (0.5) 25.4 (0.6) 24.7 (0.5) 0.05
Blood lead, µg/dL† 3.2 (2.8, 3.6) 3.6 (3.2, 4.0) 4.3 (3.9, 4.8) 5.5 (4.9, 6.3) < 0.001
Serum selenium, ng/mL 126.5 (2.7) 126.7 (1.1) 127.3 (1.3) 121.7 (1.3) 0.05
*Mean or percentage (standard error)
†Geometric mean (95% confidence interval)Page 3 of 7
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BMC Public Health 2008, 8:72 http://www.biomedcentral.com/1471-2458/8/72icant, positive association between urinary cadmium and
free testosterone concentrations (p-trend = 0.09).
Discussion
In this large, representative sample of US adult men, uri-
nary cadmium levels were not associated with sex steroid
hormone levels after adjustment for confounders. In our
analysis, smoking was an important confounder of the
association between cadmium and sex steroid hormone
levels. The lack of association between cadmium and sex
steroid hormones was also evident after stratifying by
smoking status, although we identified a marginally sig-
nificant association between cadmium and total testoster-
one among never smokers and free testosterone among
current smokers. These findings may be explained as
chance findings or a result of residual confounding,
although we cannot exclude a modest association.
Four previous studies have evaluated the association of
urine or blood cadmium with sex steroid hormone levels
in men [10-13]. In a cross-sectional study of Chinese men
with environmental exposure to cadmium, blood and
urine cadmium did not meet the criteria for inclusion in
stepwise models predicting testosterone levels [10]. Blood
cadmium was positively associated with testosterone in
two separate studies of Croatian men who had never been
occupationally exposed to cadmium [11,12] and in a
study of Chinese male smelter workers [13]. These studies
Table 2: Adjusted geometric means (95% confidence interval) by quartile of creatinine corrected urinary cadmium
Quartile 1 < 0.18 µg/g Quartile 2 0.18–0.33 µg/g Quartile 3 0.34–0.62 µg/g Quartile 4 ≥ 0.63 µg/g p-trend
Total testosterone, ng/mL
Age and race-ethnicity adjusted 4.69 (4.40, 4.99) 4.85 (4.45, 5.27) 5.13 (4.78, 5.52) 5.64 (5.27, 6.04) < 0.001
Multivariable model 1† 5.06 (4.78, 5.36) 5.06 (4.71, 5.44) 5.03 (4.68, 5.41) 5.09 (4.69, 5.53) 0.88
Multivariable model 2‡ 5.10 (4.85, 5.35) 5.07 (4.72, 5.45) 5.00 (4.67, 5.35) 5.08 (4.68, 5.51) 0.99
Total estradiol, pg/mL
Age and race-ethnicity adjusted 32.1 (29.6, 34.8) 34.6 (33.1, 36.1) 37.5 (35.8, 39.2) 39.8 (37.9, 41.8) < 0.001
Multivariable model 1† 34.4 (32.2, 36.8) 36.1 (34.6, 37.7) 36.9 (35.2, 38.6) 36.2 (33.8, 38.7) 0.42
Multivariable model 2‡ 34.3 (32.3, 36.4) 36.0 (34.5, 37.6) 37.1 (35.4, 38.8) 36.1 (33.7, 38.8) 0.41
SHBG, nmol/L
Age and race-ethnicity adjusted 34.2 (31.4, 37.2) 33.1 (30.9, 35.4) 34.6 (32.6, 36.7) 37.5 (34.6, 40.7) 0.009
Multivariable model 1† 35.2 (32.1, 38.6) 33.9 (31.6, 36.3) 34.4 (32.3, 36.7) 35.6 (32.7, 38.8) 0.57
Multivariable model 2‡ 35.5 (32.7, 38.5) 34.0 (31.7, 36.4) 34.3 (32.4, 36.3) 35.4 (32.5, 38.5) 0.71
Androstanediol glucuronide, ng/mL
Age and race-ethnicity adjusted 13.0 (12.2, 13.8) 11.8 (10.9, 12.9) 10.9 (9.5, 12.5) 11.2 (9.7, 13.0) 0.23
Multivariable model 1† 12.9 (12.1, 13.8) 11.8 (10.8, 12.9) 10.9 (9.5, 12.5) 11.3 (9.8, 13.1) 0.33
Multivariable model 2‡ 12.9 (12.1, 13.7) 11.7 (10.8, 12.8) 10.9 (9.5, 12.5) 11.4 (9.8, 13.2) 0.40
Estimated free testosterone, ng/mL
Age and race-ethnicity adjusted 0.092 (0.087, 0.097) 0.098 (0.091, 0.105) 0.104 (0.095, 0.113) 0.109 (0.102, 0.118) < 0.001
Multivariable model 1† 0.099 (0.094, 0.105) 0.102 (0.095, 0.108) 0.101 (0.093, 0.111) 0.100 (0.091, 0.109) 0.89
Multivariable model 2‡ 0.100 (0.094, 0.105) 0.102 (0.095, 0.109) 0.101 (0.092, 0.110) 0.100 (0.090, 0.110) 0.85
Estimated free estradiol, pg/mL
Age and race-ethnicity adjusted 0.81 (0.75, 0.89) 0.89 (0.84, 0.93) 0.96 (0.91, 1.02) 1.00 (0.94, 1.07) < 0.001
Multivariable model 1† 0.87 (0.81, 0.94) 0.92 (0.87, 0.97) 0.95 (0.90, 1.00) 0.91 (0.84, 0.99) 0.69
Multivariable model 2‡ 0.87 (0.81, 0.93) 0.92 (0.87, 0.97) 0.95 (0.90, 1.01) 0.91 (0.83, 1.00) 0.69
Estradiol*1000/total testosterone
Age and race-ethnicity adjusted 7.24 (6.57, 7.99) 7.56 (6.81, 8.39) 7.74 (7.18, 8.34) 7.47 (6.98, 8.00) 0.80
Multivariable model 1† 7.20 (6.55, 7.91) 7.55 (6.83, 8.34) 7.75 (7.14, 8.42) 7.52 (6.90, 8.20) 0.70
Multivariable model 2‡ 7.12 (6.60, 7.69) 7.52 (6.80, 8.31) 7.85 (7.23, 8.53) 7.54 (6.86, 8.28) 0.61
Total testosterone/SHBG
Age and race-ethnicity adjusted 0.476 (0.445, 0.510) 0.508 (0.475, 0.543) 0.514 (0.469, 0.564) 0.522 (0.480, 0.566) 0.05
Multivariable model 1† 0.498 (0.461, 0.538) 0.518 (0.488, 0.551) 0.507 (0.460, 0.558) 0.495 (0.444, 0.553) 0.71
Multivariable model 2‡ 0.498 (0.461, 0.538) 0.518 (0.485, 0.554) 0.505 (0.458, 0.555) 0.497 (0.442, 0.559) 0.79
Estradiol*1000/SHBG
Age and race-ethnicity adjusted 3.45 (3.03, 3.92) 3.84 (3.52, 4.20) 3.98 (3.66, 4.32) 3.90 (3.49, 4.35) 0.15
Multivariable model 1† 3.59 (3.14, 4.09) 3.91 (3.56, 4.30) 3.93 (3.60, 4.28) 3.72 (3.29, 4.22) 0.98
Multivariable model 2‡ 3.55 (3.16, 3.99) 3.90 (3.55, 4.28) 3.97 (3.66, 4.30) 3.75 (3.29, 4.27) 0.87
SHBG = Sex hormone-binding globulin
†Adjusted for age (continuous) and race-ethnicity (non-Hispanic white, non-Hispanic black, Mexican-American, and other), smoking status (never, 
former, and current), and serum cotinine (continuous)
‡Adjusted for variables in model 1 and household income (< $20,000 and ≥ $20,000), physical activity (none, 1–2, and ≥ 3 times a week), alcohol 
consumption (< 12 and ≥ 12 drinks in the past year), percent body fat (continuous), blood lead (log-transformed, continuous), and serum selenium 
(continuous)Page 4 of 7
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BMC Public Health 2008, 8:72 http://www.biomedcentral.com/1471-2458/8/72were relatively small: the largest study included 263 par-
ticipants, and their combined sample size was 701. Addi-
tionally, three of these studies did not report smoking
adjusted results [10-12], although smoking was included
in stepwise regression algorithms. The importance of
tobacco use as a confounder of the cadmium-sex hor-
mone relationship may differ across populations due to
varying levels of cadmium in tobacco, prevalence of
tobacco use, and exposure to cadmium from other sources
(e.g., occupational exposure, food, air pollution). How-
ever, our analysis indicates that studies of the association
of cadmium with sex steroid hormones need to carefully
control for tobacco use.
Our findings pertain to low-level chronic environmental
cadmium exposure and may not be generalizable to envi-
ronmental or occupational settings involving higher dos-
ages of cadmium. Indeed, differences in cadmium levels
may account for the inconsistent results in previous
research. Additionally, urinary cadmium reflects predom-
inantly cumulative long-term exposure and we cannot
rule out short-term effects of cadmium exposure on sex
steroid hormone levels. Our analysis was based on single
measures of sex steroid hormones in plasma and of cad-
mium in spot urine samples, all of which were subject to
substantial within person variability and laboratory meas-
urement error. Consequently, we cannot exclude the exist-
ence of a modest association between urine cadmium and
sex steroid hormone levels. However, the inconsistent
findings in experimental models and the lack of a clearly
delineated biological mechanism that could explain an
effect of chronic environmental cadmium exposure on sex
Table 3: Adjusted* geometric means (95% confidence interval) by quartile of creatinine corrected urinary cadmium and smoking 
status.
Quartile 1 < 0.18 µg/g Quartile 2 0.18–0.33 µg/g Quartile 3 0.34–0.62 µg/g Quartile 4 ≥ 0.63 µg/g p-trend
Total testosterone, ng/mL
Never smokers 5.03 (4.68, 5.41) 4.88 (4.27, 5.58) 4.12 (3.26, 5.22) 4.24 (3.24, 5.55) 0.06
Former smokers 4.34 (3.91, 4.81) 4.16 (3.60, 4.80) 4.52 (4.20, 4.87) 4.49 (4.05, 4.98) 0.49
Current smokers 5.74 (5.08, 6.48) 5.78 (5.34, 6.27) 6.09 (5.81, 6.39) 6.39 (5.86, 6.96) 0.12
Total estradiol, pg/mL
Never smokers 31.7 (29.0, 34.6) 34.0 (31.4, 36.7) 34.3 (30.8, 38.2) 30.2 (23.6, 38.7) 0.97
Former smokers 33.0 (30.1, 36.2) 33.0 (31.0, 35.0) 32.6 (30.8, 34.4) 33.5 (31.0, 36.2) 0.73
Current smokers 40.2 (36.3, 44.5) 39.1 (37.0, 41.3) 44.3 (42.3, 46.5) 43.2 (40.7, 45.8) 0.26
SHBG, nmol/L
Never smokers 32.4 (29.6, 35.3) 32.6 (29.8, 35.6) 31.3 (27.1, 36.1) 32.5 (26.8, 39.3) 0.88
Former smokers 36.2 (30.6, 42.8) 32.2 (29.7, 34.8) 37.3 (33.5, 41.7) 37.8 (34.1, 41.8) 0.28
Current smokers 39.3 (34.7, 44.5) 36.3 (31.7, 41.6) 33.7 (31.0, 36.6) 37.6 (33.2, 42.7) 0.71
Androstanediol glucuronide, ng/mL
Never smokers 12.9 (12.0, 13.8) 11.3 (9.9, 13.0) 11.7 (9.7, 14.0) 13.1 (11.0, 15.7) 0.80
Former smokers 14.0 (11.8, 16.7) 11.8 (10.3, 13.6) 10.5 (9.7, 11.3) 11.7 (9.6, 14.4) 0.64
Current smokers 12.1 (9.8, 14.9) 12.5 (10.0, 15.4) 10.8 (8.7, 13.3) 11.0 (9.3, 12.9) 0.53
Estimated free testosterone, ng/mL
Never smokers 0.102 (0.094, 0.111) 0.099 (0.088, 0.111) 0.084 (0.063, 0.112) 0.085 (0.064, 0.114) 0.14
Former smokers 0.083 (0.075, 0.091) 0.084 (0.071, 0.099) 0.086 (0.079, 0.093) 0.084 (0.076, 0.093) 0.97
Current smokers 0.109 (0.097, 0.123) 0.114 (0.106, 0.123) 0.129 (0.121, 0.137) 0.126 (0.117, 0.136) 0.09
Estimated free estradiol, pg/mL
Never smokers 0.81 (0.73, 0.90) 0.86 (0.79, 0.94) 0.89 (0.78, 1.00) 0.77 (0.60, 1.00) 0.92
Former smokers 0.84 (0.75, 0.94) 0.86 (0.80, 0.92) 0.82 (0.78, 0.87) 0.84 (0.77, 0.91) 0.87
Current smokers 1.00 (0.90, 1.10) 0.99 (0.92, 1.05) 1.16 (1.09, 1.23) 1.09 (1.01, 1.17) 0.39
Estradiol*1000/total testosterone
Never smokers 6.67 (6.06, 7.35) 7.37 (6.08, 8.93) 8.81 (6.75, 11.50) 7.54 (6.20, 9.17) 0.16
Former smokers 8.08 (6.96, 9.37) 8.41 (7.36, 9.60) 7.62 (7.02, 8.28) 7.89 (7.10, 8.77) 0.71
Current smokers 7.41 (6.75, 8.14) 7.15 (6.62, 7.72) 7.71 (7.25, 8.19) 7.16 (6.58, 7.79) 0.51
Total testosterone/SHBG
Never smokers 0.539 (0.490, 0.593) 0.520 (0.470, 0.575) 0.457 (0.337, 0.619) 0.453 (0.332, 0.619) 0.25
Former smokers 0.416 (0.364, 0.474) 0.448 (0.382, 0.525) 0.420 (0.380, 0.464) 0.412 (0.370, 0.459) 0.59
Current smokers 0.507 (0.456, 0.563) 0.552 (0.491, 0.621) 0.628 (0.575, 0.685) 0.588 (0.535, 0.646) 0.31
Estradiol*1000/SHBG
Never smokers 3.60 (3.09, 4.19) 3.83 (3.37, 4.36) 4.03 (3.29, 4.93) 3.42 (2.62, 4.45) 0.88
Former smokers 3.35 (2.70, 4.15) 3.77 (3.37, 4.20) 3.20 (2.90, 3.53) 3.25 (2.86, 3.70) 0.52
Current smokers 3.75 (3.30, 4.27) 3.95 (3.44, 4.53) 4.84 (4.35, 5.38) 4.22 (3.66, 4.86) 0.72
*Adjusted for age (continuous) and race-ethnicity (non-Hispanic white, non-Hispanic black, Mexican-American, and other), serum cotinine 
(continuous), household income (< $20,000 and ≥ $20,000), physical activity (none, 1–2, and ≥ 3 times a week), alcohol consumption (< 12 and ≥ 
12 drinks in the past year), percent body fat (continuous), blood lead (log-transformed, continuous), and serum selenium (continuous)Page 5 of 7
(page number not for citation purposes)
BMC Public Health 2008, 8:72 http://www.biomedcentral.com/1471-2458/8/72steroid hormone concentrations support our findings of
no association.
Conclusion
Cadmium binds with high affinity to the androgen recep-
tor, where it inhibits the binding of androgens and
induces androgen-like effects [29]. While cadmium itself
may exert androgen-like effects, our analysis indicates that
urinary cadmium is not an important determinant of sex
steroid hormone levels in adult men at the range of expo-
sure evaluated in the general US population.
Abbreviations
AAG – androstanediol glucuronide; SHBG – sex hor-
mone-binding globulin; NHANES III – Third National
Health and Nutrition Examination Survey
Competing interests
The author(s) declare that they have no competing inter-
ests.
Authors' contributions
AM, EG, MSS, and EAP were responsible for the concep-
tion and design, analysis and interpretation of data. AM
drafted the manuscript, that was edited by EG, MSS, and
EAP. SR, SB, NR, and WGN were responsible for interpre-
tation of the data and revising the manuscript. All authors
read and approved the final manuscript.
Acknowledgements
The Hormone Demonstration Program was supported by the Maryland 
Cigarette Restitution Fund Research Grant Program at the Johns Hopkins 
Medical Institutions.
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