|Year : 2022 | Volume
| Issue : 3 | Page : 174-177
Comorbid laboratory abnormalities in female pattern hair loss patients
Hsin-Jou Wang1, Jui-Wen Yeh2, Yin-Fan Chang1, Jin-Shang Wu3, Chao-Chun Yang4
1 Department of Family Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
2 Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
3 Department of Family Medicine, National Cheng Kung University Hospital, College of Medicine; Department of Family Medicine, National Cheng Kung University Hospital Dou-Liou Branch, College of Medicine, National Cheng Kung University, Tainan, Taiwan
4 Department of Dermatology, National Cheng Kung University Hospital, College of Medicine; International Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, Taiwan
|Date of Submission||06-Feb-2022|
|Date of Decision||30-May-2022|
|Date of Acceptance||13-Jun-2022|
|Date of Web Publication||29-Sep-2022|
Department of Dermatology, National Cheng Kung University Hospital, College of Medicine; International Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan
Source of Support: None, Conflict of Interest: None
Background: Female pattern hair loss (FPHL) is the main cause of alopecia in women and has a debilitating impact on the quality of life. However, certain comorbid conditions causing hair loss are often masked by FPHL and may remain undetected. Hence, it is imperative to identify them to administer appropriate treatment. The necessity of laboratory tests to evaluate these comorbidities in patients with FPHL has not been established. Objectives: This study aimed to identify the frequency of comorbid abnormalities detected by laboratory tests in patients with FPHL. Methods: Routine laboratory test results of patients with FPHL, who visit our hair clinic for the first time, were retrospectively collected and analyzed. These tests assessed the serum testosterone, thyroid-stimulating hormone, free thyroxin, zinc and ferritin levels, hemoglobin, as well as antinuclear antibody (ANA), and rapid plasma reagin test results. The correlation between age and hair loss severity and the frequency of comorbidities was evaluated using subgroup analysis. Results: Among the 356 patients with FPHL, coexisting zinc deficiency, iron depletion, and thyroid abnormalities were common and present in 41.7%, 39.7%, and 11.3% of them, respectively. The rate of concomitantly increased ANA titers was relatively low (4.4%), while that of syphilis and high serum testosterone levels was extremely low (0.3% and 0%, respectively). Younger patients (<50 years) with FPHL had a higher rate of coexisting iron deficiency than patients in the older age group. Conclusion: Testing for concomitant iron depletion, zinc deficiency, and thyroid disease is recommended in female patients with FPHL.
Keywords: Androgenetic alopecia, female pattern hair loss, iron deficiency, nutritional deficiency, zinc deficiency
|How to cite this article:|
Wang HJ, Yeh JW, Chang YF, Wu JS, Yang CC. Comorbid laboratory abnormalities in female pattern hair loss patients. Dermatol Sin 2022;40:174-7
Hsin-Jou Wang, Jui-Wen Yeh contributed equally to this article.
| Introduction|| |
Female pattern hair loss (FPHL) is a nonscarring alopecia that presents with progressive miniaturization of hair follicles and subsequent reduction of hair numbers, especially in the frontal, parietal, and vertex regions of the scalp. In Taiwan, FPHL is common, with a prevalence rate of 11.8%, and causes adverse social impact and psychological stress in the affected women. However, the exact mechanism of FPHL is not completely understood. Its poor response to antiandrogen treatment suggests that FPHL is a multifactorial disease, rather than being just an androgen-dependent process.,
Comorbid diseases are common in FPHL., Some of these comorbid conditions, including iron depletion, zinc deficiency, thyroid diseases, and autoimmune diseases, also contribute to hair loss, but the diagnosis is often masked by FPHL due to the overlapping features of clinical presentation. Therefore, laboratory tests are essential when evaluating patients with FPHL to identify the comorbid diseases accurately. However, the available data on the prevalence of these comorbidities in patients with FPHL are inconsistent., In addition, it is not known whether the prevalence of these disorders correlates with the severity of FPHL or whether they present differentially in the different age groups. This study aimed to identify the prevalence of these concomitant disorders using laboratory tests in patients with FPHL and discuss the feasibility of performing these tests when evaluating patients with FPHL.
| Materials and Methods|| |
Female patients with FPHL were retrospectively recruited from the clinical database of the hair clinic at our hospital between January 2018 and February 2020. FPHL was clinically diagnosed based on diffuse thinning of the hair, especially in the scalp's frontal, parietal, and vertex scalp, resulting in a widened hair parting line on the scalp. Hair follicle miniaturization, which was identified using trichoscopy, was another important finding that helped established the diagnosis of FPHL. FPHL severity was graded using the Ludwig scale from I to III. Patients without a definite diagnosis of FPHL or with other hair loss-related diseases, including alopecia areata, telogen effluvium with a known etiology, trichotillomania, or scarring alopecia, were excluded.
The results of the laboratory tests during the patient's first visit to our hair clinic were collected for analysis. These laboratory tests included those for estimating serum testosterone, thyroid-stimulating hormone (TSH), free thyroxin (FT4), zinc and ferritin levels, hemoglobin, as well as antinuclear antibody (ANA) and rapid plasma regain (RPR) test. These laboratory tests were routinely performed on all female patients who visited our hair clinic. In this study, iron depletion was defined as a ferritin level <40 ng/mL, while iron deficiency was defined as a ferritin level <13 ng/mL, based on the Nutrition and Health Survey in Taiwan. The thyroid function status was defined by the serum levels of TSH and FT4 and classified as hypothyroidism (low FT4), hyperthyroidism (high FT4), subclinical hypothyroidism (high TSH; normal FT4), and subclinical hyperthyroidism (low TSH; normal T4). An ANA titer ≥1:80 estimated through immunofluorescence was regarded as significantly elevated. A positive RPR test was followed up by the Treponema pallidum hemagglutination (TPHA) test to confirm the diagnosis of syphilis. Further subgroup analysis was carried out by stratifying the study subjects by age (<50 and ≥50 years) or hair loss severity (Ludwig scale grade I [mild] vs. II/III [moderate to severe]).
Data were analyzed using the Statistical Package for the Social Sciences (SPSS v. 20; SPSS Inc., Chicago, IL, USA). For independent samples, t-tests, Chi-square tests, and Pearson's correlation were used for statistical analysis. Values were presented as mean ± standard deviation, and noncontinuous variables were presented as numbers and percentages. In the age-stratified subgroup analysis, owing to the small number of cases, values were presented as median ± standard error and the Mann–Whitney U-test was used for statistical analysis. Statistical significance was set at P < 0.05 (two-tailed). This study was conducted in accordance with the tenets of the Declaration of Helsinki of 1975 and its later amendments. The study protocol was approved by the Institutional Review Board of our hospital (approval no.: A-ER-109-263, approval date: Sep. 28th, 2020). The requirement for patient consent was waived by the Institutional Review Board.
| Results|| |
In total, 356 patients with FPHL were included in this study. Their mean age was 33.6 years (range, 18–82 years). Regarding the severity of FPHL, 54% of the patients were classified as having Grade I, 35.3% as Grade II, and 10.7% as Grade III severity of hair loss [Table 1]. Iron depletion (serum ferritin <40 ng/mL) and iron deficiency (ferritin <13 ng/mL) were identified in 39.7% and 14.1% of patients, respectively. Serum ferritin levels were significantly lower in the younger (<50 years) subgroup than in the older (l50 years) (47.6 vs. 102 ng/mL, P < 0.01) [Table 2]. The younger subgroup also displayed a significantly higher rate of iron depletion (41.7% vs. 17.2%, P = 0.01).
|Table 1: The demographic and clinical characteristics of female pattern hair loss patients|
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|Table 2: Laboratory abnormalities in subgroups of different alopecia severity and different age|
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Zinc deficiency was identified in 41.7% of patients with FPHL. The rate of zinc deficiency was not significantly different between subgroups with different ages or FPHL severities.
For thyroid function, in the 248 patients in whom the thyroid test data were available, 21 were found to have a subclinical hypothyroid status, 4 had a subclinical hyperthyroid status, 3 had a hyperthyroid status, and none had hypothyroidism. Thyroid status was not significantly different between the subgroups. None of the patients in our study showed abnormal total testosterone levels. However, the total testosterone level was significantly lower in the older (>50 years) subgroup (10.4 vs. 22.4 ng/dL, P = 0.001).
For ANA, only 14 of 321 patients had a titer of >1:80. None of these 14 patients had an established diagnosis of autoimmune diseases or symptoms related to autoimmune disease during the follow-up visits. The serological tests, including the anti-double-stranded deoxyribonucleic acid antibody and complement levels in these patients, were all normal. A positive RPR test was identified in one patient with a titer of 1:1, but the subsequent TPHA test result was negative.
| Discussion|| |
In this study, zinc deficiency, iron depletion, and thyroid abnormalities were identified in 41.7%, 39.7%, and 11.3% of the patients with FPHL, respectively. The comorbidity rates were high; therefore, it is important to properly identify these comorbidities when managing patients with FPHL. The clinical presentation of hair loss caused by zinc deficiency, iron depletion, and thyroid diseases overlaps with the clinical presentation of FPHL. It is not easy to differentiate the coexistence of these disorders by clinical observation; therefore, performing laboratory tests to determine the presence of zinc deficiency, iron depletion, and thyroid diseases in patients with FPHL are highly recommended. However, the laboratory tests did not detect coexistent autoimmune diseases or syphilis in our FPHL patients; therefore, these tests may not be required to be performed routinely. Screening for autoimmune disease or syphilis was only prompted in FPHL patients when there were suggestive symptoms and signs other than diffuse hair loss.
Iron is a rate-limiting cofactor for ribonucleotide reductase, and iron deficiency may affect fast-proliferating hair follicle matrix cells significantly, even at a minor scale. Gropper et al. first reported hair growth after iron supplementation in a group of nonanemic iron-deficient female patients with hair loss. Hair loss may be initiated or exacerbated when the ferritin levels are <40 ng/mL (iron depletion). Many studies have attempted to clarify the role of iron deficiency in hair loss, but the results of these studies are inconsistent. Some studies support the role of iron deficiency in hair loss by demonstrating lower ferritin levels in patients with AGA or chronic telogen effluvium, compared to those in healthy controls,,,, or by demonstrating a positive response to iron supplementation for treating hair loss. On the other hand, some studies have demonstrated that the rate of iron deficiency was not significantly different between the FPHL, chronic telogen effluvium, and control groups.,, The discrepancies could be partially attributed to the different definitions of iron deficiency and different types of hair loss included for analysis. In our study, a significant proportion (14.1%) of patients with FPHL had iron deficiency. In a national nutritional survey, the prevalence of iron deficiency in women of menstrual age (19–44 years) was 24.1%. Our study included women of similar ages, but the prevalence of iron deficiency was much lower. The disparity in such results may be related to selection bias, laboratory settings, or the relatively small sample size in our study.
Zinc is frequently discussed in recent studies regarding its role in hair loss. Lower serum zinc levels have been reported in patients with FPHL than in controls. However, there are currently insufficient and inconsistent data to support the beneficial effects of zinc supplementation in patients with hair loss., More studies are required to elucidate the effect of zinc supplements in treating hair loss of different etiologies.
The thyroid abnormalities identified in our patient group were mostly subclinical (25/28; 89.3%). Most individuals with asymptomatic subclinical hypothyroidism or hyperthyroidism are observed without treatment. However, treatment may be indicated depending on the patient's age or symptoms. Therefore, prompt identification of these conditions and referral to endocrinologists for further evaluation are required.
There were no cases with high testosterone levels in our study. Our data showed that a significant decrease in testosterone levels was noted in the postmenopausal (≥50 years) subgroup, in line with the data in another report. As dehydroepiandrosterone and dehydroepiandrosterone sulfate levels decline with aging, their metabolite, testosterone, also decreases. The reduction of testosterone in the older subgroup suggested that the mechanism of FPHL was multifactorial and not necessarily androgen-mediated. For these reasons, total testosterone level is not a necessary screening test when evaluating patients with FPHL unless obvious virilizing features are observed.
A limitation of the study was the lack of a control group without hair loss, owing to the retrospective nature of the study. The average values of these laboratory parameters in the general Taiwanese population are mostly unavailable in the literature. A further study with larger sample size and a control group is warranted.
| Conclusions|| |
Routine tests for iron depletion, zinc deficiency, and thyroid diseases are recommended when encountering patients with FPHL because the comorbidity rates of these disorders are high. Tests for testosterone, syphilis, and ANA are only required when there is high clinical suspicion.
The authors would like to thank Dr. Jia-Ruey Wang for his support preparing the manuscript
Financial support and sponsorship
Conflicts of interest
Prof. Chao-Chun Yang, an associate editor at Dermatologica Sinica, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.
| References|| |
Ramos PM, Miot HA. Female pattern hair loss: A clinical and pathophysiological review. An Bras Dermatol 2015;90:529-43.
Su LH, Chen LS, Chen HH. Factors associated with female pattern hair loss and its prevalence in Taiwanese women: A community-based survey. J Am Acad Dermatol 2013;69:e69-77.
Chen W, Yang CC, Todorova A, Al Khuzaei S, Chiu HC, Worret WI, et al
. Hair loss in elderly women. Eur J Dermatol 2010;20:145-51.
Yang CC, Hsieh FN, Lin LY, Hsu CK, Sheu HM, Chen W. Higher body mass index is associated with greater severity of alopecia in men with male-pattern androgenetic alopecia in Taiwan: A cross-sectional study. J Am Acad Dermatol 2014;70:297-302.e1.
Trost LB, Bergfeld WF, Calogeras E. The diagnosis and treatment of iron deficiency and its potential relationship to hair loss. J Am Acad Dermatol 2006;54:824-44.
Gowda D, Premalatha V, Imtiyaz DB. Prevalence of nutritional deficiencies in hair loss among Indian participants: Results of a cross-sectional study. Int J Trichology 2017;9:101-4.
Siah TW, Muir-Green L, Shapiro J. Female pattern hair loss: A retrospective study in a tertiary referral center. Int J Trichology 2016;8:57-61.
Rasheed H, Mahgoub D, Hegazy R, El-Komy M, Abdel Hay R, Hamid MA, et al
. Serum ferritin and vitamin d in female hair loss: Do they play a role? Skin Pharmacol Physiol 2013;26:101-7.
Harries M, Tosti A, Bergfeld W, Blume-Peytavi U, Shapiro J, Lutz G, et al
. Towards a consensus on how to diagnose and quantify female pattern hair loss – The 'female pattern hair loss severity index (FPHL-SI)'. J Eur Acad Dermatol Venereol 2016;30:667-76.
Olsen EA, Reed KB, Cacchio PB, Caudill L. Iron deficiency in female pattern hair loss, chronic telogen effluvium, and control groups. J Am Acad Dermatol 2010;63:991-9.
Pan WH. Nutrition and Health Survey in Taiwan 2013–2016; July 12, 2019. Ministry of Health and Welfare, Health Promotion Administration
Gropper SS, Kerr S, Barksdale JM. Non-anemic iron deficiency, oral iron supplementation, and oxidative damage in college-aged females. J Nutr Biochem 2003;14:409-15.
Kantor J, Kessler LJ, Brooks DG, Cotsarelis G. Decreased serum ferritin is associated with alopecia in women. J Invest Dermatol 2003;121:985-8.
Park SY, Na SY, Kim JH, Cho S, Lee JH. Iron plays a certain role in patterned hair loss. J Korean Med Sci 2013;28:934-8.
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.
Kil MS, Kim CW, Kim SS. Analysis of serum zinc and copper concentrations in hair loss. Ann Dermatol 2013;25:405-9.
Almohanna HM, Ahmed AA, Tsatalis JP, Tosti A. The role of vitamins and minerals in hair loss: A review. Dermatol Ther (Heidelb) 2019;9:51-70.
Biondi B, Cappola AR, Cooper DS. Subclinical hypothyroidism: A review. JAMA 2019;322:153-60.
Yasui T, Matsui S, Tani A, Kunimi K, Yamamoto S, Irahara M. Androgen in postmenopausal women. J Med Invest 2012;59:12-27.
[Table 1], [Table 2]