A POTENTIAL RELATION BETWEEN TELOGEN EFFLUVIUM AND IRON DEFICIENCY IN ADULT FEMALES

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1 A POTENTIAL RELATION BETWEEN TELOGEN EFFLUVIUM AND IRON DEFICIENCY IN ADULT FEMALES Nidal A. Obaidat, MD*, Basel T. Rawashdeh, MD*, Abdul-Razzaq A. Wreikat, MD**, Ahlam A. Awamleh, MD** ABSTRACT Objective: To examine the association between chronic telogen effluvium and iron deficiency in adult females. Methods: Seventy-two adult menstruating women with chronic telogen effluvium and 30 healthy adult females were enrolled into the study. All women were interviewed and clinically examined. The hair pull test was additionally utilized as part of the physical examination for the assessment of hair growth. Laboratory tests included measurements of hematocrit, serum ferritin levels, liver function tests, renal function tests, thyroid hormones, serum testosterone, and dehydroepiandrosterone. The results of hematocrit values and serum ferritin levels in patients and controls were analyzed and statistically compared. Patients with chronic telogen effluvium and low serum ferritin levels were given oral iron treatment in the form of ferrous sulphate 600 mg daily for 4 months. At the end of the study period improvement in their hair growth and serum ferritin levels were re-assessed. Results: The mean age for patients was 26 years and for controls was 32 years. Hematocrit measurements were similar in both groups, but there was a statistically significant difference in the mean serum ferritin levels (p < 0.05) between patients and controls (18.7 and 47.6 ng/ml, respectively). All patients treated with iron had elevation in their serum ferritin levels, and most of them experienced improvement in their hair growth. Conclusion: There was a significant association between low serum ferritin levels and chronic telogen effluvium, therefore, serum ferritin levels may be of value in the evaluation of adult menstruating women with chronic diffuse hair loss. Key words: Hair, Chronic telogen effluvium, Iron, Females, Jordan. JRMS June 2005; 12(1): Introduction The growth of the hair follicle goes through 4 phases (1,2) : (1) an anagen phase, which lasts approximately 3 years with active growth in the hair follicle determining the total length a hair will achieve, (2) a telogen phase, which lasts roughly 3 months, where hair follicles appear to be dormant, (3) a catagen phase, which lasts around 3 weeks, characterized by involution of the lower transient portion of the hair follicle, and (4) an exogen phase, marked by shedding of the dead hair from the follicle and occurs either late in telogen or early in anagen phase. Trichograms of the scalp show that 86% of hairs are in anagen, 1% in catagen and 13% in From the Departments of: * Dermatology, Prince Rashed Bin Al-Hassan Hospital, (PRHH), Irbid - Jordan **Laboratory Medicine (PRHH) Correspondence should be addressed to Dr N. Obaidat P. O. Box 263 Zarqa Jordan nobaidat@yahoo.com Manuscript received September 21, Accepted March 31, telogen. Hair loss is a common problem that affects both males and females of all ages (3). It affects over 25% of women in developed countries (4), and has a great psychological impact on the life of the affected subjects (2,3). Common causes of diffuse hair loss include heredity, androgenetic alopecia, telogen effluvium (TE), anagen effluvium, and due to systemic diseases such as systemic lupus erythematosus, syphilis, and others (5,6). The causative etiology is usually elicited by a full history, complete physical examination, and laboratory tests. Telogen effluvium is a form of non-scarring diffuse loss of hair (2). It is characterised by the premature entrance of a large number of hairs into telogen phase at

2 one time (7). Shedding does not occur, however, until the new anagen hairs begin to grow 6 to 16 weeks (average 10 weeks) after the triggering event. Conditions that cause TE may be classified into: acute illness (such as fever, major surgery, haemorrhage, burns, and prolonged difficult childbirth), chronic illness (such as crash dieting, emotional stress, systemic lupus erythematosus, end-stage renal disease and malignancies), hormonal changes (such as hypopituitarism, and hypothyroidism), starting a new medication (such as beta-blockers, anticoagulants, retinoid and the oral contraceptive pills), immunizations and chronic ingestion of heavy metals. Chronic telogen effluvium (CTE) is defined as hair shedding which lasts longer than six months. Its onset is often insidious, and it can be difficult to identify a triggering factor (8). The aetiology of CTE includes many metabolic disturbances such as hypothyroidism, hypopituitarism, and end-stage renal disease. Although iron deficiency has been reported to be a cause of CTE (4,8,9), only few recent studies examined this assumed relationship between hair loss and serum ferritin levels (SFLs) (7,10,11). Since adult menstruating females are thought to be more iron deficient than postmenopausal women (12,13), our study was set up to examine the relationship between CTE and iron status in these women, and to report on the improvement of hair growth after oral iron therapy. Methods Our study was conducted at Prince Rashed Bin Al- Hassan Military Hospital/Irbid during the period between March and December It involved 102 adult menstruating female subjects, 72 were patients with CTE and 30 were healthy volunteers randomly recruited into the study as controls. Patient and control subjects were from a similar referral base and source population. Strict selection criteria were applied. All patients fitted in the definition of CTE (8), with diffuse hair loss of at least 6 months duration. The diagnosis was based on increased hair shedding by medical history and physical examination, and confirmed by a positive hair pull test (3,14). The test was recorded as positive when greater than 25% of hairs are in telogen after the forced extraction of around 20 hairs, confirming the diagnosis of telogen effluvium. Subjects with identifiable causes of hair loss were excluded from the study, e.g. patients with thyroid disease or hyperandrogenism as measured by the appropriate tests (thyroid function tests, serum testosterone and dehydroepiandrosterone (DHEA) levels). All females were clinically examined and had laboratory blood tests. Investigations included measurements of hematocrit, SFLs, liver function tests, and renal function tests. Laboratory tests for controls included only measurements of hematocrit and SFLs. All patients with CTE found to have low SFLs were given oral iron treatment in the form of ferrous sulphate 600 mg daily for 4 months. At the end of the study period their SFLs were re-measured. All patients (with low or normal serum ferritin levels) were asked to subjectively assess the improvement in their hair growth toward the end of the 4-month study period, stating whether there was great improvement; some improvement; or none compared with that at the start of the study. This method has been used in previous studies and is considered acceptable in the assessment of hair growth (15). Results The mean age, hematocrit value, and SFLs of patients and controls are listed in Table I, together with their respective ranges and standard deviations (SD). The statistics programme SPSS for Windows version 10.0 was used for the statistical analysis. The significance level was set at 5%. The patients had an age range from 23 to 45 years with a mean age of 26 years. The controls were all females and comparable in terms of age (range from 21 to 50 years and a mean age of 32 years). Hematocrit measurements were normally distributed in both groups with similar standard deviations. Using the t-test, we found that the difference in hematocrit mean values was not statistically significant (p>0.05) between patients and controls. Statistical significance of differences in SFLs was tested by analysis of the Mann-Whitney U test where appropriate. The Chi square test was employed to measure how different is the data obtained from those expected if there was no association between low SFLs and CTE. The serum ferritin levels in patients ranged from 1.5 to 86 ng/ml with a mean of 18.7 ng/ml. The control group had serum ferritin levels ranging from 3.3 to 310 ng/ml with a mean of 47.6 ng/ml. A Mann- Whitney U test comparing the mean SFLs in both groups revealed a statistically significant difference (p<0.05). This test was used since the mean values of SFLs for patients and controls were neither normally distributed nor with similar SDs. Both groups were categorised for SFLs using a cut-off point of 20 ng/ml as the acceptable minimum normal value (Table II). Decreased SFLs were seen in 50 patients, and in only 8 controls. A Chi square test was used to investigate the association between CTE and low SFLs in both groups, showing a statistically significant difference (p<0.05). This means that there was an association between decreased SFLs and CTE, which might be clinically significant. Renal function tests, liver function tests, and hormonal levels were all within normal limits in all patients. The 50 patients with CTE and decreased SFLs were prescribed ferrous sulphate for four months. Nine patients (18%) complained of nausea and gastrointestinal upset and were given lower doses of iron. At the end of this treatment period, all treated patients had elevation of their SFLs (Table III). Using the independent-samples t-

3 test to compare the mean SFLs for patients before and after treatment with oral iron, revealed a significant difference between the two groups. A patient-dependent subjective method was used for the assessment of improvement in hair growth at the end of the treatment period (Table IV). Out of the 50 patients who received iron therapy, 21 reported great improvement, 15 some improvement, and 14 no improvement. Patients with CTE and a normal serum ferritin level (22 patients) were not given iron. Among these, one patient reported great improvement, nine some improvement and 12 reported no improvement in their hair growth. Discussion Patients with chronic telogen effluvium (CTE) usually complain of decreased scalp hair density or that their hair appears thin. The physician usually does not appreciate a decrease in hair density unless the process has been going on for several months. Physical findings in telogen effluvium show no signs of scalp inflammation. In active TE, the gentle hair pull test will yield at least 4 hairs with each pull. If the patient's active shedding has ceased, the hair pull test will be normal. Forced extraction of hairs will yield a large percentage of telogen hairs (identified by a white bulb and the lack of a gelatinous hair sheath). If greater than 25% of extracted hairs are in telogen, the diagnosis of TE is confirmed (7). However, there should be no reliance on strict physical findings or numerical criteria in the diagnosis of TE, as patients have individual variations in their hair growth cycles. History alone usually guides the physician to the correct diagnosis in many cases. In the overall assessment of response to therapy (15). A recent Japanese study (16) used phototrichgram analysis and measurement of hair diameters in the assessment of hair growth. However, we did not utilize this method due to lack of resources. We employed a subjective assessment of improvement in hair growth after treatment with iron, as this is a recognized method, and albeit is not an objective one, The differential diagnosis of CTE (3,6,8) includes alopecia areata, androgenetic alopecia, and trichotillomania. Appropriate laboratory tests should be performed in any female suspected to have androgenetic alopecia (8,9,17). This may be suggested by other features indicative of hyperandrogenism, including severe acne (of grades 7, 8, 9 and 10), hirsutism, menstrual irregularity, and infertility. Laboratory testing in patients with CTE should be directed towards causes that are common and correctable (2,3,8,9). For example, screening for thyroid functions may detect hypothyroidism and evaluation of complete blood count (CBC) and serum ferritin may reveal anemia or iron deficiency, which is common in premenopausal women, particularly in developing countries (12,18). It is important to note that the CBC may be within normal limits in women with mild iron deficiency and hair loss. This is because decreased iron stores in the body will lead to hair shedding before the development of microcytic anemia (19). Therefore, measurements of hematocrit and the mean corpuscular volume alone cannot identify patients with decreased iron stores (12,20,21). It is recommended that hematocrit measurements should not be solely relied on in the assessment of hair loss, as they were not significantly different between patients with CTE and controls in our study. The most useful single test to make the diagnosis of iron deficiency is the serum ferritin assay (22). Iron deficiency most frequently results from blood loss and low intake of diet containing iron (12,13,20). Dietary iron deficiency is most common in poor communities especially in the third world and in infants and geriatrics (22,23). The mean SFLs in our control group (47.6 ng/ml) is only slightly lower than values obtained (54.9 ng/ml) in recently published studies of mean SFLs in normal women (24). Twenty-seven percent of our controls of healthy volunteer adult females had decreased SFLs. This might reflect the prevalent low iron body stores of adult females. This idea is supported by data from a large-scale study undertaken by Waalen et al. (25), who demonstrated iron deficiency in 38% of San Diego women. Although the number of subjects in our study was rather small, a recent analytical study (10) involved just 108 patients with different types of alopecia and only 11 controls. Just 30 of their patients had telogen effluvium with a mean SFL of 15 ng/ml in the group below the age of 40 years. Their conclusion was similar to ours in that SFLs were significantly decreased in these patients. Previous authors claimed conflicting results; some suggesting an association between telogen effluvium and decreased iron stores (4,7,26,27), while others did not (11). These studies were only observational and did not rely on statistical analysis to draw their conclusions. Our study is one of the largest studies to address iron status in female patients with CTE. Most previous studies addressed both men and women as patients, and included other types of hair loss in addition to CTE. We found a statistically significant difference in the mean SFLs between patients with CTE and controls (18.7 and 47.6 ng/ml, respectively), suggesting that decreased SFLs was associated with CTE. The treatment of patients with CTE and reduced SFLs with oral iron lead to significant elevation in the mean SFLs and to improvement of hair growth in most patients after 4 months of therapy. CTE is unlikely to resolve rapidly, but it is reassuring that hair loss will not progress to baldness. Decreased SFLs are best corrected with oral iron therapy, which is safe, relatively inexpensive, and generally well tolerated. The normalisation of these levels may take four to six months or longer, and therapy may be discontinued once these levels exceed 70 ng/ml. (23,26,28) Limitation of the study: Small sample size

4 Conclusion There was a significant association between low serum ferritin levels and chronic telogen effluvium. Therefore, serum ferritin levels may be of value in the evaluation of adult menstruating women with chronic diffuse hair loss. Table I. Mean age, hematocrit values, and SFLs in patients and controls. Mean age (± SD)* Mean hematocrit (± SD)* Mean SFL (± SD)* Patients 26 (±9.2) [16-45] 34.3 (±3.41) [24-42] 18.7 (±19.6) [1.5-86] Controls 32 (±11.6) [17-50] 34.5 (±2.87) [30-39] 47.6 (±73.6) [ ] * Mean age is given in years, hematocrit values in %, and SFLs in ng/ml & Mean + standard deviation. Table II. Mean values for SFLs in patients and controls. Category Low Normal Total Patients Controls Total Normal range for SFL is ng/ml. Table III. Mean values for SFLs (ng/ml) in the treatment group. Category Mean SFL Range SD Pre-treatment Post-treatment Table IV. Patients subjective assessment of improvement in hair growth. Great improvement Some improvement No improvement Total Treated patients Untreated patients Total References 1. Costarelis G, Miller SE. Towards a molecular understanding of hair loss and its treatment. Trends in Moelcular Medicine 2001; 7: Headington JT. Telogen effluvium. New Concepts and Review. Arch Dermatol 1993; 129: Springer K, Brown M, Stulberg DL. Common hair loss disorders. Am Fam Physician 2003; 68: Van Neste DJ, Rushton DH. Hair problems in women. Clinics Dermatol 1997; 15: Nielson TA, Reichel M. Alopecia: Diagnosis and management. Am Fam Physician 1995; 51: Fielder VC, Hafeez A. Diffuse alopecia: Telogen hair loss. In: Oslen E. ed. Disorders of hair growth. New York: McGraw-Hill 1994; Harrison S, Sinclair R. Telogen Effluvium. Clin Exp Dermatol 2002; 27: Chartier MB, Hoss DM, Grant-Kels JM. Approach to the adult female patient with diffuse nonscarring alopecia. J Am Acad Dermatol 2002; 47: Barth JH. Rational investigations in the diagnosis and management of women with Hirsutism or Androgenetic Alopecia. Clin Dermatol 2001; 19: Kantor J, Kessler LJ, Brooks DG, Costarelis G. Decreased serum ferritin is associated with alopecia in women. J Invest Dermatol 2003; 121: Sinclair R. There is no clear association between low serum ferritin and chronic diffuse telogen hair loss. Br J Dermatol 2002; 147: Andrews NC. Disorders of iron metabolism. N Eng J Med 1999; 341: Creed-Kanashiro HM, Uribe TG, Bartolini RM, et al. Improving dietary intake to prevent anemia in adolescent girls through community kitchens in a periurban population of Lima, Peru. J Nutr 2000; 130 (suppl 2S): 459S-461S. 14. Rietschel RL. A simplified approach to the diagnosis of alopecia. Dermatologic Clinics 1996; 14: Chamberlain AJ, Dawber RPR. Methods of evaluating hair growth. Aust J Dermatol 2003; 44: Ueki R, Tsuboi R, Inaba Y, Ogawa H. Phototrichogram analysis of Japanese female subjects with chronic diffuse hair loss. J Invest Dermatol 2003; 8: Tosti A, Camacho-Martinez F, Dawber R. Management of androgenetic alopecia. J Eur Acad Dermatol Venereol 1999; 12: Tapiero H, Gaté L, Tew KD. Iron: Deficiencies and requirements. Biomed Pharmacother 2001; 55: Rushton DH, Ramsay ID. The importance of adequate serum ferritin levels during oral cyproterone acetate and ethinyl oestradiol treatment of diffuse

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