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Low iron stores: a risk factor for excessive hair loss in non-menopausal women

European Journal of Dermatology. Volume 17, Number 6, 507-12, November-December 2007, Investigative report

DOI : 10.1684/ejd.2007.0265

Summary

Author(s) : Claire Deloche, Philippe Bastien, Stéphanie Chadoutaud, Pilar Galan, Sandrine Bertrais, Serge Hercberg, Olivier de Lacharrière , L’Oréal Recherche, Clichy, FranceFax: (+33)1 47 56 82 21, U557 Inserm (UMR INSERM/INRA/CNAM), 5 rue du Vertbois, Paris, 75003 France.

Summary : Iron deficiency has been suspected to represent one of the possible causes of excessive hair loss in women. The aim of our study was to assess this relationship in a very large population of 5110 women aged between 35 and 60 years. Hair loss was evaluated using a standardized questionnaire sent to all volunteers. The iron status was assessed by a serum ferritin assay carried out in each volunteer. Multivariate analysis allowed us to identify three categories: “absence of hair loss” (43%), “moderate hair loss” (48%) and “excessive hair loss” (9%). Among the women affected by excessive hair loss, a larger proportion of women (59%) had low iron stores (<\; 40 µg/L) compared to the remainder of the population (48%). Analysis of variance and logistic regression show that a low iron store represents a risk factor for hair loss in non-menopausal women.

Keywords : hair loss, non-menopausal women, serum ferritin

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ARTICLE

Auteur(s) : Claire Deloche¹, Philippe Bastien¹, Stéphanie Chadoutaud¹, Pilar Galan², Sandrine Bertrais², Serge Hercberg², Olivier de Lacharrière¹

¹L’Oréal Recherche, Clichy, FranceFax: (+33)1 47 56 82 21
²U557 Inserm (UMR INSERM/INRA/CNAM), 5 rue du Vertbois, Paris, 75003 France

accepté le 6 Juin 2007

Hair loss in women is a common trait and the prevalence is age dependent [1]. When a woman consults a dermatologist about hair loss, her condition may or may not lead to alopecia, defined as a decrease in hair density. Patterned androgenic alopecia occurs in 37% of post-menopausal women [2] but only in 10-13% of non-menopausal women [2, 3]. Another hair trouble in non-menopausal women is increased hair loss or hair shedding, also known as chronic telogen effluvium (CTE) [3], affecting around 30% of women in the USA, UK and Japan [4]. Both diffuse androgen-dependent alopecia and chronic telogen effluvium are a major concern in dermatology [5]. However, it is important to remember that in clinical practice, women’s complaint of hair loss is still unclear or controversial [6, 7]; other causes must be taken into consideration.Iron deficiency has been suspected to represent one of the possible causes of excessive hair loss in women. Iron deficiency has been reported to be associated with chronic diffuse hair loss [5, 6, 8, 9]. A total iron depletion was observed when the serum ferritin was below 15 µg/L, and low iron stores with serum ferritin was between 15 and 30 µg/L [10]; Rushton [11] reported that the critical threshold of serum ferritin was 40 µg/L, a level under which increased telogen hair shedding was observed. So far, a direct relationship between ferritin levels and hair loss has not been confirmed by other studies [12, 13] and is still a matter of debate [14-16]. Some evidence was provided in a recent report [17] that decreased serum ferritin is associated with hair loss or alopecia in women; however, several parameters in this study, such as sample sizes, the ferritin thresholds and the clinical features [16, 17] need further explanation.To further investigate the relationship between iron store and hair loss, we decided to explore this relationship by assessing hair loss and measuring serum ferritin concentration, which is closely related to iron stores [10], in a very large sample of subjects by taking the advantage of the SU.VI.MAX epidemiological study, which provided us with the opportunity to study, for the first time, a large cohort of 5110 women. The aim of the study was to evaluate a possible link between iron stores based on the assessed ferritin level, and hair loss in women.

Materials and methods

Volunteers

5110 women aged between 35 and 60 years were involved in the study. This cohort of volunteers was part of the SU.VI.MAX trial, a large French epidemiological study [18, 19] approved by the ethical Committee of Paris-Cochin. SU.VI.MAX, which stood for “SUpplementation en VItamines et Minéraux AntioXydants”, was a randomized double blind, placebo-controlled, primary-prevention trial designed to test the efficiency of daily supplementation with anti-oxidant, vitamins and minerals at nutritional doses, in reducing the incidence of cancers and ischemic vascular diseases in a middle-age general population. Detailed description of the SU.VI.MAX study-design, randomization and participant characteristics have been previously reported [18, 19].

Hair loss assessment

Hair loss was assessed with the help of a set of descriptive questions extracted from a self-assessment questionnaire which had been sent to all volunteers at inclusion in the study (table 1). The quantification of hair loss was estimated by quantification of the hairs lost during washing, brushing, after drying with a towel, on the pillow after a night’s sleep and on clothes. Hairs that shed were quantified as none or a little, a few and a lot of hairs. Questions concerning the degree of self-perceived hair loss were also provided to establish if the volunteers consider themselves to be concerned by hair loss (non existent, normal, abnormal) and were included in the data analysis. Multiple correspondence analysis and hierarchical cluster analysis (HCA) [20] were used to group the answers with similar expression patterns. This allowed us to identify three distinct groups of volunteers characterized by “absence of hair loss”, “moderate hair loss” and “excessive hair loss” (table 2).

Table 1 Hair loss questionnaire

• Do you feel involved by hair loss?	□ Yes	□ No
• If you feel involved by hair loss, do you estimate that your hair loss corresponds to a transient hair loss? do you estimate that your hair loss corresponds to a persistent hair loss?	□ Yes □ Yes	□ No □ No
• Currently, during hair washing, how much do you estimate your hair loss?	□ Many hairs	□ Few hairs	□ Very few or None
• Currently, drying your hair with a bath towel, how much do you estimate your hair loss?	□ Many hairs	□ Few hairs	□ Very few or None
• Currently, during hair brushing, how much do you estimate your hair loss?	□ Many hairs	□ Few hairs	□ Very few or None
• Currently, after a night sleep, how much do you estimate your hair loss on the pillow?	□ Many hairs	□ Few hairs	□ Very few or None
• Currently, during a day how much do you estimate your hair loss on your clothes?	□ Many hairs	□ Few hairs	□ Very few or None

Table 2 Hair loss classification according to descriptive questions on hair loss signs and hierarchical cluster analysis

Cluster 1“Absence of Hair Loss”	Cluster 2 “Moderate Hair Loss”	Cluster 3 “Excessive Hair Loss
“not concerned by hair loss”	“hair loss self-perceived as normal hair loss”	“hair loss self-perceived as abnormal hair loss”
“no hair loss or a little during the washing”	“lose a few hairs during the washing”	“lose a lot of hairs during the washing”
“no hair loss or a little during hair brushing”	“lose a few hairs during hair brushing”	“lose a lot of hairs during hair brushing”
“no hair loss or a little on the bath towel”	“lose a few hairs on the bath towel”	“lose a lot of hairs on the bath towel”
“no hair loss or a little on the pillow”		“lose a few or a lot of hairs:
“no hair loss or a little on the clothes”	on the pillow”
	“lose a few or a lot of hairs on the clothes”

Biochemical measurements

The iron status was assessed by measuring the serum ferritin level and haemoglobin levels in each volunteer. At entry in the study, a 35 mL venous blood sample was collected. After collection (Becton Dickinson tubes), haemoglobin was measured immediately (cyanmethemoglobin method) and kept at + 4 °C in the dark until centrifugation and preparation of the aliquots. Serum ferritin levels were measured using a nephelometric assay (BNII Berhing) [21].

Statistical analysis

Descriptive and inferential analyses were performed using SPSS 11.0, SPAD 5.1 and SAS 8.2 statistical softwares. The detection limit of the serum ferritin assay caused some departure from normality even for log-transformed data. Therefore analyses based on ranks have been preferred. Analysis of variance (ANOVA) of serum ferritin level based on ranks has been carried out independently in post-menopausal and non-menopausal women, taking into account the age factors, “hemoglobin” and “hair loss classes” (table 2). For non-menopausal women, the use of intra-uterine devices or contraceptives was also taken into consideration. Comparisons of mean ranked serum ferritin levels relative to the hair loss classes were carried out using the Tukey-Kramer procedure for pairwise comparisons [22]. The relationship between the hair loss classes and serum ferritin levels were fitted using generalized logits [23] controlled for age, haemoglobin, and contraceptives or intra-uterine devices. The “excessive hair loss” class was chosen as the reference class; the significance level was set up at 0.05.

Results

Hair loss quantification

Based on the questionnaire, hierarchical cluster analysis (HCA) using Ward’s criteria clearly identified three well-defined classes of women [20]. The planar projection of individuals (figure 1) displays the three clusters on the first factorial plan. The clusters are stretched along the first component, corresponding to an intensity hair loss axis. The U-shape representation of the clusters is characteristic of a Guttman effect [20] which opposes the classes “absence of hair loss” and “excessive hair loss” classes to “moderate hair loss” class on the second factorial axis. The three classes were characterized using modalities over-expressed in respect to the whole population (table 2). The ellipsoids displays the classes “absence of hair loss”, “moderate hair loss”, and “excessive hair loss” which correspond to 43%, 48%, and 9% of the 5110 women, respectively. Each point on this figure corresponds to a particular profile and is sized proportionally to the frequency of the profile in the studied population.

Link between hair loss and serum ferritin levels

In non-menopausal women, 41.5%, 48.6% and 10% displayed absence, moderate and excessive hair loss, respectively (table 3A). Among them, 23% (881/3759) presented iron depleted stores (serum ferritin levels < 15 µg/L). In addition, 57% [(881+1269)/3759] of non-menopausal women presented low iron stores (serum ferritin < 40 µg/L) (table 3A, figure 2).

In post-menopausal women, the iron loss caused by bleeding during menstruation does not occur anymore. Among them, 47.4%, 46% and 6.6% display absence, moderate and excessive hair loss respectively (table 3B). At that time, only 5% (67/1351) had depleted iron stores (serum ferritin < 15 µg/L) (table 3B). Similarly, the low iron stores (serum ferritin < 40 µg/L) affected only 23% [(67+243)/1351] of post-menopausal women versus 57% of non-menopausal women.

The detection limit of the serum ferritin assay caused some deviation from normality, even for log-transformed data. Since the parametric analyses could thus be biased, we decided to perform analyse based on ranks, The ANOVA based on ranks showed a significant effect of the mean serum ferritin level on hair loss (p = 0.01) only in non-menopausal women. The Tukey-Kramer test for pairwise comparisons showed significant differences between excessive hair loss and both absence (p = 0.01) and moderate (p = 0.02) hair loss (figure 3).

In non-menopausal women, with serum ferritin levels below 40 µg/L or below 15 µg/L, excessive hair loss was significantly more frequent (11.4% [(90+156)/(881+1269)] and 10.2%, respectively), compared to women with optimal levels of ferritin, above 70 µg/L (6.8%) (table 3A). Anemia (defined as hemoglobin < 120 g/L) concerned 10% [(173+43)/(881+1269)] and 19.6% of women presenting a serum ferritin level lower than 40 µg/L or 15 µg/L, respectively. With a serum ferritin level above 40 µg/L, only 1.8% [(23+7)/(937+672)] of the women showed anemia (table 4). Thus, a relationship between hair loss and anemia was noticed only when the body’s iron stores was below 40 µg/L.

Adjusted for age, haemoglobin, and the use of contraceptives or intra-uterine devices [21], generalized logits based on ranks for the absence versus excessive hair loss and moderate versus excessive hair loss were performed. A generalized logits model was preferred over a conventional polytomic logistic regression, since the assumption of proportional odds was rejected (score test for the proportional assumption, p = 0.009). The results showed that low serum ferritin levels appeared to be highly significantly linked to the presence of excessive hair loss in non-menopausal women (p = 0.005 for excessive hair loss versus absence of hair loss; p = 0.005 for excessive hair loss versus moderate hair loss). Model adequacy was supported by Hosmer and Lemeshow Goodness-of-Fit test [23]. In addition, the model based on the log transformed ferritin data (figure 4) shows similar results.

Table 3A Impact of iron store levels on hair loss status in non-menopausal women (n = 3759)

Ferritin (µg L^-1)			Hair loss		Total
Absence of hair loss	Moderate hair loss	Excessive hair loss
< 15	Count	365	426	90	881
% within ferritin	41.4%	48.4%	10.2%	100.0%
[15-40]	Count	512	601	156	1269
% within ferritin	40.3%	47.4%	12.3%	100.0%
[40-70]	Count	385	469	83	937
% within ferritin	41.1%	50.1%	8.9%	100.0%
≥ 70	Count	297	329	46	672
% within ferritin	44.2%	49.0%	6.8%	100.0%
Total	Count	1559	1825	375	3759
% within ferritin	41.5%	48.6%	10.0%	100.0%

Table 3B Impact of iron store levels on hair loss status in post-menopausal women (n = 1351)

Ferritin (µg L^-1)		Hair loss			Total
Absence of hair loss	Moderate hair loss	Excessive hair loss
< 15	Count	30	30	7	67
% within ferritin	44.8%	44.8%	10.4%	100.0%
[15-40]	Count	106	117	20	243
% within ferritin	43.6%	48.1%	8.2%	100.0%
[40-70]	Count	175	142	21	338
% within ferritin	51.8%	42.0%	6.2%	100.0%
≥ 70	Count	330	332	41	703
% within ferritin	46.9%	47.2%	5.8%	100.0%
Total	Count	641	621	89	1351
% within ferritin	47.4%	46.0%	6.6%	100.0%

Table 4 Impact of iron store levels on hemoglobin level in non-menopausal women (n = 3759)

Ferritin (µg /L)		Hemoglobin
		< 120 g/L	≥120 g/L	Total
< 15	number	173	708	881
%	19.6%	80.4%	100.0%
[15-40]	number	43	1226	1269
%	3.4%	96.6%	100.0%
[40-70]	number	23	914	937
%	2.5%	97.5%	100.0%
≥ 70	number	7	665	672
%	1.0%	99.0%	100.0%
Total	number	246	3513	3759
%	6.5%	93.5%	100.0%

Discussion

This study, carried out for the first time on a very large cohort of women, provides strong arguments in favor of an association between depleted iron stores and hair loss, particularly excessive hair loss in women before menopause. It is likely that women classified in the present study under “excessive hair loss” were mainly women with androgenetic alopecia [17], however considering their large number, women with CTE [3] might also be included. Since serum ferritin measurement has been reported to be the most sensitive assay for estimating the iron status in an adult population [24], we used this assay to verify a possible link between iron status and hair loss.

Our results fully agreed with previous reports [5, 6, 8, 9] and provide further evidence that the iron status has to be taken into consideration when studying hair loss in women [5] and contrasts with some previous studies where no link between iron deficiency and hair loss was detected. This discrepancy could be explained by differences in the design of the studies. None of the previous studies was performed on an important sample of the general population nor did they take into consideration parameters such as age and haemoglobin concentration in post-menopausal women, and also neglecting the adjustment of the results with the use of contraceptives or intra-uterine devices in non-menopausal women. It is known that menstruating women using intra-uterine devices have significantly lower serum ferritin levels than those without contraception, or using oral contraception [21]. A potential weakness of our study, based on the way the data on hair loss were collected, was compensated by the successful logistic regression model, establishing a link between serum ferritin level and excessive hair loss in non-menopausal women.

According to these results, a decrease in ferritin levels might be considered as a potential risk factor for excessive hair loss. For example, a decrease in 30 units of serum ferritin level in non-menopausal women presenting an initial serum ferritin concentration of 70 µg/L (reference mean value of serum ferritin) would lead to a 28% increase in the odds of excessive hair loss.

Our results support the “threshold hypothesis” [17], which states that decreased iron stores lower the threshold for developing different types of alopecia. Nevertheless, additional studies are required to better understand the biological significance of the critical iron status level of 40 µg/L in the etiology of hair loss.

In hair follicles, iron is implicated as a metabolic factor. Iron is also a main constituent for hemoglobin, and iron depletion leads to anemia. The present study indicates that anemia appears for a ferritin threshold much lower than for hair loss. Consequently in clinical practice, an excessive hair loss supports the need to check serum ferritin levels. The optimum serum ferritin levels to reach for effectiveness on hair loss are higher than those usually recommended for treatment of anemia.

Acknowledgements

We would like to thank Mrs M. Cartron for her help, Mrs A. Bielicki for her technical assistance, Pr A.M. Roussel (Joseph-Fourier University), Drs P. Preziosi (U557 Inserm), B.A. Bernard and C. Bouillon for critical comments of the manuscript.

Disclosure: The authors attest that they have no conflicts of interest to disclose.

References

1 Birch MP, Messenger JF, Messenger AG. Hair density, hair diameter and the prevalence of female pattern hair loss. Br J Dermatol 2001; 144: 297-304.

2 Venning VA, Dawber RP. Patterned androgenic alopecia in women. J Am Acad Dermatol 1998; 18: 1073-7.

3 Rushton DH, Norris MJ, Dover R, Busuttil N. Causes of hair loss and the developments in hair rejunevation. Int J cosm Sci 2002; 24: 17-23.

4 Rushton DH. Nutritional factors and hair loss. Clin Exp Dermatol 2002; 27: 396-404.

5 Rushton DH. Management of hair loss in women. Dermatol Clin 1993; 11: 47-53.

6 Rushton DH, Ramsay ID, James KC, Norris MJ, Gilkes JJH. Biochemical and trichological characterization of diffuse alopecia in women. Br J Dermatol 1990; 123: 187-97.

7 Futterweit MD, Dunaif A, Yeh H-C, et al. The prevalence of hyperandrogenism in 109 consecutive female patients with diffuse alopecia. J Am Acad Dermatol 1988; 19: 831-6.

8 Roberts JL. Examining the etiology of telogen effluvium in pre-and postmenaupausal women: a chart review study. Tokyo, Japan: Proceeding, Tri-continental hair research Meeting, 2001; (Poster 157).

9 Haycox C. The incidence of depleted iron stores in North american females presenting with hair loss. Tokyo, Japan: Proceedings, Tri-Continental hair research Meeting, 2001; (Poster 159).

10 Milman N, Kirchhoff M. Iron stores in 1359, 30-to 60-year old Danish women: evaluation by serum ferritin and hemoglobin. Ann Hematol 1992; 64: 22-7.

11 Rushton DH, Ramsay ID. The importance of adequate serum ferritin levels during oral cyproterone acetate and ethinyl oestradiol treatment of diffuse androgen-dependent alopecia in women. Clin Endocrinol (Oxf) 1992; 36: 421-7.

12 Aydingöz IE, Ferhanoglu B, Guney O. Does tissue iron status have a role in female alopecia? J Eur Acad Dermatol Venereol 1999; 13: 65-7.

13 Auerbach R. Low iron levels. Arch Dermatol 1968; 98: 681.

14 Sinclair R. There is no clear association between low serum ferritin and chronic diffuse telogen hair loss. Br J Dermatol 2002; 147: 982-4.

15 Chamberlain AJ, Dawber RPR. Significance of iron status in hair loss in women. Br J Dermatol 2003; 149: 428.

16 Rushton DH, Dover R, Norris MJ. Is there really no clear association between low serum feritin and chronic diffuse telogen hair loss? Br J Dermatol 2003; 148: 1282-4.

17 Kantor J, Kessler LJ, Brooks DG, Cotsarelis G. Decreased serum ferritin is associated with alopecia in women. J Invest Dermatol 2003; 121: 985-8.

18 Hercberg S, Preziosi P, Briançon S, et al. A primary prevention trial using nutritional doses of antioxidant vitamins and minerals in cardiovascular diseases and cancers in a general population: the SU. VI. MAX study-design, methods, and participant characteristics. Control Clin Trials 1998; 19: 336-51.

19 Hercberg S, Galan P, Preziosi P, Bertrais S, Mennen L, Malvy D, Roussel AM, Favier A, Briançon S. The SU.VI.MAX study: a randomized, placebo controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med 2004; 164: 2335-42.

20 Lebart L, Morineau A, Piron M. In: Statistique exploratoire multidimensionnelle. Paris: Dunod, 1995: 93-176.

21 Galan P, Yoon HC, Preziosi P, et al. Determining factors in the iron status of adult women in the Suvimax women. Eur J Clin Nutr 1998; 52: 383-8.

22 Westfall PH, Tobias RD, Rom D, et al. In: Multiple comparisons and multiple tests using the SAS system. Cary, NC: SAS Institute Inc, 1999: 73-6.

23 Stokes ME, Davis CS, Koch GG. In: Categorical data analysis using the SAS system. Cary, NC: SAS Institute Inc, 2000: 211-70.

24 Hercberg S, Galan P. Nutritional anaemias. In: Flemming AF, ed. Clinical Haematology_International Practice and Research. Bailllière, London: Tindall, 1992: 145-68.