Association between iron deficiency and telogen effluvium: a systematic review and meta- analysis

Association between iron deficiency and telogen effluvium: a systematic review and meta- analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Association between iron deficiency and telogen effluvium: a systematic review and meta- analysis Xiaojing Kang, Jingzhan Zhang, Mengmeng Guan, Yuan Ding, Yunxia Ma, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1519227/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Iron deficiency has been associated with telogen effluvium, but currently, the data regarding their association are conflicting. To derive a more precise estimation of this association, we performed a systematic review and meta-analysis to investigate serum ferritin level, serum iron level, and prevalence of ferritin deficiency in all published studies. Databases including PubMed, Google Scholar, Offshore Vessel Inspection Database, and Cochrane Library, were systematically searched. The association was assessed using standardized mean differences, odds ratios, and 95% confidence intervals. Statistical analysis was performed using Review Manager version 5.4.1. A total of 20 studies were identified. The results showed that in patients with telogen effluvium, including those with acute and chronic telogen effluvium, serum iron and serum ferritin levels were lower than those in the normal population. There was no significant difference in serum ferritin and iron levels between patients with acute and chronic telogen effluvium. In patients with chronic telogen effluvium, the prevalence of ferritin deficiency was higher than that in the general population when ferritin levels were 20 ng/dl and 30 ng/dl as the threshold for the diagnosis of iron deficiency. This meta-analysis revealed that iron deficiency is associated with telogen effluvium and clarified the critical serum ferritin level for defining iron deficiency in patients with telogen effluvium. Iron deficiency telogen effluvium serum ferritin serum iron Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Telogen effluvium is a diffuse, non-scarring alopecia characterized by the simultaneous loss of a large number of telogen hairs and was named by Kligman in 1961[ 1 ]. Changes in the hair follicle cycle, such as shortening or lengthening of the anagen and telogen phases and synchronous hair follicle cycling, can induce hair shafts to fall out synchronously during the telogen phase, resulting in telogen effluvium[ 2 ]. Telogen effluvium is common in non-menopausal women, with an incidence rate of approximately 30% in the United States, Britain, and Japan, which seriously increases the economic and psychological burden on patients[ 3 , 4 ]. Telogen effluvium does not have a specific predisposing ethnicity, but women are more likely than men to seek medical attention for telogen effluvium[ 5 ]. Depending on the disease duration, it can be divided into acute and chronic[ 6 ]. When the onset of telogen effluvium is acute, the daily amount of hair loss is > 300 hairs, the incubation period is generally 2–3 months, and it can occur at any age [ 2 , 7 ]. The course of the disease lasts for 4–6 months, and 95% of patients can control their hair loss within 6 months. Chronic telogen effluvium usually lasts for more than 6 months and up to 2–3 years, occurs most often in women aged 30–60 years, and has a long and fluctuating course[ 8 , 9 ]. Although telogen effluvium is a common dermatological disease, the cause of hair loss remains unclear. However, this hypothesis is controversial. Telogen effluvium is associated with a variety of endogenous and exogenous factors, including surgery, bleeding, childbirth, severe illness, malnutrition, micronutrient deficiencies, drugs, and major stressful events[ 10 – 14 ]. Iron deficiency is a potential cause of hair loss. Many studies have investigated the association between iron deficiency and telogen effluvium. The studies have mainly focused on the association between the reduction in serum iron and ferritin levels and hair loss. Iron in the human body is divided into three components: iron storage, iron transport, and functional iron. Iron deficiency is divided into three stages: reduced iron storage, reduced iron storage plus transported iron, and iron deficiency anemia[ 15 ]. Serum iron is a marker of iron transport and can reflect the state of iron deficiency in the body. Serum ferritin is a complex formed between apoferritin and iron core Fe3+, which is the storage form of iron, and ferritin is a marker of iron storage[ 16 , 17 ]. Ferritin is the first to be affected when iron is deficient[ 18 ]. Serum ferritin can reliably reflect iron deficiency and is synchronized with bone marrow iron staining with high sensitivity and specificity[ 19 ]. However, there is currently no universally accepted serum ferritin level for defining iron deficiency. In studies on iron deficiency and alopecia, serum ferritin was used to define the cut-off value of iron deficiency ranging from 10 to 70 ug/L[ 1 , 20 , 21 ]. Studies evaluating the association between iron deficiency and telogen effluvium have yielded conflicting results, and the value of iron supplementation in patients remains unclear[ 22 – 24 ]. Currently, there is no published evidence-based medical evidence on the association between iron deficiency and telogen effluvium and accepted serum ferritin level for defining iron deficiency. Therefore, we conducted a meta-analysis of the relationship between iron deficiency and telogen effluvium. Results Study characteristics We retrieved 1642 studies. After removing duplicates, 890 studies were evaluated. By reading the titles and abstracts and excluding irrelevant articles and reviews, the remaining 346 articles were further evaluated. After reading the full text, a total of 20 studies were included in the final meta-analysis. Seventeen were case-control studies[25-41], and three were cross-sectional studies[42-44]. The publication years ranged from 2005 to 2021, with a total of 3642 participants. The NOS results showed that the methodological quality was generally high. The vast majority of participants were young and middle-aged women, including people in Asia, Europe, and North America. Among them, Egypt, Turkey, and Iran included three studies; India and Iran included two studies; and Bangladesh, China, Jordan, Nepal, Pakistan, Saudi Arabia, and the United States included one study each. The included studies evaluated serum ferritin level, serum iron level, and prevalence of ferritin deficiency. The subjects were patients with acute and chronic telogen effluvium. We performed a subgroup analysis of different hair loss types to explore the similarities and differences in serum iron and ferritin levels. The subjects with acute and chronic telogen effluvium were placed in separate subgroups, and those with unclassified telogen effluvium were placed in the telogen effluvium group. The literature search flowchart is shown in Figure 1. Table 1 presents the characteristics of the included studies. Table 1 Baseline characteristics of the included studies. Author (year) Type of study Sample size(P/C) country Sex (P/C) Age(P/C) (mean ± SD, y) Type Diagnosis Data collected NOS Alizadeh et al.2021 Case-control 83/83 Iran Female 36.78±5.88 CTE History, physical examination, pull test,dermoscopy serum ferritin, prevalence of ferritin deficiency 7 Cheng et al.2021 Cross-Sectional 193/183 China NA/Female 28.37±5.11/29.11±5.46 TE, ATE, CTE History, physical examination, pull test,dermoscopy serum iron, serum ferritin 7 Chisti et al.2012 Case-control 100/100 India Female 26.6±7.25/26.83±9.97 ATE, CTE History, physical examination serum ferritin 7 Elethawi et al.2012 Case-control 38/25 Iraq Female 30.15±6.5 CTE History, physical examination, pull test serum ferritin 7 Ertug et al.2018 Case-control 455/196 Turkey Female 29.01±8.71/31.29±8.7 TE History, physical examination, pull test serum iron 7 Fatani et al.2015 Cross-Sectional 160/425 Saudi Arabia Female 28.94±10.6/34.24±11.4 TE History, physical examination serum ferritin 6 Hamad et al.2010 Case-control 34/26 Egypt Female 22.95±7.31/19.06±9.82 TE History, physical examination, pull test, trichogram serum iron 7 Hasseeb et al.2020 Case-control 53/26 Iraq Female Range 18–45 ATE, CTE History, physical examination serum iron, serum ferritin 7 Hodeib et al.2017 Case-control 40/20 Egypt Female 28.10±4.65/27.45±6.41 TE, ATE, CTE History, physical examination, pull test,dermoscopy serum iron, serum ferritin 7 Karadag et al.2011 Case-control 63/50 Turkey Female 29.1±11.9/28.4±9.4 TE, ATE, CTE History, physical examination, dermoscopy serum ferritin 7 Karim et al.2010 Case-control 30/30 Bangladesh Female 25.4 ±7/24.8 ±5.6 TE History, physical examination, pull test serum ferritin 7 Moeinvaziri et al.2009 Case-control 30/30 Iran Female 28.1±8.5/29.4±8.2 CTE History, physical examination, trichogram serum iron, serum ferritin, prevalence of ferritin deficiency 7 Naser et al.2021 Cross-sectional 60/60 Iraq Female 32.6±6.47/41.3±4.59 CTE History, physical examination, pull test serum ferritin, prevalence of ferritin deficiency 7 Obaidat et al.2005 Case-control 72/30 Jordan Female 26±9.2/32±11.6 CTE History, physical examination, pull test serum ferritin, prevalence of ferritin deficiency 7 Olsen et al.2010 Case-control 381/76 USA Female Range 18-65 TE History, physical examination serum ferritin, prevalence of ferritin deficiency 7 Pradhan et al.2018 Case-control 60/60 Nepal Female 33.93±11.02/34.97±10.42 TE History, physical examination serum ferritin 7 Rasheed et al.2013 Case-control 80/40 Egypt Female 29.8 ± 9.3/30.8 ± 8.56 TE History, physical examination, pull test, trichogram, dermoscopy serum ferritin 7 Sarkar et al.2013 Case-control 40/40 India Female 24.28 ± 6.17/23.11±4.67 CTE History, physical examination, pull test, trichogram serum ferritin, prevalence of ferritin deficiency 7 Ullah et al.2019 Case-control 50/50 Pakistan Female 26±7.61/31.88±6.62 TE History, physical examination, pull test serum ferritin 7 Yavuz et al.2018 Case-control 40/30 Turkey NA/Female NA CTE NA serum iron 7 Abbreviations: P, patients; C, control; TE, telogen effluvium; ATE, acute telogen effluvium; CTE, chronic telogen effluvium; NA, not applicable. Main results Serum ferritin level in telogen effluvium Ten studies measured serum ferritin level in telogen effluvium[27,28,30,31,34,35,37,39,43,44]. Significant heterogeneity was observed (P < 0.00001, I 2 = 93%), and a random-effects model was applied. These results showed that serum ferritin levels were lower in the telogen effluvium group than in the control group (P < 0.00001, SMD = −1.09, 95% CI = −1.50 to −0.69). Four studies measured serum ferritin level in acute telogen effluvium[26,28-30]. Heterogeneity was observed (P = 0.04, I 2 = 63%). A random-effects model was used. The acute telogen effluvium group had a lower serum ferritin level than the control group (P = 0.03, SMD = −0.53, 95% CI = −1.00 to −0.06). Nine studies measured serum ferritin level in chronic telogen effluvium[26,28-30,32,33,36,40,42]. Heterogeneity was observed (P = 0.0001, I 2 = 75%). A random-effects model was used. The chronic telogen effluvium group had lower serum ferritin level than the control group (P < 0.0001, SMD = −0.73, 95% CI = −1.06 to −0.40). Serum ferritin levels were lower in patients with different types of telogen effluvium than in the normal population. The results are shown in Figure 2. Serum iron level in telogen effluvium Three studies had a measurement of serum iron level in telogen effluvium[27,28,39]. Heterogeneity was found (P < 0.00001, I 2 = 93%), and the random-effects model was applied. These results showed that serum iron level was reduced in the telogen effluvium compared to the control group (P = 0.03, SMD =−1.09, 95% CI =−2.06 to −0.11). Only two studies had a measurement of serum iron level in acute telogen effluvium[28,29]. No significant heterogeneity was observed (P = 0.52, I 2 = 0%). To maintain the consistency of the results, we used the random-effects model. The acute telogen effluvium group had significantly lower serum iron level than the control group (P = 0.001, SMD = −0.77, 95% CI = −1.25 to −0.30). We also switched the fixed-effects model analysis, which is consistent with the random-effects model. Three studies had a measurement of the serum iron level in chronic telogen effluvium[28,29,32]. Heterogeneity was observed (P = 0.04, I 2 = 68%). A random-effects model was applied. The chronic telogen effluvium group had significantly lower serum iron level than the control group (P = 0.005, SMD = −0.84, 95% CI = −1.42 to −0.26). In patients with different types of telogen effluvium, serum iron levels were lower than those in the normal population. The results are shown in Figure 3. Serum ferritin and iron levels in acute and chronic telogen effluvium Four studies had a measurement of serum ferritin level in acute and chronic telogen effluvium[26,28-30]. Only two studies had a measurement of serum iron level in acute and chronic telogen effluvium[28,29]. No significant heterogeneity was observed, and the fixed-effects model was applied. There was no significant difference in serum ferritin level between acute and chronic telogen effluvium (P = 0.62, SMD = 0.08, 95% CI = −0.23–0.38), nor were serum iron levels (P = 0.26, SMD = 0.26, 95% CI = −0.19–0.72). The results are shown in Figure 4. Prevalence of ferritin deficiency and telogen effluvium Six studies on chronic telogen effluvium have reported the prevalence of ferritin deficiency, which has not been publicly reported in patients with acute telogen effluvium. Due to the small number of included studies, we directly used a random-effects model for analysis. Three studies reported the prevalence of ferritin deficiency and chronic telogen effluvium with ferritin level below 10–15 μg/L (ng/mL)[25,32,41]. There was no significant difference between the chronic telogen effluvium and control groups (P = 0.51, SMD = 1.57, 95% CI = 0.41–5.95). Two studies reported the prevalence of ferritin deficiency and chronic telogen effluvium with ferritin levels of 20 μg/L[33,36], 30 μg/L[32,42], 40 μg/L[25,41], and ≤ 70 μg/L[41,42]. The prevalence of ferritin deficiency in the chronic telogen effluvium group was significantly higher than that in the control group at serum ferritin levels of 20 μg/L (P = 0.0002, SMD = 4.32, 95% CI = 1.99–9.38) and 30 μg/L (P < 0.00001, SMD = 18.62, 95% CI = 8.28–41.90). No significant difference was observed between the chronic telogen effluvium and control groups with ferritin levels of 40 μg/L (P = 0.43, SMD = 1.22, 95% CI = 0.74–2.00) and ≤ 70 μg/L (P = 0.54, SMD = 1.97, 95% CI = 0.23–16.74). In patients with chronic telogen effluvium, the prevalence of iron deficiency was higher than that in the general population with ferritin levels at thresholds of 20 μg/L and 30 μg/L, and the difference was statistically significant. The results are shown in Figure 5. Sensitivity analysis The contribution of each study to the pooled estimate was evaluated to assess the sensitivity of the analyses. Yavuz et al. had an undue influence on the summary SMD under the serum iron level in acute telogen effluvium[38]. This was excluded from the analysis. Other studies did not substantially change the pooled point estimates. We also converted the random- and fixed-effects models in all studies. No substantial changes were observed in these data. These results confirm the reliability of the present study. Publication bias Funnel plots were used to evaluate the publication bias. In the study of serum ferritin and iron levels in patients with telogen effluvium, the funnel plot was symmetrical, suggesting that the overall publication bias was small (Figure 6). In the studies on the prevalence of serum ferritin deficiency, because only two to three studies were included in each subgroup, the number was relatively small, and no further publication bias testing was performed. Discussion This study used evidence-based medicine to assess the association between iron deficiency and telogen effluvium, including studies from several countries in Asia, Europe, and the United States. The serum ferritin and iron levels of patients with acute and chronic telogen effluvium were lower than those of controls. There was no significant difference in serum ferritin levels or serum iron reduction levels between patients with acute and chronic telogen effluvium. In patients with chronic telogen effluvium, the prevalence of ferritin deficiency is higher than that in the general population when ferritin levels are 20 ng/dl and 30 ng/dl as the threshold for the diagnosis of iron deficiency. However, the mechanism by which iron affects hair growth remains unclear. Iron metabolism is the basis of the interaction between oxidative stress and antioxidants[ 45 ]. Iron can regulate the oxidative activity of tyrosinase, which is significantly associated with hair whitening[ 46 ]. Iron is a cofactor of ribonucleotide reductase, the rate-limiting enzyme in DNA synthesis. Iron deficiency prevents the normal function of this enzyme, thus inhibiting proliferation and other iron-dependent enzymes and leading to hair loss[ 47 ]. The level of ferritin in non-dividing cells, such as hair follicle stem cells and terminal differentiated cells, increased, whereas the level of ferritin in rapidly proliferating hair follicle stromal cells was low, and the level of free iron was high. This balance between ferritin and iron is partially controlled by the transcription factor c-myc, and overexpression of c-myc may cause hair loss[ 48 , 49 ]. Some genes in the human hair follicles may be regulated by iron. Iron deficiency may have an effect on gene expression, but its specific mechanism remains unclear[ 50 ]. Currently, the majority of the women in the current study are premenopausal, and therefore are more like to have hair loss due to loss of iron stores through menstruation. The research subjects were mainly young and middle-aged female patients, and only one study explicitly identified premenopausal and postmenopausal female patients with telogenic hair loss[ 41 ]. This study defined iron deficiency as ferritin ≤ 15 µg/L or ≤ 40 µg/L and found no significant difference in the prevalence of iron deficiency in women with chronic telogen effluvium or female pattern hair loss compared with controls and premenopausal or postmenopausal iron deficiency. There was no significant difference in the prevalence. Serum ferritin levels are the most specific and effective measure of whole-body iron stores and are commonly used[ 51 ]. The prevalence of reduced serum ferritin levels (< 30–40 µg/L) appears to be higher in women with telogen effluvium than in the general population[ 52 ]. Serum ferritin levels below 30 µg/L were found in 40–50% of women in Cambodia[ 53 ], Portugal [ 54 ], Norway, and Denmark [ 55 ]. Although values < 12–15 µg/L can confirm iron deficiency, serum ferritin level < 30 µg/L is more widely used due to its higher sensitivity (92%) and similar specificity (98%) [ 16 , 56 , 57 ]. This study shows that if serum ferritin ≤ 15 µg/L or ≤ 70 µg/L is used as the cut-off value for the diagnosis of iron deficiency in patients with chronic telogen effluvium, the prevalence of iron deficiency in the telogen effluvium group and the control group was not statistically different. If serum ferritin level was 20 µg/L or 30 µg/L for the diagnosis of iron deficiency, the prevalence of iron deficiency was statistically different compared to that in the non-alopecia population. There are few intervention trials of iron supplementation in patients with alopecia, which may be due to conflicting conclusions from previous studies on whether patients with alopecia are iron-deficient. Several studies have been published using different interventions, including iron with L-lysine[ 24 , 58 ], iron alone[ 59 ], and iron with spironolactone[ 60 ]. Two studies targeted interventions with ferritin levels > 50 µg/L[ 61 ] or 70 µg/L[ 23 ]. These studies were limited by small sample sizes and differences in ferritin levels. However, monitoring serum iron levels is important in patients taking oral iron supplements. Taking iron supplements without monitoring is associated with a risk of potentially serious complications[ 62 , 63 ]. This study has certain limitations. First, there were ethnic differences among the included participants, different dietary habits, and differences in their intake of iron. Second, ferritin levels can be elevated in diseases such as inflammation, chronic kidney disease, and tumors[ 64 , 65 ]. Although this study was screened, there may still have been some selection bias. Third, the sample size of the included population was small, and there may be differences in the examination methods of serum ferritin, which reduces the reliability of the conclusion of this study. However, this study also has some clinical significance. This study is the first to use evidence-based medicine to confirm that serum iron and serum ferritin levels are decreased in patients with telogen effluvium. This study also found that in some studies using ferritin to define iron deficiency, the prevalence of alopecia was not significantly lower than that of the non-alopecia population, which may be due to the selection of a critical value that is significantly low or significantly high. Conclusion This study shows that iron deficiency is associated with telogen effluvium and provides evidence-based medical evidence for the treatment of telogen effluvium with iron supplementation. Simultaneously, this study clarified the critical value of serum ferritin to define iron deficiency in patients with telogen effluvium and provided a reference value for the screening of iron deficiency in patients with alopecia. Materials And Methods The study was carried out based on the principles of the PRISMA statement[66]. This protocol was registered in PROSPERO (ID 42022310129). The raw data and fully reproducible code are available on the OSF (https://osf.io/d58at/). Literature search We searched for literature describing the association between iron deficiency and telogen effluvium. Literature was retrieved by a formal search of electronic databases (PubMed, Offshore Vessel Inspection Database, Cochrane Library, and Google Scholar) and by manually searching the reference lists of related articles. The computer searches were limited before February 2022, using the keywords: “iron” OR “ferrum” OR “ferritin” AND “hair loss” OR “alopecia” OR “telogen effluvium”. The language used was limited to English. There were no ethnic restrictions. Inclusion criteria The diagnosis of telogen effluvium was based on the examination results of physical examination, pull test, history, dermoscopy, and/or trichogram. The inclusion criteria were as follows: (1) published literatures related to the association of serum iron level, serum ferritin level, or prevalence of ferritin deficiency with telogen effluvium; (2) independent case-control or cross-sectional studies; and (3) original studies providing the mean and standard of serum iron level and the number of each group, serum ferritin level, or prevalence of ferritin deficiency. Exclusion criteria The exclusion criteria were as follows: (1) studies with original data that could not be extracted; (2) studies with duplicated data; and (3) studies with study participants having specific diseases that may have an effect on serum iron or ferritin, such as acute infections, fever, and chronic wasting disease; with patients undergoing bariatric surgery, or with patients with cancer. Data extraction Two authors (J.Z.Z. and M.M.G.) independently extracted the original data. They independently decided whether to include each study. Disagreements were resolved by discussion with the third investigator (L.D.). The extracted data consisted of the following items: the first author’s name, year of publication, method of diagnosis, type of study, sample size, sex, age, country, and measures of iron deficiency. Quality assessment Study quality was assessed using the Newcastle-Ottawa Scale (NOS)[67]. Three aspects were considered in the NOS criteria: (1) selection of research objects (0–4 stars), (2) comparability of research objects (0–2 stars), and (3) exposure or outcome (0–3 stars). NOS scores range from 0 (worst) to 9 stars (best); a score equal to or higher than 7 indicated that the study was of good quality. Two investigators (Y.D. and Y.X.M.) independently assessed the quality of each included study. Disagreements were resolved by discussion with the participation of the third investigator (T.T.L.). Statistical analyses Review Manager 5.41 (The Nordic Cochrane Centre, Copenhagen) was used to perform the meta-analysis. Continuous variables were analyzed using standardized mean differences (SMDs) with 95% confidence intervals (CIs). Dichotomous data were analyzed using odds ratios (ORs) corresponding to 95% CI. Heterogeneity among the studies was assessed using the I 2 statistic[68]. If heterogeneity existed among the studies (P 50%), the random effects model was used to estimate[69]. Otherwise, a fixed-effects model was adopted[70]. Sensitivity analysis was performed to assess the robustness and heterogeneity of the combined results. Funnel plots were used to assess the potential publication bias. Declarations Funding This study was funded by the Key R & D projects of Xinjiang Uygur Autonomous Region (Research on key technologies for prevention and treatment of common and difficult skin diseases in Xinjiang, 2021B03001-1). Conflicts of interest The authors declared no competing interests exist. Acknowledgements We would like to thank Editage (www.editage.com) for English language editing. Author Contributions J.Z. Z. and X.J.K. designed the study. J.Z.Z., M.M.G. and L.D. screened the articles, extracted the data. Y.D., Y.X.M., and T.T.L. assessed the risk of bias, and analysed and interpreted the data. J.Z. Z. wrote the first draft of the manuscript. X.J.K. reviewed the subsequent versions and the final draft. All authors approved the final version. References Grover, C.; Khurana, A. Telogen effluvium. Indian journal of dermatology, venereology and leprology 2013 , 79 , 591-603, doi:10.4103/0378-6323.116731. Asghar, F.; Shamim, N.; Farooque, U.; Sheikh, H.; Aqeel, R. Telogen Effluvium: A Review of the Literature. Cureus 2020 , 12 , e8320, doi:10.7759/cureus.8320. Harfmann, K.L.; Bechtel, M.A. Hair Loss in Women. Clinical Obstetrics & Gynecology 2015 , 58 , 185-199. 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Makurat, J.; Friedrich, H.; Kuong, K.; Wieringa, F.T.; Chamnan, C.; Krawinkel, M.B. Nutritional and Micronutrient Status of Female Workers in a Garment Factory in Cambodia. Nutrients 2016 , 8 , doi:10.3390/nu8110694. Fonseca, C.; Marques, F.; Robalo Nunes, A.; Belo, A.; Brilhante, D.; Cortez, J. Prevalence of anaemia and iron deficiency in Portugal: the EMPIRE study. Intern Med J 2016 , 46 , 470-478, doi:10.1111/imj.13020. Milman, N.; Taylor, C.L.; Merkel, J.; Brannon, P.M. Iron status in pregnant women and women of reproductive age in Europe. The American journal of clinical nutrition 2017 , 106 , 1655s-1662s, doi:10.3945/ajcn.117.156000. Lopez, A.; Cacoub, P.; Macdougall, I.C.; Peyrin-Biroulet, L. Iron deficiency anaemia. Lancet (London, England) 2016 , 387 , 907-916, doi:10.1016/s0140-6736(15)60865-0. Mast, A.E.; Blinder, M.A.; Gronowski, A.M.; Chumley, C.; Scott, M.G. Clinical utility of the soluble transferrin receptor and comparison with serum ferritin in several populations. Clinical chemistry 1998 , 44 , 45-51. Rushton, D.H.; Norris, M.J.; Dover, R.; Busuttil, N. Causes of hair loss and the developments in hair rejuvenation. International journal of cosmetic science 2002 , 24 , 17-23, doi:10.1046/j.0412-5463.2001.00110.x. NON-ANEMIC IRON DEFICIENCY AS AN ETIOLOGIC FACTOR IN DIFFUSE LOSS OF HAIR OF THE SCALP IN WOMEN. Acta dermato-venereologica 1963 , 43 , 562-569. Sinclair, R. There is no clear association between low serum ferritin and chronic diffuse telogen hair loss. The British journal of dermatology 2002 , 147 , 982-984, doi:10.1046/j.1365-2133.2002.04997.x. St Pierre, S.A.; Vercellotti, G.M.; Donovan, J.C.; Hordinsky, M.K. Iron deficiency and diffuse nonscarring scalp alopecia in women: more pieces to the puzzle. Journal of the American Academy of Dermatology 2010 , 63 , 1070-1076, doi:10.1016/j.jaad.2009.05.054. Coates, T.D.; Carson, S.; Wood, J.C.; Berdoukas, V. Management of iron overload in hemoglobinopathies: what is the appropriate target iron level? Annals of the New York Academy of Sciences 2016 , 1368 , 95-106, doi:10.1111/nyas.13060. Guo, E.L.; Katta, R. Diet and hair loss: effects of nutrient deficiency and supplement use. Dermatol Pract Concept 2017 , 7 , 1-10, doi:10.5826/dpc.0701a01. Coyne, D.W. Iron Indices: What do they really mean? Kidney international. Supplement 2006 , 69 , S4-8. Rivella, S.; Crielaard, B.J. Disorders of Iron Metabolism: Iron Deficiency and Iron Overload and Anemia of Chronic Diseases - ScienceDirect. Pathobiology of Human Disease 2014 , 1471-1487. . Stang, A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. European journal of epidemiology 2010 , 25 , 603-605, doi:10.1007/s10654-010-9491-z. Higgins, J.P.; Thompson, S.G.; Deeks, J.J.; Altman, D.G. Measuring inconsistency in meta-analyses. Bmj 2003 , 327 , 557-560, doi:10.1136/bmj.327.7414.557. DerSimonian, R.; Kacker, R. Random-effects model for meta-analysis of clinical trials: an update. Contemporary clinical trials 2007 , 28 , 105-114, doi:10.1016/j.cct.2006.04.004. Mantel, N.; Haenszel, W. Statistical aspects of the analysis of data from retrospective studies of disease. Journal of the National Cancer Institute 1959 , 22 , 719-748. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1519227","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":99817952,"identity":"436c76d2-3ddf-460a-82ec-bede654f6891","order_by":0,"name":"Xiaojing Kang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3klEQVRIiWNgGAWjYDCCA2xgipmfvfngg4SKGhK0SPYcSzZ4cOYY8VoYDGb4qEk+bGEmrIPv9rHEzwW/DrMbSPCwVSQ2sDHwt3cn4NUieS7tsPTMvjRmc+neYzcSd8gwSJw5uwGvFoMz7A3SvD02zJZzzqXdSDzDxmAgkUtQS/Nv3h4JZoMbOWYFiW3MxGhhOybN88MGrIWBKC2SZ9jSrHkb0sCBLJFw5hgPQb/wnWEzvs3z53AyKCo//qiokeNv78WvBQwY2xiSYWwewsrB4A+DHZEqR8EoGAWjYCQCAKctSzjh0yKuAAAAAElFTkSuQmCC","orcid":"","institution":"People's Hospital of Xinjiang Uygur Autonomous Region","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Xiaojing","middleName":"","lastName":"Kang","suffix":""},{"id":99817946,"identity":"6f9aa092-5291-4fe3-a9d8-f5b0de4f8356","order_by":1,"name":"Jingzhan Zhang","email":"","orcid":"","institution":"People's Hospital of Xinjiang Uygur Autonomous Region","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jingzhan","middleName":"","lastName":"Zhang","suffix":""},{"id":99817947,"identity":"4cbb3b3c-8eb5-4902-b207-fac3fc2facd4","order_by":2,"name":"Mengmeng Guan","email":"","orcid":"","institution":"People's Hospital of Xinjiang Uygur Autonomous Region","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mengmeng","middleName":"","lastName":"Guan","suffix":""},{"id":99817948,"identity":"a5e2f096-b361-421d-8bbd-1c9c282f2f33","order_by":3,"name":"Yuan Ding","email":"","orcid":"","institution":"People's Hospital of Xinjiang Uygur Autonomous Region","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yuan","middleName":"","lastName":"Ding","suffix":""},{"id":99817949,"identity":"a2139e21-efe8-4833-b627-7bb85e292d03","order_by":4,"name":"Yunxia Ma","email":"","orcid":"","institution":"People's Hospital of Xinjiang Uygur Autonomous 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15:14:02","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1519227/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1519227/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":20624019,"identity":"9632afd6-f05f-4dfc-85e4-9bb929db9ff9","added_by":"auto","created_at":"2022-04-21 19:42:48","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":118081,"visible":true,"origin":"","legend":"\u003cp\u003eFlow of the selection of literature that reported the relationship of iron deficiency and telogen effluvium.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-1519227/v1/35e91a64ff018d053fb84e3e.png"},{"id":20623802,"identity":"b0c03131-2d32-42cb-8e4d-78dcd1c5e3b5","added_by":"auto","created_at":"2022-04-21 19:37:48","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":213644,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of the serum ferritin level in different types of telogen effluvium compared to the control groups.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-1519227/v1/dddee25f5d438f90e5debef3.png"},{"id":20623806,"identity":"8135f540-7efd-4f30-a788-6f3ea4d0aaf6","added_by":"auto","created_at":"2022-04-21 19:37:48","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":150683,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of the serum iron level in different types of telogen effluvium compared to the control groups.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-1519227/v1/2a88c274d0d26ad16abf4df2.png"},{"id":20624166,"identity":"ae15b2db-ed20-4a1d-b521-b2f6351cfdfd","added_by":"auto","created_at":"2022-04-21 19:47:48","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":101066,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of the serum ferritin and iron level in acute telogen effluvium compared to chronic telogen effluvium.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-1519227/v1/3f7cd0f426e2e08419343688.png"},{"id":20623803,"identity":"1d6ad25d-fc08-4ddc-86c0-76a36242b16c","added_by":"auto","created_at":"2022-04-21 19:37:48","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":152489,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of the prevalence of ferritin deficiency in chronic telogen effluvium compared to the control groups.\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-1519227/v1/c4e350bb244b3e86b250835d.png"},{"id":20624208,"identity":"1965ebad-90c4-4dc9-8f69-e7f592ce5121","added_by":"auto","created_at":"2022-04-21 19:52:48","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":67123,"visible":true,"origin":"","legend":"\u003cp\u003eFunnel plot for publication bias tests. Each point represents a separate study for the indicated association. (a): serum ferritin level in different types of telogen effluvium vs. control groups; (b): serum iron level in different types of telogen effluvium vs. control groups; (c): serum ferritin and iron level in acute telogen effluvium vs. chronic telogen effluvium.\u003c/p\u003e","description":"","filename":"Figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-1519227/v1/d8a0aa41ec8cc74bbc9e11ec.png"},{"id":24384979,"identity":"262bc191-5f79-4f48-a8c0-2f2af7fb9c9e","added_by":"auto","created_at":"2022-07-27 06:44:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1222271,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1519227/v1/6329c792-12d0-4794-b47e-b4ac43ed9e4c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association between iron deficiency and telogen effluvium: a systematic review and meta- analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTelogen effluvium is a diffuse, non-scarring alopecia characterized by the simultaneous loss of a large number of telogen hairs and was named by Kligman in 1961[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Changes in the hair follicle cycle, such as shortening or lengthening of the anagen and telogen phases and synchronous hair follicle cycling, can induce hair shafts to fall out synchronously during the telogen phase, resulting in telogen effluvium[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Telogen effluvium is common in non-menopausal women, with an incidence rate of approximately 30% in the United States, Britain, and Japan, which seriously increases the economic and psychological burden on patients[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Telogen effluvium does not have a specific predisposing ethnicity, but women are more likely than men to seek medical attention for telogen effluvium[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Depending on the disease duration, it can be divided into acute and chronic[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. When the onset of telogen effluvium is acute, the daily amount of hair loss is \u0026gt;\u0026thinsp;300 hairs, the incubation period is generally 2\u0026ndash;3 months, and it can occur at any age [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The course of the disease lasts for 4\u0026ndash;6 months, and 95% of patients can control their hair loss within 6 months. Chronic telogen effluvium usually lasts for more than 6 months and up to 2\u0026ndash;3 years, occurs most often in women aged 30\u0026ndash;60 years, and has a long and fluctuating course[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Although telogen effluvium is a common dermatological disease, the cause of hair loss remains unclear. However, this hypothesis is controversial. Telogen effluvium is associated with a variety of endogenous and exogenous factors, including surgery, bleeding, childbirth, severe illness, malnutrition, micronutrient deficiencies, drugs, and major stressful events[\u003cspan additionalcitationids=\"CR11 CR12 CR13\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIron deficiency is a potential cause of hair loss. Many studies have investigated the association between iron deficiency and telogen effluvium. The studies have mainly focused on the association between the reduction in serum iron and ferritin levels and hair loss. Iron in the human body is divided into three components: iron storage, iron transport, and functional iron. Iron deficiency is divided into three stages: reduced iron storage, reduced iron storage plus transported iron, and iron deficiency anemia[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Serum iron is a marker of iron transport and can reflect the state of iron deficiency in the body. Serum ferritin is a complex formed between apoferritin and iron core Fe3+, which is the storage form of iron, and ferritin is a marker of iron storage[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Ferritin is the first to be affected when iron is deficient[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Serum ferritin can reliably reflect iron deficiency and is synchronized with bone marrow iron staining with high sensitivity and specificity[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. However, there is currently no universally accepted serum ferritin level for defining iron deficiency. In studies on iron deficiency and alopecia, serum ferritin was used to define the cut-off value of iron deficiency ranging from 10 to 70 ug/L[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Studies evaluating the association between iron deficiency and telogen effluvium have yielded conflicting results, and the value of iron supplementation in patients remains unclear[\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Currently, there is no published evidence-based medical evidence on the association between iron deficiency and telogen effluvium and accepted serum ferritin level for defining iron deficiency. Therefore, we conducted a meta-analysis of the relationship between iron deficiency and telogen effluvium.\u003c/p\u003e"},{"header":"Results","content":"\u003ch2\u003eStudy characteristics\u003c/h2\u003e\n\u003cp\u003eWe retrieved 1642 studies. After removing duplicates, 890 studies were evaluated. By reading the titles and abstracts and excluding irrelevant articles and reviews, the remaining 346 articles were further evaluated. After reading the full text, a total of 20 studies were included in the final meta-analysis. Seventeen were case-control studies[25-41], and three were cross-sectional studies[42-44]. The publication years ranged from 2005 to 2021, with a total of 3642 participants. The NOS results showed that the methodological quality was generally high. The vast majority of participants were young and middle-aged women, including people in Asia, Europe, and North America. Among them, Egypt, Turkey, and Iran included three studies; India and Iran included two studies; and Bangladesh, China, Jordan, Nepal, Pakistan, Saudi Arabia, and the United States included one study each. The included studies evaluated serum ferritin level, serum iron level, and prevalence of ferritin deficiency. The subjects were patients with acute and chronic telogen effluvium. We performed a subgroup analysis of different hair loss types to explore the similarities and differences in serum iron and ferritin levels. The subjects with acute and chronic telogen effluvium were placed in separate subgroups, and those with unclassified telogen effluvium were placed in the telogen effluvium group. The literature search flowchart is shown in Figure 1. Table 1 presents the characteristics of the included studies.\u0026nbsp;\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eBaseline characteristics of the included studies.\u003c/p\u003e\n\u003ctable align=\"left\" border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.567877629063098%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAuthor (year)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.891013384321223%\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of study\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.21414913957935%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSample size(P/C)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.7877629063097515%\"\u003e\n \u003cp\u003e\u003cstrong\u003ecountry\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.692160611854685%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(P/C)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.288718929254301%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge(P/C)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(mean \u0026plusmn; SD, y)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.74378585086042%\"\u003e\n \u003cp\u003e\u003cstrong\u003eType\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414913957934992%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiagnosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.906309751434035%\"\u003e\n \u003cp\u003e\u003cstrong\u003eData collected\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.493307839388145%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNOS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.567877629063098%\"\u003e\n \u003cp\u003eAlizadeh et al.2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.891013384321223%\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.21414913957935%\"\u003e\n \u003cp\u003e83/83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.7877629063097515%\"\u003e\n \u003cp\u003eIran\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.692160611854685%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.288718929254301%\"\u003e\n \u003cp\u003e36.78\u0026plusmn;5.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.74378585086042%\"\u003e\n \u003cp\u003eCTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414913957934992%\"\u003e\n \u003cp\u003eHistory, physical examination, pull test,dermoscopy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.906309751434035%\"\u003e\n \u003cp\u003eserum ferritin, prevalence of ferritin deficiency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.493307839388145%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.567877629063098%\"\u003e\n \u003cp\u003eCheng et al.2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.891013384321223%\"\u003e\n \u003cp\u003eCross-Sectional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.21414913957935%\"\u003e\n \u003cp\u003e193/183\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.7877629063097515%\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.692160611854685%\"\u003e\n \u003cp\u003eNA/Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.288718929254301%\"\u003e\n \u003cp\u003e28.37\u0026plusmn;5.11/29.11\u0026plusmn;5.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.74378585086042%\"\u003e\n \u003cp\u003eTE, ATE, CTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414913957934992%\"\u003e\n \u003cp\u003eHistory, physical examination, pull test,dermoscopy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.906309751434035%\"\u003e\n \u003cp\u003eserum iron, serum ferritin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.493307839388145%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.567877629063098%\"\u003e\n \u003cp\u003eChisti et al.2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.891013384321223%\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.21414913957935%\"\u003e\n \u003cp\u003e100/100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.7877629063097515%\"\u003e\n \u003cp\u003eIndia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.692160611854685%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.288718929254301%\"\u003e\n \u003cp\u003e26.6\u0026plusmn;7.25/26.83\u0026plusmn;9.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.74378585086042%\"\u003e\n \u003cp\u003eATE, CTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414913957934992%\"\u003e\n \u003cp\u003eHistory, physical examination\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.906309751434035%\"\u003e\n \u003cp\u003eserum ferritin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.493307839388145%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.567877629063098%\"\u003e\n \u003cp\u003eElethawi et al.2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.891013384321223%\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.21414913957935%\"\u003e\n \u003cp\u003e38/25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.7877629063097515%\"\u003e\n \u003cp\u003eIraq\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.692160611854685%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.288718929254301%\"\u003e\n \u003cp\u003e30.15\u0026plusmn;6.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.74378585086042%\"\u003e\n \u003cp\u003eCTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414913957934992%\"\u003e\n \u003cp\u003eHistory, physical examination, pull test\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.906309751434035%\"\u003e\n \u003cp\u003eserum ferritin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.493307839388145%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.567877629063098%\"\u003e\n \u003cp\u003eErtug et al.2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.891013384321223%\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.21414913957935%\"\u003e\n \u003cp\u003e455/196\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.7877629063097515%\"\u003e\n \u003cp\u003eTurkey\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.692160611854685%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.288718929254301%\"\u003e\n \u003cp\u003e29.01\u0026plusmn;8.71/31.29\u0026plusmn;8.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.74378585086042%\"\u003e\n \u003cp\u003eTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414913957934992%\"\u003e\n \u003cp\u003eHistory, physical examination, pull test\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.906309751434035%\"\u003e\n \u003cp\u003eserum iron\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.493307839388145%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.567877629063098%\"\u003e\n \u003cp\u003eFatani et al.2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.891013384321223%\"\u003e\n \u003cp\u003eCross-Sectional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.21414913957935%\"\u003e\n \u003cp\u003e160/425\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.7877629063097515%\"\u003e\n \u003cp\u003eSaudi Arabia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.692160611854685%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.288718929254301%\"\u003e\n \u003cp\u003e28.94\u0026plusmn;10.6/34.24\u0026plusmn;11.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.74378585086042%\"\u003e\n \u003cp\u003eTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414913957934992%\"\u003e\n \u003cp\u003eHistory, physical examination\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.906309751434035%\"\u003e\n \u003cp\u003eserum ferritin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.493307839388145%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.567877629063098%\"\u003e\n \u003cp\u003eHamad et al.2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.891013384321223%\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.21414913957935%\"\u003e\n \u003cp\u003e34/26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.7877629063097515%\"\u003e\n \u003cp\u003eEgypt\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.692160611854685%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.288718929254301%\"\u003e\n \u003cp\u003e22.95\u0026plusmn;7.31/19.06\u0026plusmn;9.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.74378585086042%\"\u003e\n \u003cp\u003eTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414913957934992%\"\u003e\n \u003cp\u003eHistory, physical examination, pull test, trichogram\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.906309751434035%\"\u003e\n \u003cp\u003eserum iron\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.493307839388145%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.567877629063098%\"\u003e\n \u003cp\u003eHasseeb et al.2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.891013384321223%\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.21414913957935%\"\u003e\n \u003cp\u003e53/26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.7877629063097515%\"\u003e\n \u003cp\u003eIraq\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.692160611854685%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.288718929254301%\"\u003e\n \u003cp\u003eRange 18\u0026ndash;45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.74378585086042%\"\u003e\n \u003cp\u003eATE, CTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414913957934992%\"\u003e\n \u003cp\u003eHistory, physical examination\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.906309751434035%\"\u003e\n \u003cp\u003eserum iron, serum ferritin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.493307839388145%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.567877629063098%\"\u003e\n \u003cp\u003eHodeib et al.2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.891013384321223%\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.21414913957935%\"\u003e\n \u003cp\u003e40/20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.7877629063097515%\"\u003e\n \u003cp\u003eEgypt\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.692160611854685%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.288718929254301%\"\u003e\n \u003cp\u003e28.10\u0026plusmn;4.65/27.45\u0026plusmn;6.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.74378585086042%\"\u003e\n \u003cp\u003eTE, ATE, CTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414913957934992%\"\u003e\n \u003cp\u003eHistory, physical examination, pull test,dermoscopy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.906309751434035%\"\u003e\n \u003cp\u003eserum iron, serum ferritin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.493307839388145%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.567877629063098%\"\u003e\n \u003cp\u003eKaradag et al.2011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.891013384321223%\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.21414913957935%\"\u003e\n \u003cp\u003e63/50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.7877629063097515%\"\u003e\n \u003cp\u003eTurkey\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.692160611854685%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.288718929254301%\"\u003e\n \u003cp\u003e29.1\u0026plusmn;11.9/28.4\u0026plusmn;9.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.74378585086042%\"\u003e\n \u003cp\u003eTE, ATE, CTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414913957934992%\"\u003e\n \u003cp\u003eHistory, physical examination, dermoscopy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.906309751434035%\"\u003e\n \u003cp\u003eserum ferritin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.493307839388145%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.567877629063098%\"\u003e\n \u003cp\u003eKarim et al.2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.891013384321223%\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.21414913957935%\"\u003e\n \u003cp\u003e30/30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.7877629063097515%\"\u003e\n \u003cp\u003eBangladesh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.692160611854685%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.288718929254301%\"\u003e\n \u003cp\u003e25.4 \u0026plusmn;7/24.8 \u0026plusmn;5.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.74378585086042%\"\u003e\n \u003cp\u003eTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414913957934992%\"\u003e\n \u003cp\u003eHistory, physical examination, pull test\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.906309751434035%\"\u003e\n \u003cp\u003eserum ferritin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.493307839388145%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.567877629063098%\"\u003e\n \u003cp\u003eMoeinvaziri et al.2009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.891013384321223%\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.21414913957935%\"\u003e\n \u003cp\u003e30/30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.7877629063097515%\"\u003e\n \u003cp\u003eIran\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.692160611854685%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.288718929254301%\"\u003e\n \u003cp\u003e28.1\u0026plusmn;8.5/29.4\u0026plusmn;8.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.74378585086042%\"\u003e\n \u003cp\u003eCTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414913957934992%\"\u003e\n \u003cp\u003eHistory, physical examination, trichogram\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.906309751434035%\"\u003e\n \u003cp\u003eserum iron, serum ferritin, prevalence of ferritin deficiency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.493307839388145%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.567877629063098%\"\u003e\n \u003cp\u003eNaser et al.2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.891013384321223%\"\u003e\n \u003cp\u003eCross-sectional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.21414913957935%\"\u003e\n \u003cp\u003e60/60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.7877629063097515%\"\u003e\n \u003cp\u003eIraq\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.692160611854685%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.288718929254301%\"\u003e\n \u003cp\u003e32.6\u0026plusmn;6.47/41.3\u0026plusmn;4.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.74378585086042%\"\u003e\n \u003cp\u003eCTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414913957934992%\"\u003e\n \u003cp\u003eHistory, physical examination, pull test\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.906309751434035%\"\u003e\n \u003cp\u003eserum ferritin, prevalence of ferritin deficiency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.493307839388145%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.567877629063098%\"\u003e\n \u003cp\u003eObaidat et al.2005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.891013384321223%\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.21414913957935%\"\u003e\n \u003cp\u003e72/30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.7877629063097515%\"\u003e\n \u003cp\u003eJordan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.692160611854685%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.288718929254301%\"\u003e\n \u003cp\u003e26\u0026plusmn;9.2/32\u0026plusmn;11.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.74378585086042%\"\u003e\n \u003cp\u003eCTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414913957934992%\"\u003e\n \u003cp\u003eHistory, physical examination, pull test\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.906309751434035%\"\u003e\n \u003cp\u003eserum ferritin, prevalence of ferritin deficiency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.493307839388145%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.567877629063098%\"\u003e\n \u003cp\u003eOlsen et al.2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.891013384321223%\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.21414913957935%\"\u003e\n \u003cp\u003e381/76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.7877629063097515%\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.692160611854685%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.288718929254301%\"\u003e\n \u003cp\u003eRange 18-65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.74378585086042%\"\u003e\n \u003cp\u003eTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414913957934992%\"\u003e\n \u003cp\u003eHistory, physical examination\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.906309751434035%\"\u003e\n \u003cp\u003eserum ferritin, prevalence of ferritin deficiency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.493307839388145%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.567877629063098%\"\u003e\n \u003cp\u003ePradhan et al.2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.891013384321223%\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.21414913957935%\"\u003e\n \u003cp\u003e60/60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.7877629063097515%\"\u003e\n \u003cp\u003eNepal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.692160611854685%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.288718929254301%\"\u003e\n \u003cp\u003e33.93\u0026plusmn;11.02/34.97\u0026plusmn;10.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.74378585086042%\"\u003e\n \u003cp\u003eTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414913957934992%\"\u003e\n \u003cp\u003eHistory, physical examination\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.906309751434035%\"\u003e\n \u003cp\u003eserum ferritin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.493307839388145%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.567877629063098%\"\u003e\n \u003cp\u003eRasheed et al.2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.891013384321223%\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.21414913957935%\"\u003e\n \u003cp\u003e80/40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.7877629063097515%\"\u003e\n \u003cp\u003eEgypt\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.692160611854685%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.288718929254301%\"\u003e\n \u003cp\u003e29.8 \u0026plusmn; 9.3/30.8 \u0026plusmn; 8.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.74378585086042%\"\u003e\n \u003cp\u003eTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414913957934992%\"\u003e\n \u003cp\u003eHistory, physical examination, pull test, trichogram, dermoscopy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.906309751434035%\"\u003e\n \u003cp\u003eserum ferritin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.493307839388145%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.567877629063098%\"\u003e\n \u003cp\u003eSarkar et al.2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.891013384321223%\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.21414913957935%\"\u003e\n \u003cp\u003e40/40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.7877629063097515%\"\u003e\n \u003cp\u003eIndia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.692160611854685%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.288718929254301%\"\u003e\n \u003cp\u003e24.28 \u0026plusmn; 6.17/23.11\u0026plusmn;4.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.74378585086042%\"\u003e\n \u003cp\u003eCTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414913957934992%\"\u003e\n \u003cp\u003eHistory, physical examination, pull test, trichogram\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.906309751434035%\"\u003e\n \u003cp\u003eserum ferritin, prevalence of ferritin deficiency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.493307839388145%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.567877629063098%\"\u003e\n \u003cp\u003eUllah et al.2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.891013384321223%\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.21414913957935%\"\u003e\n \u003cp\u003e50/50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.7877629063097515%\"\u003e\n \u003cp\u003ePakistan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.692160611854685%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.288718929254301%\"\u003e\n \u003cp\u003e26\u0026plusmn;7.61/31.88\u0026plusmn;6.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.74378585086042%\"\u003e\n \u003cp\u003eTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414913957934992%\"\u003e\n \u003cp\u003eHistory, physical examination, pull test\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.906309751434035%\"\u003e\n \u003cp\u003eserum ferritin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.493307839388145%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"11.567877629063098%\"\u003e\n \u003cp\u003eYavuz et al.2018\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.891013384321223%\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"6.21414913957935%\"\u003e\n \u003cp\u003e40/30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"6.7877629063097515%\"\u003e\n \u003cp\u003eTurkey\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"6.692160611854685%\"\u003e\n \u003cp\u003eNA/Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.288718929254301%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"7.74378585086042%\"\u003e\n \u003cp\u003eCTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"21.414913957934992%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.906309751434035%\"\u003e\n \u003cp\u003eserum iron\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"4.493307839388145%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u0026nbsp;\u003c/strong\u003eP, patients; C, control; TE, telogen effluvium; ATE, acute telogen effluvium; CTE, chronic telogen effluvium; NA, not applicable.\u003c/p\u003e\n\u003ch2\u003eMain results\u003c/h2\u003e\n\u003ch2\u003eSerum\u0026nbsp;ferritin\u0026nbsp;level\u0026nbsp;in\u0026nbsp;telogen effluvium\u003c/h2\u003e\n\u003cp\u003eTen studies measured\u0026nbsp;serum\u0026nbsp;ferritin\u0026nbsp;level\u0026nbsp;in\u0026nbsp;telogen effluvium[27,28,30,31,34,35,37,39,43,44]. Significant heterogeneity was observed (P \u0026lt; 0.00001, I\u003csup\u003e2\u003c/sup\u003e = 93%), and a random-effects model was applied. These results showed that serum ferritin levels were lower in the telogen effluvium group than in the control group (P \u0026lt; 0.00001, SMD = \u0026minus;1.09, 95% CI = \u0026minus;1.50 to \u0026minus;0.69). Four studies measured serum ferritin level in acute telogen effluvium[26,28-30]. Heterogeneity was observed (P = 0.04, I\u003csup\u003e2\u003c/sup\u003e = 63%). A random-effects model was used. The acute telogen effluvium group had a lower serum ferritin level than the control group (P = 0.03, SMD = \u0026minus;0.53, 95% CI = \u0026minus;1.00 to \u0026minus;0.06). Nine studies measured serum ferritin level in chronic telogen effluvium[26,28-30,32,33,36,40,42]. Heterogeneity was observed (P = 0.0001, I\u003csup\u003e2\u003c/sup\u003e = 75%). A random-effects model was used. The chronic telogen effluvium group had lower serum ferritin level than the control group (P \u0026lt; 0.0001, SMD = \u0026minus;0.73, 95% CI = \u0026minus;1.06 to \u0026minus;0.40). Serum ferritin levels were lower in patients with different types of telogen effluvium than in the normal population. The results are shown in Figure 2.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eSerum\u0026nbsp;iron level\u0026nbsp;in\u0026nbsp;telogen effluvium\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eThree studies had a measurement of\u0026nbsp;serum\u0026nbsp;iron\u0026nbsp;level\u0026nbsp;in\u0026nbsp;telogen effluvium[27,28,39].\u0026nbsp;Heterogeneity was found\u0026nbsp;(P \u0026lt; 0.00001, I\u003csup\u003e2\u003c/sup\u003e = 93%), and the random-effects model was applied. These results showed that serum iron level was reduced in the telogen effluvium compared to the control group (P = 0.03, SMD =\u0026minus;1.09, 95% CI =\u0026minus;2.06 to \u0026minus;0.11). Only two studies had a measurement of serum iron level in acute telogen effluvium[28,29]. No significant heterogeneity was observed (P = 0.52, I\u003csup\u003e2\u003c/sup\u003e = 0%). To maintain the consistency of the results, we used the random-effects model. The acute telogen effluvium group had significantly lower serum iron level than the control group (P = 0.001, SMD = \u0026minus;0.77, 95% CI = \u0026minus;1.25 to \u0026minus;0.30). We also switched the fixed-effects model analysis, which is consistent with the random-effects model. Three studies had a measurement of the serum iron level in chronic telogen effluvium[28,29,32]. Heterogeneity was observed (P = 0.04, I\u003csup\u003e2\u003c/sup\u003e = 68%). A random-effects model was applied. The chronic telogen effluvium group had significantly lower serum iron level than the control group (P = 0.005, SMD = \u0026minus;0.84, 95% CI = \u0026minus;1.42 to \u0026minus;0.26). In patients with different types of telogen effluvium, serum iron levels were lower than those in the normal population. The results are shown in Figure 3.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eSerum\u0026nbsp;ferritin and iron levels\u0026nbsp;in acute\u0026nbsp;and\u0026nbsp;chronic\u0026nbsp;telogen effluvium\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eFour studies had a measurement of\u0026nbsp;serum\u0026nbsp;ferritin\u0026nbsp;level\u0026nbsp;in\u0026nbsp;acute and chronic telogen effluvium[26,28-30]. Only two studies had a measurement of serum iron level in acute and chronic telogen effluvium[28,29]. No significant heterogeneity was observed, and the fixed-effects model was applied. There was no significant difference in serum ferritin level between acute and chronic telogen effluvium (P = 0.62, SMD = 0.08, 95% CI = \u0026minus;0.23\u0026ndash;0.38), nor were serum iron levels (P = 0.26, SMD = 0.26, 95% CI = \u0026minus;0.19\u0026ndash;0.72). The results are shown in Figure 4. \u0026nbsp;\u003c/p\u003e\n\u003ch2\u003ePrevalence of\u0026nbsp;ferritin\u0026nbsp;deficiency\u0026nbsp;and\u0026nbsp;telogen effluvium\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eSix studies on chronic telogen effluvium have reported the prevalence of ferritin deficiency, which has not been publicly reported in patients with acute telogen effluvium. Due to the small number of included studies, we directly used a random-effects model for analysis. Three studies reported the prevalence of ferritin deficiency and chronic telogen effluvium with ferritin level below 10\u0026ndash;15 \u0026mu;g/L (ng/mL)[25,32,41]. There was no significant difference between the chronic telogen effluvium and control groups (P = 0.51, SMD = 1.57, 95% CI = 0.41\u0026ndash;5.95). Two studies reported the prevalence of ferritin deficiency and chronic telogen effluvium with ferritin levels of 20 \u0026mu;g/L[33,36], 30 \u0026mu;g/L[32,42], 40 \u0026mu;g/L[25,41], and \u0026le; 70 \u0026mu;g/L[41,42]. The prevalence of ferritin deficiency in the chronic telogen effluvium group was significantly higher than that in the control group at serum ferritin levels of 20 \u0026mu;g/L (P = 0.0002, SMD = 4.32, 95% CI = 1.99\u0026ndash;9.38) and 30 \u0026mu;g/L (P \u0026lt; 0.00001, SMD = 18.62, 95% CI = 8.28\u0026ndash;41.90). No significant difference was observed between the chronic telogen effluvium and control groups with ferritin levels of 40 \u0026mu;g/L (P = 0.43, SMD = 1.22, 95% CI = 0.74\u0026ndash;2.00) and \u0026le; 70 \u0026mu;g/L (P = 0.54, SMD = 1.97, 95% CI = 0.23\u0026ndash;16.74). In patients with chronic telogen effluvium, the prevalence of iron deficiency was higher than that in the general population with ferritin levels at thresholds of 20 \u0026mu;g/L and 30 \u0026mu;g/L, and the difference was statistically significant. The results are shown in Figure 5.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eSensitivity analysis\u003c/h2\u003e\n\u003cp\u003eThe contribution of each study to the pooled estimate was evaluated to assess the sensitivity of the analyses. Yavuz et al. had an undue influence on the summary\u0026nbsp;SMD\u0026nbsp;under the\u0026nbsp;serum\u0026nbsp;iron\u0026nbsp;level\u0026nbsp;in acute\u0026nbsp;telogen effluvium[38]. This was excluded from the analysis. Other studies did not substantially change the pooled point estimates. We also converted the random- and fixed-effects models in all studies. No substantial changes were observed in these data. These results confirm the reliability of the present study.\u003c/p\u003e\n\u003ch2\u003ePublication bias\u003c/h2\u003e\n\u003cp\u003eFunnel plots were used to evaluate the publication bias. In the study of serum ferritin and iron levels in patients with telogen effluvium, the funnel plot was symmetrical, suggesting that the overall publication bias was small (Figure 6). In the studies on the prevalence of serum ferritin deficiency, because only two to three studies were included in each subgroup, the number was relatively small, and no further publication bias testing was performed.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study used evidence-based medicine to assess the association between iron deficiency and telogen effluvium, including studies from several countries in Asia, Europe, and the United States. The serum ferritin and iron levels of patients with acute and chronic telogen effluvium were lower than those of controls. There was no significant difference in serum ferritin levels or serum iron reduction levels between patients with acute and chronic telogen effluvium. In patients with chronic telogen effluvium, the prevalence of ferritin deficiency is higher than that in the general population when ferritin levels are 20 ng/dl and 30 ng/dl as the threshold for the diagnosis of iron deficiency.\u003c/p\u003e \u003cp\u003eHowever, the mechanism by which iron affects hair growth remains unclear. Iron metabolism is the basis of the interaction between oxidative stress and antioxidants[\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. Iron can regulate the oxidative activity of tyrosinase, which is significantly associated with hair whitening[\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. Iron is a cofactor of ribonucleotide reductase, the rate-limiting enzyme in DNA synthesis. Iron deficiency prevents the normal function of this enzyme, thus inhibiting proliferation and other iron-dependent enzymes and leading to hair loss[\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. The level of ferritin in non-dividing cells, such as hair follicle stem cells and terminal differentiated cells, increased, whereas the level of ferritin in rapidly proliferating hair follicle stromal cells was low, and the level of free iron was high. This balance between ferritin and iron is partially controlled by the transcription factor c-myc, and overexpression of c-myc may cause hair loss[\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e, \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. Some genes in the human hair follicles may be regulated by iron. Iron deficiency may have an effect on gene expression, but its specific mechanism remains unclear[\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCurrently, the majority of the women in the current study are premenopausal, and therefore are more like to have hair loss due to loss of iron stores through menstruation. The research subjects were mainly young and middle-aged female patients, and only one study explicitly identified premenopausal and postmenopausal female patients with telogenic hair loss[\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. This study defined iron deficiency as ferritin\u0026thinsp;\u0026le;\u0026thinsp;15 \u0026micro;g/L or \u0026le;\u0026thinsp;40 \u0026micro;g/L and found no significant difference in the prevalence of iron deficiency in women with chronic telogen effluvium or female pattern hair loss compared with controls and premenopausal or postmenopausal iron deficiency. There was no significant difference in the prevalence.\u003c/p\u003e \u003cp\u003eSerum ferritin levels are the most specific and effective measure of whole-body iron stores and are commonly used[\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. The prevalence of reduced serum ferritin levels (\u0026lt;\u0026thinsp;30\u0026ndash;40 \u0026micro;g/L) appears to be higher in women with telogen effluvium than in the general population[\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. Serum ferritin levels below 30 \u0026micro;g/L were found in 40\u0026ndash;50% of women in Cambodia[\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e], Portugal [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e], Norway, and Denmark [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e]. Although values\u0026thinsp;\u0026lt;\u0026thinsp;12\u0026ndash;15 \u0026micro;g/L can confirm iron deficiency, serum ferritin level\u0026thinsp;\u0026lt;\u0026thinsp;30 \u0026micro;g/L is more widely used due to its higher sensitivity (92%) and similar specificity (98%) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e, \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e]. This study shows that if serum ferritin\u0026thinsp;\u0026le;\u0026thinsp;15 \u0026micro;g/L or \u0026le;\u0026thinsp;70 \u0026micro;g/L is used as the cut-off value for the diagnosis of iron deficiency in patients with chronic telogen effluvium, the prevalence of iron deficiency in the telogen effluvium group and the control group was not statistically different. If serum ferritin level was 20 \u0026micro;g/L or 30 \u0026micro;g/L for the diagnosis of iron deficiency, the prevalence of iron deficiency was statistically different compared to that in the non-alopecia population.\u003c/p\u003e \u003cp\u003eThere are few intervention trials of iron supplementation in patients with alopecia, which may be due to conflicting conclusions from previous studies on whether patients with alopecia are iron-deficient. Several studies have been published using different interventions, including iron with L-lysine[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e], iron alone[\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e], and iron with spironolactone[\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e]. Two studies targeted interventions with ferritin levels\u0026thinsp;\u0026gt;\u0026thinsp;50 \u0026micro;g/L[\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e] or 70 \u0026micro;g/L[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. These studies were limited by small sample sizes and differences in ferritin levels. However, monitoring serum iron levels is important in patients taking oral iron supplements. Taking iron supplements without monitoring is associated with a risk of potentially serious complications[\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e, \u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study has certain limitations. First, there were ethnic differences among the included participants, different dietary habits, and differences in their intake of iron. Second, ferritin levels can be elevated in diseases such as inflammation, chronic kidney disease, and tumors[\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e, \u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e]. Although this study was screened, there may still have been some selection bias. Third, the sample size of the included population was small, and there may be differences in the examination methods of serum ferritin, which reduces the reliability of the conclusion of this study. However, this study also has some clinical significance. This study is the first to use evidence-based medicine to confirm that serum iron and serum ferritin levels are decreased in patients with telogen effluvium. This study also found that in some studies using ferritin to define iron deficiency, the prevalence of alopecia was not significantly lower than that of the non-alopecia population, which may be due to the selection of a critical value that is significantly low or significantly high.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study shows that iron deficiency is associated with telogen effluvium and provides evidence-based medical evidence for the treatment of telogen effluvium with iron supplementation. Simultaneously, this study clarified the critical value of serum ferritin to define iron deficiency in patients with telogen effluvium and provided a reference value for the screening of iron deficiency in patients with alopecia.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003eThe study was carried out based on the principles of the PRISMA statement[66]. This protocol was registered in PROSPERO (ID 42022310129). The raw data and fully reproducible code are available on the OSF (https://osf.io/d58at/).\u003c/p\u003e\n\u003ch2\u003eLiterature search\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eWe searched for literature describing the association between\u0026nbsp;iron deficiency and telogen effluvium. Literature was retrieved by a formal search of electronic databases (PubMed, Offshore Vessel Inspection Database, Cochrane Library, and Google Scholar) and by manually searching the reference lists of related articles. The computer searches were limited before February 2022, using the keywords: \u0026ldquo;iron\u0026rdquo; OR \u0026ldquo;ferrum\u0026rdquo; OR \u0026ldquo;ferritin\u0026rdquo; AND \u0026ldquo;hair loss\u0026rdquo; OR \u0026ldquo;alopecia\u0026rdquo; OR \u0026ldquo;telogen effluvium\u0026rdquo;. The language used was limited to English. There were no ethnic restrictions.\u003c/p\u003e\n\u003ch2\u003eInclusion criteria\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eThe diagnosis of telogen effluvium was based on the examination results of physical examination, pull test, history, dermoscopy, and/or trichogram. The inclusion criteria were as follows: (1) published literatures related to the association of serum iron level, serum ferritin level, or prevalence of ferritin deficiency with telogen effluvium; (2) independent case-control or cross-sectional studies; and (3) original studies providing the mean and standard of serum iron level and the number of each group, serum ferritin level, or prevalence of ferritin deficiency. \u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eExclusion criteria\u0026nbsp;\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eThe exclusion criteria were as follows: (1) studies with original data that could not be extracted; (2) studies with duplicated data; and (3) studies with study participants having specific diseases that may have an effect on serum iron or ferritin, such as acute infections, fever, and chronic wasting disease; with patients undergoing bariatric surgery, or with patients with cancer.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eData extraction\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eTwo authors (J.Z.Z. and M.M.G.) independently extracted the original data. They independently decided whether\u0026nbsp;to include each study.\u0026nbsp;Disagreements were resolved by discussion with the third investigator (L.D.). The extracted data consisted of the following items: the first author\u0026rsquo;s name, year of publication, method of diagnosis, type of study, sample size, sex, age, country, and measures of iron deficiency.\u003c/p\u003e\n\u003ch2\u003eQuality assessment\u003c/h2\u003e\n\u003cp\u003eStudy quality was assessed using the Newcastle-Ottawa Scale (NOS)[67]. Three aspects were considered in the NOS criteria: (1) selection of research objects (0\u0026ndash;4 stars), (2) comparability of research objects (0\u0026ndash;2 stars), and (3) exposure or outcome (0\u0026ndash;3 stars). NOS scores range from 0 (worst) to 9 stars (best); a score equal to or higher than 7 indicated that the study was of good quality. Two investigators (Y.D. and Y.X.M.) independently assessed the quality of each included study. Disagreements were resolved by discussion\u0026nbsp;with the participation of the third investigator\u0026nbsp;(T.T.L.).\u003c/p\u003e\n\u003ch2\u003eStatistical analyses\u003c/h2\u003e\n\u003cp\u003eReview Manager 5.41 (The Nordic Cochrane Centre, Copenhagen) was used to perform the meta-analysis. Continuous variables were analyzed using standardized mean differences (SMDs) with 95% confidence intervals (CIs). Dichotomous data were analyzed using odds ratios (ORs) corresponding to 95% CI. Heterogeneity among the studies was assessed using the I\u003csup\u003e2\u003c/sup\u003e statistic[68]. If heterogeneity existed among the studies (P\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u0026lt; 0.10 and I\u003csup\u003e2\u003c/sup\u003e \u0026gt; 50%), the random effects model was used to estimate[69]. Otherwise, a fixed-effects model was adopted[70]. Sensitivity analysis was performed to assess the robustness and heterogeneity of the combined results. Funnel plots were used to assess the potential publication bias.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by the Key R \u0026amp; D projects of Xinjiang Uygur Autonomous Region (Research on key technologies for prevention and treatment of common and difficult skin diseases in Xinjiang, 2021B03001-1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declared no competing interests exist.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank Editage (www.editage.com) for English language editing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJ.Z. Z. and X.J.K. designed the study. J.Z.Z., M.M.G. and L.D. screened the articles, extracted the data. Y.D., Y.X.M., and T.T.L. assessed the risk of bias, and analysed and interpreted the data. J.Z. Z. wrote the first draft of the manuscript. X.J.K. reviewed the subsequent versions and the final draft. All authors approved the final version.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e Grover, C.; Khurana, A. Telogen effluvium. \u003cem\u003eIndian journal of dermatology, venereology and leprology\u003c/em\u003e\u003cstrong\u003e2013\u003c/strong\u003e, \u003cem\u003e79\u003c/em\u003e, 591-603, doi:10.4103/0378-6323.116731.\u003c/li\u003e\n \u003cli\u003e Asghar, F.; Shamim, N.; Farooque, U.; Sheikh, H.; Aqeel, R. 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Measuring inconsistency in meta-analyses. \u003cem\u003eBmj\u003c/em\u003e\u003cstrong\u003e2003\u003c/strong\u003e, \u003cem\u003e327\u003c/em\u003e, 557-560, doi:10.1136/bmj.327.7414.557.\u003c/li\u003e\n \u003cli\u003e DerSimonian, R.; Kacker, R. Random-effects model for meta-analysis of clinical trials: an update. \u003cem\u003eContemporary clinical trials\u003c/em\u003e\u003cstrong\u003e2007\u003c/strong\u003e, \u003cem\u003e28\u003c/em\u003e, 105-114, doi:10.1016/j.cct.2006.04.004.\u003c/li\u003e\n \u003cli\u003e Mantel, N.; Haenszel, W. Statistical aspects of the analysis of data from retrospective studies of disease. \u003cem\u003eJournal of the National Cancer Institute\u003c/em\u003e\u003cstrong\u003e1959\u003c/strong\u003e, \u003cem\u003e22\u003c/em\u003e, 719-748.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Iron deficiency, telogen effluvium, serum ferritin, serum iron","lastPublishedDoi":"10.21203/rs.3.rs-1519227/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1519227/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIron deficiency has been associated with telogen effluvium, but currently, the data regarding their association are conflicting. To derive a more precise estimation of this association, we performed a systematic review and meta-analysis to investigate serum ferritin level, serum iron level, and prevalence of ferritin deficiency in all published studies. Databases including PubMed, Google Scholar, Offshore Vessel Inspection Database, and Cochrane Library, were systematically searched. The association was assessed using standardized mean differences, odds ratios, and 95% confidence intervals. Statistical analysis was performed using Review Manager version 5.4.1. A total of 20 studies were identified. The results showed that in patients with telogen effluvium, including those with acute and chronic telogen effluvium, serum iron and serum ferritin levels were lower than those in the normal population. There was no significant difference in serum ferritin and iron levels between patients with acute and chronic telogen effluvium. In patients with chronic telogen effluvium, the prevalence of ferritin deficiency was higher than that in the general population when ferritin levels were 20 ng/dl and 30 ng/dl as the threshold for the diagnosis of iron deficiency. This meta-analysis revealed that iron deficiency is associated with telogen effluvium and clarified the critical serum ferritin level for defining iron deficiency in patients with telogen effluvium.\u003c/p\u003e","manuscriptTitle":"Association between iron deficiency and telogen effluvium: a systematic review and meta- analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-04-21 19:37:46","doi":"10.21203/rs.3.rs-1519227/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4c94e4e9-cc52-4f2f-a230-cbd8f6d6487c","owner":[],"postedDate":"April 21st, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-07-27T06:44:24+00:00","versionOfRecord":[],"versionCreatedAt":"2022-04-21 19:37:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1519227","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1519227","identity":"rs-1519227","version":["v1"]},"buildId":"rHA-KDH7Qsr4HCuvH75dn","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}