The authors have declared that no competing interests exist.
Conceived and designed the experiments: ZNM XBY ZFL HYZ FHY SJZ. Performed the experiments: YG AHT XQ HYZ CLW ZL YJZ ML. Wrote the paper: ZFL FHY QX BZ LLH BBY.
The ferritin is an important participant of iron-storage but its regulation and related factors were not well defined. The present objective was to explore the potential association between serum ferritin levels and sex hormones.
1999 Chinese men in the Fangchenggang Area Male Health and Examination Survey (FAMHES) were recruited in this cross-sectional study. Levels of serum ferritin, total testosterone (free testosterone was calculated from the total one), estradiol and sex hormone-binding protein were detected in venous blood samples. The effects of age, BMI, smoking as well as alcohol consumption were analyzed on ferritin levels, respectively, and then the Pearson’s correlation analysis was used to evaluate the association between ferritin levels and sex hormones adjusting for the above factors.
The age, BMI and alcohol consumption significantly affected serum ferritin levels, but there was no significant difference between smokers and nonsmokers. Ferritin levels were significantly and negatively associated with total testosterone (
The large scale of epidemic results showed the significantly negative associations between serum ferritin levels and sex hormones, which may provide more clues to explore the potential regulation and biological mechanism of ferritin.
Ferritin is a protein that contributes to the iron-storage mainly in our body and distributes widely in all tissues, especially in some organs such as the liver, spleen and bone marrow
It was reported that the two subunits of ferritin was synthesized under the control of different genes in chromosomes 11 and 19, respectively
In view of common diseases and the regulation mechanism of ferritin that were mentioned above, sex hormones may potentially take part in the regulation of ferritin, and then emerge some evidences of correlations between them and serum ferritin levels. However, few studies did describe the relationships between serum ferritin levels and sex hormones
The Fangchenggang Area Male Health and Examination Survey (FAMHES) was designed to investigate the effects that environmental and genetic factors and their interaction had on the development of age-related chronic diseases and the people who participated in this investigation was non-institutionalized men from 17 to 88 years old in Guangxi, China. A total number of 4303 continuous participants in a large-scale physical examination in the Medical Center of Fangchenggang First People’s Hospital from September 2009 to December 2009 were under a comprehensive demographic and health survey. All trained interviewers used this questionnaire to collect epidemiological data through face- to-face interview following the structured guidelines in condition of obtaining written informed consent and the Ethics and Human Subjects Committee of the Guangxi Medical University did approve of this study. Of the 4303 participants, 3136 was self-reported pure Han nationality for three generations and Fangchenggang residents. We excluded the participants with the self-reported information of neoplastic condition, diagnosis of chronic disease, infection with acute infectious diseases, use of any drug with a known effect on the endocrine system or who was considered as prescribed in the past two weeks and people whose data was incomplete about smoking and alcohol consumption were also excluded. Thus, 1999 men was finally recruited and then 10.0 ml venous blood samples was collected from everyone
In the present study, age, body mass index (BMI), smoking, alcohol consumption were considered as potential confounding predictors for ferritin and/or sex hormones
Ferritin, total testosterone, sex hormone-binding protein (SHBG) and estradiol were measured with electrochemiluminescence immunoassay on COBAS 6000 system E601 (Elecsys module) immunoassay analyzers (Roche Diagnostics, IN, Germany) with the same batch of reagents. The interassay coefficients of variation were 3.4%, 3.6%, 4.4% and 3.4%, respectively. The free testosterone (FT) and free testosterone index (FTI) were calculated from the detected total testosterone by the described procedure
Basic characteristics and information of variables were shown by Mean±Standard Deviation (SD), data of serum total testosterone, free testosterone, estradiol and SHBG were normally distributed. Additionally, data of serum ferritin was shown by median and interquartile range, and it was normally distributed after logarithmic transformation (log-ferritin). The One-way ANOVA was used to make comparison in subgroups of age, BMI, smoking and alcohol consumption for log-ferritin. Especially, the multiple comparisons between subgroups were carried under Fisher's LSD method. The analysis of Pearson’s correlation coefficient and Partial correlation coefficient were performed to explore the correlations between log-ferritin and other variables respectively, and the latter was in condition of age and alcohol consumption were adjusted because BMI was correlated with ferritin and age. Besides, the quartile of serum total testosterone, free testosterone and SHBG was obtained and the correlation between them and relevant log-ferritin was explored respectively. All the analysis was performed by SPSS 17.0.
Basic characteristics and information of variables were shown in
Variable | Mean±SD |
Age (year) | 37.54±11.10 |
BMI (kg/m2) | 23.30±3.35 |
Ferritina (ng/ml) | 318.00 (221.40, 459.90) |
Estradiol (pg/ml) | 34.44±9.99 |
SHBGb (nM) | 42.21±20.56 |
Total testosterone (ng/ml) | 6.27±1.91 |
Free testosterone (nM) | 0.42±0.12 |
Free testosterone index (%) | 58.28±22.58 |
Ferritina: the data was shown by median and interquartile range;
SHBGb: sex hormone-binding globulin.
Comparisons for levels of serum ferritin in different subgroups were performed based on age, BMI, smoking and alcohol consumption (
Variable | Number (%) | Serum ferritina (ng/ml) | |
Age (year) | <0.001 | ||
20–29 | 556 (27.81) | 2.44±0.24 | |
30–39 | 682 (34.12) | 2.52±0.26 | |
40–49 | 474 (23.71) | 2.53±0.25 | |
50–59 | 172 (8.60) | 2.47±0.34 | |
60–69 | 115 (5.75) | 2.47±0.36 | |
BMI (kg/m2) | <0.001 | ||
<25 | 1409 (70.49) | 2.45±0.28 | |
≥25 | 590 (29.51) | 2.59±0.23 | |
Smoking | 0.447 | ||
yes | 1021 (51.08) | 2.50±0.27 | |
no | 978 (48.92) | 2.49±0.27 | |
Alcohol consumption | 0.011 | ||
yes | 1651 (82.59) | 2.50±0.27 | |
no | 348 (17.41) | 2.46±0.28 |
Serum ferritina: the data of serum ferritin was log-transformed and the results were present by Mean ± SD.
We firstly investigated the direct correlation between ferritin and sex hormone levels without any adjustment of potential confounding factors. Our data showed that the correlation between serum log-ferritin and all sex hormones were significant and negative (
Variables | ||||
Total testosterone (ng/ml) | –0.205 | <0.001 | –0.200 | <0.001 |
Free testosterone (nM/L) | –0.097 | <0.001 | –0.083 | <0.001 |
SHBGc (nM/L) | –0.161 | <0.001 | –0.182 | <0.001 |
Estradiol (pg/ml) | –0.048 | 0.034 | –0.039 | 0.083 |
R1a: Pearson’s correlation coefficient in condition of none was adjusted; R2b: Partial correlation coefficient in condition of age and alcohol consumption was adjusted; SHBGc: sex hormone-binding globulin;
Additionally, we stratified all subjects into four subgroups according to the quartiles of sex hormone levels, and those subjects with the free testosterone levels from 0.42 to 0.47 nM had higher ferritin levels than those with levels from 0.35–0.41 nM,
In our population-based cross-sectional study, data showed that levels of serum ferritin were negatively associated with sex hormones. For serum total testosterone, free testosterone and SHBG, the associations were significant whether those potential confounding factors were adjusted or not.
The small quantity of human serum ferritin was regulated by several factors and associated with several diseases
Interestingly, the correlation between serum ferritin and sex hormones was value of a deeper exploration in term of hematopoiesis. For erythrocytosis, it was significantly related with sex hormones, especially the testosterone, because the iron was stimulated into erythrocyte by testosterone
To our knowledge, there was no direct investigation to explore relationships between sex hormones
Some study limitations needed to be addressed when interpreting these results. Firstly, this present study was a cross-sectional design so that the direction and convincingness of association should be validated by some experiments
In conclusion, our data showed significantly negative associations between levels of serum ferritin and sex hormones, and these results may be helpful to the further exploration about the regulation or mechanisms of the ferritin.
We thank the local research teams from Fangchenggang First People’s Hospital, Fangchenggang, China, for their contribution to the survey sincerely.